Advances in transition-metal-mediated Di- and monofluoroalkylations

Abstract

Transition-metal-mediated fluoroalkylation is a hot research topic in current organofluorine chemistry. In the past five years, due to the development of new perfluoroalkylation reagents and methodologies, significant progress has been made in the field of transition-metal-mediated perfluoroalkylation. Compared with perfluoroalkylation, di- and monofluoroalkylation can not only introduce fluorine atom(s) into a molecule, but also install a non-fluorinated moiety simultaneously; therefore, in organic synthesis, these reactions are of higher step economy than the direct fluorination reactions. Although analogous to transition-metal-mediated perfluoroalkylations, the di- and monofluoroalkylation have been relatively less developed; therefore, there are still many opportunities for their development. In this review, we have made a survey on transition- metal-mediated di- and monofluoroalkylation reactions that were published in the past nearly 30 years. To our knowledge, this is the first rather comprehensive review on this topic. This review is divided into five sections. The first section is the general introduction on di- and monofluoroalkylation. The second and third sections focus on the historical development of transition-metal-mediated di- and monofluoroalkylation with reagents that contain functional groups. These two sections are subdivided according to the reactions types, that is, fluoroalkylation of unsaturated organohalides, fluoroalkylation of the carbon-hydrogen bonds of unsaturated systems (arenes, alkenes, alkynes, and carbonyl compounds), fluoroalkylation of organoborane reagents and organometallic reagents, fluoroalkyl addition to unsaturated carbon-carbon bonds. The fourth section puts an emphasis on the transition-metal-promoted di- and monofluoromethylation reactions. The final section gives some perspectives on the future development of this chemistry.