Deuterated-Alkylation Reagents based on Sulfonium Salts as Cation and Radical Sources

The replacement of C-H bonds with more stable C-D bonds at the a-position of heteroatoms, which is the typical metabolic site for cytochrome P450, is important in drug discovery. Recently, we have developed dn (deuterated)-alkylated sulfonium salts (1a-dn), which were easily prepared by deuteration (H/D exchange reaction) with D2O of the corresponding alkyl diphenylsulfonium salts (1a), as electrophilic dn-alkylating reagents (cation sources). Herein, we newly report an improved preparation method of 1a and one-pot synthesis of dn-alkylated compounds via the deuteration of 1a with D2O and the subsequent nucleophilic substitution under basic conditions. Additionally, dn-alkyl thianthrenium salts (1b-dn) were also found to work as dn-alkylating reagents (cation sources). Furthermore, 1b-dn surved as radical sources under photo-induced reaction conditions with Ir photocatalyst, Hantzsch ester, or triphenylamine to obtain various regioselectively deuterium-incorporated alkyl compounds. These dn-alkylating reagents will contribute to advance the drug discovery.