Conversion of five-, six-, and seven-membered lactams to racemic or scalemic 2-substituted heterocycles by amidoalkylation.
Conversion of five-, six-, and seven-membered lactams to racemic or scalemic 2-substituted heterocycles by amidoalkylation.
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通过酰胺烷基化将五元、六元和七元内酰胺转化为外消旋或鳞片2-取代杂环。
DOI：
10.1021/jo048484v
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Gawley,RobertE
中科院分区：
文献类型：
--
作者：
Madan,Sachin;Milano,Peter;Eddings,DanielB;Gawley,RobertE
提出了一种从外消旋或对映体纯形式的内酰胺合成 2-烷基-和 2-芳基吡咯烷、哌啶和氮杂环庚烷的有效方法。内酰胺氮被 Boc 酸酐或反式枯基环己基 (TCC) 氯甲酸酯酰化。将内酰胺羰基选择性还原为甲醇酰胺，然后用苯并三唑处理。苯并三唑的取代是通过用有机金属化合物处理来完成的，产生2-取代的杂环。使用 TCC，可实现高达 90% 的非对映选择性。非对映异构体纯化后，还原除去助剂，得到对映体纯的2-取代杂环。提出了一个机制假设，详细说明了关键步骤的构象平衡。
An efficient method for the synthesis of 2-alkyl- and 2-aryl pyrrolidines, piperidines, and azepanes from lactams, in either racemic or enantiopure form, is presented. The lactam nitrogens are acylated with either Boc anhydride ortrans-cumylcyclohexyl (TCC) chloroformate. Selective reduction of the lactam carbonyl to the carbinolamide is followed by treatment with benzotriazole. Substitution of the benzotriazole is accomplished by treatment with organometallics, yielding the 2-substituted heterocycles. With TCC, up to 90% diastereoselectivity is achieved. After diastereomer purification, reductive removal of the auxiliary affords enantiopure 2-substituted heterocycles. A mechanistic hypothesis is presented that details the conformational equilibria of the key step.