BIS ANNELATIONS VIA 6-METHYL-2-VINYLPYRIDINE - EFFICIENT SYNTHESIS OF D,L-D-HOMOESTRONE
BIS ANNELATIONS VIA 6-METHYL-2-VINYLPYRIDINE - EFFICIENT SYNTHESIS OF D,L-D-HOMOESTRONE
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DOI：
10.1021/ja00835a028
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发表时间：
1975-01-01
影响因子：
15
通讯作者：
NAGEL, A
中科院分区：
文献类型：
--
作者：
DANISHEFSKY, S;CAIN, P;NAGEL, A
证明了6-甲基-2-乙烯基吡啶与3-乙烯基环己-2-烯-1-酮的合成等效性。乙烯基甲基吡啶在a位通过迈克尔加成与酮相连。以6-位上带有RCH_2取代基的2-甲基吡啶为原料，经金属氨还原、水解、羟醛缩合反应，合成了3-位上带有RCH_2取代基的2-环己烯-1-酮。描述了通过这种策略将Wieland-Miescher酮有效转化为iTZ-D-高雌酮。甲基乙烯基酮（MVK）构建环己烯酮2 - 4的方法中固有的合成逻辑在多环天然产物的合成中得到了广泛的应用。虽然在这一战略的框架中引入了各种各样的变化，但这种融合的特点是两个阶段。第一个涉及烯醇化物（或烯醇）亲核试剂与亲电子末端（E）的结合。该试剂被构造成使得含碳官能团X可转化为酮。在最后阶段，1，5-己二酮系统进行分子内羟醛缩合。在这种环化反应中，亲核烯醇化物（或烯醇）衍生自螯合剂，而受体羰基则来自最初的亲核试剂。这些修改主要涉及亲电末端性质的变化和解开环化所需的1，5-己二酮的新方法。鹳学校的研究6a_d已被部分-
The synthetic equivalence of 6-methyl-2-vinylpyridine with 3-vinylcyclohex-2-en-l-one has been demonstrated. The vinylpicoline is attached at theposition a to a ketone by Michael addition. The cyclohex-2-en-l-one system bearing the substituent RCH2 at the3-position is elaborated from the 2-picoline bearing the substituent RCH2 at the6-position by a se-quence involving metal-ammonia reduction, hydrolysis, and aldolization. An efficient conversion of the Wieland-Miescher ketone to iTZ-D-homoestrone, via this strategy is described.The synthetic logic inherent in the methyl vinyl ketone (MVK) approach to the construction of cyclohexenones2" 4 has found extensive application in the synthesis of polycyclic natural products. While a wide assortment of variations has been introduced into the framework of this strategy, such annelations are characterized bytwo stages. The first involves the merger of an enolate (or enol) nucleophile with the electrophilic terminus (E) of an annelating agent. The agent is so constructed that the carbon-bearing function X is transformable to a ketone. In the final stage, a 1, 5-hexanedione system undergoes intramolecular aldolization. In this cyclization, the nucleophilic enolate (or enol) is derived from the annelating agent, while the receptor carbonyl group arises from what was originally the nucleophile. The modifications have dealt primarily with variations in the nature of the electrophilic terminus and with new meth-ods for unraveling the 1, 5-hexanedione requiredfor cyclization. The researches of the Stork school6a_d have been par-