Abstract
Due 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 Introduction
2 Stereoselective Introduction of a CF3 Group
2.1 Nucleophilic Addition to Carbonyls and Imines
2.2 Electrophilic Substitution at the α Position of Carbonyls
2.3 Allylic Nucleophilic Substitution
3 Stereoselective Functionalization of CF3-Substituted Molecules
3.1 Electrophilic Substitution of α-CF3 Carbonyls
3.2 Substitution of α-Halo CF3 Compounds
3.3 Addition-Type Reactions with CF3-Substituted Alkenes
4 Conclusion and Outlook
Key words
addition
asymmetric catalysis
fluorine
substitution
trifluoromethyl group
