Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• DOI: 10.3762/bjoc.20.126
• Publication Date: 2024-06-28T07:04:35Z
• Authors: Xiu-Yu Chen; Ying Han; Jing Sun; Chao-Guo Yan
• Keywords: electron-deficient alkyne; isocyanide; QD241-441; cyclopenta-1,3-diene; 1,4-dihydropyridine; Science; cyclopenta[4,5]pyrrolo[2,3-b]pyridine; Q; Organic chemistry; [3 + 2] cycloaddition; Full Research Paper

An efficient protocol for the synthesis of polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates was developed by a three-component reaction. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile afforded polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates in high yields and with high diastereoselectivity. The reaction was finished by in situ generation of activated 5-(alkylimino)cyclopenta-1,3-dienes from addition of alkyl isocyanide to two molecules of but-2-ynedioates and sequential formal [3 + 2] cycloaddition reaction with 5,6-unsubstituted 1,4-dihydropyridine.