Intramolecular "hydroiminiumation" of alkenes: Application to the synthesis of conjugate acids of cyclic alkyl amino carbenes (CAACs)
Intramolecular "hydroiminiumation" of alkenes: Application to the synthesis of conjugate acids of cyclic alkyl amino carbenes (CAACs)
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DOI：
10.1002/anie.200605083
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Bertrand, Guy
中科院分区：
文献类型：
--
作者：
Jazzar, Rodolphe;Dewhurst, Rian D.;Bertrand, Guy
多年来，含氮杂环体系引起了人们极大的兴趣，因为它们构成了天然产物的核心结构，并且是天然产物的关键中间体。 [1]最有吸引力的制备方法之一是烯烃的分子内氢胺化，其中氮-碳键是通过将胺加成到烯烃上而形成的。 [2]各种催化剂已被用来实现这种转变，其中包括碱金属[3]早期[4]和晚期过渡金属[5]和f区元素。[6]有趣的是，尽管胺具有缓冲作用，但分子内[7]甚至分子间[8]酸催化的氢胺化反应最近已被开发出来。 Schlummer 和 Hartwig [7a] 报道了通过三氟甲磺酸或硫酸（20 mol%；方案 1）催化，氮原子上带有吸电子基团的氨基烯烃的环化。对这一过程的机理研究表明，与使用各种亲电子试剂作为促进剂（例如碘、[9]溴、[10]和硒基亲电子试剂[11]）的类似转化相反，第一步是胺的质子化，然后在速率决定步骤中将质子分子内转移到双键，最后由氨基捕获生成的阳离子。因此，在氮原子上不存在吸电子基团的情况下，由于氨基的碱性过高，环化不会发生，从而阻止了质子向烯烃的转移。亚胺的碱性肯定低于胺，因此决定研究“加氢亚胺化”反应的可行性，这将是制备环状亚胺盐A的原子经济途径（方案1）。如果氮原子上有一个大的芳基取代基，并且在铝亚胺碳原子的 α 位有一个季碳原子，则盐 A' 是稳定的环烷基氨基卡宾 (CAAC) B 的直接前体。 [12]我们已经证明，CAAC 可以与 N-杂环卡宾 (NHC) [13] 竞争作为过渡金属基催化剂的配体，[12a] 并且还可以制备非常低配位的过渡金属中心。 [12b] 我们在此报告了关于热诱导加氢亚胺化反应范围及其在各种 CAAC 前体合成中的应用的初步结果。
Nitrogen-containing heterocyclic systems have attracted considerable interest over the years because they form the core structures, and are key intermediates, of natural products.[1] One of the most appealing synthetic approaches for their preparation is the intramolecular hydroamination of alkenes, in which the nitrogen–carbon bond is formed by addition of an amine to an olefin.[2] Various catalysts have been used to effect this transformation, which include alkali metals,[3] early [4] and late transition metals,[5] and f-block elements.[6] Interestingly, despite the buffering effect of amines, intramolecular [7] and even intermolecular [8] acid-catalyzed hydroaminations have recently been developed. Schlummer and Hartwig [7a] reported the cyclization of amino alkenes bearing an electron-withdrawing group on the nitrogen atom by catalysis with triflic or sulfuric acid (20 mol%; Scheme 1). A mechanistic study of this process suggested that in contrast to similar transformations using various electrophiles as promoters (for example, iodine-,[9] bromine-,[10] and selenium-based electrophiles [11]), the first step was protonation of the amine, followed by intramolecular transfer of the proton to the double bond in the rate-determining step, and lastly trapping of the generated cation by the amino group. Accordingly, in the absence of electron-withdrawing groups on the nitrogen atom, the cyclization does not occur because of the excessive basicity of the amino group, which prevents the transfer of the proton to the olefin.Imines are certainly less basic than amines, and therefore it was decided to investigate the feasibility of “hydroiminiumation” reactions, which would be an atom-economical route to cyclic iminum salts A (Scheme 1). Providing there is a bulky aryl substituent on the nitrogen atom and that there is a quaternary carbon atom in the position α to the aldiminium carbon atom, salts A′ are the direct precursors of stable cyclic alkyl amino carbenes (CAACs) B.[12] We have shown that CAACs can compete with N-heterocyclic carbenes (NHCs)[13] as ligands for transition-metal-based catalysts,[12a] and also allow the preparation of very low coordinate transition-metal centers.[12b] We report herein our preliminary results on the scope of the thermally induced hydroiminiumation reaction and its application to the synthesis of a variety of CAAC precursors.