价廉金属催化环烷烃经烯丙基金属络合物参与的不对称环加成反应

Nobel metal catalyzed cycloadditions of cycloalkane via zwitter ionic pi-allylmetal complex received great attentions over the past years. However, the reaction is very limited in substrate scope and it is very difficult to control the selectivity especially diastereoselectivity of the reaction. In the project, the cheap metal catalyzed enantioselective cycloadditions of vinyl cycloalkanes (cyclopropanes and cyclobutanes and derivatives) with small ring are expected to be realized. By the choice of suitable metals and chiral ligands, the modification of substrate as well as the double activation in which both cycloalkanes and dipoles are activated by different catalysts respectively, the steric or electron effect is tuned and both the reactivity and selectivity of the reaction would be controlled. The structurally and optically enriched cyclohexane or cyclopentane derivatives are thus available. The stereoslective cycloadditions of vinyl cycloalkanes and imines, aldehydes, electro-deficient alkenes as well as the transient formed imines are to be investigated. The reaction mechanism is further elucidated based on the reaction dynamics, and the new synthetic methodologies are to be developed and applied in the total synthesis of complicated organic compounds.

钯催化环烷烃经两性烯丙基金属络合物参与的环加成反应取得了重要的进展，但反应底物严重受限、反应选择性尤其是非对映选择性难以控制。本项目旨在发展价廉金属催化具有环张力的乙烯基环状烷烃如环丙烷、环丁烷及其衍生物经两性烯丙基金属络合物参与的高选择性环加成反应。通过选择合适的价廉金属催化剂和手性配体、对反应底物进行结构修饰以及在反应中加入布朗斯特酸等添加剂对反应底物进行双活化等方法调节反应的立体和电子效应，控制反应的选择性包括对映选择性和非对映选择性，实现具有环张力的环状烷烃如环丙烷、环丁烷及其衍生物经过两性烯丙基金属络合物中间体与亲偶极体如亚胺、醛、富烯、缺电子烯烃以及原位生成亚胺的高选择性环加成反应；探讨高度官能化、光学活性环戊烷及环己烷衍生物的快速、简洁、高效合成方法。利用现代方法研究反应的动力学，阐述其反应机理，发展有机合成方法学，为复杂化合物的合成提供方法学基础。

本项目成功实现了以简单的手性亚膦酰胺作为配体，在金属钯的催化下，实现了乙烯基环丙烷与亚胺的不对称环加成反应，底物范围既适用于醛亚胺，也适应于酮亚胺；实现了手性铑催化吲哚重氮化合物与富电子二烯(Danishefsky diene)二烯的形式上不对称[4+1]环加成反应得到了光学活性吲哚螺环戊烯酮及其衍生物，而当重氮化合物为-重氮苯基乙酸酯时，手性二烯铑络合物催化剂催化反应得到含有一个手性碳的环戊烯酮化合物，以此方法首次合成了光学活性的(−)-1,13-Herbertenediol；以手性铜-噁唑啉衍生物或手性铜双膦络合物为催化剂实现了二芳基甲亚基苯醌或芳基芳甲基甲亚基苯醌的1，6-不对称还原反应，得到了最高96% ee的用其他方法难以合成的高度光能化的三芳基甲烷或乙烷化合物。