Synthesis of 2,4-Disubstituted Oxazoles and Thiazoles via Brønsted Acid-Catalyzed Cyclization of α-diazoketones with Amides

Abstract

A novel method is described for the synthesis of 2,4-disubstituted oxazole and thiazole derivates via the coupling of αdiazoketones with (thio)amides or thioureas using trifluoromethanesulfonic acid (TfOH) as a catalyst. This protocol is characterized by mild reaction conditions, metal-free, and simplicity and also features good functional group tolerance, good to excellent yields, and a broad substrate scope with more than 40 examples. Experimental studies suggest a mechanism involving 2-oxo-2-phenylethyl trifluoromethanesulfonate as the key intermediate.

Trideuteromethylthiolation through Reaction of Arynes, S-Methyl-d3 Sulfonothioate with Sulfonamides or Amides: Access to Trideuteromethylated Sulfilimines

“…The 1a′ - D was synthesized according to previously reported method . To an oven-dried 25 mL Schlenk sealed tube equipped with a magnetic stir bar was added the amides 1a′ - D (0.3 mmol, 1.5 equiv), CsF (182.3 mg, 1.2 mmol, 6.0 equiv) and 18-crown-6 (317.2 mg, 1.2 mmol, 6.0 equiv).…”

Electrochemical Enaminone-Thioamide Annulation and Thioamide Dimeric Annulation for the Tunable Synthesis of Thiazoles and 1,2,4-Thiadiazole

“…In this context, thioamides, as isosteres of amides with higher lipophilicity and stability, have been extensively used as precursors to synthesize 2-alkyl/aryl thiazoles. An array of thioamide-based methods have been established for thiazole synthesis, including metal-catalyzed cyclizations, visible-light-induced cascade processes, cyclization with ylides, multicomponent reactions, and others . However, these existing methods suffer from one or more of the drawbacks of using a heavy metal catalyst, stoichiometric oxidant/reductant utilization, harsh reaction conditions, and a narrow substrate scope.…”