含磷配体调控多组分环化反应选择性的理论研究

Multicomponent cycloaddition reaction assisted by phosphorus-containing ligand is one of the effective methods to construct functionalized cyclics, and plays an important role in many areas such as asymmetric synthesis. Carrying out theoretical studies about this kind of reactions can help to figure out many ambiguous issues which could not be accounted for through experimental measures, such as the nature of transition metal-catalysis, and the key role which phosphorus-containing ligand palys in controlling the selectivity of reactions mentioned above. This program aims at conducting theoretical studies about transition metal-catalyzed multicomponent cycloaddition reaction assisted by phosphorus-containing ligand, employing density functional theory (DFT) methods such as B3LYP, B3LYP-D, M062X, etc. According to optimizing geometrical structures of all stationary points on reaction pathways, we can get corresponding structural parameters, energies and corresponding potential energy surfaces (PESs), and sequentially disclose the reaction mechanism, as well as the important role which phosphorus-containing ligand palys in controlling the chemoselectivity, regioselectivity or stereoselectivity of transition metal-catalyzed multicomponent cycloaddition reactions. The intrinsic reaction coordinates (IRC) will be traced and the connecting relationship between key transition states and the reactants, products will be confirmed. Theory of Atoms in Molecules (AIM), assisted by Natural Bond Orbital (NBO) theory, will be employed for topological analysis of electronic density of key stationary points for the sake of obtaining corresponding bonding properties and nature, and then offer some necessary theoretical supports and hints for the experimental preparation of other effective catalysts containing phosphorus ligands, as well as for the development of new reaction systems possessing predictable selectivities.

含磷配体辅助调控选择性的多组分环化反应是构筑功能环状化合物的有效方法之一，在不对称合成等诸多领域具有十分重要的地位，对其开展理论研究有助于深入认识过渡金属催化的本质以及含磷配体在调控此类反应的选择性方面所起的关键作用。申请项目旨在采用密度泛函的B3LYP、B3LYP-D、M062X等方法对含磷配体辅助的过渡金属催化多组分环化反应开展理论研究。通过优化反应途径上所有可能驻点的几何构型，得到其结构参数、能量以及对应的势能剖面图，借以揭示过渡金属催化多组分环化反应的微观反应机制，从理论层面探究含磷配体在控制此类反应的化学、区域或立体选择性方面所扮演的重要角色。对反应路径上的关键过渡态使用IRC分析加以确认，对关键驻点使用AIM理论进行电子密度拓扑分析，并结合NBO理论等研究其电子特性和成键性质，为制备其他含磷配体参与的高效催化剂以及开发具有可预见选择性的新反应系统提供必要的理论支持与指引。

含磷配体辅助调控选择性的多组分环化反应是构筑功能环状化合物的有效方法之一，在不对称合成等诸多领域具有十分重要的地位。实验上已可通过膦配体辅助过渡金属催化体系成功合成一系列结构新颖、性质独特的多环、稠环或螺环化合物，但相应的微观机理、反应选择性控制因素、取代基作用机制等尚不明确。本项目运用密度泛函理论的B3LYP、CAM-B3LYP、B3LYP-D3、M06-2X、LC-ωPBE等方法，对一系列膦配体辅助的过渡金属催化环化反应如镍催化乙烯基环丙烷与亚胺的分子间[3+2]环化反应、钯催化乙烯基氧杂环丙烷与对苯醌甲基化物的分子间[3+2]扩环反应、铑催化烯炔与端炔衍生物的[2+2+2]环加成反应、钯催化邻乙烯基芳基溴化物与溴苯的顺序交叉偶联/环加成反应、钯催化炔基类芳基碘化物与邻溴萘酚的[2+2+1]螺环化反应等开展了理论研究。通过优化反应途径上所有可能的反应物、中间体、过渡态和产物的几何构型，获得了各反应路径上所有驻点的几何结构参数、相对能量以及对应的势能剖面图，从而确定了目标反应的微观机理、最优反应路径和决速步。对于被研究的每一类反应，都从不同角度对实验中所观测到的取代基效应、化学选择性、区域选择性、以及溶剂、添加剂等所扮演的角色等给出了合理的理论解释。该研究成果对于人们深入认识过渡金属催化的本质以及膦配体在控制此类反应的化学选择性、区域选择性、立体选择性方面所起的作用等具有一定意义，对于开发过渡金属催化的高选择性和可预见选择性反应体系、制备更多结构独特、性质优异的多环、稠环或螺环化合物也有一定的参考价值。