Palladium(II)-Catalyzed Enantioselective C(sp3)-H Activation Using a Chiral Hydroxamic Acid Ligand

An enantioselective method for Pd(II)-catalyzed cross-coupling of methylene beta-C(sp(3))-H bonds in cyclobutanecarboxylic acid derivatives with arylboron reagents is described. High yields and enantioselectivities were achieved through the development of chiral mono-N-protected alpha-amino-O-methylhydroxamic acid (MPAHA) ligands, which form a chiral complex with the Pd(II) center. This reaction provides an alternative approach to the enantioselective synthesis of cyclobutanecarboxylates containing alpha-chiral quaternary stereocenters. This new class of chiral catalysts also show promises for enantioselective beta-C(sp(3))-H activation of acyclic amides.