Control of axial stereochemistry for the enantioselective construction of a QUINAP library.

QUINAP, a classic axially chiral P,N-ligand based on the skeleton of an atropisomeric heterobiaryl, has been widely applied in various types of enantioselective transformations. To date, the efficient construction of a QUINAP library with high enantioselectivity is still underdeveloped. Herein, we report a two-step synthesis of QUINAP derivatives from racemic QUINOLs with high enantioselectivity by controlling the dynamic axial stereochemistry in heterobiaryl skeletons. Under heating, solvent-dependent crystallization-induced deracemization (CID) of QUINOLs was realized with chiral ammonium salt. Subsequently, palladium-catalyzed stereospecific phosphination of enantioenriched QUINOLs delivered QUINAP products with high enantiopurity. The bidentate phosphine ligand dppp (1,3-bis(diphenylphosphino)propane) plays a key role in favoring the phosphination pathway over axial rotation. Density functional theory (DFT) calculations have provided clear insights into the palladium-catalyzed stereospecific phosphination pathway. Finally, construction of a QUINAP library was accomplished with excellent enantiopurity, and it was successfully applied in the A3-coupling and alkene hydroboration reactions.