Necopidem

A metal‐free and oxidant‐free electrochemically enabled strategy for C‐3 formylation of imidazopyridines using trimethylamine as a one‐carbon source has been established. This conversion has high functional group compatibility under mild conditions and ensures late‐stage functionalization of pharmaceutical molecules. Furthermore, unexpected hexafluoroisopropoxylation products have been observed in some cases. Mechanistic studies using cyclic voltammetry and control experiments reveal the key intermediate of the formylation process.

Our studies have led to the development of an unprecedented intramol. dehydrogenative aminooxygenation process that produces imidazo[1,2-a]pyridine-3-carbaldehydes, e.g. I (R¹ = Me, Br, R² = H; R¹ = H, R² = Cl, Br) , and 1,2-disubstituted imidazole-4-carbaldehydes, e.g. II (R¹ = Ph, R² = Ph, Me; R¹ = 4-MeOC₆H₄, 4-BrC₆H₄, R² = Me), from readily available N-allyl-2-aminopyridines and substituted N-allylamidines, resp.The reaction, carried out by using 20 mol % of Cu(II) catalyst in DMF or DMA under dioxygen, is efficient and environmentally benign because it does not require addnl. organic or inorganic oxidants.Substituted imidazo[1,2-a]pyridine-3-carbaldehydes and imidazole-4-carbaldehydes, which can serve as versatile synthetic intermediates, are obtained in moderate to good yields by a reaction that possesses a broad substrate scope and good functionality tolerance.