Development of a Parallel Strategy for the Synthesis of a Library of 2-(3-Formyl-5-arylfuran-2-yl)ethylcarbamates from Dihydropyridinones

Abstract

2,3-Dihydropyridin-4(1H)-ones were utilized as scaffolds for the syntheses of libraries of 5-arylethynyl-2,3-dihydropyridin-4(1H)-ones and 2-(3-formyl-5-arylfuran-2-yl)ethylcarbamates. 2,3-Dihydropyridin-4(1H)-ones were prepared from piperidones, ynones, and pyridones and used for the synthesis of a library of 5-arylethynyl-2,3-dihydropyridin-4(1H)-ones employing a Sonogashira reaction. Further reaction of these compounds using an Au(III)-catalyzed cyclization method yielded formylfurans. N-Boc and N-benzyl protected 2,3-dihydropyridin-4(1H)-ones were prepared for the Sonogashira reaction. N-Boc-protected 5-iodo-2,3-dihydropyridin-4(1H)-ones provided tert-butyl 5-arylethynyl-4-oxo-3,4-dihydropyridine-1(2H)-carboxylates in moderate to excellent yields while the N-Bn-protected enaminones provided low yields of 5-arylethynyl-1-benzyl-2,3-dihydropyridin-4(1H)-ones. Furan formation was achieved by Au(III)-catalyzed and Cu-mediated cyclizations. (±)tert-Butyl 1-(3-formyl-5-phenylfuran-2-yl)propan-2-ylcarbamates were obtained during the Sonogashira reactions catalyzed by Cu(I), while (±)tert-Butyl 1-(3-formyl-5-phenylfuran-2-yl)-3-phenylpropan-2-ylcarbamates were formed by the Au(III)-catalyzed cyclization. A library of 16 compounds of highly substituted furans was synthesized in moderate to excellent yields.