新型手性叔膦催化联烯与甲基酮亚胺/烯胺之间的不对称[4+1]环加成反应

本项目针对手性环状烯胺酮和含全碳季碳中心的β-酮亚胺等重要化合物的合成难题，围绕叔膦催化环加成反应，突破现有反应模式，通过发展新型双功能手性氨基叔膦催化剂，建立实用型高效、高立体选择性均相催化环加成反应。基于此，本项目将完成以下研究工作：（1）基于本课题组前期发展的新型1,3-二醇骨架分子，经三步反应合成含多手性中心和取代基易微调的手性氨基叔膦催化剂；（2）利用极性反转策略，发展手性叔膦催化联烯酰亚胺与甲基酮亚胺/烯胺之间的不对称[4+1]环加成反应，重点解决反应产率和立体选择性问题；（3）结合催化产物的绝对构型，以及基于密度泛函理论和非共价键作用力的理论计算，建立催化反应的过渡态模型，理解手性传递放大机制与规律；（4）考察催化产物的合成应用，为相关手性杂环化合物提供合成新思路。最终希望在完成本项目工作的基础上，发展其它类型不对称[4+n]环加成反应，解决更多重要骨架分子的合成难题。

In order to develop novel highly efficient, stereoselective and practical homogeneous catalysis system, we herein will address two key research problems including the synthesis of chiral cyclopentenoyl enamine and imine motifs based on the unprecedented phosphine-catalyzed asymmetric [4+1] cycloadditions of an allenyl imides and methyl ketimines/enamines, as well as understanding the related reaction mechanism and origin of stereochemistry. In this context, new chiral amino tertiary phosphine catalysts are designed and to be synthesized through three steps by using 1,3-diol starting materials developed by our own group. The application of the new chiral phosphine catalysts in the asymmetric [4+1] cycloadditions of allenyl imides and methyl ketimines/enamines is to be launched, which will provide access to target chiral cyclopentenoyl enamines and imines containing an all-C quaternary stereogenic center in satisfactory yields and ee’s. Density functional theory (DFT) and non-covalent interaction (NCI) calculations will be carried out to understand the stereochemistry. The synthetic utility of this new chemistry will be also exhibited. Founded on this new synthetic strategy, novel asymmetric [4+n] cycloadditions of allenyl imides and other reaction components can be anticipated.