ArticleNature communications2026
Disulfide modification and thiol protection via tris(trimethylsilyl)silane-mediated hydrosilylation of disulfides.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Thiol functionalities are indispensable in both biological and synthetic chemistry. However, unlike the powerful silylation strategies for hydroxyl groups, widespread applications in sulfur chemistry are severely hampered by the weak and hydrolytically labile nature of the Si-S bond. Here, we report that tris(trimethylsilyl)silane (TTMSS), a unique trisilyl-substituted reagent, efficiently enables the rapid hydrosilylation of disulfides under exceptionally mild conditions. This reaction affords robust silyl sulfides that show significantly enhanced hydrolytic stability compared to conventional analogues. The robust platform enables a practical, readily available strategy for orthogonal thiol protection and late-stage disulfide modification in complex molecules. Crucially, this finding reveals that the kinetic and thermodynamic properties of the Si-S bond can be finely tuned by strategic silyl substitution, establishing a general principle that reinvigorates silyl-protective methods for challenging sulfur chemistry.
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