Deuterated-alkylation reagents based on sulfonium salts as cation and radical sources.

The article focuses on the development and improved synthesis of deuterated (dₙ) alkylating reagents, specifically alkyl diphenylsulfonium salts (1a) and alkyl thianthrenium salts (1b), which are used to introduce stable carbon–deuterium (C–D) bonds at the α-position of heteroatoms in drug molecules. These reagents are prepared via deuteration using D₂O as an inexpensive deuterium source under basic conditions, enabling one-pot synthesis of dₙ-alkylated compounds with high deuterium content. Additionally, alkyl thianthrenium salts serve as radical sources under photo-induced conditions, allowing regioselective incorporation of deuterium without transition metal catalysts. This methodology aims to advance drug discovery by improving pharmacokinetic and toxicity profiles through stable C–D bond incorporation at metabolic sites commonly targeted by cytochrome P450 enzymes.