Activation of DMSO(-d6) via heterogeneous photo-Fenton-like process with in situ production of Hydroxyl radicals for the C-H (trideutero)methylation of (iso)quinoliniums

Abstract

To activate dimethyl sulfoxide (DMSO, CH3SOCH3) as a methylation agent in the C-H functionalization of (iso)quinoliniums (1), a heterogeneous photo-Fenton-like method involving the in situ generation of hydroxyl radicals by a gCN/MnO/MnO(OH) photocatalyst under visible light irradiation was realized for the first time. In the developed methodology, only a small amount of gCN/MnO/MnO(OH) photocatalysts (15 mg) was needed for the methylation of (iso)quinoliniums (1.0 mmol-scale of 1) to achieve moderate to good yields of the expected methylated-products (2) under ambient conditions. Mechanistically, hydroxyl radicals (OH) are produced when the gCN/MnO/MnO(OH) photocatalyst reacts with H2O and O-2 under visible light illumination, and then they are added to DMSO, where they subsequently fragment into CH3 radicals. The product is generated via the nucleophilic attack of the CH3 radical at the most electron-deficient position of 1, followed by deprotonation reaction. The same procedure could also be used to create trideuteromethylated (iso)quinolines (3) when DMSO-d(6) (CD3SOCD3) was used in place of DMSO. The presented novel strategy for DMSO or DMSO-d(6) activation herein is more practical, cost-effective, and risk-free compared to the conventional Fenton reagent (H2O2 and Fe2+/Fe3+) systems available in the literature. Additionally, the gCN/MnO/MnO(OH) photocatalyst is easy to prepare, practical and economical together with being easy recoverable and reusable for several runs without considerable loss in its initial activity.