Chemodivergent Coupling of 1,3-Enynes with Anilines to Access Dihydropyrrole Skeleton under Palladium Catalysis

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. Conventional methods for constructing 2,5-dihydropyrroles often rely on elaborate multi-step procedures or complex starting materials. Herein, the authors describe a palladium-catalyzed chemodivergent protocol for synthesizing functionalized 2,5-dihydropyrrole scaffolds from readily accessible 1,3-enynes and anilines.