钴催化还原二卤甲烷非稳定卡宾转移(不对称)环丙烷化反应

  环丙烷是最小的环状有机化合物之一，具有全碳平面三元环结构、高度的环张力以及独特的化学性质和物理性质。手性环丙烷在有机合成和药物设计中具有重要的应用。不仅天然产物分子和众多商业化药物分子含有对其生物活性有重要影响的手性环丙烷结构单元，而且具有较高反应活性的手性环丙烷化合物作为合成子也被应用于天然产物和生物活性小分子的合成。因此，发展高效、高对映选择性的不对称催化合成手性环丙烷化合物的方法和策略，是不对称催化研究领域的科学问题之一，不仅具有非常重要的科学意义，而且也有潜在的工业应用价值，一直是化学家的研究兴趣和有机合成的重要研究方向。由于环丙烷的高度环张力，手性环丙烷的高效不对称催化合成依然十分具有挑战性。本课题研究通过发展手性配体和催化剂来调控反应立体选择性，在还原剂作用下，实现过渡金属钴催化还原二卤甲烷形成金属类卡宾，再经历类似Simmons-Smith机制转移非稳定卡宾与烯烃反应形成手性环丙烷。本文研究主要包括两部分内容：

  （1）设计合成了一系列含N,N,N-三齿手性配体，并成功应用于过渡金属Co催化还原二溴甲烷与α,β-不饱和羰基化合物非稳定卡宾的不对称环丙烷化反应，以高产率（85-98%）和中等至优秀对映选择性（62-96% ee）得到手性环丙烷产物。该反应体系适用于α,β-不饱和酮、酯、酰胺底物，有20个底物被成功构建手性环丙烷化合物。对非导向苯乙烯类内烯烃的不对称催化还原卡宾转移环丙烷化反应也进行了初步研究，最高可以获得80% ee。

  （2）利用吡啶二亚胺配体/过渡金属作为催化剂，在还原剂锌的作用下，催化还原廉价易得二氯甲烷与二烯化合物的非稳定卡宾转移环丙烷化反应，高效合成含环丙烷的高能量密度燃料化合物。降冰片二烯进行反应能以优秀的产率（大于99%）得到双环丙烷产物，并且环戊二烯同样适用于该反应体系，以优秀（大于99%）产率得到双环丙烷化合物。当使用4 mol%的催化剂，反应底物放大至10 mmol时，降冰片二烯与双环戊二烯也能以优秀的产率得到双环丙烷化合物。

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