Organocatalytic synthesis of chiral allene catalyzed by chiral phosphoric acid via asymmetric 1,8-addition of indole imine methide: Mechanism and origin of enantioselectivity

Abstract

Organocatalytic synthesis of chiral allene can be successfully achieved through the reaction between propargylic alcohol and 3-phenylindole catalyzed by chiral phosphoric acid with high yield and high enantioselectivity. The detailed reaction mechanism and origin of enantioselectivity were uncovered by quantum mechanical calculations. The results indicate that the reactions undergo the dehydration process, the C–C bonding reaction, the hydrogen abstraction and the regeneration of catalyst. Eight possible pathways were found and the most favorable reaction paths leading to the major and minor products were evaluated which were consistent with the experimental results. The distortion/interaction analyses of the transition states in enantioselectivity-determining steps confirm the most favorable pathway in leading the major product. QTAIM and IGM analyses are used to illustrate the role of intermolecular interactions. EDA analysis is also employed to understand the origin of selectivity. This work would provide insightful viewpoints on the asymmetric organocatalytic reaction by chiral phosphoric acid.