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 O₂ 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-d₆ (CD₃SOCD₃) was used in place of DMSO. The presented novel strategy for DMSO or DMSO-d₆ 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.