Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, Fuzhou 350207, P. R. of China.
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
J Am Chem Soc. 2022 Aug 10;144(31):14288-14296. doi: 10.1021/jacs.2c05356. Epub 2022 Jul 27.
The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical hydrodifluoromethylation of unactivated alkenes with an inexpensive industrial chemical, chlorodifluoromethane (ClCFH, Freon-22). This protocol is realized by merging tertiary amine-ligated boryl radical-induced halogen atom transfer (XAT) with organophotoredox catalysis under blue light irradiation. A broad scope of readily accessible alkenes featuring a variety of functional groups and drug and natural product moieties could be selectively difluoromethylated with good efficiency in a metal-free manner. Combined experimental and computational studies suggest that the key XAT process of ClCFH is both thermodynamically and kinetically favored over the hydrogen atom transfer pathway owing to the formation of a strong boron-chlorine (B-Cl) bond and the low-lying antibonding orbital of the carbon-chlorine (C-Cl) bond.
将丰富且廉价的氟原料应用于合成氟化化合物是一种很有吸引力但尚未得到充分探索的策略。在这里，我们报告了一种用光催化自由基氢二氟甲基化的方法，该方法使用廉价的工业化学品二氯二氟甲烷（ClCFH，氟利昂-22）对未活化的烯烃进行反应。该方案通过将叔胺配位的硼自由基诱导的卤原子转移（XAT）与有机光氧化还原催化在蓝光照射下合并实现。在无金属的条件下，具有各种官能团和药物及天然产物部分的广泛易得的烯烃可以以良好的效率选择性地进行二氟甲基化。实验和计算研究表明，ClCFH 的关键 XAT 过程在热力学和动力学上都优于氢原子转移途径，这是由于形成了强的硼-氯（B-Cl）键和低占据的碳-氯（C-Cl）键反键轨道。
