Asymmetric Synthesis of Biaryl Atropisomers Using an Organocatalyst-Mediated Domino Reaction as the Key Step.

Abstract

A three-pot synthetic method that features the use of an organocatalyst as the key step was developed for the preparation of biaryl atropisomers. The first reaction is an asymmetric domino Michael-Henry reaction catalyzed by diphenylprolinol silyl ether to afford the substituted nitrocyclohexanecarbaldehyde with four stereogenic centers and one defined configuration of a stereogenic axis with excellent enantioselectivity. Removal of the central chirality from the domino products afforded biaryl atropisomers having axial chirality with excellent enantioselectivity.