亚铜催化芳基硼酸三氟甲基化反应的理论研究

Mechanistic insights into copper-catalyzed trifluoromethylation of aryl boronic acids:a theoretical study

本文运用密度泛函理论(DFT)计算研究了以Togni试剂为氟源,CuI/邻二氮菲催化的芳基硼酸三氟甲基化反应机理.计算结果表明,该反应经历转金属化-协同亲电取代路径,通过协同的五元环过渡态亲电取代过程实现三氟甲基转移.反应势能面分析显示,芳基硼酸与铜催化剂的转金属化是整个反应路径的决速步,其活化能是21.7 kcal/mol.在此基础上,对比计算了苯乙基硼酸与铜催化剂的转金属化过程,研究结果表明,与苯基硼酸相比,烷基硼酸的转金属化的能垒更高,是动力学不利的过程.

Density functional theory （DFT） calculations were employed to study the mechanism for copper-catalyzed trifluoromethylation of aryl boronic acids by Togni＇s reagent. Computational results suggest that the catalytic cycle proceeds with the transmetallation between phenylboronic acid and copper（I） species, which generates a phenylcopper（I） intermediate. Subsequent coordination of Togni＇s reagent and the electrophilic substitution of CF3 group to phenyl group finally afford the trifluoromethylation product through a concerted five-membered ring transition state. The transmetallation process with an activation free energy of 21.7 kcal/mol is determined to be the rate-determining step of this reaction. Moreover, the reactivity of alkylboronic acid was also calculated and proven to be unfavorable due to the higher activation free energy of transmetallation process.