Enantioconvergent and diastereoselective synthesis of atropisomeric hydrazides bearing a cyclic quaternary stereocenter through ternary catalysis

Abstract

An efficient and highly enantioconvergent and diastereoselective ternary catalysis in a one-pot process is reported, which represents an integrated strategy for the synthesis of atropisomeric hydrazides with defined vicinal central and axial chirality from readily available racemic α-amino-ynones, azodicarboxylates, and Morita–Baylis–Hillman (MBH) carbonates. This method utilizes in situ-generated racemic pyrrolin-4-ones via hydroamination of racemic α-amino-ynones by AuCl catalysis as a novel and versatile C1 synthon, which engage commercially available azodicarboxylates to generate amination products in high yields and uniformly excellent enantioselectivities under the catalysis of a chiral phosphoric acid. Following amination, N-alkylation catalyzed by diastereoselective organocatalyst afforded axially chiral hydrazides with excellent diastereoselectivities (>98 : 2 dr). The synthetic utility of the amination products and axially chiral hydrazides was also demonstrated by their facile conversion to diverse molecules in high yields with excellent stereopurity. Density functional theory calculations were performed to understand the origin of diastereoselectivity.