Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

Molecules bearing 1,3-dual axial and more distal axial chiralities are widely applied in chiral ligands, natural products, and anticancer agents, with their unique spatial configurations endowing them with distinctive functions and values. Although significant progress has been made in the asymmetric synthesis of distal biaxial chirality, overcoming the challenges of steric complexity and dynamic stability to achieve efficient and general construction remains a critical issue. This review summarizes recent advances in the field of distal biaxial chirality, highlighting three major synthetic strategies: direct one-step construction of distal biaxial chirality, multistep sequential generation, and conversion from central to biaxial chirality, with the aim of providing new perspectives and methodologies for further development in this area.