Enantioselective synthesis of cyclic amides and amines through Mo-catalyzed asymmetric ring-closing metathesis
Enantioselective synthesis of cyclic amides and amines through Mo-catalyzed asymmetric ring-closing metathesis
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DOI：
10.1021/ja051330s
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发表时间：
2005-06-15
影响因子：
15
通讯作者：
Hoveyda, AH
中科院分区：
文献类型：
--
作者：
Sattely, ES;Cortez, GA;Hoveyda, AH
首先，报道了一种合成光富集n -聚变双环结构的有效方法。通过mo催化的非手性多烯底物的反对称反应，5,6-,5,7-和5,8-双环酰胺可以在高达> 98%的ee下合成。考察并详细讨论了催化剂结构、烯烃取代、路易斯官能团位置和环尺寸等因素对反应的影响。在研究的第二阶段，报道了一种催化不对称方法，用于高度对映选择性（高达97% ee）合成中小环不饱和环胺；光学富集的产品具有仲胺或易于去除的Cbz或乙酰胺单元。在光学富集的胺产物中进行了烯烃的区域选择性和非立体选择性功能化。两种催化不对称方法都包括导致形成三取代环烯烃和二取代环烯烃的转化。本文概述的方案提供各种高光学纯度的环胺；这些产物不容易通过替代方案获得，并且可以用于生物活性分子的对映选择性全合成。
First, an efficient method for the synthesis of optically enriched N-fused bicyclic structures is reported. Through Mo-catalyzed desymmetrization of readily available achiral polyene substrates, 5,6-, 5,7-, and 5,8-bicyclic amides can be synthesized in up to > 98% ee. The effects of catalyst structure, olefin substitution, positioning of Lewis basic functional groups and ring size are examined and discussed in detail. In the second phase of investigations, a catalytic asymmetric method for highly enantioselective (up to 97% ee) synthesis of small- and medium-ring unsaturated cyclic amines is reported; optically enriched products bear a secondary amine or a readily removable Cbz or acetamide unit. Regio- and diastereo-selective functionalizations of olefins within the optically enriched amine products have been carried out. Both catalytic asymmetric methods include transformations that lead to the formation of trisubstituted as well as disubstituted cyclic alkenes. The protocols outlined herein afford various cyclic amines of high optical purity; such products are not easily accessed by alternative protocols and can be used in enantioselective total syntheses of biologically active molecules.