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Five-carbon (C5) structural units are the fundamental building blocks of many natural products. An unprecedented palladium-catalyzed three-component dehydrogenative cascade coupling of indoles, 2-methylbut-2-ene, and carboxylic acids has been developed. The approach enables the straightforward introduction of a C3'-bonded five-carbon structural unit with a tertiary alcohol quaternary carbon center into indoles. The protocol employs 2-methylbut-2-ene as the C5 source and is featured by a broad substrate scope, atom and step economies, and high chemo- and regioselectivies.
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http://dx.doi.org/10.1021/acs.orglett.1c03776 | DOI Listing |
Org Lett
September 2025
College of Chemistry and Environmental Science, The Key Laboratory of Xinjiang Native Medicinal and Edible Plant Resources Chemistry, Kashi University, Kashi 844000, China.
A palladium-catalyzed oxygenative amidation of metal carbynoids via three-component reaction of α-bromo diazoacetates, alcohols, and imines is reported. This strategy enables the simultaneous formation of C═O and C-N bonds at the carbynoid center, affording a broad range of oxindole-derived oxalamides in good to high yields under mild conditions. Mechanistic studies confirm that the carbonyl oxygen originates from the alcohol.
View Article and Find Full Text PDFACS Catal
August 2025
University of Texas at Austin, Austin, Texas 78712, United States.
Alkyl boronic acids and esters are versatile synthetic intermediates that generally require several steps to synthesize. Three-component alkene arylboration reactions allow for the rapid synthesis of alkyl boronic esters. Herein, we report the base-free aerobic Pd-catalyzed three-component alkene arylboration, which allows direct access, in a single step, to alkyl boronic esters from readily available precursors: aryl boronic acids, alkenes, and bis(pinacol)diboron.
View Article and Find Full Text PDFChem Commun (Camb)
September 2025
College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, P. R. China.
A palladium-catalyzed divergent three-component reaction employing norbornene derivatives as controlled switches toward phosphonate-containing indenes and indanes was established. When using norbornadiene, norbornene or 7-oxabenzonorbornadiene as a substrate, alkylphosphonate-containing indanes were synthesized through a cascade [3+2] cyclization and alkylation of P(O)H process. Alternatively, oxanorbornadiene enabled the assembly of phosphonate-containing indenes a subsequent retro-Diels-Alder reaction.
View Article and Find Full Text PDFOrg Lett
July 2025
Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Laboratory of Molecule-Based Materials (State Key Laboratory Cultivation Base), College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, P.R. China.
A three-component construction of eight-membered nitrogen-containing heterocycles via palladium-catalyzed imidoylative cyclization of 2-isocyano--(propa-1,2-dien-1-yl)benzamides with aryl halides and carbon nucleophiles has been developed. Sequential isocyanide and allene insertion reactions facilitated the formation of medium-sized rings, overcoming the unfavorable transannular interactions and entropic factors, followed by an allylic substitution to yield benzodiazocine derivatives under mild reaction conditions. When the nucleophile was linked with aryl iodide, challenging diazocine-fused macrocycles could be accessed through an intramolecular allylic substitution process.
View Article and Find Full Text PDFOrg Lett
July 2025
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, China.
Herein, we disclose a palladium-catalyzed three-component coupling strategy enabling the efficient synthesis of 2,3,5-trisubstituted thiophenes with a high step- and atom-economy. This convergent protocol synergistically integrates alkenyl bromides, isocyanides (including 1°, 2°, and 3° variants), and potassium thiocarboxylates, the latter functioning dually as a sulfur donor and acyl electrophile. The reaction exhibits broad substrate compatibility, delivering diverse thiophene architectures in good yields from readily available building blocks.
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