Development of a parallel strategy for the synthesis of a library of 2-(3-formyl-5-arylfuran-2-yl)ethylcarbamates from dihydropyridinones.

摘要

2,3-Dihydropyridin-4(1H)-ones were utilized as scaffolds for the syntheses of libraries of 5-arylethynyl-2,3-dihydropyridin-4(1 H)-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(1 H)-ones employing a Sonogashira coupling 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 coupling reaction. N-Boc-protected 5-iodo-2,3-dihydropyridin-4(1 H)-ones provided tert-butyl 5-arylethynyl-4-oxo-3,4-dihydropyridine-1(2 H)-carboxylates in moderate to excellent yields while the N-Bn-protected enaminones provided very low yields of 5-arylethynyl-1-benzyl-2,3-dihydropyridin-4(1 H)-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 coupling 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. Some of the furans were obtained by both methods. Only in the case of tert-butyl 4-methoxy-2-p-tolyl-6,7-dihydrofuro[3,2-c]pyridine-5(4 H)-carboxylate was the –OMe group retained under Au(III)-catalyzed cyclization conditions, which involved methanol as a nucleophile. In all other cases, N-Boc 3-formyl furans were formed. A library of 16 compounds of functionalized furans possessing the N-Boc adehyde functionality was constructed in moderate to excellent yields.