基于EnT二氟烷基自由基引发新策略及其在光促C(sp3)-H不对称二氟烷基化中的应用

本项目拟发展一种新型的具有双催化功能的手性喹唑啉酮催化剂，并将其应用于催化C(sp3)-H键不对称二氟烷基化反应。通过苯乙醛α位C(sp3)-H键不对称二氟烷基化模板反应研究，揭示催化剂、激发波长、溶剂及温度等反应条件与实验结果的关联，解决催化体系内各组分匹配性问题。在此基础上对催化体系再优化，以苯丙醛作为模板底物，考察光化学条件下调控醛酮衍生物α或β位C(sp3)-H键不对称二氟烷基化可行性，明确影响反应区域选择性及立体选择性的关键因素。通过GC-MS、EPR、IR等检测手段，结合自由基捕捉及荧光淬灭等实验方法，深入探究反应过程中光敏剂的激发和淬灭及能量(EnT)、电子转移(SET)等反应历程，提出合理的协同催化机理。将较优的催化剂应用于系列醛酮衍生物与溴代二氟烷基试剂的不对称偶联反应，拓展催化剂在有机合成中的应用范围，发展一种条件绿色、催化效率高、适用性广的制备手性二氟烷基化合物方法。

This research aims to develop a new chiral quinazolone catalyst with double catalytic sites, which was applied to catalyze the asymmetric difluoroalkylation of C(sp3)-H bonds. Through the investigation of the asymmetric difluoroalkylation of α-C(sp3)-H bond of phenylacetaldehyde, the correlation between experiment results and the reaction conditions including catalysts, excitation wavelength, solvent and temperature was revealed, and the problem of catalytic system matching was solved. Subsequently, the catalytic system was further optimized to investigate the feasibility of regulating asymmetric difluoroalkylation of α-or β-C(sp3)-H bonds of aldehydes and ketones by using phenylpropanal as a template substrate, identifying the key factors which affect regioselectivity and stereoselectivity of the reaction. After employing chemical instruments such as GC-MS, EPR, IR, combining with radical capture and fluorescence quenching experiments, the excitation and quenching of photosensitizer, energy transfer (EnT) or electron transfer (EnT) in the reaction process were deeply explored, and the reasonable mechanism of this synergistic catalysis was proposed. The optimized catalysts were then applied to the asymmetric coupling reaction of aldehyde and ketone derivatives with brominated difluoroalkyl reagents to expand the application of catalytic systems in organic synthesis. This research contributes to develoing a new method for the preparation of chiral difluoroalkyl compounds with green conditions, high catalytic efficiency and wide applicability.