ACS Publications. Most Trusted. Most Cited. Most Read
Metallomimetic C–F Activation Catalysis by Simple Phosphines
More

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Am. Chem. Soc. 2024, 146, 3, 2005-2014
  • Open Access
ADDITION/CORRECTION. This article has been corrected. View the notice.
Article

Metallomimetic C–F Activation Catalysis by Simple Phosphines
Click to copy article linkArticle link copied!

Open PDFSupporting Information (1)

Journal of the American Chemical Society

Cite this: J. Am. Chem. Soc. 2024, 146, 3, 2005–2014
Click to copy citationCitation copied!
https://doi.org/10.1021/jacs.3c10614
Published January 11, 2024

Copyright © 2024 The Authors. Published by American Chemical Society. This publication is licensed under

CC-BY 4.0 .

Abstract

Click to copy section linkSection link copied!
High Resolution Image
Download MS PowerPoint Slide

Delivering metallomimetic reactivity from simple p-block compounds is highly desirable in the search to replace expensive, scarce precious metals by cheap and abundant elements in catalysis. This contribution demonstrates that metallomimetic catalysis, involving facile redox cycling between the P(III) and P(V) oxidation states, is possible using only simple, cheap, and readily available trialkylphosphines without the need to enforce unusual geometries at phosphorus or use external oxidizing/reducing agents. Hydrodefluorination and aminodefluorination of a range of fluoroarenes was realized with good to very good yields under mild conditions. Experimental and computational mechanistic studies show that the phosphines undergo oxidative addition of the fluoroaromatic substrate via a Meisenheimer-like transition state to form a fluorophosphorane. This undergoes a pseudotransmetalation step with a silane, via initial fluoride transfer from P to Si, to give experimentally observed phosphonium ions. Hydride transfer from a hydridosilicate counterion then leads to a hydridophosphorane, which undergoes reductive elimination of the product to reform the phosphine catalyst. This behavior is analogous to many classical transition-metal-catalyzed reactions and so is a rare example of both functional and mechanistically metallomimetic behavior in catalysis by a main-group element system. Crucially, the reagents used are cheap, readily available commercially, and easy to handle, making these reactions a realistic prospect in a wide range of academic and industrial settings.

This publication is licensed under

CC-BY 4.0 .
  • cc licence
  • by licence
Copyright © 2024 The Authors. Published by American Chemical Society

Subjects

what are subjects

Introduction

Click to copy section linkSection link copied!
There has been a significant amount of interest in recent years in the activation and functionalization of small molecules and strong bonds by main-group-element compounds acting in similar ways to transition metals. (1−4) In addition to fundamental interest and the development of novel reactivity, this has been driven, in part, by a desire to find more sustainable alternatives to the low-abundant, expensive, and potentially toxic precious metals that are commonly used in homogeneous catalysis. A key foundation of this work is the concept of metallomimetic behavior, (5,6) where main-group-element species can be prompted to display analogous reactivity to transition metals, e.g., through the formation of unusual bonding modes, oxidation states, coordination geometries, and of course, the huge efforts around frustrated Lewis pairs. (7−15) Of all the transition-metal like reactivity, the ability to undergo reversible two-electron redox processes, such as oxidative addition (OA) and reductive elimination (RE), is at the core of many traditional homogeneous catalytic cycles. Similarly facile redox cycling in main-group elements is much rarer, although promoting OA and RE processes have been a highly active area of study in recent years. (16) A key challenge with many main-group species is that there are often larger differences in stability between different oxidation states when compared to transition metals, which results in either rapid OA or RE, but then a much more challenging reverse process that renders catalysis difficult. However, among the main group elements the pnictogens stand out in this regard, often allowing access to stable species in different oxidation states, and as such they are ideal candidates for the development of metallomimetic reactivity and catalysis. (17) A key design concept that has led to observations of redox-cycling within these systems is the introduction of geometrical constraints around the pnictogen atoms, moving them away from their preferred pyramidal to more planar geometries, resulting in changes in orbital energies and reactivity. (18−24) Pincer ligands are often used for this purpose, promoting ambiphilic behavior and unusual reactivity of the pnictogen, (25−34) although metal–ligand cooperativity is also frequently observed in these systems. (35−43)
Key reactions in which main-group systems have been studied are catalytic hydrodefluorination (HDF) and related defluorination processes (Scheme 1). These are important approaches to prepare complex fluorinated molecules, which have applications in pharmaceuticals, (44,45) agrochemicals, (46) and materials chemistry, (47) from readily available polyfluorinated precursors. (48) Transition-metal-based C–F functionalization is relatively well established, (49−52) and a range of main-group systems have also been explored for HDF. (53,54) These include non-redox systems such as strong Lewis acids, (55) including electron-deficient phosphonium ions, (56−58) and FLPs, (59) which allow HDF of aliphatic C–F bonds, tetrabutylammonium triphenyldifluorosilicate (TBAT), (60) NaBH4, (61) and diazaphospholenes, (62,63) which can catalyze HDF of aromatic C–F bonds and trifluoromethylalkenes. Important recent studies have elegantly demonstrated that geometrically constrained pnictogen systems can promote HDF, either through a series of stoichiometric steps or catalytically, via P(III)/P(V) or Bi(I)/Bi(III) redox cycling. Crucially, the three key processes of OA, ligand metathesis (LM)/transmetalation (TM), and RE that underpin many transition-metal catalytic mechanisms were seen in these systems (Scheme 1). (21,23,24) These are remarkable demonstrations that main-group systems can mechanistically mimic the key steps in transition-metal catalysis. However, complex ligand architectures were used, and these were proposed to play an important role in the observed reactivity through geometrically constraining the pnictogen. Inspired by reports of stoichiometric reactivity of simple phosphines with fluoroarenes, we set out to explore whether geometric constraints are a necessary prerequisite of redox-cycling in HDF using pnictogen catalysts. (64−66) We now report that a simple catalyst system constituted from commercially available alkyl phosphines and silanes is able to perform the HDF reaction on a range of aromatic substrates.

Scheme 1

Scheme 1. Comparison of Recent Aromatic Hydrodefluorination (HDF) Reactions Promoted or Catalysed by Main Group Compounds Through Redox-Neutral (A) or Redox-Cycling (B) Pathways and the Present Work (C)
High Resolution Image
Download MS PowerPoint Slide

Results and Discussion

Click to copy section linkSection link copied!
Initial investigations into the catalytic HDF of pentafluoropyridine (1) by simple phosphines probed whether 1 and PhSiH3 could form 2,3,5,6-tetrafluoropyridine (2) in the presence of catalytic PiPr3 (10 mol %) under similar reaction conditions to those used by Dobrovetsky and co-workers (o-C6H4F2 at 60 °C, Table 1, entry 1) with a geometrically constrained phosphine catalyst. (21) After 18 h, we were pleased to find that 2 was formed, albeit in only modest, 26%, yield. The 19F NMR spectra of the reaction mixture showed peaks at δ = −92.9 and −141.5 ppm indicative of the ortho- and meta-fluorine environments of 2, respectively. Unreacted 1 could also clearly be seen (65%) and 9% of the product of reductive coupling of 1, perfluoro 4,4′-bipyridine (3) was also formed, identified through 19F NMR signals at δ = −95.0 and −137.2 ppm. A control experiment under the same conditions showed that 1 and PhSiH3 did not form 2 in the absence of a phosphine (see Supporting Information for details). These results demonstrate for the first time that catalytic HDF is possible using only a simple trialkylphosphine as the catalyst. However, the reaction was significantly slower than that reported by Dobrovetsky and co-workers, who observed 95% yield of 2 in only 3 h at 80 °C with a geometrically constrained P(III) catalyst. The simple nature of the phosphine and silane in our system allowed for straightforward reaction optimization with a range of potential catalysts and hydride sources. Our focus here was not only on rate and selectivity, but also to make use of the simplest, most widely available and cheapest catalysts and supporting reagents in order to ensure that reactions are widely applicable.
Table 1. Reaction Optimization for HDF of Pentafluoropyridine (1)a
entryPR3PR3 mol %silanesilane equiv.solventtemp./°Ctime/hyield of 2/%
1PiPr310PhSiH31o-C6H4F2601826
2PiPr310PhSiH31MeCN604476
3PiPr310Ph2SiH21MeCN201884
4PiPr310Ph3SiH2MeCN20182
5PnBu310PhSiH31MeCN602100
6PnBu310Ph2SiH21MeCN200.3393
7PnBu310Ph3SiH2MeCN20186
8PnBu310Ph2SiH20.55MeCN20387
9PnBu35Ph2SiH21MeCN20193
10PnBu31Ph2SiH21MeCN201883
a

NMR yields determined by integration of 19F NMR spectra using trifluorotoluene as an internal standard (see Supporting Information).

Reaction Optimization

Click to copy section linkSection link copied!
A range of conditions were tested to explore phosphine, silane, and solvent effects on the HDF of 1 (Table 1). Changing the solvent from o-C6H4F2 to MeCN had a significant, positive effect on the reaction, and gave 67% of 2 after 18 h at 60 °C and 76% after 44 h (Table 1, entry 2) alongside a small amount of 3 (4%), trace unreacted 1 and small quantities of other unidentified fluorinated products. Changing the silane to Ph2SiH2 significantly increased the reaction rate (Table 1, entry 3), allowing a lower temperature to be used and giving 84% of 2 after only 18 h at 20 °C, in addition to a small amount of 3 (7%). Further H/Ph substitution on the silane, however, only led to trace amounts of 2 when Ph3SiH was used (Table 1, entry 4) with most of the starting material 1 left unreacted, alongside the formation of 8% of 3.
Another substantial improvement in catalytic performance was found when PiPr3 was substituted for PnBu3, with the silanes showing the same trend for the two phosphines (Table 1 entries 5–7). The combination of PnBu3 and Ph2SiH2 provided optimal reaction conditions allowing HDF of 1 to give 2 in excellent yield (93%) in only 20 min at 20 °C (Table 1 entry 6). This is among the best catalytic aromatic HDF performance so far reported by a main-group-element catalyst. (21,24,60,62) Pleasingly, this combination of phosphine and silane were also the cheapest (67) and most readily available that were tested. In addition, PnBu3 and Ph2SiH2 gave HDF that was selective for 2 under these conditions, no other HDF products were observed, e.g., other regioisomers and/or multiple HDFs.
Experiments to reduce the phosphine and silane loadings (Table 1, entries 8–10) showed that using a close to stoichiometric (in terms of hydride equivalents) amount of Ph2SiH2 still allowed good conversion to 2 (87%), although the reaction was slower and a small amount of 3 (2%) was formed alongside the desired product (Table 1, entry 8). Reduction of the phosphine loading to 5 mol % was still very effective, albeit slower (93% 2 after 1 h), and at 1 mol % selective formation of 2 was still possible, but reaction times were much longer (83% yield after 18 h) and some unreacted 1 (11%) was present after this time. Given the low cost of both PnBu3 and Ph2SiH2 it was decided to use the reaction conditions in entry 6 in Table 1, for further studies, as these led to fast reactions without a significant increase in cost.

Substrate Scope

Click to copy section linkSection link copied!
The substrate scope was explored for HDF of a range of other fluoroarenes and heterocycles (Scheme 2, HDF products 2–11). In addition, it was possible to determine conditions for the selective reductive coupling of 1 to 3 and to explore preliminary aminodefluorination reactions (products 12–15) to allow C–F functionalization by amines.

Scheme 2

Scheme 2. Results of Substrate Scope Studiesa
High Resolution Image
Download MS PowerPoint Slide

aPh2SiH2 was used for all HDF reactions and Ph2Si(Cl)(NR2) were used for aminodefluorination reactions.

bIsolated yield after flash column chromatography shown in parentheses.

cReactions were stirred at 60 °C for 4 days, followed by the remaining period at 80 °C.

dStoichiometric reaction between PiPr3 and 1 in MeCN (other phosphines behave similarly).

Exploration of the degree of fluorination of fluoropyridines and the regioselectivity of the HDF reaction gave insights into the reaction mechanism and synthetic possibilities. With 2,3,5,6-tetrafluoropyridine as a substrate, it was possible to observe the formation of 4, but in low yield and with much more forcing conditions (13% after 5 days at 70 °C). 19F NMR spectroscopy clearly showed the presence of 4, with peaks at δ = −92.3, −129.0, and −136.5 ppm, unreacted tetrafluoropyridine (25%) and some additional low-intensity signals that were consistent with other tri- and difluoropyridine isomers. This explains the selectivity of the HDF conditions in Table 1, entry 6, as a second HDF at the less activated ortho-position of the pyridine is substantially slower than the initial reaction at the para-position of 1. The presence of other tri- and difluoropyridines suggests that the rate of HDF at the ortho- and meta-positions is similar to each other and slower than the rate of HDF at the para-position. Reducing the degree of fluorination of the substrate but maintaining a C–F bond at the most reactive para-position also allowed HDF and formation of 5 (79% yield), but the reaction was relatively slow and a small amount of unreacted 2,4,6-trifluoropyridine (5%) was present, along with some 2,4-difluoropyridine (14%), which results from ortho-HDF, after 6 days. It is clear that more electron-poor heteroaromatics lead to faster reactions, which is consistent with the mechanistic proposal (see below).
The catalytic HDF reaction is not limited to pyridines. Reaction of other electron-poor aromatics, such as pentafluorobenzonitrile and perfluorotoluene, led to rapid formation of 6 and 7 in very good yields (86 and 89%, respectively). Simple fluorobenzenes showed trends similar to those seen with the fluoropyridines, with hexafluorobenzene undergoing double HDF to ultimately form tetrafluorobenzene (Scheme 2, 8a). Formation of 8a can be seen after 2 h, with the amount increasing after 18 h, but interestingly only trace amounts of pentafluorobenzene were seen in the 19F NMR spectra at these time periods. It appears that the rates of HDF of hexa- and pentafluorobenzene are similar and overall significantly slower than perfluorotoluene. This was confirmed by direct HDF of pentafluorobenzene (Scheme 2, 8b), which occurred on a similar time scale to 8a under similar conditions. The ultimate yields of 1,2,4,5-tetrafluorobenzene were very good in both cases (84 and 93%, respectively). Perfluorobiphenyl also converted effectively to the doubly hydrodefluorinated product 11, in 87% yield after 24 h at 60 °C. During the course of the reaction the monohydrodefluorinated product was seen (39%) in the 19F NMR spectra after 1 h with signals at δ = −139.5, −152.6, and −162.9 ppm, alongside 11 (15%) and unreacted perfluorobiphenyl (42%).
Introduction of an electron-donating substituent, in pentafluoroanisole, was not tolerated in this system, with only traces of hydrodefluorinated products observed after 7 days at 60 °C alongside the majority of the starting material remaining unreacted. The use of bromopentafluorobenzene as a substrate also resulted in no conversion to the hydrodefluorinated product 9 after 20 min at 20 °C. However, in this case a small amount of pentafluorobenzene (3%) was formed and a new species was seen in the 19F NMR spectrum at δ = −128.4, −142.9, and −158.3 ppm (11%). This was associated with a signal in the 31P NMR spectrum at 36.6 ppm, which was the major phosphorus-containing product. Addition of a further 0.9 equiv of PnBu3 significantly increased the intensity of the signals from this species in the 19F and 31P NMR spectra (recorded after 30 min at 20 °C), along with the consumption of the majority of the bromopentafluorobenzene. This new species was assigned as the phosphonium salt [P(C6F5)(nBu)3]Br ([16]Br), which results from C–Br rather than C–F activation of the fluoroarene. At this point, additional formation of pentafluorobenzene was also seen (21%) and after 18 h at 20 °C, this had increased slightly to 35%. For this substrate, it appears that hydrodebromination is favored over HDF, although higher phosphine loadings are required, as the system appears to rest as the relatively unreactive salt [16]Br, which has implications in terms of the mechanistic proposal (discussed below).
Extending the catalytic methodology to other C–F functionalization reactions was also explored. Preliminary studies investigated C–F amination by silylamides in the presence of catalytic PnBu3. (21) Thus, when 1 was reacted with Ph2Si(Cl)(NEt2) with 10 mol % of PnBu3 at 60 °C for 18 h a good yield (75%) of the aminated product 12 was seen, alongside a small amount of unreacted 1 (10%). This was characterized by signals in the 19F NMR at δ = −96.7 and −157.0 ppm, in the 1H NMR at δ = 3.43 (qt, 3JHH = 7 Hz, and 5JHF = 2 Hz) and 1.22 (t, 3JHH = 7 Hz) ppm and by an M+ ion of 222.07810 m/z (2.85 ppm deviation from theoretical) in the EI-MS. Unlike most of the HDF reactions described above, which were generally very selective, under aminodefluorination conditions an additional product (10%) was observed in the 19F NMR at δ = −89.0, −125.2, and −151.3 ppm. This was associated with a new signal in the 31P NMR spectrum at δ = 36.4 ppm, whose chemical shift was typical of a phosphonium salt, which represented the major phosphorus-containing species. Extending this reaction to more complex amines also proved possible, and we were delighted to see that the reaction of 1 with Ph2Si(Cl)(pro) (where pro is l-proline methyl ester) gave a very good yield of 13 (88%) alongside a small amount of unreacted 1. The 19F NMR spectrum of 13 was similar to that of 12, with 19F signals at δ = −97.0 and −160.1 ppm. The 1H NMR spectrum was consistent with retention of the proline methyl ester moiety (see Supporting Information) and EI-MS confirmed the accurate mass of the [M]+ ion at 278.06880 m/z (5.41 ppm deviation from theoretical). This demonstrated that potentially sensitive functional groups are tolerated by this catalytic aminodefluorination reaction and that it may find application in the preparation of highly functionalized, fluorinated amines, e.g., in pharmaceutical or agrochemical synthesis. Extending the fluoroarene substrates beyond 1 also proved possible, with both pentafluorobenzonitrile and perfluorotoluene also reacting with Ph2Si(Cl)(NEt2) in the presence of 10 mol % PnBu3 to give 14 and 15 in 82 and 50% yield, respectively. However, these substrates proved more sluggish under the reaction conditions optimized for HDF and further optimization is desirable in future studies to extend the aminodefluorination reactions beyond these preliminary results.
Significant amounts of reductive coupling of pentafluoropyridine to form 3 were not seen under the catalytic conditions described above. In an attempt to optimize this simple phosphine system for the preparation of 3, stoichiometric conditions for this reaction were explored. Thus, when PiPr3 (1 equiv) and 1 were allowed to react in MeCN at 20 °C for 30 min, 3 was formed in 84% yield, alongside an equivalent amount of PF2(iPr)3 and a small amount of unreacted 1 (16%). We have observed similar reactivity with other phosphines under stoichiometric conditions and analogous reactivity has been described before for P(NEt2)3. (68) Although this is stoichiometric in phosphine, rather than catalytic, given the generally low cost of the phosphines used and the simple and mild reaction conditions, it may prove a useful route to 3.
Overall, it is clear that both HDF and aminodefluorination are feasible for a range of substrates using only a simple, readily commercially available phosphine as the catalysts. The product yields and reaction times are among the best observed for main-group catalysts for highly electron-poor fluoroarenes. The performance of this system is often better than that in related geometrically constrained P(III)/P(V) systems, although the silane/solvent used there is different, suggesting that geometric constraints are not required for useable reactivity. However, this is an effective design principle for some substrates/reactions. The key features of the catalytic system described here, however, are simplicity and cost. As all reagents are commercially available and easy to handle, there is no barrier to entry into these catalytic reactions, broadening their potential applicability in a range of settings.

Mechanistic Studies

Click to copy section linkSection link copied!
Experimental and computational mechanistic studies were undertaken to probe the pathways underpinning the HDF reaction. Under the optimized reaction conditions for the HDF of 1 (Table 1, entry 6) the reaction occurred too quickly to observe any intermediates. However, for slower reactions it was possible to gain insights through the observation of intermediate phosphorus-containing species. When 1 was reacted with PhSiH3, with 10 mol % PnBu3 in MeCN at 20 °C, after 1 h the 31P NMR spectrum showed very clean conversion of PnBu3 into a new species with an apparent septet resonance at δ = 38.1 ppm (J = ca. 5 Hz). This was accompanied by new complex multiplet signals in the 19F NMR spectrum at δ = −88.5 and −130.3 ppm. The only other resonances present in the 19F NMR were from unreacted 1, the HDF product 2 and the fluorosilane produced by H/F exchange. The resonance at δ = 38.1 ppm in the 31P NMR spectrum is characteristic of a phosphonium cation and was therefore assigned to the [(C5F4N)PnBu3]+ ion, [17]+. This was confirmed by independent preparation of [(C5F4N)PnBu3]Br ([17]Br) by reaction of PnBu3 with 4-bromo-2,3,5,6-tetrafluoropyridine (Scheme 3), which displayed virtually identical spectroscopic signals (31P δ = 37.9 ppm and 19F δ = −89.2 and 130.3 ppm) and coupling patterns. Similar addition of phosphines (e.g., PPh3) to activated pyridines (N-trifluoromethanesulfonylpyridinium salts) to give phosphonium salts has been observed previously. (69) In addition, phosphonium salts derived from fluoroalkanes have been formed by FLP systems through aliphatic C–F activation by a strong Lewis acid (e.g., B(C6F5)3), followed by trapping of the resulting carbocation by PR3. (70,71) Related fluorinated phosphonium salts, e.g., [(C6F5)3PF][B(C6F5)4], have also been used in the catalytic HDF of fluoroalkanes. (56−58) However, these species are substantially more Lewis acidic than ions such as [17]+ and directly abstract fluoride from aliphatic C–F bonds, which is very different from the role of the phosphonium salts described here (see below). At the end of the catalytic reaction, when 1 was fully consumed, the signal for [17]+ disappeared and free phosphine was observed in the reaction mixture (31P δ = −32.1 ppm), suggesting its role as a resting state.

Scheme 3

Scheme 3. Preparation of Phosphonium Ions Proposed to be Intermediates in the Catalytic Reactions and their Reactivity Toward Silanes in the Presence, and Absence, of a Fluoride Source
High Resolution Image
Download MS PowerPoint Slide
To investigate whether [17]+ was a relevant catalytic intermediate, Ph2SiH2 was added to the independently prepared sample of [17]Br in MeCN (Scheme 3). After 10 min at 20 °C, there was no change in the 31P or 19F NMR spectra. The mixture was heated to 40 °C overnight and similarly showed no reaction between [17]Br and the silane. However, on addition of 1 equiv. anhydrous [Me4N]F to the system at 20 °C, 2 was seen to form after only 10 min, alongside the formation of fluorosilane Ph2Si(F)nH2–n and some unreacted [17]+. Over time, the amount of 2 increased as the concentration of [17]+ decreased. This suggested that [17]+ is an intermediate in the catalytic cycle but that it does not react directly with the silane to form the HDF product. We propose that the addition of fluoride to the silane to form a silicate anion, [Ph2Si(F)H2]−, is necessary to promote H– transfer and liberation of the hydrodefluorinated product. Similar silane/silicate reactivity has been reported by Ogoshi and co-workers in metal-free HDF reactions using catalytic [Bu4N][Ph3SiF2] (TBAT). (60) In their case, it was proposed that fluoride transfer from TBAT to silanes, such as Ph3SiH, generated hydrofluorosilicate ions that through ligand redistribution form transient dihydrosilicate ions, ultimately performing HDF of fluoroarenes. In the present work, it is not clear whether mono- or dihydrosilicate ions are involved in hydride transfer to phosphonium ions like [17]+. In order to assess the potential role of hydride transfer directly from a hydrosilicate anion to 1, i.e., bypassing the phosphine-induced HDF, a control reaction was run where 1, Ph2SiH2 and 10 mol % of [NMe4]F were allowed to react in MeCN at 20 °C. After 20 min some of the HDF product 2 was formed, but only in 19% yield, alongside mostly unreacted 1. After 18 h, the same reaction had reached a yield of 64% of 2. This contrasts strongly with the reactivity mediated by PnBu3 (Table 1, entry 6) where 93% of 2 was formed under analogous conditions after only 20 min. Thus, it is possible to conclude that for 1 as a substrate, direct HDF of 1 by catalytic hydrosilicate anions, formed in situ by reaction of 1 with PnBu3, is possible but significantly slower than HDF through a phosphine-mediated pathway.
An additional possibility that was explored to explain the need for fluoride to be present to initiate a reaction between [17]+ and Ph2SiH2 was fluoride addition to [17]+ to form a fluorophosphorane, which could aid Ph2SiH2 activation through an FLP-type mechanism similar to that proposed by Piers for Si–H activation. (72,73) This would involve activation of the silane by the fluorophosphorane, acting as a Lewis base and donating a fluoride to the silane, alongside [17]+ acting as a Lewis acid to abstract a hydride from the silane in a concerted manner. DFT studies explored this, but a transition state associated with a concerted P–H/Si–F bond formation mechanism was not found. Instead, a two-step pathway, where fluoride transfer to Si to form a fluorosilicate anion occurs prior to hydride transfer to a phosphonium ion, was seen (see Supporting Information). Thus, we conclude from these computational studies and the fact that cations such as [17]+ are seen as intermediates in the 31P NMR spectra that fluorosilicate anion formation is a key step in the catalytic reaction mechanism.
Although the above mechanistic studies focused on intermediates in the HDF of 1, similar observations were made in other reactions. For example, when perfluorotoluene was reacted with Ph2SiH2 at 20 °C in MeCN with PnBu3 as the catalyst (10 mol %), after 10 min, the formation of a phosphonium ion was seen (31P δ = −38.1 ppm, apparent septet, ca. 4 Hz; 19F δ = −58.0 (t, 4JFF = 18 Hz), −126.8 (m), −137.3 (m) ppm), which was assigned as [(C6F4CF3)PnBu3]+ ([18]+). Also, when bromopentafluorobenzene was used as a substrate, the formation of the phosphonium salt [C6F5PnBu3]Br ([16]Br) was observed under catalytic conditions, and its concentration could be increased by addition of an extra 0.9 equiv of PnBu3, as described above and shown in Scheme 3. Under these conditions, some pentafluorobenzene was formed (35%) as a result of hydrodebromination, but the reaction was sluggish due to the slow reactivity of [16]Br with the silane. Addition of 1 equiv. [NMe4]F to this solution led to the disappearance of the peaks associated with [16]Br in the 19F NMR after 10 min at 20 °C, and to an increase in the amount of pentafluorobenzene (43%) along with the formation of some tetrafluorobenzene (16%). In addition, a new phosphonium ion was seen with 31P δ = 36.3 ppm and 19F δ = −129.7 and −135.7 ppm, which represented 43% of the fluoroarene-derived species. This was assigned as [C6F4HPnBu3]+ ([19]+) and results from the C–F activation of pentafluorobenzene in the reaction mixture by the phosphine. After 18 h at 20 °C the system evolved, leading to a slightly reduced amount of pentafluorobenzene (41%), increased amount of tetrafluorobenzene (23%), and a similar amount of the phosphonium ion [19]+ (41%). Addition of fluoride to the system appears to have significantly increased the rate of hydrodebromination, which was then followed by HDF of the pentafluorobenzene product (cf. Scheme 2, 8b). This is consistent with the proposed importance of the hydrosilicate anions in this system. Reaction of [16]Br with Ph2SiH2 to form [Ph2Si(Br)H2]− would be significantly less favorable than fluoride transfer to the silane to form [Ph2Si(F)H2]−, therefore the concentration of the hydrosilicate ions remained low and hydrodebromination was slow until a source of fluoride was added to the system.
One final observation is important to note in a mechanistic context. As described above, stoichiometric reaction of PR3 with 1 in MeCN leads to rapid formation of reductive coupling product 3 (Scheme 2, 3) alongside the formation of difluorophosphorane PR3F2. Dobrovetsky and co-workers observed similar reactivity when a geometrically constrained tetrafluoropyridyl-substituted fluorophosphorane was heated to 110 °C for 10 h in o-C6H4F2, i.e., 3 and a difluorophosphorane are formed. (21) In our system, the related phosphorane R3P(C5F4N)F is not observed, as the reaction to form 3 is fast at room temperature. However, the observation of 3 in both systems suggests that a fluorophosphorane resulting from OA of 1 to PR3 is also a likely intermediate in the PR3-promoted reaction.
Looking at the catalytic reaction as a whole, the experimental mechanistic studies suggested that the phosphine catalyst adds to the fluoroarene/heteroarene to initially form a fluorophosphorane, e.g., P(F)(nBu)3(C5F4N), but that the silane then acts as a Lewis acid to abstract a fluoride ion from the phosphorane to form a phosphonium salt, e.g., [(C5F4N)PnBu3][Ph2Si(F)H2]. We note that this reactivity is very similar to the addition of phosphines to the fluoroarene rings of B(C6F5)3, which is also followed by fluoride transfer to a Lewis acid to form a phosphonium borate salt. (7) The hydrosilicate anion then transfers a hydride to the phosphonium ion to form another phosphorane that eliminates the hydrodefluorinated product and regenerates the phosphine (Scheme 4). This H/F exchange between P and Si is driven by differences in the fluoride ion and hydride ion affinities of the phosphorane and silane, which have been discussed and computed for related species. (74−76) The reactivity of non-fluorinated pyridylphosphonium salts with nucleophiles to form substituted pyridines has also been reported and, like the processes observed here, is proposed to occur via phosphorane intermediates. (77−79) Underpinning all of this reactivity is the facile redox cycling between P(III) and P(V) oxidation states that is remarkable to see in simple trialkylphosphines.

Scheme 4

Scheme 4. Proposed Catalytic Cycle and Computed Potential Energy Surface (PES) for R = Mea
High Resolution Image
Download MS PowerPoint Slide

aAll energies at the PBE0/def2-TZVP//BP86/SV(P) level in MeCN. Relative Gibbs energies (in kJ mol–1 at 298 K) shown outside brackets and relative enthalpies (in kJ mol–1 at 298 K) shown in brackets. See Supporting Information for details of solvent and dispersion corrections applied.

DFT calculations were performed to support the experimental mechanistic studies (see Supporting Information for details). These showed that initial reaction of the phosphine with pentafluoropyridine takes place through a Meisenheimer-like transition state (Scheme 4, TS12) to form a fluorophosphorane (M2) in a similar manner to that proposed by Garcı́a and co-workers for reaction of 1 with PEt3. (64,65) This is associated with a low barrier of 55 kJ mol–1. The structure of TS12 (Figure 1) shows the early nature of this transition state, where P–C bond formation and C–F bond elongation precede fluorine transfer to phosphorus to form the phosphorane. This step is effectively initiated by a nucleophilic addition of PR3 to the pentafluoropyridine and explains the preference for electron-poor arenes and heteroarenes in this reaction, where this will be promoted. No additional intermediates or transition states for fluorine transfer to phosphorus were identified. The addition of 1 to the phosphine leads to a formal oxidation state change from P(III) to P(V) and so can be characterized as an OA process, albeit one that is highly asynchronous in terms of C–F bond cleavage and reminiscent of concerted SNAr mechanisms. (80) The key structural parameters of TS12 are almost identical to those calculated by Dobrovetsky and co-workers for addition of 1 to a geometrically constrained σ3-P compound, suggesting a similar activation process, despite the very different structural frameworks involved. (21)

Figure 1

Figure 1. Transition states for the addition of PMe3 to 1 (TS12) and elimination of 2 from phosphorane M6 (TS61). Hydrogen is shown in white, carbon in gray, phosphorus in orange, nitrogen in blue, and fluorine in green. Selected distances (in Å) are shown.

High Resolution Image
Download MS PowerPoint Slide
The fluorophosphorane that is initially formed (M2) can undergo isomerization to a lower energy isomer (M3) with fluorine trans to the tetrafluoropyridyl group, both in the apical positions. Fluoride transfer to Ph2SiH2 results in the formation of the observed phosphonium ion [6]+, in this case as the salt M4. Moving between neutral and ionic manifolds in this way will be strongly influenced by solvation effects. This leads to a small mismatch between the computed energies and the experimental observations, where M4 is higher in energy than the phosphoranes, although phosphonium ions and not the phosphoranes are observed experimentally. This is likely due to limitations in using a dielectric continuum solvation model, which undersolvates the ions and raises their energies relative to neutral species. The neutral/ionic manifold switch may help to explain the solvent effect seen in this system, where moving from o-C6H4F2 (ε 13.4 = at 25 °C) to the more polar MeCN (ε = 35.9 at 25 °C) led to an increase in the catalytic rate. (81,82) It is well-known that more polar solvents like MeCN promote the formation of ionic species from phosphoranes, and this would facilitate the formation of M4.
Hydride transfer from the silicate anion then leads to phosphorane M5, which can isomerize to form M6. This is very different from the mechanistic proposal of Dobrovetsky for HDF by geometrically constrained σ3-P systems, (21) where it was suggested that PhSiH3 reacts directly with the fluorophosphorane through a transition state that involves concerted hydride transfer to P and fluoride transfer to Si. The experiments described above showed that for simple trialkylphosphines, phosphonium ions are intermediates, and these do not react directly with the neutral silanes. It may be that the positive charge on Dobrovetsky’s constrained σ3-P systems disfavors this pathway and leads to this divergence in mechanistic behavior.
The final step involves the RE of 2 from M6 via TS61 (Figure 1). This transition state is more concerted than TS12, although still somewhat asynchronous, presumably because direct concerted RE from the axial and equatorial positions of a phosphorane is symmetry forbidden. (83) TS61 is again Meisenheimer-like, although less so than in the constrained σ3-P systems of Radosevich, (23) where the C–H bond length of a related RE TS is 1.33 Å, and Dobrovetsky where it is 1.53 Å. (21) It seems as though the substituents and geometric environment around phosphorus have a significant impact on the RE process. These final steps give rise to the energetic span for the reaction, which is defined by turnover-determining intermediate (TDI) M5 and transition state (TDTS) TS61, and give an overall barrier for the catalytic reaction of 79 kJ mol–1. This low barrier is consistent with the observed fast reaction between 1 and Ph2SiH2 when a sterically relatively small phosphine like PnBu3 is used as the catalyst (full conversion in 20 min at 20 °C in MeCN). The calculated energetic span for HDF of 1 by a constrained σ3-P system was significantly larger (140 kJ mol–1), which is consistent with the slower reactions observed in that study. (21)

Conclusions

Click to copy section linkSection link copied!
These data demonstrate that complex molecular architectures are not required to allow P(III) systems to act as catalysts for HDF or aminodefluorination of highly fluorinated arenes and heterocycles. In fact, simple trialkylphosphines were found to be fast and effective catalysts for these reactions for a range of substrates, but especially those that are highly electron poor. This is an important observation as some trialkylphosphines, especially the PnBu3 used here, are cheap, readily available from commercial suppliers and simple to handle. This eliminates the barrier to entry that exists for some main-group catalyst systems, and so these reactions can be widely applied in a range of academic and industrial settings.
Mechanistic studies demonstrated that the catalytic HDF reactions described here are underpinned by metallomimetic behavior that is remarkable for such simple phosphines. Facile P(III)/P(V) redox cycling allows the phosphine to undergo OA of the substrates and RE of the products. Phosphonium ions, e.g., [(C5F4N)PnBu3]+ ion, [17]+, were identified as key intermediates during catalysis. These are proposed to undergo hydride transfer from their hydrosilicate counterions, as part of a transition-metal-like transmetalation step in the catalytic cycle, prior to elimination of the products. This helps to explain the solvent and silane dependence of the observed reactions, where more polar solvents promote the formation of the phosphonium salts and specific substituents on the silane favor/disfavor formation of the silicate anions.

Supporting Information

Click to copy section linkSection link copied!

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.3c10614.

  • Experimental and computational methods, key spectroscopic data, and computational results, including energies and xyz coordinates (PDF)

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Author Information

Click to copy section linkSection link copied!

Acknowledgments

Click to copy section linkSection link copied!

This work has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 860322. We are grateful to the CNRS (Centre National de la Recherche Scientifique) and the University of York for providing access to facilities. J.M.L. is supported by an Industry Fellowship from the Royal Society (INF\R1\221057). Part of the computational work in this project was undertaken on the Viking Cluster, which is a high-performance computer facility provided by the University of York. The authors are grateful for computational support from the University of York High Performance Computing service, Viking and the Research Computing team. The authors are grateful to Professor Robin Perutz for very helpful and insightful discussions.

References

Click to copy section linkSection link copied!

This article references 83 other publications.

  1. 1
    Power, P. P. Main-Group Elements as Transition Metals. Nature 2010, 463, 171– 177,  DOI: 10.1038/nature08634
    Google Scholar
    1
    Main-group elements as transition metals
    Power, Philip P.
    Nature (London, United Kingdom) (2010), 463 (7278), 171-177CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)
    A review. The last quarter of the twentieth century and the beginning decade of the twenty-first witnessed spectacular discoveries in the chem. of the heavier main-group elements. The discoveries that led to this change originated from a simple desire to synthesize main-group compds. that were unknown as stable species. These featured one or more of the following: (1) multiple bonds between heavier main-group elements such as Al, Si, P or their heavier congeners; (2) stable low-valent derivs. with open coordination sites; (3) mols. with quasi-open coordination sites as a result of frustrated Lewis pairs; (4) stable paramagnetic electron configurations (that is radicals) with unpaired electrons centered on heavier main-group elements; or (5) stable singlet diradicaloid electron configurations. The new compds. that were synthesized highlighted the fundamental differences between their electronic properties and those of the lighter elements to a degree that was not previously apparent. This led to new structural and bonding insights as well as a gradually increasing realization that the chem. of the heavier main-group elements more resembles that of transition-metal complexes than that of their lighter main-group congeners. The similarity is underlined by recent work, which showed that many of the new compds. react with small mols. such as H2, NH3, C2H4 or CO under mild conditions and display potential for applications in catalysis.
  2. 2
    Weetman, C.; Inoue, S. The Road Travelled: After Main-Group Elements as Transition Metals. ChemCatChem 2018, 10, 4213– 4228,  DOI: 10.1002/cctc.201800963
    Google Scholar
    2
    The Road Travelled: After Main-Group Elements as Transition Metals
    Weetman, Catherine; Inoue, Shigeyoshi
    ChemCatChem (2018), 10 (19), 4213-4228CODEN: CHEMK3; ISSN:1867-3880. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Since the latter quarter of the twentieth century, main group chem. has undergone significant advances. Power's timely review in 2010 highlighted the inherent differences between the lighter and heavier main group elements, and that the heavier analogs resemble transition metals as shown by their reactivity towards small mols. In this concept article, we present an overview of the last 10 years since Power's seminal review, and the progress made for catalytic application. This examines the use of low oxidn. state and/or low coordinate group 13 and 14 complexes towards small mol. activation (oxidative addn. step in a redox based cycle) and how ligand design plays a crucial role in influencing subsequent reactivity. The challenge in these redox based catalytic cycles still centers on the main group complexes' ability to undergo reductive elimination, however considerable progress in this field has been reported via reversible oxidative addn. reactions. Within the last 5 years, the first examples of well-defined low valent main group catalysts have begun to emerge, representing a bright future ahead for main group chem.
  3. 3
    Melen, R. L. Frontiers in Molecular p-Block Chemistry: From Structure to Reactivity. Science 2019, 363, 479– 484,  DOI: 10.1126/science.aau5105
    Google Scholar
    3
    Frontiers in molecular p-block chemistry: From structure to reactivity
    Melen, Rebecca L.
    Science (Washington, DC, United States) (2019), 363 (6426), 479-484CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
    A review. This year marks the 350th anniversary of the discovery of phosphorus by the alchemist Hennig Brand. However, this element was not included in the p-block of the periodic table until more recently. 2019 also marks the 150th anniversary of the preliminary tabular arrangement of the elements into the periodic system by Mendeleev. Of the 63 elements known in 1869, almost one-third of them belonged to what ultimately became the p-block, and Mendeleev predicted the existence of both gallium and germanium as well. The elements of the p-block have a disparate and varied history. Their chem. structure, reactivity, and properties vary widely. Nevertheless, in recent years, a better understanding of trends in p-block reactivity, particularly the behavior of those elements not typically found in biol. systems, has led to a promising array of emerging applications, highlighted herein.
  4. 4
    Weetman, C. Main Group Multiple Bonds for Bond Activations and Catalysis. Chem.─Eur. J. 2021, 27, 1941– 1954,  DOI: 10.1002/chem.202002939
    Google Scholar
    4
    Main Group Multiple Bonds for Bond Activations and Catalysis
    Weetman, Catherine
    Chemistry - A European Journal (2021), 27 (6), 1941-1954CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. Since the discovery that the so-called "double-bond" rule could be broken, the field of mol. main group multiple bonds has expanded rapidly. With the majority of homodiat. double and triple bonds realized within the p-block, along with many heterodiat. combinations, this Minireview examines the reactivity of these compds. with a particular emphasis on small mol. activation. Furthermore, while their ability to act as transition metal mimics has been explored, their catalytic behavior is somewhat limited. This Minireview aims to highlight the potential of these complexes towards catalytic application and their role as synthons in further functionalizations making them a versatile tool for the modern synthetic chemist.
  5. 5
    Braunschweig, H.; Krummenacher, I.; Legare, M. A.; Matler, A.; Radacki, K.; Ye, Q. Main-Group Metallomimetics: Transition Metal-like Photolytic CO Substitution at Boron. J. Am. Chem. Soc. 2017, 139, 1802– 1805,  DOI: 10.1021/jacs.6b13047
    Google Scholar
    5
    Main-Group Metallomimetics: Transition Metal-like Photolytic CO Substitution at Boron
    Braunschweig, Holger; Krummenacher, Ivo; Legare, Marc-Andre; Matler, Alexander; Radacki, Krzysztof; Ye, Qing
    Journal of the American Chemical Society (2017), 139 (5), 1802-1805CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    The carbon monoxide adduct of an unhindered and highly reactive CAAC-bound arylborylene, [(CAAC)B(CO)Ar] (CAAC = cyclic (alkyl) (amino)carbene), has been prepd. using a transfer reaction from the linear iron borylene complex [(PMe3) (CO)3Fe:BAr]. [(CAAC)B(CO)Ar] is a source of the dicoordinate [(CAAC)ArB:] borylene that can be liberated by selective photolytic CO extrusion and that, although highly reactive, is sufficiently long-lived to react intermolecularly. Through trapping of the borylene generated in this manner, we present, among others, the first metal-free borylene(I) species contg. a nitrogen-based donor, as well as a new boron-contg. radical.
  6. 6
    Légaré, M. A.; Pranckevicius, C.; Braunschweig, H. Metallomimetic Chemistry of Boron. Chem. Rev. 2019, 119, 8231– 8261,  DOI: 10.1021/acs.chemrev.8b00561
    Google Scholar
    6
    Metallomimetic Chemistry of Boron
    Legare, Marc-Andre; Pranckevicius, Conor; Braunschweig, Holger
    Chemical Reviews (Washington, DC, United States) (2019), 119 (14), 8231-8261CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
    A review. The study of main-group mols. that behave and react similarly to transition metal (TM) complexes has attracted significant interest in the recent decades. Most notably, the attractive idea of replacing the all-too-often rare and costly metals from catalysis has motivated efforts to develop main group element-mediated reactions. Main group elements, however, lack the electronic flexibility of many TM complexes that arise from combinations of empty and filled d-orbitals and that seem ideally suited to bind and activate many substrates. In this review, we look at boron, an element that despite its nonmetal nature, low at. wt., and relative redox staticity has achieved great milestones in terms of TM-like reactivity. We show how in interelement cooperative systems, diboron mols. and hypovalent complexes, the fifth element can acquire a truly metallomimetic character. As we discuss, this character is particularly demonstrated by the reactivity of boron-based mols. with H2, CO, alkynes, alkenes and even with N2.
  7. 7
    Welch, G. C.; Juan, R. R. S.; Masuda, J. D.; Stephan, D. W. Reversible, Metal-Free Hydrogen Activation. Science 2006, 314, 1124– 1126,  DOI: 10.1126/science.1134230
    Google Scholar
    7
    Reversible, Metal-Free Hydrogen Activation
    Welch, Gregory C.; San Juan, Ronan R.; Masuda, Jason D.; Stephan, Douglas W.
    Science (Washington, DC, United States) (2006), 314 (5802), 1124-1126CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
    Although reversible covalent activation of mol. hydrogen (H2) is a common reaction at transition metal centers, it has proven elusive in compds. of the lighter elements. The compd. (C6H2Me3)2PH(C6F4)BH(C6F5)2 (Me, methyl), which was derived through an unusual reaction involving dimesitylphosphine substitution at a para carbon of tris(pentafluorophenyl)borane, cleanly loses H2 at temps. above 100°. Preliminary kinetic studies reveal this process to be first order. Remarkably, the dehydrogenated product (C6H2Me3)2P(C6F4)B(C6F5)2 is stable and reacts with 1 atm of H2 at 25° to reform the starting complex. Deuteration studies were also carried out to probe the mechanism.
  8. 8
    Stephan, D. W.; Erker, G. Frustrated Lewis Pairs: Metal-free Hydrogen Activation and More. Angew. Chem., Int. Ed. 2010, 49, 46– 76,  DOI: 10.1002/anie.200903708
    Google Scholar
    8
    Frustrated Lewis Pairs: Metal-free Hydrogen Activation and More
    Stephan, Douglas W.; Erker, Gerhard
    Angewandte Chemie, International Edition (2010), 49 (1), 46-76CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. Sterically encumbered Lewis acid and Lewis base combinations do not undergo the ubiquitous neutralization reaction to form classical Lewis acid/Lewis base adducts. Rather, both the unquenched Lewis acidity and basicity of such sterically frustrated Lewis pairs (FLPs) is available to carry out unusual reactions. Typical examples of frustrated Lewis pairs are inter- or intramol. combinations of bulky phosphines or amines with strongly electrophilic RB(C6F5)2 components. Many examples of such frustrated Lewis pairs are able to cleave dihydrogen heterolytically. The resulting H+/H- pairs (stabilized for example, as the resp. phosphonium cation/hydridoborate anion salts) serve as active metal-free catalysts for the hydrogenation of, for example, bulky imines, enamines, or enol ethers. Frustrated Lewis pairs also react with alkenes, aldehydes, and a variety of other small mols., including carbon dioxide, in cooperative three-component reactions, offering new strategies for synthetic chem.
  9. 9
    Stephan, D. W.; Erker, G. Frustrated Lewis Pair Chemistry of Carbon, Nitrogen and Sulfur Oxides. Chem. Sci. 2014, 5, 2625– 2641,  DOI: 10.1039/C4SC00395K
    Google Scholar
    9
    Frustrated Lewis pair chemistry of carbon, nitrogen and sulfur oxides
    Stephan, Douglas W.; Erker, Gerhard
    Chemical Science (2014), 5 (7), 2625-2641CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
    Frustrated Lewis pairs have been used to activate a variety of small mols. In this review we focus on the recent chem. of FLPs with CO2, CO, N2O, NO and SO2. While FLP capture of these small mol. is achieved in all of these cases, subsequent applications of the products include stoichiometric and catalytic redns. of CO2, C-O bond scission of CO and use of FLP-NO radicals in polymn.
  10. 10
    Stephan, D. W. Frustrated Lewis Pairs. J. Am. Chem. Soc. 2015, 137, 10018– 10032,  DOI: 10.1021/jacs.5b06794
    Google Scholar
    10
    Frustrated Lewis Pairs
    Stephan, Douglas W.
    Journal of the American Chemical Society (2015), 137 (32), 10018-10032CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    A review. The articulation of the notion of "frustrated Lewis pairs" (FLPs), which emerged from the discovery that H2 can be reversibly activated by combinations of sterically encumbered Lewis acids and bases, has prompted a great deal of recent activity. Perhaps the most remarkable consequence has been the development of FLP catalysts for the hydrogenation of a range of org. substrates. In the past 9 years, the substrate scope has evolved from bulky polar species to include a wide range of unsatd. org. mols. In addn., effective stereoselective metal-free hydrogenation catalysts have begun to emerge. The mechanism of this activation of H2 has been explored, and the nature and range of Lewis acid/base combinations capable of effecting such activation have also expanded to include a variety of non-metal species. The reactivity of FLPs with a variety of other small mols., including olefins, alkynes, and a range of element oxides, has also been developed. Although much of this latter chem. has uncovered unique stoichiometric transformations, metal-free catalytic hydroamination, CO2 redn. chem., and applications in polymn. have also been achieved. The concept is also beginning to find applications in bioinorg. and materials chem. as well as heterogeneous catalysis. This Perspective highlights many of these developments and discusses the relationship between FLPs and established chem. Some of the directions and developments that are likely to emerge from FLP chem. in the future are also presented.
  11. 11
    Stephan, D. W. Frustrated Lewis Pairs: From Concept to Catalysis. Acc. Chem. Res. 2015, 48, 306– 316,  DOI: 10.1021/ar500375j
    Google Scholar
    11
    Frustrated Lewis Pairs: From Concept to Catalysis
    Stephan, Douglas W.
    Accounts of Chemical Research (2015), 48 (2), 306-316CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)
    A review. Frustrated Lewis pair (FLP) chem. has emerged in the past decade as a strategy that enables main-group compds. to activate small mols. This concept is based on the notion that combinations of Lewis acids and bases that are sterically prevented from forming classical Lewis acid-base adducts have Lewis acidity and basicity available for interaction with a third mol. This concept has been applied to stoichiometric reactivity and then extended to catalysis. This Account describes three examples of such developments: hydrogenation, hydroamination, and CO2 redn. The most dramatic finding from FLP chem. was the discovery that FLPs can activate H2, thus countering the long-existing dogma that metals are required for such activation. This finding of stoichiometric reactivity was subsequently evolved to employ simple main-group species as catalysts in hydrogenations. While the initial studies focused on imines, subsequent studies uncovered FLP catalysts for a variety of org. substrates, including enamines, silyl enol ethers, olefins, and alkynes. Moreover, FLP redns. of arom. anilines and N-heterocycles have been developed, while very recent extensions have uncovered the utility of FLP catalysts for ketone redns. FLPs have also been shown to undergo stoichiometric reactivity with terminal alkynes. Typically, either deprotonation or FLP addn. reaction products are obsd., depending largely on the basicity of the Lewis base. While a variety of acid/base combinations have been exploited to afford a variety of zwitterionic products, this reactivity can also be extended to catalysis. When secondary aryl amines are employed, hydroamination of alkynes can be performed catalytically, providing a facile, metal-free route to enamines. In a similar fashion, initial studies of FLPs with CO2 demonstrated their ability to capture this greenhouse gas. Again, modification of the constituents of the FLP led to the discovery of reaction systems that demonstrated stoichiometric redn. of CO2 to either methanol or CO. Further modification led to the development of catalytic systems for the redn. of CO2 by hydrosilylation and hydroboration or deoxygenation. As each of these areas of FLP chem. has advanced from the observation of unusual stoichiometric reactions to catalytic processes, it is clear that the concept of FLPs provides a new strategy for the design and application of main-group chem. and the development of new metal-free catalytic processes.
  12. 12
    Lam, J.; Szkop, K. M.; Mosaferi, E.; Stephan, D. W. FLP Catalysis: Main Group Hydrogenations of Organic Unsaturated Substrates. Chem. Soc. Rev. 2019, 48, 3592– 3612,  DOI: 10.1039/C8CS00277K
    Google Scholar
    12
    FLP catalysis: main group hydrogenations of organic unsaturated substrates
    Lam, Jolie; Szkop, Kevin M.; Mosaferi, Eliar; Stephan, Douglas W.
    Chemical Society Reviews (2019), 48 (13), 3592-3612CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
    A review. This article is focused on recent developments in main group mediated hydrogenation chem. and catalysis using 'frustrated Lewis pairs' (FLPs). The broading range of substrates and catalyst systems is reviewed and the advances in catalytic redns. and the development of stereoselective, asym. redns. made since 2012 was considered.
  13. 13
    Paradies, J. From Structure to Novel Reactivity in Frustrated Lewis Pairs. Coord. Chem. Rev. 2019, 380, 170– 183,  DOI: 10.1016/j.ccr.2018.09.014
    Google Scholar
    13
    From structure to novel reactivity in frustrated Lewis pairs
    Paradies, Jan
    Coordination Chemistry Reviews (2019), 380 (), 170-183CODEN: CCHRAM; ISSN:0010-8545. (Elsevier B.V.)
    A review. The coexistence of a strong Lewis acid and a Lewis base in soln., the so called frustrated Lewis pair, has led to the discovery of metal-free hydrogen activation. Since then, this observation has inspired numerous chemists to develop more examples. Metal-free hydrogenation is so far the most studied application of frustrated Lewis pairs in chem. and highly efficient methodologies for a no. of substrates have been developed. However, the targeted choice of a FLP-catalyst is yet rather intricate, due to the lack of an in depth understanding of FLP-reactivity. The presented structure-reactivity-relationship for hydrogenation reactions allowed the targeted development and optimization of unprecedented reactions using FLPs as catalysts. This article provides insight into FLP-reactivity by summarizing our mechanistic and synthetic work in this field.
  14. 14
    Li, N.; Zhang, W. X. Frustrated Lewis Pairs: Discovery and Overviews in Catalysis. Chin. J. Chem. 2020, 38, 1360– 1370,  DOI: 10.1002/cjoc.202000027
    Google Scholar
    14
    Frustrated Lewis Pairs: Discovery and Overviews in Catalysis
    Li, Nan; Zhang, Wen-Xiong
    Chinese Journal of Chemistry (2020), 38 (11), 1360-1370CODEN: CJOCEV; ISSN:1001-604X. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. Frustrated Lewis Pairs (FLPs) are derived from simple combinations of Lewis acids (electron acceptors) and Lewis bases (electron donors), in which steric demands prevent from forming classical Lewis acid-base adducts. Since 2006, FLP chem. has emerged as a novel strategy for the design and application of main-group chem. and development of new metal-free catalytic processes. This strategy has been applied to stoichiometric reactivity and then extended to catalysis. In this review, the representative discoveries and developments of FLP chem. in the field of catalysis, including hydrogenation, hydrosilylation, redn. of CO2, transformations of alkynes to org. derivs., C-H bond borylation and polymn. have been briefly summarized.
  15. 15
    Stephan, D. W.; Erker, G. Frustrated Lewis Pair Chemistry: Development and Perspectives. Angew. Chem., Int. Ed. 2015, 54, 6400– 6441,  DOI: 10.1002/anie.201409800
    Google Scholar
    15
    Frustrated Lewis Pair Chemistry: Development and Perspectives
    Stephan, Douglas W.; Erker, Gerhard
    Angewandte Chemie, International Edition (2015), 54 (22), 6400-6441CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. Frustrated Lewis pairs (FLPs) are combinations of Lewis acids and Lewis bases in soln. that are deterred from strong adduct formation by steric and/or electronic factors. This opens pathways to novel cooperative reactions with added substrates. Small-mol. binding and activation by FLPs has led to the discovery of a variety of new reactions through unprecedented pathways. Hydrogen activation and subsequent manipulation in metal-free catalytic hydrogenations is a frequently obsd. feature of many FLPs. The current state of this young but rapidly expanding field is outlined in this Review and the future directions for its broadening sphere of impact are considered.
  16. 16
    Chu, T.; Nikonov, G. I. Oxidative Addition and Reductive Elimination at Main-Group Element Centers. Chem. Rev. 2018, 118, 3608– 3680,  DOI: 10.1021/acs.chemrev.7b00572
    Google Scholar
    16
    Oxidative Addition and Reductive Elimination at Main-Group Element Centers
    Chu, Terry; Nikonov, Georgii I.
    Chemical Reviews (Washington, DC, United States) (2018), 118 (7), 3608-3680CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
    A review. Oxidative addn. and reductive elimination are key steps in a wide variety of catalytic reactions mediated by transition-metal complexes. Historically, this reactivity was considered to be the exclusive domain of d-block elements. However, this paradigm has changed in recent years with the demonstration of transition-metal-like reactivity by main-group compds. This Review highlights the substantial progress achieved in the past decade for the activation of robust single bonds by main-group compds. and the more recently realized activation of multiple bonds by these elements. The authors also discuss the significant discovery of reversible activation of single bonds and distinct examples of reductive elimination at main-group element centers. The review consists of three major parts, starting with oxidative addn. of single bonds, proceeding to cleavage of multiple bonds, and culminated by the discussion of reversible bond activation and reductive elimination. Within each subsection, the discussion is arranged according to the type of bond being cleaved or formed and considers elements from the left to the right of each period and down each group of the periodic table. The majority of results discussed in this Review come from the past decade; however, earlier reports are also included to ensure completeness.
  17. 17
    Lipshultz, J. M.; Li, G.; Radosevich, A. T. Main Group Redox Catalysis of Organopnictogens: Vertical Periodic Trends and Emerging Opportunities in Group 15. J. Am. Chem. Soc. 2021, 143, 1699– 1721,  DOI: 10.1021/jacs.0c12816
    Google Scholar
    17
    Main Group Redox Catalysis of Organopnictogens: Vertical Periodic Trends and Emerging Opportunities in Group 15
    Lipshultz, Jeffrey M.; Li, Gen; Radosevich, Alexander T.
    Journal of the American Chemical Society (2021), 143 (4), 1699-1721CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    A review. A growing no. of organopnictogen redox catalytic methods have emerged-esp. within the past 10 years-that leverage the plentiful reversible two-electron redox chem. within Group 15. The goal of this Perspective is to provide readers the context to understand the dramatic developments in organopnictogen catalysis over the past decade with an eye toward future development. An exposition of the fundamental differences in the at. structure and bonding of the pnictogens, and thus the mol. electronic structure of organopnictogen compds., is presented to establish the backdrop against which organopnictogen redox reactivity-and ultimately catalysis-is framed. A deep appreciation of these underlying periodic principles informs an understanding of the differing modes of organopnictogen redox catalysis and evokes the key challenges to the field moving forward. We close by addressing forward-looking directions likely to animate this area in the years to come. What new catalytic manifolds can be developed through creative catalyst and reaction design that take advantage of the intrinsic redox reactivity of the pnictogens to drive new discoveries in catalysis.
  18. 18
    Abbenseth, J.; Goicoechea, J. M. Recent Developments in the Chemistry of Non-Trigonal Pnictogen Pincer Compounds: From Bonding to Catalysis. Chem. Sci. 2020, 11, 9728– 9740,  DOI: 10.1039/D0SC03819A
    Google Scholar
    18
    Recent developments in the chemistry of non-trigonal pnictogen pincer compounds: from bonding to catalysis
    Abbenseth, Josh; Goicoechea, Jose M.
    Chemical Science (2020), 11 (36), 9728-9740CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
    The combination of well-established meridionally coordinating, tridentate pincer ligands with group 15 elements affords geometrically constrained non-trigonal pnictogen pincer compds. These species show remarkable activity in challenging element-hydrogen bond scission reactions, such as the activation of ammonia. The electronic structures of these compds. and the implications they have on their electrochem. properties and transition metal coordination are described. Furthermore, stoichiometric and catalytic bond forming reactions involving B-H, N-H and O-H bonds as well as carbon nucleophiles are presented.
  19. 19
    Kundu, S. Pincer-Type Ligand-Assisted Catalysis and Small-Molecule Activation by Non-VSEPR Main-Group Compounds. Chem.─Asian J. 2020, 15, 3209– 3224,  DOI: 10.1002/asia.202000800
    Google Scholar
    19
    Pincer-Type Ligand-Assisted Catalysis and Small-Molecule Activation by non-VSEPR Main-Group Compounds
    Kundu, Subrata
    Chemistry - An Asian Journal (2020), 15 (20), 3209-3224CODEN: CAAJBI; ISSN:1861-4728. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review focuses on the synthesis and the structural aspects of the geometry constrained main-group compds. using pincer ligands with emphasis placed on their applications on catalytic activity and small mols. activation. In 2005, a facile dihydrogen activation is reported by the Power group using an alkyne analog of Ge [ArGe GeAr; Ar = 2,6-Trip2-C6H3 (Trip = 2,4,6-iPr3-C6H2)]. After that, a significant progress was made in the activation of various small mols. by main-group compds., and a variety of stoichiometric and catalytic processes were formulated using the p-block elements. In this regard, compds. contg. low-valent main-group elements with a frontier orbitals of relatively small energy gaps or compds. forming frustrated Lewis pair (FLP) became quite successful. In spite of these promising stoichiometric and catalytic transformations, redox-cycling catalysts based on main-group elements remain extremely rare. Recently, pincer type ligands supported geometry constrained main-group compds. are capable of acting as redox catalysts similar to those of the transition metals.
  20. 20
    Brand, A.; Uhl, W. Sterically Constrained Bicyclic Phosphines: A Class of Fascinating Compounds Suitable for Application in Small Molecule Activation and Coordination Chemistry. Chem.─Eur. J. 2019, 25, 1391– 1404,  DOI: 10.1002/chem.201803331
    Google Scholar
    20
    Sterically Constrained Bicyclic Phosphines: A Class of Fascinating Compounds Suitable for Application in Small Molecule Activation and Coordination Chemistry
    Brand, Alexander; Uhl, Werner
    Chemistry - A European Journal (2019), 25 (6), 1391-1404CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review of bicyclic phosphines with two annulated, electronically unsatd. five-membered heterocycles are available through facile routes. In most cases, their P atoms are bound to heteroatoms such as O or N (PN3 or PN2O), whereas homoleptic coordination by three sp2-hybridized C atoms is reported only recently. Steric strain causes unique reactivity. Oxidative addn. of halogens, N-H or O-H bonds have afforded phosphoranes as valuable materials for secondary processes. Ring opening was identified as an important step for the understanding of these reactions and was obsd. exptl. with a diphosphorus-based ring system. A PH2 deriv. was considered as a model system for small mol. activation, and H transfer to a diazo compd. was obsd. exptl. Several of these phosphines are excellent ligands for the coordination of transition-metal atoms. The very bulky PC3 compd. has a basicity similar to that of PPh3 and may gave complexes with unusually low coordination nos. at the metal atoms. These phosphines found recently renewed interest as promising reagents in various secondary transformations such as the activation of σ-bonds or in coordination chem.
  21. 21
    Chulsky, K.; Malahov, I.; Bawari, D.; Dobrovetsky, R. Metallomimetic Chemistry of a Cationic, Geometrically Constrained Phosphine in the Catalytic Hydrodefluorination and Amination of Ar-F Bonds. J. Am. Chem. Soc. 2023, 145, 3786– 3794,  DOI: 10.1021/jacs.2c13318
    Google Scholar
    21
    Metallomimetic Chemistry of a Cationic, Geometrically Constrained Phosphine in the Catalytic Hydrodefluorination and Amination of Ar-F Bonds
    Chulsky, Karina; Malahov, Irina; Bawari, Deependra; Dobrovetsky, Roman
    Journal of the American Chemical Society (2023), 145 (6), 3786-3794CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    The synthesis, isolation and reactivity of a cationic, geometrically constrained σ3-P compd. in the hexaphenyl-carbodiphosphoranyl-based pincer-type ligand (1+) are reported. The compd. 1+ reacted with electron-poor fluoroarenes via an oxidative addn.-type reaction of the C-F bond to the PIII-center, yielding new fluorophosphorane-type species (PV). This reactivity of 1+ was used in the catalytic hydrodefluorination of Ar-F bonds with PhSiH3 to afford defluorinated arenes and in a catalytic C-N bond-forming cross-coupling reactions between fluoroarenes and aminosilanes to afford the corresponding fluorinated anilines. Importantly, the compd. 1+ in these catalytic reactions closely mimics the mode of action of the transition metal-based catalysts.
  22. 22
    Dunn, N. L.; Ha, M.; Radosevich, A. T. Main Group Redox Catalysis: Reversible PIII/PV Redox Cycling at a Phosphorus Platform. J. Am. Chem. Soc. 2012, 134, 11330– 11333,  DOI: 10.1021/ja302963p
    Google Scholar
    22
    Main Group Redox Catalysis: Reversible PIII/PV Redox Cycling at a Phosphorus Platform
    Dunn, Nicole L.; Ha, Minji; Radosevich, Alexander T.
    Journal of the American Chemical Society (2012), 134 (28), 11330-11333CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    A planar, trivalent phosphorus compd. is shown to undergo reversible two-electron redox cycling (PIII/PV) enabling its use as catalyst for a transfer hydrogenation reaction. The trivalent phosphorus compd. activates ammonia-borane to furnish a 10-P-5 dihydridophosphorane, which in turn is shown to transfer hydrogen cleanly to azobenzene, yielding diphenylhydrazine and regenerating the initial trivalent phosphorus species. This result constitutes a rare example of two-electron redox catalysis at a main group compd. and suggests broader potential for this nonmetal platform to support bond-modifying redox catalysis dominated by transition metal catalysts.
  23. 23
    Lim, S.; Radosevich, A. T. Round-Trip Oxidative Addition, Ligand Metathesis, and Reductive Elimination in a PIII/PV Synthetic Cycle. J. Am. Chem. Soc. 2020, 142, 16188– 16193,  DOI: 10.1021/jacs.0c07580
    Google Scholar
    23
    Round-Trip Oxidative Addition, Ligand Metathesis, and Reductive Elimination in a PIII/PV Synthetic Cycle
    Lim, Soohyun; Radosevich, Alexander T.
    Journal of the American Chemical Society (2020), 142 (38), 16188-16193CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    A synthetic cycle for aryl C-F substitution comprising oxidative addn., ligand metathesis, and reductive elimination at a Cs-sym. phosphorus triamide PN(2-MeNC6H4)2 (1) is reported. Reaction of 1 with perfluoroarenes (ArF-F) results in C-F oxidative addn., yielding fluorophosphoranes 1·[F][ArF]. The P-fluoro substituent is exchanged for hydride by treatment with DIBAL-H, generating hydridophosphoranes 1·[H][ArF]. Heating of 1·[H][ArF] regenerates 1 by C-H reductive elimination of ArF-H, where exptl. and computational studies establish a concerted but highly asynchronous mechanism. The results provide well-characterized examples of the full triad of elementary mechanistic aryl C-X substitution steps at a single main-group site.
  24. 24
    Pang, Y.; Leutzsch, M.; Nothling, N.; Katzenburg, F.; Cornella, J. Catalytic Hydrodefluorination via Oxidative Addition, Ligand Metathesis, and Reductive Elimination at Bi(I)/Bi(III) Centers. J. Am. Chem. Soc. 2021, 143, 12487– 12493,  DOI: 10.1021/jacs.1c06735
    Google Scholar
    24
    Catalytic Hydrodefluorination via Oxidative Addition, Ligand Metathesis, and Reductive Elimination at Bi(I)/Bi(III) Centers
    Pang, Yue; Leutzsch, Markus; Noethling, Nils; Katzenburg, Felix; Cornella, Josep
    Journal of the American Chemical Society (2021), 143 (32), 12487-12493CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Herein, authors report a hydrodefluorination reaction of polyfluoroarenes catalyzed by bismuthinidenes, Phebox-Bi(I) and OMe-Phebox-Bi(I). Mechanistic studies on the elementary steps support a Bi(I)/Bi(III) redox cycle that comprises C(sp2)-F oxidative addn., F/H ligand metathesis, and C(sp2)-H reductive elimination. Isolation and characterization of a cationic Phebox-Bi(III)(4-tetrafluoropyridyl) triflate manifests the feasible oxidative addn. of Phebox-Bi(I) into the C(sp2)-F bond. Spectroscopic evidence was provided for the formation of a transient Phebox-Bi(III)(4-tetrafluoropyridyl) hydride during catalysis, which decomps. at low temp. to afford the corresponding C(sp2)-H bond while regenerating the propagating Phebox-Bi(I). This protocol represents a distinct catalytic example where a main-group center performs three elementary organometallic steps in a low-valent redox manifold.
  25. 25
    Lee, K.; Blake, A. V.; Tanushi, A.; McCarthy, S. M.; Kim, D.; Loria, S. M.; Donahue, C. M.; Spielvogel, K. D.; Keith, J. M.; Daly, S. R.; Radosevich, A. T. Validating the Biphilic Hypothesis of Nontrigonal Phosphorus(III) Compounds. Angew. Chem., Int. Ed. 2019, 58, 6993– 6998,  DOI: 10.1002/anie.201901779
    Google Scholar
    25
    Validating the Biphilic Hypothesis of Nontrigonal Phosphorus(III) Compounds
    Lee, Kyounghoon; Blake, Anastasia V.; Tanushi, Akira; McCarthy, Sean M.; Kim, Daniel; Loria, Sydney M.; Donahue, Courtney M.; Spielvogel, Kyle D.; Keith, Jason M.; Daly, Scott R.; Radosevich, Alexander T.
    Angewandte Chemie, International Edition (2019), 58 (21), 6993-6998CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Constraining σ3-P compds. in nontrigonal, entatic geometries proved to be an effective strategy for promoting biphilic oxidative addn. reactions more typical of transition metals. Although qual. descriptions of the impact of structure and symmetry on σ3-P complexes are proposed, electronic structure variations responsible for biphilic reactivity have yet to be elucidated exptl. Reported here are P K-edge XANES data and complementary TDDFT calcns. for structurally modified P(N)3 complexes that both validate and quantify electronic structure variations proposed to give rise to biphilic reactions at P. These data are presented alongside exptl. referenced electronic structure calcns. that reveal nontrigonal structures predicted to further enhance biphilic reactivity in σ3-P ligands and catalysts.
  26. 26
    King, A. J.; Abbenseth, J.; Goicoechea, J. M. Reactivity of a Strictly T-Shaped Phosphine Ligated by an Acridane Derived NNN Pincer Ligand. Chem.─Eur. J. 2023, 29, e202300818  DOI: 10.1002/chem.202300818
    Google Scholar
    26
    Reactivity of a Strictly T-Shaped Phosphine Ligated by an Acridane Derived NNN Pincer Ligand
    King, Aaron J.; Abbenseth, Josh; Goicoechea, Jose M.
    Chemistry - A European Journal (2023), 29 (39), e202300818CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
    The steric tuning of a tridentate acridane-derived NNN pincer ligand allows for the isolation of a strictly T-shaped phosphine that exhibits ambiphilic reactivity. Well-defined phosphorus-centered reactivity towards nucleophiles and electrophiles is reported, contrasting with prior reports on this class of compds. Reactions towards oxidants are also described. The latter result in the two-electron oxidn. of the phosphorus atom from +III to +V and are accompanied by a strong geometric distortion of the NNN pincer ligand. By contrast, cooperative activation of E-H (HCl, HBcat, HOMe) bonds proceeds with retention of the phosphorus redox state. When using H2O as a substrate, the reaction results in the full disassembly of H2O to its constituent atoms, highlighting the potential of this platform for small mol. activation reactions.
  27. 27
    Wang, P. L.; Zhu, Q.; Wang, Y.; Zeng, G. X.; Zhu, J.; Zhu, C. Q. Carbon-Halogen Bond Activation by a Structurally Constrained Phosphorus(III) Platform. Chin. Chem. Lett. 2021, 32, 1432– 1436,  DOI: 10.1016/j.cclet.2020.11.005
    Google Scholar
    27
    Carbon-halogen bond activation by a structurally constrained phosphorus(III) platform
    Wang, Penglong; Zhu, Qin; Wang, Yi; Zeng, Guixiang; Zhu, Jun; Zhu, Congqing
    Chinese Chemical Letters (2021), 32 (4), 1432-1436CODEN: CCLEE7; ISSN:1001-8417. (Elsevier B.V.)
    The σ-bond activation by main group element has received enormous attention from theor. and exptl. chemists. Here, the reaction of C-X (X = Cl, Br, I) bonds in benzyl and allyl halides with a pincer-type phosphorus(III) species was reported. A series of structurally robust phosphorus(V) compds. were formed via the formal oxidative addn. reactions of C-X bonds to the phosphorus(III) center. D. functional theory calcns. show that the nucleophilic addn. process is more favorable than the direct oxidative addn. mechanism. Isomerization of bent structures of phosphorus(III) compd. to poorly nucleophilic compds. to undergo further C-X bond activation can be rationalized by frontier MO anal. This study not only provides a deep understanding of the reactivity of phosphorus(III) species but also demonstrates a potential of main group elements for the small-mol. activation.
  28. 28
    Volodarsky, S.; Dobrovetsky, R. Ambiphilic Geometrically Constrained Phosphenium Cation. Chem. Commun. 2018, 54, 6931– 6934,  DOI: 10.1039/C8CC02423E
    Google Scholar
    28
    Ambiphilic geometrically constrained phosphenium cation
    Volodarsky, Solomon; Dobrovetsky, Roman
    Chemical Communications (Cambridge, United Kingdom) (2018), 54 (50), 6931-6934CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
    In this work the synthesis of a geometrically constrained phosphenium cation is shown. In contrast to previously reported phosphenium cations, the geometrical constriction of the P-center in this cation makes it ambiphilic and reactive towards small mols. such as H2O, ROH and NH3.
  29. 29
    Hentschel, A.; Brand, A.; Wegener, P.; Uhl, W. A Sterically Constrained Tricyclic PC3 Phosphine: Coordination Behavior and Insertion of Chalcogen Atoms into P-C Bonds. Angew. Chem., Int. Ed. 2018, 57, 832– 835,  DOI: 10.1002/anie.201711373
    Google Scholar
    29
    A Sterically Constrained Tricyclic PC3 Phosphine-Coordination Behavior and Insertion of Chalcogen Atoms into P-C Bonds
    Hentschel, Anne; Brand, Alexander; Wegener, Philipp; Uhl, Werner
    Angewandte Chemie, International Edition (2018), 57 (3), 832-835CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A tricyclic phosphine has been generated that has a rigid mol. backbone with the P atoms exclusively bound to C(sp2) atoms as well as a very large Tolman angle and buried vol. It is an interesting new ligand in coordination chem. (Au, Pd complexes) and shows unusual insertion reactions into its endocyclic P-C bonds facilitated by its inherent mol. strain.
  30. 30
    Robinson, T. P.; De Rosa, D.; Aldridge, S.; Goicoechea, J. M. On the Redox Reactivity of a Geometrically Constrained Phosphorus(III) Compound. Chem.─Eur. J. 2017, 23, 15455– 15465,  DOI: 10.1002/chem.201703119
    Google Scholar
    30
    On the redox reactivity of a geometrically constrained phosphorus(III) compound
    Robinson, Thomas P.; De Rosa, Daniel; Aldridge, Simon; Goicoechea, Jose M.
    Chemistry - A European Journal (2017), 23 (61), 15455-15465CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
    The reactivity of a geometrically constrained phosphorus(III) complex bearing the N,N-bis(3,5-di-tert-butyl-2-phenolate)amide pincer ligand, 1,1'-(3,5-tBu2C6H2-6-O)2NP [1, P(ONO)] towards oxidants and reductants is explored. This compd. can be readily oxidized to the phosphorus(V) dihalo-derivs. P(ONO)X2 (2-4; X = Cl, Br, I). Attempts at isolating the analogous difluoride through oxidn. of 1 were unsuccessful yielding only the hydrofluoride P(ONO)(H)F (5), however P(ONO)F2 (6) can be accessed via a halide exchange reaction of 2 with KF. Compd. 2 can be employed as a precursor to novel cationic species through chloride ion displacement using strong Lewis bases. Thus, reaction of 2 with two or three molar equiv of dimethylaminopyridine (DMAP) affords [P(ONO)(Cl)(DMAP)2]+ (7) and [P(ONO)(DMAP)3]2+ (8). Reaction of 2 with the weaker bidentate base 2,2'-bipyridine (bipy) affords [P(ONO)(Cl)(bipy)]+ (9), although this species was only accessible upon addn. of a halide abstracting agent. The dicationic tris(pyridine) adduct [P(ONO)(py)3]2+ (10) is also accessible by reaction of 4 with pyridine. Oxidn. of 1 using oxygen gas proceeds slowly and allows for the observation of two compds., a mixed valence dimeric phosphorus(III)/phosphorus(V) compd. [P(ONO)(μ2-O)(μ2:κ1,κ2-ONO)P] (11) and the fully oxidized species [P(ONO)(μ2-O)(μ2:κ1,κ2-ONO)P(O)] (12). Finally, reaction of 1 using KC8 results in the dimerization of the putative radical anion [P(ONO)]•- through formation of a P-P bond to afford [P(ONO)]22- (13). Reactions with TEMPO result in the formation of the trigonal bipyramidal species P(ONO)(TEMPO)2 (14).
  31. 31
    Lin, Y. C.; Hatzakis, E.; McCarthy, S. M.; Reichl, K. D.; Lai, T. Y.; Yennawar, H. P.; Radosevich, A. T. P-N Cooperative Borane Activation and Catalytic Hydroboration by a Distorted Phosphorous Triamide Platform. J. Am. Chem. Soc. 2017, 139, 6008– 6016,  DOI: 10.1021/jacs.7b02512
    Google Scholar
    31
    P-N Cooperative Borane Activation and Catalytic Hydroboration by a Distorted Phosphorous Triamide Platform
    Lin, Yi-Chun; Hatzakis, Emmanuel; McCarthy, Sean M.; Reichl, Kyle D.; Lai, Ting-Yi; Yennawar, Hemant P.; Radosevich, Alexander T.
    Journal of the American Chemical Society (2017), 139 (16), 6008-6016CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Studies of the stoichiometric and catalytic reactivity of a geometrically constrained phosphorous triamide 1 with pinacolborane (HBpin) are reported. The addn. of HBpin to phosphorous triamide 1 results in cleavage of the B-H bond of pinacolborane through addn. across the electrophilic phosphorus and nucleophilic N-methylanilide sites in a cooperative fashion. The kinetics of this process of were investigated by NMR spectroscopy, with the detd. overall second-order empirical rate law given by ν = -k[1][HBpin], where k = 4.76 × 10-5 M-1 s-1 at 25 °C. The B-H bond activation process produces P-hydrido-1,3,2-diazaphospholene intermediate 2, which exhibits hydridic reactivity capable of reacting with imines to give phosphorous triamide intermediates, as confirmed by independent synthesis. These phosphorous triamide intermediates are typically short lived, evolving with elimination of the N-borylamine product of imine hydroboration with regeneration of the deformed phosphorous triamide 1. The kinetics of this latter process are shown to be first-order, indicative of a unimol. mechanism. Consequently, catalytic hydroboration of a variety of imine substrates can be realized with 1 as the catalyst and HBpin as the terminal reagent. A mechanistic proposal implicating a P-N cooperative mechanism for catalysis that incorporates the various independently verified stoichiometric steps is presented, and a comparison to related phosphorus-based systems is offered.
  32. 32
    Robinson, T. P.; Lo, S. K.; De Rosa, D.; Aldridge, S.; Goicoechea, J. M. On the Ambiphilic Reactivity of Geometrically Constrained Phosphorus(III) and Arsenic(III) Compounds: Insights into their Interaction with Ionic Substrates. Chem.─Eur. J. 2016, 22, 15712– 15724,  DOI: 10.1002/chem.201603135
    Google Scholar
    32
    On the Ambiphilic Reactivity of Geometrically Constrained Phosphorus(III) and Arsenic(III) Compounds: Insights into Their Interaction with Ionic Substrates
    Robinson, Thomas P.; Lo, Siu-Kwan; De Rosa, Daniel; Aldridge, Simon; Goicoechea, Jose M.
    Chemistry - A European Journal (2016), 22 (44), 15712-15724CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
    The ambiphilic nature of geometrically constrained Group 15 complexes bearing the N,N-bis(3,5-di-tert-butyl-2-phenolate)amide pincer ligand (ONO3-) is explored. Despite their differing reactivity towards nucleophilic substrates with polarized element-hydrogen bonds (e.g., NH3), both the phosphorus(III), P(ONO) (1a), and arsenic(III), As(ONO) (1b), compds. exhibit similar reactivity towards charged nucleophiles and electrophiles. Reactions of 1a and 1b with KOtBu or KNPh2 afford anionic complexes in which the nucleophilic anion assocs. with the pnictogen center [(tBuO)Pn(ONO)]- (Pn = P (2a), As (2b)) and [(Ph2N)Pn(ONO)]- (Pn = P (3a), As (3b)). Compd. 2a can subsequently be reacted with a proton source or benzyl bromide to afford the phosphorus(V) compds. (tBuO)HP(ONO) (4a) and (tBuO)BzP(ONO) (5a), resp., whereas analogous arsenic(V) compds. are inaccessible. Electrophilic substrates, such as HOTf and MeOTf, preferentially assoc. with the nitrogen atom of the ligand backbone of both 1a and 1b, giving rise to cationic species that can be rationalized as either ammonium salts or as amine-stabilized phosphenium or arsenium complexes ([Pn{ON(H)O}]+ (Pn = P (6a), As (6b)) and [Pn{ON(Me)O}]+ (Pn = P (7a), As (7b))). Reaction of 1a with an acid bearing a nucleophilic counter-anion (such as HCl) gives rise to a phosphorus(V) compd. HPCl(ONO) (8a), whereas the analogous reaction with 1b results in the addn. of HCl across one of the As-O bonds to afford ClAs{(H)ONO} (8b). Functionalization at both the pnictogen center and the ligand backbone is also possible by reaction of 7a/7b with KOtBu, which affords the neutral species (tBuO)Pn{ON(Me)O} (Pn = P (9a), As (9b)). The ambiphilic reactivity of these geometrically constrained complexes allows some insight into the mechanism of reactivity of 1a towards small mols., such as ammonia and water.
  33. 33
    Robinson, T. P.; De Rosa, D. M.; Aldridge, S.; Goicoechea, J. M. E-H Bond Activation of Ammonia and Water by a Geometrically Constrained Phosphorus(III) Compound. Angew. Chem., Int. Ed. 2015, 54, 13758– 13763,  DOI: 10.1002/anie.201506998
    Google Scholar
    33
    E-H Bond Activation of Ammonia and Water by a Geometrically Constrained Phosphorus(III) Compound
    Robinson, Thomas P.; De Rosa, Daniel M.; Aldridge, Simon; Goicoechea, Jose M.
    Angewandte Chemie, International Edition (2015), 54 (46), 13758-13763CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    The synthesis of a P(III) compd. bearing a N,N-bis(3,5-di-tert-butyl-2-phenoxy)amide ligand is reported. This species was found to react with NH3 and H2O, activating the E-H bonds in both substrates by formal oxidative addn. to afford the corresponding P(V) compds. In the case of H2O, both O-H bonds can be activated, splitting the mol. into its constituent elements. This is the 1st example of a compd. based on main group elements that sequentially activates H2O in this manner.
  34. 34
    McCarthy, S. M.; Lin, Y. C.; Devarajan, D.; Chang, J. W.; Yennawar, H. P.; Rioux, R. M.; Ess, D. H.; Radosevich, A. T. Intermolecular N–H Oxidative Addition of Ammonia, Alkylamines, and Arylamines to a Planar σ3-Phosphorus Compound via an Entropy-Controlled Electrophilic Mechanism. J. Am. Chem. Soc. 2014, 136, 4640– 4650,  DOI: 10.1021/ja412469e
    Google Scholar
    34
    Intermolecular N-H oxidative addition of ammonia, alkylamines, and arylamines to a planar σ3-phosphorus compound via an entropy-controlled electrophilic mechanism
    McCarthy, Sean M.; Lin, Yi-Chun; Devarajan, Deepa; Chang, Ji Woong; Yennawar, Hemant P.; Rioux, Robert M.; Ess, Daniel H.; Radosevich, Alexander T.
    Journal of the American Chemical Society (2014), 136 (12), 4640-4650CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Ammonia, alkyl amines, and aryl amines undergo rapid intermol. N-H oxidative addn. to a planar mononuclear σ3-phosphorus compd., [(tBuC(O):CHNCH:C(O)tBu-κN,κO,κO')P] ([(ONO)P], 1). The pentacoordinate phosphorane products [(ONO)P(H)(NHR)] (R = H, n-Pr, PhCH2, iPr, 2,4,6-Me3C6H2) are structurally robust, permitting full characterization by multinuclear NMR spectroscopy and single-crystal x-ray diffraction (R = 2,4,6-Me3C6H2). Isothermal titrn. calorimetry was employed to quantify the enthalpy of the N-H oxidative addn. of n-propylamine to 1, n-PrNH2 + 1 → [(ONO)P(H)(NHn-Pr)], ΔHrxn298 = -10.6 kcal/mol. The kinetics of n-propylamine N-H oxidative addn. were monitored by in situ UV absorption spectroscopy and detn. of the rate law showed an unusually large molecularity (ν = k[1][PrNH2]3). Kinetic expts. conducted over the temp. range of 10-70° revealed that the reaction rate decreased with increasing temp. Activation parameters extd. from an Eyring anal. (ΔH⧧ = -0.8 ± 0.4 kcal/mol, ΔS⧧ = -72 ± 2 cal/(mol·K)) indicate that the cleavage of strong N-H bonds by 1 is entropy controlled due to a highly ordered, high molecularity transition state. D. functional calcns. indicate that a concerted oxidative addn. via a classical three-center transition structure is energetically inaccessible. Rather, a stepwise heterolytic pathway is preferred, proceeding by initial amine-assisted N-H heterolysis upon complexation to the electrophilic phosphorus center followed by rate-controlling N → P proton transfer.
  35. 35
    Zeng, G. X.; Maeda, S.; Taketsugu, T.; Sakaki, S. Catalytic Transfer Hydrogenation by a Trivalent Phosphorus Compound: Phosphorus-Ligand Cooperation Pathway or PIII/PV Redox Pathway?. Angew. Chem., Int. Ed. 2014, 53, 4633– 4637,  DOI: 10.1002/anie.201311104
    Google Scholar
    35
    Catalytic Transfer Hydrogenation by a Trivalent Phosphorus Compound: Phosphorus-Ligand Cooperation Pathway or PIII/PV Redox Pathway?
    Zeng, Guixiang; Maeda, Satoshi; Taketsugu, Tetsuya; Sakaki, Shigeyoshi
    Angewandte Chemie, International Edition (2014), 53 (18), 4633-4637CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Main-group-element catalysts are a desirable alternative to transition-metal catalysts because of natural abundance and cost. However, the examples are very limited. Catalytic cycles involving a redox process and E-ligand cooperation (E = main-group element), which are often found in catalytic cycles of transition-metal catalysts, have not been reported. Herein theor. investigations of a catalytic hydrogenation of azobenzene with ammonia-borane using a trivalent phosphorus compd., which was exptl. proposed to occur through PIII/PV redox processes via an unusual pentavalent dihydridophosphorane, were performed. DFT and ONIOM(CCSD(T):MP2) calcns. disclosed that this catalytic reaction occurs through a P-O cooperation mechanism, which resembles the metal-ligand cooperation mechanism of transition-metal catalysts.
  36. 36
    Pal, A.; Vanka, K. Small Molecule Activation by Constrained Phosphorus Compounds: Insights from Theory. Inorg. Chem. 2016, 55, 558– 565,  DOI: 10.1021/acs.inorgchem.5b01074
    Google Scholar
    36
    Small Molecule Activation by Constrained Phosphorus Compounds: Insights from Theory
    Pal, Amrita; Vanka, Kumar
    Inorganic Chemistry (2016), 55 (2), 558-565CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)
    An exciting new development in main group chem. has been the use of a constrained, "flat", phosphorus-based complex to mediate in reactions such as the dehydrogenation of ammonia borane (AB), and the activation of the N-H bond in primary amines. Its importance is based on the fact that it shows that main group compds., when properly designed, can be as effective as transition metal complexes for doing significant chem. transformations. What the current computational study, employing d. functional theory (DFT), reveals is that a common, general mechanism exists that accounts for the behavior of the flat phosphorus compd. in the different reactions that have been exptl. reported to date. This mechanism, which involves the mediation by a base as a proton transfer agent, is simpler and energetically more favorable than the previous mechanisms that have been proposed for the same reactions in the literature. It is likely that the knowledge gained from the current work about the chem. behavior of this phosphorus compd. can be utilized to design new constrained phosphorus-based compds.
  37. 37
    Volodarsky, S.; Bawari, D.; Dobrovetsky, R. Dual Reactivity of a Geometrically Constrained Phosphenium Cation. Angew. Chem., Int. Ed. 2022, 61, e202208401  DOI: 10.1002/anie.202208401
    Google Scholar
    37
    Dual Reactivity of a Geometrically Constrained Phosphenium Cation
    Volodarsky, Solomon; Bawari, Deependra; Dobrovetsky, Roman
    Angewandte Chemie, International Edition (2022), 61 (36), e202208401CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A geometrically constrained phosphenium cation in bis(pyrrolyl)pyridine based NNN pincer type ligand (1+) was synthesized, isolated and its preliminary reactivity was studied with small mols. 1+ Reacts with MeOH and Et2NH, activating the O-H and N-H bonds via a P-center/ligand assisted path. The reaction of 1+ with one equiv. of H3NBH3 leads to its dehydrogenation producing 5. Interestingly, reaction of 1+ with an excess H3NBH3 leads to phosphinidene (PI) species coordinating to two BH3 mols. (6). In contrast, [1+][OTf] reacts with Et3SiH by hydride abstraction yielding 1-H and Et3SiOTf, while [1+][B(C6F5)4] reacts with Et3SiH via an oxidative addn. type reaction of Si-H bond to P-center, affording a new PV compd. (8). However, 8 is not stable over time and degrades to a complex mixt. of compds. in matter of minutes. Despite this, the ability of [1+][B(C6F5)4] to activate Si-H bond could still be tested in catalytic hydrosilylation of benzaldehyde, where 1+ closely mimics transition metal behavior.
  38. 38
    Bawari, D.; Volodarsky, S.; Ginzburg, Y.; Jaiswal, K.; Joshi, P.; Dobrovetsky, R. Intramolecular C-N Bond Activation by a Geometrically Constrained P-III-Centre. Chem. Commun. 2022, 58, 12176– 12179,  DOI: 10.1039/D2CC04359A
    Google Scholar
    38
    Intramolecular C-N bond activation by a geometrically constrained PIII-centre
    Bawari, Deependra; Volodarsky, Solomon; Ginzburg, Yael; Jaiswal, Kuldeep; Joshi, Pooja; Dobrovetsky, Roman
    Chemical Communications (Cambridge, United Kingdom) (2022), 58 (87), 12176-12179CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
    Reaction of phenoxide-functionalized imidazolidinylidene NHC, 1,3-R2-C3H4N2 (R = 3,5-tBu-2-LiO-C6H2) (1-Li2C:) with PCl3 is accompanied by insertion of carbene C atom into C-H bond of MeCN solvent with subsequent elimination and formation of phosphoranes (tBu2C6H2(O)NCH2CH2N(O)C6H2tBu2)PX (4, 5; X = ClCHCH2CN, H). In this work the first examples of C-N bond activation by insertion into a geometrically constrained PIII-center are shown. The mechanisms of these activation processes leading to new PV species were studied both exptl. and computationally. Interestingly, in the case of insertion of the PIII-center into an N-C(O)H bond, an unstable phosphoranyl-formaldehyde intermediate is probably formed, which undergoes decarbonylation in the presence of a catalytic amt. of HCl producing a hydrophosphorane.
  39. 39
    Abbenseth, J.; Townrow, O. P. E.; Goicoechea, J. M. Thermoneutral N-H Bond Activation of Ammonia by a Geometrically Constrained Phosphine. Angew. Chem., Int. Ed. 2021, 60, 23625– 23629,  DOI: 10.1002/anie.202111017
    Google Scholar
    39
    Thermoneutral N-H Bond Activation of Ammonia by a Geometrically Constrained Phosphine
    Abbenseth, Josh; Townrow, Oliver P. E.; Goicoechea, Jose M.
    Angewandte Chemie, International Edition (2021), 60 (44), 23625-23629CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A geometrically constrained phosphine I (2, X = lone pair) bearing a tridentate NNS pincer ligand is reported; its structure is confirmed by x-ray anal. of the selenide (3, X = Se). The effect of the geometric constraint on the electronic structure was probed by theor. calcns. and derivatization reactions. Reactions with N-H bonds result in formation of cooperative addn. products. The thermochem. of these transformations is strongly dependent on the substrate, with ammonia activation being thermoneutral. This represents the first example of a mol. compd. that reversibly activates ammonia via N-H bond scission in soln. upon mild heating.
  40. 40
    Lipshultz, J. M.; Fu, Y.; Liu, P.; Radosevich, A. T. Organophosphorus-Catalyzed Relay Oxidation of H-Bpin: Electrophilic C-H Borylation of Heteroarenes. Chem. Sci. 2021, 12, 1031– 1037,  DOI: 10.1039/D0SC05620K
    Google Scholar
    40
    Organophosphorus-catalyzed relay oxidation of H-Bpin: electrophilic C-H borylation of heteroarenes
    Lipshultz, Jeffrey M.; Fu, Yue; Liu, Peng; Radosevich, Alexander T.
    Chemical Science (2021), 12 (3), 1031-1037CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
    A nontrigonal phosphorus triamide (1, P{N[o-NMe-C6H4]2}) is shown to catalyze C-H borylation of electron-rich heteroarenes with pinacolborane (HBpin) in the presence of a mild chloroalkane reagent. C-H borylation proceeds for a range of electron-rich heterocycles including pyrroles, indoles, and thiophenes of varied substitution. Mechanistic studies implicate an initial P-N cooperative activation of HBpin by 1 to give P-hydrido diazaphospholene 2, which is diverted by Atherton-Todd oxidn. with chloroalkane to generate P-chloro diazaphospholene 3. DFT calcns. suggest subsequent oxidn. of pinacolborane by 3 generates chloropinacolborane (ClBpin) as a transient electrophilic borylating species, consistent with obsd. substituent effects and regiochem. outcomes. These results illustrate the targeted diversion of established reaction pathways in organophosphorus catalysis to enable a new mode of main group-catalyzed C-H borylation.
  41. 41
    Zeng, G. X.; Maeda, S.; Taketsugu, T.; Sakaki, S. Catalytic Hydrogenation of Carbon Dioxide with Ammonia-Borane by Pincer-Type Phosphorus Compounds: Theoretical Prediction. J. Am. Chem. Soc. 2016, 138, 13481– 13484,  DOI: 10.1021/jacs.6b07274
    Google Scholar
    41
    Catalytic Hydrogenation of Carbon Dioxide with Ammonia-Borane by Pincer-Type Phosphorus Compounds: Theoretical Prediction
    Zeng, Guixiang; Maeda, Satoshi; Taketsugu, Tetsuya; Sakaki, Shigeyoshi
    Journal of the American Chemical Society (2016), 138 (41), 13481-13484CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Two theor. designed and one exptl. reported pincer-type phosphorus compds. are active for the hydrogenation of carbon dioxide with ammonia-borane. DFT, ONIOM(CCSD(T):MP2), and CCSD(T) computational results demonstrated that the reaction occurs through phosphorus-ligand cooperative catalysis, which provides an unprecedented protocol for metal-free CO2 conversion. The phosphorus compds. with the NNN ligand are more active than those with the ONO ligand. The planar conjugate ligand considerably improves the efficiency of the catalyst.
  42. 42
    Cui, J. J.; Li, Y. X.; Ganguly, R.; Kinjo, R. Reactivity Studies on a Diazadiphosphapentalene. Chem.─Eur. J. 2016, 22, 9976– 9985,  DOI: 10.1002/chem.201600935
    Google Scholar
    42
    Reactivity Studies on a Diazadiphosphapentalene
    Cui, Jingjing; Li, Yongxin; Ganguly, Rakesh; Kinjo, Rei
    Chemistry - A European Journal (2016), 22 (29), 9976-9985CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
    The reactivity of diazadiphosphapentalene 1 towards various substrates was studied. Reaction of 1 with NH3-borane resulted in transfer hydrogenolysis concomitantly with the cleavage of a P-N bond. By treatment of 1 with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), oxidn. took place at one of the P atoms of 1, and a P(V)/P(III) mixed-valence deriv. was isolated. At the same time, only one of the P atoms in 1 behaves as an electron donor for electrophiles and Lewis acids. The former afforded an intramolecularly coordinated phosphine-phosphenium species, whereas the latter demonstrates the ligand property of 1. UV irradn. induced rearrangement of 1 into another example of another diazadiphosphapentalene.
  43. 43
    Cui, J. J.; Li, Y. X.; Ganguly, R.; Inthirarajah, A.; Hirao, H.; Kinjo, R. Metal-Free Sigma-Bond Metathesis in Ammonia Activation by a Diazadiphosphapentalene. J. Am. Chem. Soc. 2014, 136, 16764– 16767,  DOI: 10.1021/ja509963m
    Google Scholar
    43
    Metal-Free σ-Bond Metathesis in Ammonia Activation by a Diazadiphosphapentalene
    Cui, Jingjing; Li, Yongxin; Ganguly, Rakesh; Inthirarajah, Anusiya; Hirao, Hajime; Kinjo, Rei
    Journal of the American Chemical Society (2014), 136 (48), 16764-16767CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    A diazadiphosphapentalene deriv. (I) featuring a bent geometry with two phosphorus atoms at the bridgehead was synthesized. Under mild conditions, compd. I readily activated ammonia to afford 1-aza-2,3-diphospholene deriv. (II) bearing an enamine group. The reaction is therefore viewed as a formal σ-bond metathesis between an N-H bond of ammonia and an endocyclic P-N bond of I. Details of the reaction mechanism for ammonia activation as well as subsequent isomerization were explored by d. functional theory calcns.
  44. 44
    Müller, K.; Faeh, C.; Diederich, F. Fluorine in Pharmaceuticals: Looking Beyond Intuition. Science 2007, 317, 1881– 1886,  DOI: 10.1126/science.1131943
    Google Scholar
    44
    Fluorine in Pharmaceuticals: Looking Beyond Intuition
    Mueller, Klaus; Faeh, Christoph; Diederich, Francois
    Science (Washington, DC, United States) (2007), 317 (5846), 1881-1886CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
    A review. Fluorine substituents have become a widespread and important drug component, their introduction facilitated by the development of safe and selective fluorinating agents. Organofluorine affects nearly all phys. and adsorption, distribution, metab., and excretion properties of a lead compd. Its inductive effects are relatively well understood, enhancing bioavailability, for example, by reducing the basicity of neighboring amines. In contrast, exploration of the specific influence of carbon-fluorine single bonds on docking interactions, whether through direct contact with the protein or through stereoelectronic effects on mol. conformation of the drug, has only recently begun. Here, we review exptl. progress in this vein and add complementary anal. based on comprehensive searches in the Cambridge Structural Database and the Protein Data Bank.
  45. 45
    Wang, J.; Sanchez-Rosello, M.; Acena, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Fluorine in Pharmaceutical Industry: Fluorine-Containing Drugs Introduced to the Market in the Last Decade (2001–2011). Chem. Rev. 2014, 114, 2432– 2506,  DOI: 10.1021/cr4002879
    Google Scholar
    45
    Fluorine in Pharmaceutical Industry: Fluorine-Containing Drugs Introduced to the Market in the Last Decade (2001-2011)
    Wang, Jiang; Sanchez-Rosello, Maria; Acena, Jose Luis; del Pozo, Carlos; Sorochinsky, Alexander E.; Fustero, Santos; Soloshonok, Vadim A.; Liu, Hong
    Chemical Reviews (Washington, DC, United States) (2014), 114 (4), 2432-2506CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
    A historic review. As expected from the fluorine position on the periodic table of elements, it possesses some extreme properties, in particular, ultimate electronegativity and oxidn. potential. Therefore,elemental fluorine can not be prepd. by chem. reaction, and its isolation in 1886 by Henri Moissan required scientific ingenuity and great personal courage. His historic effort earned him a Noble Prize (1906), and the developed electrolysis method is still in use for industrial prodn. of fluorine gas. However, further development of fluorine chem. was extremely sluggish, pursued by a handful of experts capable of handling the violent gas using specially designed lab. equipment. Industrial-scale prodn. of fluorochems. dates back to late 1930s. Currently, there are about 200 pharmaceuticals containingfluorine, including the 40 new compds. discussed in this review. One may agree that the contribution of the past decade indicates a significant 20% increase in the no. of fluorinated drugs on the market.
  46. 46
    Jeschke, P. The Unique Role of Fluorine in the Design of Active Ingredients for Modern Crop Protection. Chembiochem 2004, 5, 570– 589,  DOI: 10.1002/cbic.200300833
    Google Scholar
    46
    The unique role of fluorine in the design of active ingredients for modern crop protection
    Jeschke, Peter
    ChemBioChem (2004), 5 (5), 570-589CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. The task of inventing and developing active ingredients with useful biol. activities requires a search for novel chem. substructures. This process may trigger the discovery of whole classes of chems. of potential com. interest. Similar biol. effects can often be achieved by completely different compds. However, compds. within a given structural family may exhibit quite different biol. activities depending on their interactions with different intracellular proteins like enzymes or receptors. By varying the functional groups and structural elements of a lead compd., its interaction with the active site of the target protein, as well as its physicochem., pharmacokinetic, and dynamic properties can be improved. In this context, the introduction of fluorine into active ingredients has become an important concept in the quest for a modern crop protection product with optimal efficacy, environmental safety, user friendliness, and economic viability. Fluorinated org. compds. represent an important and growing family of com. agrochems. A no. of recently developed agrochem. candidates represent novel classes of chem. compds. with new modes of action; several of these compds. contain new fluorinated substituents. However, the complex structure-activity relationships assocd. with biol.-active mols. mean that the introduction of fluorine can lead to either an increase or a decrease in the efficacy of a compd., depending on its changed mode of action, physicochem. properties, target interaction, or metabolic susceptibility and transformation. Therefore, it is still difficult to predict the sites in a mol. at which fluorine substitution will result in optimal desired effects.
  47. 47
    Hird, M. Fluorinated Liquid Crystals─Properties and Applications. Chem. Soc. Rev. 2007, 36, 2070– 2095,  DOI: 10.1039/b610738a
    Google Scholar
    47
    Fluorinated liquid crystals - properties and applications
    Hird, Michael
    Chemical Society Reviews (2007), 36 (12), 2070-2095CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
    This crit. review begins with a brief, but essential, introduction to the special nature of liq. crystal materials, their peculiar properties, and their com. applications, followed by an introductory insight into the remarkable nature of the fluoro substituent, and its fascinating influence on the properties of org. compds. However, the main focus of the review is to discuss the enormous amt. of exciting research on fluorinated liq. crystals that is reported. The small size of the fluoro substituent enables its incorporation into all types of liq. crystal, including calamitic, discotic, banana, lyotropic, and polymers, without ruining the liq. cryst. nature of the material. However the fluoro substituent is larger than H, and hence causes a significant steric effect, which combined with the high polarity, confers many fascinating, and often remarkable, modifications to m.p., mesophase morphol. and transition temps., and the many other very important phys. properties, such as dielec. anisotropy, optical anisotropy, and visco-elastic properties. There are many different positions within a liq. crystal structure where a fluoro substituent can be located, including (i) a terminal position, (ii) within a terminal chain, as a semi-fluorinated or as a perfluorinated chain, or as one fluoro substituent at a chiral center, (iii) as part of a linking group, and (iv) a lateral position in the core section. Such variety enables the interesting and advantageous tailoring of properties, both for the fundamental purposes of establishing structure-property relations, and for materials targeted towards com.-successful liq. crystal display applications.
  48. 48
    Hooker, L. V.; Bandar, J. S. Synthetic Advantages of Defluorinative C-F Bond Functionalization. Angew. Chem., Int. Ed. 2023, 62, e202308880  DOI: 10.1002/anie.202308880
    Google Scholar
    48
    Synthetic Advantages of Defluorinative C-F Bond Functionalization
    Hooker, Leidy V.; Bandar, Jeffrey S.
    Angewandte Chemie, International Edition (2023), 62 (49), e202308880CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. Much progress has been made in the development of methods to both create compds. that contain C-F bonds and to functionalize C-F bonds. As such, C-F bonds are becoming common and versatile synthetic functional handles. This review summarizes the advantages of defluorinative functionalization reactions for small mol. synthesis. The coverage is organized by the type of carbon framework the fluorine is attached to for mono- and polyfluorinated motifs. The main challenges, opportunities and advances of defluorinative functionalization are discussed for each class of organofluorine. Most of the text focuses on case studies that illustrate how defluorofunctionalization can improve routes to synthetic targets or how the properties of C-F bonds enable unique mechanisms and reactions. The broader goal is to showcase the opportunities for incorporating and exploiting C-F bonds in the design of synthetic routes, improvement of specific reactions and advent of new methods.
  49. 49
    Ahrens, T.; Kohlmann, J.; Ahrens, M.; Braun, T. Functionalization of Fluorinated Molecules by Transition-Metal-Mediated C-F Bond Activation to Access Fluorinated Building Blocks. Chem. Rev. 2015, 115, 931– 972,  DOI: 10.1021/cr500257c
    Google Scholar
    49
    Functionalization of Fluorinated Molecules by Transition-Metal-Mediated C-F Bond Activation To Access Fluorinated Building Blocks
    Ahrens, Theresia; Kohlmann, Johannes; Ahrens, Mike; Braun, Thomas
    Chemical Reviews (Washington, DC, United States) (2015), 115 (2), 931-972CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
    A review that deals with transition-metal-mediated C1F bond activations which involve a cleavage of a C-F bond in polyfluorinated mols. and its transformation into carbon-element bonds, excluding hydrodefluorination or defluorination reactions.
  50. 50
    Hu, J.-Y.; Zhang, J.-L. Hydrodefluorination Reactions Catalyzed by Transition-Metal Complexes. In Organometallic Fluorine Chemistry; Braun, T., Hughes, R. P., Eds.; Springer International Publishing: Cham, 2015; pp 143– 196.
    Google Scholar
    There is no corresponding record for this reference.
  51. 51
    Whittlesey, M. K.; Peris, E. Catalytic Hydrodefluorination with Late Transition Metal Complexes. ACS Catal. 2014, 4, 3152– 3159,  DOI: 10.1021/cs500887p
    Google Scholar
    51
    Catalytic Hydrodefluorination with Late Transition Metal Complexes
    Whittlesey, Michael K.; Peris, Eduardo
    ACS Catalysis (2014), 4 (9), 3152-3159CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)
    A review. This perspective article focuses its attention on the most recent advances in hydrodefluorination processes catalyzed by late transition metal complexes, a field that has been a matter of increasing interest during the past decade. The evolution of catalytic hydrodefluorination is treated by giving precise information on the nature of the catalysts, reductants and fluoroorg. substrates that have been used until now. An overview of the mechanistic studies that have been performed so far is also given.
  52. 52
    Das, A.; Chatani, N. The Directing Group: A Tool for Efficient and Selective C-F Bond Activation. ACS Catal. 2021, 11, 12915– 12930,  DOI: 10.1021/acscatal.1c03896
    Google Scholar
    52
    The Directing Group: A Tool for Efficient and Selective C-F Bond Activation
    Das, Amrita; Chatani, Naoto
    ACS Catalysis (2021), 11 (21), 12915-12930CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)
    A review. In this Review, focus on the directed strategy for the activation of inert C-F bonds.
  53. 53
    Chen, W.; Bakewell, C.; Crimmin, M. R. Functionalisation of Carbon-Fluorine Bonds with Main Group Reagents. Synthesis 2017, 49, 810– 821,  DOI: 10.1055/s-0036-1588663
    Google Scholar
    53
    Functionalisation of Carbon-Fluorine Bonds with Main Group Reagents
    Chen, Wenyi; Bakewell, Clare; Crimmin, Mark R.
    Synthesis (2017), 49 (4), 810-821CODEN: SYNTBF; ISSN:1437-210X. (Georg Thieme Verlag)
    A review. Synthetic approaches to produce reactive chem. building blocks from fluorinated mols. by the functionalization of carbon-fluorine bonds with main group reagents are reviewed. The reaction types can be categorized as: the formal 1,2-addn. of C-F bonds across Si-Si, B-B, or Mg-Mg bonds; the oxidative addn. of C-F bonds to Si(II), Ge(II), and Al(I) centers; and the dehydrogenative coupling of C-F bonds with Al-H or B-H bonds. Many of the advances have emerged between 2015-2016 and are largely focused upon arom. substrates that contain sp2 C-F bonds. Topics discussed include: C-F borylation of arom. sp2 C-F bonds ; rhodium catalysis ; nickel catalysis ; C-F alumination of sp2 C-F arom. and sp3 C-F aliph. bonds ; C-F silylation and germylation of arom. sp2 C-F bonds ; C-F magnesiation of arom. sp2 C-F bonds ; and C-F silylation and borylation of alkenes.
  54. 54
    Muthuvel, K.; Gandhi, T. C-F Bond Activation and Functionalizations Enabled by Metal-Free NHCs and their Metal Complexes. ChemCatChem 2022, 14, e202101579  DOI: 10.1002/cctc.202101579
    Google Scholar
    54
    C-F Bond Activation and Functionalizations Enabled by Metal-free NHCs and Their Metal Complexes
    Muthuvel, Karthick; Gandhi, Thirumanavelan
    ChemCatChem (2022), 14 (8), e202101579CODEN: CHEMK3; ISSN:1867-3880. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. This minireview provides the prominence of NHC and metal-NHC in the area of catalytic C-F bond functionalization.
  55. 55
    Stahl, T.; Klare, H. F. T.; Oestreich, M. Main-Group Lewis Acids for C-F Bond Activation. ACS Catal. 2013, 3, 1578– 1587,  DOI: 10.1021/cs4003244
    Google Scholar
    55
    Main-Group Lewis Acids for C-F Bond Activation
    Stahl, Timo; Klare, Hendrik F. T.; Oestreich, Martin
    ACS Catalysis (2013), 3 (7), 1578-1587CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)
    A review. The significant benefits of fluorinated compds. have inspired the development of diverse techniques for the activation and subsequent (de)functionalization of rather inert C-F bonds. Although substantial progress has been made in the selective activation of C(sp2)-F bonds employing transition metal complexes, protocols that address nonactivated C(sp3)-F bonds are much less established. In this regard, the use of strong main-group Lewis acids has emerged as a powerful tool to selectively activate C(sp3)-F bonds in satd. fluorocarbons. This Perspective provides a concise overview of various cationic and neutral silicon-, boron-, and aluminum-based Lewis acids that have been identified to facilitate the heterolytic fluoride abstraction from aliph. fluorides. The potential of these Lewis acids in hydrodefluorination as well as defluorinative C-F bond functionalization reactions is highlighted. Emphasis is placed on the underlying mechanistic principles to provide a systematic classification of the individual reactions. Finally, brief insight into the related C-F bond activation chem. using carbocations or Bronsted acids is presented.
  56. 56
    Caputo, C. B.; Hounjet, L. J.; Dobrovetsky, R.; Stephan, D. W. Lewis Acidity of Organofluorophosphonium Salts: Hydrodefluorination by a Saturated Acceptor. Science 2013, 341, 1374– 1377,  DOI: 10.1126/science.1241764
    Google Scholar
    56
    Lewis Acidity of Organofluorophosphonium Salts: Hydrodefluorination by a Saturated Acceptor
    Caputo, Christopher B.; Hounjet, Lindsay J.; Dobrovetsky, Roman; Stephan, Douglas W.
    Science (Washington, DC, United States) (2013), 341 (6152), 1374-1377CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
    Prototypical Lewis acids, such as boranes, derive their reactivity from electronic unsatn. Here, the authors report the Lewis acidity and catalytic application of electronically satd. P-centered electrophilic acceptors. Organofluorophosphonium salts [(C6F5)3-xPhxPF][B(C6F5)4] (x = 0 or 1; Ph, phenyl) form adducts with neutral Lewis bases and react rapidly with fluoroalkanes to produce difluorophosphoranes. In the presence of hydrosilane, [(C6F5)3PF]+ catalyzes the hydrodefluorination of fluoroalkanes, affording alkanes and fluorosilane. The mechanism demonstrates the impressive F- ion affinity of this highly electron-deficient phosphonium center.
  57. 57
    Zhu, J.; Pérez, M.; Caputo, C. B.; Stephan, D. W. Use of Trifluoromethyl Groups for Catalytic Benzylation and Alkylation with Subsequent Hydrodefluorination. Angew. Chem., Int. Ed. 2016, 55, 1417– 1421,  DOI: 10.1002/anie.201510494
    Google Scholar
    57
    Use of Trifluoromethyl Groups for Catalytic Benzylation and Alkylation with Subsequent Hydrodefluorination
    Zhu, Jiangtao; Perez, Manuel; Caputo, Christopher B.; Stephan, Douglas W.
    Angewandte Chemie, International Edition (2016), 55 (4), 1417-1421CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    The electrophilic organofluorophosphonium catalyst [(C6F5)3PF][B(C6F5)4] is shown to effect benzylation or alkylation by aryl and alkyl CF3 groups with subsequent hydrodefluorination, thus resulting in a net transformation of CF3 into CH2-aryl fragments [e.g., PhCF3 → CH2Ph2 (63%)]. In the case of alkyl CF3 groups, Friedel-Crafts alkylation by the difluorocarbocation proceeded without cation rearrangement, in contrast to the corresponding reactions of alkyl monofluorides.
  58. 58
    Zhu, J.; Pérez, M.; Stephan, D. W. C-C Coupling of Benzyl Fluorides Catalyzed by an Electrophilic Phosphonium Cation. Angew. Chem., Int. Ed. 2016, 55, 8448– 8451,  DOI: 10.1002/anie.201603627
    Google Scholar
    58
    C-C Coupling of Benzyl Fluorides Catalyzed by an Electrophilic Phosphonium Cation
    Zhu, Jiangtao; Perez, Manuel; Stephan, Douglas W.
    Angewandte Chemie, International Edition (2016), 55 (29), 8448-8451CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    The activation and cleavage of benzyl fluorides by the electrophilic organofluorophosphonium catalyst, [(C6F5)3PF][B(C6F5)4], is reported and used for the prepn. of 1,1-diarylalkanes (37 examples) and substituted aryl homoallylic alkenes (14 examples). This procedure involves mild conditions, avoids harmful waste, and is compatible with a range of substituted arenes and allylic silanes.
  59. 59
    Bayne, J. M.; Stephan, D. W. C-F Bond Activation Mediated by Phosphorus Compounds. Chem.─Eur. J. 2019, 25, 9350– 9357,  DOI: 10.1002/chem.201900542
    Google Scholar
    59
    C-F Bond Activation Mediated by Phosphorus Compounds
    Bayne, Julia M.; Stephan, Douglas W.
    Chemistry - A European Journal (2019), 25 (40), 9350-9357CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. The activation and functionalization of C-F bonds has garnered significant attention in the scientific community as a strategy to mitigate toxicity and environmental concerns, as well as provide new pathways to agro- and pharmaceutical chems. and materials. Although several transition-metal-based systems have been developed for this transformation, the use of main-group compds. remains less explored. In recent years, several strategies for C-F bond activation have focused on the use of phosphorus-based reagents. In this Minireview, an overview of strategies is provided that exploits PV and PIII-based Lewis acids as well as PIII Lewis bases in frustrated Lewis pair (FLP) protocols for hydrodefluorination, C-C couplings and C-F derivatizations.
  60. 60
    Kikushima, K.; Grellier, M.; Ohashi, M.; Ogoshi, S. Transition-Metal-Free Catalytic Hydrodefluorination of Polyfluoroarenes by Concerted Nucleophilic Aromatic Substitution with a Hydrosilicate. Angew. Chem., Int. Ed. 2017, 56, 16191– 16196,  DOI: 10.1002/anie.201708003
    Google Scholar
    60
    Transition-Metal-Free Catalytic Hydrodefluorination of Polyfluoroarenes by Concerted Nucleophilic Aromatic Substitution with a Hydrosilicate
    Kikushima, Kotaro; Grellier, Mary; Ohashi, Masato; Ogoshi, Sensuke
    Angewandte Chemie, International Edition (2017), 56 (51), 16191-16196CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Polyfluorinated arenes underwent regioselective transition metal-free hydrodefluorination with Ph3SiH or Et2SiH2 in the presence of tetrabutylammonium difluorotriphenylsilicate (TBAT) in THF. For example, hexafluorobenzene underwent hydrodefluorination with Et2SiH2 at 60° to yield pentafluorobenzene in 19% yield, 1,2,4,5-tetrafluorobenzene in 70% yield, and 1,2,3,5-tetrafluorobenzene and 1,2,3,4-tetrafluorobenzene in 2% yields. The reaction involves direct hydride transfer from a hydrosilicate as the key intermediate, which is generated from a hydrosilane and a fluoride salt; the eliminated fluoride regenerates the hydrosilicate to complete the catalytic cycle. The mechanism was studied using stoichiometric reactions of silicates and using dispersion-cor. DFT calcns.; hydrodefluorination likely proceeds via concerted nucleophilic arom. substitution.
  61. 61
    Schoch, T. D.; Mondal, M.; Weaver, J. D. Catalyst-Free Hydrodefluorination of Perfluoroarenes with NaBH4. Org. Lett. 2021, 23, 1588– 1593,  DOI: 10.1021/acs.orglett.0c04305
    Google Scholar
    61
    Catalyst-Free Hydrodefluorination of Perfluoroarenes with NaBH4
    Schoch, Timothy D.; Mondal, Mukulesh; Weaver, Jimmie D.
    Organic Letters (2021), 23 (5), 1588-1593CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
    An economical means of removing fluorine from various highly fluorinated arenes using NaBH4 for synthesis of partially fluorinated arenes was presented. The procedure was adapted for different classes of perfluoroarenes. A novel isomer of an emerging class of org. dyes based on the carbazole phthalonitrile motif was succinctly synthesized in two steps from tetrafluorophthalonitrile, demonstrating the utility of the hydrodefluorination procedure. Initial exploration of the dye showed it to be photoactive and capable of facilitating contrathermodynamic styrenoid E/Z isomerization.
  62. 62
    Zhang, J. J.; Zhao, X.; Yang, J. D.; Cheng, J. P. Diazaphospholene-Catalyzed Hydrodefluorination of Polyfluoroarenes with Phenylsilane via Concerted Nucleophilic Aromatic Substitution. J. Org. Chem. 2022, 87, 294– 300,  DOI: 10.1021/acs.joc.1c02360
    Google Scholar
    62
    Diazaphospholene-Catalyzed Hydrodefluorination of Polyfluoroarenes with Phenylsilane via Concerted Nucleophilic Aromatic Substitution
    Zhang, Jingjing; Zhao, Xiao; Yang, Jin-Dong; Cheng, Jin-Pei
    Journal of Organic Chemistry (2022), 87 (1), 294-300CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
    The metal-free catalytic C-F bond activation of polyfluoroarenes was achieved with diazaphospholene as the catalyst and phenylsilane as the terminal reductant. D. functional theory calcns. suggested a concerted nucleophilic arom. substitution mechanism.
  63. 63
    Zhang, J. J.; Yang, J. D.; Cheng, J. P. Chemoselective Catalytic Hydrodefluorination of Trifluoromethylalkenes Towards Mono-/Gem-Di-Fluoroalkenes Under Metal-Free Conditions. Nat. Commun. 2021, 12, 2835,  DOI: 10.1038/s41467-021-23101-3
    Google Scholar
    63
    Chemoselective catalytic hydrodefluorination of trifluoromethylalkenes towards mono-/gem-di-fluoroalkenes under metal-free conditions
    Zhang, Jingjing; Yang, Jin-Dong; Cheng, Jin-Pei
    Nature Communications (2021), 12 (1), 2835CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)
    Here, a diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively construct gem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry was described. This metal-free hydrodefluorination featured mild reaction conditions, good group compatibility, and almost quant. yields for both product types. Stoichiometric expts. indicated a stepwise mechanism: hydridic addn. to fluoroalkenes and subsequent β-F elimination from hydrophosphination intermediates. D. functional theory calcns. disclosed the origin of chemoselectivity, regioselectivity and stereoselectivity, suggesting an electron-donating effect of the alkene-terminal fluorine atom.
  64. 64
    Arevalo, A.; Tlahuext-Aca, A.; Flores-Alamo, M.; Garcia, J. J. On the Catalytic Hydrodefluorination of Fluoroaromatics Using Nickel Complexes: The True Role of the Phosphine. J. Am. Chem. Soc. 2014, 136, 4634– 4639,  DOI: 10.1021/ja412268y
    Google Scholar
    64
    On the Catalytic Hydrodefluorination of Fluoroaromatics Using Nickel Complexes: The True Role of the Phosphine
    Arevalo, Alma; Tlahuext-Aca, Adrian; Flores-Alamo, Marcos; Garcia, Juventino J.
    Journal of the American Chemical Society (2014), 136 (12), 4634-4639CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Homogeneous catalytic hydrodefluorination (HDF) of fluoroaroms. under thermal conditions was achieved using nickel(0) compds. of the type [(dippe)Ni(η2-C6F6-nHn)] where n = 0-2, as the catalytic precursors. These complexes were prepd. in situ by reacting the compd. [(dippe)Ni(μ-H)]2 with the resp. fluoroarom. substrate. HDF seems to occur homogeneously, as tested by mercury drop expts., producing the hydrodefluorinated products. However, despite previous findings by other groups, we found that these HDF reactions were actually the result of direct reaction of the alkylphosphine with the fluoroarom. substrate. This metal- and silane-free system is the first reported example of a phosphine being able to hydrodefluorinate on its own.
  65. 65
    Facundo, A. A.; Arevalo, A.; Fundora-Galano, G.; Flores-Alamo, M.; Orgaz, E.; Garcia, J. J. Hydrodefluorination of Functionalized Fluoroaromatics with Triethylphosphine: A Theoretical and Experimental Study. New J. Chem. 2019, 43, 6897– 6908,  DOI: 10.1039/C9NJ00721K
    Google Scholar
    65
    Hydrodefluorination of functionalized fluoroaromatics with triethylphosphine: a theoretical and experimental study
    Facundo, Aldo A.; Arevalo, Alma; Fundora-Galano, Gabriela; Flores-Alamo, Marcos; Orgaz, Emilio; Garcia, Juventino J.
    New Journal of Chemistry (2019), 43 (18), 6897-6908CODEN: NJCHE5; ISSN:1144-0546. (Royal Society of Chemistry)
    A new mechanism avoids the highly energetic β-elimination step of roughly 71 kcal mol-1 for hexafluorobenzene and pentafluoropyridine at 393.15 K, invoking the participation of water. The use of D2O confirmed the role of water as the hydrogen source, yielding the corresponding deutero-defluorinated products; DFT calcns. agree with this new proposed mechanism. The use of this one-pot hydrodefluorination method applied to a broader no. of fluoroarom. derivs. as e.g., 2,3,4,5,6-pentafluoro-1-trifluoromethylbenzene and some of them allowed the collection of key mechanistic evidence were reported.
  66. 66
    Bardin, V. V. Reactions of Polyfluoroaromatic Compounds with Electrophilic Agents in the Presence of Tris(dialkylamino) Phosphines. 8. Replacement of Fluorine by Hydrogen in Polyfluoroaromatic Compounds. Russ. Chem. Bull. 1997, 46, 1434– 1436,  DOI: 10.1007/BF02505680
    Google Scholar
    66
    Reaction of polyfluoroaromatic compounds with electrophilic agents in the presence of tris(dialkylamino)phosphines 8. Replacement of fluorine by hydrogen in polyfluoroaromatic compounds
    Bardin, V. V.
    Russian Chemical Bulletin (Translation of Izvestiya Akademii Nauk, Seriya Khimicheskaya) (1997), 46 (8), 1434-1436CODEN: RCBUEY; ISSN:1066-5285. (Consultants Bureau)
    When reacted with P(NEt2)3 and a proton donor, pentafluoropyridine, 3-chlorotetrafluoropyridine, pentafluorobenzonitrile, and octafluorotoluene yield products of replacement of the fluorine atom by hydrogen at position 4. This process is accompanied by the side reaction of aminodefluorination. In the case of 3H-heptafluorotoluene and octafluoronaphthalene, aminodefluorination is the main reaction. Reactions of perfluoro-4-isopropyltoluene, 4H-heptafluorotoluene, and 4-methylheptafluorotoluene do not occur under the above-mentioned conditions.
  67. 67

    List prices from Merck August 2023: PnBu3 £0.87/g (100g quantity), PhSiH3 £7.92/g (25g quantity), PhSiH2 £2.43/g (25g quantity), Ph3SiH £3.09/g (25g quantity). List price from Fischer Scientific August 2023: PiPr3 £29.6/g (10g quantity).

    There is no corresponding record for this reference.
  68. 68
    Gutov, A. V.; Rusanov, E. B.; Ryabitskii, A. B.; Chernega, A. N. Octafluoro-4,4′-Bipyridine and its Derivatives: Synthesis, Molecular and Crystal Structure. J. Fluorine Chem. 2010, 131, 278– 281,  DOI: 10.1016/j.jfluchem.2009.11.022
    Google Scholar
    68
    Octafluoro-4,4'-bipyridine and its derivatives: Synthesis, molecular and crystal structure
    Gutov, Alexey V.; Rusanov, Eduard B.; Ryabitskii, Alexey B.; Chernega, Alexander N.
    Journal of Fluorine Chemistry (2010), 131 (2), 278-281CODEN: JFLCAR; ISSN:0022-1139. (Elsevier B.V.)
    The structure and chem. properties of perfluoro-4,4'-bipyridine have been studied. It was found that octafluoro-4,4'-bipyridine is a quite electron deficient system stable to the action of alkylating agents and sensitive to nucleophilic substitution of fluorine atoms. Depending on the reaction conditions and reagents used products could be obtained in which two and six fluorine atoms are substituted by nucleophiles. For all isolated compds. X-ray structure detn. has been performed and the main peculiarities of the mol. and crystal structure of fluorine-contg. bipyridines have been detd.
  69. 69
    Anders, E.; Markus, F. Neue methode zur regiospezifischen substitution einiger reaktionsträcer N-heteroaromatischer ringsysteme. Tetrahedron Lett. 1987, 28, 2675– 2676,  DOI: 10.1016/S0040-4039(00)96178-1
    Google Scholar
    69
    A new method for the regiospecific substitution of a reaction tracing of N-heteroaromatic ring systems
    Anders, Ernst; Markus, Fritz
    Tetrahedron Letters (1987), 28 (24), 2675-6CODEN: TELEAY; ISSN:0040-4039.
    N-Trifluoromethanesulfonylheteroarylium salts, prepd. by the reaction of trifluoromethanesulfonic anhydride with pyridines, undergo regioselective substitution reaction with Ph3P to give phosphonium salts I (R = H, Et, CH2Ph, Br). Similar substitution reaction of I (R = H) gave diphosphonium salt II which regioselectively reacts with NaN3 to give iminophosphonium salt III. Hydrolytic cleavage of III gave 64% iminophosphorane IV.
  70. 70
    Mandal, D.; Gupta, R.; Young, R. D. Selective Monodefluorination and Wittig Functionalization of gem-Difluoromethyl Groups to Generate Monofluoroalkenes. J. Am. Chem. Soc. 2018, 140, 10682– 10686,  DOI: 10.1021/jacs.8b06770
    Google Scholar
    70
    Selective Monodefluorination and Wittig Functionalization of gem-Difluoromethyl Groups to Generate Monofluoroalkenes
    Mandal, Dipendu; Gupta, Richa; Young, Rowan D.
    Journal of the American Chemical Society (2018), 140 (34), 10682-10686CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Geminal difluorides underwent chemoselective monodefluorination with triarylphosphines such as (2-MeC6H4)3P and Ph3P and boron or aluminum complexes such as B(C6F5)3 and BF3·Et2O via frustrated Lewis pairs to yield monofluoroalkyl phosphonium salts such as I·FBX3 (R = 2-MeC6H4, Ph, 2,4,6-Me3C6H2; X = F, C6F5). The reaction relied on the reduced reactivity of the product monofluoroalkylphosphonium salts towards defluorination compared to the starting geminal difluorides. α-Fluoroalkylphosphonium salts such as I·FB(C6F5)3 (R = 2-MeC6H4) underwent stereoselective Wittig reactions with aldehydes R1CHO [R1 = Ph, 4-MeC6H4, 4-BrC6H4, 4-MeSC6H4, 3,4-Cl2C6H3, 2-BrC6H4, 4-Me2NC6H4, 4-O2NC6H4, 4-NCC6H4, Me(CH2)8, (E)-R2CH:CH, H, 4-Br-2-FC6H3; R2 = Ph, 4-Me2NC6H4, 4-O2NC6H4] mediated by LiHMDS to yield monofluoroalkenes such as II [R1 = Ph, 4-MeC6H4, 4-BrC6H4, 4-MeSC6H4, 3,4-Cl2C6H3, 2-BrC6H4, 4-Me2NC6H4, 4-O2NC6H4, 4-NCC6H4, Me(CH2)8, (E)-R2CH:CH, H, 4-Br-2-FC6H3; R2 = Ph, 4-Me2NC6H4, 4-O2NC6H4] in 27-94% yields. The structure of I·FB(C6F5)3 (R = 2-MeC6H4) was detd. by X-ray crystallog.
  71. 71
    Mandal, D.; Gupta, R.; Jaiswal, A. K.; Young, R. D. Frustrated Lewis-Pair-Meditated Selective Single Fluoride Substitution in Trifluoromethyl Groups. J. Am. Chem. Soc. 2020, 142, 2572– 2578,  DOI: 10.1021/jacs.9b12167
    Google Scholar
    71
    Frustrated Lewis-Pair-Mediated Selective Single Fluoride Substitution in Trifluoromethyl Groups
    Mandal, Dipendu; Gupta, Richa; Jaiswal, Amit K.; Young, Rowan D.
    Journal of the American Chemical Society (2020), 142 (5), 2572-2578CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Single fluoride substitution in trifluoromethylarenes is an ongoing synthetic challenge that often leads to "over-reaction", where multiple fluorides are replaced. Development of this reaction would allow simple access to a vast range of difluoromethyl derivs. of current interest to pharmaceutical, agrochem., and materials sciences. Using a catalytic frustrated Lewis pair approach, we have developed a generic protocol that allows a single substitution of one fluoride in trifluoromethyl groups with neutral phosphine and pyridine bases. The resulting phosphonium and pyridinium salts can be further functionalized via nucleophilic substitution, photoredox coupling, and electrophilic transfer reactions allowing the generation of a vast array of difluoromethyl products.
  72. 72
    Parks, D. J.; Piers, W. E. Tris(pentafluorophenyl)boron-Catalyzed Hydrosilation of Aromatic Aldehydes, Ketones, and Esters. J. Am. Chem. Soc. 1996, 118, 9440– 9441,  DOI: 10.1021/ja961536g
    Google Scholar
    72
    Tris(pentafluorophenyl)boron-Catalyzed Hydrosilation of Aromatic Aldehydes, Ketones, and Esters
    Parks, Daniel J.; Piers, Warren E.
    Journal of the American Chemical Society (1996), 118 (39), 9440-9441CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Tris(pentafluorophenyl)borane (1-4 mol %) catalyzes the addn. of Ph3SiH to carbonyl functions of arom. substrates p-XC6H4COR (X = Me, H, Cl, NO2; R = H, Me, OEt). Turnover frequencies for X = H substrates are 19, 45 and 637 h for R = H, Me and OEt, resp. and rates of hydrosilation increase as X becomes more electron withdrawing. Mechanistic studies, including substrate/borane binding equil., structural studies on substrate/borane adducts and kinetic measurements support a hydrosilation mechanism characterized by borane activation of the silane reagent rather than the carbonyl substrate. Key observations in support of this unusual nucleophilic/electrophilic hydrosilation mechanism were the obsd. inhibition of the reaction by increased concns. of substrate and the obsd. order of reactivity which indicates that the weaker binding substrates are reduced faster.
  73. 73
    Parks, D. J.; Blackwell, J. M.; Piers, W. E. Studies on the Mechanism of B(C6F5)3-Catalyzed Hydrosilation of Carbonyl Functions. J. Org. Chem. 2000, 65, 3090– 3098,  DOI: 10.1021/jo991828a
    Google Scholar
    73
    Studies on the Mechanism of B(C6F5)3-Catalyzed Hydrosilation of Carbonyl Functions
    Parks, Daniel J.; Blackwell, James M.; Piers, Warren E.
    Journal of Organic Chemistry (2000), 65 (10), 3090-3098CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
    The strong organoborane Lewis acid B(C6F5)3 catalyzes the hydrosilation (using R3SiH) of arom. and aliph. carbonyl functions at convenient rates with loadings of 1-4%. For aldehydes and ketones, the product silyl ethers were isolated in 75-96% yield; for esters, the aldehydes produced upon workup of the silyl acetal products can be obtained in 45-70% yield. Extensive mechanistic studies point to an unusual silane activation mechanism rather than one involving borane activation of the carbonyl function. Quant. kinetic studies show that the least basic substrates are hydrosilated at the fastest rates; furthermore, increased concns. of substrate have an inhibitory effect on the obsd. reaction rate. Paradoxically, the most basic substrates are reduced selectively, albeit at a slower rate, in competition expts. The borane thus must dissoc. from the carbonyl to activate the silane via hydride abstraction; the incipient silylium species then coordinates the most basic function, which is selectively reduced by [HB(C6F5)3]-. In addn. to the kinetic data, this mechanistic proposal is supported by a kinetic isotope effect of 1.4(5) for the hydrosilation of acetophenone, the observation that B(C6F5)3 catalyzes H/D and H/H scrambling in silanes in the absence of substrate, computational studies, the synthesis of models for proposed intermediates, and other isotope labeling and crossover expts.
  74. 74
    Eisenstein, O.; Milani, J.; Perutz, R. N. Selectivity of C-H Activation and Competition between C-H and C-F Bond Activation at Fluorocarbons. Chem. Rev. 2017, 117, 8710– 8753,  DOI: 10.1021/acs.chemrev.7b00163
    Google Scholar
    74
    Selectivity of C-H Activation and Competition between C-H and C-F Bond Activation at Fluorocarbons
    Eisenstein, Odile; Milani, Jessica; Perutz, Robin N.
    Chemical Reviews (Washington, DC, United States) (2017), 117 (13), 8710-8753CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
    Partially fluorinated alkanes, arenes, and alkenes can be transformed by a variety of transition metal and lanthanide systems. Although the C-H bond is weaker than the C-F bond regardless of the hybridization of the carbon, the reaction of the C-F bond at the metal is usually more exothermic than the corresponding reaction of the C-H bonds. Both bonds are activated by the metal systems, but the preference for activating these bonds depends on the nature of the hydrocarbon and of the metal system, so that the reaction can be directed exclusively toward C-H or C-F bonds or yield a mixt. of products. Addnl., the presence of fluorine differentiates between C-H bonds at different positions resulting in regioselective C-H bond activation; paradoxically, the strongest C-H bond reacts preferentially. The purpose of this review is to describe the field of reactions of partially fluorinated substrates with transition metal atoms, ions, and mol. complexes. The controlling phys. properties (thermodn. and kinetics) are described first, followed by a description of stoichiometric reactions, with the competition between the C-H and C-F activations as focus. A few representative catalytic systems are discussed. The review also highlights the benefit of combining exptl. and theor. studies.
  75. 75
    Slattery, J. M.; Hussein, S. How Lewis Acidic is Your Cation? Putting Phosphenium Ions on the Fluoride Ion Affinity Scale. Dalton Trans. 2012, 41, 1808– 1815,  DOI: 10.1039/C1DT11636C
    Google Scholar
    75
    How Lewis acidic is your cation? Putting phosphenium ions on the fluoride ion affinity scale
    Slattery, John M.; Hussein, Sharifa
    Dalton Transactions (2012), 41 (6), 1808-1815CODEN: DTARAF; ISSN:1477-9226. (Royal Society of Chemistry)
    The fluoride ion affinities (FIAs) of 33 phosphenium ions with a range of substituents were calcd. using ab initio and DFT methods. The use of these FIA data as a measure of the Lewis acidities of phosphenium ions is described and the FIAs of the species studied here are compared to FIA data for more commonly encountered Lewis acids. Phosphenium ions are often stronger Lewis acids than neutral species, but in many cases are less Lewis acidic than highly electrophilic cations such as [Me3C]+ or [Me3Si]+. The impact of mesomeric, inductive and steric substituent effects on FIAs are discussed and related to the underlying electronic structures of different cation types. A comparison between the FIAs of known "free" phosphenium ions with those that are currently unknown and other highly electrophilic cations suggests that some diaryl- and dialkyl phosphenium ions may yet be accessible under the right conditions.
  76. 76
    Gusev, D. G.; Ozerov, O. V. Calculated Hydride and Fluoride Affinities of a Series of Carbenium and Silylium Cations in the Gas Phase and in C6H5Cl Solution. Chem.─Eur. J. 2011, 17, 634– 640,  DOI: 10.1002/chem.201000696
    Google Scholar
    76
    Calculated Hydride and Fluoride Affinities of a Series of Carbenium and Silylium Cations in the Gas Phase and in C6H5Cl Solution
    Gusev, Dmitry G.; Ozerov, Oleg V.
    Chemistry - A European Journal (2011), 17 (2), 634-640, S634/1-S634/4CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
    We report the hydride and fluoride affinities for a group of silylium and carbenium cations. With comparable substituents on the central atom, the silylium cations have the higher fluoride affinity, whereas the carbenium ions have the higher hydride affinity. In the first approxn., the hydride and the fluoride affinities vary in parallel with changes in substitution, but the deviations from linear correspondence of hydride and fluoride affinities are more pronounced for carbenium ions. The hydride and fluoride affinities of silylium cations are very similar, whereas for carbenium ions, the hydride affinities are 35-60 kcal mol-1 higher than fluoride affinities. These results are placed in the context of studies of hydrodefluorination of aliph. C-F bonds enabled by silylium carborane catalysts. The abstraction of fluoride from perfluoroalkanes by a trialkylsilylium cation is neither thermodynamically favorable nor kinetically accessible and, if at all possible, will require a much more fluorophilic silylium cation.
  77. 77
    Hilton, M. C.; Dolewski, R. D.; McNally, A. Selective Functionalization of Pyridines via Heterocyclic Phosphonium Salts. J. Am. Chem. Soc. 2016, 138, 13806– 13809,  DOI: 10.1021/jacs.6b08662
    Google Scholar
    77
    Selective Functionalization of Pyridines via Heterocyclic Phosphonium Salts
    Hilton, Michael C.; Dolewski, Ryan D.; McNally, Andrew
    Journal of the American Chemical Society (2016), 138 (42), 13806-13809CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Methods that directly functionalize pyridines are in high demand due to their presence in pharmaceuticals, agrochems., and materials. A reaction that selectively transforms the 4-position C-H bonds in pyridines into C-PPh3+ groups that are subsequently converted into heteroaryl ethers is presented. The two step sequence is effective on complex pyridines, pharmaceutical mols., and other classes of heterocycles. Initial studies show that C-C, C-N, and C-S bond formations are also amenable.
  78. 78
    Anderson, R. G.; Jett, B. M.; McNally, A. Selective Formation Of Heteroaryl Thioethers via a Phosphonium Ion Coupling Reaction. Tetrahedron 2018, 74, 3129– 3136,  DOI: 10.1016/j.tet.2017.12.040
    Google Scholar
    78
    Selective formation of heteroaryl thioethers via a phosphonium ion coupling reaction
    Anderson, Ryan G.; Jett, Brianna M.; McNally, Andrew
    Tetrahedron (2018), 74 (25), 3129-3136CODEN: TETRAB; ISSN:0040-4020. (Elsevier Ltd.)
    Heteroaryl thioethers, comprised of pyridines and diazines, are an important class of compds. with relevance to medicinal chem. Metal-catalyzed cross-couplings and SNAr reactions are traditionally used to form C-S bonds in these systems but are limited by available halogenated precursors. An alternative approach is presented where pyridines and diazines are transformed into heterocyclic phosphonium salts and then C-S bonds are formed by adding thiolate nucleophiles. The process is 4-selective for pyridines, simple to execute and can be used to make derivs. of complex pharmaceuticals.
  79. 79
    Anderson, R. G.; Jett, B. M.; McNally, A. A Unified Approach to Couple Aromatic Heteronucleophiles to Azines and Pharmaceuticals. Angew. Chem., Int. Ed. 2018, 57, 12514– 12518,  DOI: 10.1002/anie.201807322
    Google Scholar
    79
    A Unified Approach to Couple Aromatic Heteronucleophiles to Azines and Pharmaceuticals
    Anderson, Ryan G.; Jett, Brianna M.; McNally, Andrew
    Angewandte Chemie, International Edition (2018), 57 (38), 12514-12518CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Coupling arom. heteronucleophiles to arenes is a common way to assemble drug-like mols. Many methods operate via nucleophiles intercepting organometallic intermediates, via Pd-, Cu-, and Ni-catalysis, that facilitate carbon-heteroatom bond formation and a variety of protocols. We present an alternative, unified strategy where phosphonium salts can replicate the behavior of organometallic intermediates. Under a narrow set of reaction conditions, a variety of arom. heteronucleophile classes can be coupled to pyridines and diazines that are often problematic in metal-catalyzed couplings, such as where (pseudo)halide precursors are unavailable in complex structures with multiple polar functional groups.
  80. 80
    Kwan, E. E.; Zeng, Y. W.; Besser, H. A.; Jacobsen, E. N. Concerted Nucleophilic Aromatic Substitutions. Nat. Chem. 2018, 10, 917– 923,  DOI: 10.1038/s41557-018-0079-7
    Google Scholar
    80
    Concerted nucleophilic aromatic substitutions
    Kwan, Eugene E.; Zeng, Yuwen; Besser, Harrison A.; Jacobsen, Eric N.
    Nature Chemistry (2018), 10 (9), 917-923CODEN: NCAHBB; ISSN:1755-4330. (Nature Research)
    Nucleophilic arom. substitution (SNAr) is one of the most widely applied reaction classes in pharmaceutical and chem. research, providing a broadly useful platform for the modification of arom. ring scaffolds. The generally accepted mechanism for SNAr reactions involves a two-step addn.-elimination sequence via a discrete, non-arom. Meisenheimer complex. Here the authors use 12C/13C kinetic isotope effect (KIE) studies and computational analyses to provide evidence that prototypical SNAr reactions in fact proceed through concerted mechanisms. The KIE measurements were made possible by a new technique that leverages the high sensitivity of 19F as an NMR nucleus to quantitate the degree of isotopic fractionation. This sensitive technique permits the measurement of KIEs on 10 mg of natural abundance material in one overnight acquisition. As a result, it provides a practical tool for performing detailed mechanistic analyses of reactions that form or break C-F bonds.
  81. 81
    Pike, S. D.; Crimmin, M. R.; Chaplin, A. B. Organometallic Chemistry Using Partially Fluorinated Benzenes. Chem. Commun. 2017, 53, 3615– 3633,  DOI: 10.1039/C6CC09575E
    Google Scholar
    81
    Organometallic chemistry using partially fluorinated benzenes
    Pike, Sebastian D.; Crimmin, Mark R.; Chaplin, Adrian B.
    Chemical Communications (Cambridge, United Kingdom) (2017), 53 (26), 3615-3633CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
    A review of fluorobenzenes, in particular fluorobenzene (FB) and 1,2-difluorobenzene (1,2-DiFB), which are increasingly becoming recognized as versatile solvents for conducting organometallic chem. and transition-metal-based catalysis. The presence of F substituents reduces the ability to donate π-electron d. from the arene and consequently fluorobenzenes generally bind weakly to metal centers, allowing them to be used as essentially noncoordinating solvents or as readily displaced ligands. In this context, examples of well-defined complexes of fluorobenzenes are discussed, including trends in binding strength with increasing fluorination and different substitution patterns. Compared to more highly fluorinated benzenes, FB and 1,2-DiFB typically demonstrate greater chem. inertness, however, C-H and C-F bond activation reactions can be induced using appropriately reactive transition metal complexes. Such reactions are surveyed, including catalytic examples, not only to provide perspective for the use of FB and 1,2-DiFB as innocent solvent media, but also to highlight opportunities for their exploitation in contemporary org. synthesis.
  82. 82
    Côté, J.-F.; Brouillette, D.; Desnoyers, J. E.; Rouleau, J. F.; StArnaud, J. M.; Perron, G. Dielectric Constants of Acetonitrile, Gamma-Butyrolactone, Propylene Carbonate, and 1,2-Dimethoxyethane as a Function of Pressure and Temperature. J. Solution Chem. 1996, 25, 1163– 1173,  DOI: 10.1007/BF00972644
    Google Scholar
    82
    Dielectric constants of acetonitrile, γ-butyrolactone, propylene carbonate, and 1,2-dimethoxyethane as a function of pressure and temperature
    Cote, Jean-francois; Brouillette, Dany; Desnoyers, Jacques E.; Rouleau, Jean-Francois; St-Arnaud, Jean-Marie; Perron, Gerald
    Journal of Solution Chemistry (1996), 25 (12), 1163-1173CODEN: JSLCAG; ISSN:0095-9782. (Plenum)
    The dielec. consts. ε of 1,2-dimethoxyethane, acetonitrile, γ-butyrolactone, and propylene carbonate were detd. from capacitance measurements extrapolated to infinite frequency; ln ε are reported as a function of pressure up to 80 MPa at 15, 25, 35, 45° and as a function of temp. in the range 10 to 50° at 0.10133 MPa. The variation of ln ε with temp. or pressure can be expressed by a second order polynomial expression. The isothermal compressibilities β of the solvents were detd. at 25° from sound velocities, densities, ad heat capacities. A simple correlation can be established between .vdelta. ln ε/.vdelta.P and β for most aprotic solvent.
  83. 83
    Hoffmann, R.; Howell, J. M.; Muetterties, E. L. Molecular-Orbital Theory of Pentacoordinate Phosphorus. J. Am. Chem. Soc. 1972, 94, 3047– 3058,  DOI: 10.1021/ja00764a028
    Google Scholar
    83
    Molecular orbital theory of pentacoordinate phosphorus
    Hoffmann, Roald; Howell, James M.; Muetterties, Earl L.
    Journal of the American Chemical Society (1972), 94 (9), 3047-58CODEN: JACSAT; ISSN:0002-7863.
    The electronic structure of some idealized PH5 geometries of D3h, C4v, and Cs symmetries is analyzed. Each geometry is characterized by a low-lying nodeless orbital, 3 singly noded orbitals close in energy, and a high-lying doubly noded nonbonding orbital. The latter orbital is the only one significantly stabilized by the inclusion of 3d orbitals in the P basis set and also dets. the relative stability of substituted compds. differing in electronegativity from H. A potential surface connecting the D3h and C4v geometries through C2v structures is constructed. It shows a small barrier for the Berry pseudorotation process. Optimum Cs structures are at higher energy than the C4v geometry. An examn. of substituent effects rationalizes favored apical substitution in the trigonal bipyramid and preferred basal substitution in the square pyramid by more electroneg. groups. It is predicted that π acceptors will prefer axial sites in the trigonal bipyramid, π donors equatorial positions. If a substituent has a single π system and is located in the equatorial position it will prefer to have its acceptor orbital perpendicular to the equatorial plane or its donor orbital in that plane. In the square pyramid, π donors will favor the apical position, π acceptors the basal sites. The concerted fragmentation reaction PR5 ↹ PR3 + R2 is symmetry forbidden for the least-motion axial-equatorial departure from a trigonal bipyramid, and allowed for axial-axial or equatorial-equatorial departure.

Cited By

Click to copy section linkSection link copied!
Citation Statements
Explore this article's citation statements on scite.ai
powered by  Scite

This article is cited by 19 publications.

  1. Nimisha Gautam, Sreejyothi P, Kaushik Soni, Subhajit Chakraborty, Subir Maji, Kalishankar Bhattacharyya, Swadhin K. Mandal. aNHC-Stabilized Low-Valent Phosphorus Compound: Exploring Dual Catalytic Activity via Nucleophilicity and P(I)/P(III) Redox Reactivity. Journal of the American Chemical Society 2025, Article ASAP.
  2. Wenbang Yang, Andrew J. P. White, Mark R. Crimmin. Boron, Aluminum, and Gallium Fluorides as Catalysts for the Defluorofunctionalization of Electron-Deficient Arenes: The Role of NaBArF4 Promoters. Inorganic Chemistry 2025, 64 (12) , 6092-6099. https://doi.org/10.1021/acs.inorgchem.4c05381
  3. Ruihan Wang, Sebastián Martínez, Johannes Schwarzmann, Christopher Z. Zhao, Jacqueline Ramler, Crispin Lichtenberg, Yi-Ming Wang. Transition Metal Mimetic π-Activation by Cationic Bismuth(III) Catalysts for Allylic C–H Functionalization of Olefins Using C═O and C═N Electrophiles. Journal of the American Chemical Society 2024, 146 (32) , 22122-22128. https://doi.org/10.1021/jacs.4c06235
  4. Bryce C. Nussbaum, Cameron R. Cavicchi, Mark D. Smith, Perry J. Pellechia, Dmitry V. Peryshkov. Redox-Active Carboranyl Diphosphine as an Electron and Proton Transfer Agent. Inorganic Chemistry 2024, 63 (32) , 15053-15060. https://doi.org/10.1021/acs.inorgchem.4c02022
  5. Minghao Huang, Kunlong Li, Zichen Zhang, Jiliang Zhou. Antimony Redox Catalysis: Hydroboration of Disulfides through Unique Sb(I)/Sb(III) Redox Cycling. Journal of the American Chemical Society 2024, 146 (29) , 20432-20438. https://doi.org/10.1021/jacs.4c05905
  6. John S. Wenger, Timothy C. Johnstone. A Sterically Accessible Monomeric Stibine Oxide Activates Organotetrel(IV) Halides, Including C–F and Si–F Bonds. Journal of the American Chemical Society 2024, 146 (28) , 19350-19359. https://doi.org/10.1021/jacs.4c05394
  7. Sreejyothi P, Nimisha Gautam, Subir Maji, Kalishankar Bhattacharyya, Swadhin K. Mandal. Transition Metal-Mimicking Relay Catalysis by a Low-Valent Phosphorus Compound. Journal of the American Chemical Society 2024, 146 (24) , 16743-16752. https://doi.org/10.1021/jacs.4c04376
  8. John C. Hoefler, Devin Jackson, Janet Blümel. Surface-Assisted Selective Air Oxidation of Phosphines Adsorbed on Activated Carbon. Inorganic Chemistry 2024, 63 (20) , 9275-9287. https://doi.org/10.1021/acs.inorgchem.4c01027
  9. Soodeh Mollasalehi, Mike Ahrens, Thomas Braun. Activation of perfluoro(methyl vinyl ether) at Rh( i ) complexes: metal-centered versus phosphine-mediated decarbonylation. Chemical Science 2025, 16 (24) , 10928-10934. https://doi.org/10.1039/D5SC02056E
  10. Nathan C. Frey, Samir Kumar Sarkar, Diane A. Dickie, Andrew Molino, Robert J. Gilliard. Borinine-FLP ring expansion: isolation of eight-membered B–P rings bridged by μ 2 chalcogenide and chloronium ions. Chemical Science 2025, 16 (24) , 10857-10866. https://doi.org/10.1039/D5SC02000J
  11. Deependra Bawari, Donia Toami, Roman Dobrovetsky. Advancing metallomimetic catalysis through structural constraints of cationic P III species. Chemical Communications 2025, 61 (32) , 5871-5882. https://doi.org/10.1039/D5CC00723B
  12. Sara Bonfante, Theo F. N. Tanner, Christian Lorber, Jason M. Lynam, Antoine Simonneau, John M. Slattery. Zirconium-mediated carbon–fluorine bond functionalisation through cyclohexyne “umpolung”. Chemical Science 2025, 16 (8) , 3552-3559. https://doi.org/10.1039/D4SC08522A
  13. Deependra Bawari, Irina Malahov, Roman Dobrovetsky. Sb‐to‐P Metathesis: A Direct Route to Structurally Constrained, Cationic P III Compound. Angewandte Chemie International Edition 2025, 64 (7) https://doi.org/10.1002/anie.202419772
  14. Deependra Bawari, Irina Malahov, Roman Dobrovetsky. Sb‐to‐P Metathesis: A Direct Route to Structurally Constrained, Cationic P III Compound. Angewandte Chemie 2025, 137 (7) https://doi.org/10.1002/ange.202419772
  15. Zhuchunguang Liu, Zhijun Wang, Huan Mu, Yihan Zhou, Jiliang Zhou, Zhaowen Dong. Synthesis and redox catalysis of Carbodiphosphorane ligated stannylene. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-024-54321-y
  16. Jia-Wei Chen, Wen-Jun Ji, Xue-Ying Huang, Danhua Ge, Zhi-Liang Shen, Kai Guo, Xue-Qiang Chu. Chemo-, regio-, and stereoselective tetrafunctionalization of fluoroalkynes enables divergent synthesis of 5-7-membered azacycles. Chemical Science 2024, 15 (30) , 12026-12035. https://doi.org/10.1039/D4SC03230F
  17. Aaron J. King, Jose M. Goicoechea. Ligand Centered Reactivity of a Transition Metal Bound Geometrically Constrained Phosphine. Chemistry – A European Journal 2024, 30 (26) https://doi.org/10.1002/chem.202400624
  18. Andrew McNally. Towards Catalytic C–H Activation Using Main Group Elements. Synlett 2024, 35 (08) , 877-882. https://doi.org/10.1055/a-2290-6711
  19. . Trialkylphosphines-Catalyzed C–F Activation of Highly Fluorinated Arenes and Heteroarenes. Synfacts 2024, 0408. https://doi.org/10.1055/s-0043-1763878
Download PDF
Go to Journal of the American Chemical Society
Get e-Alerts
Get e-Alerts

Journal of the American Chemical Society

Cite this: J. Am. Chem. Soc. 2024, 146, 3, 2005–2014
Click to copy citationCitation copied!
https://doi.org/10.1021/jacs.3c10614
Published January 11, 2024

Copyright © 2024 The Authors. Published by American Chemical Society. This publication is licensed under

CC-BY 4.0 .

Article Views

15k

Altmetric

-

Citations

19
Learn about these metrics

Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.

  • Abstract

    High Resolution Image
    Download MS PowerPoint Slide

    Scheme 1

    Scheme 1. Comparison of Recent Aromatic Hydrodefluorination (HDF) Reactions Promoted or Catalysed by Main Group Compounds Through Redox-Neutral (A) or Redox-Cycling (B) Pathways and the Present Work (C)
    High Resolution Image
    Download MS PowerPoint Slide

    Scheme 2

    Scheme 2. Results of Substrate Scope Studiesa
    High Resolution Image
    Download MS PowerPoint Slide

    aPh2SiH2 was used for all HDF reactions and Ph2Si(Cl)(NR2) were used for aminodefluorination reactions.

    bIsolated yield after flash column chromatography shown in parentheses.

    cReactions were stirred at 60 °C for 4 days, followed by the remaining period at 80 °C.

    dStoichiometric reaction between PiPr3 and 1 in MeCN (other phosphines behave similarly).

    Scheme 3

    Scheme 3. Preparation of Phosphonium Ions Proposed to be Intermediates in the Catalytic Reactions and their Reactivity Toward Silanes in the Presence, and Absence, of a Fluoride Source
    High Resolution Image
    Download MS PowerPoint Slide

    Scheme 4

    Scheme 4. Proposed Catalytic Cycle and Computed Potential Energy Surface (PES) for R = Mea
    High Resolution Image
    Download MS PowerPoint Slide

    aAll energies at the PBE0/def2-TZVP//BP86/SV(P) level in MeCN. Relative Gibbs energies (in kJ mol–1 at 298 K) shown outside brackets and relative enthalpies (in kJ mol–1 at 298 K) shown in brackets. See Supporting Information for details of solvent and dispersion corrections applied.

    Figure 1

    Figure 1. Transition states for the addition of PMe3 to 1 (TS12) and elimination of 2 from phosphorane M6 (TS61). Hydrogen is shown in white, carbon in gray, phosphorus in orange, nitrogen in blue, and fluorine in green. Selected distances (in Å) are shown.

    High Resolution Image
    Download MS PowerPoint Slide

  • References

    This article references 83 other publications.

    1. 1
      Power, P. P. Main-Group Elements as Transition Metals. Nature 2010, 463, 171– 177,  DOI: 10.1038/nature08634
      1
      Main-group elements as transition metals
      Power, Philip P.
      Nature (London, United Kingdom) (2010), 463 (7278), 171-177CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)
      A review. The last quarter of the twentieth century and the beginning decade of the twenty-first witnessed spectacular discoveries in the chem. of the heavier main-group elements. The discoveries that led to this change originated from a simple desire to synthesize main-group compds. that were unknown as stable species. These featured one or more of the following: (1) multiple bonds between heavier main-group elements such as Al, Si, P or their heavier congeners; (2) stable low-valent derivs. with open coordination sites; (3) mols. with quasi-open coordination sites as a result of frustrated Lewis pairs; (4) stable paramagnetic electron configurations (that is radicals) with unpaired electrons centered on heavier main-group elements; or (5) stable singlet diradicaloid electron configurations. The new compds. that were synthesized highlighted the fundamental differences between their electronic properties and those of the lighter elements to a degree that was not previously apparent. This led to new structural and bonding insights as well as a gradually increasing realization that the chem. of the heavier main-group elements more resembles that of transition-metal complexes than that of their lighter main-group congeners. The similarity is underlined by recent work, which showed that many of the new compds. react with small mols. such as H2, NH3, C2H4 or CO under mild conditions and display potential for applications in catalysis.
    2. 2
      Weetman, C.; Inoue, S. The Road Travelled: After Main-Group Elements as Transition Metals. ChemCatChem 2018, 10, 4213– 4228,  DOI: 10.1002/cctc.201800963
      2
      The Road Travelled: After Main-Group Elements as Transition Metals
      Weetman, Catherine; Inoue, Shigeyoshi
      ChemCatChem (2018), 10 (19), 4213-4228CODEN: CHEMK3; ISSN:1867-3880. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Since the latter quarter of the twentieth century, main group chem. has undergone significant advances. Power's timely review in 2010 highlighted the inherent differences between the lighter and heavier main group elements, and that the heavier analogs resemble transition metals as shown by their reactivity towards small mols. In this concept article, we present an overview of the last 10 years since Power's seminal review, and the progress made for catalytic application. This examines the use of low oxidn. state and/or low coordinate group 13 and 14 complexes towards small mol. activation (oxidative addn. step in a redox based cycle) and how ligand design plays a crucial role in influencing subsequent reactivity. The challenge in these redox based catalytic cycles still centers on the main group complexes' ability to undergo reductive elimination, however considerable progress in this field has been reported via reversible oxidative addn. reactions. Within the last 5 years, the first examples of well-defined low valent main group catalysts have begun to emerge, representing a bright future ahead for main group chem.
    3. 3
      Melen, R. L. Frontiers in Molecular p-Block Chemistry: From Structure to Reactivity. Science 2019, 363, 479– 484,  DOI: 10.1126/science.aau5105
      3
      Frontiers in molecular p-block chemistry: From structure to reactivity
      Melen, Rebecca L.
      Science (Washington, DC, United States) (2019), 363 (6426), 479-484CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
      A review. This year marks the 350th anniversary of the discovery of phosphorus by the alchemist Hennig Brand. However, this element was not included in the p-block of the periodic table until more recently. 2019 also marks the 150th anniversary of the preliminary tabular arrangement of the elements into the periodic system by Mendeleev. Of the 63 elements known in 1869, almost one-third of them belonged to what ultimately became the p-block, and Mendeleev predicted the existence of both gallium and germanium as well. The elements of the p-block have a disparate and varied history. Their chem. structure, reactivity, and properties vary widely. Nevertheless, in recent years, a better understanding of trends in p-block reactivity, particularly the behavior of those elements not typically found in biol. systems, has led to a promising array of emerging applications, highlighted herein.
    4. 4
      Weetman, C. Main Group Multiple Bonds for Bond Activations and Catalysis. Chem.─Eur. J. 2021, 27, 1941– 1954,  DOI: 10.1002/chem.202002939
      4
      Main Group Multiple Bonds for Bond Activations and Catalysis
      Weetman, Catherine
      Chemistry - A European Journal (2021), 27 (6), 1941-1954CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. Since the discovery that the so-called "double-bond" rule could be broken, the field of mol. main group multiple bonds has expanded rapidly. With the majority of homodiat. double and triple bonds realized within the p-block, along with many heterodiat. combinations, this Minireview examines the reactivity of these compds. with a particular emphasis on small mol. activation. Furthermore, while their ability to act as transition metal mimics has been explored, their catalytic behavior is somewhat limited. This Minireview aims to highlight the potential of these complexes towards catalytic application and their role as synthons in further functionalizations making them a versatile tool for the modern synthetic chemist.
    5. 5
      Braunschweig, H.; Krummenacher, I.; Legare, M. A.; Matler, A.; Radacki, K.; Ye, Q. Main-Group Metallomimetics: Transition Metal-like Photolytic CO Substitution at Boron. J. Am. Chem. Soc. 2017, 139, 1802– 1805,  DOI: 10.1021/jacs.6b13047
      5
      Main-Group Metallomimetics: Transition Metal-like Photolytic CO Substitution at Boron
      Braunschweig, Holger; Krummenacher, Ivo; Legare, Marc-Andre; Matler, Alexander; Radacki, Krzysztof; Ye, Qing
      Journal of the American Chemical Society (2017), 139 (5), 1802-1805CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      The carbon monoxide adduct of an unhindered and highly reactive CAAC-bound arylborylene, [(CAAC)B(CO)Ar] (CAAC = cyclic (alkyl) (amino)carbene), has been prepd. using a transfer reaction from the linear iron borylene complex [(PMe3) (CO)3Fe:BAr]. [(CAAC)B(CO)Ar] is a source of the dicoordinate [(CAAC)ArB:] borylene that can be liberated by selective photolytic CO extrusion and that, although highly reactive, is sufficiently long-lived to react intermolecularly. Through trapping of the borylene generated in this manner, we present, among others, the first metal-free borylene(I) species contg. a nitrogen-based donor, as well as a new boron-contg. radical.
    6. 6
      Légaré, M. A.; Pranckevicius, C.; Braunschweig, H. Metallomimetic Chemistry of Boron. Chem. Rev. 2019, 119, 8231– 8261,  DOI: 10.1021/acs.chemrev.8b00561
      6
      Metallomimetic Chemistry of Boron
      Legare, Marc-Andre; Pranckevicius, Conor; Braunschweig, Holger
      Chemical Reviews (Washington, DC, United States) (2019), 119 (14), 8231-8261CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
      A review. The study of main-group mols. that behave and react similarly to transition metal (TM) complexes has attracted significant interest in the recent decades. Most notably, the attractive idea of replacing the all-too-often rare and costly metals from catalysis has motivated efforts to develop main group element-mediated reactions. Main group elements, however, lack the electronic flexibility of many TM complexes that arise from combinations of empty and filled d-orbitals and that seem ideally suited to bind and activate many substrates. In this review, we look at boron, an element that despite its nonmetal nature, low at. wt., and relative redox staticity has achieved great milestones in terms of TM-like reactivity. We show how in interelement cooperative systems, diboron mols. and hypovalent complexes, the fifth element can acquire a truly metallomimetic character. As we discuss, this character is particularly demonstrated by the reactivity of boron-based mols. with H2, CO, alkynes, alkenes and even with N2.
    7. 7
      Welch, G. C.; Juan, R. R. S.; Masuda, J. D.; Stephan, D. W. Reversible, Metal-Free Hydrogen Activation. Science 2006, 314, 1124– 1126,  DOI: 10.1126/science.1134230
      7
      Reversible, Metal-Free Hydrogen Activation
      Welch, Gregory C.; San Juan, Ronan R.; Masuda, Jason D.; Stephan, Douglas W.
      Science (Washington, DC, United States) (2006), 314 (5802), 1124-1126CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
      Although reversible covalent activation of mol. hydrogen (H2) is a common reaction at transition metal centers, it has proven elusive in compds. of the lighter elements. The compd. (C6H2Me3)2PH(C6F4)BH(C6F5)2 (Me, methyl), which was derived through an unusual reaction involving dimesitylphosphine substitution at a para carbon of tris(pentafluorophenyl)borane, cleanly loses H2 at temps. above 100°. Preliminary kinetic studies reveal this process to be first order. Remarkably, the dehydrogenated product (C6H2Me3)2P(C6F4)B(C6F5)2 is stable and reacts with 1 atm of H2 at 25° to reform the starting complex. Deuteration studies were also carried out to probe the mechanism.
    8. 8
      Stephan, D. W.; Erker, G. Frustrated Lewis Pairs: Metal-free Hydrogen Activation and More. Angew. Chem., Int. Ed. 2010, 49, 46– 76,  DOI: 10.1002/anie.200903708
      8
      Frustrated Lewis Pairs: Metal-free Hydrogen Activation and More
      Stephan, Douglas W.; Erker, Gerhard
      Angewandte Chemie, International Edition (2010), 49 (1), 46-76CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. Sterically encumbered Lewis acid and Lewis base combinations do not undergo the ubiquitous neutralization reaction to form classical Lewis acid/Lewis base adducts. Rather, both the unquenched Lewis acidity and basicity of such sterically frustrated Lewis pairs (FLPs) is available to carry out unusual reactions. Typical examples of frustrated Lewis pairs are inter- or intramol. combinations of bulky phosphines or amines with strongly electrophilic RB(C6F5)2 components. Many examples of such frustrated Lewis pairs are able to cleave dihydrogen heterolytically. The resulting H+/H- pairs (stabilized for example, as the resp. phosphonium cation/hydridoborate anion salts) serve as active metal-free catalysts for the hydrogenation of, for example, bulky imines, enamines, or enol ethers. Frustrated Lewis pairs also react with alkenes, aldehydes, and a variety of other small mols., including carbon dioxide, in cooperative three-component reactions, offering new strategies for synthetic chem.
    9. 9
      Stephan, D. W.; Erker, G. Frustrated Lewis Pair Chemistry of Carbon, Nitrogen and Sulfur Oxides. Chem. Sci. 2014, 5, 2625– 2641,  DOI: 10.1039/C4SC00395K
      9
      Frustrated Lewis pair chemistry of carbon, nitrogen and sulfur oxides
      Stephan, Douglas W.; Erker, Gerhard
      Chemical Science (2014), 5 (7), 2625-2641CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
      Frustrated Lewis pairs have been used to activate a variety of small mols. In this review we focus on the recent chem. of FLPs with CO2, CO, N2O, NO and SO2. While FLP capture of these small mol. is achieved in all of these cases, subsequent applications of the products include stoichiometric and catalytic redns. of CO2, C-O bond scission of CO and use of FLP-NO radicals in polymn.
    10. 10
      Stephan, D. W. Frustrated Lewis Pairs. J. Am. Chem. Soc. 2015, 137, 10018– 10032,  DOI: 10.1021/jacs.5b06794
      10
      Frustrated Lewis Pairs
      Stephan, Douglas W.
      Journal of the American Chemical Society (2015), 137 (32), 10018-10032CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      A review. The articulation of the notion of "frustrated Lewis pairs" (FLPs), which emerged from the discovery that H2 can be reversibly activated by combinations of sterically encumbered Lewis acids and bases, has prompted a great deal of recent activity. Perhaps the most remarkable consequence has been the development of FLP catalysts for the hydrogenation of a range of org. substrates. In the past 9 years, the substrate scope has evolved from bulky polar species to include a wide range of unsatd. org. mols. In addn., effective stereoselective metal-free hydrogenation catalysts have begun to emerge. The mechanism of this activation of H2 has been explored, and the nature and range of Lewis acid/base combinations capable of effecting such activation have also expanded to include a variety of non-metal species. The reactivity of FLPs with a variety of other small mols., including olefins, alkynes, and a range of element oxides, has also been developed. Although much of this latter chem. has uncovered unique stoichiometric transformations, metal-free catalytic hydroamination, CO2 redn. chem., and applications in polymn. have also been achieved. The concept is also beginning to find applications in bioinorg. and materials chem. as well as heterogeneous catalysis. This Perspective highlights many of these developments and discusses the relationship between FLPs and established chem. Some of the directions and developments that are likely to emerge from FLP chem. in the future are also presented.
    11. 11
      Stephan, D. W. Frustrated Lewis Pairs: From Concept to Catalysis. Acc. Chem. Res. 2015, 48, 306– 316,  DOI: 10.1021/ar500375j
      11
      Frustrated Lewis Pairs: From Concept to Catalysis
      Stephan, Douglas W.
      Accounts of Chemical Research (2015), 48 (2), 306-316CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)
      A review. Frustrated Lewis pair (FLP) chem. has emerged in the past decade as a strategy that enables main-group compds. to activate small mols. This concept is based on the notion that combinations of Lewis acids and bases that are sterically prevented from forming classical Lewis acid-base adducts have Lewis acidity and basicity available for interaction with a third mol. This concept has been applied to stoichiometric reactivity and then extended to catalysis. This Account describes three examples of such developments: hydrogenation, hydroamination, and CO2 redn. The most dramatic finding from FLP chem. was the discovery that FLPs can activate H2, thus countering the long-existing dogma that metals are required for such activation. This finding of stoichiometric reactivity was subsequently evolved to employ simple main-group species as catalysts in hydrogenations. While the initial studies focused on imines, subsequent studies uncovered FLP catalysts for a variety of org. substrates, including enamines, silyl enol ethers, olefins, and alkynes. Moreover, FLP redns. of arom. anilines and N-heterocycles have been developed, while very recent extensions have uncovered the utility of FLP catalysts for ketone redns. FLPs have also been shown to undergo stoichiometric reactivity with terminal alkynes. Typically, either deprotonation or FLP addn. reaction products are obsd., depending largely on the basicity of the Lewis base. While a variety of acid/base combinations have been exploited to afford a variety of zwitterionic products, this reactivity can also be extended to catalysis. When secondary aryl amines are employed, hydroamination of alkynes can be performed catalytically, providing a facile, metal-free route to enamines. In a similar fashion, initial studies of FLPs with CO2 demonstrated their ability to capture this greenhouse gas. Again, modification of the constituents of the FLP led to the discovery of reaction systems that demonstrated stoichiometric redn. of CO2 to either methanol or CO. Further modification led to the development of catalytic systems for the redn. of CO2 by hydrosilylation and hydroboration or deoxygenation. As each of these areas of FLP chem. has advanced from the observation of unusual stoichiometric reactions to catalytic processes, it is clear that the concept of FLPs provides a new strategy for the design and application of main-group chem. and the development of new metal-free catalytic processes.
    12. 12
      Lam, J.; Szkop, K. M.; Mosaferi, E.; Stephan, D. W. FLP Catalysis: Main Group Hydrogenations of Organic Unsaturated Substrates. Chem. Soc. Rev. 2019, 48, 3592– 3612,  DOI: 10.1039/C8CS00277K
      12
      FLP catalysis: main group hydrogenations of organic unsaturated substrates
      Lam, Jolie; Szkop, Kevin M.; Mosaferi, Eliar; Stephan, Douglas W.
      Chemical Society Reviews (2019), 48 (13), 3592-3612CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
      A review. This article is focused on recent developments in main group mediated hydrogenation chem. and catalysis using 'frustrated Lewis pairs' (FLPs). The broading range of substrates and catalyst systems is reviewed and the advances in catalytic redns. and the development of stereoselective, asym. redns. made since 2012 was considered.
    13. 13
      Paradies, J. From Structure to Novel Reactivity in Frustrated Lewis Pairs. Coord. Chem. Rev. 2019, 380, 170– 183,  DOI: 10.1016/j.ccr.2018.09.014
      13
      From structure to novel reactivity in frustrated Lewis pairs
      Paradies, Jan
      Coordination Chemistry Reviews (2019), 380 (), 170-183CODEN: CCHRAM; ISSN:0010-8545. (Elsevier B.V.)
      A review. The coexistence of a strong Lewis acid and a Lewis base in soln., the so called frustrated Lewis pair, has led to the discovery of metal-free hydrogen activation. Since then, this observation has inspired numerous chemists to develop more examples. Metal-free hydrogenation is so far the most studied application of frustrated Lewis pairs in chem. and highly efficient methodologies for a no. of substrates have been developed. However, the targeted choice of a FLP-catalyst is yet rather intricate, due to the lack of an in depth understanding of FLP-reactivity. The presented structure-reactivity-relationship for hydrogenation reactions allowed the targeted development and optimization of unprecedented reactions using FLPs as catalysts. This article provides insight into FLP-reactivity by summarizing our mechanistic and synthetic work in this field.
    14. 14
      Li, N.; Zhang, W. X. Frustrated Lewis Pairs: Discovery and Overviews in Catalysis. Chin. J. Chem. 2020, 38, 1360– 1370,  DOI: 10.1002/cjoc.202000027
      14
      Frustrated Lewis Pairs: Discovery and Overviews in Catalysis
      Li, Nan; Zhang, Wen-Xiong
      Chinese Journal of Chemistry (2020), 38 (11), 1360-1370CODEN: CJOCEV; ISSN:1001-604X. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. Frustrated Lewis Pairs (FLPs) are derived from simple combinations of Lewis acids (electron acceptors) and Lewis bases (electron donors), in which steric demands prevent from forming classical Lewis acid-base adducts. Since 2006, FLP chem. has emerged as a novel strategy for the design and application of main-group chem. and development of new metal-free catalytic processes. This strategy has been applied to stoichiometric reactivity and then extended to catalysis. In this review, the representative discoveries and developments of FLP chem. in the field of catalysis, including hydrogenation, hydrosilylation, redn. of CO2, transformations of alkynes to org. derivs., C-H bond borylation and polymn. have been briefly summarized.
    15. 15
      Stephan, D. W.; Erker, G. Frustrated Lewis Pair Chemistry: Development and Perspectives. Angew. Chem., Int. Ed. 2015, 54, 6400– 6441,  DOI: 10.1002/anie.201409800
      15
      Frustrated Lewis Pair Chemistry: Development and Perspectives
      Stephan, Douglas W.; Erker, Gerhard
      Angewandte Chemie, International Edition (2015), 54 (22), 6400-6441CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. Frustrated Lewis pairs (FLPs) are combinations of Lewis acids and Lewis bases in soln. that are deterred from strong adduct formation by steric and/or electronic factors. This opens pathways to novel cooperative reactions with added substrates. Small-mol. binding and activation by FLPs has led to the discovery of a variety of new reactions through unprecedented pathways. Hydrogen activation and subsequent manipulation in metal-free catalytic hydrogenations is a frequently obsd. feature of many FLPs. The current state of this young but rapidly expanding field is outlined in this Review and the future directions for its broadening sphere of impact are considered.
    16. 16
      Chu, T.; Nikonov, G. I. Oxidative Addition and Reductive Elimination at Main-Group Element Centers. Chem. Rev. 2018, 118, 3608– 3680,  DOI: 10.1021/acs.chemrev.7b00572
      16
      Oxidative Addition and Reductive Elimination at Main-Group Element Centers
      Chu, Terry; Nikonov, Georgii I.
      Chemical Reviews (Washington, DC, United States) (2018), 118 (7), 3608-3680CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
      A review. Oxidative addn. and reductive elimination are key steps in a wide variety of catalytic reactions mediated by transition-metal complexes. Historically, this reactivity was considered to be the exclusive domain of d-block elements. However, this paradigm has changed in recent years with the demonstration of transition-metal-like reactivity by main-group compds. This Review highlights the substantial progress achieved in the past decade for the activation of robust single bonds by main-group compds. and the more recently realized activation of multiple bonds by these elements. The authors also discuss the significant discovery of reversible activation of single bonds and distinct examples of reductive elimination at main-group element centers. The review consists of three major parts, starting with oxidative addn. of single bonds, proceeding to cleavage of multiple bonds, and culminated by the discussion of reversible bond activation and reductive elimination. Within each subsection, the discussion is arranged according to the type of bond being cleaved or formed and considers elements from the left to the right of each period and down each group of the periodic table. The majority of results discussed in this Review come from the past decade; however, earlier reports are also included to ensure completeness.
    17. 17
      Lipshultz, J. M.; Li, G.; Radosevich, A. T. Main Group Redox Catalysis of Organopnictogens: Vertical Periodic Trends and Emerging Opportunities in Group 15. J. Am. Chem. Soc. 2021, 143, 1699– 1721,  DOI: 10.1021/jacs.0c12816
      17
      Main Group Redox Catalysis of Organopnictogens: Vertical Periodic Trends and Emerging Opportunities in Group 15
      Lipshultz, Jeffrey M.; Li, Gen; Radosevich, Alexander T.
      Journal of the American Chemical Society (2021), 143 (4), 1699-1721CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      A review. A growing no. of organopnictogen redox catalytic methods have emerged-esp. within the past 10 years-that leverage the plentiful reversible two-electron redox chem. within Group 15. The goal of this Perspective is to provide readers the context to understand the dramatic developments in organopnictogen catalysis over the past decade with an eye toward future development. An exposition of the fundamental differences in the at. structure and bonding of the pnictogens, and thus the mol. electronic structure of organopnictogen compds., is presented to establish the backdrop against which organopnictogen redox reactivity-and ultimately catalysis-is framed. A deep appreciation of these underlying periodic principles informs an understanding of the differing modes of organopnictogen redox catalysis and evokes the key challenges to the field moving forward. We close by addressing forward-looking directions likely to animate this area in the years to come. What new catalytic manifolds can be developed through creative catalyst and reaction design that take advantage of the intrinsic redox reactivity of the pnictogens to drive new discoveries in catalysis.
    18. 18
      Abbenseth, J.; Goicoechea, J. M. Recent Developments in the Chemistry of Non-Trigonal Pnictogen Pincer Compounds: From Bonding to Catalysis. Chem. Sci. 2020, 11, 9728– 9740,  DOI: 10.1039/D0SC03819A
      18
      Recent developments in the chemistry of non-trigonal pnictogen pincer compounds: from bonding to catalysis
      Abbenseth, Josh; Goicoechea, Jose M.
      Chemical Science (2020), 11 (36), 9728-9740CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
      The combination of well-established meridionally coordinating, tridentate pincer ligands with group 15 elements affords geometrically constrained non-trigonal pnictogen pincer compds. These species show remarkable activity in challenging element-hydrogen bond scission reactions, such as the activation of ammonia. The electronic structures of these compds. and the implications they have on their electrochem. properties and transition metal coordination are described. Furthermore, stoichiometric and catalytic bond forming reactions involving B-H, N-H and O-H bonds as well as carbon nucleophiles are presented.
    19. 19
      Kundu, S. Pincer-Type Ligand-Assisted Catalysis and Small-Molecule Activation by Non-VSEPR Main-Group Compounds. Chem.─Asian J. 2020, 15, 3209– 3224,  DOI: 10.1002/asia.202000800
      19
      Pincer-Type Ligand-Assisted Catalysis and Small-Molecule Activation by non-VSEPR Main-Group Compounds
      Kundu, Subrata
      Chemistry - An Asian Journal (2020), 15 (20), 3209-3224CODEN: CAAJBI; ISSN:1861-4728. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review focuses on the synthesis and the structural aspects of the geometry constrained main-group compds. using pincer ligands with emphasis placed on their applications on catalytic activity and small mols. activation. In 2005, a facile dihydrogen activation is reported by the Power group using an alkyne analog of Ge [ArGe GeAr; Ar = 2,6-Trip2-C6H3 (Trip = 2,4,6-iPr3-C6H2)]. After that, a significant progress was made in the activation of various small mols. by main-group compds., and a variety of stoichiometric and catalytic processes were formulated using the p-block elements. In this regard, compds. contg. low-valent main-group elements with a frontier orbitals of relatively small energy gaps or compds. forming frustrated Lewis pair (FLP) became quite successful. In spite of these promising stoichiometric and catalytic transformations, redox-cycling catalysts based on main-group elements remain extremely rare. Recently, pincer type ligands supported geometry constrained main-group compds. are capable of acting as redox catalysts similar to those of the transition metals.
    20. 20
      Brand, A.; Uhl, W. Sterically Constrained Bicyclic Phosphines: A Class of Fascinating Compounds Suitable for Application in Small Molecule Activation and Coordination Chemistry. Chem.─Eur. J. 2019, 25, 1391– 1404,  DOI: 10.1002/chem.201803331
      20
      Sterically Constrained Bicyclic Phosphines: A Class of Fascinating Compounds Suitable for Application in Small Molecule Activation and Coordination Chemistry
      Brand, Alexander; Uhl, Werner
      Chemistry - A European Journal (2019), 25 (6), 1391-1404CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review of bicyclic phosphines with two annulated, electronically unsatd. five-membered heterocycles are available through facile routes. In most cases, their P atoms are bound to heteroatoms such as O or N (PN3 or PN2O), whereas homoleptic coordination by three sp2-hybridized C atoms is reported only recently. Steric strain causes unique reactivity. Oxidative addn. of halogens, N-H or O-H bonds have afforded phosphoranes as valuable materials for secondary processes. Ring opening was identified as an important step for the understanding of these reactions and was obsd. exptl. with a diphosphorus-based ring system. A PH2 deriv. was considered as a model system for small mol. activation, and H transfer to a diazo compd. was obsd. exptl. Several of these phosphines are excellent ligands for the coordination of transition-metal atoms. The very bulky PC3 compd. has a basicity similar to that of PPh3 and may gave complexes with unusually low coordination nos. at the metal atoms. These phosphines found recently renewed interest as promising reagents in various secondary transformations such as the activation of σ-bonds or in coordination chem.
    21. 21
      Chulsky, K.; Malahov, I.; Bawari, D.; Dobrovetsky, R. Metallomimetic Chemistry of a Cationic, Geometrically Constrained Phosphine in the Catalytic Hydrodefluorination and Amination of Ar-F Bonds. J. Am. Chem. Soc. 2023, 145, 3786– 3794,  DOI: 10.1021/jacs.2c13318
      21
      Metallomimetic Chemistry of a Cationic, Geometrically Constrained Phosphine in the Catalytic Hydrodefluorination and Amination of Ar-F Bonds
      Chulsky, Karina; Malahov, Irina; Bawari, Deependra; Dobrovetsky, Roman
      Journal of the American Chemical Society (2023), 145 (6), 3786-3794CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      The synthesis, isolation and reactivity of a cationic, geometrically constrained σ3-P compd. in the hexaphenyl-carbodiphosphoranyl-based pincer-type ligand (1+) are reported. The compd. 1+ reacted with electron-poor fluoroarenes via an oxidative addn.-type reaction of the C-F bond to the PIII-center, yielding new fluorophosphorane-type species (PV). This reactivity of 1+ was used in the catalytic hydrodefluorination of Ar-F bonds with PhSiH3 to afford defluorinated arenes and in a catalytic C-N bond-forming cross-coupling reactions between fluoroarenes and aminosilanes to afford the corresponding fluorinated anilines. Importantly, the compd. 1+ in these catalytic reactions closely mimics the mode of action of the transition metal-based catalysts.
    22. 22
      Dunn, N. L.; Ha, M.; Radosevich, A. T. Main Group Redox Catalysis: Reversible PIII/PV Redox Cycling at a Phosphorus Platform. J. Am. Chem. Soc. 2012, 134, 11330– 11333,  DOI: 10.1021/ja302963p
      22
      Main Group Redox Catalysis: Reversible PIII/PV Redox Cycling at a Phosphorus Platform
      Dunn, Nicole L.; Ha, Minji; Radosevich, Alexander T.
      Journal of the American Chemical Society (2012), 134 (28), 11330-11333CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      A planar, trivalent phosphorus compd. is shown to undergo reversible two-electron redox cycling (PIII/PV) enabling its use as catalyst for a transfer hydrogenation reaction. The trivalent phosphorus compd. activates ammonia-borane to furnish a 10-P-5 dihydridophosphorane, which in turn is shown to transfer hydrogen cleanly to azobenzene, yielding diphenylhydrazine and regenerating the initial trivalent phosphorus species. This result constitutes a rare example of two-electron redox catalysis at a main group compd. and suggests broader potential for this nonmetal platform to support bond-modifying redox catalysis dominated by transition metal catalysts.
    23. 23
      Lim, S.; Radosevich, A. T. Round-Trip Oxidative Addition, Ligand Metathesis, and Reductive Elimination in a PIII/PV Synthetic Cycle. J. Am. Chem. Soc. 2020, 142, 16188– 16193,  DOI: 10.1021/jacs.0c07580
      23
      Round-Trip Oxidative Addition, Ligand Metathesis, and Reductive Elimination in a PIII/PV Synthetic Cycle
      Lim, Soohyun; Radosevich, Alexander T.
      Journal of the American Chemical Society (2020), 142 (38), 16188-16193CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      A synthetic cycle for aryl C-F substitution comprising oxidative addn., ligand metathesis, and reductive elimination at a Cs-sym. phosphorus triamide PN(2-MeNC6H4)2 (1) is reported. Reaction of 1 with perfluoroarenes (ArF-F) results in C-F oxidative addn., yielding fluorophosphoranes 1·[F][ArF]. The P-fluoro substituent is exchanged for hydride by treatment with DIBAL-H, generating hydridophosphoranes 1·[H][ArF]. Heating of 1·[H][ArF] regenerates 1 by C-H reductive elimination of ArF-H, where exptl. and computational studies establish a concerted but highly asynchronous mechanism. The results provide well-characterized examples of the full triad of elementary mechanistic aryl C-X substitution steps at a single main-group site.
    24. 24
      Pang, Y.; Leutzsch, M.; Nothling, N.; Katzenburg, F.; Cornella, J. Catalytic Hydrodefluorination via Oxidative Addition, Ligand Metathesis, and Reductive Elimination at Bi(I)/Bi(III) Centers. J. Am. Chem. Soc. 2021, 143, 12487– 12493,  DOI: 10.1021/jacs.1c06735
      24
      Catalytic Hydrodefluorination via Oxidative Addition, Ligand Metathesis, and Reductive Elimination at Bi(I)/Bi(III) Centers
      Pang, Yue; Leutzsch, Markus; Noethling, Nils; Katzenburg, Felix; Cornella, Josep
      Journal of the American Chemical Society (2021), 143 (32), 12487-12493CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Herein, authors report a hydrodefluorination reaction of polyfluoroarenes catalyzed by bismuthinidenes, Phebox-Bi(I) and OMe-Phebox-Bi(I). Mechanistic studies on the elementary steps support a Bi(I)/Bi(III) redox cycle that comprises C(sp2)-F oxidative addn., F/H ligand metathesis, and C(sp2)-H reductive elimination. Isolation and characterization of a cationic Phebox-Bi(III)(4-tetrafluoropyridyl) triflate manifests the feasible oxidative addn. of Phebox-Bi(I) into the C(sp2)-F bond. Spectroscopic evidence was provided for the formation of a transient Phebox-Bi(III)(4-tetrafluoropyridyl) hydride during catalysis, which decomps. at low temp. to afford the corresponding C(sp2)-H bond while regenerating the propagating Phebox-Bi(I). This protocol represents a distinct catalytic example where a main-group center performs three elementary organometallic steps in a low-valent redox manifold.
    25. 25
      Lee, K.; Blake, A. V.; Tanushi, A.; McCarthy, S. M.; Kim, D.; Loria, S. M.; Donahue, C. M.; Spielvogel, K. D.; Keith, J. M.; Daly, S. R.; Radosevich, A. T. Validating the Biphilic Hypothesis of Nontrigonal Phosphorus(III) Compounds. Angew. Chem., Int. Ed. 2019, 58, 6993– 6998,  DOI: 10.1002/anie.201901779
      25
      Validating the Biphilic Hypothesis of Nontrigonal Phosphorus(III) Compounds
      Lee, Kyounghoon; Blake, Anastasia V.; Tanushi, Akira; McCarthy, Sean M.; Kim, Daniel; Loria, Sydney M.; Donahue, Courtney M.; Spielvogel, Kyle D.; Keith, Jason M.; Daly, Scott R.; Radosevich, Alexander T.
      Angewandte Chemie, International Edition (2019), 58 (21), 6993-6998CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Constraining σ3-P compds. in nontrigonal, entatic geometries proved to be an effective strategy for promoting biphilic oxidative addn. reactions more typical of transition metals. Although qual. descriptions of the impact of structure and symmetry on σ3-P complexes are proposed, electronic structure variations responsible for biphilic reactivity have yet to be elucidated exptl. Reported here are P K-edge XANES data and complementary TDDFT calcns. for structurally modified P(N)3 complexes that both validate and quantify electronic structure variations proposed to give rise to biphilic reactions at P. These data are presented alongside exptl. referenced electronic structure calcns. that reveal nontrigonal structures predicted to further enhance biphilic reactivity in σ3-P ligands and catalysts.
    26. 26
      King, A. J.; Abbenseth, J.; Goicoechea, J. M. Reactivity of a Strictly T-Shaped Phosphine Ligated by an Acridane Derived NNN Pincer Ligand. Chem.─Eur. J. 2023, 29, e202300818  DOI: 10.1002/chem.202300818
      26
      Reactivity of a Strictly T-Shaped Phosphine Ligated by an Acridane Derived NNN Pincer Ligand
      King, Aaron J.; Abbenseth, Josh; Goicoechea, Jose M.
      Chemistry - A European Journal (2023), 29 (39), e202300818CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
      The steric tuning of a tridentate acridane-derived NNN pincer ligand allows for the isolation of a strictly T-shaped phosphine that exhibits ambiphilic reactivity. Well-defined phosphorus-centered reactivity towards nucleophiles and electrophiles is reported, contrasting with prior reports on this class of compds. Reactions towards oxidants are also described. The latter result in the two-electron oxidn. of the phosphorus atom from +III to +V and are accompanied by a strong geometric distortion of the NNN pincer ligand. By contrast, cooperative activation of E-H (HCl, HBcat, HOMe) bonds proceeds with retention of the phosphorus redox state. When using H2O as a substrate, the reaction results in the full disassembly of H2O to its constituent atoms, highlighting the potential of this platform for small mol. activation reactions.
    27. 27
      Wang, P. L.; Zhu, Q.; Wang, Y.; Zeng, G. X.; Zhu, J.; Zhu, C. Q. Carbon-Halogen Bond Activation by a Structurally Constrained Phosphorus(III) Platform. Chin. Chem. Lett. 2021, 32, 1432– 1436,  DOI: 10.1016/j.cclet.2020.11.005
      27
      Carbon-halogen bond activation by a structurally constrained phosphorus(III) platform
      Wang, Penglong; Zhu, Qin; Wang, Yi; Zeng, Guixiang; Zhu, Jun; Zhu, Congqing
      Chinese Chemical Letters (2021), 32 (4), 1432-1436CODEN: CCLEE7; ISSN:1001-8417. (Elsevier B.V.)
      The σ-bond activation by main group element has received enormous attention from theor. and exptl. chemists. Here, the reaction of C-X (X = Cl, Br, I) bonds in benzyl and allyl halides with a pincer-type phosphorus(III) species was reported. A series of structurally robust phosphorus(V) compds. were formed via the formal oxidative addn. reactions of C-X bonds to the phosphorus(III) center. D. functional theory calcns. show that the nucleophilic addn. process is more favorable than the direct oxidative addn. mechanism. Isomerization of bent structures of phosphorus(III) compd. to poorly nucleophilic compds. to undergo further C-X bond activation can be rationalized by frontier MO anal. This study not only provides a deep understanding of the reactivity of phosphorus(III) species but also demonstrates a potential of main group elements for the small-mol. activation.
    28. 28
      Volodarsky, S.; Dobrovetsky, R. Ambiphilic Geometrically Constrained Phosphenium Cation. Chem. Commun. 2018, 54, 6931– 6934,  DOI: 10.1039/C8CC02423E
      28
      Ambiphilic geometrically constrained phosphenium cation
      Volodarsky, Solomon; Dobrovetsky, Roman
      Chemical Communications (Cambridge, United Kingdom) (2018), 54 (50), 6931-6934CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
      In this work the synthesis of a geometrically constrained phosphenium cation is shown. In contrast to previously reported phosphenium cations, the geometrical constriction of the P-center in this cation makes it ambiphilic and reactive towards small mols. such as H2O, ROH and NH3.
    29. 29
      Hentschel, A.; Brand, A.; Wegener, P.; Uhl, W. A Sterically Constrained Tricyclic PC3 Phosphine: Coordination Behavior and Insertion of Chalcogen Atoms into P-C Bonds. Angew. Chem., Int. Ed. 2018, 57, 832– 835,  DOI: 10.1002/anie.201711373
      29
      A Sterically Constrained Tricyclic PC3 Phosphine-Coordination Behavior and Insertion of Chalcogen Atoms into P-C Bonds
      Hentschel, Anne; Brand, Alexander; Wegener, Philipp; Uhl, Werner
      Angewandte Chemie, International Edition (2018), 57 (3), 832-835CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A tricyclic phosphine has been generated that has a rigid mol. backbone with the P atoms exclusively bound to C(sp2) atoms as well as a very large Tolman angle and buried vol. It is an interesting new ligand in coordination chem. (Au, Pd complexes) and shows unusual insertion reactions into its endocyclic P-C bonds facilitated by its inherent mol. strain.
    30. 30
      Robinson, T. P.; De Rosa, D.; Aldridge, S.; Goicoechea, J. M. On the Redox Reactivity of a Geometrically Constrained Phosphorus(III) Compound. Chem.─Eur. J. 2017, 23, 15455– 15465,  DOI: 10.1002/chem.201703119
      30
      On the redox reactivity of a geometrically constrained phosphorus(III) compound
      Robinson, Thomas P.; De Rosa, Daniel; Aldridge, Simon; Goicoechea, Jose M.
      Chemistry - A European Journal (2017), 23 (61), 15455-15465CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
      The reactivity of a geometrically constrained phosphorus(III) complex bearing the N,N-bis(3,5-di-tert-butyl-2-phenolate)amide pincer ligand, 1,1'-(3,5-tBu2C6H2-6-O)2NP [1, P(ONO)] towards oxidants and reductants is explored. This compd. can be readily oxidized to the phosphorus(V) dihalo-derivs. P(ONO)X2 (2-4; X = Cl, Br, I). Attempts at isolating the analogous difluoride through oxidn. of 1 were unsuccessful yielding only the hydrofluoride P(ONO)(H)F (5), however P(ONO)F2 (6) can be accessed via a halide exchange reaction of 2 with KF. Compd. 2 can be employed as a precursor to novel cationic species through chloride ion displacement using strong Lewis bases. Thus, reaction of 2 with two or three molar equiv of dimethylaminopyridine (DMAP) affords [P(ONO)(Cl)(DMAP)2]+ (7) and [P(ONO)(DMAP)3]2+ (8). Reaction of 2 with the weaker bidentate base 2,2'-bipyridine (bipy) affords [P(ONO)(Cl)(bipy)]+ (9), although this species was only accessible upon addn. of a halide abstracting agent. The dicationic tris(pyridine) adduct [P(ONO)(py)3]2+ (10) is also accessible by reaction of 4 with pyridine. Oxidn. of 1 using oxygen gas proceeds slowly and allows for the observation of two compds., a mixed valence dimeric phosphorus(III)/phosphorus(V) compd. [P(ONO)(μ2-O)(μ2:κ1,κ2-ONO)P] (11) and the fully oxidized species [P(ONO)(μ2-O)(μ2:κ1,κ2-ONO)P(O)] (12). Finally, reaction of 1 using KC8 results in the dimerization of the putative radical anion [P(ONO)]•- through formation of a P-P bond to afford [P(ONO)]22- (13). Reactions with TEMPO result in the formation of the trigonal bipyramidal species P(ONO)(TEMPO)2 (14).
    31. 31
      Lin, Y. C.; Hatzakis, E.; McCarthy, S. M.; Reichl, K. D.; Lai, T. Y.; Yennawar, H. P.; Radosevich, A. T. P-N Cooperative Borane Activation and Catalytic Hydroboration by a Distorted Phosphorous Triamide Platform. J. Am. Chem. Soc. 2017, 139, 6008– 6016,  DOI: 10.1021/jacs.7b02512
      31
      P-N Cooperative Borane Activation and Catalytic Hydroboration by a Distorted Phosphorous Triamide Platform
      Lin, Yi-Chun; Hatzakis, Emmanuel; McCarthy, Sean M.; Reichl, Kyle D.; Lai, Ting-Yi; Yennawar, Hemant P.; Radosevich, Alexander T.
      Journal of the American Chemical Society (2017), 139 (16), 6008-6016CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Studies of the stoichiometric and catalytic reactivity of a geometrically constrained phosphorous triamide 1 with pinacolborane (HBpin) are reported. The addn. of HBpin to phosphorous triamide 1 results in cleavage of the B-H bond of pinacolborane through addn. across the electrophilic phosphorus and nucleophilic N-methylanilide sites in a cooperative fashion. The kinetics of this process of were investigated by NMR spectroscopy, with the detd. overall second-order empirical rate law given by ν = -k[1][HBpin], where k = 4.76 × 10-5 M-1 s-1 at 25 °C. The B-H bond activation process produces P-hydrido-1,3,2-diazaphospholene intermediate 2, which exhibits hydridic reactivity capable of reacting with imines to give phosphorous triamide intermediates, as confirmed by independent synthesis. These phosphorous triamide intermediates are typically short lived, evolving with elimination of the N-borylamine product of imine hydroboration with regeneration of the deformed phosphorous triamide 1. The kinetics of this latter process are shown to be first-order, indicative of a unimol. mechanism. Consequently, catalytic hydroboration of a variety of imine substrates can be realized with 1 as the catalyst and HBpin as the terminal reagent. A mechanistic proposal implicating a P-N cooperative mechanism for catalysis that incorporates the various independently verified stoichiometric steps is presented, and a comparison to related phosphorus-based systems is offered.
    32. 32
      Robinson, T. P.; Lo, S. K.; De Rosa, D.; Aldridge, S.; Goicoechea, J. M. On the Ambiphilic Reactivity of Geometrically Constrained Phosphorus(III) and Arsenic(III) Compounds: Insights into their Interaction with Ionic Substrates. Chem.─Eur. J. 2016, 22, 15712– 15724,  DOI: 10.1002/chem.201603135
      32
      On the Ambiphilic Reactivity of Geometrically Constrained Phosphorus(III) and Arsenic(III) Compounds: Insights into Their Interaction with Ionic Substrates
      Robinson, Thomas P.; Lo, Siu-Kwan; De Rosa, Daniel; Aldridge, Simon; Goicoechea, Jose M.
      Chemistry - A European Journal (2016), 22 (44), 15712-15724CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
      The ambiphilic nature of geometrically constrained Group 15 complexes bearing the N,N-bis(3,5-di-tert-butyl-2-phenolate)amide pincer ligand (ONO3-) is explored. Despite their differing reactivity towards nucleophilic substrates with polarized element-hydrogen bonds (e.g., NH3), both the phosphorus(III), P(ONO) (1a), and arsenic(III), As(ONO) (1b), compds. exhibit similar reactivity towards charged nucleophiles and electrophiles. Reactions of 1a and 1b with KOtBu or KNPh2 afford anionic complexes in which the nucleophilic anion assocs. with the pnictogen center [(tBuO)Pn(ONO)]- (Pn = P (2a), As (2b)) and [(Ph2N)Pn(ONO)]- (Pn = P (3a), As (3b)). Compd. 2a can subsequently be reacted with a proton source or benzyl bromide to afford the phosphorus(V) compds. (tBuO)HP(ONO) (4a) and (tBuO)BzP(ONO) (5a), resp., whereas analogous arsenic(V) compds. are inaccessible. Electrophilic substrates, such as HOTf and MeOTf, preferentially assoc. with the nitrogen atom of the ligand backbone of both 1a and 1b, giving rise to cationic species that can be rationalized as either ammonium salts or as amine-stabilized phosphenium or arsenium complexes ([Pn{ON(H)O}]+ (Pn = P (6a), As (6b)) and [Pn{ON(Me)O}]+ (Pn = P (7a), As (7b))). Reaction of 1a with an acid bearing a nucleophilic counter-anion (such as HCl) gives rise to a phosphorus(V) compd. HPCl(ONO) (8a), whereas the analogous reaction with 1b results in the addn. of HCl across one of the As-O bonds to afford ClAs{(H)ONO} (8b). Functionalization at both the pnictogen center and the ligand backbone is also possible by reaction of 7a/7b with KOtBu, which affords the neutral species (tBuO)Pn{ON(Me)O} (Pn = P (9a), As (9b)). The ambiphilic reactivity of these geometrically constrained complexes allows some insight into the mechanism of reactivity of 1a towards small mols., such as ammonia and water.
    33. 33
      Robinson, T. P.; De Rosa, D. M.; Aldridge, S.; Goicoechea, J. M. E-H Bond Activation of Ammonia and Water by a Geometrically Constrained Phosphorus(III) Compound. Angew. Chem., Int. Ed. 2015, 54, 13758– 13763,  DOI: 10.1002/anie.201506998
      33
      E-H Bond Activation of Ammonia and Water by a Geometrically Constrained Phosphorus(III) Compound
      Robinson, Thomas P.; De Rosa, Daniel M.; Aldridge, Simon; Goicoechea, Jose M.
      Angewandte Chemie, International Edition (2015), 54 (46), 13758-13763CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      The synthesis of a P(III) compd. bearing a N,N-bis(3,5-di-tert-butyl-2-phenoxy)amide ligand is reported. This species was found to react with NH3 and H2O, activating the E-H bonds in both substrates by formal oxidative addn. to afford the corresponding P(V) compds. In the case of H2O, both O-H bonds can be activated, splitting the mol. into its constituent elements. This is the 1st example of a compd. based on main group elements that sequentially activates H2O in this manner.
    34. 34
      McCarthy, S. M.; Lin, Y. C.; Devarajan, D.; Chang, J. W.; Yennawar, H. P.; Rioux, R. M.; Ess, D. H.; Radosevich, A. T. Intermolecular N–H Oxidative Addition of Ammonia, Alkylamines, and Arylamines to a Planar σ3-Phosphorus Compound via an Entropy-Controlled Electrophilic Mechanism. J. Am. Chem. Soc. 2014, 136, 4640– 4650,  DOI: 10.1021/ja412469e
      34
      Intermolecular N-H oxidative addition of ammonia, alkylamines, and arylamines to a planar σ3-phosphorus compound via an entropy-controlled electrophilic mechanism
      McCarthy, Sean M.; Lin, Yi-Chun; Devarajan, Deepa; Chang, Ji Woong; Yennawar, Hemant P.; Rioux, Robert M.; Ess, Daniel H.; Radosevich, Alexander T.
      Journal of the American Chemical Society (2014), 136 (12), 4640-4650CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Ammonia, alkyl amines, and aryl amines undergo rapid intermol. N-H oxidative addn. to a planar mononuclear σ3-phosphorus compd., [(tBuC(O):CHNCH:C(O)tBu-κN,κO,κO')P] ([(ONO)P], 1). The pentacoordinate phosphorane products [(ONO)P(H)(NHR)] (R = H, n-Pr, PhCH2, iPr, 2,4,6-Me3C6H2) are structurally robust, permitting full characterization by multinuclear NMR spectroscopy and single-crystal x-ray diffraction (R = 2,4,6-Me3C6H2). Isothermal titrn. calorimetry was employed to quantify the enthalpy of the N-H oxidative addn. of n-propylamine to 1, n-PrNH2 + 1 → [(ONO)P(H)(NHn-Pr)], ΔHrxn298 = -10.6 kcal/mol. The kinetics of n-propylamine N-H oxidative addn. were monitored by in situ UV absorption spectroscopy and detn. of the rate law showed an unusually large molecularity (ν = k[1][PrNH2]3). Kinetic expts. conducted over the temp. range of 10-70° revealed that the reaction rate decreased with increasing temp. Activation parameters extd. from an Eyring anal. (ΔH⧧ = -0.8 ± 0.4 kcal/mol, ΔS⧧ = -72 ± 2 cal/(mol·K)) indicate that the cleavage of strong N-H bonds by 1 is entropy controlled due to a highly ordered, high molecularity transition state. D. functional calcns. indicate that a concerted oxidative addn. via a classical three-center transition structure is energetically inaccessible. Rather, a stepwise heterolytic pathway is preferred, proceeding by initial amine-assisted N-H heterolysis upon complexation to the electrophilic phosphorus center followed by rate-controlling N → P proton transfer.
    35. 35
      Zeng, G. X.; Maeda, S.; Taketsugu, T.; Sakaki, S. Catalytic Transfer Hydrogenation by a Trivalent Phosphorus Compound: Phosphorus-Ligand Cooperation Pathway or PIII/PV Redox Pathway?. Angew. Chem., Int. Ed. 2014, 53, 4633– 4637,  DOI: 10.1002/anie.201311104
      35
      Catalytic Transfer Hydrogenation by a Trivalent Phosphorus Compound: Phosphorus-Ligand Cooperation Pathway or PIII/PV Redox Pathway?
      Zeng, Guixiang; Maeda, Satoshi; Taketsugu, Tetsuya; Sakaki, Shigeyoshi
      Angewandte Chemie, International Edition (2014), 53 (18), 4633-4637CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Main-group-element catalysts are a desirable alternative to transition-metal catalysts because of natural abundance and cost. However, the examples are very limited. Catalytic cycles involving a redox process and E-ligand cooperation (E = main-group element), which are often found in catalytic cycles of transition-metal catalysts, have not been reported. Herein theor. investigations of a catalytic hydrogenation of azobenzene with ammonia-borane using a trivalent phosphorus compd., which was exptl. proposed to occur through PIII/PV redox processes via an unusual pentavalent dihydridophosphorane, were performed. DFT and ONIOM(CCSD(T):MP2) calcns. disclosed that this catalytic reaction occurs through a P-O cooperation mechanism, which resembles the metal-ligand cooperation mechanism of transition-metal catalysts.
    36. 36
      Pal, A.; Vanka, K. Small Molecule Activation by Constrained Phosphorus Compounds: Insights from Theory. Inorg. Chem. 2016, 55, 558– 565,  DOI: 10.1021/acs.inorgchem.5b01074
      36
      Small Molecule Activation by Constrained Phosphorus Compounds: Insights from Theory
      Pal, Amrita; Vanka, Kumar
      Inorganic Chemistry (2016), 55 (2), 558-565CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)
      An exciting new development in main group chem. has been the use of a constrained, "flat", phosphorus-based complex to mediate in reactions such as the dehydrogenation of ammonia borane (AB), and the activation of the N-H bond in primary amines. Its importance is based on the fact that it shows that main group compds., when properly designed, can be as effective as transition metal complexes for doing significant chem. transformations. What the current computational study, employing d. functional theory (DFT), reveals is that a common, general mechanism exists that accounts for the behavior of the flat phosphorus compd. in the different reactions that have been exptl. reported to date. This mechanism, which involves the mediation by a base as a proton transfer agent, is simpler and energetically more favorable than the previous mechanisms that have been proposed for the same reactions in the literature. It is likely that the knowledge gained from the current work about the chem. behavior of this phosphorus compd. can be utilized to design new constrained phosphorus-based compds.
    37. 37
      Volodarsky, S.; Bawari, D.; Dobrovetsky, R. Dual Reactivity of a Geometrically Constrained Phosphenium Cation. Angew. Chem., Int. Ed. 2022, 61, e202208401  DOI: 10.1002/anie.202208401
      37
      Dual Reactivity of a Geometrically Constrained Phosphenium Cation
      Volodarsky, Solomon; Bawari, Deependra; Dobrovetsky, Roman
      Angewandte Chemie, International Edition (2022), 61 (36), e202208401CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A geometrically constrained phosphenium cation in bis(pyrrolyl)pyridine based NNN pincer type ligand (1+) was synthesized, isolated and its preliminary reactivity was studied with small mols. 1+ Reacts with MeOH and Et2NH, activating the O-H and N-H bonds via a P-center/ligand assisted path. The reaction of 1+ with one equiv. of H3NBH3 leads to its dehydrogenation producing 5. Interestingly, reaction of 1+ with an excess H3NBH3 leads to phosphinidene (PI) species coordinating to two BH3 mols. (6). In contrast, [1+][OTf] reacts with Et3SiH by hydride abstraction yielding 1-H and Et3SiOTf, while [1+][B(C6F5)4] reacts with Et3SiH via an oxidative addn. type reaction of Si-H bond to P-center, affording a new PV compd. (8). However, 8 is not stable over time and degrades to a complex mixt. of compds. in matter of minutes. Despite this, the ability of [1+][B(C6F5)4] to activate Si-H bond could still be tested in catalytic hydrosilylation of benzaldehyde, where 1+ closely mimics transition metal behavior.
    38. 38
      Bawari, D.; Volodarsky, S.; Ginzburg, Y.; Jaiswal, K.; Joshi, P.; Dobrovetsky, R. Intramolecular C-N Bond Activation by a Geometrically Constrained P-III-Centre. Chem. Commun. 2022, 58, 12176– 12179,  DOI: 10.1039/D2CC04359A
      38
      Intramolecular C-N bond activation by a geometrically constrained PIII-centre
      Bawari, Deependra; Volodarsky, Solomon; Ginzburg, Yael; Jaiswal, Kuldeep; Joshi, Pooja; Dobrovetsky, Roman
      Chemical Communications (Cambridge, United Kingdom) (2022), 58 (87), 12176-12179CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
      Reaction of phenoxide-functionalized imidazolidinylidene NHC, 1,3-R2-C3H4N2 (R = 3,5-tBu-2-LiO-C6H2) (1-Li2C:) with PCl3 is accompanied by insertion of carbene C atom into C-H bond of MeCN solvent with subsequent elimination and formation of phosphoranes (tBu2C6H2(O)NCH2CH2N(O)C6H2tBu2)PX (4, 5; X = ClCHCH2CN, H). In this work the first examples of C-N bond activation by insertion into a geometrically constrained PIII-center are shown. The mechanisms of these activation processes leading to new PV species were studied both exptl. and computationally. Interestingly, in the case of insertion of the PIII-center into an N-C(O)H bond, an unstable phosphoranyl-formaldehyde intermediate is probably formed, which undergoes decarbonylation in the presence of a catalytic amt. of HCl producing a hydrophosphorane.
    39. 39
      Abbenseth, J.; Townrow, O. P. E.; Goicoechea, J. M. Thermoneutral N-H Bond Activation of Ammonia by a Geometrically Constrained Phosphine. Angew. Chem., Int. Ed. 2021, 60, 23625– 23629,  DOI: 10.1002/anie.202111017
      39
      Thermoneutral N-H Bond Activation of Ammonia by a Geometrically Constrained Phosphine
      Abbenseth, Josh; Townrow, Oliver P. E.; Goicoechea, Jose M.
      Angewandte Chemie, International Edition (2021), 60 (44), 23625-23629CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A geometrically constrained phosphine I (2, X = lone pair) bearing a tridentate NNS pincer ligand is reported; its structure is confirmed by x-ray anal. of the selenide (3, X = Se). The effect of the geometric constraint on the electronic structure was probed by theor. calcns. and derivatization reactions. Reactions with N-H bonds result in formation of cooperative addn. products. The thermochem. of these transformations is strongly dependent on the substrate, with ammonia activation being thermoneutral. This represents the first example of a mol. compd. that reversibly activates ammonia via N-H bond scission in soln. upon mild heating.
    40. 40
      Lipshultz, J. M.; Fu, Y.; Liu, P.; Radosevich, A. T. Organophosphorus-Catalyzed Relay Oxidation of H-Bpin: Electrophilic C-H Borylation of Heteroarenes. Chem. Sci. 2021, 12, 1031– 1037,  DOI: 10.1039/D0SC05620K
      40
      Organophosphorus-catalyzed relay oxidation of H-Bpin: electrophilic C-H borylation of heteroarenes
      Lipshultz, Jeffrey M.; Fu, Yue; Liu, Peng; Radosevich, Alexander T.
      Chemical Science (2021), 12 (3), 1031-1037CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
      A nontrigonal phosphorus triamide (1, P{N[o-NMe-C6H4]2}) is shown to catalyze C-H borylation of electron-rich heteroarenes with pinacolborane (HBpin) in the presence of a mild chloroalkane reagent. C-H borylation proceeds for a range of electron-rich heterocycles including pyrroles, indoles, and thiophenes of varied substitution. Mechanistic studies implicate an initial P-N cooperative activation of HBpin by 1 to give P-hydrido diazaphospholene 2, which is diverted by Atherton-Todd oxidn. with chloroalkane to generate P-chloro diazaphospholene 3. DFT calcns. suggest subsequent oxidn. of pinacolborane by 3 generates chloropinacolborane (ClBpin) as a transient electrophilic borylating species, consistent with obsd. substituent effects and regiochem. outcomes. These results illustrate the targeted diversion of established reaction pathways in organophosphorus catalysis to enable a new mode of main group-catalyzed C-H borylation.
    41. 41
      Zeng, G. X.; Maeda, S.; Taketsugu, T.; Sakaki, S. Catalytic Hydrogenation of Carbon Dioxide with Ammonia-Borane by Pincer-Type Phosphorus Compounds: Theoretical Prediction. J. Am. Chem. Soc. 2016, 138, 13481– 13484,  DOI: 10.1021/jacs.6b07274
      41
      Catalytic Hydrogenation of Carbon Dioxide with Ammonia-Borane by Pincer-Type Phosphorus Compounds: Theoretical Prediction
      Zeng, Guixiang; Maeda, Satoshi; Taketsugu, Tetsuya; Sakaki, Shigeyoshi
      Journal of the American Chemical Society (2016), 138 (41), 13481-13484CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Two theor. designed and one exptl. reported pincer-type phosphorus compds. are active for the hydrogenation of carbon dioxide with ammonia-borane. DFT, ONIOM(CCSD(T):MP2), and CCSD(T) computational results demonstrated that the reaction occurs through phosphorus-ligand cooperative catalysis, which provides an unprecedented protocol for metal-free CO2 conversion. The phosphorus compds. with the NNN ligand are more active than those with the ONO ligand. The planar conjugate ligand considerably improves the efficiency of the catalyst.
    42. 42
      Cui, J. J.; Li, Y. X.; Ganguly, R.; Kinjo, R. Reactivity Studies on a Diazadiphosphapentalene. Chem.─Eur. J. 2016, 22, 9976– 9985,  DOI: 10.1002/chem.201600935
      42
      Reactivity Studies on a Diazadiphosphapentalene
      Cui, Jingjing; Li, Yongxin; Ganguly, Rakesh; Kinjo, Rei
      Chemistry - A European Journal (2016), 22 (29), 9976-9985CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
      The reactivity of diazadiphosphapentalene 1 towards various substrates was studied. Reaction of 1 with NH3-borane resulted in transfer hydrogenolysis concomitantly with the cleavage of a P-N bond. By treatment of 1 with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), oxidn. took place at one of the P atoms of 1, and a P(V)/P(III) mixed-valence deriv. was isolated. At the same time, only one of the P atoms in 1 behaves as an electron donor for electrophiles and Lewis acids. The former afforded an intramolecularly coordinated phosphine-phosphenium species, whereas the latter demonstrates the ligand property of 1. UV irradn. induced rearrangement of 1 into another example of another diazadiphosphapentalene.
    43. 43
      Cui, J. J.; Li, Y. X.; Ganguly, R.; Inthirarajah, A.; Hirao, H.; Kinjo, R. Metal-Free Sigma-Bond Metathesis in Ammonia Activation by a Diazadiphosphapentalene. J. Am. Chem. Soc. 2014, 136, 16764– 16767,  DOI: 10.1021/ja509963m
      43
      Metal-Free σ-Bond Metathesis in Ammonia Activation by a Diazadiphosphapentalene
      Cui, Jingjing; Li, Yongxin; Ganguly, Rakesh; Inthirarajah, Anusiya; Hirao, Hajime; Kinjo, Rei
      Journal of the American Chemical Society (2014), 136 (48), 16764-16767CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      A diazadiphosphapentalene deriv. (I) featuring a bent geometry with two phosphorus atoms at the bridgehead was synthesized. Under mild conditions, compd. I readily activated ammonia to afford 1-aza-2,3-diphospholene deriv. (II) bearing an enamine group. The reaction is therefore viewed as a formal σ-bond metathesis between an N-H bond of ammonia and an endocyclic P-N bond of I. Details of the reaction mechanism for ammonia activation as well as subsequent isomerization were explored by d. functional theory calcns.
    44. 44
      Müller, K.; Faeh, C.; Diederich, F. Fluorine in Pharmaceuticals: Looking Beyond Intuition. Science 2007, 317, 1881– 1886,  DOI: 10.1126/science.1131943
      44
      Fluorine in Pharmaceuticals: Looking Beyond Intuition
      Mueller, Klaus; Faeh, Christoph; Diederich, Francois
      Science (Washington, DC, United States) (2007), 317 (5846), 1881-1886CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
      A review. Fluorine substituents have become a widespread and important drug component, their introduction facilitated by the development of safe and selective fluorinating agents. Organofluorine affects nearly all phys. and adsorption, distribution, metab., and excretion properties of a lead compd. Its inductive effects are relatively well understood, enhancing bioavailability, for example, by reducing the basicity of neighboring amines. In contrast, exploration of the specific influence of carbon-fluorine single bonds on docking interactions, whether through direct contact with the protein or through stereoelectronic effects on mol. conformation of the drug, has only recently begun. Here, we review exptl. progress in this vein and add complementary anal. based on comprehensive searches in the Cambridge Structural Database and the Protein Data Bank.
    45. 45
      Wang, J.; Sanchez-Rosello, M.; Acena, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Fluorine in Pharmaceutical Industry: Fluorine-Containing Drugs Introduced to the Market in the Last Decade (2001–2011). Chem. Rev. 2014, 114, 2432– 2506,  DOI: 10.1021/cr4002879
      45
      Fluorine in Pharmaceutical Industry: Fluorine-Containing Drugs Introduced to the Market in the Last Decade (2001-2011)
      Wang, Jiang; Sanchez-Rosello, Maria; Acena, Jose Luis; del Pozo, Carlos; Sorochinsky, Alexander E.; Fustero, Santos; Soloshonok, Vadim A.; Liu, Hong
      Chemical Reviews (Washington, DC, United States) (2014), 114 (4), 2432-2506CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
      A historic review. As expected from the fluorine position on the periodic table of elements, it possesses some extreme properties, in particular, ultimate electronegativity and oxidn. potential. Therefore,elemental fluorine can not be prepd. by chem. reaction, and its isolation in 1886 by Henri Moissan required scientific ingenuity and great personal courage. His historic effort earned him a Noble Prize (1906), and the developed electrolysis method is still in use for industrial prodn. of fluorine gas. However, further development of fluorine chem. was extremely sluggish, pursued by a handful of experts capable of handling the violent gas using specially designed lab. equipment. Industrial-scale prodn. of fluorochems. dates back to late 1930s. Currently, there are about 200 pharmaceuticals containingfluorine, including the 40 new compds. discussed in this review. One may agree that the contribution of the past decade indicates a significant 20% increase in the no. of fluorinated drugs on the market.
    46. 46
      Jeschke, P. The Unique Role of Fluorine in the Design of Active Ingredients for Modern Crop Protection. Chembiochem 2004, 5, 570– 589,  DOI: 10.1002/cbic.200300833
      46
      The unique role of fluorine in the design of active ingredients for modern crop protection
      Jeschke, Peter
      ChemBioChem (2004), 5 (5), 570-589CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. The task of inventing and developing active ingredients with useful biol. activities requires a search for novel chem. substructures. This process may trigger the discovery of whole classes of chems. of potential com. interest. Similar biol. effects can often be achieved by completely different compds. However, compds. within a given structural family may exhibit quite different biol. activities depending on their interactions with different intracellular proteins like enzymes or receptors. By varying the functional groups and structural elements of a lead compd., its interaction with the active site of the target protein, as well as its physicochem., pharmacokinetic, and dynamic properties can be improved. In this context, the introduction of fluorine into active ingredients has become an important concept in the quest for a modern crop protection product with optimal efficacy, environmental safety, user friendliness, and economic viability. Fluorinated org. compds. represent an important and growing family of com. agrochems. A no. of recently developed agrochem. candidates represent novel classes of chem. compds. with new modes of action; several of these compds. contain new fluorinated substituents. However, the complex structure-activity relationships assocd. with biol.-active mols. mean that the introduction of fluorine can lead to either an increase or a decrease in the efficacy of a compd., depending on its changed mode of action, physicochem. properties, target interaction, or metabolic susceptibility and transformation. Therefore, it is still difficult to predict the sites in a mol. at which fluorine substitution will result in optimal desired effects.
    47. 47
      Hird, M. Fluorinated Liquid Crystals─Properties and Applications. Chem. Soc. Rev. 2007, 36, 2070– 2095,  DOI: 10.1039/b610738a
      47
      Fluorinated liquid crystals - properties and applications
      Hird, Michael
      Chemical Society Reviews (2007), 36 (12), 2070-2095CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
      This crit. review begins with a brief, but essential, introduction to the special nature of liq. crystal materials, their peculiar properties, and their com. applications, followed by an introductory insight into the remarkable nature of the fluoro substituent, and its fascinating influence on the properties of org. compds. However, the main focus of the review is to discuss the enormous amt. of exciting research on fluorinated liq. crystals that is reported. The small size of the fluoro substituent enables its incorporation into all types of liq. crystal, including calamitic, discotic, banana, lyotropic, and polymers, without ruining the liq. cryst. nature of the material. However the fluoro substituent is larger than H, and hence causes a significant steric effect, which combined with the high polarity, confers many fascinating, and often remarkable, modifications to m.p., mesophase morphol. and transition temps., and the many other very important phys. properties, such as dielec. anisotropy, optical anisotropy, and visco-elastic properties. There are many different positions within a liq. crystal structure where a fluoro substituent can be located, including (i) a terminal position, (ii) within a terminal chain, as a semi-fluorinated or as a perfluorinated chain, or as one fluoro substituent at a chiral center, (iii) as part of a linking group, and (iv) a lateral position in the core section. Such variety enables the interesting and advantageous tailoring of properties, both for the fundamental purposes of establishing structure-property relations, and for materials targeted towards com.-successful liq. crystal display applications.
    48. 48
      Hooker, L. V.; Bandar, J. S. Synthetic Advantages of Defluorinative C-F Bond Functionalization. Angew. Chem., Int. Ed. 2023, 62, e202308880  DOI: 10.1002/anie.202308880
      48
      Synthetic Advantages of Defluorinative C-F Bond Functionalization
      Hooker, Leidy V.; Bandar, Jeffrey S.
      Angewandte Chemie, International Edition (2023), 62 (49), e202308880CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. Much progress has been made in the development of methods to both create compds. that contain C-F bonds and to functionalize C-F bonds. As such, C-F bonds are becoming common and versatile synthetic functional handles. This review summarizes the advantages of defluorinative functionalization reactions for small mol. synthesis. The coverage is organized by the type of carbon framework the fluorine is attached to for mono- and polyfluorinated motifs. The main challenges, opportunities and advances of defluorinative functionalization are discussed for each class of organofluorine. Most of the text focuses on case studies that illustrate how defluorofunctionalization can improve routes to synthetic targets or how the properties of C-F bonds enable unique mechanisms and reactions. The broader goal is to showcase the opportunities for incorporating and exploiting C-F bonds in the design of synthetic routes, improvement of specific reactions and advent of new methods.
    49. 49
      Ahrens, T.; Kohlmann, J.; Ahrens, M.; Braun, T. Functionalization of Fluorinated Molecules by Transition-Metal-Mediated C-F Bond Activation to Access Fluorinated Building Blocks. Chem. Rev. 2015, 115, 931– 972,  DOI: 10.1021/cr500257c
      49
      Functionalization of Fluorinated Molecules by Transition-Metal-Mediated C-F Bond Activation To Access Fluorinated Building Blocks
      Ahrens, Theresia; Kohlmann, Johannes; Ahrens, Mike; Braun, Thomas
      Chemical Reviews (Washington, DC, United States) (2015), 115 (2), 931-972CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
      A review that deals with transition-metal-mediated C1F bond activations which involve a cleavage of a C-F bond in polyfluorinated mols. and its transformation into carbon-element bonds, excluding hydrodefluorination or defluorination reactions.
    50. 50
      Hu, J.-Y.; Zhang, J.-L. Hydrodefluorination Reactions Catalyzed by Transition-Metal Complexes. In Organometallic Fluorine Chemistry; Braun, T., Hughes, R. P., Eds.; Springer International Publishing: Cham, 2015; pp 143– 196.
      There is no corresponding record for this reference.
    51. 51
      Whittlesey, M. K.; Peris, E. Catalytic Hydrodefluorination with Late Transition Metal Complexes. ACS Catal. 2014, 4, 3152– 3159,  DOI: 10.1021/cs500887p
      51
      Catalytic Hydrodefluorination with Late Transition Metal Complexes
      Whittlesey, Michael K.; Peris, Eduardo
      ACS Catalysis (2014), 4 (9), 3152-3159CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)
      A review. This perspective article focuses its attention on the most recent advances in hydrodefluorination processes catalyzed by late transition metal complexes, a field that has been a matter of increasing interest during the past decade. The evolution of catalytic hydrodefluorination is treated by giving precise information on the nature of the catalysts, reductants and fluoroorg. substrates that have been used until now. An overview of the mechanistic studies that have been performed so far is also given.
    52. 52
      Das, A.; Chatani, N. The Directing Group: A Tool for Efficient and Selective C-F Bond Activation. ACS Catal. 2021, 11, 12915– 12930,  DOI: 10.1021/acscatal.1c03896
      52
      The Directing Group: A Tool for Efficient and Selective C-F Bond Activation
      Das, Amrita; Chatani, Naoto
      ACS Catalysis (2021), 11 (21), 12915-12930CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)
      A review. In this Review, focus on the directed strategy for the activation of inert C-F bonds.
    53. 53
      Chen, W.; Bakewell, C.; Crimmin, M. R. Functionalisation of Carbon-Fluorine Bonds with Main Group Reagents. Synthesis 2017, 49, 810– 821,  DOI: 10.1055/s-0036-1588663
      53
      Functionalisation of Carbon-Fluorine Bonds with Main Group Reagents
      Chen, Wenyi; Bakewell, Clare; Crimmin, Mark R.
      Synthesis (2017), 49 (4), 810-821CODEN: SYNTBF; ISSN:1437-210X. (Georg Thieme Verlag)
      A review. Synthetic approaches to produce reactive chem. building blocks from fluorinated mols. by the functionalization of carbon-fluorine bonds with main group reagents are reviewed. The reaction types can be categorized as: the formal 1,2-addn. of C-F bonds across Si-Si, B-B, or Mg-Mg bonds; the oxidative addn. of C-F bonds to Si(II), Ge(II), and Al(I) centers; and the dehydrogenative coupling of C-F bonds with Al-H or B-H bonds. Many of the advances have emerged between 2015-2016 and are largely focused upon arom. substrates that contain sp2 C-F bonds. Topics discussed include: C-F borylation of arom. sp2 C-F bonds ; rhodium catalysis ; nickel catalysis ; C-F alumination of sp2 C-F arom. and sp3 C-F aliph. bonds ; C-F silylation and germylation of arom. sp2 C-F bonds ; C-F magnesiation of arom. sp2 C-F bonds ; and C-F silylation and borylation of alkenes.
    54. 54
      Muthuvel, K.; Gandhi, T. C-F Bond Activation and Functionalizations Enabled by Metal-Free NHCs and their Metal Complexes. ChemCatChem 2022, 14, e202101579  DOI: 10.1002/cctc.202101579
      54
      C-F Bond Activation and Functionalizations Enabled by Metal-free NHCs and Their Metal Complexes
      Muthuvel, Karthick; Gandhi, Thirumanavelan
      ChemCatChem (2022), 14 (8), e202101579CODEN: CHEMK3; ISSN:1867-3880. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. This minireview provides the prominence of NHC and metal-NHC in the area of catalytic C-F bond functionalization.
    55. 55
      Stahl, T.; Klare, H. F. T.; Oestreich, M. Main-Group Lewis Acids for C-F Bond Activation. ACS Catal. 2013, 3, 1578– 1587,  DOI: 10.1021/cs4003244
      55
      Main-Group Lewis Acids for C-F Bond Activation
      Stahl, Timo; Klare, Hendrik F. T.; Oestreich, Martin
      ACS Catalysis (2013), 3 (7), 1578-1587CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)
      A review. The significant benefits of fluorinated compds. have inspired the development of diverse techniques for the activation and subsequent (de)functionalization of rather inert C-F bonds. Although substantial progress has been made in the selective activation of C(sp2)-F bonds employing transition metal complexes, protocols that address nonactivated C(sp3)-F bonds are much less established. In this regard, the use of strong main-group Lewis acids has emerged as a powerful tool to selectively activate C(sp3)-F bonds in satd. fluorocarbons. This Perspective provides a concise overview of various cationic and neutral silicon-, boron-, and aluminum-based Lewis acids that have been identified to facilitate the heterolytic fluoride abstraction from aliph. fluorides. The potential of these Lewis acids in hydrodefluorination as well as defluorinative C-F bond functionalization reactions is highlighted. Emphasis is placed on the underlying mechanistic principles to provide a systematic classification of the individual reactions. Finally, brief insight into the related C-F bond activation chem. using carbocations or Bronsted acids is presented.
    56. 56
      Caputo, C. B.; Hounjet, L. J.; Dobrovetsky, R.; Stephan, D. W. Lewis Acidity of Organofluorophosphonium Salts: Hydrodefluorination by a Saturated Acceptor. Science 2013, 341, 1374– 1377,  DOI: 10.1126/science.1241764
      56
      Lewis Acidity of Organofluorophosphonium Salts: Hydrodefluorination by a Saturated Acceptor
      Caputo, Christopher B.; Hounjet, Lindsay J.; Dobrovetsky, Roman; Stephan, Douglas W.
      Science (Washington, DC, United States) (2013), 341 (6152), 1374-1377CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
      Prototypical Lewis acids, such as boranes, derive their reactivity from electronic unsatn. Here, the authors report the Lewis acidity and catalytic application of electronically satd. P-centered electrophilic acceptors. Organofluorophosphonium salts [(C6F5)3-xPhxPF][B(C6F5)4] (x = 0 or 1; Ph, phenyl) form adducts with neutral Lewis bases and react rapidly with fluoroalkanes to produce difluorophosphoranes. In the presence of hydrosilane, [(C6F5)3PF]+ catalyzes the hydrodefluorination of fluoroalkanes, affording alkanes and fluorosilane. The mechanism demonstrates the impressive F- ion affinity of this highly electron-deficient phosphonium center.
    57. 57
      Zhu, J.; Pérez, M.; Caputo, C. B.; Stephan, D. W. Use of Trifluoromethyl Groups for Catalytic Benzylation and Alkylation with Subsequent Hydrodefluorination. Angew. Chem., Int. Ed. 2016, 55, 1417– 1421,  DOI: 10.1002/anie.201510494
      57
      Use of Trifluoromethyl Groups for Catalytic Benzylation and Alkylation with Subsequent Hydrodefluorination
      Zhu, Jiangtao; Perez, Manuel; Caputo, Christopher B.; Stephan, Douglas W.
      Angewandte Chemie, International Edition (2016), 55 (4), 1417-1421CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      The electrophilic organofluorophosphonium catalyst [(C6F5)3PF][B(C6F5)4] is shown to effect benzylation or alkylation by aryl and alkyl CF3 groups with subsequent hydrodefluorination, thus resulting in a net transformation of CF3 into CH2-aryl fragments [e.g., PhCF3 → CH2Ph2 (63%)]. In the case of alkyl CF3 groups, Friedel-Crafts alkylation by the difluorocarbocation proceeded without cation rearrangement, in contrast to the corresponding reactions of alkyl monofluorides.
    58. 58
      Zhu, J.; Pérez, M.; Stephan, D. W. C-C Coupling of Benzyl Fluorides Catalyzed by an Electrophilic Phosphonium Cation. Angew. Chem., Int. Ed. 2016, 55, 8448– 8451,  DOI: 10.1002/anie.201603627
      58
      C-C Coupling of Benzyl Fluorides Catalyzed by an Electrophilic Phosphonium Cation
      Zhu, Jiangtao; Perez, Manuel; Stephan, Douglas W.
      Angewandte Chemie, International Edition (2016), 55 (29), 8448-8451CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      The activation and cleavage of benzyl fluorides by the electrophilic organofluorophosphonium catalyst, [(C6F5)3PF][B(C6F5)4], is reported and used for the prepn. of 1,1-diarylalkanes (37 examples) and substituted aryl homoallylic alkenes (14 examples). This procedure involves mild conditions, avoids harmful waste, and is compatible with a range of substituted arenes and allylic silanes.
    59. 59
      Bayne, J. M.; Stephan, D. W. C-F Bond Activation Mediated by Phosphorus Compounds. Chem.─Eur. J. 2019, 25, 9350– 9357,  DOI: 10.1002/chem.201900542
      59
      C-F Bond Activation Mediated by Phosphorus Compounds
      Bayne, Julia M.; Stephan, Douglas W.
      Chemistry - A European Journal (2019), 25 (40), 9350-9357CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. The activation and functionalization of C-F bonds has garnered significant attention in the scientific community as a strategy to mitigate toxicity and environmental concerns, as well as provide new pathways to agro- and pharmaceutical chems. and materials. Although several transition-metal-based systems have been developed for this transformation, the use of main-group compds. remains less explored. In recent years, several strategies for C-F bond activation have focused on the use of phosphorus-based reagents. In this Minireview, an overview of strategies is provided that exploits PV and PIII-based Lewis acids as well as PIII Lewis bases in frustrated Lewis pair (FLP) protocols for hydrodefluorination, C-C couplings and C-F derivatizations.
    60. 60
      Kikushima, K.; Grellier, M.; Ohashi, M.; Ogoshi, S. Transition-Metal-Free Catalytic Hydrodefluorination of Polyfluoroarenes by Concerted Nucleophilic Aromatic Substitution with a Hydrosilicate. Angew. Chem., Int. Ed. 2017, 56, 16191– 16196,  DOI: 10.1002/anie.201708003
      60
      Transition-Metal-Free Catalytic Hydrodefluorination of Polyfluoroarenes by Concerted Nucleophilic Aromatic Substitution with a Hydrosilicate
      Kikushima, Kotaro; Grellier, Mary; Ohashi, Masato; Ogoshi, Sensuke
      Angewandte Chemie, International Edition (2017), 56 (51), 16191-16196CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Polyfluorinated arenes underwent regioselective transition metal-free hydrodefluorination with Ph3SiH or Et2SiH2 in the presence of tetrabutylammonium difluorotriphenylsilicate (TBAT) in THF. For example, hexafluorobenzene underwent hydrodefluorination with Et2SiH2 at 60° to yield pentafluorobenzene in 19% yield, 1,2,4,5-tetrafluorobenzene in 70% yield, and 1,2,3,5-tetrafluorobenzene and 1,2,3,4-tetrafluorobenzene in 2% yields. The reaction involves direct hydride transfer from a hydrosilicate as the key intermediate, which is generated from a hydrosilane and a fluoride salt; the eliminated fluoride regenerates the hydrosilicate to complete the catalytic cycle. The mechanism was studied using stoichiometric reactions of silicates and using dispersion-cor. DFT calcns.; hydrodefluorination likely proceeds via concerted nucleophilic arom. substitution.
    61. 61
      Schoch, T. D.; Mondal, M.; Weaver, J. D. Catalyst-Free Hydrodefluorination of Perfluoroarenes with NaBH4. Org. Lett. 2021, 23, 1588– 1593,  DOI: 10.1021/acs.orglett.0c04305
      61
      Catalyst-Free Hydrodefluorination of Perfluoroarenes with NaBH4
      Schoch, Timothy D.; Mondal, Mukulesh; Weaver, Jimmie D.
      Organic Letters (2021), 23 (5), 1588-1593CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
      An economical means of removing fluorine from various highly fluorinated arenes using NaBH4 for synthesis of partially fluorinated arenes was presented. The procedure was adapted for different classes of perfluoroarenes. A novel isomer of an emerging class of org. dyes based on the carbazole phthalonitrile motif was succinctly synthesized in two steps from tetrafluorophthalonitrile, demonstrating the utility of the hydrodefluorination procedure. Initial exploration of the dye showed it to be photoactive and capable of facilitating contrathermodynamic styrenoid E/Z isomerization.
    62. 62
      Zhang, J. J.; Zhao, X.; Yang, J. D.; Cheng, J. P. Diazaphospholene-Catalyzed Hydrodefluorination of Polyfluoroarenes with Phenylsilane via Concerted Nucleophilic Aromatic Substitution. J. Org. Chem. 2022, 87, 294– 300,  DOI: 10.1021/acs.joc.1c02360
      62
      Diazaphospholene-Catalyzed Hydrodefluorination of Polyfluoroarenes with Phenylsilane via Concerted Nucleophilic Aromatic Substitution
      Zhang, Jingjing; Zhao, Xiao; Yang, Jin-Dong; Cheng, Jin-Pei
      Journal of Organic Chemistry (2022), 87 (1), 294-300CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
      The metal-free catalytic C-F bond activation of polyfluoroarenes was achieved with diazaphospholene as the catalyst and phenylsilane as the terminal reductant. D. functional theory calcns. suggested a concerted nucleophilic arom. substitution mechanism.
    63. 63
      Zhang, J. J.; Yang, J. D.; Cheng, J. P. Chemoselective Catalytic Hydrodefluorination of Trifluoromethylalkenes Towards Mono-/Gem-Di-Fluoroalkenes Under Metal-Free Conditions. Nat. Commun. 2021, 12, 2835,  DOI: 10.1038/s41467-021-23101-3
      63
      Chemoselective catalytic hydrodefluorination of trifluoromethylalkenes towards mono-/gem-di-fluoroalkenes under metal-free conditions
      Zhang, Jingjing; Yang, Jin-Dong; Cheng, Jin-Pei
      Nature Communications (2021), 12 (1), 2835CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)
      Here, a diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively construct gem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry was described. This metal-free hydrodefluorination featured mild reaction conditions, good group compatibility, and almost quant. yields for both product types. Stoichiometric expts. indicated a stepwise mechanism: hydridic addn. to fluoroalkenes and subsequent β-F elimination from hydrophosphination intermediates. D. functional theory calcns. disclosed the origin of chemoselectivity, regioselectivity and stereoselectivity, suggesting an electron-donating effect of the alkene-terminal fluorine atom.
    64. 64
      Arevalo, A.; Tlahuext-Aca, A.; Flores-Alamo, M.; Garcia, J. J. On the Catalytic Hydrodefluorination of Fluoroaromatics Using Nickel Complexes: The True Role of the Phosphine. J. Am. Chem. Soc. 2014, 136, 4634– 4639,  DOI: 10.1021/ja412268y
      64
      On the Catalytic Hydrodefluorination of Fluoroaromatics Using Nickel Complexes: The True Role of the Phosphine
      Arevalo, Alma; Tlahuext-Aca, Adrian; Flores-Alamo, Marcos; Garcia, Juventino J.
      Journal of the American Chemical Society (2014), 136 (12), 4634-4639CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Homogeneous catalytic hydrodefluorination (HDF) of fluoroaroms. under thermal conditions was achieved using nickel(0) compds. of the type [(dippe)Ni(η2-C6F6-nHn)] where n = 0-2, as the catalytic precursors. These complexes were prepd. in situ by reacting the compd. [(dippe)Ni(μ-H)]2 with the resp. fluoroarom. substrate. HDF seems to occur homogeneously, as tested by mercury drop expts., producing the hydrodefluorinated products. However, despite previous findings by other groups, we found that these HDF reactions were actually the result of direct reaction of the alkylphosphine with the fluoroarom. substrate. This metal- and silane-free system is the first reported example of a phosphine being able to hydrodefluorinate on its own.
    65. 65
      Facundo, A. A.; Arevalo, A.; Fundora-Galano, G.; Flores-Alamo, M.; Orgaz, E.; Garcia, J. J. Hydrodefluorination of Functionalized Fluoroaromatics with Triethylphosphine: A Theoretical and Experimental Study. New J. Chem. 2019, 43, 6897– 6908,  DOI: 10.1039/C9NJ00721K
      65
      Hydrodefluorination of functionalized fluoroaromatics with triethylphosphine: a theoretical and experimental study
      Facundo, Aldo A.; Arevalo, Alma; Fundora-Galano, Gabriela; Flores-Alamo, Marcos; Orgaz, Emilio; Garcia, Juventino J.
      New Journal of Chemistry (2019), 43 (18), 6897-6908CODEN: NJCHE5; ISSN:1144-0546. (Royal Society of Chemistry)
      A new mechanism avoids the highly energetic β-elimination step of roughly 71 kcal mol-1 for hexafluorobenzene and pentafluoropyridine at 393.15 K, invoking the participation of water. The use of D2O confirmed the role of water as the hydrogen source, yielding the corresponding deutero-defluorinated products; DFT calcns. agree with this new proposed mechanism. The use of this one-pot hydrodefluorination method applied to a broader no. of fluoroarom. derivs. as e.g., 2,3,4,5,6-pentafluoro-1-trifluoromethylbenzene and some of them allowed the collection of key mechanistic evidence were reported.
    66. 66
      Bardin, V. V. Reactions of Polyfluoroaromatic Compounds with Electrophilic Agents in the Presence of Tris(dialkylamino) Phosphines. 8. Replacement of Fluorine by Hydrogen in Polyfluoroaromatic Compounds. Russ. Chem. Bull. 1997, 46, 1434– 1436,  DOI: 10.1007/BF02505680
      66
      Reaction of polyfluoroaromatic compounds with electrophilic agents in the presence of tris(dialkylamino)phosphines 8. Replacement of fluorine by hydrogen in polyfluoroaromatic compounds
      Bardin, V. V.
      Russian Chemical Bulletin (Translation of Izvestiya Akademii Nauk, Seriya Khimicheskaya) (1997), 46 (8), 1434-1436CODEN: RCBUEY; ISSN:1066-5285. (Consultants Bureau)
      When reacted with P(NEt2)3 and a proton donor, pentafluoropyridine, 3-chlorotetrafluoropyridine, pentafluorobenzonitrile, and octafluorotoluene yield products of replacement of the fluorine atom by hydrogen at position 4. This process is accompanied by the side reaction of aminodefluorination. In the case of 3H-heptafluorotoluene and octafluoronaphthalene, aminodefluorination is the main reaction. Reactions of perfluoro-4-isopropyltoluene, 4H-heptafluorotoluene, and 4-methylheptafluorotoluene do not occur under the above-mentioned conditions.
    67. 67

      List prices from Merck August 2023: PnBu3 £0.87/g (100g quantity), PhSiH3 £7.92/g (25g quantity), PhSiH2 £2.43/g (25g quantity), Ph3SiH £3.09/g (25g quantity). List price from Fischer Scientific August 2023: PiPr3 £29.6/g (10g quantity).

      There is no corresponding record for this reference.
    68. 68
      Gutov, A. V.; Rusanov, E. B.; Ryabitskii, A. B.; Chernega, A. N. Octafluoro-4,4′-Bipyridine and its Derivatives: Synthesis, Molecular and Crystal Structure. J. Fluorine Chem. 2010, 131, 278– 281,  DOI: 10.1016/j.jfluchem.2009.11.022
      68
      Octafluoro-4,4'-bipyridine and its derivatives: Synthesis, molecular and crystal structure
      Gutov, Alexey V.; Rusanov, Eduard B.; Ryabitskii, Alexey B.; Chernega, Alexander N.
      Journal of Fluorine Chemistry (2010), 131 (2), 278-281CODEN: JFLCAR; ISSN:0022-1139. (Elsevier B.V.)
      The structure and chem. properties of perfluoro-4,4'-bipyridine have been studied. It was found that octafluoro-4,4'-bipyridine is a quite electron deficient system stable to the action of alkylating agents and sensitive to nucleophilic substitution of fluorine atoms. Depending on the reaction conditions and reagents used products could be obtained in which two and six fluorine atoms are substituted by nucleophiles. For all isolated compds. X-ray structure detn. has been performed and the main peculiarities of the mol. and crystal structure of fluorine-contg. bipyridines have been detd.
    69. 69
      Anders, E.; Markus, F. Neue methode zur regiospezifischen substitution einiger reaktionsträcer N-heteroaromatischer ringsysteme. Tetrahedron Lett. 1987, 28, 2675– 2676,  DOI: 10.1016/S0040-4039(00)96178-1
      69
      A new method for the regiospecific substitution of a reaction tracing of N-heteroaromatic ring systems
      Anders, Ernst; Markus, Fritz
      Tetrahedron Letters (1987), 28 (24), 2675-6CODEN: TELEAY; ISSN:0040-4039.
      N-Trifluoromethanesulfonylheteroarylium salts, prepd. by the reaction of trifluoromethanesulfonic anhydride with pyridines, undergo regioselective substitution reaction with Ph3P to give phosphonium salts I (R = H, Et, CH2Ph, Br). Similar substitution reaction of I (R = H) gave diphosphonium salt II which regioselectively reacts with NaN3 to give iminophosphonium salt III. Hydrolytic cleavage of III gave 64% iminophosphorane IV.
    70. 70
      Mandal, D.; Gupta, R.; Young, R. D. Selective Monodefluorination and Wittig Functionalization of gem-Difluoromethyl Groups to Generate Monofluoroalkenes. J. Am. Chem. Soc. 2018, 140, 10682– 10686,  DOI: 10.1021/jacs.8b06770
      70
      Selective Monodefluorination and Wittig Functionalization of gem-Difluoromethyl Groups to Generate Monofluoroalkenes
      Mandal, Dipendu; Gupta, Richa; Young, Rowan D.
      Journal of the American Chemical Society (2018), 140 (34), 10682-10686CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Geminal difluorides underwent chemoselective monodefluorination with triarylphosphines such as (2-MeC6H4)3P and Ph3P and boron or aluminum complexes such as B(C6F5)3 and BF3·Et2O via frustrated Lewis pairs to yield monofluoroalkyl phosphonium salts such as I·FBX3 (R = 2-MeC6H4, Ph, 2,4,6-Me3C6H2; X = F, C6F5). The reaction relied on the reduced reactivity of the product monofluoroalkylphosphonium salts towards defluorination compared to the starting geminal difluorides. α-Fluoroalkylphosphonium salts such as I·FB(C6F5)3 (R = 2-MeC6H4) underwent stereoselective Wittig reactions with aldehydes R1CHO [R1 = Ph, 4-MeC6H4, 4-BrC6H4, 4-MeSC6H4, 3,4-Cl2C6H3, 2-BrC6H4, 4-Me2NC6H4, 4-O2NC6H4, 4-NCC6H4, Me(CH2)8, (E)-R2CH:CH, H, 4-Br-2-FC6H3; R2 = Ph, 4-Me2NC6H4, 4-O2NC6H4] mediated by LiHMDS to yield monofluoroalkenes such as II [R1 = Ph, 4-MeC6H4, 4-BrC6H4, 4-MeSC6H4, 3,4-Cl2C6H3, 2-BrC6H4, 4-Me2NC6H4, 4-O2NC6H4, 4-NCC6H4, Me(CH2)8, (E)-R2CH:CH, H, 4-Br-2-FC6H3; R2 = Ph, 4-Me2NC6H4, 4-O2NC6H4] in 27-94% yields. The structure of I·FB(C6F5)3 (R = 2-MeC6H4) was detd. by X-ray crystallog.
    71. 71
      Mandal, D.; Gupta, R.; Jaiswal, A. K.; Young, R. D. Frustrated Lewis-Pair-Meditated Selective Single Fluoride Substitution in Trifluoromethyl Groups. J. Am. Chem. Soc. 2020, 142, 2572– 2578,  DOI: 10.1021/jacs.9b12167
      71
      Frustrated Lewis-Pair-Mediated Selective Single Fluoride Substitution in Trifluoromethyl Groups
      Mandal, Dipendu; Gupta, Richa; Jaiswal, Amit K.; Young, Rowan D.
      Journal of the American Chemical Society (2020), 142 (5), 2572-2578CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Single fluoride substitution in trifluoromethylarenes is an ongoing synthetic challenge that often leads to "over-reaction", where multiple fluorides are replaced. Development of this reaction would allow simple access to a vast range of difluoromethyl derivs. of current interest to pharmaceutical, agrochem., and materials sciences. Using a catalytic frustrated Lewis pair approach, we have developed a generic protocol that allows a single substitution of one fluoride in trifluoromethyl groups with neutral phosphine and pyridine bases. The resulting phosphonium and pyridinium salts can be further functionalized via nucleophilic substitution, photoredox coupling, and electrophilic transfer reactions allowing the generation of a vast array of difluoromethyl products.
    72. 72
      Parks, D. J.; Piers, W. E. Tris(pentafluorophenyl)boron-Catalyzed Hydrosilation of Aromatic Aldehydes, Ketones, and Esters. J. Am. Chem. Soc. 1996, 118, 9440– 9441,  DOI: 10.1021/ja961536g
      72
      Tris(pentafluorophenyl)boron-Catalyzed Hydrosilation of Aromatic Aldehydes, Ketones, and Esters
      Parks, Daniel J.; Piers, Warren E.
      Journal of the American Chemical Society (1996), 118 (39), 9440-9441CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Tris(pentafluorophenyl)borane (1-4 mol %) catalyzes the addn. of Ph3SiH to carbonyl functions of arom. substrates p-XC6H4COR (X = Me, H, Cl, NO2; R = H, Me, OEt). Turnover frequencies for X = H substrates are 19, 45 and 637 h for R = H, Me and OEt, resp. and rates of hydrosilation increase as X becomes more electron withdrawing. Mechanistic studies, including substrate/borane binding equil., structural studies on substrate/borane adducts and kinetic measurements support a hydrosilation mechanism characterized by borane activation of the silane reagent rather than the carbonyl substrate. Key observations in support of this unusual nucleophilic/electrophilic hydrosilation mechanism were the obsd. inhibition of the reaction by increased concns. of substrate and the obsd. order of reactivity which indicates that the weaker binding substrates are reduced faster.
    73. 73
      Parks, D. J.; Blackwell, J. M.; Piers, W. E. Studies on the Mechanism of B(C6F5)3-Catalyzed Hydrosilation of Carbonyl Functions. J. Org. Chem. 2000, 65, 3090– 3098,  DOI: 10.1021/jo991828a
      73
      Studies on the Mechanism of B(C6F5)3-Catalyzed Hydrosilation of Carbonyl Functions
      Parks, Daniel J.; Blackwell, James M.; Piers, Warren E.
      Journal of Organic Chemistry (2000), 65 (10), 3090-3098CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
      The strong organoborane Lewis acid B(C6F5)3 catalyzes the hydrosilation (using R3SiH) of arom. and aliph. carbonyl functions at convenient rates with loadings of 1-4%. For aldehydes and ketones, the product silyl ethers were isolated in 75-96% yield; for esters, the aldehydes produced upon workup of the silyl acetal products can be obtained in 45-70% yield. Extensive mechanistic studies point to an unusual silane activation mechanism rather than one involving borane activation of the carbonyl function. Quant. kinetic studies show that the least basic substrates are hydrosilated at the fastest rates; furthermore, increased concns. of substrate have an inhibitory effect on the obsd. reaction rate. Paradoxically, the most basic substrates are reduced selectively, albeit at a slower rate, in competition expts. The borane thus must dissoc. from the carbonyl to activate the silane via hydride abstraction; the incipient silylium species then coordinates the most basic function, which is selectively reduced by [HB(C6F5)3]-. In addn. to the kinetic data, this mechanistic proposal is supported by a kinetic isotope effect of 1.4(5) for the hydrosilation of acetophenone, the observation that B(C6F5)3 catalyzes H/D and H/H scrambling in silanes in the absence of substrate, computational studies, the synthesis of models for proposed intermediates, and other isotope labeling and crossover expts.
    74. 74
      Eisenstein, O.; Milani, J.; Perutz, R. N. Selectivity of C-H Activation and Competition between C-H and C-F Bond Activation at Fluorocarbons. Chem. Rev. 2017, 117, 8710– 8753,  DOI: 10.1021/acs.chemrev.7b00163
      74
      Selectivity of C-H Activation and Competition between C-H and C-F Bond Activation at Fluorocarbons
      Eisenstein, Odile; Milani, Jessica; Perutz, Robin N.
      Chemical Reviews (Washington, DC, United States) (2017), 117 (13), 8710-8753CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
      Partially fluorinated alkanes, arenes, and alkenes can be transformed by a variety of transition metal and lanthanide systems. Although the C-H bond is weaker than the C-F bond regardless of the hybridization of the carbon, the reaction of the C-F bond at the metal is usually more exothermic than the corresponding reaction of the C-H bonds. Both bonds are activated by the metal systems, but the preference for activating these bonds depends on the nature of the hydrocarbon and of the metal system, so that the reaction can be directed exclusively toward C-H or C-F bonds or yield a mixt. of products. Addnl., the presence of fluorine differentiates between C-H bonds at different positions resulting in regioselective C-H bond activation; paradoxically, the strongest C-H bond reacts preferentially. The purpose of this review is to describe the field of reactions of partially fluorinated substrates with transition metal atoms, ions, and mol. complexes. The controlling phys. properties (thermodn. and kinetics) are described first, followed by a description of stoichiometric reactions, with the competition between the C-H and C-F activations as focus. A few representative catalytic systems are discussed. The review also highlights the benefit of combining exptl. and theor. studies.
    75. 75
      Slattery, J. M.; Hussein, S. How Lewis Acidic is Your Cation? Putting Phosphenium Ions on the Fluoride Ion Affinity Scale. Dalton Trans. 2012, 41, 1808– 1815,  DOI: 10.1039/C1DT11636C
      75
      How Lewis acidic is your cation? Putting phosphenium ions on the fluoride ion affinity scale
      Slattery, John M.; Hussein, Sharifa
      Dalton Transactions (2012), 41 (6), 1808-1815CODEN: DTARAF; ISSN:1477-9226. (Royal Society of Chemistry)
      The fluoride ion affinities (FIAs) of 33 phosphenium ions with a range of substituents were calcd. using ab initio and DFT methods. The use of these FIA data as a measure of the Lewis acidities of phosphenium ions is described and the FIAs of the species studied here are compared to FIA data for more commonly encountered Lewis acids. Phosphenium ions are often stronger Lewis acids than neutral species, but in many cases are less Lewis acidic than highly electrophilic cations such as [Me3C]+ or [Me3Si]+. The impact of mesomeric, inductive and steric substituent effects on FIAs are discussed and related to the underlying electronic structures of different cation types. A comparison between the FIAs of known "free" phosphenium ions with those that are currently unknown and other highly electrophilic cations suggests that some diaryl- and dialkyl phosphenium ions may yet be accessible under the right conditions.
    76. 76
      Gusev, D. G.; Ozerov, O. V. Calculated Hydride and Fluoride Affinities of a Series of Carbenium and Silylium Cations in the Gas Phase and in C6H5Cl Solution. Chem.─Eur. J. 2011, 17, 634– 640,  DOI: 10.1002/chem.201000696
      76
      Calculated Hydride and Fluoride Affinities of a Series of Carbenium and Silylium Cations in the Gas Phase and in C6H5Cl Solution
      Gusev, Dmitry G.; Ozerov, Oleg V.
      Chemistry - A European Journal (2011), 17 (2), 634-640, S634/1-S634/4CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
      We report the hydride and fluoride affinities for a group of silylium and carbenium cations. With comparable substituents on the central atom, the silylium cations have the higher fluoride affinity, whereas the carbenium ions have the higher hydride affinity. In the first approxn., the hydride and the fluoride affinities vary in parallel with changes in substitution, but the deviations from linear correspondence of hydride and fluoride affinities are more pronounced for carbenium ions. The hydride and fluoride affinities of silylium cations are very similar, whereas for carbenium ions, the hydride affinities are 35-60 kcal mol-1 higher than fluoride affinities. These results are placed in the context of studies of hydrodefluorination of aliph. C-F bonds enabled by silylium carborane catalysts. The abstraction of fluoride from perfluoroalkanes by a trialkylsilylium cation is neither thermodynamically favorable nor kinetically accessible and, if at all possible, will require a much more fluorophilic silylium cation.
    77. 77
      Hilton, M. C.; Dolewski, R. D.; McNally, A. Selective Functionalization of Pyridines via Heterocyclic Phosphonium Salts. J. Am. Chem. Soc. 2016, 138, 13806– 13809,  DOI: 10.1021/jacs.6b08662
      77
      Selective Functionalization of Pyridines via Heterocyclic Phosphonium Salts
      Hilton, Michael C.; Dolewski, Ryan D.; McNally, Andrew
      Journal of the American Chemical Society (2016), 138 (42), 13806-13809CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Methods that directly functionalize pyridines are in high demand due to their presence in pharmaceuticals, agrochems., and materials. A reaction that selectively transforms the 4-position C-H bonds in pyridines into C-PPh3+ groups that are subsequently converted into heteroaryl ethers is presented. The two step sequence is effective on complex pyridines, pharmaceutical mols., and other classes of heterocycles. Initial studies show that C-C, C-N, and C-S bond formations are also amenable.
    78. 78
      Anderson, R. G.; Jett, B. M.; McNally, A. Selective Formation Of Heteroaryl Thioethers via a Phosphonium Ion Coupling Reaction. Tetrahedron 2018, 74, 3129– 3136,  DOI: 10.1016/j.tet.2017.12.040
      78
      Selective formation of heteroaryl thioethers via a phosphonium ion coupling reaction
      Anderson, Ryan G.; Jett, Brianna M.; McNally, Andrew
      Tetrahedron (2018), 74 (25), 3129-3136CODEN: TETRAB; ISSN:0040-4020. (Elsevier Ltd.)
      Heteroaryl thioethers, comprised of pyridines and diazines, are an important class of compds. with relevance to medicinal chem. Metal-catalyzed cross-couplings and SNAr reactions are traditionally used to form C-S bonds in these systems but are limited by available halogenated precursors. An alternative approach is presented where pyridines and diazines are transformed into heterocyclic phosphonium salts and then C-S bonds are formed by adding thiolate nucleophiles. The process is 4-selective for pyridines, simple to execute and can be used to make derivs. of complex pharmaceuticals.
    79. 79
      Anderson, R. G.; Jett, B. M.; McNally, A. A Unified Approach to Couple Aromatic Heteronucleophiles to Azines and Pharmaceuticals. Angew. Chem., Int. Ed. 2018, 57, 12514– 12518,  DOI: 10.1002/anie.201807322
      79
      A Unified Approach to Couple Aromatic Heteronucleophiles to Azines and Pharmaceuticals
      Anderson, Ryan G.; Jett, Brianna M.; McNally, Andrew
      Angewandte Chemie, International Edition (2018), 57 (38), 12514-12518CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Coupling arom. heteronucleophiles to arenes is a common way to assemble drug-like mols. Many methods operate via nucleophiles intercepting organometallic intermediates, via Pd-, Cu-, and Ni-catalysis, that facilitate carbon-heteroatom bond formation and a variety of protocols. We present an alternative, unified strategy where phosphonium salts can replicate the behavior of organometallic intermediates. Under a narrow set of reaction conditions, a variety of arom. heteronucleophile classes can be coupled to pyridines and diazines that are often problematic in metal-catalyzed couplings, such as where (pseudo)halide precursors are unavailable in complex structures with multiple polar functional groups.
    80. 80
      Kwan, E. E.; Zeng, Y. W.; Besser, H. A.; Jacobsen, E. N. Concerted Nucleophilic Aromatic Substitutions. Nat. Chem. 2018, 10, 917– 923,  DOI: 10.1038/s41557-018-0079-7
      80
      Concerted nucleophilic aromatic substitutions
      Kwan, Eugene E.; Zeng, Yuwen; Besser, Harrison A.; Jacobsen, Eric N.
      Nature Chemistry (2018), 10 (9), 917-923CODEN: NCAHBB; ISSN:1755-4330. (Nature Research)
      Nucleophilic arom. substitution (SNAr) is one of the most widely applied reaction classes in pharmaceutical and chem. research, providing a broadly useful platform for the modification of arom. ring scaffolds. The generally accepted mechanism for SNAr reactions involves a two-step addn.-elimination sequence via a discrete, non-arom. Meisenheimer complex. Here the authors use 12C/13C kinetic isotope effect (KIE) studies and computational analyses to provide evidence that prototypical SNAr reactions in fact proceed through concerted mechanisms. The KIE measurements were made possible by a new technique that leverages the high sensitivity of 19F as an NMR nucleus to quantitate the degree of isotopic fractionation. This sensitive technique permits the measurement of KIEs on 10 mg of natural abundance material in one overnight acquisition. As a result, it provides a practical tool for performing detailed mechanistic analyses of reactions that form or break C-F bonds.
    81. 81
      Pike, S. D.; Crimmin, M. R.; Chaplin, A. B. Organometallic Chemistry Using Partially Fluorinated Benzenes. Chem. Commun. 2017, 53, 3615– 3633,  DOI: 10.1039/C6CC09575E
      81
      Organometallic chemistry using partially fluorinated benzenes
      Pike, Sebastian D.; Crimmin, Mark R.; Chaplin, Adrian B.
      Chemical Communications (Cambridge, United Kingdom) (2017), 53 (26), 3615-3633CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
      A review of fluorobenzenes, in particular fluorobenzene (FB) and 1,2-difluorobenzene (1,2-DiFB), which are increasingly becoming recognized as versatile solvents for conducting organometallic chem. and transition-metal-based catalysis. The presence of F substituents reduces the ability to donate π-electron d. from the arene and consequently fluorobenzenes generally bind weakly to metal centers, allowing them to be used as essentially noncoordinating solvents or as readily displaced ligands. In this context, examples of well-defined complexes of fluorobenzenes are discussed, including trends in binding strength with increasing fluorination and different substitution patterns. Compared to more highly fluorinated benzenes, FB and 1,2-DiFB typically demonstrate greater chem. inertness, however, C-H and C-F bond activation reactions can be induced using appropriately reactive transition metal complexes. Such reactions are surveyed, including catalytic examples, not only to provide perspective for the use of FB and 1,2-DiFB as innocent solvent media, but also to highlight opportunities for their exploitation in contemporary org. synthesis.
    82. 82
      Côté, J.-F.; Brouillette, D.; Desnoyers, J. E.; Rouleau, J. F.; StArnaud, J. M.; Perron, G. Dielectric Constants of Acetonitrile, Gamma-Butyrolactone, Propylene Carbonate, and 1,2-Dimethoxyethane as a Function of Pressure and Temperature. J. Solution Chem. 1996, 25, 1163– 1173,  DOI: 10.1007/BF00972644
      82
      Dielectric constants of acetonitrile, γ-butyrolactone, propylene carbonate, and 1,2-dimethoxyethane as a function of pressure and temperature
      Cote, Jean-francois; Brouillette, Dany; Desnoyers, Jacques E.; Rouleau, Jean-Francois; St-Arnaud, Jean-Marie; Perron, Gerald
      Journal of Solution Chemistry (1996), 25 (12), 1163-1173CODEN: JSLCAG; ISSN:0095-9782. (Plenum)
      The dielec. consts. ε of 1,2-dimethoxyethane, acetonitrile, γ-butyrolactone, and propylene carbonate were detd. from capacitance measurements extrapolated to infinite frequency; ln ε are reported as a function of pressure up to 80 MPa at 15, 25, 35, 45° and as a function of temp. in the range 10 to 50° at 0.10133 MPa. The variation of ln ε with temp. or pressure can be expressed by a second order polynomial expression. The isothermal compressibilities β of the solvents were detd. at 25° from sound velocities, densities, ad heat capacities. A simple correlation can be established between .vdelta. ln ε/.vdelta.P and β for most aprotic solvent.
    83. 83
      Hoffmann, R.; Howell, J. M.; Muetterties, E. L. Molecular-Orbital Theory of Pentacoordinate Phosphorus. J. Am. Chem. Soc. 1972, 94, 3047– 3058,  DOI: 10.1021/ja00764a028
      83
      Molecular orbital theory of pentacoordinate phosphorus
      Hoffmann, Roald; Howell, James M.; Muetterties, Earl L.
      Journal of the American Chemical Society (1972), 94 (9), 3047-58CODEN: JACSAT; ISSN:0002-7863.
      The electronic structure of some idealized PH5 geometries of D3h, C4v, and Cs symmetries is analyzed. Each geometry is characterized by a low-lying nodeless orbital, 3 singly noded orbitals close in energy, and a high-lying doubly noded nonbonding orbital. The latter orbital is the only one significantly stabilized by the inclusion of 3d orbitals in the P basis set and also dets. the relative stability of substituted compds. differing in electronegativity from H. A potential surface connecting the D3h and C4v geometries through C2v structures is constructed. It shows a small barrier for the Berry pseudorotation process. Optimum Cs structures are at higher energy than the C4v geometry. An examn. of substituent effects rationalizes favored apical substitution in the trigonal bipyramid and preferred basal substitution in the square pyramid by more electroneg. groups. It is predicted that π acceptors will prefer axial sites in the trigonal bipyramid, π donors equatorial positions. If a substituent has a single π system and is located in the equatorial position it will prefer to have its acceptor orbital perpendicular to the equatorial plane or its donor orbital in that plane. In the square pyramid, π donors will favor the apical position, π acceptors the basal sites. The concerted fragmentation reaction PR5 ↹ PR3 + R2 is symmetry forbidden for the least-motion axial-equatorial departure from a trigonal bipyramid, and allowed for axial-axial or equatorial-equatorial departure.

  • Supporting Information

    Supporting Information

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.3c10614.

    • Experimental and computational methods, key spectroscopic data, and computational results, including energies and xyz coordinates (PDF)


    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.