Organocatalyzed atroposelective dynamic kinetic resolutions via transient seven-membered cyclic hemiacetals

Abstract

Catalytic atroposelective dynamic kinetic resolution via the formation of transient bridged biaryl intermediates represents an expedient route for the synthesis of axially chiral biaryls. Progress in this field has been limited to the reactions promoted by bridged biaryl intermediates with five- or six-membered rings. Herein we demonstrate the first example of a carbene-catalyzed atroposelective dynamic kinetic acylation reaction via transient seven-membered cyclic hemiacetals. The key for the success of this reaction relies on the formation and configurational instability of the transient seven-membered cyclic hemiacetal intermediate. The axially chiral biaryl aldehyde products obtained via this method can undergo a series of further transformations. Notably, one of the axially chiral biaryl aldehyde products can be used as the key and common intermediate for the asymmetric synthesis of natural product steganone. Preliminary density functional theory calculations reveal the molecular origins underlying the observed chemo- and enantioselectivity outcomes.