Regio- and Stereospecific Synthesis of C-3 Functionalized Proline Derivatives by Palladium Catalyzed Directed C(sp3)-H Arylation

Functionalization of C(sp(3)) H bonds at the unactivated 3-position of proline derivatives has been achieved using aryl iodides and palladium catalysis. This directly affords cis-2,3-disubstituted pyrrolidines as single stereoisomers. 3-Arylation occurs in high yield under solvent-free conditions with aminoquinoline and methoxyaminoquinoline directing groups. The latter was readily removed to give primary amide derivatives with physicochemical properties appropriate for use as fragments in drug discovery.