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A copper-catalyzed efficient, operationally simple, general method for straightforward syntheses of polysubstituted pyrroles employing ethynyl methylene cyclic carbamates as precursors reacting with commercially available amines was first reported. A wide variety of polysubstituted pyrroles were obtained in acceptable to good yields under mild conditions. This protocol features broad substrate scope, high functional group tolerance, and easy operation, therefore enabling late-stage functionalization and rapid synthesis of bioactive compounds, including structurally complex marketed drugs and natural products. In addition, a scale-up experiment further highlighted the synthetic utility.
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http://dx.doi.org/10.1021/acs.orglett.4c03334 | DOI Listing |
J Org Chem
August 2025
School of Chemistry and Materials Science, Jiangsu Key Laboratory of Green Synthesis for Functional Materials, Jiangsu Normal University, Xuzhou, Jiangsu 221116, China.
A controlled silver-catalyzed cycloaddition reaction of α,β-unsaturated nitroketones with isocyanides has been developed, facilitating the construction of polysubstituted pyrroles. This protocol addresses the issue of side reactions associated with the high reactivity of the aldehyde group in conventional reactions by employing a synergistic strategy for the protection and deprotection of the aldehyde group. Additionally, the nitrone moiety stabilizes the cycloaddition transition state through spatial electronic effects and is spontaneously deprotected to yield aromatization products.
View Article and Find Full Text PDFJ Am Chem Soc
July 2025
Department of Chemistry and Life Science, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan.
The synthesis of polysubstituted (hetero)aromatic compounds is essential in various fields, including pharmaceuticals, where such compounds are fundamental to many approved drugs. In this study, we present a novel electrochemical method for single-carbon insertion targeting various (hetero)aromatic compounds, with a particular focus on pyridines. In this process, the electrochemical oxidation of pyrrole derivatives produces a radical cation intermediate, which then undergoes nucleophilic attack by diazo compounds to yield polysubstituted pyridine derivatives.
View Article and Find Full Text PDFJ Org Chem
June 2025
College of Material, Chemistry and Chemical Engineering, Key Laboratory of Organosilicon Chemistry and Material Technology, Hangzhou Normal University, Hangzhou 311121, P. R. China.
A protocol for synthesizing polysubstituted 1-pyrrolines (3,4-dihydro-2-pyrrole) via base-mediated [3 + 2] cycloaddition of vinyl sulfoxides with -benzyl ketimines under mild conditions has been developed. The methodology exhibits exceptional functional group compatibility, demonstrating applicability to both terminal and internal vinyl sulfoxide substrates. Control experiments and H NMR analyses have been conducted to propose a plausible reaction pathway.
View Article and Find Full Text PDFOrg Lett
May 2025
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russia.
Terminal (het)arylacetylenes react (KOBu/DMSO, 60 °C, 1 h) with -allyl ketimines to afford 2-(het)aryl-4-(het)arylmetyl-5-ethylpyrroles in up to 71% yield as a result of the interaction of acetylenic and azadienic carbanions with C=N and C≡C bonds. This new reaction opens a one-pot access to synthetically and pharmaceutically prospective compounds.
View Article and Find Full Text PDFChem Commun (Camb)
June 2025
College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang, 473061, China.
We report a novel photocatalytic [3+2] annulation strategy employing -aryl glycinates and 2-benzylidenemalononitrile partners for the efficient construction of polysubstituted pyrrole architectures. This methodology features operationally mild, redox-neutral conditions with exceptional functional group tolerance and broad substrate generality, while maintaining remarkable atom economy. Notably, the transformation utilizes dimethyl sulfoxide as both a reaction medium and a green oxidant.
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