Synthesis of 2-Sulfonylthiazoles via Heteroaryl C–H Sulfonylation of Thiazole N-Oxides

Abstract

AbstractDescribed here is an efficient method for the modular synthesis of 2-sulfonylthiazole derivatives via heteroaryl C–H sulfonylation. The protocol is composed of two stages involving O-activation of thiazole N-oxides and nucleophilic addition of a sulfinate, which induces N(3)-deoxygenation and C(2)-sulfonylation. The vicarious substitution is performed most effectively by using 4-methoxybenzoyl chloride for O-acylation while employing sodium [tert-butyl(dimethyl)silyloxy]methanesulfinate (TBSOMS-Na) as the nucleophile. The sulfones thus obtained can be converted to an array of thiazolyl sulfones, sulfonamides, and sulfonyl fluorides by displacing the silyloxymethyl moiety with alkyl, aryl, amino, and fluoro groups. The C–H sulfonylation approach, in combination with a sulfoxylate (SO2 2–) strategy, provides direct access to sulfonylated thiazole scaffolds without recourse to the use of 2-halothiazoles.