Mechanistic Features of Asymmetric Vinylidene ortho-Quinone Methide Construction and Subsequent Transformations

Abstract

Vinylidene ortho-quinone methide (VQM), an elusive dearomatized intermediate, is widely used in asymmetric catalysis. Due to its transient nature, the current understanding of VQM was largely acquired based on computational studies and trapping experiments. Herein, the enantioselective construction of stable VQM intermediates by an organocatalyzed bromination was achieved. Kinetic studies, control experiments, and nonlinear effects were realized to obtain insights into the two sequential mechanistic events in VQM-involved reactions. The results elucidated that the stereocontrol was enforced by one catalyst molecule in the generation of the axially chiral VQM, but the subsequent transformation was independent of the catalyst. The efficiency of the VQM as axially chiral synthetic reagents was demonstrated by its reactions with carboxylic acids, cyclo-1,3-diones, and nitrone. In all cases, the VQM reacted smoothly to provide the axially chiral esters and ethers via an axial-to-axial chirality transfer, as well as the chiral α-bromo ketones through an axial-to-central chirality conversion. The properties of the isolated VQM exhibited its high potential in organic chemistry.