Recent Applications of Hexamethyldisilathiane (TMS 2 S) in Organic Synthesis

Hexamethyldisilathiane (TMS2S), also named bis(trimethylsilyl) sulfide, (CAS: 3385-94-2), was reported for the first time in the early 1950’s.1 This liquid compound (bp 160 °C) was prepared by the reaction between iodotrimethylsilane and silver sulfide. Alternatively, bis(trimethylsilyl) sulfide has been also prepared by the addition of disodium sulfide on chlorotrimethylsilane.1,2 TMS2S is nowadays commercially available (ca. 28 €/g).3 This reagent can be viewed as a S1 source of sulfide that is less toxic, less flammable, and easier to handle than gaseous hydrogen sulfide (H2S). On contact with water, TMS2S releases H2S and should be stored in a cold and dry place in an oxygen-free atmosphere. TMS2S is used as a sulfur transfer agent for the synthesis of alkyl sulfides, thioaldehydes, or thioketones but also as a reducing agent.4 TMS2S is also employed in the synthesis of inorganic–organic hybrid clusters5 or phosphinidene sulfide compounds.6 It is noteworthy that the number of publications describing the use of TMS2S has steadily increased since the 1950’s to reach an average of 65 publications per year from 2015 to 2022.7 This Spotlight article highlights the versatility of TMS2S as a S1 source of sulfides and its recent applications in organic synthesis. In 1999, Hu and Fox reported a trimethylsilylthioxy dehalogenation reaction for the synthesis of functionalized thiols (Table 1, A).8 In this process, tetrabutylammonium trimethylsilylthiolate (Me3SiSBu4N), generated in situ Dr Damien Hazelard (right) obtained his PhD in 2005 under the supervision of Dr A. Fadel (Paris-Sud University). In 2006, he performed a postdoctoral training in the field of organocatalysis in the group of Prof. Y. Hayashi at the Tokyo University of Science. Then he joined the group of Prof. F. Colobert to work on total synthesis at the University of Strasbourg. He was appointed in 2010 as assistant professor at the same university in the group of Prof. P. Compain. In July 2019, he defended his habilitation (‘Habilitation à Diriger des Recherches’). His main research interests are the development of new synthetic methodologies for the synthesis of glycomimetics.