Work

Synthesis of Chiral Saturated Heterocycles Bearing Quaternary Centers via Enantioselective β-C(sp3)–H Activation of Lactams

Year: 2024

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.4c15834