DMSO (dimethyl sulfoxide) as a two-methyl source: C–H (trideutero)methylation of (iso)quinolines and their N-oxides

Abstract

(Trideutero)methylation is an important process in both chemistry and biology. In this context, DMSO(-d₆) has largely been used as a source of ˙CH₃/˙CD₃. Typically, all known DMSO(-d₆)-based (trideutero)methylation procedures: (i) employ a significant excess of DMSO(-d₆) as a reagent and solvent and (ii) cleave and utilize only one of the two (trideutero)methyl groups of DMSO(-d₆). For the first time, using persulfate (S₂O₈²⁻) and graphitic carbon nitride (g-C₃N₄) as the visible-light photocatalyst, we herein describe a methodology that works with merely stoichiometric quantities of DMSO(-d₆) and cleaves and utilizes both of the (trideutero)methyl groups of DMSO(-d₆) for the C–H (trideutero)methylation of (iso)quinolines and their N-oxides. We also describe the reusability of the g-C₃N₄ catalyst and a plausible reaction mechanism. The use of DMSO-d₆ requires careful financial management due to its fairly high retail price (around 600 USD for 100 mL). We thus feel that the (trideutero)methylation method described here, which uses merely stoichiometric amounts of DMSO(-d₆), is far less expensive and environmentally benign than the methods described in the literature.