Nucleophilicity parameters of enamides and their implications for organocatalytic transformations

The kinetics of the reactions of eleven substituted enamides with benzhydrylium ions (diarylcarbenium ions) were determined in acetonitrile solution. The second-order rate constants follow the correlation log k ₂(20°C)=s _N(E+N), which allowed us to derive reactivity parameters N and s _N. With 4.6<N<7.1, enamides had similar nucleophilicities to enol ethers and non-or weakly activated indoles and pyrroles. The combination of the N and s _N parameters with the previously reported E parameters of typical Michael acceptors, α,β-unsaturated iminium ions, and the chlorinating agent hexachlorocyclohexa-2,4-dienone allowed us to reliably reproduce the experimental rate constants of the reactions with these electrophiles. The reactions of enamides with α,β-unsaturated iminium ions only proceeded in the presence of bases (e.g., 2,6-lutidine), which was explained by the low Lewis acidities of the iminium ions. The consequences of these results for the use of enamides in organocatalytic reactions are discussed. Nucleophile-specific parameters N and s _N of enamides allowed a prediction of the rates of their reactions with various electrophiles and enabled a resolution of the mechanism of iminium-activated reactions of α,β-unsaturated aldehydes with enamides (see scheme).