Magnesium Coordination-Directed N-Selective Stereospecific Alkylation of 2-Pyridones, Carbamates, and Amides Using α-Halocarboxylic Acids

被引：54

作者：

Fang, Yuan-Qing ^{[1
]}

Bio, Matthew M. ^{[1
]}

Hansen, Karl B. ^{[1
]}

Potter, Matthew S. ^{[2
]}

Clausen, Andrew ^{[2
]}

机构：

[1] Amgen Inc, Dept Chem Proc Res & Dev, Cambridge, MA 02142 USA

[2] Amgen Inc, Dept Analyt Res & Dev, Cambridge, MA 02142 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2010年 / 132卷 / 44期

关键词：

ASYMMETRIC HYDROGENATION; INHIBITORS; AGONIST; DESIGN;

D O I：

10.1021/ja107709w

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A general inversion-stereospecific, N-selective alkylation of substituted 2-pyridones (and analogues), amides, and carbamates using chiral alpha-chloro- or bromocarboxylic acids in the presence of KOt-Bu (or KHMDS) and Mg(Ot-Bu)(2) is reported. The resulting a-chiral carboxylic acid products were isolated by crystallization in good chemical yields and in high ee (>90% ee). Mechanistic evidence suggests that the reaction proceeds through 2-pyridone O-coordinated Mg carboxylate intermediates, which afford the product through an intramolecular S(N)2 alkylation.

引用

页码：15525 / 15527

页数：3