Catalytic three-component coupling of alkynes, imines, and organoboron reagents.
Catalytic three-component coupling of alkynes, imines, and organoboron reagents.
复制标题
DOI：
10.1002/anie.200390349
复制
发表时间：
2003-03
影响因子：
--
通讯作者：
Sejal J. Patel;T. Jamison
中科院分区：
文献类型：
--
作者：
Sejal J. Patel;T. Jamison
作为我们对选择性催化多组分反应的兴趣的一部分，[1]我们报道了一种前所未有的烯丙基胺从三种简单的取代基--炔、亚胺和有机硼试剂（硼酸或有机硼烷）的催化组装。由于烯丙基胺是各种重要的天然分子[2]和药物[3]中的关键结构元素，并且是合成其他重要分子中最通用的中间体之一[4]，因此它们引起了广泛的关注。[5]以前，已经描述了几种Ni催化的涉及羰基化合物加成的多组分偶联反应。[1a本文所述的方法是涉及亚胺的第一个这样的实施例，也是第一个利用硼酸的实施例（方案1）。[7]我们的初步调查也支持一个机制框架，占在这些反应中观察到的高选择性。亚胺相对于醛的亲电性显著降低[8]在我们的初始实验中提出了重大挑战。在对不同的亚胺、[9]溶剂[10]和有机金属试剂[11]进行了广泛的研究后，我们观察到了有机硼试剂和羟基溶剂同时使用时的异常结果。[12]特别是甲醇提供了产率的显著增加，并且还显示出对烷基化偶联产物1相对于还原偶联产物2的高选择性（表1）。[13]当使用乙酸甲酯作为共溶剂并且使用富电子的三-（仲烷基）-膦配体时，获得最佳结果（表1，条目3和4）。[14]如表2中所总结的，涉及具有至少一个烷基取代基的内部炔的反应通常是高度选择性的，并且在某些情况下观察到几乎定量的产率（1c和1f）。衍生自脂肪族醛的亚胺也经历三个-
As part of our interest in selective, catalytic multicomponent reactions,[1] we report an unprecedented catalytic assembly of allylic amines from three simple precursors—alkynes, imines, and organoboron reagents (boronic acids or organoboranes). As allylic amines are key structural elements in a variety of important naturally occurring molecules [2] and pharmaceuticals [3] and are among the most versatile intermediates in the synthesis of other important molecules,[4] they have attracted much attention.[5] Previously, several Ni-catalyzed multicomponent coupling reactions involving additions to carbonyl compounds have been described.[1a, 6] The process described herein is the first such example involving imines and also the first that utilizes boronic acids (Scheme 1).[7] Our preliminary investigations also support a mechanistic framework that accounts for the high selectivities observed in these reactions. The markedly diminished electrophilicity of imines relative to aldehydes [8] presented significant challenges in our initial experiments. After extensive studies with different imines,[9] solvents,[10] and organometallic reagents,[11] we observed exceptional results when both organoboron reagents and hydroxylic solvents were employed.[12] Methanol in particular provided substantial increases in yield, and also displayed high selectivity for alkylative coupling product 1 over reductive coupling product 2 (Table 1).[13] Best results were obtained when methyl acetate was used as a cosolvent and electron-rich, tri-(sec-alkyl)-phosphane ligands were employed (Table 1, entries 3 and 4).[14] As summarized in Table 2, reactions involving internal alkynes with at least one alkyl substituent are typically highly selective, and nearly quantitative yields are observed in some cases (1c and 1 f). Imines derived from aliphatic aldehydes also undergo three-