Will We Witness Enzymatic or Pd-(Oligo)peptide Catalysis in Suzuki Cross-Coupling Reactions?

Despite the development of numerous advanced ligands for Pd-catalyzed Suzuki cross-coupling reactions, the potential of (oligo)peptides serving as ligands has remained largely unexplored. This study demonstrates, via DFT modeling, that (oligo)peptide ligands can exhibit superior activity compared to classic phosphines in these reactions. The utilization of natural amino acids such as Met, SeMet, and His offers strong binding of the Pd center, thereby ensuring substantial stability of the system. The increasing sustainability and economic viability of (oligo)peptide synthesis open new prospects for applying Pd-(oligo)peptide systems as greener catalysts. The feasibility of de novo engineering an artificial Pd-based enzyme for Suzuki cross-coupling is discussed, laying the groundwork for future innovations in catalytic systems.