A highly effective protocol for the synthesis of C-3-substituted prolines has been developed. Pd-catalyzed C(sp³)–H activation is used for the straightforward functionalization of prolines. The use of an 8-aminoquinolinecarboxamide directing group allows direct arylation, alkenylation, and alkylation at the C-3 position of prolines in moderate to high yields with diverse iodo- or bromo precursors. The resulting 3-substituted proline derivatives are important units in many biologically active compounds and are useful promoters for a variety of functional group transformations.

A highly effective protocol for the synthesis of C-3-substituted prolines has been developed. Pd-catalyzed C(sp³)–H activation is used for the straightforward functionalization of prolines. The use of an 8-aminoquinolinecarboxamide directing group allows direct arylation, alkenylation, and alkylation at the C-3 position of prolines in moderate to high yields with diverse iodo- or bromo precursors. The resulting 3-substituted proline derivatives are important units in many biologically active compounds and are useful promoters for a variety of functional group transformations.