Silver-Catalyzed Hydrotrifluoromethylation of Unactivated Alkenes with CF3SiMe3

摘要

As a result of the strong electron-withdrawing nature and large hydrophobic domain of the trifluoromethyl group (CF3), the incorporation of a trifluoromethyl group into organic molecules can dramatically modify a variety of properties, including lipophilicity, metabolic stability, and bioavailability. Notably, many billion-dollar pharmaceuticals as well as agrochemicals contain a trifluoromethyl group. Therefore, intensive attention has been recently paid to the development of new methods for the introduction of the trifluoromethyl group into organic compounds. Recently, significant advances have been achieved in transition-metal-mediated/ catalyzed trifluoromethylation. For example, in the presence of a palladium or copper catalyst the replacement of a halide, boron, or even C-H bond with a trifluoromethyl group can be accomplished under mild reaction conditions. In addition, two rare but interesting examples of silver-mediated direct trifluoromethylation of aryl C—H bonds also have been reported. Silver is readily available and silver-mediated/ catalyzed reactions have emerged as versatile synthetic methods for a wide range of organic transformations, including fluorination reactions, trifluoromcthylthiolation reactions, and trifluoromethoxylalion reactions.The exploration of metal catalysts such as silver, as opposed to palladium and copper, could lead to new opportunities for trifluoromethylation. Despite the pioneering work of Sanford and Brase, current silver-mediated trifluoromethylation reactions are limited to the construction of C_(aryl)—CF3 bonds. Furthermore, these transformations require stoichiometric silver salts to generate the reactive intermediate AgCF3. To address these limitations, we herein describe a silver-catalyzed hydrotrifluoromethylation of unactivated alkenes.