PPM-Level Palladium-Catalyzed Sonogashira Coupling Promoted by Fe3(CO)12 and α,β-Ynone Ligands

The development of sustainable cross-coupling methodologies that drastically reduce reliance on precious metals represents a central challenge in modern synthetic chemistry. Here we report a synergistic Pd/Fe bimetallic catalytic system for Sonogashira coupling that operates at a palladium loading of 200 ppm PdCl2 in conjunction with 0.1 mol% Fe3(CO)12. Using α,β-ynone ligands in methanol at 60 °C, this system achieves 69% to 98% yield across 24 examples encompassing diverse aryl iodides and terminal alkynes. Catalytic experiments reveal that Fe3(CO)12 is uniquely effective among iron sources, with its cluster structure proving essential for the observed rate enhancement, while the α,β-ynone ligands improve catalytic performance relative to ligand-free conditions. Ligand structure–activity studies identify L6 (3-(4-bromophenyl)-1-(4-methoxyphenyl)prop-yn-1-one), bearing a 4-methoxybenzoyl and 4-bromophenylethenyl motif, as the optimal ligand, affording 98% yield. The system exhibits broad functional group tolerance, accommodating both electron-rich and electron-deficient aryl iodides, while higher yields are achieved when using aryl-acetylenes as compared with their alkyl- analogs. This work demonstrates that the combination of an iron carbonyl cluster additive with tailored α,β-ynone ligands enables a dramatic reduction in noble metal loading while maintaining high catalytic efficiency under mild conditions, offering a practical and sustainable route to aryl alkynes.