Theoretical study of the BINOL–zinc complex-catalyzed asymmetric inverse-electron-demand imino Diels–Alder reaction: mechanism and stereochemistry

Abstract

The mechanism and stereochemistry of an inverse electron-demand imino Diels–Alder (IEDIDA) reaction between a cyclic imine and an electron-poor chromone-derived diene catalyzed by a chiral BINOL–zinc complex have been studied using a combination of DFT calculations, chemical reactivity indices and distortion/interaction analyses. The calculations reveal that the coordination of Lewis acid zinc catalyst to the ester CO group of the electrophilic diene significantly lowers the energy barriers of the cycloaddition reaction by an increase of the electrophilic character of the diene. Herein, both the catalytic mechanism and stereochemistry of the cycloadduct depend on the configuration of the diene. An energy-favored stepwise mechanism is adopted when the ester CO group of the diene takes the trans configuration. This configuration allows a stabilizing interaction to form between the zinc center of the catalyst and the phenyl moiety of the dienophile and favors the steric discrimination from the naphthalene ring of the BINOL ligand at the ring-closure transition state that is rate-determining and stereo-controlling for the entire cycloaddition process. The electrophilic/nucleophilic interaction defines the most favored alignment between the dienophile and the diene–catalyst complex, which overwhelms the distortion of these fragments and realizes the exo-selectivity of the cycloadduct.