Ligand Enabled Pd(II)-Catalyzed γ-C(sp3)-H Lactamization of Native Amides

被引：36

作者：

Liu, Shuang ^{[1
]}

Zhuang, Zhe ^{[1
]}

Qiao, Jennifer X. ^{[2
]}

Yeung, Kap-Sun ^{[3
]}

Su, Shun ^{[4
]}

Cherney, Emily C. ^{[2
]}

Ruan, Zheming ^{[2
]}

Ewing, William R. ^{[2
]}

Poss, Michael A. ^{[2
]}

Yu, Jin-Quan ^{[1
]}

机构：

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

[2] Bristol Myers Squibb Co, Discovery Chem, Princeton, NJ 08543 USA

[3] Bristol Myers Squibb Res & Dev, Cambridge, MA 02142 USA

[4] Bristol Myers Squibb, San Diego, CA 92121 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2021年 / 143卷 / 51期

关键词：

C-H FUNCTIONALIZATION; CATALYZED INTRAMOLECULAR AMINATION; DIRECTING-GROUP; ALIPHATIC-AMINES; BOND FORMATION; GAMMA; PD; C(SP(3))-H; CEREBLON; ACTIVATION;

D O I：

10.1021/jacs.1c10183

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

gamma-Lactams form important structural cores of a range of medicinally relevant natural products and clinical drugs, principal examples being the new generation of immunomodulatory imide drugs (IMiDs) and the brivaracetam family. Compared to conventional multistep synthesis, an intramolecular gamma-C-H amination of aliphatic amides would allow for the direct construction of valuable.-lactam motifs from abundant amino acid precursors. Herein we report a novel 2-pyridone ligand enabled Pd(II)-catalyzed gamma-C(sp(3))-H lactamization of amino acid derived native amides, providing the convenient synthesis of.lactams, isoindolinones, and 2-imidazolidinones. C6-Substitution of the 2-pyridone ligand is crucial for the lactam formation. This protocol features the use of N-acyl amino acids, which serve as both the directing group and cyclization partner, practical and environmentally benign tert-butyl hydrogen peroxide (TBHP) as the sole bystanding oxidant, and a broad substrate scope. The utility of this protocol was demonstrated through the two-step syntheses of a lenalidomide analog and brivaracetam from readily available carboxylic acids and amino acids.

引用

页码：21657 / 21666

页数：10

共 73 条

[1] Reductive C(sp2)-N Elimination from Isolated Pd(IV) Amido Aryl Complexes Prepared Using H2O2 as Oxidant [J].