Development of Pentafluoroethylation Methods

Abstract

Compared to the smallest perfluoroalkyl group, i.e. trifluoromethyl (CF3), the pentafluoroethyl group (C2F5) has rather been overlooked in terms of synthetic methods and applications in pharmaceuticals/agrochemicals. However, this situation has changed in the last decade or so where more reports have appeared in the literature describing the reagents and reactions that can allow the efficient preparation of C2F5-containing compounds. This review summarizes the methods of pentafluoroethylation for the period of ca. 2015-2025 organized by reagents including transition metal-based reagents, perfluoroalkyl silanes, gaseous reagents, hypervalent iodine, sulfonium ylide and sulfoximine reagents, and miscellaneous reagents. These methods have significantly advanced our access to structurally diverse pentafluoroethylated compounds and will have a major impact on their potential applications in medicinal chemistry as drug candidates and in organic synthesis as building blocks.