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

Taku Nakayama; Sayaka Fujiki; Tomokatsu Enda; Shoko Kikkawa; Hidemasa Hikawa; Isao Azumaya

doi:10.1039/d3ob01815f

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

Org Biomol Chem. 2024 Jan 24;22(4):759-766. doi: 10.1039/d3ob01815f.

Authors

Taku Nakayama¹, Sayaka Fujiki¹, Tomokatsu Enda¹, Shoko Kikkawa¹, Hidemasa Hikawa¹, Isao Azumaya¹

Affiliation

¹ Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. hidemasa.hikawa@phar.toho-u.ac.jp.

PMID: 38168691
DOI: 10.1039/d3ob01815f

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.