Catalytic Asymmetric Construction of CF3-Substituted Chiral sp3 Carbon Centers

Abstract

AbstractDue to the unique steric and electronic nature of the fluorine atom, organofluorine compounds have received significant attention in the fields of pharmaceuticals and agrochemicals. In particular, the CF3 group is frequently found in biologically active compounds. However, compared to aryl- and alkenyl-CF3-containing molecules, the construction of sp3 carbon-based alkyl-CF3-containing molecules, particularly via catalytic enantioselective synthesis, remains a considerable challenge in spite of their high potential in medicinal applications. This short review focuses on recent advances in this research area, and the reported strategies are categorized according to reaction types and starting substrates. In addition, chiral catalysts, substrate scope, and reaction mechanisms are briefly summarized. 1 Introduction2 Stereoselective Introduction of a CF3 Group2.1 Nucleophilic Addition to Carbonyls and Imines2.2 Electrophilic Substitution at the α Position of Carbonyls2.3 Allylic Nucleophilic Substitution3 Stereoselective Functionalization of CF3-Substituted Molecules3.1 Electrophilic Substitution of α-CF3 Carbonyls3.2 Substitution of α-Halo CF3 Compounds3.3 Addition-Type Reactions with CF3-Substituted Alkenes4 Conclusion and Outlook