Palladium-Catalyzed Cross-Coupling Reactions Of Compounds Containing N Or S Hetero-atom With Aryl Bromides

Palladium catalysts had been widely used in chemical synthesis. Many pharmaceutical intermediums, pesticides and biologically active compounds were synthesized through palladium-catalyzed reactions. The catalytic effects of palladium catalysts in two different reaction systems were studied.The first part is palladium-catalyzed reactions of 3-methylthiophenylboronic acid with aryl bromides. Nine kinds of biaryl compounds, among which 4-cyano-3'-methylthiobiphenyl, 4-nitro-3'-methylthiobiphenyl, 4-acetyl-3'-methylthio-biphenyl, 3-methoxy-3'-methylthiobiphenyl, 4-methyl-3'-methylthiobiphenyl, 2-(3-methyl-thiophenyl)thiophene and 2-(3-methylthiophenyl)pyridine were not reported before, were synthesized in the presence of base (K₂CO₃) and solvent (THF, dioxane or toluene), highly effective air-stable palladium-phosphinous acid complex [(t-Bu)₂P(OH)]₂PdCl₂ (abbreviated as POPd) as a catalyst, reacting under N₂. The structures of target products-biaryl compounds were characterized through IR, NMR, MS or HRMS.The effects of the different substrates of bromobenzene (the electron-withdrawing groups such as-COCH₃, -NO₂, -CN, etc.; electron-donating groups such as -OCH₃, -CH₃, etc.) upon the time and the yields of Suzuki coupling reactions have been studied. We found that bromobenzene with electron-withdrawing groups can accelerate Suzuki coupling reactions, shorten the reaction time and enhance the yields, while bromobenzene with electron-donating groups can hinder Suzuki coupling reactions, prolong the reaction time and cut down the yields.The second part is palladium-catalyzed reactions of indole with substituted bromobenzenes. Herein, to our knowledge, we first report the direct C-3 arylation of indoles with unprotected heterocyclic nitrogen atom to form 3-phenylindole, which demonstrates the high selectivity of palladium catalyst with phosphinous acid complexes (abbreviated as POPd), formed in situ, in the presence of a mild base. A series of 3- arylindole were synthesized and the structures of the products were confirmed by IR, NMR and MS. We examined the effect of different bases (KOH, K₂CO₃, KO(t-Bu), NaO(t-Bu), etc.), catalysts (POPd, POPd1, POPd2, etc.), solvents, molar ratios and substrates on this reaction.