A sequential reaction of picolinamide with benzaldehydes promoted by Pd(TFA)2: rapid access to 4,5-disubstituted 2-(pyridin-2-yl)oxazoles in n-octane

Abstract

We developed a synthetic method for obtaining 4,5-disubstituted 2-(pyridin-2-yl)oxazoles from picolinamide and aldehydes by employing Pd(TFA)₂ as the catalyst in n-octane. This cascade reaction involves the condensation of picolinamide and two aldehyde molecules promoted by trifluoroacetic acid (TFA) generated in situ from Pd(TFA)₂. This one-pot protocol provides rapid access to synthetically valuable triaryloxazoles from readily available starting materials under mild conditions. An ¹⁸O labeling study revealed that this tandem reaction proceeded via a different reaction mechanism compared to the Robinson–Gabriel oxazole synthesis.