Mechanistic Features of Asymmetric Vinylidene <i>ortho</i>-Quinone Methide Construction and Subsequent Transformations

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.