Pd-PEPPSI N-Heterocyclic Carbene Complexes from Caffeine: Application in Suzuki, Heck, and Sonogashira Reactions

The first synthesis of Pd-PEPPSI N-heterocyclic carbene complexes derived from the abundant and renewable natural product caffeine is reported. The catalysts bearing 3-chloro-pyridine, pyridine, and N-methylimidazole ancillary ligands were readily prepared from the corresponding N9-Me caffeine imidazolium salt by direct deprotonation and coordination to PdX₂in the presence of N-heterocycles or by ligand displacement of PdX₂(Het)₂. The model Pd-PEPPSI-caffeine complex has been characterized by X-ray crystallography. The complexes were successfully employed in the Suzuki cross-coupling of aryl bromides, Suzuki cross-coupling of amides, Heck cross-coupling, and Sonogashira cross-coupling. Computational studies were employed to determine frontier molecular orbitals and bond order analysis of caffeine-derived Pd-PEPPSI complexes. This class of catalysts offers an entry to utilize benign and sustainable biomass-derived xanthine NHC ligands in the popular Pd-PEPPSI systems in organic synthesis and catalysis.