Two series of well-defined palladium(0) complexes with phosphine-functionalized N-heterocyclic carbene ligands were prepared. These complexes featured six- and seven-membered chelate rings in the two series. Among the seven-membered chelate complexes, those featuring the PCy2 moiety exhibited observable fluxional behavior on the NMR time scale, corresponding to the interchange between two sets of conformations. Most of these novel complexes were successfully structurally characterized by single-crystal X-ray diffraction studies. These two series of palladium(0) complexes were tested for their potential catalytic applications in two mechanistically distinct reactions, namely, Mizoroki-Heck coupling and direct C-H functionalization reactions. One of the six-membered chelate complexes was found to be an efficient pre-catalyst for mediating the coupling reactions between aryl chlorides and alkenes. The palladium(0) complex could also be effectively applied in the direct C-H functionalization reactions of aryl bromides with 1,2-dimethylimidazole.

A series of new imidazolium salts was synthesized by simple quaternization reactions of 1-benzyl-1H-imidazole or 1-benzyl-2-methyl-1H-imidazole and their derivatives with 2-chloro-N-(pyridin-2-ylmethyl)­acetamide. These resulting imidazolium salts were successfully employed as ligand precursors for the syntheses of novel palladium­(II) complexes bearing tridentate ligands of N-heterocyclic carbene, amidate, and pyridine donor moieties. Simple tuning of the reaction conditions allowed selective coordination of the N-heterocyclic carbene moiety in either “normal” or “abnormal” binding modes. An isomeric pair of palladium complexes with “normal” and “abnormal” N-heterocyclic carbenes was successfully characterized by single-crystal X-ray diffraction studies. Theoretical calculations indicated that the palladium complex with “normal” NHC coordination was more thermally stable than its isomeric complex with “abnormal” NHC binding. The potential of these two sets of palladium complexes as anticancer drugs was evaluated, and the results showed that some of these novel complexes exhibited promising inhibition activity against human ovarian cancer cell lines. The inhibition activity of these novel complexes was highly structurally dependent. While the nNHC complex bearing an N-3-methoxybenzyl group appeared to be the most active compound, its isomeric aNHC complex did not exhibit any inhibition activity toward TOV21G cells. In contrast, in the case of an isomeric pair of palladium complexes bearing N-4-fluorobenzyl groups, the aNHC complex showed activity superior to that of the nNHC complex.

A series of new imidazolium chlorides were straightforwardly prepared from the reactions between chloroacetone and imidazole derivatives. Deprotonation of the methylene proton next to the ketone group in these salts by pyridine led to the formation of a monodentate ligand that coordinated to palladium, readily forming zwitterionic anionic palladium pyridine complexes bearing a formal positive charge on the ligand ancillary. The pyridine ligand in the zwitterionic complexes can be facilely replaced by phosphine ligands. Seven of these new complexes were successfully characterized by Xray crystallography. The zwitterionic phosphine complexes were highly efficient in catalyzing room-temperature Suzuki− Miyaura reactions between sterically hindered aryl chlorides and arylboronic acids in an aqueous medium.

A series of dimetallic palladium(II)-NHC complexes comprised of 1,4-naphthalenyl or 9,10anthracenyl spacer sandwiched between two imidazole rings was successfully synthesized. These complexes were characterized by 1 H and 13 C{ 1 H} NMR spectroscopy and elemental analysis. The structures of two dimetallic palladium complexes and a related mononuclear palladium complex to be used for comparative studies were further characterized by X-ray diffraction. The dimetallic palladium complex with the 9,10anthracenyl linker was very efficient in catalyzing direct CÀ H arylation reactions of heteroaromatic compounds (imidazoles, imidazo[1,2-a]pyridine, and thioazole) with a broad range of aryl chlorides, employing a mild monopalladium loading of 1.5 mol%. It allows for the effective use of aryl chlorides to prepare arylated heterocycles, previously only accessible with the more reactive bromide counterparts. Importantly, the catalytic activity of the dimetallic precatalyst was found to be higher than that of an analogous mononuclear complex. Scheme 1. Synthesis of ligand precursors. Scheme 2. Synthesis of Dinuclear Palladium-NHC Complexes. Scheme 3. Synthesis of Mononuclear Palladium-NHC Complexes.