Copper-Complex-Catalyzed Asymmetric Aerobic Oxidative Cross-Coupling of 2-Naphthols: Enantioselective Synthesis of 3,3'-Substituted C1 -Symmetric BINOLs

Abstract

A novel chiral 1,5-N,N-bidentate ligand based on a spirocyclic pyrrolidine oxazoline backbone was designed and prepared, and it coordinates CuBr in situ to form an unprecedented catalyst that enables efficient oxidative cross-coupling of 2-naphthols. Air serves as an external oxidant and generates a series of C₁ -symmetric chiral BINOL derivatives with high enantioselectivity (up to 99 % ee) and good yield (up to 87 %). This approach is tolerant of a broader substrates scope, particularly substrates bearing various 3- and 3'-substituents. A preliminary investigation using one of the obtained C₁ -symmetric BINOL products was used as an organocatalyst, exhibiting better enantioselectivity than the previously reported organocatalyst, for the asymmetric α-alkylation of amino esters.

Keywords: BINOLs; copper; cross-coupling; enantioselectivity; synthetic methods.