One-pot Mo(CO)6-facilitated transformation of anilines into benzophenones via in situ pyridinium reconfiguration

Abstract

A novel, mechanochemical, one-pot transformation of anilines to benzophenones using molybdenum hexacarbonyl (Mo(CO)₆) was achieved, avoiding pre-functionalization steps inherent in such conversions. The reaction capitalizes on the activation of the C(sp²)–NH₂ bond in anilines via in situ formation of pyridinium salts: a strategy impeded by the inertness of the C–N bond. For this envisioned methodology, pyrylium tetrafluoroborate was used to convert anilines into reactive pyridinium intermediates, which undergo carbonylation in the presence of Mo(CO)₆. The corresponding acyl pyridinium intermediates, in turn, are amenable for C–C coupling under transition metal catalyst-free conditions, driven by the piezoelectric nature of barium titanate in a mechanochemical reaction setup. This approach shows a very general substrate scope, good functional group tolerance, and fair-to-excellent yields (50–92%, depending on the aniline derivative used) of benzophenone analogues. This acyl-intermediate-based method has been further applied to the synthesis of 3-benzoylchromones, attesting to its broad scope. Therefore, the described late-stage functionalization strategy, free of transition metals, represents progress in the scope of bioactive compound syntheses for medicinal chemistry.