亚胺离子促进的炔-羰复分解反应研究

The alkyne-carbonyl metathesis based on a [2+2] cycloaddition/cycloreversion strategy provides an attractive method for the construction of conjugated enone substructures and cyclic systems, owing to its environmentally benign and atom-efficient features. Despite this reaction has been established for decades, but only a handful of successful studies have been reported to date, largely due to the relatively low reactivity of the carbonyl group and the carbon-carbon triple bond that greatly impedes the occurrence of the reaction. The utility of this chemistry in organic synthesis is still a challenge and often hampered by the need for special starting materials or the use of expensive and toxic metallic salts as catalysts. In this project, we planned to develop a new catalytic protocol for the alkyne-carbonyl metathesis by combining an amine with a Lewis or Brønsted acid catalyst, which will provide an efficient and sustainable methodology for the construction of carbon-carbon bonds and cyclic ring systems. To the best of our knowledge, the alkyne-carbonyl metathesis involving an in situ formed iminium ion, instead of the carbonyl group, acting as the reactive intermediate has not been investigated previously. This study will not only enrich the catalytic methods for alkyne-carbonyl metathesis, but also lay a foundation for the atom-economical synthesis of important organic intermediates and complicated molecular skeletons.

由于环境友好而且具有很高的原子效率，基于[2+2]环加成/环裂解策略的炔-羰复分解反应为构建烯酮结构和环状体系提供了一条非常具有吸引力的途径。虽然这一反应的发现已有几十年，但到目前为止，只有少量成功的研究被报道，主要是由于羰基和碳碳叁键弱的反应活性严重阻碍了反应的发生。这一反应经常需要使用特殊的反应底物或者昂贵有毒的金属催化剂，这影响了反应的广泛应用。应用炔-羰复分解反应进行有机合成目前还是一个具有挑战性的工作。本申请项目将对有机小分子胺和路易斯酸或质子酸共催化的炔-羰复分解反应开展研究，发展高效、环境友好的构建碳碳键及环状化合物的方法。利用原位生成的亚胺离子活化羰基进行的炔-羰复分解反应未见研究报道，本项目的研究内容可以丰富炔-羰复分解反应的催化类型，并为原子经济性地合成重要有机中间体和复杂分子骨架提供研究基础。

发展高效方法和策略构建碳环及杂环化合物是有机化学的重要研究领域。在这一领域，复分解反应和串联反应的研究成果极大地拓展了化学家研究有机分子的手段，也为简洁、高效地合成药物分子、材料和其它化学品奠定了基础。在本基金项目中，我们通过对炔-羰复分解和串联反应的研究，发展了一系列新颖的构建碳环、杂环和芳环体系的反应方法和催化体系。这些反应具有很高的原子经济性和步数经济性，大多生成水为副产物，环境友好；同时我们发展的方法具有操作简单、底物普适性好、合成效率高等特点。本课题的研究成果可以丰富炔-羰复分解和串联反应在有机合成中的应用，并为高效合成具有良好应用价值的多环芳烃、联苯、茚、芴、苯并芴、吖啶、吡喃、吡咯并异喹啉、N,O-九元杂环、[6,n]碳环化合物提供新的方法和策略。