Synthesis of Chiral Saturated Heterocycles Bearing Quaternary Centers via Enantioselective β-C(sp<sup>3</sup>)–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<i>-</i>C(sp<sup>3</sup>)-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.
Authors
- Bryan J. Simmons (ORCID: https://orcid.org/0000-0003-2745-2042)
- Kap‐Sun Yeung (ORCID: https://orcid.org/0000-0003-3995-6555)
- Shuang Liu (ORCID: https://orcid.org/0000-0001-6341-8103)
- Jennifer X. Qiao (ORCID: https://orcid.org/0000-0002-6685-2092)
- Peng Lu (ORCID: https://orcid.org/0000-0002-8121-8065)
- Jin‐Quan Yu (ORCID: https://orcid.org/0000-0003-3560-5774)
- William R. Burgenson
Institutions
- Scripps Research Institute (US)
- Bristol-Myers Squibb (United States) (US)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2024-12-31
- DOI
- https://doi.org/10.1021/jacs.4c15834
- Citations
- 9
- Primary Topic
- Catalytic C–H Functionalization Methods
- Type
- article
- Field-Weighted Citation Impact
- 2.25
Funders
- Bristol-Myers Squibb
- Thailand Science Research and Innovation
- National Institutes of Health
- University of California, San Diego
- National Institute of General Medical Sciences