Mechanisms and origins of the stereoselectivity in copper/Lewis base cooperatively catalyzed asymmetric allylic alkylation: a DFT perspective

Abstract

Combining a Lewis base with a transition metal offers a promising new strategy for asymmetric synthesis under one-pot reaction conditions. Stereoselectivity in cooperative catalysis has a more complex origin than that in well-studied single-catalyst systems. Therefore, clearly elucidating the mechanism and identifying the role of each catalyst in cooperative catalytic systems remain important research directions. Herein, the mechanism and origin of the stereoselectivity of the allylic alkylation reaction under Cu/LB cooperative catalysis have been systematically investigated using density functional theory (DFT). The computational results show that the nucleophilic addition between the Cu-bound ylide and LB-activated MBH adduct determines the stereoselectivity and chemoselectivity. The non-covalent interactions (NCI) and atoms-in-molecules (AIM) analyses results show that the number and strength of non-covalent intermolecular interactions play an important role in achieving a high level of stereoselectivity. The local reactivity index analysis shows that the chemoselectivity is controlled by the reactivity of the electrophile. The novel activation mode found for the Cu/LB cooperative catalysis system not only deepens our understanding of organocatalysis/transition-metal cooperative-catalyzed reactions but also provides valuable guidance for the development of novel metal catalysts, organocatalysts, and reactions.