Trifluoromethanesulfonyl Azide as a Bifunctional Reagent for Metal-Free Azidotrifluoromethylation of Unactivated Alkenes
Wen-Bo Liu presents trifluoromethanesulfonyl azide as a bifunctional reagent.
Trifluoromethyl-containing molecules have significant im-portance in medicinal chemistry due to the unique physico-chemical and electronic properties of fluorinated substituents. However, the trifluoromethyl group is entirely xenobiotic – e.g. not found in nature – so the only accessible entry to CF3-substituted molecules is chemical synthesis. Alkene azido-trifluoromethylation is a straightforward strategy to concomitantly install a trifluoromethyl group and an azide group in a single step across a carbon–carbon double bond. However, the state-of-the-art catalytic methods based on azido-trifluoromethylation are limited to transition-metal-catalyzed three-component reactions. Therefore, the development of more environmentally benign and atom-economic alternatives is synthetically appealing, besides being conceptually novel.
The group of Professor Wen-Bo Liu at Wuhan University (P. R. of China) was investigating the use of trifluoromethanesulfonyl azide (N3SO2CF3) as a nitrene precursor in the iron-catalyzed intermolecular allylic C–H amination reaction, when a serendipitous discovery, namely a direct azido-tri-fluoromethylation of the alkene by N3SO2CF3, occurred.