Monofluoroalkenes can be useful, e.g., in drug development, where they can serve as a replacement for peptide bonds. One synthetic path to monofluoroalkenes is the C–F activation of gem-difluoroalkenes. However, existing methods for this often have drawbacks such as a need for prefunctionalized starting materials or limited substrate scopes. Thus, new methods for the synthesis of alkylated monofluoroalkenes via C–H/C–F bond coupling could be useful.

Wengang Xu, Mingbo Wu, China University of Petroleum (East China), Qingdao, and colleagues have developed an effective method for the synthesis of monofluroalkenes—in particular, α-fluoroalkenyl alcohols—by the defluoroalkylation of gem-difluoroalkenes with alcohols via a C–F/C–H coupling (example reaction pictured). The team reacted different aryl-substituted gem-difluoroalkenes with a variety of alcohols under blue LED light, using 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) as a photocatalyst in the presence of quinuclidine, ZnCl₂, and K₃PO₄, with dimethyl sulfoxide (DMSO) as the solvent.

Under these conditions, the team obtained the desired defluoroalkylation products in mostly moderate to excellent yields. The team proposes a reaction mechanism that involves the formation of a quinuclidinyl N-radical cation, which reacts with an alkoxide zinc intermediate formed from the alcohol in a hydrogen atom transfer (HAT) reaction to give an alkyl radical. This radical combines with an alkenyl radical that is formed via fluoride elimination from the gem-difluoroalkene. Overall, the work allows the visible-light-promoted defluorinative alkylation of gem-difluoroalkenes with alcohols as the alkyl source under mild conditions.

• Defluoroalkylation of gem-Difluoroalkenes with Alcohols via C–F/C–H Coupling,
  Congjian Xia, Haiyang Hu, Wengang Xu, Baokai Yang, Qi Shao, Mingbo Wu,
  Org. Lett. 2023.
  https://doi.org/10.1021/acs.orglett.3c03982