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

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, alpha-H elimination for the formation of enolate, beta-H elimination for the formation of a Breslow intermediate, beta-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.

Automated summary

A general mechanistic map has been proposed and studied for NHC-catalyzed transformation reactions of saturated carboxylic anhydrides, predicting the origin of chemo- and stereo-selectivities. The fundamental pathway of this reaction includes processes such as C-O bond cleavage, alpha-H elimination, beta-H elimination, functionalization with benzylidene diketone, acyl migration, aldol addition, catalyst dissociation, and decarboxylation. The chemoselectivities in other pathways and the stereoselectivity-determining step have also been investigated.