手性磷酸导向离子对催化不对称反应理论计算与实验探索研究

The interaction of asymmetric ion-pairing, such as chiral ionic species with anionic and cationic small molecules or intermediates, has emerged as a powerfull strategy for catalytic, enantioselective sysnthesis. The identification of effeicient, catalytic methods to do so represents a current frontier of the field. Due to the often weak and non-directional nature of such noncovalent interactions in the ion-pairs, determining the basis for catalysis and enantioselectivity is generally extremely challenging. The increasing power of computational methods is enabling the study of noncovalent interactions in such catalytic reactions with increasing accuracy. By means of theoretical calculations, the asymmetric ion- pairing mechanisms would be studied systematically, for the reported asymmetric counteranion directed ractions proceeding via positive charged intermediates or complexes noncovalent binding to a chiral phosphate catalyst, and the detailed information about the particular electronic and conformational structures of chiral ion-pairs should be obtained. Accordingly, the reasonable interacting modes among the invetigated chiral phosphate and the correspounding countercation is able to be elucidated. The intrinsic factors of controlling the reaction activity and selectivity, especially enantioselectivity, would be realized and used to improve the known reactions in terms of the significant results obtained from computation. Furthermore, based on the understanding of the studied asymmetric ion-pairing mechanisms, in combination of the experimental investigations, we will try to design and test asymmetric conteranion directed ion-pairing catalytic reactions with new and better chiral phosphate catalyst by systematic computational study in light of this important mode of catalysis.

基于离子对相互作用原理，利用手性结构的抗衡离子对在相互作用时的识别与匹配导致的手性诱导作用实现不对称催化反应，成为不对称合成反应新的重要策略。借助实验方法研究离子对间的非共价键弱相互作用，获得的有关反应机理信息十分有限，而高精度量子力学计算可给出这种弱相互作用的定量评估和空间结构信息。通过对文献报道的手性磷酸根导向离子对催化不对称反应性的分子模拟计算研究，获取抗衡离子对间相互作用的电子结构和三维空间结构信息，探讨手性磷酸根与抗衡阳离子中间体及其它反应底物间的相互作用机制，研究不同结构阳离子中间体与不同结构手性磷酸根间形成的抗衡离子对相互作用影响因素，从而认识抗衡离子对的活化作用模式和立体控制机制，解决手性离子对催化不对称反应机理认识模糊问题，为提高该类不对称催化反应活性、拓展底物适用范围提供理论依据和具有实际意义的指导，在此基础上开展新型手性磷酸根导向离子对作用催化不对称反应体系的研究。

本项目通过对手性膦酸及其衍生物与金属阳离子和反应底物间的弱相互作用的探索，发展了几种新型手性催化反应体系，实现了杂环骨架的不对称构建、C-H键活化及不对称烯丙基化等反应，取得了一些有特色的研究成果。我们利用手性膦酸银实现了立体选择性和区域选择性控制的氮杂-[4+2]环加成反应构建手性六元含氮杂环骨架；利用金复合物分解重氮卡宾再与手性膦酸接力催化，立体选择性实现了氮杂-烯反应；利用手性亚膦酰胺与钯的联合催化，“一锅法”实现烯丙基型sp3 C-H键活化、不对称烯丙基化串联反应。项目执行期间，共发表学术论文5篇，其中包括Angew. Chem. Int. Ed. 1篇、Org. Lett. 2篇。