新型手性氢转移试剂研究

Asymmetric transfer-hydrogenation represents one type of asymmetric reductive reactions with mild reaction conditions and easy operations, which provides an effective approach for the synthesis of optically active compounds. At present, high catalyst loading, low catalytic efficiency, and low atom-economic hydrogen donor still remain as main challenges for metal-free transfer-hydrogenations. Therefore, a novel strategy for the development of regenerable chiral transfer-hydrogen reagents is put forward in the current project. Ammonia borane with low molecular weight and high hydrogen capacity is selected as the hydrogen donor, which reacts with readily available and structure diverse chiral Brønsted acids via a hydrogen-releasing reaction to generate chiral ammonia boranes in situ. After the transfer-hydrogenation of unsaturated compounds, water or alcohols are used to regenerate chiral Brønsted acids through hydrolysis or alcoholysis, which further react with ammonia borane to regenerate chiral ammonia boranes. Using these chiral ammonia boranes as transfer-hydrogen reagents, the asymmetric transfer-hydrogenation of some challenging substrates, such as vicinal diketones, vicinal diimines, aromatic N-heterocycles, and tetra-substituted alkenes, will be investigated. Moreover, one pot reductive amination of ketones and amines will be studied. Mechanistic studies will be conducted to have a better insight on this reaction. The aim of the current project is to develop highly effective, highly selective, and practical systems for asymmetric transfer-hydrogenation.

不对称转移氢化是一类条件温和，操作简便的不对称还原反应，是获得光学活性化合物的重要途径之一。目前，无金属的不对称转移氢化反应面临着手性催化剂用量大，催化效率低，氢供体原子经济性差等亟待解决的关键科学问题。因此，本项目拟提出发展可再生手性氢转移试剂的新策略，即采用低分子量、高含氢量的氨硼烷作为氢供体，与易得、结构多样的手性布朗斯特酸通过放氢反应，原位制备手性氨硼烷作为氢转移试剂，与不饱和化合物发生不对称转移氢化反应，制备光学活性化合物，进而通过水解或醇解实现手性布朗斯特酸的再生，其与氨硼烷继续反应，完成手性氨硼烷的原位再生。拟利用所发展的手性氨硼烷作为氢转移试剂，开展一些重要挑战性底物，如1,2-二酮，1,2-二亚胺、芳香氮杂环化和四取代烯烃等化合物的不对称转移氢化反应，以及酮和胺类化合物的一锅法不对称还原胺化反应，同时探索反应的内在机制，力争发展高效、高选择性、实用的不对称转移氢化新体系。

不对称转移氢化是一类条件温和，操作简便的不对称还原反应，是获得光学活性化合物的重要途径之一。本项目针对无金属的不对称转移氢化反应中存在的手性催化剂用量大，催化效率低，氢供体原子经济性差等关键科学问题，围绕氨硼烷作为氢源的不对称转移氢化反应以及基于氨硼烷发展的新型FLP催化新体系，开展了以下工作：1）使用低分子量、高含氢量的氨硼烷作为氢供体，与易得、结构多样的手性布朗斯特酸通过放氢反应，原位制备手性氨硼烷作为氢转移试剂，实现了β-烯胺腈、N-非保护吲哚、大位阻酮等不饱和化合物的不对称转移氢化反应。2）使用手性胺作为Lewis碱，与非手性硼Lewis酸组成FLP催化剂，实现氢气异裂，得到手性氨硼烷类似物，开发了新型手性氨硼烷，实现了简单酮、烯酮、色酮等衍生物的不对称氢化反应。3）使用非手性硼烷和手性磷酸组合催化剂，成功实现了色酮类化合物的不对称接力催化氢化反应。4）结合计算化学和控制实验，进行了机理研究。本项目共发表学术论文8篇，其中Angew. Chem. Int. Ed. (1篇)，Org. Lett. (2篇)，Chem. Commun. (1篇)，Tetrahedron Lett. (1篇)，Chin. J. Chem. (2篇)，Chin. J. Org. Chem. (1篇)。