Enantioselective Cycloaddition Desymmetrization En Route to Multi-Stereogenic Atropisomers

Abstract

The catalytic desymmetrization of prochiral molecules provides a powerful and step-economical strategy for constructing complex chiral architectures. Herein, we report a general organocatalytic asymmetric cycloaddition desymmetrization of both biaryl and biaryl ether dialdehydes, enabling the simultaneous construction of axial and central chirality in a single operation. By employing a chiral phosphoric acid as the catalyst, this method allows efficient access to two distinct classes of atropisomers bearing multiple stereogenic elements. The reactions proceed under mild conditions with broad substrate scope, delivering the target scaffolds in high yields with excellent enantioselectivity and diastereoselectivity. The synthetic utility of the products is further demonstrated through diverse functionalizations, highlighting the potential of these chiral building blocks for further applications.