Department of Chemistry and Winship Cancer Institute , Emory University , Atlanta 30322 , Georgia , United States.
J Am Chem Soc. 2019 Aug 21;141(33):13203-13211. doi: 10.1021/jacs.9b06004. Epub 2019 Aug 9.
Fluorinated organic molecules are pervasive within the pharmaceutical and agrochemical industries due to the range of structural and physicochemical properties that fluorine imparts. Currently, the most abundant methods for the synthesis of the aryl-CF functionality have relied on the deoxyfluorination of ketones and aldehydes using expensive and poorly atom economical reagents. Here, we report a general method for the synthesis of aryl-CFR and aryl-CFH compounds through activation of the corresponding trifluoromethyl arene precursors. This strategy is enabled by an endergonic electron transfer event that provides access to arene radical anions that lie outside of the catalyst reduction potential. Fragmentation of these reactive intermediates delivers difluorobenzylic radicals that can be intercepted by abundant alkene feedstocks or a hydrogen atom to provide a diverse array of difluoalkylaromatics.
由于氟赋予的一系列结构和物理化学性质，含氟有机分子在制药和农用化学品行业内广泛存在。目前，合成芳基-CF 官能团最丰富的方法依赖于使用昂贵且原子经济性差的试剂对酮和醛进行脱氧氟化。在这里，我们报告了一种通过激活相应的三氟甲基芳基前体来合成芳基-CFR 和芳基-CFH 化合物的通用方法。这种策略是通过一个吸电子电子转移事件实现的，该事件提供了芳基自由基阴离子的通道，而这些自由基阴离子的还原电势超出了催化剂的还原电势。这些反应中间体的断裂会产生二氟苄基自由基，这些自由基可以与丰富的烯烃原料或氢原子发生反应，从而提供各种不同的二氟烷基芳烃。
