Origin of the α-Effect in Aminolysis of Y-Substituted Phenyl Diphenylphosphinates: Ground-state Versus Transition-state Contribution

Abstract

Figure 1. Bronsted-type plot for reactions of 2,4-dinitrophenyl diphenylphosphinate (1a) with primary amines in 80 mol% H2O/20 mol% DMSO at 25 ± 0.1 C. The identity of amines: 1 = ethylamine, 2 = ethylenediamine, 3 = ethanolamine, 4 = benzylamine, 5 = glycylglycine, 6 = hydrazine, 7 = glycine ethyl ester, 8 = 1,2-diaminopropane-H, 9 = trifluoroethylamine. The kinetic data were taken from ref. 22 except for the reaction of 1a with hydrazine, 6. Nucleophiles possessing one or more nonbonding electron pairs at the atom α to the nucleophilic site have often been reported to exhibit abnormally higher reactivity than would be expected from their basicity. Accordingly, these nucleophiles and the enhanced reactivity were termed as α-nucleophiles and the α-effect, respectively. Numerous studies have been performed to investigate the origin of the α-effect. Some theories advanced to explain the cause of the α-effect are: (1) destabilization of the groundstate (GS) due to repulsion of the nonbonding electron pairs, (2) stabilization of transition state (TS) including general acid/base catalysis, (3) thermodynamic product stability, (4) solvent effects. However, the origin of the α-effect is not clearly understood. Particularly, solvent effects on the α-effect remain controversial. Recent calculations have shown that the α-effect is present in gas-phase reactions. Thus, solvent effect has been suggested to be unimportant for the αeffect. However, our systematic study has revealed that solvent effect on the α-effect is significantly important. The evidence provided was that the α-effect is strongly dependent on solvent compositions for reactions of aryl acetates, benzoates and thionobenzoates with butane-2,3-dione monoximate (an α-nucleophile) and 4-chlorophenoxide (a reference nucleophile) in DMSO-H2O mixtures of varying compositions, e.g., the magnitude of the α-effect increases as the DMSO content in the medium increases up to ca. 50 mol% DMSO and then decreases thereafter (a bell-shaped α-effect profile). Dissection of the α-effect into GS and TS contributions through combination of the kinetic data with our calorimetric data has led us to conclude that GS destabilization is mainly responsible for the increasing α-effect up to ca. 50 mol% DMSO, while differential TS stabilization contributes to the decreasing αeffect in the DMSO-rich region. We have also reported that TS stabilization through general acid/base catalysis plays an important role for the α-effect found in reactions of Y-substituted phenyl benzoates with hydrazine and glycylglycine. Our study has been extended to reactions of Y-substituted phenyl diphenylphosphinates (1a-f) with hydrazine and glycine ethyl ester (Scheme 1) to investigate the origin of the α-effect (e.g., GS and TS contributions).