新型氮膦配体的设计与合成及其在铁催化不对称还原反应中的应用

During the last decade, the asymmetric reduction reaction promoted by chiral iron complexes has been a hot research topic in organic synthesis. In this context, the chiral ligand is critical for ensuring the high efficiency and selectivity of such catalytic systems. Considering the limited robust chiral ligands and the scope of substrates in such processes, we will try to design and synthesize a series of novel chiral N/P-ligands by analyzing the possible stereo-controlling model. Furthermore, their catalytic efficiencies will be tested in the asymmetric reduction reaction. The research work here will mainly cover the following aspects:1) four kinds of new N/P-ligands will be rationally designed and efficiently synthesized from available natural amino acids; 2)the catalytic performances of iron complexes generated form these ligands and various iron source will be investigated in the asymmetric reduction of prochiral ketones and their imines, as well as the dynamic kinetic resolution of racemic carbonyl compounds;3) application of these complexes to the enantioselective reduction of aza-arenes will be continued to provide optically active aza-heterocycles; 4) studying the reaction mechanism by analyzing the X-ray structures of these chiral iron complexes will be conducted, which is significant for the further optimization of these chiral N/P-ligands. In conclusion, this study will focus on the design and synthesis of novel N/P-ligand from available natural amino acids and pave the way for developing more efficient iron complex-catalyzed asymmetric reductive process.

近十年来，手性铁络合物促进的不对称还原反应已经成为有机合成领域中一大研究热点。其中，手性配体是实现其高效、高选择性的关键。针对目前铁催化领域中仍缺少高效、高选择性的手性配体和较窄的底物适用范围，本项目拟设计并合成一系列新型的手性氮膦配体，并将其应用于铁催化的不对称还原反应。主要内容包括：1）从天然的氨基酸出发，设计并合成四类新型的C2-对称的手性氮膦配体；2）研究上述手性配体与铁形成的络合物在前手性酮、酮亚胺的不对称还原，以及消旋羰基化合物的动态动力学拆分中的催化性能；3）进一步将这些催化体系应用于氮杂芳环的不对称还原，合成具有重要生物活性的手性氮杂环化合物；4）通过分析铁络合物的晶体结构来研究其在反应中的立体控制机制，为进一步优化配体结构奠定基础。本项目的实施为手性配体的合理设计与合成，以及铁催化不对称还原反应的进一步发展提供一定的理论指导和实验依据。

本项目主要集中于新型手性氮膦配体的设计、合成及其相关的铁催化还原反应、环加成研究，重点探索绿色、经济的有机合成方法学研究。主要研究内容包括三个方面：（1）手性氮膦配体的设计、合成与应用探索；（2）羰基铁-铁Lewis酸序列催化α-酮酸酯仿生还原反应研究；（3）羰基铁-手性布朗斯特酸序列催化苯并恶嗪酮的不对称氢化反应研究；（4）羰基铁络合物催化的脱羧[4+1]环加成合成3-烯基-2-酰基吲哚啉。与此同时，在该基金的资助下，我们基于发展绿色有机合成方法学的理念，也探索了可见光催化的绿色有机反应，为未来的基金申请和科学研究做准备。.在本项目的资助下，我们在Nat. Commun.、J. Am. Chem. Soc.、Angew. Chem. Int. Ed.、Org. Lett.、Chem. Eur. J.等国际学术刊物上共发表学术论文13篇，申请发明专利2项。同时，培养的4名硕士研究生继续攻读博士学位，共同培养的2名博士研究生顺利毕业。项目负责人应邀参加了和项目相关的国内学术会议6次。