Gold/HNTf₂-Cocatalyzed Asymmetric Annulation of Diazo-Alkynes: Divergent Construction of Atropisomeric Biaryls and Arylquinones

Abstract

Due to the inherent challenges posed by the linear coordination of gold(I) complexes, asymmetric gold-catalyzed processes remain challenging, particularly in the atroposelective synthesis of axially chiral skeletons. Except for extremely few examples of intramolecular annulations, the construction of axial chirality via asymmetric goldcatalyzed intermolecular alkyne transformation is still undeveloped. Herein, a gold/HNTf 2 -cocatalyzed asymmetric diazo-alkyne annulation is developed, allowing the atroposelective and divergent synthesis of chiral non-C 2symmetric biaryls and arylquinones in generally good to excellent yield (up to 93% yield) and enantioselectivity (up to 99% ee), with broad substrate scope. Notably, this work represents the first gold-catalyzed atroposelective construction in an intermolecular manner. More interestingly, this strategy is successfully extended to the first asymmetric construction of sevenmembered-ring atropisomers bearing one carbon-centered chirality in excellent diastereoselectivity and high enantioselectivity (up to 93% ee and 50:1 dr). Remarkably, the utility of this methodology is further illustrated by the successful application of a representative axially chiral ligand in a series of enantioselective reactions. Importantly, the Brønsted acid as a proton-shuttle cocatalyst significantly promotes this asymmetric annulation. Additionally, the origin of enantioselectivity of this annulation and the role of HNTf 2 are disclosed by density functional calculations and control experiments.