Copper(II) Triflate Catalyzed Synthesis of 2,4-Disubstituted Oxazoles from α-Diazoketones

Abstract

A novel method is devised for the synthesis of 2,4-disubstituted oxazole derivatives via the coupling of α-diazoketones with amides using copper(II) triflate as the catalyst. The synthetic versatility of this approach is exemplified in the synthesis of an analogue of balsoxin.

Recent Development and Green Approaches for Synthesis of Oxazole Derivatives: A Review

“…Gao et al [55] synthesized oxazole in the presence of iodine and potassium carbonate in DMF at 80° using bromoacetophenone and benzylamine as starting reagents to give 2,5-diphenyloxazole in the 46 % yield. Reddy et al [56] describe an easy and convenient synthesis of 2,4-disubstituted oxazoles by coupling substituted α-diazoketones with substituted amides in 1,2-dichloroethane in the presence of copper(II) triflate [Cu(OTf) 2 ].The desired product, 2,4-disubstituted oxazole, is obtained at an 87 % yield after increasing the temperature from 25° to 80°. Bailey et al [57] identified the optimal reaction conditions for the synthesis of 2,4-disubstituted and 2,4,5-trisubstituted oxazoles by using haloketones and substituted arylamides in the presence of ethyl acetate and silver triflate (AgOTF) as a catalyst used for promotion of cyclization reaction, observing the effect of temperature, stoichiometry, and optimum light on the process.…”

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

“…Indeed, expensive catalysts and reaction conditions of microwave have been largely limited to the reactions. 5 Recently, Li and co-workers reported the copper-catalyzed cyclization of α-fluoroalkyl-α-diazoketones with amides to construct 5-fluoroalkylated trisubstituted oxazoles (Figure 1b). 6 In comparison, although the cheaper copper catalyst has been used, attempts to realize a similar transformation of α-fluoroalkyl-α-diazoketones have been beset by both harsh reaction conditions and limited scope.…”

“…However, the reported example of trifluoroacetyl diazoketoester behaves somewhat differently to its nonfluorinated counterpart, displaying a narrow substrate scope. Indeed, expensive catalysts and reaction conditions of microwave have been largely limited to the reactions . Recently, Li and co-workers reported the copper-catalyzed cyclization of α-fluoroalkyl-α-diazoketones with amides to construct 5-fluoroalkylated trisubstituted oxazoles (Figure b) .…”