Enantioselective Construction of Bridged Biaryl Atropisomers With Medium- and Macrocyclic Architectures

The catalytic asymmetric construction of bridged biaryl atropisomers has emerged as a powerful platform for accessing three-dimensional chiral architectures with broad applications in synthesis, catalysis, medicinal chemistry, and molecular design. This review summarizes recent advances in the enantioselective synthesis of medium- and macrocyclic bridged biaryls, highlighting diverse catalytic strategies that achieve precise stereocontrol, efficient macrocyclization, and access to structurally compact yet conformationally complex atropisomeric frameworks. These strategies enable the simultaneous formation of stereogenic axes and centers, facilitate the assembly of strained or conformationally intricate ring systems, and provide streamlined access to complex natural products and functional molecules. Remaining challenges, including precise conformational control, expansion of scaffold diversity, improvement of configurational stability, and scalable atroposelective macrocyclization, underscore the need for continued innovation in this rapidly evolving field.