Stereocontrolled synthesis of Carbocyclic Compounds with a Quaternary Carbon Atom based on SN2' Alkylation of γ,δ-Epoxy-α,β-unsaturated Ketones
Stereocontrolled synthesis of Carbocyclic Compounds with a Quaternary Carbon Atom based on SN2' Alkylation of γ,δ-Epoxy-α,β-unsaturated Ketones
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基于γ,δ-环氧-α,β-不饱和酮的SN2烷基化立体控制合成季碳碳环化合物
DOI：
10.1039/c2ob25719j
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发表时间：
2012
影响因子：
3.2
通讯作者：
ほか1名
中科院分区：
文献类型：
--
作者：
谷野圭持、吉村文彦;ほか1名
基于γ，δ-环氧-α，β-不饱和环酮的SN 2 ′烷基化反应，发展了一种立体选择性地在碳环上构筑全碳季胺立体中心的新方法.通过3-乙氧基-2-环烯酮与α，β-环氧醛的羟醛缩合反应，可以得到对映体纯的酮，用R2 Zn-CuCN试剂处理，立体选择性地得到反SN 2 ′产物。相反，通过两步转化相同的γ，δ-环氧-α，β-不饱和环酮，可以立体选择性地获得相应的syn-SN 2 ′产物：（1）通过MgCl 2处理将环氧部分转化为氯醇，（2）随后用R2 Zn-CuCN试剂对氯醇进行SN 2 ′取代。这些具有手性反式烯丙醇结构的取代产物是合成复杂分子的理想前体。例如，取代产物之一的Rehenmoser-Claisen重排导致立体选择性地形成具有连续的季和叔立体中心的酮酰胺。
We developed a new method for stereoselective construction of an all-carbon quaternary stereogenic center on a carbocyclic ring based on regio- and stereoselective SN2′ alkylation reactions of γ,δ-epoxy-α,β-unsaturated cyclic ketones. Treatment of the ketones, which were readily prepared in enantiomerically pure form by means of aldol condensations between 3-ethoxy-2-cycloalkenones and α,β-epoxy aldehydes, with a R2Zn–CuCN reagent afforded anti-SN2′ products stereoselectively. Conversely, the corresponding syn-SN2′ products were stereoselectively obtained through two-step transformations of the same γ,δ-epoxy-α,β-unsaturated cyclic ketones: (1) conversion of the epoxide moiety to a chlorohydrin by treatment with MgCl2 and (2) subsequent SN2′ substitution of the chlorohydrin with a R2Zn–CuCN reagent. These substitution products with their chiral trans-allylic alcohol moieties are promising precursors for complex molecules. For example, Eschenmoser–Claisen rearrangement of one of the substitution products resulted in stereoselective formation of a keto amide having contiguous quaternary and tertiary stereogenic centers.