新型手性伯胺催化剂的设计优化及其在不对称alpha-支链酮催化转化中的应用

With an aim to developing a "privileged" chiral primary amine catalyst, this project focuses on the further evolution of our de novo designed chiral primary amine catalyst by merging with supramolecular or redox tuning strategy. By doing so, we hope to address the daunting challenge always associated with aminocatalysis such as low efficiency, poor applicability and lack of diversification of catalytic modes. With the evolved catalyst, we would push the limits of aminocatalysis in those challenging substrates and transformations, particularly asymmetric reactions of notoriously hindered alpha-branched ketones. Such reactions would lead to facile accesses to chiral acyclic quaternary carbons beyond the reach otherwise. This project would also put huge emphasis on mechanistic studies as well as the elucidations of SAR of chiral primary amine catalysts. Hopefully, these efforts may eventually lead to the inventions of new reactions with unprecedented catalytic mode.

本项目旨在设计发展新一代广谱高效手性伯胺催化剂。围绕催化效率低下、催化模式单一和适应性差等固有难题，本研究在自主发展的仿生伯胺催化体系基础之上，利用“三官能团协同”的指导思想，结合超分子主客体识别和氧化还原调控等新策略，设计发展新一代高效伯胺催化体系；开拓其在挑战性反应特别是alpha-支链酮不对称催化转化新反应中的应用，发展不对称合成手性开链季碳系列新方法；系统研究催化机理和系列伯胺催化体系的构效关系，探讨开辟氨基催化新模式。

本项目围绕手性伯胺催化剂的设计开发以及在α-取代醛酮类化合物催化转化中的应用开展了系统深入研究，取得的主要成果如下：（1）发展了一类包含芳烃配位的多功能手性伯胺催化剂，开拓了配位诱导的协同催化新模式，实现了氨基催化与过渡金属催化的完美结合，拓展了α-取代醛酮类底物的不对称烯丙基化反应。(2)发展了亚胺自由基催化新模式，实现了伯胺催化不对称炔基化反应；(3)拓展了伯胺与光敏化催化、电催化等多种协同催化策略，实现了α-取代醛酮类化合物的多种不对称催化转化过程，实现了多种具有潜在应用价值的手性季碳中心的构筑；（5）系统开展了伯胺催化机制与规律研究，提出了配位效应模型，双层Sterimol位阻控制模型等多种手性控制模式与反应机制。项目研究四年来发表论文33篇，授权专利2项，培养博士研究生7人，硕士研究生3人，圆满完成预期目标。