Abstract
The integration of fluorine into medicinal compounds has become a widely used strategy to improve the biochemical and therapeutic properties of drugs. Inclusion of -CF(2)H and -OCF(3) fluoroalkyl groups has garnered attention due to their bioisosteric properties, enhanced lipophilicity, and potential hydrogen-bonding capability in bioactive substances. In this study, we prepared a series of stable Cu[CF(OCF(3))(CF(2)H)]L (n) complexes by insertion of commercially available perfluoro(methyl vinyl ether), CF(2)=CF(OCF(3)), into Cu-H bonds derived from Stryker's reagent, [CuH(PPh(3))](6), using ancillary ligands L. Notably, certain of these complexes effectively transfer the fluoroalkyl group to aroyl chlorides. Through reaction optimization and computational analysis, we identified dimethylsulfoxide as a pivotal coligand, playing a distinctive role in enabling the fluoroalkylation of a range of aroyl chlorides and aryl iodides. The latter also benefits from addition of CuBr to abstract PPh(3), generating solvent-stabilized Cu[CF(OCF(3))(CF(2)H)]. These methodologies allow for the introduction of geminal -OCF(3) and -CF(2)H groups in a single transformation.