Synthesis and Post-Resolution Modification of New Axially Chiral Ligands for Asymmetric Catalysis

The synthesis of four new members of the Quinazolinap series of ligands is described. Three of these ligands were prepared by post-resolution modification of the known ligand (R) -7-chloro-2-isopropyl-Quinazolinap, a new approach which offers an expedient route to a range of enantiopure ligands as it precludes the need for resolution of each ligand prepared. The remaining ligand, 7-chloro-2-methyl-Quinazolinap, was prepared in a seven-step synthetic sequence incorporating palladium- and nickel-catalyzed transformations as the key steps. A diastereomerically pure palladacycle of this ligand was characterised by X-ray crystallography. (R)-7-Chloro-2-isopropyl-Quinazolinap was applied to the rhodium-catalyzed hydroboration of vinylarenes with regioselectivities of up to > 99:1 and ee values of up to 68 %. Each of the Quinazolinap ligands prepared were applied to the palladium-catalyzed allylic alkylation of 1,3-diphenylprop-2-enyl acetate resulting in conversions of up to 100% and ee values of up to 85%. Solution-phase NMR studies on a palladium complex of one of the ligands provided a rationale for the sense of asymmetric induction.