Facile C–F Bond Formation through a Concerted Nucleophilic Aromatic Substitution Mediated by the PhenoFluor Reagent

4 years ago

Facile C–F Bond Formation through a Concerted Nucleophilic Aromatic Substitution Mediated by the PhenoFluor Reagent

Tobias Ritter, Constanze N. Neumann

Late-stage fluorination reactions aim to reduce the synthetic limitations of conventional organofluorine chemistry with respect to substrate scope and functional group tolerance. C–F bond formation is commonly thermodynamically favorable but almost universally associated with high kinetic barriers. Apart from PhenoFluor chemistry, most modern aromatic fluorination methods reported to date rely on the use of transition metal catalysts, with C–F bonds often formed through reductive elimination. Reductive elimination chemistry to make C–X bonds becomes increasingly challenging when moving to higher atomic numbers in the periodic table from C–C to C–F, in part because of higher metal–X bond dissociation energies. The formation of C–C, C–N, and C–O bonds via reductive elimination has become routine in the 20th century, but it took until the 21st century to develop complexes that could afford general C–F bond formation. The availability of such complexes enabled the substrate scope of modern fluorination chemistry to exceed that of conventional fluorination.

Publisher URL: http://dx.doi.org/10.1021/acs.accounts.7b00413

DOI: 10.1021/acs.accounts.7b00413