亲电三氟甲硫基化试剂的结构―SCF3基团转移能力关系及反应机理的理论研究

In response to a growing demand for CF3S-containing compounds in pharmaceuticals, agrochemicals and materials, chemists are continuously seeking new and efficient reagents and practical strategies for selective installation of the CF3S group onto target molecules. Although a series of power-variable electrophilic trifluoromethylthiolating reagents are available to organic chemists nowadays, scant attention has been devoted to the detailed structure−SCF3 transfer ability relationship studies. Furthermore, the mechanism of SCF3 transfer process for these reagents is still poorly understood. Consequently, the rational design of novel reagents and new reactions has been seriously hampered. In this project, we will start with the computation of Tt+DA (Trifluoromethylthio cation Donating Ability) parameter of electrophilic trifluoromethylthiolating reagents using the same method described in our previous study, with an aim to establish a comprehensive Tt+DA database. Then, we will investigate the substituent effect and the influence of Lewis/Brønsted acid activators on the trifluoromethylthio cation donating abilities of electrophilic trifluoromethylthiolating reagents. Further, we will check whether the Tt+DA values of these reagents have correlations with the activation energies of SCF3 transfer processes. Lastly, we will investigate the detailed mechanisms of some important electrophilic trifluoromethylthiolation reactions to unravel factors controlling rates and chemo-, regio-, and stereoselectivities. This study will contribute to a better understanding of SCF3 transfer mechanism and the reactivity of electrophilic trifluoromethylthiolating reagents, and thus would facilitate future rational design of novel reagents and new electrophilic trifluoromethylthiolation reactions.

随着含三氟甲硫基的有机分子在医药、农药、材料等领域的需求日益增加，发展向分子中引入该基团的新试剂和新方法显得十分迫切。本项目针对制约理性设计新试剂和新反应的两个关键问题—亲电三氟甲硫基化试剂的结构-基团转移能力关系尚未阐明以及反应机理存在诸多盲区，拟借助计算化学方法开展如下研究：1）采用我们前期建立的方法，对表征试剂转移“三氟甲硫基阳离子”能力的Tt+DA （Trifluoromethylthio-cation-Donating-Ability）参数进行计算，构建Tt+DA数据库，阐明取代基效应、Lewis/Brønsted酸活化剂效应，以及Tt+DA参数与SCF3转移反应活化自由能的关系; 2) 对几类代表性亲电三氟甲硫基化反应的机理进行深入研究，揭示控制反应活性与选择性的关键因素。本项目的实施有助于深入认识理解亲电三氟甲硫基化试剂的反应特性和规律，为理性开发新试剂和反应提供策略和思路。

随着含三氟甲硫基的有机分子在医药、农药、材料等领域的需求日益增加，发展向分子中引入该基团的新试剂和新方法成为有机化学研究的重要课题。在本项目的支持下，针对制约理性设计新试剂和反应面临的问题，开展了如下研究：1）采用我们前期建立的方法，对表征试剂转移“三氟甲硫基阳离子”能力的Tt+DA参数进行计算，构建了目前已知的所有常用试剂的Tt+DA标度，阐明了取代基以及Lewis/Brønsted酸活化剂效应。测定了常用试剂的亲电性参数E，并发现了N-SCF3试剂的Tt+DA参数与亲电性参数E存在线性相关; 2) 阐明了几类代表性亲电三氟甲硫基化反应的机理，揭示了控制反应活性与选择性的关键因素。本项目的研究成果，为理性开发新试剂和反应提供理论依据。在本项目的支持下，以第一或通讯作者共发表SCI论文学术18篇，其中影响因子大于10的SCI论文学术8篇（包括Acc. Chem. Res. 1篇、J. Am. Chem. Soc. 3篇、Angew. Chem. Int. Ed. 2篇、Nat. Commun. 1篇、ACS Catal. 1篇）。