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

Abstract

Described 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 N3-deoxygenation and C2-sulfonylation. The vicarious substitution is performed most effectively by using 4-methoxybenzoyl chloride for O-acylation while employing sodium tert-butyldimethylsilyloxymethanesulfinate (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.

Cluster Preface: Special Issue Honoring Masahiro Murakami’s Contributions to Science

“…12 The modularity of in situ generated Rh carbenes is additionally covered by Lacour, showing the potential of N-substituted oxazolidines as a vehicle for preparing eight-membered 1,3,6-or 1,4,6-oxadiazocines in a regiodivergent manner. 13 This Cluster also includes a contribution from Lee on the synthesis of 2-sulfonylthiazoles via heteroaryl C-H sulfonylation without recourse to the utilization of halogenated derivatives, 14 whilst Fensterbank, Ollivier and Lemiere describe a Ni-catalyzed coupling of organosilicates as a platform to rapidly and reliably construct sp 2 -sp 3 architectures. 15 Li reports a Rh-catalyzed regioselective N-reverse prenylation of indoles under neutral conditions by using triphenyl phosphite ligands.…”