主客体协同效应促进多相酸-碱双功能催化剂绿色高效催化不对称串联反应

Tandem reactions, in which multiple reactions are combined into one synthetic operation, have been widely applied to produce elaborate and/or useful molecules especially for chiral pharmaceuticals. However, compatibility of diverse chiral active sites to realize both high activity and enatioselectivity is still a great challenge. Herein, we propose efficient asymmetric concurrent tandem reactions on heterogeneous bifunctional catalysts with inherent achiral silanols of mesoporous silica as acidic sites and immobilized chiral amines as basic sites by the host-guest synergistic effect, further developing efficient and environmental routines to synthesize chiral pharmaceuticals. The innovative features of this research are proposed to include the following three points: (1) The synergic catalysis between the surface-inherent acids and immobilized bases is proposed to enhance the activity and ee in each step. More importantly, the synergistic effect includes the spatial cooperation, the confinement effect, and/or the interfacial synergy; (2) By varying the surface curvature of the support, the distribution of acidic sites, and/or the intensity and the spatial configuration of basic sites, the synergic effect is proposed to be tailored; (3) Several efficient and environmental routines to synthesize chiral pharmaceuticals are proposed to be developed in this study.

串联反应可以实现多步反应一步完成，符合绿色化工的研究趋势，尤其在不对称合成药物中间体等领域的价值尤为突出。然而，如何实现多种催化活性中心的有效协同，同时得到高活性和高对映体选择性，仍是目前亟待解决的巨大难点。本项目提出通过主客体协同效应构筑以无机载体表面羟基为酸中心、手性有机分子为碱中心的双功能手性催化剂，高效绿色催化不对称串联反应，以环境友好的化学反应路线制备新型绿色化工产品，特点在于：(1) 主客体协同效应不仅局限于酸中心与手性碱中心的协同提高不对称串联反应的活性，还可通过空间协同、限域效应及界面协同强化不对称选择性；(2) 主客体协同效应的调控可以通过调控载体的表面曲率与表面性质、酸中心分布、碱中心强度与空间构型等因素实现；(3) 基于催化剂结构的创新，设计与发展几种环境友好的不对称串联反应路线，开展几种重要医药中间体的绿色催化合成研究。

串联反应可以实现多步反应一步完成，符合绿色化工的研究趋势，尤其在不对称合成药物中间体等领域的价值尤为突出。然而，如何实现不同催化活性中心的有效协同，同时得到高活性和高对映体选择性，仍是目前亟待解决的巨大难点。本项目重点针对手性苯并吡喃、手性有机磷酸酯等几种重要医药中间体的绿色催化合成开展基础研究及应用基础研究。利用具有限域空间结构的介孔二氧化硅材料以及二维层状水滑石材料无机载体构筑主客体协同多相手性催化材料，通过主客体协同作用形成的多相酸-碱双功能高效催化不对称串联反应，利用限域空间内的载体空间协同提高多相不对称反应的不对称选择性，利用载体表面功能协同提高活性。结合DFT等理论计算方法，探究主客体协同效应强化反应性能的本质，给出了可能的多相主客体协同催化机制。