Radical Amido‐ and Azido‐Fluorination of α‐Fluorostyrene Derivatives: An Innovative Approach Towards β‐Aryl‐β,β‐difluoroamino Motifs

Abstract

An innovative one-step synthesis towards β-aryl-β,β-difluorocarbamates and β-aryl-β,β-difluoroazides is presented. The described approach relies on the use of α-fluorostyrene substrates in a radical addition/fluorination reaction with N-centered radicals in the presence of Selectfluor®. The best results were obtained for the azidofluorination reaction. The resultant β-arylβ,β-difluoroazides were further transformed into Nitrogenbased heterocycles (e. g. pyrrole, triazole, and tetrazole) and in more elaborated azide derivatives.

Silver‐Catalyzed Carbofluorination of Olefins and α‐Fluoroolefins with Carbamoyl Radicals

“…In addition, a five-fold increase (entry 13) or decrease (entry 14) of the reaction's concentration altered significantly the efficiency of the transformation. The influence of the ratio acetone:water on the reactivity was then investigated (entries [15][16][17][18]. Thus, increasing or decreasing the proportion of water in the mixture of solvent resulted in the formation 4 aa in low NMR yields (0-12 %).…”

“…In this context, we decided to explore further the reactivity of carbamoyl radicals in carbofluorination reaction of olefins (Scheme 1k). In continuation of our work on exploiting α ‐fluoroolefins in radical addition/fluorination sequences for the synthesis of molecules containing a gem ‐difluoromethylene motif (−CF 2 −), [15] we also envisaged to investigate the aforementioned carbofluorination reaction with such olefinic substrates (Scheme 1l). Thus, β ‐fluoroamides G and β , β ‐difluoroamides H could be respectively obtained from radical adducts I and J in the presence of a radicophilic fluorine source.…”

Recent Advances in C—F Bond Formation from Carbon‐Centered Radicals

“…In 2022, the Brioche group reported azidofluorination of α‐fluorostyrenes to access β‐aryl‐β , β‐difluoroazides making use of azido radical (Scheme 42). [ 106 ] The authors indicated N‐radical addition to styrenes to generate a benzyl radical that could either undergo fluorine atom abstraction or oxidation to carbocation by selectfluor followed by trapping with fluoride. The products can be employed in useful post‐functionalization reactions towards synthesis of heterocycles by taking advantage of the azide functional group either as an amine precursor or as a 1,3‐dipole.…”