Magnesium Coordination-Directed N-Selective Stereospecific Alkylation of 2-Pyridones, Carbamates, and Amides Using α-Halocarboxylic Acids
Magnesium Coordination-Directed N-Selective Stereospecific Alkylation of 2-Pyridones, Carbamates, and Amides Using α-Halocarboxylic Acids
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DOI：
10.1021/ja107709w
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发表时间：
2010-11-10
影响因子：
15
通讯作者：
Clausen, Andrew
中科院分区：
文献类型：
--
作者：
Fang, Yuan-Qing;Bio, Matthew M.;Clausen, Andrew
在KOt-Bu（或KHMDS）和Mg（Ot-Bu）的存在下，用手性-氯或溴羧酸对取代的2-吡啶酮（和类似物）、酰胺和氨基甲酸酯进行了一般的逆立体定向、n选择性烷基化反应(2)。通过结晶分离得到的a-手性羧酸产物，收率高，ee高（> - 90% ee）。机理证据表明，该反应通过2-吡啶酮o配位羧酸镁中间体进行，使产物通过分子内S(N)2烷基化。
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.