New Avenues in Copper-Mediated Trifluoromethylation Reactions Using Fluoroform as the CF3 Source

Abstract Organic molecules containing the trifluoromethyl (CF3) group play a vital role in pharmaceuticals, agrochemicals, and materials. New trifluoromethylation methods should encompass capabilities to address issues in efficiency, selectivity, and CF3 source all at once. Fluoroform (CF3H), an industrial byproduct, has emerged as an attractive CF3 source. The reaction profile of the [CuCF3] reagent derived from fluo­roform has surpassed its original applications in cross-coupling-type trifluoromethylation. We have discovered a host of unique copper-mediated trifluoromethylation reactions using [CuCF3] from fluoroform, especially under oxidative conditions, to deliver efficient and selective synthesis of trifluoromethylated compounds. 1 Introduction 2 Construction of C–CF3 Bonds for the Synthesis of Trifluoromethylated Building Blocks 2.1 C(sp)–CF3 Bond Formation 2.2 C(sp2)–CF3 Bond Formation 2.3 C(sp3)–CF3 Bond Formation 3 Domino Synthesis of Trifluoromethylated Heterocycles 3.1 3-(Trifluoromethyl)indoles 3.2 3-(Trifluoromethyl)benzofurans 3.3 2-(Trifluoromethyl)indoles 4 Trifluoromethylative Difunctionalization of Arynes 4.1 Trifluoromethylation–Allylation of Arynes 4.2 1,2-Bis(trifluoromethylation) of Arynes 5 Pentafluoroethylation of Unactivated Alkenes 6 Conclusion