Copper-Mediated\n−CF(OCF<sub>3</sub>)(CF<sub>2</sub>H) Transfer to Organic Electrophiles

The integration of\nfluorine into medicinal compounds has become\na widely used strategy to improve the biochemical and therapeutic\nproperties of drugs. Inclusion of −CF<sub>2</sub>H and −OCF<sub>3</sub> fluoroalkyl groups has garnered attention due to their bioisosteric\nproperties, enhanced lipophilicity, and potential hydrogen-bonding\ncapability in bioactive substances. In this study, we prepared a series\nof stable Cu[CF(OCF<sub>3</sub>)(CF<sub>2</sub>H)]L<i><sub>n</sub></i> complexes by insertion of commercially available perfluoro(methyl\nvinyl ether), CF<sub>2</sub>CF(OCF<sub>3</sub>), into Cu–H\nbonds derived from Stryker’s reagent, [CuH(PPh<sub>3</sub>)]<sub>6</sub>, using ancillary ligands L. Notably, certain of these complexes\neffectively transfer the fluoroalkyl group to aroyl chlorides. Through\nreaction optimization and computational analysis, we identified dimethylsulfoxide\nas a pivotal coligand, playing a distinctive role in enabling the\nfluoroalkylation of a range of aroyl chlorides and aryl iodides. The\nlatter also benefits from addition of CuBr to abstract PPh<sub>3</sub>, generating solvent-stabilized Cu[CF(OCF<sub>3</sub>)(CF<sub>2</sub>H)]. These methodologies allow for the introduction of geminal −OCF<sub>3</sub> and −CF<sub>2</sub>H groups in a single transformation.