Enantioselective synthesis of trans-4-methylpipecolic acid
Enantioselective synthesis of trans-4-methylpipecolic acid
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DOI：
10.1021/jo071220z
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发表时间：
2007-09-28
影响因子：
3.6
通讯作者：
Riera, Antoni
中科院分区：
文献类型：
--
作者：
Alegret, Carlos;Santacana, Ferran;Riera, Antoni
[图示]描述了制备反式甲基哌啶酸的两种对映体的不对称合成。它基于 Sharpless 环氧化作为手性源，用烯丙胺进行区域选择性开环，并通过闭环复分解来构建哌啶环。 C-4 处的立体中心是通过立体选择性氢化作用设定的，该氢化作用由中间体的醇官能团引导，并在良好的非对映体控制下进行（反式/顺式 16/1）。 Boc 保护的氨基酸的结晶使目标产物具有优异的化学纯度 (98% de) 和对映体纯度 (99% ee)。
[GRAPHICS]An asymmetric synthesis for the preparation of both enantiomers of trans-methylpipecolic acids is described. It is based on Sharpless epoxidation as a chirality source, regioselective ring opening with allylamine, and ring-closing metathesis to construct the piperidine ring. The stereogenic center at C-4 is set by stereoselective hydrogenation that is directed by the alcohol functionality of an intermediate and proceeds with good diastereomeric control (trans/cis 16/1). Crystallization of the Boc-protected amino acid afforded the target products with excellent chemical (98% de) and enantiomeric purity (99% ee).