ACS Publications. Most Trusted. Most Cited. Most Read
Highly Nucleophilic Pyridinamide Anions in Apolar Organic Solvents due to Asymmetric Ion Pair Association
More

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Am. Chem. Soc. 2025, 147, 6, 5043-5050
  • Open Access
Article

Highly Nucleophilic Pyridinamide Anions in Apolar Organic Solvents due to Asymmetric Ion Pair Association
Click to copy article linkArticle link copied!

  • Veronika Burger
    Veronika Burger
    Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany
    More by Veronika Burger
  • Maximilian Franta
    Maximilian Franta
    Institute for Organic Chemistry, University Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany
    More by Maximilian Franta
  • Armin R. Ofial*
    Armin R. Ofial
    Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany
    *Email: [email protected]
    More by Armin R. Ofial
  • Ruth M. Gschwind*
    Ruth M. Gschwind
    Institute for Organic Chemistry, University Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany
    *Email: [email protected]
    More by Ruth M. Gschwind
  • Hendrik Zipse*
    Hendrik Zipse
    Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany
    *Email: [email protected]
    More by Hendrik Zipse
    Orcidhttps://orcid.org/0000-0002-0534-3585
Open PDFSupporting Information (1)

Journal of the American Chemical Society

Cite this: J. Am. Chem. Soc. 2025, 147, 6, 5043–5050
Click to copy citationCitation copied!
https://doi.org/10.1021/jacs.4c14825
Published January 24, 2025

Copyright © 2025 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

Free ions in organic solvents of low polarity would be valuable tools for the activation of low-reactivity substrates. However, the formation of unreactive ion pairs at concentrations relevant for synthesis has prevented the success of this concept so far. On the example of highly nucleophilic pyridinamide phosphonium salts in dichloromethane, we show that asymmetric aggregation offers a solution to this general problem. A combination of conductivity, diffusion-ordered NMR (DOSY), and kinetic measurements utilizing a refined ionic strength-controlled benzhydrylium ion methodology enables unique insight into the aggregation/association state of the ions and the nucleophilicity of the involved anions. This approach reveals that pyridinamide tetraphenylphosphonium salts aggregate in dichloromethane solution asymmetrically to form sandwich-type cations and anions together with their free counterions. The nucleophilicity of free pyridinamide ions exceeds that of the neutral reference nucleophile 9-azajulolidine (TCAP) by up to 2 orders of magnitude. Based on these results, we suggest that asymmetric aggregation in organic solvents of low polarity might be a general pathway to boost the reactivity of anionic nucleophiles.

This publication is licensed under

CC-BY 4.0 .
  • cc licence
  • by licence
Copyright © 2025 The Authors. Published by American Chemical Society

Subjects

what are subjects

Introduction

Click to copy section linkSection link copied!
Lewis basic pyridines, such as 4-(dimethylamino)pyridine (DMAP, 1) (1) or the more reactive 9-azajulolidine (TCAP, 2), (2) are frequently used catalysts for group transfer reactions such as acylations, (3−6) esterifications, (4,6) alkylations, (7) and silylations (Chart 1). (8,9) The nucleophilicity of these catalysts, together with other donor-substituted pyridines, has been quantified using Mayr’s benzhydrylium ion method. (10−13) Even higher nucleophilicities and possibly also higher catalytic activities in Lewis base-mediated reactions may be expected for anionic Lewis bases. Given that anionic reagents unavoidably require a countercation, such salts tend to form ion pairs when dissolved in organic solvents of low polarity, such as dichloromethane (DCM). (14,15) This ion clustering has beneficially been used in ion pair catalysis, (16−18) which extends from classical cationic phase-transfer (PT) catalysis (19) to applications in asymmetric synthesis. (16,20−22) Recently, the Zipse group introduced Lewis basic pyridinamide ion pair catalysts, which outperformed TCAP and other neutral organocatalysts in selected catalytic benchmark reactions. (23,24)

Chart 1

Chart 1. Structures of Neutral Organocatalysts DMAP (1) and TCAP (2) and of Pyridinamide Ion Pair Catalysts 3a and 4a
High Resolution Image
Download MS PowerPoint Slide
The pyridinamide phosphonium salts (such as 3a and 4a in Chart 1) investigated so far show the general usefulness of the concept of anionic nucleophilic organocatalysis, whose development tails that of neutral systems. (25−27)
In order to minimize ion pairing effects, most kinetic studies aiming at the quantification of the reactivity of anionic nucleophiles have been performed in highly polar solvents (water, DMSO, etc.), often in combination with crown ether additives to further reduce the interactions between metal counterions and the reacting anion. (28) In solvents of low polarity, the intrinsic nucleophilicity of a free anion should be far higher than that in more polar media. However, the reactivity of anions is attenuated by ion pair formation, which also gives rise to nonlinear effects and, thus, complicates systematic kinetic studies in organic solvents of low polarity [dichloromethane (DCM), tetrahydrofuran (THF), toluene, etc.] commonly employed in organocatalysis.
In order to elucidate the underlying principles responsible for the experimentally observed high nucleophilicity of the anions in salts such as 3a and 4a, we report here a combination of conductivity measurements, diffusion-ordered NMR (DOSY) measurements at very low concentrations, and photometric kinetic measurements by utilizing an ionic strength-controlled benzhydrylium methodology. This combination of physicochemical methods is expected to be generally applicable to ion pair chemistry and catalysis and may help to uncover the full potential of this field.

Results and Discussion

Click to copy section linkSection link copied!

Conductivity

Conductivity measurements have frequently been employed to quantify ion pairing effects. (29−32) This method was therefore applied to determine the association of the cationic and anionic components of phosphonium salt 3a selected here as a reference system in DCM and acetonitrile (MeCN). In both solvents, 3a is expected to be more reactive toward electrophiles than DMAP (1). Conductivity measurements were performed for concentrations ranging from 0.02 to 1.0 mM, as this appears to represent the onset of ion pair formation from free ions. At low electrolyte concentrations and for the case of noninteracting ions, the experimentally determined conductivity κ depends on the specific molar conductivity Λm and the ion concentration [A], as expressed in eq 1.
κ=Λm[A]
(1)
In the polar aprotic solvent MeCN, the ions of 3a are well stabilized and exist mainly as free ions, as indicated by a nearly perfect linear increase of conductivity with [3a] (see the SI, Figure S1). In the less polar solvent DCM, the situation is more complex, and two different domains can be seen in Figure 1B: (a) At low 3a concentrations (region I, blue background, [3a] < 0.04 mM), the conductivity κ correlates linearly with [3a], and (b) a nonlinear part II at higher concentrations of 3a (see Figure 1B beige background). While linear region I is assumed to represent the behavior of free anions (3) and cations (a), three ion association models were tested for nonlinear region II. The first corresponds to the formation of ion pair 3a (purple box in Figure 1A), while the second model involves the formation of “sandwich cation” a3a together with free anion 3 (gray box in Figure 1A), and the third model considers the formation of an analogous sandwich anion 3a3 (blue box in Figure 1A). The latter model was originally proposed to account for the properties of tetraalkyl ammonium salts in apolar solution (33) and subsequently employed for a variety of systems in organic solvents. (34−37) In order to compare both models on equal footing, the respective equilibrium constants KIP and KCAC are defined relative to two equivalents, each of free cation a and free anion 3.

Figure 1

Figure 1. (A) 1:1 ion pair 3a, sandwich cation a3a, and sandwich anion 3a3 as potential association models for anion 3 and cation a together with single-molecule dataset (SMD)-derived molecular volumes; (B) conductivity profile for 3a in DCM fits to the calculated conductivity data for the 1:1 association model (purple dotted/dashed line), and the two sandwich association models (gray and blue line); (C) DOSY-derived ion volumes (in Å3) compared to SMD-derived volumes (dashed horizontal lines) for single anion 3, single cation a, ion pair 3a, cation sandwich a3a, and anion sandwich 3a3.

High Resolution Image
Download MS PowerPoint Slide
The 1:1 ion pair model retains the specific molar conductivity Λm derived from the linear region I and adds the effects of reducing the number of conducting species through the formation of overall neutral (and thus inactive) ion pairs 3a. Fitting this model to the observed conductivities up to an overall concentration of 1.0 mM yields ion pair formation constant KIP = 6.86 × 105 M–2 with good accuracy. The second model involves the formation of sandwich cation a3a together with one equivalent of free anion 3 (gray box in Figure 1A), again combined with the specific molar conductivity Λm value obtained from the linear region I. This model fits the observed conductivity values in the region up to 1.0 mM with a sandwich association constant KCAC = 6.38 × 106 M–2 with equally good accuracy. This is also true for the third model involving the formation of sandwich anion 3a3 (blue box in Figure 1A), for which the optimized association constant is KACA = 6.38 × 106 M–2, numerically identical with KCAC. The measured conductivity values, together with the model predictions, are depicted in Figure 1B (gray line for the a3a sandwich model, blue line for the 3a3 sandwich model, and purple dotted line for the 1:1 ion pair), which illustrates that all models fit the experimental conductivity curve equally well, as indicated by largely similar RMSE values of RMSE(KCAC) = 0.17, RMSE(KACA) = 0.17, and RMSE(KIP) = 0.30, respectively.

DOSY-NMR

Since conductivity measurements alone cannot provide direct information on the size of the contributing ions, DOSY-NMR measurements of 3a were performed in DCM-d2 for concentrations ranging from 0.005 to 1.0 mM (see Figure 1C and SI, Chapter 4 for detailed information). To enable DOSY measurements at these low concentrations, a 600 MHz spectrometer with a helium cryo probe and measurement times up to 16 h per sample were employed. The DOSY results were compared to calculated volumes of anion 3 (215 Å3), cation a (362 Å3), and contact ion pair 3a (570 Å3), which are based on the van der Waals cavities employed in the SMD continuum solvation model at the SMD(DCM)/B3LYP-D3/6-31+G(d) level of theory and indicated through the horizontal dashed lines in Figure 1C. At [3a] = 0.005 mM as the lowest concentration accessible for DOSY measurements, we determined volumes of 367 Å3 for cation a and 192 Å3 for anion 3, both of which agree closely with the SMD-derived volumes for cation a and anion 3. At any concentration of 3a > 0.005 mM, considerably larger cation and anion volumes were observed already in region I (for full data, see the SI, Chapter 4). In the 1:1 association model shown in the purple box in Figure 1A, the volumes of both species are expected to converge to the SMD-derived value of 570 Å3 for 1:1 ion pair 3a. Instead, we persistently detected substantially different effective volumes for cation a and anion 3 also at higher concentrations (region II), and we also note that the DOSY-derived volume for the cationic species exceeds that calculated for the 1:1 ion pair 3a.
This latter observation can be rationalized with the sandwich ion models, where the DOSY-derived cation volume is expected to approach that of the a3a sandwich cation of 925 Å3. Combining the SMD-derived molecular volumes of ions with the equilibrium constants obtained from conductivity measurements allows us to predict concentration-dependent effective cation and anion volumes. These are shown in Figure 1C as a green line for the anion and an orange line for the cation volumes. Comparing experimentally derived with theoretically predicted volumes shows these to coincide quite well between 0.4 and 1.0 mM for the cation sandwich model. (38) In contrast, the 1:1 model predicts volumes for both ions, which are significantly lower than the experimental values (by more than 200 Å3 for the cation and >100 Å3 for the anion; see the SI). This is also true for the 3a3 anion sandwich model that predicts larger anion than cation volumes, not consistent with the DOSY experiments. The agreement between experimentally determined DOSY volumes and model predictions can be further improved by combining the two sandwich models considered here. This requires optimization of the two scaling factors α and β shown in Figure 1A, such that the agreement with the conductivity data and the DOSY volumes is optimized. The best agreement for ion pair 3a is found for α = 0.44 and β = 0.21, which implies that 50% of the anion 3 is free while the other 50% is stored in the two sandwich complexes at I = 1.0 mM. In contrast, the DOSY experiments for 4a show inverted relative ion volumes with larger values for the anionic species (see the SI, Chapter 4). This is reflected by the mixing coefficients for salt 4a amounting to α = 0.12 and β = 0.61. This implies that 34% of anion 4 is free, and 66% is hidden in the two sandwich complexes. The performance of these “mixed sandwich” models is quite satisfactory in concentration region II but less so in region I with its rapid increase of ion volumes with salt concentration. It is an intriguing aspect of the formation of sandwich cation a3a that it generates one equivalent of free anion 3 as the counterion. The concentration of free anion 3 will quite obviously impact the efficiency of pyridinamide anion-based catalytic systems, where free anion 3 is expected to account for most of the observed activity.

Kinetics

To characterize the nucleophilic reactivity of 3a and 4a in an organic solvent of low polarity, such as DCM, we refined Mayr’s well-known benzhydrylium ion method by implementing an ionic strength control. This enabled the characterization of free anionic nucleophiles for the first time in DCM. Mayr’s methodology has repeatedly demonstrated its utility to describe the reactivity of a wide range of carbon-, nitrogen, oxygen-, sulfur-, and phosphor-based nucleophiles in different solvents, (39) including DMAP (1) and TCAP (2). (10,11,39) In short, the benzhydrylium ion method involves the photometric monitoring of the reactions of colored benzhydrylium salts, such as 5a–c (Table 1), whose electrophilic reactivities are characterized by the solvent-independent parameters E, with nucleophiles used in excess concentration to achieve kinetics under pseudo-first-order conditions. The first-order rate constants kobs (s–1) can then be obtained by fitting a monoexponential decay function to the decreasing absorption of 5 during the reaction with 3. The conductivity measurements (see the SI, Figure S1) showed that 3a and 4a fully dissociate into anions and cations when dissolved in MeCN. Accordingly, a linear increase of pseudo-first-order rate constants kobs with nucleophile concentrations [3] (or [3a]) was observed in the kinetics of reactions of 3a with 5 (eq 2).
kobs=k2[3]
(2)
log⁡k2=sN(N+E)
(3)
Table 1. Second-Order Rate Constants k2 for the Reactions of DMAP (1), TCAP (2), and Pyridinamide Salts 3a and 4a with Reference Electrophiles 5a, 5b, and 5c in MeCN (at 20 °C) Analyzed by Equation 3 to Give the Nucleophile-Specific Reactivity Parameters N (and sN)
 k2 [M–1 s–1] 
cat5a5b5cN (sN)
1a2.11 × 1035.30 × 1031.29 × 10415.51 (0.62)e
2b6.30 × 103 4.17 × 10415.60 (0.68)e
3c7.16 × 1031.53 × 1044.13 × 10416.38 (0.60)
4d5.11 × 1041.36 × 1053.47 × 10517.28 (0.65)
a

Second-order rate constants k2 from ref (10).

b

Second-order rate constants k2 from ref (11).

c

Assuming that [3] = [3a]0.

d

Assuming that [4] = [4a]0.

e

Additional k2 values from refs (10,11) were used to determine N (and sN).

Equation 2 thus yields second-order rate constants k2 (M–1 s–1) for the reactions of 3 with 5a–c in acetonitrile (Table 1). The rate constants k2 for 3 are approximately three times larger than those for analogous reactions of 5 with DMAP (1) and quite similar to those for reactions with TCAP (2). Analyzing the kinetic data with the Mayr–Patz eq 3 yields the nucleophilicity N = 16.38 (sN = 0.60) of 3 in MeCN. Following the same approach for 4a yields N(4a) = 17.28 (sN = 0.65), in excellent agreement with the results obtained for these two systems in selected catalytic transformations. (23)
The kinetics of reactions of 3a with reference electrophiles 5 in DCM solution, however, showed a more complex dependence of kobs on [3a] in the concentration range from 0.01 to 1.0 mM (red and blue diamonds in Figure 2). In analogy to the conductivity measurements, an initial region I with linear kobs vs [3a]0 relation was observed (Figure 2, blue background, experimental values marked in red). At higher [3a] values, this is followed by nonlinear region II (blue diamonds on a beige background in Figure 2), where the observed rate constants deviate negatively from the linear correlation extrapolated from region I. The degree of deviation reflects the fraction of anion 3 captured in the (presumably) unreactive sandwich cation a3a and the (presumably) less reactive sandwich anion 3a3.

Figure 2

Figure 2. (A) Benzhydrylium ion reaction applied for the quantification of the nucleophilicity of 3. (B) Correlation of kobs for the reaction of 5a with 3a for salt concentrations [3a] from 0.01 to 1.0 mM in DCM at 20 °C (blue diamonds) and in the presence of additive PPh4BF4 (6) (turquoise dots).

High Resolution Image
Download MS PowerPoint Slide
Analysis of the kinetic data in region I (0.01–0.03 mM) is straightforward, as conductivity measurements in combination with the sandwich association models indicate almost complete (>97%) dissociation into separate ions 3 and a, that is, [3] = [3a]0. Application of eq 2 then yields k2(5a) = 1.84 × 106 M–1 s–1, as indicated by the dashed line in Figure 2.
In synthetic applications, the concentration of ion pair catalysts is usually 1.0 mM or higher, which is far into the nonlinear region II. Increasing ion concentrations may impact the reaction rates not only through shifting the association equilibrium toward a higher fraction of ionic aggregates but also through nonspecific polarity effects. To assess the influence of the high salt concentration on the solvent polarity, we determined Reichardt’s ET(30) values in DCM solutions with increasing concentrations of pyridinamide salt 3a and additive Ph4P+BF4– (6). As shown in Figure 2, this additive combines the common unreactive ions in the reaction mixture, that is, the BF4– of the benzhydrylium salts and the unreactive Ph4P+ countercation of the pyridinamide salts. We observed insignificant changes of the ET(30) values even at total salt concentrations of up to 6.0 mM (see the SI).
We conclude, therefore, that addition of 6 to a reaction mixture of 3a and 5a–c does not change the overall polarity of the solvent system and affects only the position of the ion pairing equilibrium shown in Figure 2, where higher concentrations of Ph4P+ (=a) give rise to an increase of [a3a]. To further investigate the effect of the Ph4P+BF4– (6) additive, the ion volumes of selected 3a + 6 mixtures were determined by DOSY measurements. The DOSY experiments show that the volumes of the cation and anion determined for 3a + 6 mixtures at an ionic strength of I = 1.0 mM are in the same region as the volumes obtained for a pure 3a solution at [3a] = 1.0 mM (for details, see the SI). (40) The kinetics of the reaction of 3a + 5a was subsequently studied at a constant ionic strength (I) of I = 1.0 mM, as this represents the highest concentration of 3a in this study. At [3a] < 1.0 mM, the ionic strength of the DCM solution was adjusted by addition of 6 such that in each kinetic measurement, the condition [3a] + [6] + [5a] = 1.0 mM is fulfilled. By maintaining I = 1.0 mM, the rate constants kobs for 3a + 5a reactions in DCM correlated linearly with [3a] in the entire concentration range from 0.01 to 1.0 mM (turquoise points in Figure 2). When we account for the fact that variable fractions of anion 3 are caught in unreactive sandwich cation a3a (and to a smaller extent also in anion sandwich 3a3) and also consider the effect of additive 6 on [Ph4P+], we obtain k2(5a) = 5.42 × 105 M–1 s–1 for the reaction of 3 with 5a, which is by a factor of 3.5 lower than k2 obtained in the low-concentration (LC) region (Table 2). Analogous kinetic measurements at I = 1.0 mM were performed for reactions of 3a with more reactive benzhydryl salts 5b and 5c (Table 2).
Table 2. Second-Order Rate Constants k2 of the Reactions of DMAP (1), TCAP (2), and Pyridinamide Salt 3a with Reference Electrophiles 5a, 5b, and 5c in DCM (at 20 °C)
 k2 [M–1 s–1]
cat5a5b5c
1a6.45 × 1039.84 × 1034.96 × 104
2b1.42 × 1043.11 × 1041.28 × 105
3c1.84 × 106 (LC)4.23 × 106 (LC)1.98 × 107 (LC)
3d5.42 × 105 (mix)1.25 × 106 (mix)4.64 × 106 (mix)
4e1.69 × 106 (mix)4.19 × 106 (mix)1.15 × 107 (mix)
a

Second-order rate constants k2 from ref (10a).

b

This work, see the Supporting Information for details of the kinetic experiments.

c

Determined at [3] < 0.03 mM, that is, in the low-concentration (LC) region I (Figure 2), by assuming [3] = [3a]0.

d

Determined over a concentration range [3a] = 0.1 to 0.3 mM at constant ionic strength I = 1.0 mM (kept by addition of salt 6) by assuming a mixed sandwich association model (see the SI for details).

e

Determined over a concentration range [4a] = 0.04 to 0.1 mM at constant ionic strength I = 1.0 mM (kept by addition of salt 6) by assuming a mixed sandwich association model.

In DCM as the solvent, we note a moderate increase in the bimolecular rate constants k2 when going from DMAP (1) to TCAP (2) but a significantly larger increase of the k2 values for 3a (Table 2). The k2 values for the reaction of 3a with 5a–c in DCM in the low-concentration (LC) region I (as defined in Figure 2) exceed those for 2 by approximately 2 orders of magnitude. Analyzing the LC kinetic data by the Mayr–Patz equation in eq 3 gives N = 17.78 (sN = 0.81) for 3a. Rate constants k2 for reactions of 3 with all three benzhydryl cations 5a–c decrease slightly (by a factor of 3.5–4.5) under conditions of constant ion strength (I = 1.0 mM). The resulting N-parameter for 3 is, however, hardly changed at N = 17.88 (sN = 0.73). Following the same mode of analysis for 4a under reaction conditions where I = 1.0 mM, we find that anion 4 exceeds the nucleophilicity of 3 by a factor of 3.0 ± 0.5 in its reaction with benzhydryl cations 5a–c, which is also reflected in the respective nucleophilicity parameter of N(4) = 19.63 (sN = 0.65).
These measurements thus establish 3a and 4a as potent and highly nucleophilic pyridine derivatives in solvents of low polarity (Figure 3). That 4a is more nucleophilic than 3a is in full agreement with the results for selected organocatalytic transformations performed in CDCl3 as the solvent. (23) The combined methodology developed here thus allows for a quantitative assessment of catalyst nucleophilicity at synthetically relevant concentrations.

Figure 3

Figure 3. Mayr nucleophilicities N (and sN) of DMAP (1), TCAP (2), and pyridinamide anions 3 and 4 (Ani = p-methoxyphenyl) in MeCN and DCM.

High Resolution Image
Download MS PowerPoint Slide

Conclusions

Click to copy section linkSection link copied!
Pyridinamide salts 3a and 4a exceed the nucleophilic reactivity of the highly reactive neutral Lewis base TCAP (2) by up to 2 orders of magnitude in DCM. Employing a combination of conductivity and DOSY measurements, we have deciphered an asymmetric association behavior of both pyridinamide ion pairs in the low polarity solvent DCM, which includes both cationic and anionic sandwich complexes but not the commonly assumed and unreactive 1:1 ion pair. Without the combination of conductivity and DOSY measurements, this result could not have been achieved since conductivity alone does not give insight into the type of charged species that are being measured. The reactivity of the supernucleophilic anions 3 and 4 was quantified with the newly developed ionic strength-controlled benzhydrylium ion method, which facilitates the comparison of 3a and 4a with neutral nucleophilic catalysts, such as DMAP or TCAP. In DCM, we were able to evaluate kinetic data not only at low salt concentrations but also at synthetically relevant higher concentrations by keeping the ionic strength constant throughout the measurement to prevent the interference of ion association. The direct comparison of k2 values for reactions with cationic reference electrophiles reveals reactivity values of pyridinamide anions 3 and 4 (at high concentration) that are 39 and 90 times higher than that of TCAP (2). The superior reactivity of pyridinamide anions 3 and 4 has recently been observed in catalytic reactions with isocyanates and Michael acceptors as electrophiles. (23,24) This indicates that the higher nucleophilicity of 3 and 4 in comparison to neutral nucleophilic catalysts might be comparably effective for reactions with neutral electrophiles in low polarity media (alkanes, THF, and Et2O). The asymmetric ion association described here opens the general avenue for employing highly reactive free anions to activate so far inaccessible substrates in catalytic transformations.

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.4c14825.

  • Additional experimental and computational details, analysis procedures, and methods, including step by step descriptions (PDF)

Accession Codes

CCDC accession codes 2310788–2310789 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing [email protected], or by contacting the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.

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!
  • Corresponding Authors
    • Armin R. Ofial - Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany;  Email: [email protected]
    • Ruth M. Gschwind - Institute for Organic Chemistry, University Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany;  Email: [email protected]
    • Hendrik Zipse - Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany;  Orcidhttps://orcid.org/0000-0002-0534-3585;  Email: [email protected]
  • Authors
    • Veronika Burger - Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany
    • Maximilian Franta - Institute for Organic Chemistry, University Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany
  • Author Contributions

    The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

  • Notes
    The authors declare no competing financial interest.

Acknowledgments

Click to copy section linkSection link copied!

This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-426795949 through the Research Training Group (RTG) 2620 “Ion Pair Effects in Molecular Reactivity.” The authors are thankful to Dr. Robert J. Mayer (LMU) for help with the conductivity measurements, Nathalie Hampel (LMU) for the synthesis of 5a–c, Dr. Fabian Zott (LMU) for help with kinetics simulations, and Christian Scholtes (RU) for providing a Python script for the DOSY evaluation.

References

Click to copy section linkSection link copied!

This article references 40 other publications.

  1. 1
    (a) Litvinenko, L. M.; Kirichenko, A. I. Basicity and Stereospecificity in Nucleophile Catalysis by Tertiary Amines. Dokl. Akad. Nauk. SSSR 1967, 176, 97– 100
    Google Scholar
    There is no corresponding record for this reference.
    (b) Steglich, W.; Höfle, G. N,N-Dimethyl-4-pyridinamine, a Very Effective Acylation Catalyst. Angew. Chem., Int. Ed. 1969, 8 (12), 981,  DOI: 10.1002/anie.196909811
    Google Scholar
    There is no corresponding record for this reference.
  2. 2
    Heinrich, M. R.; Klisa, H. S.; Mayr, H.; Steglich, W.; Zipse, H. Enhancing the Catalytic Activity of 4-(Dialkylamino)Pyridines by Conformational Fixation. Angew. Chem., Int. Ed. 2003, 42 (39), 4826– 4828,  DOI: 10.1002/anie.200352289
    Google Scholar
    There is no corresponding record for this reference.
  3. 3
    Steglich, W.; Höfle, G. Über eine einfache darstellung von acyl-oxazolinonen-(5) aus 5-acyloxy-oxazolen II. Mitteilung über hypernucleophile acylierungskatalysatoren. Tetrahedron Lett. 1970, 11 (54), 4727– 4730,  DOI: 10.1016/S0040-4039(00)89379-X
    Google Scholar
    There is no corresponding record for this reference.
  4. 4
    Hassner, A.; Alexanian, V. Direct room temperature esterification of carboxylic acids. Tetrahedron Lett. 1978, 19 (46), 4475– 4478,  DOI: 10.1016/S0040-4039(01)95256-6
    Google Scholar
    There is no corresponding record for this reference.
  5. 5
    Höfle, G.; Steglich, W.; Vorbrüggen, H. 4-Dialkylaminopyridines as Highly Active Acylation Catalysts. Angew. Chem., Int. Ed. 1978, 17, 569– 583,  DOI: 10.1002/anie.197805691
    Google Scholar
    There is no corresponding record for this reference.
  6. 6
    Neises, B.; Steglich, W. Simple Method for the Esterification of Carboxylic Acids. Angew. Chem., Int. Ed. 1978, 17 (7), 522– 524,  DOI: 10.1002/anie.197805221
    Google Scholar
    There is no corresponding record for this reference.
  7. 7
    Chaudhary, S. K.; Hernandez, O. A Simplified Procedure for the Preparation of Triphenylmethylethers. Tetrahedron Lett. 1979, 20 (2), 95– 98,  DOI: 10.1016/S0040-4039(01)85892-5
    Google Scholar
    There is no corresponding record for this reference.
  8. 8
    Patschinski, P.; Zhang, C.; Zipse, H. The Lewis Base-Catalyzed Silylation of Alcohols-a Mechanistic Analysis. J. Org. Chem. 2014, 79 (17), 8348– 8357,  DOI: 10.1021/jo5016568
    Google Scholar
    8
    The Lewis Base-Catalyzed Silylation of Alcohols-A Mechanistic Analysis
    Patschinski, Pascal; Zhang, Cong; Zipse, Hendrik
    Journal of Organic Chemistry (2014), 79 (17), 8348-8357CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
    Reaction rates for the base-catalyzed silylation of primary, secondary, and tertiary alcs. depend strongly on the choice of solvent and catalyst. The reactions are significantly faster in Lewis basic solvents such as DMF (DMF) compared with those in chloroform or dichloromethane (DCM). The effects of added Lewis base catalysts such as 4-N,N-dimethylaminopyridine (DMAP) or 4-pyrrolidinopyridine (PPY) are much larger in apolar solvents than in DMF. The presence of an auxiliary base such as triethylamine is required in order to drive the reaction to full conversion.
  9. 9
    Chaudhary, S. K.; Hernandez, O. 4-Dimethylaminopyridine: An Efficient and Selective Catalyst for the Silylation of Alcohols. Tetrahedron Lett. 1979, 20 (2), 99– 102,  DOI: 10.1016/S0040-4039(01)85893-7
    Google Scholar
    There is no corresponding record for this reference.
  10. 10

    For the nucleophilic reactivity of DMAP (1) in MeCN, see:

    (a) Brotzel, F.; Kempf, B.; Singer, T.; Zipse, H.; Mayr, H. Nucleophilicities and Carbon Basicities of Pyridines. Chem. - Eur. J. 2007, 13 (1), 336– 345,  DOI: 10.1002/chem.200600941
    Google Scholar
    There is no corresponding record for this reference.

    For supplementary kinetic data and revised N (and sN) parameters for DMAP (1), see:

    (b) Nigst, T. A.; Ammer, J.; Mayr, H. Photogeneration of Benzhydryl Cations by Near-UV Laser Flash Photolysis of Pyridinium Salts. J. Phys. Chem. A 2012, 116 (33), 8494– 8499,  DOI: 10.1021/jp3049247
    Google Scholar
    10b
    Photogeneration of Benzhydryl Cations by Near-UV Laser Flash Photolysis of Pyridinium Salts
    Nigst, Tobias A.; Ammer, Johannes; Mayr, Herbert
    Journal of Physical Chemistry A (2012), 116 (33), 8494-8499CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)
    Laser flash irradn. of substituted N-benzhydryl pyridinium salts yields benzhydryl cations (diarylcarbenium ions) and/or benzhydryl radicals (diarylmethyl radicals). The use of 3,4,5-triamino-substituted pyridines as photoleaving groups allowed the authors to employ the third harmonic of a Nd/YAG laser (355 nm) for the photogeneration of benzhydryl cations. In this way, benzhydryl cations can also be photogenerated in the presence of arom. compds. and in solvents which are opaque at the wavelength of the quadrupled Nd/YAG laser (266 nm). To demonstrate the scope and limitations of this method, the rate consts. for the bimol. reactions of benzhydryl cations with several substituted pyridines were detd. in acetonitrile and with water in acetone. The obtained data agree with results obtained by stopped-flow UV-vis spectroscopic measurements. The rate consts. for the reaction of the 4,4'-bis[methyl(2,2,2-trifluoroethyl)amino]benzhydrylium ion with 4-(dimethylamino)pyridine were also detd. in DMSO, N,N-dimethylformamide, and acetone. From the second-order rate consts., the authors derived the nucleophilicity parameters N and sN for the substituted pyridines, as defined by the linear free energy relationship, log k2 = sN(N + E).
  11. 11
    Tandon, R.; Unzner, T.; Nigst, T. A.; De Rycke, N.; Mayer, P.; Wendt, B.; David, O. R. P.; Zipse, H. Annelated Pyridines as Highly Nucleophilic and Lewis Basic Catalysts for Acylation Reactions. Chem. - Eur. J. 2013, 19 (20), 6435– 6442,  DOI: 10.1002/chem.201204452
    Google Scholar
    There is no corresponding record for this reference.
  12. 12
    Mayr, H. Reactivity scales for quantifying polar organic reactivity: the benzhydrylium methodology. Tetrahedron 2015, 71, 5095– 5111,  DOI: 10.1016/j.tet.2015.05.055
    Google Scholar
    12
    Reactivity scales for quantifying polar organic reactivity: the benzhydrylium methodology
    Mayr, Herbert
    Tetrahedron (2015), 71 (32), 5095-5111CODEN: TETRAB; ISSN:0040-4020. (Elsevier Ltd.)
    A review. The construction and uses of the nucleophilicity and electrophilicity scales, nucleofugality and electrofugality scales, and Lewis basicity and acidity scales are discussed.
  13. 13
    Lakhdar, S. Lewis Base Catalysis in Organic Synthesis, 1st ed.; Vedejs, E.; Denmark, S. E., Eds.; Wiley-VCH: Weinheim, 2016; Chapter 4, pp 85– 116.
    Google Scholar
    There is no corresponding record for this reference.
  14. 14
    Marcus, Y.; Hefter, G. Ion Pairing. Chem. Rev. 2006, 106 (11), 4585– 4621,  DOI: 10.1021/cr040087x
    Google Scholar
    14
    Ion pairing
    Marcus, Yizhak; Hefter, Glenn
    Chemical Reviews (Washington, DC, United States) (2006), 106 (11), 4585-4621CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
    A review illustrates the status of the ion-pairing concept with examples of well characterized ion pairs formed in electrolyte solns. in various solvents. It focuses on electrolyte composed of simple, monat., and mainly sym. polyat. ions. The main theories proposed for dealing with ion pairing are presented.
  15. 15
    Reichardt, C. Solvents and Solvent Effects in Organic Chemistry, 3rd ed.; VCH: Weinheim, 2003; Chapter 5.5.5.
    Google Scholar
    There is no corresponding record for this reference.
  16. 16
    Brak, K.; Jacobsen, E. N. Asymmetric Ion-Pairing Catalysis. Angew. Chem., Int. Ed. 2013, 52 (2), 534– 561,  DOI: 10.1002/anie.201205449
    Google Scholar
    16
    Asymmetric ion-pairing catalysis
    Brak, Katrien; Jacobsen, Eric N.
    Angewandte Chemie, International Edition (2013), 52 (2), 534-561CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. Charged intermediates and reagents are ubiquitous in org. transformations. The interaction of these ionic species with chiral neutral, anionic, or cationic small mols. emerged as a powerful strategy for catalytic, enantioselective synthesis. This review described developments in the burgeoning field of asym. ion-pairing catalysis with an emphasis on the insights that were gleaned into the structural and mechanistic features that contribute to high asym. induction.
  17. 17
    (a) Waser, M.; Novacek, J.; Gratzer, K. Cooperative Catalysis Involving Chiral Ion Pair Catalysts. In Cooperative Catalysis; Peters, R., Ed.; Wiley-VCH: Weinheim (Germany), 2015; Chapter 7, pp 197– 226.
    Google Scholar
    There is no corresponding record for this reference.
    (b) Otevrel, J.; Waser, M. Asymmetric Phase-Transfer Catalysis─From Classical Application to New Concepts. In Asymmetric Organocatalysis: New Strategies, Catalysts, and Opportunities, Albrecht, Ł.; Albrecht, A.; Dell’Amico, L., Eds.; Wiley-VCH, 2023; Chapter 3, pp 71– 120.
    Google Scholar
    There is no corresponding record for this reference.
  18. 18
    Ye, X.; Tan, C. H. Enantioselective Transition Metal Catalysis Directed by Chiral Cations. Chem. Sci. 2021, 12 (2), 533– 539,  DOI: 10.1039/D0SC05734G
    Google Scholar
    There is no corresponding record for this reference.
  19. 19
    Shirakawa, S.; Maruoka, K. Recent Developments in Asymmetric Phase-Transfer Reactions. Angew. Chem., Int. Ed. 2013, 52 (16), 4312– 4348,  DOI: 10.1002/anie.201206835
    Google Scholar
    19
    Recent Developments in Asymmetric Phase-Transfer Reactions
    Shirakawa, Seiji; Maruoka, Keiji
    Angewandte Chemie, International Edition (2013), 52 (16), 4312-4348CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. Phase-transfer catalysis has been recognized as a powerful method for establishing practical protocols for org. synthesis, because it offers several advantages, such as operational simplicity, mild reaction conditions, suitability for large-scale synthesis, and the environmentally benign nature of the reaction system. A wide variety of asym. transformations catalyzed by chiral onium salts and crown ethers have been developed for the synthesis of valuable org. compds. in the past several decades, esp. in recent years.
  20. 20
    Merten, C.; Pollok, C. H.; Liao, S.; List, B. Stereochemical Communication within a Chiral Ion Pair Catalyst. Angew. Chem., Int. Ed. 2015, 54 (30), 8841– 8845,  DOI: 10.1002/anie.201501271
    Google Scholar
    20
    Stereochemical Communication within a Chiral Ion Pair Catalyst
    Merten, Christian; Pollok, Corina H.; Liao, Saihu; List, Benjamin
    Angewandte Chemie, International Edition (2015), 54 (30), 8841-8845CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Ionic interactions are increasingly appreciated as a key, asymmetry-inducing factor in enantioselective catalytic transformations, including those involving Bronsted acid or base catalysis, phase-transfer catalysis, and related processes. However, a detailed understanding of these interactions is often lacking. Herein, we show how an enantiopure anion enforces a chiral conformation onto a catalytically relevant achiral cation. Specifically, we use vibrational CD (VCD) spectroscopy to monitor the transmission of stereochem. information from a chiral phosphate anion to a flexible manganese(III)-salen cation. We show that VCD can be used to study solvent effects and that the obtained chiroptical data directly and quant. correlate with the exptl. obsd. enantioselectivity in an asym. olefin epoxidn. reaction.
  21. 21
    Mahlau, M.; List, B. Asymmetric Counteranion-Directed Catalysis: Concept, Definition, and Applications. Angew. Chem., Int. Ed. 2013, 52 (2), 518– 533,  DOI: 10.1002/anie.201205343
    Google Scholar
    21
    Asymmetric Counteranion-Directed Catalysis: Concept, Definition, and Applications
    Mahlau, Manuel; List, Benjamin
    Angewandte Chemie, International Edition (2013), 52 (2), 518-533CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. Recently, the use of enantiomerically pure counter anions for the induction of asymmetry in reactions proceeding through cationic intermediates has emerged as an exciting new concept, which has been termed asym. counteranion-directed catalysis (ACDC). Despite its success, the concept has not been fully defined and systematically discussed to date. This Review closes this gap by providing a clear definition of ACDC and by examg. both clear cases as well as more ambiguous examples to illustrate the differences and overlaps with other catalysis concepts.
  22. 22
    Phipps, R. J.; Hamilton, G. L.; Toste, F. D. The Progression of Chiral Anions from Concepts to Applications in Asymmetric Catalysis. Nat. Chem. 2012, 4 (8), 603– 614,  DOI: 10.1038/nchem.1405
    Google Scholar
    22
    The progression of chiral anions from concepts to applications in asymmetric catalysis
    Phipps, Robert J.; Hamilton, Gregory L.; Toste, F. Dean
    Nature Chemistry (2012), 4 (8), 603-614CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
    A review. Despite the tremendous advances of the past four decades, chemists are far from being able to use chiral catalysts to control the stereoselectivity of any desired reaction. New concepts for the construction and mode of operation of chiral catalysts have the potential to open up previously inaccessible reaction space. The recognition and categorization of distinct approaches seems to play a role in triggering rapid exploration of new territory. This review both reflects on the origins as well as details a selection of the latest examples of an area that has advanced considerably within the past five years or so: the use of chiral anions in asym. catalysis. Defining reactions as involving chiral anions is a difficult task owing to uncertainties over the exact catalytic mechanisms. Nevertheless, the authors attempted to provide an overview of the breadth of reactions that could reasonably fall under this umbrella.
  23. 23
    Helberg, J.; Ampßler, T.; Zipse, H. Pyridinyl Amide Ion Pairs as Lewis Base Organocatalysts. J. Org. Chem. 2020, 85, 5390– 5402,  DOI: 10.1021/acs.joc.0c00114
    Google Scholar
    23
    Pyridinyl Amide Ion Pairs as Lewis Base Organocatalysts
    Helberg, Julian; Ampssler, Torsten; Zipse, Hendrik
    Journal of Organic Chemistry (2020), 85 (8), 5390-5402CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
    Pyridinyl amide ion pairs carrying various electron-withdrawing substituents were synthesized with selected ammonium or phosphonium counterions. Compared to neutral pyridine-based organocatalysts, these new ion pair Lewis bases display superior catalytic reactivity in the reaction of isocyanates with alcs. and the aza-Morita-Baylis-Hillman reaction of hindered electrophiles. The high catalytic activity of ion pair catalysts appears to be due to their high Lewis basicities toward neutral electrophiles as quantified through quantum chem. calcd. affinity data.
  24. 24
    Dempsey, S. H.; Lovstedt, A.; Kass, S. R. Electrostatically Enhanced 3- and 4-Pyridyl Borate Salt Nucleophiles and Bases. J. Org. Chem. 2023, 88 (15), 10525– 10538,  DOI: 10.1021/acs.joc.3c00523
    Google Scholar
    There is no corresponding record for this reference.
  25. 25
    Dale, H. J. A.; Hodges, G. R.; Lloyd-Jones, G. C. Kinetics and Mechanism of Azole N–π*-Catalyzed Amine Acylation. J. Am. Chem. Soc. 2023, 145 (32), 18126– 18140,  DOI: 10.1021/jacs.3c06258
    Google Scholar
    There is no corresponding record for this reference.
  26. 26
    Yang, X.; Birman, V. B. Acyl Transfer Catalysis with 1,2,4-Triazole Anion. Org. Lett. 2009, 11 (7), 1499– 1502,  DOI: 10.1021/ol900098q
    Google Scholar
    26
    Acyl Transfer Catalysis with 1,2,4-Triazole Anion
    Yang, Xing; Birman, Vladimir B.
    Organic Letters (2009), 11 (7), 1499-1502CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)
    1,2,4-Triazole anion has been identified as an active acyl transfer catalyst suitable for the aminolysis and transesterification of esters.
  27. 27
    Mai, B. K.; Koenigs, R. M.; Nguyen, T. V.; Lyons, D. J. M.; Empel, C.; Pace, D. P.; Dinh, A. H. Tropolonate Salts as Acyl-Transfer Catalysts under Thermal and Photochemical Conditions: Reaction Scope and Mechanistic Insights. ACS Catal. 2020, 10 (21), 12596– 12606,  DOI: 10.1021/acscatal.0c03702
    Google Scholar
    There is no corresponding record for this reference.
  28. 28
    Liotta, C. L.; Harris, H. P. The Chemistry of “Naked” Anions. I. Reactions of the 18-Crown-6 Complex of Potassium Fluoride with Organic Substrates in Aprotic Organic Solvents. J. Am. Chem. Soc. 1974, 96, 2250– 2252,  DOI: 10.1021/ja00814a044
    Google Scholar
    28
    Chemistry of naked anions. I. Reactions of the 18-crown-6 complex of potassium fluoride with organic substrates in aprotic organic solvents
    Liotta, Charles L.; Harris, Henry P.
    Journal of the American Chemical Society (1974), 96 (7), 2250-2CODEN: JACSAT; ISSN:0002-7863.
    1,4,7,10,13,16-Hexaoxacyclooctadecane (18-Crown-6) is an effective agent for the solubilization of KF in polar and non-polar, aprotic org. solvents. This solubilized fluoride, which we have termed naked fluoride, is both a potent nucleophile and base and provides a facile and efficient means of obtaining a wide variety of org. fluoride compds. in high yields.
  29. 29
    Coury, L. Conductance Measurements Part 1: Theory. Current 1999, 3 (2), 91– 96
    Google Scholar
    There is no corresponding record for this reference.
  30. 30
    Mizuhata, M. Electrical Conductivity Measurement of Electrolyte Solution. Electrochemistry 2022, 90 (10), 1– 12,  DOI: 10.5796/electrochemistry.22-66111
    Google Scholar
    There is no corresponding record for this reference.
  31. 31
    Martínez, L. Measuring the Conductivity of Very Dilute Electrolyte Solutions, Drop by Drop. Quim. Nova 2018, 41 (7), 814– 817,  DOI: 10.21577/0100-4042.20170216
    Google Scholar
    There is no corresponding record for this reference.
  32. 32
    Schneider, R.; Mayr, H.; Plesch, P. H. Ionisation and Dissociation of Diarylmethyl Chlorides in BCl3/CH2Cl2 Solution: Spectroscopic Evidence for Carbenium Ion Pairs. Ber. Bunsenges. Phys. Chem. 1987, 91, 1369– 1374,  DOI: 10.1002/bbpc.19870911212
    Google Scholar
    There is no corresponding record for this reference.
  33. 33

    The triple ion sandwich model has first been proposed in:

    Fuoss, R. M.; Kraus, C. A. Properties of Electrolytic Solutions. IV. The Conductance Minimum and the Formation of Triple Ions Due to the Action of Coulomb Forces. J. Am. Chem. Soc. 1933, 55, 2387– 2399,  DOI: 10.1021/ja01333a026
    Google Scholar
    33
    Properties of electrolytic solutions. IV. The conductance minimum and the formation of triple ions due to the action of Coulomb forces
    Fuoss, Raymond M.; Kraus, Charles A.
    Journal of the American Chemical Society (1933), 55 (), 2387-99CODEN: JACSAT; ISSN:0002-7863.
    cf. C. A. 27, 2083. The presence of triple ions, formed from a neutral mol. and a simple ion, largely account for the min. in cond. curves with solvents of low dielec. const. Dissocn. consts. calcd. theoretically agree with those obtained from cond. expts. The observed shift of the cond. min. toward higher concn. with increasing dielec. const. can also be explained.
  34. 34
    Jiang, J.; Dennis, K. P. N. G. A Decade Journey in the Chemistry of Sandwich-Type Tetrapyrrolato-Rare Earth Complexes. Acc. Chem. Res. 2009, 42 (1), 79– 88,  DOI: 10.1021/ar800097s
    Google Scholar
    34
    A Decade Journey in the Chemistry of Sandwich-Type Tetrapyrrolato-Rare Earth Complexes
    Jiang, Jianzhuang; Ng, Dennis K. P.
    Accounts of Chemical Research (2009), 42 (1), 79-88CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)
    A review. Phthalocyanines and porphyrins are versatile functional pigments with a wide range of applications. These macrocyclic compds. contain four isoindole or pyrrole nitrogen atoms, which can complex with a range of metal ions. Large rare earth metal ions can bring together these tetrapyrrole derivs. to form sandwich-type double- and triple-decker complexes. Depending on the metal centers and the nature of the macrocyclic ligands, these compds. exhibit tunable spectroscopic, electronic, and redox properties, and different extents of intramol. π-π interactions. Some of the properties of the sandwich-type complexes are unique and enable them to be used as advanced materials for various applications. Over the last two decades, a vast no. of homoleptic and heteroleptic double- and triple-decker complexes have been synthesized. With improvements in synthetic procedures, researchers have prepd. novel sandwich complexes that could not have been prepd. by traditional methods. This Account highlights our work over the last decade on this important class of compds. We have focused both on the development of facile and efficient synthetic methodol. and on the various properties and potential applications of these complexes. For both the double- and triple-decker series, we have performed systematic investigations on several series of closely related analogs to reveal the correlations among the structures, electronic properties, spectroscopic characteristics, electrochem., and degree of π-π interactions. We have also performed detailed studies of the self-assembly of amphiphilic analogs in Langmuir-Blodgett films, metal-induced assembly of crown ether contg. sandwich compds., and the use of these complexes in org. field-effect transistors.
  35. 35
    Hojo, M.; Moriyama, H. Conductance in Isodielectric Mixed Solvents Containing Triple Ions. J. Solution Chem. 1996, 25 (7), 681– 694,  DOI: 10.1007/BF00972682
    Google Scholar
    There is no corresponding record for this reference.
  36. 36
    Hojo, M.; Ueda, T.; Inoue, T.; Ike, M.; Kobayashi, M.; Nakai, H. UV - Visible and 1H or 13C NMR Spectroscopic Studies on the Specific Interaction between Lithium Ions and the Anion from Tropolone or 4-Isopropyltropolone (Hinokitiol) and on the Formation of Protonated Tropolones in Acetonitrile or Other Solvents. J. Phys. Chem. B 2007, 111 (7), 1759– 1768,  DOI: 10.1021/jp066756n
    Google Scholar
    36
    UV-Visible and 1H or 13C NMR Spectroscopic Studies on the Specific Interaction between Lithium Ions and the Anion from Tropolone or 4-Isopropyltropolone (Hinokitiol) and on the Formation of Protonated Tropolones in Acetonitrile or Other Solvents
    Hojo, Masashi; Ueda, Tadaharu; Inoue, Tomonori; Ike, Michitaka; Kobayashi, Masato; Nakai, Hiromi
    Journal of Physical Chemistry B (2007), 111 (7), 1759-1768CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)
    The specific interaction between lithium ions and the tropolonate ion (C7H5O2-: L-) was examd. by means of UV-visible and 1H or 13C NMR spectroscopy in acetonitrile and other solvents. On the basis of the electronic spectra, the authors proposed the formation of not only coordination-type species (Li+(L-)2) and the ion pair (Li+L-) but also a "triple ion pair" ((Li+)2L-) in acetonitrile and acetone; however, no "triple pair" was found in DMF and in DMSO, solvents of higher donor ability and only ion pair formation between Li+ and L- in methanol of much higher donor and acceptor ability. The 1H NMR chem. shifts of the tropolonate ion with increasing Li+ concn. verified the formation of (Li+)2L- species in CD3CN and acetone-d6, but not in DMF-d6 or CD3OD. With increasing concn. of LiClO4 in CD3CN, the 1H NMR signals of 4-isopropyltropolone (HL') in coexistence with an equiv. amt. of Et3N shifted first toward higher and then toward lower magnetic-fields, which were explained by the formation of (Li+)(Et3NH+)L'- and by successive replacement of Et3NH+ with a second Li+ to give (Li+)2L'-. In CD3CN, the 1,2-C signal in the 13C NMR spectrum of tetrabutylammonium tropolonate (n-Bu4NC7H5O) appeared at an unexpectedly lower magnetic-field (184.4 ppm vs TMS) than that of tropolone (172.7 ppm), while other signals of the tropolonate showed normal shifts toward higher magnetic-fields upon deprotonation from tropolone. Nevertheless, with addn. of LiClO4 at higher concns., the higher and lower shifts of magnetic-fields for 1,2-C and other signals, resp., supported the formation of the (Li+)2L- species, which can cause redissoln. of LiL ppts. All of the data with UV-visible and 1H and 13C NMR spectroscopy demonstrated that the protonated tropolone (or the dihydroxytropylium ion), H2L+, was produced by addn. of trifluoromethanesulfonic or methanesulfonic acid to tropolone in acetonitrile. The order of the 5-C and 3,7-C signals in 13C NMR spectra of the tropolonate ions was altered by addn. of less than an equiv. amt. of H+ to the tropolonate ion in CD3CN. Theor. calcns. satisfied the exptl. 13C NMR chem. shift values of L-, HL, and H2L+ in acetonitrile and were in accordance with the proposed reaction schemes.
  37. 37
    Zhu, F.; Zhang, W.; Liu, H.; Wang, X.; Zhou, Y.; Fang, C.; Zhang, Y. Micro-Raman and Density Functional Theory Analyses of Ion Pairs in Concentrated Sodium Tetrahydroxyborate Droplets. Spectrochim. Acta, Part A 2020, 224 (3), 117308  DOI: 10.1016/j.saa.2019.117308
    Google Scholar
    There is no corresponding record for this reference.
  38. 38

    At concentrations lower than 0.4 mM the experimental values of ion volumes deviate considerably from the theoretical curve. This shows that the equilibrium between free ions and sandwich ion cannot be described by a simple model. However, the concentration limits of DOSY prevent further refinements.

    There is no corresponding record for this reference.
  39. 39
    A Database of Published Reactivity Parameters E, N, and sN, 2024. https://www.cup.lmu.de/oc/mayr/reaktionsdatenbank2/.
    Google Scholar
    There is no corresponding record for this reference.
  40. 40

    For 4a, where the anionic sandwich 4a4 dominates, the DOSY measurements show that addition of additive 6 (a-BF4) eventually leads to an inversion of the sandwich ion populations towards the cationic a4a (see SI, Chapter 4).

    There is no corresponding record for this reference.

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 1 publications.

  1. Veronika Burger, Maximilian Franta, AnnMarie C. O‘Donoghue, Armin R. Ofial, Ruth M. Gschwind, Hendrik Zipse. Pyridinamide Ion Pairs: Design Principles for Super-Nucleophiles in Apolar Organic Solvents. The Journal of Organic Chemistry 2025, 90 (6) , 2298-2306. https://doi.org/10.1021/acs.joc.4c02668
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. 2025, 147, 6, 5043–5050
Click to copy citationCitation copied!
https://doi.org/10.1021/jacs.4c14825
Published January 24, 2025

Copyright © 2025 The Authors. Published by American Chemical Society. This publication is licensed under

CC-BY 4.0 .

Article Views

1050

Altmetric

-

Citations

1
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

    Chart 1

    Chart 1. Structures of Neutral Organocatalysts DMAP (1) and TCAP (2) and of Pyridinamide Ion Pair Catalysts 3a and 4a
    High Resolution Image
    Download MS PowerPoint Slide

    Figure 1

    Figure 1. (A) 1:1 ion pair 3a, sandwich cation a3a, and sandwich anion 3a3 as potential association models for anion 3 and cation a together with single-molecule dataset (SMD)-derived molecular volumes; (B) conductivity profile for 3a in DCM fits to the calculated conductivity data for the 1:1 association model (purple dotted/dashed line), and the two sandwich association models (gray and blue line); (C) DOSY-derived ion volumes (in Å3) compared to SMD-derived volumes (dashed horizontal lines) for single anion 3, single cation a, ion pair 3a, cation sandwich a3a, and anion sandwich 3a3.

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 2

    Figure 2. (A) Benzhydrylium ion reaction applied for the quantification of the nucleophilicity of 3. (B) Correlation of kobs for the reaction of 5a with 3a for salt concentrations [3a] from 0.01 to 1.0 mM in DCM at 20 °C (blue diamonds) and in the presence of additive PPh4BF4 (6) (turquoise dots).

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 3

    Figure 3. Mayr nucleophilicities N (and sN) of DMAP (1), TCAP (2), and pyridinamide anions 3 and 4 (Ani = p-methoxyphenyl) in MeCN and DCM.

    High Resolution Image
    Download MS PowerPoint Slide

  • References

    This article references 40 other publications.

    1. 1
      (a) Litvinenko, L. M.; Kirichenko, A. I. Basicity and Stereospecificity in Nucleophile Catalysis by Tertiary Amines. Dokl. Akad. Nauk. SSSR 1967, 176, 97– 100
      There is no corresponding record for this reference.
      (b) Steglich, W.; Höfle, G. N,N-Dimethyl-4-pyridinamine, a Very Effective Acylation Catalyst. Angew. Chem., Int. Ed. 1969, 8 (12), 981,  DOI: 10.1002/anie.196909811
      There is no corresponding record for this reference.
    2. 2
      Heinrich, M. R.; Klisa, H. S.; Mayr, H.; Steglich, W.; Zipse, H. Enhancing the Catalytic Activity of 4-(Dialkylamino)Pyridines by Conformational Fixation. Angew. Chem., Int. Ed. 2003, 42 (39), 4826– 4828,  DOI: 10.1002/anie.200352289
      There is no corresponding record for this reference.
    3. 3
      Steglich, W.; Höfle, G. Über eine einfache darstellung von acyl-oxazolinonen-(5) aus 5-acyloxy-oxazolen II. Mitteilung über hypernucleophile acylierungskatalysatoren. Tetrahedron Lett. 1970, 11 (54), 4727– 4730,  DOI: 10.1016/S0040-4039(00)89379-X
      There is no corresponding record for this reference.
    4. 4
      Hassner, A.; Alexanian, V. Direct room temperature esterification of carboxylic acids. Tetrahedron Lett. 1978, 19 (46), 4475– 4478,  DOI: 10.1016/S0040-4039(01)95256-6
      There is no corresponding record for this reference.
    5. 5
      Höfle, G.; Steglich, W.; Vorbrüggen, H. 4-Dialkylaminopyridines as Highly Active Acylation Catalysts. Angew. Chem., Int. Ed. 1978, 17, 569– 583,  DOI: 10.1002/anie.197805691
      There is no corresponding record for this reference.
    6. 6
      Neises, B.; Steglich, W. Simple Method for the Esterification of Carboxylic Acids. Angew. Chem., Int. Ed. 1978, 17 (7), 522– 524,  DOI: 10.1002/anie.197805221
      There is no corresponding record for this reference.
    7. 7
      Chaudhary, S. K.; Hernandez, O. A Simplified Procedure for the Preparation of Triphenylmethylethers. Tetrahedron Lett. 1979, 20 (2), 95– 98,  DOI: 10.1016/S0040-4039(01)85892-5
      There is no corresponding record for this reference.
    8. 8
      Patschinski, P.; Zhang, C.; Zipse, H. The Lewis Base-Catalyzed Silylation of Alcohols-a Mechanistic Analysis. J. Org. Chem. 2014, 79 (17), 8348– 8357,  DOI: 10.1021/jo5016568
      8
      The Lewis Base-Catalyzed Silylation of Alcohols-A Mechanistic Analysis
      Patschinski, Pascal; Zhang, Cong; Zipse, Hendrik
      Journal of Organic Chemistry (2014), 79 (17), 8348-8357CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
      Reaction rates for the base-catalyzed silylation of primary, secondary, and tertiary alcs. depend strongly on the choice of solvent and catalyst. The reactions are significantly faster in Lewis basic solvents such as DMF (DMF) compared with those in chloroform or dichloromethane (DCM). The effects of added Lewis base catalysts such as 4-N,N-dimethylaminopyridine (DMAP) or 4-pyrrolidinopyridine (PPY) are much larger in apolar solvents than in DMF. The presence of an auxiliary base such as triethylamine is required in order to drive the reaction to full conversion.
    9. 9
      Chaudhary, S. K.; Hernandez, O. 4-Dimethylaminopyridine: An Efficient and Selective Catalyst for the Silylation of Alcohols. Tetrahedron Lett. 1979, 20 (2), 99– 102,  DOI: 10.1016/S0040-4039(01)85893-7
      There is no corresponding record for this reference.
    10. 10

      For the nucleophilic reactivity of DMAP (1) in MeCN, see:

      (a) Brotzel, F.; Kempf, B.; Singer, T.; Zipse, H.; Mayr, H. Nucleophilicities and Carbon Basicities of Pyridines. Chem. - Eur. J. 2007, 13 (1), 336– 345,  DOI: 10.1002/chem.200600941
      There is no corresponding record for this reference.

      For supplementary kinetic data and revised N (and sN) parameters for DMAP (1), see:

      (b) Nigst, T. A.; Ammer, J.; Mayr, H. Photogeneration of Benzhydryl Cations by Near-UV Laser Flash Photolysis of Pyridinium Salts. J. Phys. Chem. A 2012, 116 (33), 8494– 8499,  DOI: 10.1021/jp3049247
      10b
      Photogeneration of Benzhydryl Cations by Near-UV Laser Flash Photolysis of Pyridinium Salts
      Nigst, Tobias A.; Ammer, Johannes; Mayr, Herbert
      Journal of Physical Chemistry A (2012), 116 (33), 8494-8499CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)
      Laser flash irradn. of substituted N-benzhydryl pyridinium salts yields benzhydryl cations (diarylcarbenium ions) and/or benzhydryl radicals (diarylmethyl radicals). The use of 3,4,5-triamino-substituted pyridines as photoleaving groups allowed the authors to employ the third harmonic of a Nd/YAG laser (355 nm) for the photogeneration of benzhydryl cations. In this way, benzhydryl cations can also be photogenerated in the presence of arom. compds. and in solvents which are opaque at the wavelength of the quadrupled Nd/YAG laser (266 nm). To demonstrate the scope and limitations of this method, the rate consts. for the bimol. reactions of benzhydryl cations with several substituted pyridines were detd. in acetonitrile and with water in acetone. The obtained data agree with results obtained by stopped-flow UV-vis spectroscopic measurements. The rate consts. for the reaction of the 4,4'-bis[methyl(2,2,2-trifluoroethyl)amino]benzhydrylium ion with 4-(dimethylamino)pyridine were also detd. in DMSO, N,N-dimethylformamide, and acetone. From the second-order rate consts., the authors derived the nucleophilicity parameters N and sN for the substituted pyridines, as defined by the linear free energy relationship, log k2 = sN(N + E).
    11. 11
      Tandon, R.; Unzner, T.; Nigst, T. A.; De Rycke, N.; Mayer, P.; Wendt, B.; David, O. R. P.; Zipse, H. Annelated Pyridines as Highly Nucleophilic and Lewis Basic Catalysts for Acylation Reactions. Chem. - Eur. J. 2013, 19 (20), 6435– 6442,  DOI: 10.1002/chem.201204452
      There is no corresponding record for this reference.
    12. 12
      Mayr, H. Reactivity scales for quantifying polar organic reactivity: the benzhydrylium methodology. Tetrahedron 2015, 71, 5095– 5111,  DOI: 10.1016/j.tet.2015.05.055
      12
      Reactivity scales for quantifying polar organic reactivity: the benzhydrylium methodology
      Mayr, Herbert
      Tetrahedron (2015), 71 (32), 5095-5111CODEN: TETRAB; ISSN:0040-4020. (Elsevier Ltd.)
      A review. The construction and uses of the nucleophilicity and electrophilicity scales, nucleofugality and electrofugality scales, and Lewis basicity and acidity scales are discussed.
    13. 13
      Lakhdar, S. Lewis Base Catalysis in Organic Synthesis, 1st ed.; Vedejs, E.; Denmark, S. E., Eds.; Wiley-VCH: Weinheim, 2016; Chapter 4, pp 85– 116.
      There is no corresponding record for this reference.
    14. 14
      Marcus, Y.; Hefter, G. Ion Pairing. Chem. Rev. 2006, 106 (11), 4585– 4621,  DOI: 10.1021/cr040087x
      14
      Ion pairing
      Marcus, Yizhak; Hefter, Glenn
      Chemical Reviews (Washington, DC, United States) (2006), 106 (11), 4585-4621CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
      A review illustrates the status of the ion-pairing concept with examples of well characterized ion pairs formed in electrolyte solns. in various solvents. It focuses on electrolyte composed of simple, monat., and mainly sym. polyat. ions. The main theories proposed for dealing with ion pairing are presented.
    15. 15
      Reichardt, C. Solvents and Solvent Effects in Organic Chemistry, 3rd ed.; VCH: Weinheim, 2003; Chapter 5.5.5.
      There is no corresponding record for this reference.
    16. 16
      Brak, K.; Jacobsen, E. N. Asymmetric Ion-Pairing Catalysis. Angew. Chem., Int. Ed. 2013, 52 (2), 534– 561,  DOI: 10.1002/anie.201205449
      16
      Asymmetric ion-pairing catalysis
      Brak, Katrien; Jacobsen, Eric N.
      Angewandte Chemie, International Edition (2013), 52 (2), 534-561CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. Charged intermediates and reagents are ubiquitous in org. transformations. The interaction of these ionic species with chiral neutral, anionic, or cationic small mols. emerged as a powerful strategy for catalytic, enantioselective synthesis. This review described developments in the burgeoning field of asym. ion-pairing catalysis with an emphasis on the insights that were gleaned into the structural and mechanistic features that contribute to high asym. induction.
    17. 17
      (a) Waser, M.; Novacek, J.; Gratzer, K. Cooperative Catalysis Involving Chiral Ion Pair Catalysts. In Cooperative Catalysis; Peters, R., Ed.; Wiley-VCH: Weinheim (Germany), 2015; Chapter 7, pp 197– 226.
      There is no corresponding record for this reference.
      (b) Otevrel, J.; Waser, M. Asymmetric Phase-Transfer Catalysis─From Classical Application to New Concepts. In Asymmetric Organocatalysis: New Strategies, Catalysts, and Opportunities, Albrecht, Ł.; Albrecht, A.; Dell’Amico, L., Eds.; Wiley-VCH, 2023; Chapter 3, pp 71– 120.
      There is no corresponding record for this reference.
    18. 18
      Ye, X.; Tan, C. H. Enantioselective Transition Metal Catalysis Directed by Chiral Cations. Chem. Sci. 2021, 12 (2), 533– 539,  DOI: 10.1039/D0SC05734G
      There is no corresponding record for this reference.
    19. 19
      Shirakawa, S.; Maruoka, K. Recent Developments in Asymmetric Phase-Transfer Reactions. Angew. Chem., Int. Ed. 2013, 52 (16), 4312– 4348,  DOI: 10.1002/anie.201206835
      19
      Recent Developments in Asymmetric Phase-Transfer Reactions
      Shirakawa, Seiji; Maruoka, Keiji
      Angewandte Chemie, International Edition (2013), 52 (16), 4312-4348CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. Phase-transfer catalysis has been recognized as a powerful method for establishing practical protocols for org. synthesis, because it offers several advantages, such as operational simplicity, mild reaction conditions, suitability for large-scale synthesis, and the environmentally benign nature of the reaction system. A wide variety of asym. transformations catalyzed by chiral onium salts and crown ethers have been developed for the synthesis of valuable org. compds. in the past several decades, esp. in recent years.
    20. 20
      Merten, C.; Pollok, C. H.; Liao, S.; List, B. Stereochemical Communication within a Chiral Ion Pair Catalyst. Angew. Chem., Int. Ed. 2015, 54 (30), 8841– 8845,  DOI: 10.1002/anie.201501271
      20
      Stereochemical Communication within a Chiral Ion Pair Catalyst
      Merten, Christian; Pollok, Corina H.; Liao, Saihu; List, Benjamin
      Angewandte Chemie, International Edition (2015), 54 (30), 8841-8845CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Ionic interactions are increasingly appreciated as a key, asymmetry-inducing factor in enantioselective catalytic transformations, including those involving Bronsted acid or base catalysis, phase-transfer catalysis, and related processes. However, a detailed understanding of these interactions is often lacking. Herein, we show how an enantiopure anion enforces a chiral conformation onto a catalytically relevant achiral cation. Specifically, we use vibrational CD (VCD) spectroscopy to monitor the transmission of stereochem. information from a chiral phosphate anion to a flexible manganese(III)-salen cation. We show that VCD can be used to study solvent effects and that the obtained chiroptical data directly and quant. correlate with the exptl. obsd. enantioselectivity in an asym. olefin epoxidn. reaction.
    21. 21
      Mahlau, M.; List, B. Asymmetric Counteranion-Directed Catalysis: Concept, Definition, and Applications. Angew. Chem., Int. Ed. 2013, 52 (2), 518– 533,  DOI: 10.1002/anie.201205343
      21
      Asymmetric Counteranion-Directed Catalysis: Concept, Definition, and Applications
      Mahlau, Manuel; List, Benjamin
      Angewandte Chemie, International Edition (2013), 52 (2), 518-533CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. Recently, the use of enantiomerically pure counter anions for the induction of asymmetry in reactions proceeding through cationic intermediates has emerged as an exciting new concept, which has been termed asym. counteranion-directed catalysis (ACDC). Despite its success, the concept has not been fully defined and systematically discussed to date. This Review closes this gap by providing a clear definition of ACDC and by examg. both clear cases as well as more ambiguous examples to illustrate the differences and overlaps with other catalysis concepts.
    22. 22
      Phipps, R. J.; Hamilton, G. L.; Toste, F. D. The Progression of Chiral Anions from Concepts to Applications in Asymmetric Catalysis. Nat. Chem. 2012, 4 (8), 603– 614,  DOI: 10.1038/nchem.1405
      22
      The progression of chiral anions from concepts to applications in asymmetric catalysis
      Phipps, Robert J.; Hamilton, Gregory L.; Toste, F. Dean
      Nature Chemistry (2012), 4 (8), 603-614CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
      A review. Despite the tremendous advances of the past four decades, chemists are far from being able to use chiral catalysts to control the stereoselectivity of any desired reaction. New concepts for the construction and mode of operation of chiral catalysts have the potential to open up previously inaccessible reaction space. The recognition and categorization of distinct approaches seems to play a role in triggering rapid exploration of new territory. This review both reflects on the origins as well as details a selection of the latest examples of an area that has advanced considerably within the past five years or so: the use of chiral anions in asym. catalysis. Defining reactions as involving chiral anions is a difficult task owing to uncertainties over the exact catalytic mechanisms. Nevertheless, the authors attempted to provide an overview of the breadth of reactions that could reasonably fall under this umbrella.
    23. 23
      Helberg, J.; Ampßler, T.; Zipse, H. Pyridinyl Amide Ion Pairs as Lewis Base Organocatalysts. J. Org. Chem. 2020, 85, 5390– 5402,  DOI: 10.1021/acs.joc.0c00114
      23
      Pyridinyl Amide Ion Pairs as Lewis Base Organocatalysts
      Helberg, Julian; Ampssler, Torsten; Zipse, Hendrik
      Journal of Organic Chemistry (2020), 85 (8), 5390-5402CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
      Pyridinyl amide ion pairs carrying various electron-withdrawing substituents were synthesized with selected ammonium or phosphonium counterions. Compared to neutral pyridine-based organocatalysts, these new ion pair Lewis bases display superior catalytic reactivity in the reaction of isocyanates with alcs. and the aza-Morita-Baylis-Hillman reaction of hindered electrophiles. The high catalytic activity of ion pair catalysts appears to be due to their high Lewis basicities toward neutral electrophiles as quantified through quantum chem. calcd. affinity data.
    24. 24
      Dempsey, S. H.; Lovstedt, A.; Kass, S. R. Electrostatically Enhanced 3- and 4-Pyridyl Borate Salt Nucleophiles and Bases. J. Org. Chem. 2023, 88 (15), 10525– 10538,  DOI: 10.1021/acs.joc.3c00523
      There is no corresponding record for this reference.
    25. 25
      Dale, H. J. A.; Hodges, G. R.; Lloyd-Jones, G. C. Kinetics and Mechanism of Azole N–π*-Catalyzed Amine Acylation. J. Am. Chem. Soc. 2023, 145 (32), 18126– 18140,  DOI: 10.1021/jacs.3c06258
      There is no corresponding record for this reference.
    26. 26
      Yang, X.; Birman, V. B. Acyl Transfer Catalysis with 1,2,4-Triazole Anion. Org. Lett. 2009, 11 (7), 1499– 1502,  DOI: 10.1021/ol900098q
      26
      Acyl Transfer Catalysis with 1,2,4-Triazole Anion
      Yang, Xing; Birman, Vladimir B.
      Organic Letters (2009), 11 (7), 1499-1502CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)
      1,2,4-Triazole anion has been identified as an active acyl transfer catalyst suitable for the aminolysis and transesterification of esters.
    27. 27
      Mai, B. K.; Koenigs, R. M.; Nguyen, T. V.; Lyons, D. J. M.; Empel, C.; Pace, D. P.; Dinh, A. H. Tropolonate Salts as Acyl-Transfer Catalysts under Thermal and Photochemical Conditions: Reaction Scope and Mechanistic Insights. ACS Catal. 2020, 10 (21), 12596– 12606,  DOI: 10.1021/acscatal.0c03702
      There is no corresponding record for this reference.
    28. 28
      Liotta, C. L.; Harris, H. P. The Chemistry of “Naked” Anions. I. Reactions of the 18-Crown-6 Complex of Potassium Fluoride with Organic Substrates in Aprotic Organic Solvents. J. Am. Chem. Soc. 1974, 96, 2250– 2252,  DOI: 10.1021/ja00814a044
      28
      Chemistry of naked anions. I. Reactions of the 18-crown-6 complex of potassium fluoride with organic substrates in aprotic organic solvents
      Liotta, Charles L.; Harris, Henry P.
      Journal of the American Chemical Society (1974), 96 (7), 2250-2CODEN: JACSAT; ISSN:0002-7863.
      1,4,7,10,13,16-Hexaoxacyclooctadecane (18-Crown-6) is an effective agent for the solubilization of KF in polar and non-polar, aprotic org. solvents. This solubilized fluoride, which we have termed naked fluoride, is both a potent nucleophile and base and provides a facile and efficient means of obtaining a wide variety of org. fluoride compds. in high yields.
    29. 29
      Coury, L. Conductance Measurements Part 1: Theory. Current 1999, 3 (2), 91– 96
      There is no corresponding record for this reference.
    30. 30
      Mizuhata, M. Electrical Conductivity Measurement of Electrolyte Solution. Electrochemistry 2022, 90 (10), 1– 12,  DOI: 10.5796/electrochemistry.22-66111
      There is no corresponding record for this reference.
    31. 31
      Martínez, L. Measuring the Conductivity of Very Dilute Electrolyte Solutions, Drop by Drop. Quim. Nova 2018, 41 (7), 814– 817,  DOI: 10.21577/0100-4042.20170216
      There is no corresponding record for this reference.
    32. 32
      Schneider, R.; Mayr, H.; Plesch, P. H. Ionisation and Dissociation of Diarylmethyl Chlorides in BCl3/CH2Cl2 Solution: Spectroscopic Evidence for Carbenium Ion Pairs. Ber. Bunsenges. Phys. Chem. 1987, 91, 1369– 1374,  DOI: 10.1002/bbpc.19870911212
      There is no corresponding record for this reference.
    33. 33

      The triple ion sandwich model has first been proposed in:

      Fuoss, R. M.; Kraus, C. A. Properties of Electrolytic Solutions. IV. The Conductance Minimum and the Formation of Triple Ions Due to the Action of Coulomb Forces. J. Am. Chem. Soc. 1933, 55, 2387– 2399,  DOI: 10.1021/ja01333a026
      33
      Properties of electrolytic solutions. IV. The conductance minimum and the formation of triple ions due to the action of Coulomb forces
      Fuoss, Raymond M.; Kraus, Charles A.
      Journal of the American Chemical Society (1933), 55 (), 2387-99CODEN: JACSAT; ISSN:0002-7863.
      cf. C. A. 27, 2083. The presence of triple ions, formed from a neutral mol. and a simple ion, largely account for the min. in cond. curves with solvents of low dielec. const. Dissocn. consts. calcd. theoretically agree with those obtained from cond. expts. The observed shift of the cond. min. toward higher concn. with increasing dielec. const. can also be explained.
    34. 34
      Jiang, J.; Dennis, K. P. N. G. A Decade Journey in the Chemistry of Sandwich-Type Tetrapyrrolato-Rare Earth Complexes. Acc. Chem. Res. 2009, 42 (1), 79– 88,  DOI: 10.1021/ar800097s
      34
      A Decade Journey in the Chemistry of Sandwich-Type Tetrapyrrolato-Rare Earth Complexes
      Jiang, Jianzhuang; Ng, Dennis K. P.
      Accounts of Chemical Research (2009), 42 (1), 79-88CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)
      A review. Phthalocyanines and porphyrins are versatile functional pigments with a wide range of applications. These macrocyclic compds. contain four isoindole or pyrrole nitrogen atoms, which can complex with a range of metal ions. Large rare earth metal ions can bring together these tetrapyrrole derivs. to form sandwich-type double- and triple-decker complexes. Depending on the metal centers and the nature of the macrocyclic ligands, these compds. exhibit tunable spectroscopic, electronic, and redox properties, and different extents of intramol. π-π interactions. Some of the properties of the sandwich-type complexes are unique and enable them to be used as advanced materials for various applications. Over the last two decades, a vast no. of homoleptic and heteroleptic double- and triple-decker complexes have been synthesized. With improvements in synthetic procedures, researchers have prepd. novel sandwich complexes that could not have been prepd. by traditional methods. This Account highlights our work over the last decade on this important class of compds. We have focused both on the development of facile and efficient synthetic methodol. and on the various properties and potential applications of these complexes. For both the double- and triple-decker series, we have performed systematic investigations on several series of closely related analogs to reveal the correlations among the structures, electronic properties, spectroscopic characteristics, electrochem., and degree of π-π interactions. We have also performed detailed studies of the self-assembly of amphiphilic analogs in Langmuir-Blodgett films, metal-induced assembly of crown ether contg. sandwich compds., and the use of these complexes in org. field-effect transistors.
    35. 35
      Hojo, M.; Moriyama, H. Conductance in Isodielectric Mixed Solvents Containing Triple Ions. J. Solution Chem. 1996, 25 (7), 681– 694,  DOI: 10.1007/BF00972682
      There is no corresponding record for this reference.
    36. 36
      Hojo, M.; Ueda, T.; Inoue, T.; Ike, M.; Kobayashi, M.; Nakai, H. UV - Visible and 1H or 13C NMR Spectroscopic Studies on the Specific Interaction between Lithium Ions and the Anion from Tropolone or 4-Isopropyltropolone (Hinokitiol) and on the Formation of Protonated Tropolones in Acetonitrile or Other Solvents. J. Phys. Chem. B 2007, 111 (7), 1759– 1768,  DOI: 10.1021/jp066756n
      36
      UV-Visible and 1H or 13C NMR Spectroscopic Studies on the Specific Interaction between Lithium Ions and the Anion from Tropolone or 4-Isopropyltropolone (Hinokitiol) and on the Formation of Protonated Tropolones in Acetonitrile or Other Solvents
      Hojo, Masashi; Ueda, Tadaharu; Inoue, Tomonori; Ike, Michitaka; Kobayashi, Masato; Nakai, Hiromi
      Journal of Physical Chemistry B (2007), 111 (7), 1759-1768CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)
      The specific interaction between lithium ions and the tropolonate ion (C7H5O2-: L-) was examd. by means of UV-visible and 1H or 13C NMR spectroscopy in acetonitrile and other solvents. On the basis of the electronic spectra, the authors proposed the formation of not only coordination-type species (Li+(L-)2) and the ion pair (Li+L-) but also a "triple ion pair" ((Li+)2L-) in acetonitrile and acetone; however, no "triple pair" was found in DMF and in DMSO, solvents of higher donor ability and only ion pair formation between Li+ and L- in methanol of much higher donor and acceptor ability. The 1H NMR chem. shifts of the tropolonate ion with increasing Li+ concn. verified the formation of (Li+)2L- species in CD3CN and acetone-d6, but not in DMF-d6 or CD3OD. With increasing concn. of LiClO4 in CD3CN, the 1H NMR signals of 4-isopropyltropolone (HL') in coexistence with an equiv. amt. of Et3N shifted first toward higher and then toward lower magnetic-fields, which were explained by the formation of (Li+)(Et3NH+)L'- and by successive replacement of Et3NH+ with a second Li+ to give (Li+)2L'-. In CD3CN, the 1,2-C signal in the 13C NMR spectrum of tetrabutylammonium tropolonate (n-Bu4NC7H5O) appeared at an unexpectedly lower magnetic-field (184.4 ppm vs TMS) than that of tropolone (172.7 ppm), while other signals of the tropolonate showed normal shifts toward higher magnetic-fields upon deprotonation from tropolone. Nevertheless, with addn. of LiClO4 at higher concns., the higher and lower shifts of magnetic-fields for 1,2-C and other signals, resp., supported the formation of the (Li+)2L- species, which can cause redissoln. of LiL ppts. All of the data with UV-visible and 1H and 13C NMR spectroscopy demonstrated that the protonated tropolone (or the dihydroxytropylium ion), H2L+, was produced by addn. of trifluoromethanesulfonic or methanesulfonic acid to tropolone in acetonitrile. The order of the 5-C and 3,7-C signals in 13C NMR spectra of the tropolonate ions was altered by addn. of less than an equiv. amt. of H+ to the tropolonate ion in CD3CN. Theor. calcns. satisfied the exptl. 13C NMR chem. shift values of L-, HL, and H2L+ in acetonitrile and were in accordance with the proposed reaction schemes.
    37. 37
      Zhu, F.; Zhang, W.; Liu, H.; Wang, X.; Zhou, Y.; Fang, C.; Zhang, Y. Micro-Raman and Density Functional Theory Analyses of Ion Pairs in Concentrated Sodium Tetrahydroxyborate Droplets. Spectrochim. Acta, Part A 2020, 224 (3), 117308  DOI: 10.1016/j.saa.2019.117308
      There is no corresponding record for this reference.
    38. 38

      At concentrations lower than 0.4 mM the experimental values of ion volumes deviate considerably from the theoretical curve. This shows that the equilibrium between free ions and sandwich ion cannot be described by a simple model. However, the concentration limits of DOSY prevent further refinements.

      There is no corresponding record for this reference.
    39. 39
      A Database of Published Reactivity Parameters E, N, and sN, 2024. https://www.cup.lmu.de/oc/mayr/reaktionsdatenbank2/.
      There is no corresponding record for this reference.
    40. 40

      For 4a, where the anionic sandwich 4a4 dominates, the DOSY measurements show that addition of additive 6 (a-BF4) eventually leads to an inversion of the sandwich ion populations towards the cationic a4a (see SI, Chapter 4).

      There is no corresponding record for this reference.

  • Supporting Information

    Supporting Information

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.4c14825.

    • Additional experimental and computational details, analysis procedures, and methods, including step by step descriptions (PDF)

    Accession Codes

    CCDC accession codes 2310788–2310789 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing [email protected], or by contacting the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.


    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.