Vaska's complex–PMHS combination enabled mild and chemoselective reduction of sulfoxides to sulfides with low catalyst loading

• Published in: Organic chemistry frontiers an international journal of organic chemistry 2024-04, Vol.11 (9), p.2448-2456
• Main Authors: Fang-Fang, Xu, Zhong-Lei Ruan, Pei-Qiang Huang
• Format: Article
• Language: English
• Subjects: Ambient temperature; Catalysts; Deoxygenation; Functional groups; Pharmacophores; Renewable resources; Sulfides; Sulfoxides; Sustainable yield
• ISSN: 2052-4110; 2052-4110
• DOI: 10.1039/d4qo00312h

Herein, we report the catalytic deoxygenative reduction of sulfoxides to sulfides in good to excellent yields. This method was enabled by the combination of Vaska's complex with poly(methylhydrosiloxane) (PMHS). This reduction system is highly efficient, allowing the reaction to proceed at ambient temperature with a low catalyst loading (from 0.4 mol% to 0.001 mol% of Ir). This method also features versatility for diverse types of sulfoxides and high chemoselectivity for the sulfinyl group in the presence of other reducible or sensitive functional groups. Sulfoxides that were challenging using reported methods were reduced smoothly. A plausible mechanism involving two catalytic cycles was proposed. The applicability of this method was demonstrated by gram-scale syntheses and the late-stage modification of multifunctional pharmaceuticals leading to a sulfide drug, two prodrugs, and some pharmacophores. The convenient additive-free and extraction-free protocol, the efficiency allowing lowering catalyst loading to 0.001 mol% (Ir), and the use of 2-methyltetrahydrofuran, a solvent produced from renewable resources, together constitute the sustainability of this method.