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

被引：1

作者：

Lu, Peng ^{[1
]}

Burgenson, William R. ^{[1
]}

Simmons, Bryan J. ^{[2
]}

Liu, Shuang ^{[2
]}

Yeung, Kap-Sun ^{[3
]}

Qiao, Jennifer X. ^{[3
]}

Yu, Jin-Quan ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[2] Bristol Myers Squibb, Res & Dev, San Diego, CA 92121 USA

[3] Bristol Myers Squibb, Res & Dev, Cambridge, MA 02141 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2024年 / 147卷 / 02期

关键词：

CONSTRUCTION; THALIDOMIDE;

D O I：

10.1021/jacs.4c15834

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 beta-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.

引用

页码：1427 / 1433

页数：7