Hydromethylthiolation of alkynes via nucleophilic addition of dimethyl disulfide in DMSO.

• This study is the first to discover that dimethyl disulfide, which is typically used as an electrophilic methanesulfenylating reagent in organic synthesis, can be reduced by dimethyl sulfoxide under basic conditions. One equivalent of dimethyl disulfide can be reduced to produce two equivalents of nucleophilic methiolate anion. • In this study, the nucleophilic methiolate anion generated from dimethyl disulfide was utilized to achieve hydromethylthiolation through nucleophilic addition to alkynes. This method exhibits good regioselectivity and stereoselectivity for most substrates. • Besides dimethyl disulfide, this method is also applicable to other disulfides for the hydrothiolation of alkynes. A hydromethylthiolation method for various alkynes has been developed using dimethyl disulfide as a source of the nucleophilic methylthiolate anion in a DMSO/EtOH or DMSO/H 2 O solvent system, with KOH as the base. For terminal aromatic alkynes, the reactions predominantly yield (Z)-anti-Markovnikov hydromethylthiolation products. The ratio of anti-Markovnikov to Markovnikov products typically exceeds 10:1, while the ratio of (Z)- to (E)-anti-Markovnikov products usually surpasses 7:1. In contrast, terminal aliphatic alkynes primarily produce Markovnikov hydromethylthiolation products. Reactions of internal aromatic alkynes also successfully produce the corresponding hydromethylthiolation products, whereas internal aliphatic alkynes do not exhibit reactivity in this system. The proposed mechanism suggests that in a basic DMSO solvent system, each equivalent of dimethyl disulfide is converted into two equivalents of methylthiolate anion. This anion then undergoes nucleophilic addition to the alkyne substrates, yielding hydromethylthiolation products. The regioselectivity and stereoselectivity of the hydromethylthiolation are influenced by the stability of the vinyl carbanion intermediate. Additionally, this method is also applicable to the hydrothiolation of alkynes using other disulfides. [ABSTRACT FROM AUTHOR]