Novel NHC-based Pd–PEPPSI complexes: synthesis, structural characterization by X-ray diffraction, biological properties, and catalytic performance in N-alkylation reactions

Abstract

Herein, we describe the borrowing-hydrogen N-alkylation of amines with alcohols using Pd-PEPPSI-NHC complexes, representing the first example of this catalyst class applied to this transformation. For this purpose, six novel benzimidazolium chlorides and their corresponding PEPPSI-type (PEPPSI = pyridine-enhanced precatalyst preparation, stabilization and initiation) palladium complexes bearing NHC spectator ligands were synthesized and fully characterized using a range of spectroscopic techniques. Additional structural details were confirmed by single-crystal X-ray diffraction analysis of one of the complexes. All newly synthesized Pd–carbene complexes demonstrated significant catalytic activity toward the alkylation of aniline derivatives with aryl alcohols. Excellent results were obtained within 24 hours using only 2.5 mol% of catalyst, highlighting an efficient and promising approach for this type of reaction. In addition, the antimicrobial activities of PEPPSI-Pd(II)–N-heterocyclic carbene (NHC) complexes 3a–f were evaluated against Micrococcus luteus, Listeria monocytogenes, Salmonella typhimurium, Staphylococcus aureus, Candida albicans and Pseudomonas aeruginosa. We emphasize that all palladium–NHC–PEPPSI complexes are efficient compounds against bacteria and fungi as potential antimicrobial agents. In addition, the anticancer activity of these compounds was determined. Higher cytotoxicity relative to cisplatin was observed across all tested cell lines.