Efficient Reductive N-11C-Methylation Using Arylamines or Alkylamines and In Situ–Generated [11C]Formaldehyde From [11C]Methyl Iodide

Reductive N-¹¹C-methylation using [¹¹C]formaldehyde and amines has been used to prepare N-¹¹C-methylated compounds. However, the yields of the N-¹¹C-methylated compounds are often insufficient. In this study, we developed an efficient method for base-free reductive N-¹¹C-methylation that is applicable to a wide variety of substrates, including arylamines bearing electron-withdrawing and electron-donating substituents. A 2-picoline borane complex, which is a stable and mild reductant, was used. Dimethyl sulfoxide was used as the primary reaction solvent, and glacial acetic acid or aqueous acetic acid was used as a cosolvent. While reductive N-¹¹C-methylation efficiently proceeded under anhydrous conditions in most cases, the addition of water to the reductive N-¹¹C-methylation generally increased the yield of the N-¹¹C-methylated compounds. Substrates with hydroxy, carboxyl, nitrile, nitro, ester, amide, and phenone moieties and amine salts were applicable to the reaction. This proposed method for reductive N-¹¹C-methylation should be applicable to a wide variety of substrates, including thermo-labile and base-sensitive compounds because the reaction was performed under relatively mild conditions (70°C) without the need for a base.