Enantioselective synthesis of atropisomeric biaryls and heterobiaryls via transition metal-catalyzed cyclization

Abstract

Atropisomeric architectures with a chiral axis are prevalent in biologically active molecules and natural products, and they are widely put to use in privileged catalysts and chiral ligands. Axially chiral biaryls and heterobiaryls are a fundamental category of atropisomeric compounds with internal barriers caused by rotational restrictions around carbon-carbon, carbon-nitrogen or nitrogen-nitrogen axes. In this regard, the synthesis of biaryls/hetero-biaryls has witnessed substantial progress, despite the generally complicated traditional synthetic methods. Recent developments in the transition metal-catalyzed substrate activation and subsequent annulation reaction offer a straightforward approach to the preparation of various cyclic (hetero)biaryl atropisomers. In this account, we would like to present recent research advancements in transition metal-catalyzed enantioselective annulation reactions towards (hetero)biaryls featuring atropisomeric optical activity. The focus will be on mechanistic investigations, reaction limitations, and synthetic applications. Additionally, the combination of developing synthetic strategies and representative frameworks is discussed, along with some insights into the developing trend.