金属铱催化烯丙基取代反应中新配体合成及应用研究

This project will focus on the design of new ligands and their application in Ir-catalyzed allylic substitution reactions. New N-aryl phosphoramidite ligands and N-heterocyclic carbene ligands will be designed and synthesized based on the previous mechanistic studies. The active Ir catalysts derived from these ligands are expected to be formed through the aryl sp2 C-H activation pathway and therefore easily prepared. Thus, they are expected to solve the challenging problems in Ir-catalyzed allylic substitution reactions such as unfavorable ortho-substituted effects of aryl substituted allylic substrates, poor catalyst stability, and low catalyst turnover number. The expected outcomes of this project include novel efficient chiral ligands and efficient synthesis of important natural products and pharmaceuticals.

本项目拟开展金属铱催化的烯丙基取代反应中新配体的合成及应用研究。在前期机理研究基础上，设计、合成新型氮芳基磷配体及氮杂环卡宾配体，这些配体由于通过芳环上sp2碳氢键活化形成铱配合物，活性催化剂制备简单，有望解决金属铱催化烯丙基取代反应中一些挑战性问题，例如芳基取代的烯丙基底物不利的邻位取代效应、催化剂稳定性差、催化剂转化数低等等。在这一过程中获得具有自主知识产权的手性配体，并实现相关手性天然产物和药物分子的高效合成。

项目主要研究了过渡金属催化的不对称烯丙基取代反应，发展了Ir/N-芳基亚磷酰胺和Ir/氮杂环卡宾催化体系，实现了不对称烯丙基胺化反应。还发展了铱催化的苯胺分子内不对称傅克类烯丙基取代反应，铱催化醛酮作为氧亲核试剂的不对称烯丙基醚化反应，铱催化不对称烯丙基芳构化反应以及铑催化的不对称烯丙基烷基化反应。此外，项目还发展了羟基喹啉、吲哚和苯环衍生物的多个不对称去芳构化反应。从基础化学原料出发，高效创制了结构多样的手性分子，为药物研发提供新颖分子骨架的化合物库。