Catalytic asymmetric construction of remote P or other heteroatom (Si/S) stereogenic axially chiral scaffolds

Abstract

Axial chirality represents a fundamental element of stereochemistry and is a defining structural feature in many chiral compounds. Although the axial chirality of atropisomers, allenes and spiranes has been extensively studied, the chemistry of alkylidenecycloalkanes and their analogues—especially those possessing P-, S- or Si-based axial chirality—remains underdeveloped. Here we report a chiral phosphoric acid-catalyzed oxime condensation that enables the construction of remote heteroatom (P/S/Si)-stereogenic axially chiral scaffolds. The reaction accommodates a broad range of functional groups, delivering optically active axially chiral 9-heteroanthrone-based oxime ethers in good to excellent enantioselectivities (up to 98 : 2 er). We also describe a modular synthesis of dibenzoazaphosphepinones and demonstrate their application as chiral monodentate phosphine ligands in asymmetric catalysis.