Difluorinative-hydroxylation and C-3 functionalization (halogenation/SCN/NO) of imidazopyridine using Selectfluor as fluorine source or oxidant respectively

Abstract An efficient route for the difluorinative-hydroxylation through dearomative difunctionalization of imidazopyridine using Selectfluor as fluorine source has been developed in an aqueous medium. The reaction proceeds through ionic followed by radical pathway. The products are obtained in pure form without column purification. The method was successfully applied for a gram-scale production of 3,3-difluoro-2-(4-fluorophenyl)-2,3-dihydroimidazo[1,2-a]pyridin-2-ol (3m). The Zolimidine drug successfully underwent difluorinative-hydroxylation in high yield. Interestingly, addition of the tetra-n-butyl ammonium halide or NaI or KSCN or NaNO2 in the reaction provided oxidative functionalization of imidazopyridine wherein Selectfluor acted as an oxidant. The C-3 substituted (Cl, Br, I, SCN and NO) imidazo[1,2-a]pyridines were prepared in good yields. These two significant reactions provided wide functional group tolerance, metal/ base-free, and green approach.