Palladium Catalyzed Synthesis Of Five-membered Nitrogen-containing Heterocyclic Compound

Nitrogen-containing heterocyclic compounds are important intermediates of many natural products, biologically active molecules and pharmaceuticals, thus the research on the synthesis of them has wide application value and practical significance. Palladium-catalyzed intramolecular Aminohalogenation cyclization and Aza-Wacker reaction of olefin, are important methods for the synthesis of new cyclic compounds, in which C-X bond and C-N bonds can be achieved directly from C-H bond transformation. The same of intramolecular aminohalogenation cyclization and Aza-Wacker reaction is that both of these two reactions are initiated from divalent palladium catalyst and followed by attack of nucleophilic nitrogen to activated olefin to form nitrogen-containing heterocyclic palladium species, the difference is that a halogenated heterocyclic compound is formed through nucleophilic substitution of halogenation reagent in intramolecular aminohalogenation cyclization reaction, while the Aza-Wacker reaction proceeds β-H elimination and generate a nitrogen-containing heterocyclic olefin compound. Two types of reactions proceeded efficiently in the optimal condition and generated single five-membered nitrogen heterocyclic products in high regioselectivity and selectivity. The main research contents include:1. 27 kinds of nitrogen-containing olefin compounds were synthesized via two routes, including 21 kinds of unknown compounds. The structures were confirmed by IR and 1H NMR, 13 C NMR and HRMS.2. Palladium catalyzed intramolecular bromoamino cyclization reaction of nitrogen-containing Alkenes was preliminary explored. The optimum catalytic reaction system and reaction conditions were confirmed. Palladium(II) bis(triphenylphosphine) dichloride acted as the optimal source of palladium, and NBS was bromination reagent source. Single configuration of five-membered brominated pyrrolidine products were obtained at room temperature within 1 h, simultaneously high regioselectivity of the reaction was achieved. Seven kinds of bromopyrrole products were synthesized in total, including six species of unknown compounds. Finally the yield was up to 98%. The structures were confirmed by IR, 1H NMR, 13 C NMR and HRMS.3. Palladium-catalyzed intramolecular Aza-Wacker cyclization reaction of nitrogen-containing olefins was preliminary explored. The effects of palladium sources, solvents and alkaline additives on the reaction yields were examined. A total of 15 kinds of compounds were synthesized, including 13 kinds of unknown compounds. The structures were characterized by IR, 1H NMR, 13 C NMR and HRMS.The nitrogen-containing alkenes we designed and synthesized can be applied to bromoaminocyclization and Aza-Wacker cyclization reaction. The scope of the substrates of each reaction was further expanded. Both reactions proceeded smoothly, giving bromine pyrrolidine products and Aza-Wacker cyclization products respectively in good yields with high regioselectivities.