Synthesis of Chiral\nSaturated Heterocycles Bearing\nQuaternary Centers via Enantioselective β‑C(sp<sup>3</sup>)–H Activation of Lactams

The development of catalytic methods for the synthesis\nof enantiopure\nsaturated heterocycles has been a long-standing challenge in asymmetric\ncatalysis. We describe the first highly enantioselective palladium-catalyzed\nβ<i>-</i>C­(sp<sup>3</sup>)–H arylation and\nolefination of lactams for the preparation of various chiral N-heterocycles\nbearing quaternary carbon centers. The presence of strongly electron-withdrawing\ngroups on the chiral bifunctional MPAThio ligand is crucial to the\nreactivity of weakly coordinating lactams. The resulting enantioenriched\nlactams are readily converted to a family of chiral piperidines and\nimides that are highly desirable in drug discovery.