Efficient synthesis of di- and trisubstituted 2-aryloxazoles via ytterbium(III) triflate catalyzed cyclization of tertiary propargylic alcohols with aryl amides

An efficient synthetic method to prepare di- and trisubstituted 2-aryloxazoles based on Yb(OTf)3 catalyzed cyclization of trisubstituted propargylic alcohols with aryl amides is described. The reaction was accomplished in moderate to excellent product yields and with complete regioselective control. The mechanism is suggested to involve activation of the starting alcohol by the metal catalyst that results in its ionization. Subsequent cyclization of this newly generated carbocationic species with the aryl amide then affords the oxazole. In view of the mild conditions along with the low cost, commercially availability of Yb(OTf)3 and its high tolerance to air and moisture, the present synthetic approach offers an operationally simplistic and convenient route to this important aromatic heterocycle.

Graphical abstractAn efficient synthetic method to prepare di- and tri substituted 2-aryloxazoles based on Yb(OTf)3 catalyzed cyclization of trisubstituted propargylic alcohols with aryl amides is described. The reaction was accomplished in moderate to excellent product yields and as a single regioisomer. In view of the mild conditions along with the low cost, commercially available Yb(OTf)3 and its high tolerance to air and moisture, the present synthetic approach offers an operationally simplistic and convenient route to this important aromatic heterocycle.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch Highlights►Yb(OTf)3 promoted ionization of trisubstituted propargylic alcohols. ►Efficient cyclization of trisubstituted propargylic cations with aryl amides. ►Operationally simplistic and convenient synthetic route to 2-aryloxazoles.