Phosphine-free Ligands Facilitated Palladium-Catalyzed Organic Reactions

Pd-catalyzed C-C bond formation reactions such as the Heck and Suzuki cross couplings are playing increasingly more important roles in modern organic synthesis. These cross coupling reactions are usually performed with 1-5 mol%of Pd catalyst along with phosphine ligands,which sometimes creates practical problems because organophosphines tend to be cxpensive,poisonous,and air sensitive.Accordingly,an important current challenge is to develop Pd catalysts that can utilize inexpensive phosphine-free ligands.In this paper we report several novel and effective phosphine-free Pd catalytic systems.N,N-dimethyl-β-alanine was found to be a more powerful phosphine-free ligand than the previously reported ligand,N,N-dimethylglycine,in the Pd-catalyzed Heck reaction and Suzuki reaction for a variety of aryl bromides,aryl iodides,and activated aryl chlorides with a practical turnover number of 10³.Both kinetic and theoretical studies suggested that N,N-dimethyl-β-alanine led to faster oxidative addition of an aryl halide to Pd than N,N-dimethylglycine.Furthermore,we have synthesized a novel crystalline,air-stable,and moisture-stable Pd salt,Pd(N,N-dimethyl-β-alaninate)₂.This salt was demonstrated to constitute a low-priced,phosphine-free,yet high-turnover-number catalyst for the Suzuki reactions of various aryl bromides and iodides under mild and simple reaction conditions,we observed that the presence of an olefin could dramatically hamper the Suzuki reaction.To the best of our knowledge,this new finding provided interesting mechanistic insights into the lower reactivity of the Heck reaction as compared to the Suzuki reaction.N-phenylurea was found to constitute a highly efficient,yet low-priced, phosphine-free ligand for the Pd-catalyzed Heck and room-temperature Suzuki reactions of aryl bromides and iodides with very high turnover numbers(ca.10³-10⁴). It is also found that N-phenylurea can be an excellent ligand in Larock indolization of 2-bromoaniline and internal alkynes with high regioselectivity.Some 1,3-dicarbonyl compounds(such as pentane-2,4-dione)as oxygen ligands were found to constitute highiy efficient,yet low-priced and phosphine-free ligands for the Pd-catalyzed Heck and Suzuki reactions of aryl bromides and iodides with very high turnover numbers(ca.10³-10⁴).Systematic study on N,O-bidentate ligand were held.It was found that alkylamine and pyridine were good neighboring groups to enhance the effect of a carboxylate group in Pd catalysis.The best N,O-bidentate ligand turned out to be quinoline-8-carboxylatc,and Pd(quinoline-8-carboxylalc)₂ constituted an ideal Pd catalyst that was structurally simple,synthetically inexpen ive,and chemically stable. Synthetic examinations demonstrated that Pd(quinoline-8-carboxylate)₂ could smoothly catalyze the Heck and Suzuki reactions of unactivatcd aryl bromides and iodides with fairly high turnover numbers up to ca.10⁴.