Unveiling the Chemo- and Stereoselectivities of NHC-Catalyzed Reactions of an Aliphatic Ester with Aminochalcone

The possible mechanisms and origin of selectivities in N-heterocyclic carbene (NHC)-catalyzed reactions of an aliphatic ester with aminochalcone were studied using density functional theory. Herein, a general mechanistic map involving various types of possible intermediates was discovered, and the corresponding chemoselective pathways were systematically investigated. Based on the computational results, the most energetically favorable reaction pathway mainly involved in the following processes: formation of a homoenolate intermediate via alpha/beta-H elimination, formal Michael addition of a homoenolate intermediate to aminochalcone, intramolecular aldol-type reaction, and ring closure to form the lactam product. Furthermore, the formal Michael addition process was shown to be the stereoselectivity-determining step, generating the RR-configured product preferentially. The chemoselectivity was successfully predicted by comparing the omega + N index of reacting ability for a nucleophile (N) and electrophile (E). This work would provide a general guideline for predicting chemoselectivity in NHC-catalyzed reactions.