Abstract
2,5-Dihydropyrroles are prevalent structural motifs in various natural products and biologically active molecules. Conventional methods for constructing these heterocycles often rely on elaborate multi-step procedures or complex starting materials. Herein, we describe a palladium-catalyzed chemodivergent protocol for synthesizing functionalized 2,5-dihydropyrrole scaffolds from readily accessible 1,3-enynes and anilines. By modulating the relative rates of the selectivity-determining steps, either two-component annulation or three-component telomerization can be selectively achieved, affording two distinct types of functionalized 2,5-dihydropyrroles in excellent yields and with high selectivities. Mechanistic studies reveal that the reaction initially proceeds through 1,4-hydroamination of 1,3-enynes to generate an aminomethyl allene intermediate, followed by an intramolecular annulation affording 2-substituted 2,5-dihydropyrroles. This process is significantly accelerated in the presence of Pd(II) catalysts. However, employing Pd(0) precursors, strong acids, and excess ligand effectively decelerates this pathway, diverting the selectivity towards reaction with a second equivalent of 1,3-enyne to yield the telomeric products. This study not only provides an atom-economical method for constructing the 2,5-dihydropyrrole core but also offers a valuable strategy for the development of telomerization chemistry.
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Data availability
The X-ray crystallographic data for compounds have been deposited in the Cambridge Crystallographic Data Centre (CCDC) under deposition numbers CCDC 2468082 (3aa), 2468080 (4ja), 2472318 (21), 2468081 (22 E) and 2519020 (S-3aa). Data relating to the characterization data of materials and products, general methods, optimization studies, experimental procedures, mechanistic studies, mass spectrometry and NMR spectra are available in the Supplementary Information. All data are also available from the corresponding author upon request.
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Financial support from the National Natural Science Foundation of China (22201281) and the Natural Science Foundation of Liaoning Province (2025-MS-055) is acknowledged.
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Q.-A. C. conceived and supervised the project. Q.-A. C., S.-Y. X. and D.-W. J. designed the experiments. S.-Y. X., D.-W. J., X.-T. L. and Z.-H. W. performed the experiments and analyzed the data. All authors discussed the results and commented on the manuscript.
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Xu, SY., Li, XT., Wang, ZH. et al. Chemodivergent Coupling of 1,3-Enynes with Anilines to Access Dihydropyrrole Skeleton under Palladium Catalysis. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70201-z
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DOI: https://doi.org/10.1038/s41467-026-70201-z
