Recent Advances in the Synthesis of CF3- or HCF2-Substituted Cyclopropanes

CF3- or HCF2-substituted cyclopropanes are of great interest in pharmaceutical chemistry and agrochemistry, and thus significant efforts have been directed towards the development of efficient methods for the installation of these motifs. This Minireview summarizes recent efforts for the construction of CF3- or HCF2-substituted cyclopropanes. CF3-cyclopropanes are usually synthesized by a transition-metal-catalyzed cyclopropanation of alkenes with a trifluoromethylcarbene generated in situ from a diazocompound, CF3CHN2 or CF3C(Ar)N-2. The synthesis of HCF2-cyclopropanes remains largely unexplored. Some difluoromethylcarbene reagents have been developed, such as HCF2CHN2, Ph2S+CH2CF2H TfO-, and difluoroacetaldehyde N-triftosylhydrazone (DFHZ-Tfs), and cyclopropanation of alkenes with these reagents could also occur by transition metal catalysis. These protocols may find great utility in the synthesis of biologically active molecules.

Automated summary

Efforts have been directed towards developing efficient methods for the construction of CF3- or HCF2-substituted cyclopropanes in pharmaceutical and agrochemical applications. CF3-cyclopropanes are typically synthesized by transition metal-catalyzed cyclopropanation of alkenes, while the synthesis of HCF2-cyclopropanes remains largely unexplored with some difluoromethylcarbene reagents being developed for potential application. These methods may find utility in the synthesis of biologically active molecules.