Synthesis of Air-stable, Odorless Thiophenol Surrogates via Ni-Catalyzed C-S Cross-Coupling.

Abstract

Thiophenols are versatile synthetic intermediates whose practical appeal is marred by their air sensitivity, toxicity and extreme malodor. Herein we report an efficient catalytic method for the preparation of S-aryl isothiouronium salts, and demonstrate that these air-stable, odorless solids serve as user-friendly sources of thiophenols in synthesis. Diverse isothiouronium salts featuring synthetically useful functionality are readily accessible by nickel-catalyzed C-S cross-coupling of (hetero)aryl iodides and thiourea. Convenient, chromatography-free isolation of these salts is achieved by precipitation, allowing the methodology to be applied directly to large scales. Thiophenols are liberated from the corresponding isothiouronium salts upon treatment with a weak base, enabling an in situ release/S-functionalization strategy that entirely negates the need to isolate, purify or manipulate these noxious reagents.