ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Figure 1Loading Img

Elucidation of Mechanisms and Selectivities of Metal-Catalyzed Reactions using Quantum Chemical Methodology

View Author Information
Department of Chemistry, Biology and Biotechnology, University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland
§ Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, P. R. China
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden
Cite this: Acc. Chem. Res. 2016, 49, 5, 1006–1018
Publication Date (Web):April 15, 2016
https://doi.org/10.1021/acs.accounts.6b00050

Copyright © 2016 American Chemical Society. This publication is licensed under these Terms of Use.

  • Open Access

Article Views

4546

Altmetric

-

Citations

LEARN ABOUT THESE METRICS
PDF (5 MB)

Abstract

Conspectus

Quantum chemical techniques today are indispensable for the detailed mechanistic understanding of catalytic reactions. The development of modern density functional theory approaches combined with the enormous growth in computer power have made it possible to treat quite large systems at a reasonable level of accuracy. Accordingly, quantum chemistry has been applied extensively to a wide variety of catalytic systems. A huge number of problems have been solved successfully, and vast amounts of chemical insights have been gained.

In this Account, we summarize some of our recent work in this field. A number of examples concerned with transition metal-catalyzed reactions are selected, with emphasis on reactions with various kinds of selectivities. The discussed cases are (1) copper-catalyzed C–H bond amidation of indoles, (2) iridium-catalyzed C(sp3)–H borylation of chlorosilanes, (3) vanadium-catalyzed Meyer–Schuster rearrangement and its combination with aldol- and Mannich-type additions, (4) palladium-catalyzed propargylic substitution with phosphorus nucleophiles, (5) rhodium-catalyzed 1:2 coupling of aldehydes and allenes, and finally (6) copper-catalyzed coupling of nitrones and alkynes to produce β-lactams (Kinugasa reaction).

First, the methodology adopted in these studies is presented briefly. The electronic structure method in the great majority of these kinds of mechanistic investigations has for the last two decades been based on density functional theory. In the cases discussed here, mainly the B3LYP functional has been employed in conjunction with Grimme’s empirical dispersion correction, which has been shown to improve the calculated energies significantly. The effect of the surrounding solvent is described by implicit solvation techniques, and the thermochemical corrections are included using the rigid-rotor harmonic oscillator approximation.

The reviewed examples are chosen to illustrate the usefulness and versatility of the adopted methodology in solving complex problems and proposing new detailed reaction mechanisms that rationalize the experimental findings. For each of the considered reactions, a consistent mechanism is presented, the experimentally observed selectivities are reproduced, and their sources are identified. Reproducing selectivities requires high accuracy in computing relative transition state energies. As demonstrated by the results summarized in this Account, this accuracy is possible with the use of the presented methodology, benefiting of course from a large extent of cancellation of systematic errors. It is argued that as the employed models become larger, the number of rotamers and isomers that have to be considered for every stationary point increases and a careful assessment of their energies is therefore necessary in order to ensure that the lowest energy conformation is located. This issue constitutes a bottleneck of the investigation in some cases and is particularly important when analyzing selectivities, since small energy differences need to be reproduced.

 Special Issue

Published as part of the Accounts of Chemical Research special issue “Computational Catalysis for Organic Synthesis”.

1 Introduction

ARTICLE SECTIONS
Jump To

It goes without saying that quantum chemistry today is an essential tool in many disciplines of chemistry. This is particularly the case for organic and organometallic chemistry, wherein the impact has been profound over the years, from the early developments of qualitative concepts for chemical bonding and reactivity using semiempirical methods, to today’s increasingly accurate results obtained with density functional theory (DFT) methodologies.
Continuous developments of the electronic structure methods as well as technical and algorithmic improvements, coupled with the exponential growth in computational power, have made it possible to treat ever larger systems, with ever higher accuracy. Consequently, an enormous number of applications have been published over the years, solving a huge number of outstanding problems and gaining vast amounts of chemical insight.
Recent reviews, (1) as well as the various contributions constituting the current special issue of Accounts of Chemical Research, summarize very well the state-of-the-art in this field, demonstrating the great levels of depth and breadth of the problems that can be tackled. The calculations are very commonly used to rationalize experimental findings and suggest additional experiments to verify mechanistic proposals, and it is in fact quite usual today to publish joint experimental/theoretical articles in which various aspects of the reaction mechanisms are addressed with the different complementary techniques, thereby developing a better understanding of the question at hand. Quantum chemical calculations are also increasingly frequently used as a predictive tool and in the design of new catalytic systems. (2)
In this Account, we will discuss a number of illustrative examples from our recent work in this field, with emphasis on how the calculations have been able to unravel new reaction mechanisms and also elucidate the sources of various selectivities of metal-catalyzed reactions. The discussions of the experimental backgrounds of these reactions are kept to a minimum in the interest of space; extended discussions can be found in the original articles. First, however, the computational methodology adopted in these applications will be outlined and commented briefly.

2 Computational Methodology

ARTICLE SECTIONS
Jump To

Mechanistic studies of catalytic reactions require the calculation of detailed free energy profiles, including the energies of all transition states and intermediates, at a sufficient level of accuracy. The electronic structure methods used in these kinds of studies have since the 1990s almost exclusively been based on DFT. In our investigations, we employ the widely popular hybrid B3LYP functional, (3) which offers a reasonable balance between speed and accuracy. In some of the applications, we also use the more recent M06 functional. (4) A limitation of B3LYP, and indeed most other functionals, is their inability to describe the attractive dispersion interactions properly. In the studies discussed here, the widely used empirical dispersion correction developed by Grimme (5) has been added, as it has been shown to improve the results considerably for many different applications. In some of the cases discussed here, it has been critical for the correct reproduction of the selectivity in question.
The geometries are typically optimized with a medium-sized basis set (usually with effective core potentials on the metals), and more accurate energies are then obtained using single-point calculations with a considerably larger basis set. The effects of solvent are usually modeled using implicit solvation techniques, which are fast and have over the years been improved to provide reasonable accuracy. In the cases discussed here, the commonly used CPCM (6) and SMD (7) methods have been employed. Free energy corrections are very commonly taken into account using the rigid-rotor harmonic oscillator model, which is also done in the studies presented here.
The selectivity of a reaction is determined by identifying the selectivity-determining transition states from the full energy profiles for the various alternative reaction pathways. The energy differences are then converted to product ratios by classical transition state theory. Thus, the study of selectivities requires typically reproduction of small energy differences, on the order of 1–2 kcal/mol on relative TS energies, something that usually can be achieved with the computational protocol outlined above. Of course, in this case the accuracy benefits to a large extent from cancellation of systematic errors between quite similar structures.
It is important to point out here that although the methodology is very common and has been employed by many groups for many different applications, it is of course not without problems, and experience has shown that one always has to be cautious and prepared to question it. (8) Every element of the methodology can be improved, and there are indeed techniques that can achieve higher accuracy.
One very important issue that must be mentioned here is that as the size of the employed models increases, the problem with the conformational search becomes more severe. A large number of isomers and rotamers have to be calculated explicitly for every stationary point in order to make sure that the lowest energy conformation is located. In some cases, the conformational search can be very extensive and can constitute the bottleneck of the investigation. In the applications discussed in this Account, the conformational search was performed manually. That is, for every stationary point, a number of reasonable isomers and rotamers were identified systematically, their geometries were optimized, and their energies were evaluated and compared. The conformational issue is particularly important in the study of selectivity, where small energy differences must be reproduced. For example, in a recent study on the stereoselectivity of the tetrapeptide-catalyzed kinetic resolution of trans-2-N-acetamidocyclohexanol, a large number of structures of the critical TS were optimized in order to reproduce the experimental results and to identify the factors that govern the selectivity. (9) In this case, the energy span for the optimized geometries was found to be up to 10 kcal/mol, which shows that a less careful treatment of this issue can have severe consequences and lead to the wrong chemical conclusions.

3 Cu-Catalyzed C–H Bond Amidation of Indoles

ARTICLE SECTIONS
Jump To

C–H functionalization reactions have received an enormous amount of attention in recent years, and great advancements have been made in terms of their synthetic utility. A major challenge faced in the pursuit of efficient methodologies is the control of the selectivity of the process. C–H bonds are ubiquitous in organic molecules, and thus it is necessary to devise strategies to enhance the catalyst selectivity.
We have used DFT calculations to investigate the reaction mechanisms and the origins of selectivities of two different C–H functionalization reactions, namely, the Cu-catalyzed amidation of indoles (described in this section) and the Ir-catalyzed borylation of chlorosilanes (next section).
Several methodologies have been reported for the selective C–H functionalization of the indole ring, with the preferential reactivity being usually either at the C2 or C3 positions. Typically, a higher reactivity at C2 is explained by the higher acidity of this position, while a preferential reaction at C3 is rationalized by the higher nucleophilicity of this position. However, the reasons for a certain catalyst resulting in a particular selectivity are often unclear, and the possibility of different mechanisms being operative is always an option. In 2010, Li and co-workers reported a copper-catalyzed oxidative amidation of 1-methylindoles. (10) The reaction made use of tert-butyl peroxide (TBP) as oxidant and selectively afforded the products of C2-functionalization (Scheme 1). The mechanism of this reaction and the origins of the observed selectivity were not clear, which motivated a detailed computational investigation. (11)

Scheme 1

Scheme 1. Copper-Catalyzed Regioselective Amidation of Indoles
The catalytic cycle that we proposed on the basis of the calculations is shown in Scheme 2. First, it was found that copper(I) bromide can be oxidized with a feasible barrier to a Cu(III) species by TBP, in line with the mechanistic hypothesis proposed by Li and co-workers. The subsequent amide coordination and deprotonation, with one of the tert-butoxide ligand acting as a base, and t-BuOH release occur practically without a barrier. Next, the critical indole amidation step takes place. We located the transition states for this step occurring through the well-established concerted-metalation deprotonation (CMD) mechanism (12) on both C2 and C3 positions (Figure 1). It turns out that in both cases the CMD occurs concertedly with the reductive elimination (CMD-RE). The energy barriers associated with these TSs are reasonable (20.6 and 15.7 kcal/mol for C2 and C3 positions, respectively), but they result in the exclusive amidation at the C3 position, in contrast to the experimental results. Looking for alternative mechanisms that could account for the observed regioselectivity, we found that the amidation can occur through a new kind of mechanism termed four-center reductive elimination (4CRE), with the metal coordinating either C2 or C3 and the amide group attacking the adjacent position (Figure 1). These TSs also have reasonable barriers and, very importantly, the barrier for the reaction occurring on C2 through a 4CRE is lower than that for a CMD on C3 (13.7 vs 15.7 kcal/mol). Thus, the observed regioselectivity can be explained on the basis of the lower barrier found for the 4CRE mechanism compared with the CMD. The 4CRE mechanism favors the C2 functionalization because of a stabilizing interaction between electrophilic Cu(III) and the nucleophilic C3 position of indole. The 4CRE mechanism is similar to the Heck-like mechanism obtained by Wu and co-workers in their mechanistic study of the meta-selective copper-catalyzed arylation of anilides. (13)

Scheme 2

Scheme 2. Mechanism of Copper-Catalyzed Regioselective Amidation of Indoles Obtained from the Calculations

Figure 1

Figure 1. Optimized transition states of copper-catalyzed regioselective amidation of indoles. Energies relative to the common reactants are indicated in kcal/mol.

Finally, an important technical detail in our study was that the dispersion correction was found to be necessary in order to reproduce the experimental regioselectivity. (11)

4 Ir-Catalyzed C(sp3)–H Borylation of Chlorosilanes

ARTICLE SECTIONS
Jump To

In another detailed mechanistic and selectivity study of a C–H activation reaction, we considered the iridium-catalyzed C(sp3)–H borylation of chlorosilanes reported recently by Suginome and co-workers (Scheme 3). (14) The reaction was found to occur exclusively at the primary methyl C–H bond, without a secondary borylation product being generated. When C(sp2)–H bonds are present in the substrate, only C(sp2)–H borylation was observed in the reaction. Importantly, it was found that the presence of the chlorosilyl group is crucial for the reaction to take place. Upon replacement of the silicon by a carbon or change of the chlorine substituent to a methyl group, no borylation product was observed. (15) Replacement of the chlorine substituent by other moieties, such as chloromethyl or methoxy groups, led to a significant decrease in yields. It was proposed that the chlorosilyl group plays a role as a directing group to coordinate the substrate with either the iridium or one of the boron atoms in the active species [(3,4,7,8-Me4-phen)Ir(Bpin)3], which can promote the C–H oxidative addition step. (14)

Scheme 3

Scheme 3. Ir-Catalyzed C(sp3)–H Borylation of Chlorosilanes
The mechanism of the Ir-catalyzed C(sp2)–H borylation is well-established, involving Ir(III)/Ir(V) intermediates and consisting of three steps: C–H oxidative addition, C–B reductive elimination, and regeneration of active catalyst. (16) In order to elucidate the detailed mechanism of the C(sp3)–H borylation of chlorosilanes, and in particular the role of the chlorosilyl group, we performed DFT calculations using both the B3LYP and M06 functionals. (17) The catalytic cycle obtained on the basis of the calculations is shown in Scheme 4.

Scheme 4

Scheme 4. Reaction Mechanism Suggested for the Ir-Catalyzed C(sp3)–H Borylation of Chlorosilanes
The calculations showed first, consistent with previous investigations, (16) that the seven-coordinate 18-electron Ir(V)-intermediate INT0, formed by the reaction of [(3,4,7,8-Me4-phen)Ir(Bpin)3] (INT1), the commonly accepted active catalytic species, with another B2pin2 molecule, is the lowest lying intermediate of the overall cycle and constitutes thus the resting state of the catalyst. For the C(sp3)–H oxidative addition, the proposed directing role of the chlorine could not be observed in the calculations. This step was found to proceed through a transition state without any direct interaction between the chlorine and the iridium or the boron (TS1, Figure 2). Regarding the subsequent C–B reductive elimination, the two employed functionals gave slightly different conclusions. B3LYP-D3 suggested that an isomerization step from INT2 to INT3, involving a change of the hydride position, is required prior to the C–B reductive elimination, with the former step being rate-determining. M06, on the other hand, yielded that the direct C–B reductive elimination is favored. A definitive conclusion could not be drawn regarding this issue on the basis of the calculations. Interestingly, Hartwig and co-workers reported very recently an Ir-catalyzed benzylic C(sp3)–H borylation of methylarenes, where they found that the scenario with the isomerization/C–B reductive elimination is more favored on the basis of both experimental and computational results. (18)

Figure 2

Figure 2. Optimized structures of selected transition states for the mechanism of Ir-catalyzed C(sp3)–H borylation of chlorosilanes.

Both functionals reproduced quite well the observed experimental trends in the relative reactivity of the different substrates. The bond dissociation energies (BDEs) of the C–H bonds of the substrates and the Ir–C bonds of the Ir(V) hydride intermediates INT2, resulting from the C–H oxidative addition step, were calculated in order to rationalize the role of the chlorosilyl group. The results showed that the C–H BDEs are not sensitive to the substituents, while a good correlation between the barriers and the calculated Ir–C BDEs of the Ir(V) hydride intermediates was found. The accelerating role of the chlorosilyl group could thus be attributed to its strong α-carbanion stabilizing property, stemming from a combination of the silicon α-effect and the high electronegativity of the chlorine substituent.
The origin of the preferential borylation of primary over secondary C(sp3)–H was also considered and discussed in our calculations, and it was concluded that steric effects (repulsion between the alkyl group and the Ir/ligand moiety) are responsible for the experimentally observed selectivity. We found furthermore that the difference between C(sp2)–H and C(sp3)–H borylation is mainly due to the different reactivities of the intermediates resulting from the C–H oxidative addition. Distortion/interaction analysis of C–B reductive elimination transition states showed that such a reactivity difference originates from a higher interaction energy in the C(sp2)–B reductive elimination compared with the C(sp3)–B counterpart, stemming mainly from the presence of a Ph–B π* orbital that can enhance the back-bonding interaction with the d orbital of iridium.

5 Intermediate Trapping in V-Catalyzed Meyer–Schuster Rearrangement

ARTICLE SECTIONS
Jump To

A very interesting class of metal-catalyzed reactions for which quantum-chemical calculations may be very insightful for explaining the selectivity are processes involving the so-called intermediate interception strategy. In this approach, the mechanistic pathway is diverted from its ordinary tracks by trapping of a catalytic intermediate intermolecularly with an added reagent or intramolecularly with a functional group introduced into the substrate. By utilizing unique chemical reactivities of the transient species, such reactions often enable entry to otherwise not readily accessible structural motifs. However, there exists an inherent challenge associated with the intermediate interception. Namely, in order for this strategy to be successful, the trapping step must take place more efficiently compared with the pathway followed normally by the catalytic reaction. We have investigated computationally two related processes developed by the group of Trost consisting of vanadium-catalyzed Meyer–Schuster rearrangement combined with aldol- and Mannich-type additions, which at their core employ the interception of a catalytic vanadium enolate species (Scheme 5). (19)

Scheme 5

Scheme 5. Interception of Vanadium Enolate Intermediate with Aldehyde or Imine Leading to Combined Meyer–Schuster Rearrangement–Aldol/Mannich Reaction
The calculations were able to shed light on a number of aspects of the reaction mechanism that previously lacked proper understanding (Figure 3). (20) The resting state of the catalyst was identified as an off-cycle tris(triarylsilyl) orthovanadate, while the active form was found to be a mixed vanadate ester incorporating only a single propargylic alcohol reactant moiety. The study of the 1,3-migration step posed a particular challenge due to the difficulties with calculating the barrier for a dissociative ionic pathway. Considering the nonpolar nature of the reaction solvent, the barrier was estimated by the energy of the associated ion-pair, which was found to be somewhat lower than the alternative concerted transition state. This is corroborated by the experimentally observed loss of stereochemical information from an enantioenriched chiral substrate. (19b) Importantly, the initial ligand substitution and the subsequent 1,3-shift were found to constitute the largest span on the free energy profile, determining the overall rate of the reaction. This result is in contrast with the previous suggestion that the product release that takes place later in the catalytic cycle is rate-determining. (19) The calculations also provided an explanation for the preferential formation of the (Z)-isomers of the products, which were found to originate from the steric interactions blocking one face of the enolate from the approach of aldehyde or imine (Figure 4).

Figure 3

Figure 3. (A) Computationally established mechanism of the reaction from Scheme 5 and (B) the corresponding free energy profile.

Figure 4

Figure 4. Optimized structures of the transitions states for the trapping of vanadium enolate with an imine, leading to (A) (Z)-configured and (B) (E)-configured Mannich products.

Next, we examined the selectivity of the reactions with respect to following the two competing branches of the catalytic cycle. It was established that both steps diverging from the common vanadium enolate intermediate are irreversible; hence the relative energy of the corresponding transition states determines the final product ratio. The calculated values showed that for both the aldol and Mannich versions of the reaction, the trapping by the added electrophile is barely energetically favored over the normal Meyer–Schuster rearrangement pathway. These findings agree very well with the experiments, which required the use of an excess of the propargylic alcohol and its slow addition to the reaction mixture in order to secure high yields of the desired products. Namely, the former compensates for the inevitable partial conversion of propargylic alcohol into ketone, while the latter maintains a low concentration of the alcohol in the reaction mixture, slowing the undesired intermolecular transesterification/tautomerization pathway.

6 Pd-Catalyzed Propargylic Substitution with Phosphorus Nucleophiles

ARTICLE SECTIONS
Jump To

We have investigated the mechanisms and selectivities of two metal-catalyzed processes involving allene-containing compounds. In the first, the Pd-catalyzed propargylic substitution with phosphorus nucleophiles described in this section, the allenes are products of the reaction, while in the second, the Rh-catalyzed 1:2 coupling of aldehydes and allenes (next section), they play the role of substrates.
One of the most general methods providing access to a variety of allenes is the palladium-catalyzed SN2′ propargylic substitution. (21, 22) Its applicability is, however, limited to the use of hard organometallic nucleophiles, for example, organozinc reagents. Heteroatom (N- and O-centered) as well as soft carbon nucleophiles follow alternative pathways in the reaction with propargylic substrates, leading to nonallenic compounds. (22) A notable exception are H-phosphonates, which afford P-substituted allenes in good selectivity (Scheme 6). (23) The palladium-catalyzed SN2′ propargylic substitution with the phosphorus nucleophiles features several additional advantages from the synthetic point of view, such as a full control of the stereochemistry and mild reaction conditions allowing for the synthesis of complex P-allenes of interest to biological and pharmaceutical chemistry.

Scheme 6

Scheme 6. Possible Pathways in the Palladium-Catalyzed Reaction between Propargylic Carbonates and H-Phosphonate Diesters
In order to understand the intriguing selectivity observed in the reaction shown in Scheme 6, we performed a thorough computational investigation of the possible pathways and established a plausible catalytic cycle (Scheme 7). (24) It was found that the reaction takes place via consecutive oxidative addition, decarboxylation, H-phosphonate deprotonation, transmetalation (ligand exchange), and finally reductive elimination. The last step was identified as being rate-determining for the overall transformation, although it is not involved in deciding the selectivity of the reaction.

Scheme 7

Scheme 7. Computationally Established Mechanism of the Reaction from Scheme 6
The key difference in the behavior of H-phosphonates compared with other nucleophiles originates from the lack of free electron pairs on phosphorus in the incipient reagent, implying the necessity for deprotonation prior to any bond-forming event. According to the calculations, the abstraction of proton is feasible exclusively by a palladium-bound methoxide, forming a phosphite anion, whose dissociation into the solution is strongly energetically disfavored. Thus, the generated nucleophilic species can only attack on the central carbon of either η1-allenyl or η1-propargyl moiety in the parent complexes (but not η3-propargyl, present in an intermediate earlier in the cycle) or participate in the transmetalation (Figure 5). The energies calculated for the corresponding transition states clearly point to the latter alternative as the favored pathway, leading eventually to the experimentally observed product. The calculations provided also an explanation for the preferential formation of allenyl- over propargylphosphonates. Interestingly, the first irreversible steps determining this selectivity were found to be different in the two branches of the catalytic cycle (see Scheme 7), highlighting the importance of a complete computational analysis of the full mechanism.

Figure 5

Figure 5. Optimized structures of selected transitions states from the allenyl branch of the mechanism shown in Scheme 7: (A) transmetalation, (B) attack on carbon C2, and (C) reductive elimination.

7 Rh-Catalyzed 1:2 Coupling of Aldehydes and Allenes

ARTICLE SECTIONS
Jump To

Murakami and co-workers reported recently the novel rhodium-catalyzed coupling of aldehydes and allenes shown in Scheme 8. (25) It was found that instead of 1:1 coupling (hydroacylation), 1:2 coupling products formed from one molecule of aldehyde and two molecules of allene. A very intriguing feature of this reaction is its remarkable regioselectivity. In principle, there exists a large number of possible different isomers of 1:2 coupling products. However, when [RhCl(dppe)] is used as a catalyst, compound A was obtained as the major product, accompanied by two minor isomers, B and C, with a ratio of 91:6:3. Interestingly, the counterion of the rhodium catalyst was found to have a profound impact on the selectivity. Namely, upon replacing the chloride by noncoordinating counterions (e.g., TfO, BF4, or PF6), only products A and C were formed, and the selectivity switched to compound C becoming the dominant product.

Scheme 8

Scheme 8. Rh-Catalyzed 1:2 Coupling of Aldehydes and Allenes
Murakami and co-workers proposed that the reaction is initiated by oxidative cyclization of aldehyde and allene to generate a five-membered oxarhodacyclic intermediate. Subsequent insertion of allene into Rh–C bond followed by β-hydride elimination and C–H reductive elimination would give the final 1:2 coupling products. (25) Considering that rhodium complexes have been widely used in hydroacylation and cycloaddition of unsaturated compounds, alternative pathways, such as those initiated by oxidative cyclization of the two allenes or by C–H oxidative addition of aldehyde, are possible. DFT calculations were performed to elucidate the detailed mechanism of this novel reaction and to rationalize the origins of the selectivity. (26) Both neutral [RhCl(dppe)] and cationic [Rh(dppe)+] catalytic systems were considered and compared in order to understand the peculiar counterion effect.
At each step, all possible reactions were considered, and a large number of isomers and rotamers were calculated for each stationary point. The calculations suggested the following reaction mechanism (Scheme 9): (1) The reaction is initiated by oxidative cyclization of two allenes. Interestingly, instead of the expected five-membered rhodacycle intermediate, this step leads to the formation of a η31-bis(allylic) Rh(III) complex (see Figure 6). (2) The second C–C bond forming step to incorporate the aldehyde moiety into the structure was found to take place through an allylation reaction (Figure 6) that has a lower barrier than a migratory insertion into the Rh–C bond. (3) After the allylation step, the calculations showed that the following steps are different depending on the catalyst employed. For [RhCl(dppe)], η1 to η3 rearrangement, β-hydride elimination, and C–H reductive elimination were found to be responsible for the formation of the final products, while in the case of [Rh(dppe)+], an alkoxide oxidation step (Figure 6) leads directly to the 1:2 coupling products. Very importantly, this difference in the mechanism explains why three products are observed for [RhCl(dppe)] but only two for [Rh(dppe)+], and it also reproduces the experimentally observed trends in the product distribution. The calculations showed that the overall selectivity of the reaction is determined by the inherent selectivities of several elementary steps. The Rh–allyl complexes, which can adopt both η3 and η1 configurations, are key intermediates present throughout the catalytic cycle and have important implications on the selectivity.

Scheme 9

Scheme 9. Computationally Established Mechanisms for the 1:2 Coupling of Aldehyde and Allenes Catalyzed by (A) [RhCl(dppe)] and (B) [Rh(dppe)+]a

Scheme aOnly the pathway leading to the major reaction product is shown in each case.

Figure 6

Figure 6. Optimized structures of selected transition states and intermediates involved in the mechanism of 1:2 coupling of aldehyde and allenes: (A) η31-bis(allylic) Rh(III) complex; (B) allylation TS with [RhCl(dppe)]; (C) reductive elimination TS with [RhCl(dppe)]; (D) alkoxide oxidation TS with [Rh(dppe)+].

8 Cu-Catalyzed Coupling of Nitrones and Alkynes

ARTICLE SECTIONS
Jump To

The Cu(I)-catalyzed reaction between a nitrone and a terminal alkyne, known as the Kinugasa reaction, allows an easy entry to β-lactams, with perfect atom economy and generally good diastereoselectivity (Scheme 10). (27) The reaction was originally disclosed by Kinugasa in 1972 using a stoichiometric amount of copper, (28) and it was achieved in a catalytic version only 20 years later by Miura and co-workers. (29) After Miura’s reports several research groups investigated the applicability of the reaction, using a variety of ligands, bases, and solvents. Also, enantioselective versions of the reaction based on the use of chiral ligands have been reported. (27, 30) The reaction mechanism had, however, not been investigated in detail, and only speculative hypotheses were reported in the literature. (27, 31)

Scheme 10

Scheme 10. Kinugasa Reaction: Copper-Catalyzed Synthesis of Lactams
We performed a comprehensive investigation using DFT calculations with the aim of elucidating the detailed mechanism and also the origins of the enantioselectivity of an asymmetric variant of the Kinugasa reaction. (32) For the mechanistic study, phenanthroline was used as the ligand and triethylamine as the base. A number of possible pathways were examined, and the calculations suggested the mechanism shown in Scheme 11, which was found to be associated with the lowest energy barriers.

Scheme 11

Scheme 11. Suggested Mechanism for the Kinugasa Reaction on the Basis of the Calculations
The reaction starts with an initial deprotonation of the alkyne with the assistance of two copper ions. The next step involves a C–C bond formation leading to a six-membered ring intermediate (Figure 7), followed by a low-energy-barrier ring contraction resulting in the formation of a metalated isoxazoline. At this point, after release of one copper ion, it was found that protonation of isoxazoline nitrogen leads to ring opening, with the formation of a ketene intermediate. Finally, a copper-assisted intramolecular nucleophilic attack gives a four-membered ring intermediate, which after copper release and tautomerization evolves to the final product. The copper is thus involved in every step of the reaction, lowering the energy barrier for each of them: First, it acidifies the alkyne making its deprotonation feasible. Second, it allows the cycloaddition to occur in a stepwise fashion, with lower energy barriers compared with a concerted cycloaddition. Finally, copper acts as a Lewis acid on the ketene promoting the final nucleophilic attack.

Figure 7

Figure 7. Optimized structures of selected transitions states and intermediates for the mechanism shown in Scheme 11: (A) C–C bond formation TS; (B) six-membered ring intermediate; (C) ring contraction TS; (D) cyclization TS leading to the four-membered ring intermediate.

Alternative pathways involving an initial deprotonation assisted by one copper ion or the cycloaddition occurring on the parent alkyne were also tested and found to be associated with higher energy barriers. It should be considered, however, that the relative energies of the different mechanistic possibilities could be sensitive to the reaction conditions, such as the natures of the copper ligand, the base, and the solvent employed.
In addition to the reaction mechanism, the enantioselectivity was investigated for the case of the bis(azaferrocene) ligand designed by Fu that afforded enantioenriched products in up to 93% enantiomeric excess. (30) All the possible pathways studied for the nonenantioselective reaction were also considered with the chiral ligand. It was found that two different mechanisms, namely, the pathway described above involving two copper ions and a mechanism with the initial cycloaddition occurring on the parent alkyne, have quite similar energy barriers and are both able to account for the experimentally observed enantioselectivity. Considering the limitations of the computational methods, it was not possible to rule out either of the two possibilities. In both mechanisms, the preferential formation of one of the two enantiomers was found to depend on steric effects exerted by the bulky azaferrocene groups.

9 Concluding Remarks

ARTICLE SECTIONS
Jump To

We have in this Account summarized a number of studies performed recently in our group to illustrate how quantum chemical methodology can be used to develop better understanding for complex reaction mechanisms and to elucidate the origins of selectivities of metal-catalyzed catalytic processes. Quantum chemistry is a dynamic research field, with continuous developments of methods and methodologies to study various aspects of chemistry. Enormous progress has been made in the field of mechanistic homogeneous catalysis, and the future promises even greater momentum.
To speculate a bit, it is reasonable to expect that the accuracy of practically every aspect of the methodology mentioned above will witness improvement in the future. For example, more accurate electronic structure methods based on coupled cluster theory are already starting to become affordable and provide thus a viable option for this field. More accurate ways of treating the solvation and the thermal corrections are also being developed.
It is also likely that the growing computer power will allow for automated unbiased searches and conformational sampling for large systems. These developments will make quantum chemistry an even more powerful tool with even greater predictive powers. Like in other fields, some aspects of the methodology will become more of a black-box, while other elaborate aspects will continue to need the expertise of experienced computational chemists.

Author Information

ARTICLE SECTIONS
Jump To

  • Corresponding Author
    • Fahmi Himo - Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden Email: [email protected]
  • Authors
    • Stefano Santoro - Department of Chemistry, Biology and Biotechnology, University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
    • Marcin Kalek - Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland
    • Genping Huang - Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, P. R. China
  • Notes
    The authors declare no competing financial interest.

Biographies

ARTICLE SECTIONS
Jump To

Stefano Santoro

Stefano Santoro was born in Campobasso, Italy, in 1980. He received his Ph.D. degree from the University of Perugia in 2009 (under supervision of Profs. Claudio Santi and Marcello Tiecco). In the period 2010–2014, he was a postdoctoral researcher at Stockholm University with Prof. Fahmi Himo, after which he became an assistant professor at the University of Perugia.

Marcin Kalek

Marcin Kalek was born in Łódź, Poland, in 1983. He obtained his M.Sc. degree from the University of Warsaw in 2005 and his Ph.D. from Stockholm University in 2011 under supervision of Prof. Jacek Stawinski. After completing two postdoctoral fellowships with Prof. Fahmi Himo at Stockholm University (2011–2013) and with Prof. Gregory C. Fu at the California Institute of Technology (2013–2015), he returned to Poland and joined the faculty of the University of Warsaw as an assistant professor in 2016.

Genping Huang

Genping Huang was born in Anhui, China, in 1984. He received his Ph.D. (2011) at Qinghai Institute of Salt Lakes, Chinese Academy of Sciences, China, under supervision of Prof. Yahong Li and Prof. Yuanzhi Xia. After his postdoctoral work with Prof. Fahmi Himo at Stockholm University (2011–2014), he joined the faculty at Tianjin University, China, as an associate professor of chemistry.

Fahmi Himo

Fahmi Himo was born in 1973 in Hassake, Syria. He graduated from Stockholm University in 2000 under supervision of Profs. Leif Eriksson and Per Siegbahn. He then spent two years as a Wenner-Gren postdoctoral fellow with Prof. Louis Noodleman at the Scripps Research Institute (2000–2002) and three years as a Wenner-Gren Fellow at the Royal Institute of Technology in Stockholm (2002–2005). He worked then as an assistant professor at the same place (2005–2009) before moving to his current position as a professor at Stockholm University.

Acknowledgment

ARTICLE SECTIONS
Jump To

Collaborators and co-workers who have contributed to the work described in this Account are gratefully acknowledged. The work was supported financially by the Swedish Research Council, the Göran Gustafsson Foundation, the Knut and Alice Wallenberg Foundation, the Wenner-Gren Foundations, and the Carl-Trygger Foundation. M.K. acknowledges support from the Polish National Science Centre (Grant No. 2014/15/D/ST5/02579).

References

ARTICLE SECTIONS
Jump To

This article references 32 other publications.

  1. 1

    See, for example:

    (a) Lin, Z. Interplay between Theory and Experiment: Computational Organometallic and Transition Metal Chemistry Acc. Chem. Res. 2010, 43, 602 611 DOI: 10.1021/ar9002027
    (b) Fey, N.; Ridgway, B. M.; Jover, J.; McMullin, C. L.; Harvey, J. N. Organometallic reactivity: the role of metal–ligand bond energies from a computational perspective Dalton Trans. 2011, 40, 11184 11191 DOI: 10.1039/c1dt10909j
    (c) Liu, P.; Houk, K. N. Theoretical studies of regioselectivity of Ni- and Rh-catalyzed C–C bond forming reactions with unsymmetrical alkynes Inorg. Chim. Acta 2011, 369, 2 14 DOI: 10.1016/j.ica.2010.12.042
    (d) Sameera, W. M. C.; Maseras, F. Transition metal catalysis by density functional theory and density functional theory/molecular mechanics WIREs Comput. Mol. Sci. 2012, 2, 375 385 DOI: 10.1002/wcms.1092
    (e) Stirling, A.; Nair, N. N.; Lledós, A.; Ujaque, G. Challenges in modelling homogeneous catalysis: new answers from ab initio molecular dynamics to the controversy over the Wacker process Chem. Soc. Rev. 2014, 43, 4940 4952 DOI: 10.1039/c3cs60469a
    (f) Lupp, D.; Christensen, N. J.; Fristrup, P. Synergy between experimental and theoretical methods in the exploration of homogeneous transition metal catalysis Dalton Trans. 2014, 43, 11093 11105 DOI: 10.1039/c4dt00342j
    (g) Sakaki, S. Theoretical and Computational Study of a Complex System Consisting of Transition Metal Element(s): How to Understand and Predict Its Geometry, Bonding Nature, Molecular Property, and Reaction Behavior Bull. Chem. Soc. Jpn. 2015, 88, 889 938 DOI: 10.1246/bcsj.20150119
    (h) Sperger, T.; Sanhueza, I. A.; Kalvet, I.; Schoenebeck, F. Computational Studies of Synthetically Relevant Homogeneous Organometallic Catalysis Involving Ni, Pd, Ir, and Rh: An Overview of Commonly Employed DFT Methods and Mechanistic Insights Chem. Rev. 2015, 115, 9532 9586 DOI: 10.1021/acs.chemrev.5b00163
  2. 2
    (a) Nguyen, Q. N. N.; Tantillo, D. J. The Many Roles of Quantum Chemical Predictions in Synthetic Organic Chemistry Chem. - Asian J. 2014, 9, 674 680 DOI: 10.1002/asia.201301452
    (b) Jover, J.; Fey, N. The Computational Road to Better Catalysts Chem. - Asian J. 2014, 9, 1714 1723 DOI: 10.1002/asia.201301696
  3. 3
    (a) Becke, A. D. Density-functional thermochemistry. III. The role of exact exchange J. Chem. Phys. 1993, 98, 5648 5652 DOI: 10.1063/1.464913
    (b) Lee, C.; Yang, W.; Parr, R. G. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785 789 DOI: 10.1103/PhysRevB.37.785
  4. 4
    Zhao, Y.; Truhlar, D. G. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals Theor. Chem. Acc. 2008, 120, 215 241 DOI: 10.1007/s00214-007-0310-x
  5. 5
    Grimme, S. Density Functional Theory with London Dispersion Corrections WIREs Comput. Mol. Sci. 2011, 1, 211 228 DOI: 10.1002/wcms.30
  6. 6
    (a) Barone, V.; Cossi, M. Quantum calculation of molecular energies and energy gradients in solution by a conductor solvent model J. Phys. Chem. A 1998, 102, 1995 2001 DOI: 10.1021/jp9716997
    (b) Cossi, M.; Rega, N.; Scalmani, G.; Barone, V. Energies, structures, and electronic properties of molecules in solution with the C-PCM solvation model J. Comput. Chem. 2003, 24, 669 681 DOI: 10.1002/jcc.10189
  7. 7
    Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. Universal solvation model based on solute electron density and a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions J. Phys. Chem. B 2009, 113, 6378 6396 DOI: 10.1021/jp810292n
  8. 8

    For a recent critical discussion, see:

    Plata, R. E.; Singleton, D. A. A Case Study of the Mechanism of Alcohol-Mediated Morita Baylis-Hillman Reactions. The Importance of Experimental Observations J. Am. Chem. Soc. 2015, 137, 3811 3826 DOI: 10.1021/ja5111392
  9. 9
    Liao, R.-Z.; Santoro, S.; Gotsev, M.; Marcelli, T.; Himo, F. Origins of Stereoselectivity in Peptide-Catalyzed Kinetic Resolution of Alcohols ACS Catal. 2016, 6, 1165 1171 DOI: 10.1021/acscatal.5b02131
  10. 10
    Shuai, Q.; Deng, G.; Chua, Z.; Bohle, D. S.; Li, C.-J. Copper-Catalyzed Highly Regioselective Oxidative C-H Bond Amidation of 2-Arylpyridine Derivatives and 1-Methylindoles Adv. Synth. Catal. 2010, 352, 632 636 DOI: 10.1002/adsc.200900775
  11. 11
    Santoro, S.; Liao, R.-Z.; Himo, F. Theoretical Study of Mechanism and Selectivity of Copper-Catalyzed C-H Bond Amidation of Indoles J. Org. Chem. 2011, 76, 9246 9252 DOI: 10.1021/jo201447e
  12. 12
    Lapointe, D.; Fagnou, K. Overview of the Mechanistic Work on the Concerted Metallation-Deprotonation Pathway Chem. Lett. 2010, 39, 1118 1126 DOI: 10.1246/cl.2010.1118
  13. 13
    Chen, B.; Hou, X.-L.; Li, Y.-X.; Wu, Y.-D. Mechanistic Understanding of the Unexpected Meta Selectivity in Copper-Catalyzed Anilide C–H Bond Arylation J. Am. Chem. Soc. 2011, 133, 7668 7671 DOI: 10.1021/ja201425e
  14. 14
    Ohmura, T.; Torigoe, T.; Suginome, M. Catalytic Functionalization of Methyl Group on Silicon: Iridium-Catalyzed C(sp3)–H Borylation of Methylchlorosilanes J. Am. Chem. Soc. 2012, 134, 17416 17419 DOI: 10.1021/ja307956w
  15. 15

    It was subsequently found that a much higher reaction temperature had to be applied in order to observe the borylation product for the substrate without the chlorine substituent:

    Ohmura, T.; Torigoe, T.; Suginome, M. Functionalization of Tetraorganosilanes and Permethyloligosilanes at a Methyl Group on Silicon via Iridium-Catalyzed C(sp3)–H Borylation Organometallics 2013, 32, 6170 6173 DOI: 10.1021/om400900z
  16. 16
    Tamura, H.; Yamazaki, H.; Sato, H.; Sakaki, S. Iridium-Catalyzed Borylation of Benzene with Diboron. Theoretical Elucidation of Catalytic Cycle Including Unusual Iridium(V) Intermediate J. Am. Chem. Soc. 2003, 125, 16114 16126 DOI: 10.1021/ja0302937
  17. 17
    Huang, G.; Kalek, M.; Liao, R.-Z.; Himo, F. Mechanism, Reactivity, and Selectivity of the Iridium-Catalyzed C(sp3)–H Borylation of Chlorosilanes Chem. Sci. 2015, 6, 1735 1746 DOI: 10.1039/C4SC01592D
  18. 18
    Larsen, M. A.; Wilson, C. V.; Hartwig, J. F. Iridium-Catalyzed Borylation of Primary Benzylic C–H Bonds without a Directing Group: Scope, Mechanism, and Origins of Selectivity J. Am. Chem. Soc. 2015, 137, 8633 8643 DOI: 10.1021/jacs.5b04899
  19. 19
    (a) Trost, B. M.; Oi, S. Atom Economy: Aldol-Type Products by Vanadium-Catalyzed Additions of Propargyl Alcohols and Aldehydes J. Am. Chem. Soc. 2001, 123, 1230 1231 DOI: 10.1021/ja003629a
    (b) Trost, B. M.; Chung, C. K. Vanadium-Catalyzed Addition of Propargyl Alcohols and Imines J. Am. Chem. Soc. 2006, 128, 10358 10359 DOI: 10.1021/ja064011p
  20. 20
    Kalek, M.; Himo, F. Combining Meyer–Schuster Rearrangement with Aldol and Mannich Reactions: Theoretical Study of the Intermediate Interception Strategy J. Am. Chem. Soc. 2012, 134, 19159 19169 DOI: 10.1021/ja307892c
  21. 21
    Yu, S.; Ma, S. How easy are the syntheses of allenes? Chem. Commun. 2011, 47, 5384 5418 DOI: 10.1039/c0cc05640e
  22. 22
    Tsuji, J.; Mandai, T. Palladium-Catalyzed Reactions of Propargylic Compounds in Organic Synthesis Angew. Chem., Int. Ed. Engl. 1996, 34, 2589 2612 DOI: 10.1002/anie.199525891
  23. 23
    (a) Kalek, M.; Stawinski, J. Novel, Stereoselective and Stereospecific Synthesis of Allenylphosphonates and Related Compounds via Palladium-Catalyzed Propargylic Substitution Adv. Synth. Catal. 2011, 353, 1741 1755 DOI: 10.1002/adsc.201100119
    (b) Kalek, M.; Johansson, T.; Jezowska, M.; Stawinski, J. Palladium-Catalyzed Propargylic Substitution with Phosphorus Nucleophiles: Efficient, Stereoselective Synthesis of Allenylphosphonates and Related Compounds Org. Lett. 2010, 12, 4702 4704 DOI: 10.1021/ol102121j
  24. 24
    Jiménez-Halla, J. O. C.; Kalek, M.; Stawinski, J.; Himo, F. Computational Study of the Mechanism and Selectivity of Palladium-Catalyzed Propargylic Substitution with Phosphorus Nucleophiles Chem. - Eur. J. 2012, 18, 12424 12436 DOI: 10.1002/chem.201201026
  25. 25
    Toyoshima, T.; Miura, T.; Murakami, M. Selective 1:2 Coupling of Aldehydes and Allenes with Control of Regiochemistry Angew. Chem., Int. Ed. 2011, 50, 10436 10439 DOI: 10.1002/anie.201105077
  26. 26
    Huang, G.; Kalek, M.; Himo, F. Mechanism and Selectivity of Rhodium-Catalyzed 1:2 Coupling of Aldehydes and Allenes J. Am. Chem. Soc. 2013, 135, 7647 7659 DOI: 10.1021/ja4014166
  27. 27
    Stecko, S.; Furman, B.; Chmielewski, M. Kinugasa reaction: an ‘ugly duckling’ of β-lactam chemistry Tetrahedron 2014, 70, 7817 7844 DOI: 10.1016/j.tet.2014.06.024
  28. 28
    Kinugasa, M.; Hashimoto, S. The reactions of copper(I) phenylacetylide with nitrones J. Chem. Soc., Chem. Commun. 1972, 466 467 DOI: 10.1039/c39720000466
  29. 29
    (a) Okuro, K.; Enna, M.; Miura, M.; Nomura, M. Copper-catalysed reaction of arylacetylenes with C,N-diarylnitrones J. Chem. Soc., Chem. Commun. 1993, 1107 1108 DOI: 10.1039/c39930001107
    (b) Miura, M.; Enna, M.; Okuro, K.; Nomura, M. Copper-catalyzed reaction of terminal alkynes with nitrones. Selective synthesis of 1-aza-1-buten-3-yne and 2-azetidinone derivatives J. Org. Chem. 1995, 60, 4999 5004 DOI: 10.1021/jo00121a018
  30. 30

    For the first highly enantioselective Kinugasa reaction, see:

    Lo, M. M.-C.; Fu, G. C. Cu(I)/bis(azaferrocene)-catalyzed enantioselective synthesis of β-lactams via couplings of alkynes with nitrones J. Am. Chem. Soc. 2002, 124, 4572 4573 DOI: 10.1021/ja025833z
  31. 31
    (a) Ding, L. K.; Irwin, W. J. Cis- and trans-azetidin-2-ones from nitrones and copper acetylide J. Chem. Soc., Perkin Trans. 1 1976, 2382 2386 DOI: 10.1039/p19760002382
    (b) Shintani, R.; Fu, G. C. Catalytic enantioselective synthesis of β-lactams: intramolecular Kinugasa reactions and interception of an intermediate in the reaction cascade Angew. Chem., Int. Ed. 2003, 42, 4082 4085 DOI: 10.1002/anie.200352103
  32. 32
    Santoro, S.; Liao, R.-Z.; Marcelli, T.; Hammar, P.; Himo, F. Theoretical study of mechanism and stereoselectivity of catalytic Kinugasa reaction J. Org. Chem. 2015, 80, 2649 2660 DOI: 10.1021/jo502838p

Cited By

ARTICLE SECTIONS
Jump To

This article is cited by 69 publications.

  1. Denis Jacquemin, Fábris Kossoski, Franck Gam, Martial Boggio-Pasqua, Pierre-François Loos. Reference Vertical Excitation Energies for Transition Metal Compounds. Journal of Chemical Theory and Computation 2023, 19 (23) , 8782-8800. https://doi.org/10.1021/acs.jctc.3c01080
  2. Hanliang Zheng, Liu Cai, Ming Pan, Muhammet Uyanik, Kazuaki Ishihara, Xiao-Song Xue. Catalyst-Substrate Helical Character Matching Determines the Enantioselectivity in the Ishihara-Type Iodoarenes Catalyzed Asymmetric Kita-Dearomative Spirolactonization. Journal of the American Chemical Society 2023, 145 (13) , 7301-7312. https://doi.org/10.1021/jacs.2c13295
  3. Ali Hashemi, Sana Bougueroua, Marie-Pierre Gaigeot, Evgeny A. Pidko. ReNeGate: A Reaction Network Graph-Theoretical Tool for Automated Mechanistic Studies in Computational Homogeneous Catalysis. Journal of Chemical Theory and Computation 2022, 18 (12) , 7470-7482. https://doi.org/10.1021/acs.jctc.2c00404
  4. Pooja Jain, Nitesh Kumar, Vidya Avasare. A Shuttle Catalysis: Elucidating a True Reaction Mechanism Involved in the Palladium Xantphos-Assisted Transposition of Aroyl Chloride and Aryl Iodide Functional Groups. The Journal of Organic Chemistry 2022, 87 (19) , 12547-12557. https://doi.org/10.1021/acs.joc.2c00193
  5. Bangaru Bhaskararao, Madeline E. Rotella, Dong Yeon Kim, Jung-Min Kee, Kwang Soo Kim, Marisa C. Kozlowski. Ir and NHC Dual Chiral Synergetic Catalysis: Mechanism and Stereoselectivity in γ-Butyrolactone Formation. Journal of the American Chemical Society 2022, 144 (35) , 16171-16183. https://doi.org/10.1021/jacs.2c07376
  6. Yi Wang, Wei Liao, Yuanyuan Wang, Lei Jiao, Zhi-Xiang Yu. Mechanism and Stereochemistry of Rhodium-Catalyzed [5 + 2 + 1] Cycloaddition of Ene–Vinylcyclopropanes and Carbon Monoxide Revealed by Visual Kinetic Analysis and Quantum Chemical Calculations. Journal of the American Chemical Society 2022, 144 (6) , 2624-2636. https://doi.org/10.1021/jacs.1c11030
  7. Harish S. Kunchur, Maravanji S. Balakrishna. Platinum Assisted Tandem P–C Bond Cleavage and P–N Bond Formation in Amide Functionalized Bisphosphine o-Ph2PC6H4C(O)N(H)C6H4PPh2-o: Synthesis, Mechanistic, and Catalytic Studies. Inorganic Chemistry 2022, 61 (2) , 857-868. https://doi.org/10.1021/acs.inorgchem.1c02515
  8. Ali Hussain Motagamwala, James A. Dumesic. Microkinetic Modeling: A Tool for Rational Catalyst Design. Chemical Reviews 2021, 121 (2) , 1049-1076. https://doi.org/10.1021/acs.chemrev.0c00394
  9. Yu-hong Lam, Yuriy Abramov, Ravi S. Ananthula, Jennifer M. Elward, Lori R. Hilden, Sten O. Nilsson Lill, Per-Ola Norrby, Antonio Ramirez, Edward C. Sherer, Jason Mustakis, Gerald J. Tanoury. Applications of Quantum Chemistry in Pharmaceutical Process Development: Current State and Opportunities. Organic Process Research & Development 2020, 24 (8) , 1496-1507. https://doi.org/10.1021/acs.oprd.0c00222
  10. Jeremy N. Harvey, Fahmi Himo, Feliu Maseras, Lionel Perrin. Scope and Challenge of Computational Methods for Studying Mechanism and Reactivity in Homogeneous Catalysis. ACS Catalysis 2019, 9 (8) , 6803-6813. https://doi.org/10.1021/acscatal.9b01537
  11. Pedro Villar, Adán B. González-Pérez, Angel R. de Lera. Deciphering the Origin of Enantioselectivity on the Cis-Cyclopropanation of Styrene with Enantiopure Di-chloro,Di-gold(I)-SEGPHOS Carbenoids Generated from Propargylic Esters. The Journal of Organic Chemistry 2019, 84 (12) , 7664-7673. https://doi.org/10.1021/acs.joc.9b00250
  12. Nitinchandra D. Patel, Joshua D. Sieber, Sergei Tcyrulnikov, Bryan J. Simmons, Daniel Rivalti, Krishnaja Duvvuri, Yongda Zhang, Donghong A. Gao, Keith R. Fandrick, Nizar Haddad, Kendricks So Lao, Hari P. R. Mangunuru, Soumik Biswas, Bo Qu, Nelu Grinberg, Scott Pennino, Heewon Lee, Jinhua J. Song, B. Frank Gupton, Neil K. Garg, Marisa C. Kozlowski, Chris H. Senanayake. Computationally Assisted Mechanistic Investigation and Development of Pd-Catalyzed Asymmetric Suzuki–Miyaura and Negishi Cross-Coupling Reactions for Tetra-ortho-Substituted Biaryl Synthesis. ACS Catalysis 2018, 8 (11) , 10190-10209. https://doi.org/10.1021/acscatal.8b02509
  13. Guangcai Ma, Haiying Yu, Ting Xu, Xiaoxuan Wei, Jianrong Chen, Hongjun Lin, Gerrit Schüürmann. Computational Insight into the Activation Mechanism of Carcinogenic N’-Nitrosonornicotine (NNN) Catalyzed by Cytochrome P450. Environmental Science & Technology 2018, 52 (20) , 11838-11847. https://doi.org/10.1021/acs.est.8b02795
  14. Mojgan Heshmat. Unraveling the Origin of Solvent Induced Enantioselectivity in the Henry Reaction with Cinchona Thiourea as Catalyst. The Journal of Physical Chemistry A 2018, 122 (40) , 7974-7982. https://doi.org/10.1021/acs.jpca.8b04589
  15. Julien Pastor, Elixabete Rezabal, Arnaud Voituriez, Jean-François Betzer, Angela Marinetti, and Gilles Frison . Revised Theoretical Model on Enantiocontrol in Phosphoric Acid Catalyzed H-Transfer Hydrogenation of Quinoline. The Journal of Organic Chemistry 2018, 83 (5) , 2779-2787. https://doi.org/10.1021/acs.joc.7b03248
  16. Mei Zhang, Lingfei Hu, Yanmin Lang, Yang Cao, and Genping Huang . Mechanism and Origins of Regio- and Enantioselectivities of Iridium-Catalyzed Hydroarylation of Alkenyl Ethers. The Journal of Organic Chemistry 2018, 83 (5) , 2937-2947. https://doi.org/10.1021/acs.joc.8b00377
  17. Bangaru Bhaskararao, Garima Jindal, and Raghavan B. Sunoj . Exploring the Mechanism and Stereoselectivity in Chiral Cinchona-Catalyzed Heterodimerization of Ketenes. The Journal of Organic Chemistry 2017, 82 (24) , 13449-13458. https://doi.org/10.1021/acs.joc.7b02517
  18. Yuri A. Aoto, Ana Paula de Lima Batista, Andreas Köhn, and Antonio G. S. de Oliveira-Filho . How To Arrive at Accurate Benchmark Values for Transition Metal Compounds: Computation or Experiment?. Journal of Chemical Theory and Computation 2017, 13 (11) , 5291-5316. https://doi.org/10.1021/acs.jctc.7b00688
  19. Man Li, Xiao-Song Xue, and Jin-Pei Cheng . Mechanism and Origins of Stereoinduction in Natural Cinchona Alkaloid Catalyzed Asymmetric Electrophilic Trifluoromethylthiolation of β-Keto Esters with N-Trifluoromethylthiophthalimide as Electrophilic SCF3 Source. ACS Catalysis 2017, 7 (11) , 7977-7986. https://doi.org/10.1021/acscatal.7b03007
  20. Bangaru Bhaskararao and Raghavan B. Sunoj . Asymmetric Dual Chiral Catalysis using Iridium Phosphoramidites and Diarylprolinol Silyl Ethers: Insights into Stereodivergence. ACS Catalysis 2017, 7 (10) , 6675-6685. https://doi.org/10.1021/acscatal.7b02776
  21. Li Ji, Chenchen Wang, Shujing Ji, Kasper P. Kepp, and Piotr Paneth . Mechanism of Cobalamin-Mediated Reductive Dehalogenation of Chloroethylenes. ACS Catalysis 2017, 7 (8) , 5294-5307. https://doi.org/10.1021/acscatal.7b00540
  22. Marcin Kalek and Fahmi Himo . Mechanism and Selectivity of Cooperatively Catalyzed Meyer–Schuster Rearrangement/Tsuji–Trost Allylic Substitution. Evaluation of Synergistic Catalysis by Means of Combined DFT and Kinetics Simulations. Journal of the American Chemical Society 2017, 139 (30) , 10250-10266. https://doi.org/10.1021/jacs.7b01931
  23. Ellen V. Dalessandro, Hugo P. Collin, Luiz Gustavo L. Guimarães, Marcelo S. Valle, Josefredo R. Pliego, Jr.. Mechanism of the Piperidine-Catalyzed Knoevenagel Condensation Reaction in Methanol: The Role of Iminium and Enolate Ions. The Journal of Physical Chemistry B 2017, 121 (20) , 5300-5307. https://doi.org/10.1021/acs.jpcb.7b03191
  24. Arghya Deb, Avijit Hazra, Qian Peng, Robert S. Paton, and Debabrata Maiti . Detailed Mechanistic Studies on Palladium-Catalyzed Selective C–H Olefination with Aliphatic Alkenes: A Significant Influence of Proton Shuttling. Journal of the American Chemical Society 2017, 139 (2) , 763-775. https://doi.org/10.1021/jacs.6b10309
  25. Jesús Jover and Feliu Maseras . Mechanistic Investigation of Iridium-Catalyzed C–H Borylation of Methyl Benzoate: Ligand Effects in Regioselectivity and Activity. Organometallics 2016, 35 (18) , 3221-3226. https://doi.org/10.1021/acs.organomet.6b00562
  26. Abdullah, Aslihan Aycan Tanriverdi, Azmat Ali Khan, Sei-Jin Lee, Jong Bae Park, Yang Soo Kim, Umit Yildiko, Kim Min, Mahboob Alam. Selenium-substituted conjugated small molecule: Synthesis, spectroscopic, computational studies, antioxidant activity, and molecular docking. Journal of Molecular Structure 2024, 1304 , 137694. https://doi.org/10.1016/j.molstruc.2024.137694
  27. Luxuan Guo, Jeremy N. Harvey. Kinetic modelling of cobalt-catalyzed propene hydroformylation: a combined ab initio and experimental fitting protocol. Catalysis Science & Technology 2024, 14 (4) , 961-972. https://doi.org/10.1039/D3CY01625K
  28. Emma King-Smith, Simon Berritt, Louise Bernier, Xinjun Hou, Jacquelyn L. Klug-McLeod, Jason Mustakis, Neal W. Sach, Joseph W. Tucker, Qingyi Yang, Roger M. Howard, Alpha A. Lee. Probing the chemical ‘reactome’ with high-throughput experimentation data. Nature Chemistry 2024, 360 https://doi.org/10.1038/s41557-023-01393-w
  29. Ken-ichi Yamada, Tsubasa Inokuma. Evaluation of quantum chemistry calculation methods for conformational analysis of organic molecules using A -value estimation as a benchmark test. RSC Advances 2023, 13 (51) , 35904-35910. https://doi.org/10.1039/D3RA06783A
  30. Farideh Pahlavan, Sedigheh Saddat Moosavi, Amin Reza Zolghadr, Nasser Iranpoor. Electronic origins of the stereochemistry in β-lactam formed through the Staudinger reaction catalyzed by a nucleophile. RSC Advances 2023, 13 (48) , 33654-33667. https://doi.org/10.1039/D3RA05286A
  31. Hiroki Hayashi, Satoshi Maeda, Tsuyoshi Mita. Quantum chemical calculations for reaction prediction in the development of synthetic methodologies. Chemical Science 2023, 14 (42) , 11601-11616. https://doi.org/10.1039/D3SC03319H
  32. Giuseppe Sciortino, Feliu Maseras. Microkinetic modelling in computational homogeneous catalysis and beyond. Theoretical Chemistry Accounts 2023, 142 (10) https://doi.org/10.1007/s00214-023-03044-2
  33. Júlia M. A. Alves, Ivanna G. R. Domingos, Marcelo T. de Oliveira. Accelerating computations of organometallic reaction energies through hybrid basis sets. Inorganic Chemistry Frontiers 2023, 10 (8) , 2262-2267. https://doi.org/10.1039/D3QI00136A
  34. Raghavan B. Sunoj. Coming of Age of Computational Chemistry from a Resilient Past to a Promising Future. Israel Journal of Chemistry 2022, 62 (1-2) https://doi.org/10.1002/ijch.202100106
  35. Odile Eisenstein. From the Felkin‐Anh Rule to the Grignard Reaction: an Almost Circular 50 Year Adventure in the World of Molecular Structures and Reaction Mechanisms with Computational Chemistry**. Israel Journal of Chemistry 2022, 62 (1-2) https://doi.org/10.1002/ijch.202100138
  36. Akinobu Matsuzawa, Jeremy N. Harvey, Fahmi Himo. On the Importance of Considering Multinuclear Metal Sites in Homogeneous Catalysis Modeling. Topics in Catalysis 2022, 65 (1-4) , 96-104. https://doi.org/10.1007/s11244-021-01507-z
  37. Óscar López, José M. Padrón. Iridium- and Palladium-Based Catalysts in the Pharmaceutical Industry. Catalysts 2022, 12 (2) , 164. https://doi.org/10.3390/catal12020164
  38. Ting Qi, Shuai Fu, Xiang Zhang, Ting-Hao Liu, Qing-Zhu Li, Chuan Gou, Jun-Long Li. Theoretical insight into the origins of chemo- and diastereo-selectivity in the palladium-catalysed (3 + 2) cyclisation of 5-alkenyl thiazolones. Organic Chemistry Frontiers 2021, 8 (22) , 6203-6214. https://doi.org/10.1039/D1QO01071A
  39. Lucas Guillemard, Nikolaos Kaplaneris, Lutz Ackermann, Magnus J. Johansson. Late-stage C–H functionalization offers new opportunities in drug discovery. Nature Reviews Chemistry 2021, 5 (8) , 522-545. https://doi.org/10.1038/s41570-021-00300-6
  40. Agustí Lledós. Computational Organometallic Catalysis: Where We Are, Where We Are Going. European Journal of Inorganic Chemistry 2021, 2021 (26) , 2547-2555. https://doi.org/10.1002/ejic.202100330
  41. Victoria M. Ingman, Anthony J. Schaefer, Laura R. Andreola, Steven E. Wheeler. QChASM : Quantum chemistry automation and structure manipulation. WIREs Computational Molecular Science 2021, 11 (4) https://doi.org/10.1002/wcms.1510
  42. Josefredo R. Pliego. Catalytic cycle and off-cycle steps in the palladium-catalyzed fluorination of aryl bromide with biaryl monophosphine ligands: Theoretical free energy profile. Molecular Catalysis 2021, 506 , 111540. https://doi.org/10.1016/j.mcat.2021.111540
  43. Daisuke Urabe, Keisuke Fukaya. Systematic Search for Transition States in Complex Molecules: Computational Analyses of Regio- and Stereoselective Interflavan Bond Formation in Flavan-3-ols. HETEROCYCLES 2021, 102 (6) , 1061. https://doi.org/10.3987/REV-20-943
  44. Cheng-Xing Cui, Haohua Chen, Shi-Jun Li, Tao Zhang, Ling-Bo Qu, Yu Lan. Mechanism of Ir-catalyzed hydrogenation: A theoretical view. Coordination Chemistry Reviews 2020, 412 , 213251. https://doi.org/10.1016/j.ccr.2020.213251
  45. Josefredo R. Pliego. Theoretical free energy profile and benchmarking of functionals for amino-thiourea organocatalyzed nitro-Michael addition reaction. Physical Chemistry Chemical Physics 2020, 22 (20) , 11529-11536. https://doi.org/10.1039/D0CP00481B
  46. Vitor H. Menezes da Silva, Caio C. Oliveira, Carlos Roque D. Correia, Ataualpa A. C. Braga. Heck arylation of acyclic olefins employing arenediazonium salts and chiral N,N ligands: new mechanistic insights from quantum-chemical calculations. Theoretical Chemistry Accounts 2020, 139 (4) https://doi.org/10.1007/s00214-020-02588-x
  47. Erico S. Teixeira, Jorge A. Morales. Electron nuclear dynamics with plane wave basis sets: complete theory and formalism. Theoretical Chemistry Accounts 2020, 139 (4) https://doi.org/10.1007/s00214-020-2578-z
  48. Pooja Jain, Rahul K. Shukla, Sourav Pal, Vidya Avasare. Hydrogen bonding and non-covalent interaction assisted nickel(0) catalysed reversible alkenyl functional group swapping: a computational study. Catalysis Science & Technology 2020, 10 (6) , 1747-1760. https://doi.org/10.1039/C9CY02486G
  49. Binh Khanh Mai, Fahmi Himo. Mechanisms of Metal-Catalyzed Electrophilic F/CF3/SCF3 Transfer Reactions from Quantum Chemical Calculations. 2020, 39-56. https://doi.org/10.1007/3418_2020_45
  50. Yunyi Li, Zhengxing Wu, Zheng Ling, Hongjin Chen, Wanbin Zhang. Mechanistic study of the solvent-controlled Pd( ii )-catalyzed chemoselective intermolecular 1,2-aminooxygenation and 1,2-oxyamination of conjugated dienes. Organic Chemistry Frontiers 2019, 6 (4) , 486-492. https://doi.org/10.1039/C8QO01288A
  51. Bangaru Bhaskararao, Raghavan B. Sunoj. Two chiral catalysts in action: insights into cooperativity and stereoselectivity in proline and cinchona-thiourea dual organocatalysis. Chemical Science 2018, 9 (46) , 8738-8747. https://doi.org/10.1039/C8SC03078B
  52. Hongli Wu, Xiaojie Li, Xiangyang Tang, Genping Huang. Mechanism and origins of chemo- and regioselectivities of (NHC)NiH-catalyzed cross-hydroalkenylation of vinyl ethers with α-olefins: a computational study. Organic Chemistry Frontiers 2018, 5 (23) , 3410-3420. https://doi.org/10.1039/C8QO01020J
  53. Maria Besora, Feliu Maseras. Microkinetic modeling in homogeneous catalysis. WIREs Computational Molecular Science 2018, 8 (6) https://doi.org/10.1002/wcms.1372
  54. Jolene P. Reid, Matthew S. Sigman. Comparing quantitative prediction methods for the discovery of small-molecule chiral catalysts. Nature Reviews Chemistry 2018, 2 (10) , 290-305. https://doi.org/10.1038/s41570-018-0040-8
  55. Jaime Rodríguez‐Guerra, Lur Alonso‐Cotchico, Giuseppe Sciortino, Agustí Lledós, Jean‐Didier Maréchal. Computational Studies of Artificial Metalloenzymes: From Methods and Models to Design and Optimization. 2018, 99-136. https://doi.org/10.1002/9783527804085.ch4
  56. Xinzheng Yang, Xiangyang Chen. Mechanistic Insights and Computational Prediction of Base Metal Pincer Complexes for Catalytic Hydrogenation and Dehydrogenation Reactions. 2018, 101-110. https://doi.org/10.1016/B978-0-12-812931-9.00005-0
  57. Leonid I. Belen’kii, Yulia B. Evdokimenkova. The Literature of Heterocyclic Chemistry, Part XVI, 2016. 2018, 173-254. https://doi.org/10.1016/bs.aihch.2018.02.003
  58. Xiaojie Li, Hongli Wu, Yanmin Lang, Genping Huang. Mechanism, selectivity, and reactivity of iridium- and rhodium-catalyzed intermolecular ketone α-alkylation with unactivated olefins via an enamide directing strategy. Catalysis Science & Technology 2018, 8 (9) , 2417-2426. https://doi.org/10.1039/C8CY00290H
  59. Mojgan Heshmat, Timofei Privalov. Theory‐Based Extension of the Catalyst Scope in the Base‐Catalyzed Hydrogenation of Ketones: RCOOH‐Catalyzed Hydrogenation of Carbonyl Compounds with H 2 Involving a Proton Shuttle. Chemistry – A European Journal 2017, 23 (72) , 18193-18202. https://doi.org/10.1002/chem.201702149
  60. Hongyan Zou, Zhong‐Liang Wang, Genping Huang. Mechanism and Origins of the Chemo‐ and Regioselectivities in Nickel‐Catalyzed Intermolecular Cycloadditions of Benzocyclobutenones with 1,3‐Dienes. Chemistry – A European Journal 2017, 23 (51) , 12593-12603. https://doi.org/10.1002/chem.201702316
  61. Yanfei Guan, Steven E. Wheeler. Automated Quantum Mechanical Predictions of Enantioselectivity in a Rhodium‐Catalyzed Asymmetric Hydrogenation. Angewandte Chemie 2017, 129 (31) , 9229-9233. https://doi.org/10.1002/ange.201704663
  62. Yanfei Guan, Steven E. Wheeler. Automated Quantum Mechanical Predictions of Enantioselectivity in a Rhodium‐Catalyzed Asymmetric Hydrogenation. Angewandte Chemie International Edition 2017, 56 (31) , 9101-9105. https://doi.org/10.1002/anie.201704663
  63. Josefa Anaya, Ramón M. Sánchez. Four-Membered Ring Systems. 2017, 115-145. https://doi.org/10.1016/B978-0-08-102310-5.00004-7
  64. Gabriel Aullón, Margarita Crespo, Jesús Jover, Manuel Martínez. Diarylplatinum(II) Scaffolds for Kinetic and Mechanistic Studies on the Formation of Platinacycles via an Oxidative Addition/Reductive Elimination/Oxidative Addition Sequence. 2017, 195-242. https://doi.org/10.1016/bs.adioch.2017.01.001
  65. Jesús Jover. Quantitative DFT modeling of product concentration in organometallic reactions: Cu-mediated pentafluoroethylation of benzoic acid chlorides as a case study. Physical Chemistry Chemical Physics 2017, 19 (43) , 29344-29353. https://doi.org/10.1039/C7CP05709A
  66. P. Lanzafame, S. Perathoner, G. Centi, S. Gross, E. J. M. Hensen. Grand challenges for catalysis in the Science and Technology Roadmap on Catalysis for Europe: moving ahead for a sustainable future. Catalysis Science & Technology 2017, 7 (22) , 5182-5194. https://doi.org/10.1039/C7CY01067B
  67. Emilia Sicilia. Computation modeling as a tool for the exploration of complex multistep reaction cycles in homogeneous catalysis. Some selected examples in the framework of the use of hydrogen as a fuel of the future. International Journal of Quantum Chemistry 2016, 116 (21) , 1507-1512. https://doi.org/10.1002/qua.25201
  68. Xinwen Zhang, Hongyan Zou, Genping Huang. Mechanism and Origins of Ligand‐Controlled Selectivity of Rhodium‐Catalyzed Intermolecular Cycloadditions of Vinylaziridines with Alkynes. ChemCatChem 2016, 8 (15) , 2549-2556. https://doi.org/10.1002/cctc.201600349
  69. Stefano Santoro, Marcin Kalek, Genping Huang, Fahmi Himo. ChemInform Abstract: Elucidation of Mechanisms and Selectivities of Metal‐Catalyzed Reactions Using Quantum Chemical Methodology. ChemInform 2016, 47 (28) https://doi.org/10.1002/chin.201628275
  • Abstract

    Scheme 1

    Scheme 1. Copper-Catalyzed Regioselective Amidation of Indoles

    Scheme 2

    Scheme 2. Mechanism of Copper-Catalyzed Regioselective Amidation of Indoles Obtained from the Calculations

    Figure 1

    Figure 1. Optimized transition states of copper-catalyzed regioselective amidation of indoles. Energies relative to the common reactants are indicated in kcal/mol.

    Scheme 3

    Scheme 3. Ir-Catalyzed C(sp3)–H Borylation of Chlorosilanes

    Scheme 4

    Scheme 4. Reaction Mechanism Suggested for the Ir-Catalyzed C(sp3)–H Borylation of Chlorosilanes

    Figure 2

    Figure 2. Optimized structures of selected transition states for the mechanism of Ir-catalyzed C(sp3)–H borylation of chlorosilanes.

    Scheme 5

    Scheme 5. Interception of Vanadium Enolate Intermediate with Aldehyde or Imine Leading to Combined Meyer–Schuster Rearrangement–Aldol/Mannich Reaction

    Figure 3

    Figure 3. (A) Computationally established mechanism of the reaction from Scheme 5 and (B) the corresponding free energy profile.

    Figure 4

    Figure 4. Optimized structures of the transitions states for the trapping of vanadium enolate with an imine, leading to (A) (Z)-configured and (B) (E)-configured Mannich products.

    Scheme 6

    Scheme 6. Possible Pathways in the Palladium-Catalyzed Reaction between Propargylic Carbonates and H-Phosphonate Diesters

    Scheme 7

    Scheme 7. Computationally Established Mechanism of the Reaction from Scheme 6

    Figure 5

    Figure 5. Optimized structures of selected transitions states from the allenyl branch of the mechanism shown in Scheme 7: (A) transmetalation, (B) attack on carbon C2, and (C) reductive elimination.

    Scheme 8

    Scheme 8. Rh-Catalyzed 1:2 Coupling of Aldehydes and Allenes

    Scheme 9

    Scheme 9. Computationally Established Mechanisms for the 1:2 Coupling of Aldehyde and Allenes Catalyzed by (A) [RhCl(dppe)] and (B) [Rh(dppe)+]a

    Scheme aOnly the pathway leading to the major reaction product is shown in each case.

    Figure 6

    Figure 6. Optimized structures of selected transition states and intermediates involved in the mechanism of 1:2 coupling of aldehyde and allenes: (A) η31-bis(allylic) Rh(III) complex; (B) allylation TS with [RhCl(dppe)]; (C) reductive elimination TS with [RhCl(dppe)]; (D) alkoxide oxidation TS with [Rh(dppe)+].

    Scheme 10

    Scheme 10. Kinugasa Reaction: Copper-Catalyzed Synthesis of Lactams

    Scheme 11

    Scheme 11. Suggested Mechanism for the Kinugasa Reaction on the Basis of the Calculations

    Figure 7

    Figure 7. Optimized structures of selected transitions states and intermediates for the mechanism shown in Scheme 11: (A) C–C bond formation TS; (B) six-membered ring intermediate; (C) ring contraction TS; (D) cyclization TS leading to the four-membered ring intermediate.

  • References

    ARTICLE SECTIONS
    Jump To

    This article references 32 other publications.

    1. 1

      See, for example:

      (a) Lin, Z. Interplay between Theory and Experiment: Computational Organometallic and Transition Metal Chemistry Acc. Chem. Res. 2010, 43, 602 611 DOI: 10.1021/ar9002027
      (b) Fey, N.; Ridgway, B. M.; Jover, J.; McMullin, C. L.; Harvey, J. N. Organometallic reactivity: the role of metal–ligand bond energies from a computational perspective Dalton Trans. 2011, 40, 11184 11191 DOI: 10.1039/c1dt10909j
      (c) Liu, P.; Houk, K. N. Theoretical studies of regioselectivity of Ni- and Rh-catalyzed C–C bond forming reactions with unsymmetrical alkynes Inorg. Chim. Acta 2011, 369, 2 14 DOI: 10.1016/j.ica.2010.12.042
      (d) Sameera, W. M. C.; Maseras, F. Transition metal catalysis by density functional theory and density functional theory/molecular mechanics WIREs Comput. Mol. Sci. 2012, 2, 375 385 DOI: 10.1002/wcms.1092
      (e) Stirling, A.; Nair, N. N.; Lledós, A.; Ujaque, G. Challenges in modelling homogeneous catalysis: new answers from ab initio molecular dynamics to the controversy over the Wacker process Chem. Soc. Rev. 2014, 43, 4940 4952 DOI: 10.1039/c3cs60469a
      (f) Lupp, D.; Christensen, N. J.; Fristrup, P. Synergy between experimental and theoretical methods in the exploration of homogeneous transition metal catalysis Dalton Trans. 2014, 43, 11093 11105 DOI: 10.1039/c4dt00342j
      (g) Sakaki, S. Theoretical and Computational Study of a Complex System Consisting of Transition Metal Element(s): How to Understand and Predict Its Geometry, Bonding Nature, Molecular Property, and Reaction Behavior Bull. Chem. Soc. Jpn. 2015, 88, 889 938 DOI: 10.1246/bcsj.20150119
      (h) Sperger, T.; Sanhueza, I. A.; Kalvet, I.; Schoenebeck, F. Computational Studies of Synthetically Relevant Homogeneous Organometallic Catalysis Involving Ni, Pd, Ir, and Rh: An Overview of Commonly Employed DFT Methods and Mechanistic Insights Chem. Rev. 2015, 115, 9532 9586 DOI: 10.1021/acs.chemrev.5b00163
    2. 2
      (a) Nguyen, Q. N. N.; Tantillo, D. J. The Many Roles of Quantum Chemical Predictions in Synthetic Organic Chemistry Chem. - Asian J. 2014, 9, 674 680 DOI: 10.1002/asia.201301452
      (b) Jover, J.; Fey, N. The Computational Road to Better Catalysts Chem. - Asian J. 2014, 9, 1714 1723 DOI: 10.1002/asia.201301696
    3. 3
      (a) Becke, A. D. Density-functional thermochemistry. III. The role of exact exchange J. Chem. Phys. 1993, 98, 5648 5652 DOI: 10.1063/1.464913
      (b) Lee, C.; Yang, W.; Parr, R. G. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785 789 DOI: 10.1103/PhysRevB.37.785
    4. 4
      Zhao, Y.; Truhlar, D. G. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals Theor. Chem. Acc. 2008, 120, 215 241 DOI: 10.1007/s00214-007-0310-x
    5. 5
      Grimme, S. Density Functional Theory with London Dispersion Corrections WIREs Comput. Mol. Sci. 2011, 1, 211 228 DOI: 10.1002/wcms.30
    6. 6
      (a) Barone, V.; Cossi, M. Quantum calculation of molecular energies and energy gradients in solution by a conductor solvent model J. Phys. Chem. A 1998, 102, 1995 2001 DOI: 10.1021/jp9716997
      (b) Cossi, M.; Rega, N.; Scalmani, G.; Barone, V. Energies, structures, and electronic properties of molecules in solution with the C-PCM solvation model J. Comput. Chem. 2003, 24, 669 681 DOI: 10.1002/jcc.10189
    7. 7
      Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. Universal solvation model based on solute electron density and a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions J. Phys. Chem. B 2009, 113, 6378 6396 DOI: 10.1021/jp810292n
    8. 8

      For a recent critical discussion, see:

      Plata, R. E.; Singleton, D. A. A Case Study of the Mechanism of Alcohol-Mediated Morita Baylis-Hillman Reactions. The Importance of Experimental Observations J. Am. Chem. Soc. 2015, 137, 3811 3826 DOI: 10.1021/ja5111392
    9. 9
      Liao, R.-Z.; Santoro, S.; Gotsev, M.; Marcelli, T.; Himo, F. Origins of Stereoselectivity in Peptide-Catalyzed Kinetic Resolution of Alcohols ACS Catal. 2016, 6, 1165 1171 DOI: 10.1021/acscatal.5b02131
    10. 10
      Shuai, Q.; Deng, G.; Chua, Z.; Bohle, D. S.; Li, C.-J. Copper-Catalyzed Highly Regioselective Oxidative C-H Bond Amidation of 2-Arylpyridine Derivatives and 1-Methylindoles Adv. Synth. Catal. 2010, 352, 632 636 DOI: 10.1002/adsc.200900775
    11. 11
      Santoro, S.; Liao, R.-Z.; Himo, F. Theoretical Study of Mechanism and Selectivity of Copper-Catalyzed C-H Bond Amidation of Indoles J. Org. Chem. 2011, 76, 9246 9252 DOI: 10.1021/jo201447e
    12. 12
      Lapointe, D.; Fagnou, K. Overview of the Mechanistic Work on the Concerted Metallation-Deprotonation Pathway Chem. Lett. 2010, 39, 1118 1126 DOI: 10.1246/cl.2010.1118
    13. 13
      Chen, B.; Hou, X.-L.; Li, Y.-X.; Wu, Y.-D. Mechanistic Understanding of the Unexpected Meta Selectivity in Copper-Catalyzed Anilide C–H Bond Arylation J. Am. Chem. Soc. 2011, 133, 7668 7671 DOI: 10.1021/ja201425e
    14. 14
      Ohmura, T.; Torigoe, T.; Suginome, M. Catalytic Functionalization of Methyl Group on Silicon: Iridium-Catalyzed C(sp3)–H Borylation of Methylchlorosilanes J. Am. Chem. Soc. 2012, 134, 17416 17419 DOI: 10.1021/ja307956w
    15. 15

      It was subsequently found that a much higher reaction temperature had to be applied in order to observe the borylation product for the substrate without the chlorine substituent:

      Ohmura, T.; Torigoe, T.; Suginome, M. Functionalization of Tetraorganosilanes and Permethyloligosilanes at a Methyl Group on Silicon via Iridium-Catalyzed C(sp3)–H Borylation Organometallics 2013, 32, 6170 6173 DOI: 10.1021/om400900z
    16. 16
      Tamura, H.; Yamazaki, H.; Sato, H.; Sakaki, S. Iridium-Catalyzed Borylation of Benzene with Diboron. Theoretical Elucidation of Catalytic Cycle Including Unusual Iridium(V) Intermediate J. Am. Chem. Soc. 2003, 125, 16114 16126 DOI: 10.1021/ja0302937
    17. 17
      Huang, G.; Kalek, M.; Liao, R.-Z.; Himo, F. Mechanism, Reactivity, and Selectivity of the Iridium-Catalyzed C(sp3)–H Borylation of Chlorosilanes Chem. Sci. 2015, 6, 1735 1746 DOI: 10.1039/C4SC01592D
    18. 18
      Larsen, M. A.; Wilson, C. V.; Hartwig, J. F. Iridium-Catalyzed Borylation of Primary Benzylic C–H Bonds without a Directing Group: Scope, Mechanism, and Origins of Selectivity J. Am. Chem. Soc. 2015, 137, 8633 8643 DOI: 10.1021/jacs.5b04899
    19. 19
      (a) Trost, B. M.; Oi, S. Atom Economy: Aldol-Type Products by Vanadium-Catalyzed Additions of Propargyl Alcohols and Aldehydes J. Am. Chem. Soc. 2001, 123, 1230 1231 DOI: 10.1021/ja003629a
      (b) Trost, B. M.; Chung, C. K. Vanadium-Catalyzed Addition of Propargyl Alcohols and Imines J. Am. Chem. Soc. 2006, 128, 10358 10359 DOI: 10.1021/ja064011p
    20. 20
      Kalek, M.; Himo, F. Combining Meyer–Schuster Rearrangement with Aldol and Mannich Reactions: Theoretical Study of the Intermediate Interception Strategy J. Am. Chem. Soc. 2012, 134, 19159 19169 DOI: 10.1021/ja307892c
    21. 21
      Yu, S.; Ma, S. How easy are the syntheses of allenes? Chem. Commun. 2011, 47, 5384 5418 DOI: 10.1039/c0cc05640e
    22. 22
      Tsuji, J.; Mandai, T. Palladium-Catalyzed Reactions of Propargylic Compounds in Organic Synthesis Angew. Chem., Int. Ed. Engl. 1996, 34, 2589 2612 DOI: 10.1002/anie.199525891
    23. 23
      (a) Kalek, M.; Stawinski, J. Novel, Stereoselective and Stereospecific Synthesis of Allenylphosphonates and Related Compounds via Palladium-Catalyzed Propargylic Substitution Adv. Synth. Catal. 2011, 353, 1741 1755 DOI: 10.1002/adsc.201100119
      (b) Kalek, M.; Johansson, T.; Jezowska, M.; Stawinski, J. Palladium-Catalyzed Propargylic Substitution with Phosphorus Nucleophiles: Efficient, Stereoselective Synthesis of Allenylphosphonates and Related Compounds Org. Lett. 2010, 12, 4702 4704 DOI: 10.1021/ol102121j
    24. 24
      Jiménez-Halla, J. O. C.; Kalek, M.; Stawinski, J.; Himo, F. Computational Study of the Mechanism and Selectivity of Palladium-Catalyzed Propargylic Substitution with Phosphorus Nucleophiles Chem. - Eur. J. 2012, 18, 12424 12436 DOI: 10.1002/chem.201201026
    25. 25
      Toyoshima, T.; Miura, T.; Murakami, M. Selective 1:2 Coupling of Aldehydes and Allenes with Control of Regiochemistry Angew. Chem., Int. Ed. 2011, 50, 10436 10439 DOI: 10.1002/anie.201105077
    26. 26
      Huang, G.; Kalek, M.; Himo, F. Mechanism and Selectivity of Rhodium-Catalyzed 1:2 Coupling of Aldehydes and Allenes J. Am. Chem. Soc. 2013, 135, 7647 7659 DOI: 10.1021/ja4014166
    27. 27
      Stecko, S.; Furman, B.; Chmielewski, M. Kinugasa reaction: an ‘ugly duckling’ of β-lactam chemistry Tetrahedron 2014, 70, 7817 7844 DOI: 10.1016/j.tet.2014.06.024
    28. 28
      Kinugasa, M.; Hashimoto, S. The reactions of copper(I) phenylacetylide with nitrones J. Chem. Soc., Chem. Commun. 1972, 466 467 DOI: 10.1039/c39720000466
    29. 29
      (a) Okuro, K.; Enna, M.; Miura, M.; Nomura, M. Copper-catalysed reaction of arylacetylenes with C,N-diarylnitrones J. Chem. Soc., Chem. Commun. 1993, 1107 1108 DOI: 10.1039/c39930001107
      (b) Miura, M.; Enna, M.; Okuro, K.; Nomura, M. Copper-catalyzed reaction of terminal alkynes with nitrones. Selective synthesis of 1-aza-1-buten-3-yne and 2-azetidinone derivatives J. Org. Chem. 1995, 60, 4999 5004 DOI: 10.1021/jo00121a018
    30. 30

      For the first highly enantioselective Kinugasa reaction, see:

      Lo, M. M.-C.; Fu, G. C. Cu(I)/bis(azaferrocene)-catalyzed enantioselective synthesis of β-lactams via couplings of alkynes with nitrones J. Am. Chem. Soc. 2002, 124, 4572 4573 DOI: 10.1021/ja025833z
    31. 31
      (a) Ding, L. K.; Irwin, W. J. Cis- and trans-azetidin-2-ones from nitrones and copper acetylide J. Chem. Soc., Perkin Trans. 1 1976, 2382 2386 DOI: 10.1039/p19760002382
      (b) Shintani, R.; Fu, G. C. Catalytic enantioselective synthesis of β-lactams: intramolecular Kinugasa reactions and interception of an intermediate in the reaction cascade Angew. Chem., Int. Ed. 2003, 42, 4082 4085 DOI: 10.1002/anie.200352103
    32. 32
      Santoro, S.; Liao, R.-Z.; Marcelli, T.; Hammar, P.; Himo, F. Theoretical study of mechanism and stereoselectivity of catalytic Kinugasa reaction J. Org. Chem. 2015, 80, 2649 2660 DOI: 10.1021/jo502838p

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect