Study On The Transition-Metal Catalyzed 1,4-Addition Of Arylhalides

The transition-metal catalyzed 1,4-addition of nucleophiles toα,β-unsaturated carbonyl compounds is one of the effective methods for constructing C-C bonds in organic synthesis, particularly in the stereoselective synthesis of biologically important target molecules in natural product and pharmaceutical research.In this paper, the palladium-catalyzed direct 1,4-addition of arylhalides toα,β-unsaturated carbonyl compounds and the rhodium-catalyzed direct 1,4-addition of arylbromides toα,β-unsaturated carbonyl compounds were developed. The main contents were shown as below:1. The phenyliodide and (E)-4-phenylbut-3-en-2-one were initially used as the model substrates to optimize the reaction conditions such as catalysts, solvents, bases and temperatures. It was found that the best result was obtained at 80℃with 3 mol%Pd(PPh3)4 as catalyst, N,N-dimethylacetamide as the solvent, n-tributylamine as the base. Under the optimized condition, the 1,4-addition of various aryl iodides toα,β-unsaturated carbonyl compounds were performed smoothly to give the corresponding products in moderate to good yields (the maximum yield was 77%). Reactions of aryliodides bearing an electron-donating group on aromatic ring furnished 1,4-addition products in high yields, whereas aryliodides bearing an electron-withdrawing group on aromatic ring gave no reaction.2. The palladium-catalyzed 1,4-addition of arylbromides toα,β-unsaturated carbonyl compounds was also examined. It was found that the 1,4-adduct was obtained in 55%yield at 140℃with 3 mol%PdCl2(MeCN)2 as catalyst,3.3 mol%of dppb as ligand, n-Bu4NI as additive reagent, N,N-dimethylacetamide as the solvent, n-tributylamine as the base. On the other hand, the rhodium-catalyzed 1,4-addition of arylbromides toα,β-unsaturated carbonyl compounds was performed smoothly to give 1,4-addition product in 70%yield, which carried out under reaction condition with [RhOH(cod)]2 as catalyst, CuI as additive reagent, dioxane/H2O as the solvent and KOH as the base at 100℃.