biostudies-literatureLu PBristol-Myers SquibbU.S. Department of Health and Human ServicesNIGMS NIH HHS1427-1433https://www.ebi.ac.uk/biostudies/studies/S-EPMC12349376biostudies-literatureUnknown147(2)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(sp3)-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.Journal of the American Chemical SocietySynthesis of Chiral Saturated Heterocycles Bearing Quaternary Centers via Enantioselective β-C(sp3)-H Activation of Lactams.PMC12349376R01 GM084019R01GM084019Yu JQYeung KSBurgenson WRQiao JXLiu SLu PSimmons BJfalseSynthesis of Chiral Saturated Heterocycles Bearing Quaternary Centers via Enantioselective β-C(sp3)-H Activation of Lactams.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(sp3)-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.2025-01-01T00:00:00Z2025 Jan2026-05-04T21:57:56.426Z2026-04-07T21:00:47.163ZS-EPMC123493763981208410.1021/jacs.4c15834