铜催化的碳-碳键偶联反应构建芳基取代的季碳中心

The skeleton of alpha-aryl quaternary carbon of carbonyl compounds widely exist in many natural products and pharmaceutically important molecules. It is very important to construct this type of quaternary carbon center. As an extension of our research work on copper-catalyzed Ullmann-type coupling reaction,alpha-aryl quaternary carbon of carbonyl compounds would be constructed by copper salt/ligand-promoted C-C bond cross-coupling reaction from aryl halides and alpha-substituted active CH-acid compounds as well as related carbonyl compounds. Furthermore, enantioselective synthesis for this type of quaternary carbon center would be investigated by using chiral ligand or chiral copper salt complex. The applications of our method in the preparation of natural products and bioactive compounds would be attempted.

羰基化合物的alpha-位为芳基取代的季碳骨架存在于许多天然产物和药物活性分子结构中。发展构建羰基alpha-位芳基取代季碳，甚至手性季碳的方法非常重要。本项目在课题组长期以来对铜催化偶联反应的研究基础上，通过对铜催化的芳基卤代物和合适的羰基化合物的C-C键偶联反应研究，发展有效的构建羰基alpha-位芳基取代季碳的方法，进一步通过手性配体或手性铜盐复合物的引入，实现该类季碳中心对映选择性的合成。发展的有效方法将尝试用于相关天然产物和活性分子的合成。

采用项目所在课题组发展的一代氨基酸及相关杂环羧酸配体，考察了铜催化的-取代的活泼亚甲基化合物如2-取代乙酰乙酸乙酯、2-取代氰基乙酸乙酯、2-取代丙二酸二乙酯等的芳基卤代物的偶联反应，发展了相关有效的催化体系用于-位芳基取代季碳及相关重要的杂环骨架的构建。. 在研究过程中项目所在课题组发现了高效的二代草酸酰胺配体，合成了系列草酸酰胺配体用于C-C-键偶联反应的筛选。采用新一代草酸酰胺配体进一步考察了铜催化的-取代的活泼亚甲基化合物如2-取代乙酰乙酸乙酯、2-取代氰基乙酸乙酯、2-取代丙二酸二乙酯等的芳基卤代物的偶联反应，实现了芳基氯代物与与2-烷基氰乙酸乙酯的偶联并合成了一系列3,3-二取代-2-氨基-3H-吲哚。. 进一步的研究工作仍在继续。