含双芳杂环的芳香化合物的不对称催化氢化及相关机理研究

The asymmetric hydrogenation of heteroaromatic compounds is one of the most efficient methods for the preparation of chiral heterocycles. Over the past decade, some significant progress has been made in this emerging research area. However, most of the reported chiral catalytic systems still suffered from limited substrate scope and high catalyst loading, and the asymmetric hydrogenation of heteroaromatic compounds containing two heteroaromatic rings has not been reported so far. In this project, on the basis of our preliminary results on the asymmetric hydrogenation of 1,10-phenanthrolines catalyzed by Ru(diamine) complexes, we plan to study the detailed mechanism of both catalytic hydrogenation of 1,10-phenanthrolines and catalytic oxidative dehydrogenation of 1,2,3,4,7,8,9,10- octahydro-1,10-phenanthroline by using different methodologies, such as kinetics and the kinetic isotope effect, as well as computer simulation. Based on this mechanism study and with the choice of Ru-, Rh- or Ir-complexes of chiral diamines, we will further investigate the asymmetric hydrogenation of other types of substrates, including 2,2'-biquinolines, 1,1'-biisoquinolines, 2,2'-biindoles, 1,5-naphthyridines and pyrrolo[3,2-b]pyridines. In addition, some of the obtained reduced chiral products will be chosen for the preparation of chiral N-containing ligands like chiral P,N-ligands and chiral benzimidazole-based N-heterocyclic carbene ligands, which are difficult to access with other methods and has potentials as new ligands for further applications in asymmetric catalysis.

芳香杂环化合物的直接不对称催化氢化是获得手性杂环化合物的最有效途径，近年来受到很大的关注并取得重要进展，但是含双芳杂环的芳香化合物的不对称氢化还几乎没有报道。本项目拟以手性二胺金属配合物为催化剂，在我们基于1,10-邻菲啰啉的不对称氢化的前期工作基础上，首先深入研究该类底物的氢化机理以及产物八氢邻菲啰啉脱氢反应的机理，阐明氢化和脱氢过程中手性识别、手性放大与传递的本质；然后在机理研究的基础上，考察系列新底物，包括芳基取代的邻菲啰啉、联喹啉、联异喹啉、联吲哚、萘啶、吡啶并吡咯等芳香杂环化合物的不对称氢化，通过催化剂的筛选，结合底物活化策略，力争在2-4类含双芳杂环的芳香化合物新底物的不对称氢化中取得突破，建立与发展合成手性含氮化合物以及手性含氮配体的新方法。

芳香杂环化合物的直接不对称催化氢化是获得手性杂环化合物的最有效途径，但是含双个芳杂环的芳香化合物的不对称氢化还几乎没有报道。本项目以手性二胺金属配合物为催化剂，成功实现了几类挑战性含氮芳香杂环衍生物，包括吲哚、1，5-萘啶和1，8-萘啶、2,2’-联喹啉的高效高对映选择性催化氢化，并进一步拓展至酮的不对称串联反应，研究了催化反应的机理并提出了过渡态模型。这些新的发现具有很重要的意义，为多类手性含氮化合物以及手性含氮卡宾配体的合成提供了快速高效的新方法。