Exploring a general mechanistic map on NHC-catalyzed activation/transformation reactions of saturated carboxylic anhydrides

Abstract

A general mechanistic map involving multiple intermediates and pathways has been proposed and systematically studied for NHC-catalyzed transformation reactions of saturated carboxylic anhydrides. Based on the map, the origin of chemo- and stereo-selectivities has been predicted in a case study of the NHC-catalyzed reaction of saturated carboxylic anhydride with benzylidene diketone. Computational results show that the fundamental pathway of this kind of reaction mainly includes the following processes: the C–O bond cleavage for the formation of acyl azolium, α-H elimination for the formation of enolate, β-H elimination for the formation of a Breslow intermediate, β-C functionalization with benzylidene diketone, acyl migration, aldol addition, dissociation of catalyst, and decarboxylation. The Michael-type addition process is identified to be the stereoselectivity-determining step, with an SR-configured product being generated preferentially. In addition, the other two chemoselective pathways, including the hetero-Diels–Alder and Stetter pathways, are also considered. The chemoselectivity is successfully predicted by comparing the energy gap of FMO between the two interactive partners, which could provide a general guideline in that FMO analysis can be used for predicting the potential chemoselectivities of organocatalytic reactions.