General one-pot reductive gem-bis-alkylation of tertiary lactams/amides: rapid construction of 1-azaspirocycles and formal total synthesis of (±)-cephalotaxine.
General one-pot reductive gem-bis-alkylation of tertiary lactams/amides: rapid construction of 1-azaspirocycles and formal total synthesis of (±)-cephalotaxine.
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DOI：
10.1002/chem.201302096
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发表时间：
2013-09
期刊：
影响因子：
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通讯作者：
Kai-Jiong Xiao;Jie Luo;Xiao-Er Xia;Yu Wang;Pei‐Qiang Huang
中科院分区：
文献类型：
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作者：
Kai-Jiong Xiao;Jie Luo;Xiao-Er Xia;Yu Wang;Pei‐Qiang Huang
酰胺是一类高度稳定、易得的化合物。酰胺官能团构成了一类对C-C键形成具有强大指导/激活和保护作用的基团。叔烷基胺，包括1-氮杂螺环，是许多生物活性天然产物和药物的关键结构特征。酰胺转化为叔烷基胺通常需要几个步骤。本文报道了叔内酰胺/酰胺直接转化为叔烷基胺的第一种一般方法的全部细节。该方法是基于三酸酐/2,6-二叔丁基-4-甲基吡啶（DTBMP）原位活化酰胺，然后连续添加两种相同或不同种类的有机金属试剂，形成两个C-C键。烷基和功能化的有机金属试剂和烯醇化物都可以作为亲核试剂。该方法具有良好的1,2-和1,3-不对称诱导效果。从内酰胺中直接合成1-氮杂螺环仅需两步甚至一步。该方法的力量被证明了简洁正式的全合成外消旋头孢他啶。
Amides are a class of highly stable and readily available compounds. The amide functional group constitutes a class of powerful directing/activating and protecting group for C-C bond formation. Tertiary tert-alkylamine, including 1-azaspirocycle is a key structural feature found in many bioactive natural products and pharmaceuticals. The transformation of amides into tert-alkylamines generally requires several steps. In this paper, we report the full details of the first general method for the direct transformation of tertiary lactams/amides into tert-alkylamines. The method is based on in situ activation of amide with triflic anhydride/2,6-di-tert-butyl-4-methylpyridine (DTBMP), followed by successive addition of two organometallic reagents of the same or different kinds to form two C-C bonds. Both alkyl and functionalized organometallic reagents and enolates can be used as the nucleophiles. The method displayed excellent 1,2- and good 1,3-asymmetric induction. Construction of 1-azaspirocycles from lactams required only two steps or even one-step by direct spiroannelation of lactams. The power of the method was demonstrated by a concise formal total synthesis of racemic cephalotaxine.