Synthesis of Chiral Saturated Heterocycles Bearing Quaternary Centers via Enantioselective β-C(sp<sup>3</sup>)–H Activation of Lactams
Peng Lu, William R. Burgenson, Bryan J. Simmons, Shuang Liu, Kap‐Sun Yeung, Jennifer X. Qiao, Jin‐Quan Yu
Abstract
The development of catalytic methods for the synthesis of enantiopure saturated heterocycles has been a long-standing challenge in asymmetric catalysis. We describe the first highly enantioselective palladium-catalyzed β - C(sp 3 )–H arylation and olefination of lactams for the preparation of various chiral N-heterocycles bearing quaternary carbon centers. The presence of strongly electron-withdrawing groups on the chiral bifunctional MPAThio ligand is crucial to the reactivity of weakly coordinating lactams. The resulting enantioenriched lactams are readily converted to a family of chiral piperidines and imides that are highly desirable in drug discovery.