Origins of catalyst-controlled enantiodivergent hydroamination of enones with pyridazinones: A computational study

Abstract

Density functional theory calculations have been performed to investigate the dipeptide phosphine-catalyzed hydroamination of enones with pyridazinones. The computations reveal that a number of the NH···O hydrogen-bonding interactions with the pyridazinone moiety and the C–H···O hydrogen-bonding interactions with the enone moiety are present in the enantioselectivity-determining Michael addition transition states. The experimentally-observed catalyst-controlled enantiodivergence is mainly attributed to the significant impact of the substituent of the amide moiety of the dipeptide phosphine on the relative strength of the NH···O hydrogen-bonding interactions, which was found to affect the Si face attack transition state, enabling the enantioselectivity switch upon change of chiral dipeptide phosphine catalyst.