Recent advances in enantioselective trifluoromethylation reactions

Fluorinated organic compounds have received considerable attention because they possess unique properties such as greater stability, higher electronegativity, and water and oil repellency, which are potentially beneficial in terms of the development of novel pharmaceutical agents and advanced materials. Such extreme behaviors of fluoro-organic compounds however, often make their syntheses all the more complicated, especially when the synthesis of target compounds requires an enantiocontrolled methodology. Many strategies can be employed for introducing chirality into organic molecules, but enantioselective fluorination and trifluoromethylation reactions are especially attractive because non-fluorinated prochiral substrates can be directly transformed to chiral fluoro-organic compounds with a control of absolute configuration. Significant progress has been made in the development of the asymmetric fluorination reaction in recent years; however, the direct enantioselective trifluoromethylation reaction remains a challenge. In this report, we discuss recent developments in the enantioselective trifluoromethylation reactions, including nucleophilic, electrophilic, and radical approaches. Although the emphasis of this report is on the enantioselective trifluoromethylation reaction, the less-studied enantioselective difluoromethylation and monofluoromethylation reactions are also covered. (C) 2008 Elsevier Ltd. All rights reserved.