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The installation of sulfonamide pharmacophores on heterobiaryls has successfully been executed by a previously unknown palladium-catalyzed intramolecular oxidative coupling in N-arylsulfonyl heterocycles followed by novel ring opening of heterobiaryl sultams with amine nucleophiles. The protocol has a wide scope of substrates warranting broad applications in the synthesis of heterobiaryls containing an o-sulfonyl or carboxyl functional group.
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http://dx.doi.org/10.1021/acs.orglett.5b00290 | DOI Listing |
Org Lett
September 2025
School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529090, P. R. China.
3-Fluoropyrroles are privileged scaffolds in pharmaceutical and agrochemical applications, yet their synthesis remains challenging. Herein, we report a palladium(0)-catalyzed [4+1] cycloaddition/dehydration strategy for the efficient construction of 3-fluoropyrroles from readily available 3,3-difluoropent-4-en-2-ones and primary amines. This transformation proceeds via C-F bond activation to generate a key π-allyl-Pd(II) intermediate, followed by intramolecular addition/dehydration to furnish the heterocyclic core.
View Article and Find Full Text PDFOrg Biomol Chem
August 2025
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China.
A palladium-catalyzed domino Heck/cross-coupling reaction of alkene-tethered aryl iodides with β-chloroenones is reported. This reaction enables the formation of one C-O bond and two C-C bonds to construct bisheterocycles in a single operation an intramolecular carbopalladation, followed by a carbene-based cross-coupling with β-chloroenones as a non-diazo carbene precursor, providing an efficient method for synthesizing furan-linked dihydrobenzofurans/oxindoles in yields up to 98%.
View Article and Find Full Text PDFOrg Lett
August 2025
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
A palladium-catalyzed autotandem reaction between 1,4-diyn-3-yl carbonates and -functionalized activated alkenes is presented, proceeding through a sequential allenylation, vinylogous addition, and intramolecular propargylation process. A broad array of fused and spirocyclic architectures that include a cyclobutane motif are straightforwardly constructed in moderate to good yields with high regio- and diastereoselectivity.
View Article and Find Full Text PDFJ Org Chem
August 2025
Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, P. R. China.
The direct functionalization of small heterocyclic molecules is an efficient strategy for constructing large heteroatom-doped polycyclic aromatic systems. However, due to the unique reactivity of acridone, π-extension on the benzene ring generally leads to the formation of angular-shaped acridone derivatives. In this study, we present the selective synthesis of both linear and angular π-extended acridone derivatives incorporating acenaphthylene units with intervening five-membered rings.
View Article and Find Full Text PDFMolecules
July 2025
Department of Engineering, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065, Japan.
A synthesis of substituted 1,4-benzodiazepines has been developed via palladium-catalyzed cyclization of -tosyl-disubstituted 2-aminobenzylamines with propargylic carbonates. The reaction proceeds through the formation of π-allylpalladium intermediates, which undergo intramolecular nucleophilic attack by the amide nitrogen to afford seven-membered benzodiazepine cores. In reactions involving unsymmetrical diaryl-substituted carbonates, regioselectivity was observed to favor nucleophilic attack at the alkyne terminus substituted with the more electron-rich aryl group, suggesting that electronic effects play a key role in determining product distribution.
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