新型双功能双核手性铟配合物的制备及在不对称催化反应中的研究

Compared with conventional catalysts, bifunctional catalysts that can simultaneously activate both partners of a bimolecular reaction generally exhibit enhanced catalytic activity and higher levels of stereodifferentiation under milder reaction conditions, attracting much attention as next-generation catalysts for prospective practical applications. In this proposal, a novel type of bifunctional dinuclear chiral Indium(III) complexes incorporating "In" into the "O2" cavity on chiral quaterphenyl scalffod will be synthesized to address the challenge in the following two asymmetric reactions based on the cooperative catalysis concept: (1) Catalytic asymmetric trifluoromethylation reactions of trifluoromethyl boronic ester [CF3－B(pin)] with aldehydes or ketones; (2) Catalytic asymmetric allylation reactions of aryl and alkyl ketones. We will focus on the study of the structure effect of dinuclear chiral Indium complexes and substrates on the enantioselectivity. Such a study aims to explore two new reactions in high yields and enantioselectivities, and to achieve chiral α-trifluoromethyl alcohols and chiral homoallylic alcohols respectively. To illustrate the usefulness of bifunctional asymmetric catalysis, asymmetric allylation of ketones has been incorporated into the asymmetric construction of anti-HIV agent Tipranavir with 5,6-Dihydro-4-hydroxy-2-pyrones motifs. Reaction and process monitoring by NMR and Mass spectroscopy, kinetic study, and density functional theory (DFT) calculations will be carried out to elucidate the plausible mechanism.

本项目拟利用金属铟催化剂的一些独特优点，综合考虑催化过程中的双中心活化和多手性因素控制，在基于手性联苯骨架的含四羟基配体中引入双金属铟烷氧基片段，构建一类新型双核手性金属铟配合物，研究不同取代基的双核手性金属铟配合物分别在醛酮与三氟甲基硼酸酯试剂之间的不对称三氟甲基化反应，以及简单酮与烯丙基硼酸酯试剂之间的不对称烯丙基化反应中的催化活性和手性诱导能力，总结催化剂结构与催化性能之间的关系，构建温和条件下的两类不对称催化反应，进而得到手性α-三氟甲基醇和手性高烯丙基醇。采用手性高烯丙基醇为手性合成子，经多步反应合成抗癌药Tipranavir。借助波谱分析、动力学研究和密度泛函理论（DFT）计算等方法，研究反应过渡态，探讨可能的催化反应机理。