Enantiocontrolled synthesis of 2,6-disubstituted piperidines by desymmetrization of meso-n-(3,4,5)-dihydropyridinylmolybdenum complexes.: Application to the total synthesis of (-)-dihydropinidine and (-)-andrachcinidine
Enantiocontrolled synthesis of 2,6-disubstituted piperidines by desymmetrization of meso-n-(3,4,5)-dihydropyridinylmolybdenum complexes.: Application to the total synthesis of (-)-dihydropinidine and (-)-andrachcinidine
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DOI：
10.1021/ja029537y
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发表时间：
2003-03-12
影响因子：
15
通讯作者：
Liebeskind, LS
中科院分区：
文献类型：
--
作者：
Shu, CT;Liebeskind, LS
通过meso-2，6-二甲氧基-η-（3，4，5）-二氢吡啶钼配合物的去对称化反应，实现了对映体控制合成2，6-二取代哌啶的新方法。在（+）-或（-）-反式-2-（α-枯基）环己基（TCC）的哌啶氮被保护成氨基甲酸酯后，通过一锅法进行甲醇提取/亲核加成/甲醇提取/亲核加成，得到了高产率的2，6-二取代-η-（3，4，5）-二氢吡啶基钼配合物。该序列通过高度非对映选择性的甲醇提取（>40：1）进行。高产率的质子脱金属和N-脱保护提供了一个简单的和对映体控制的合成路线，以各种2，6-二取代哌啶。该方法已用于（-）-二氢匹尼定和（-）-andrachcinidine的全合成。
A conceptually new approach to the enantiocontrolled synthesis of 2,6-disubstituted piperidines was achieved by desymmetrization ofmeso-2,6-dimethoxy-η-(3,4,5)-dihydropyridinylmolybdenum complexes. After protection of the piperidine nitrogen as a urethane derived from (+)- or (−)-trans-2-(α-cumyl)cyclohexyl (TCC), a sequential, one-pot methoxide abstraction/nucleophilic addition/methoxide abstraction/nucleophilic addition generated good yields of 2,6-disubstituted-η-(3,4,5)-dihydropyridinylmolybdenum complexes. This sequence proceeds by way of a highly diastereoselective methoxide abstraction (>40:1). High yielding protodemetalation and N-deprotection provided a simple and enantiocontrolled synthetic entry to a variety of 2,6-disubstituted piperidines. This new method was used for the total synthesis of (−)-dihydropinidine and (−)-andrachcinidine.