Synthesis Of Nitriles And ?-Arylated Ketones Catalyzed By Palladium Complexes

Nitriles and a-arylated ketones are potentially important structural moieties for its vast distribution in natural products and bioactive molecules, pharmaceuticals, herbicides and a wide range of dyes. Moreover, the cyano and carbonyl group can be easily converted into other functional groups. The development of convenient and efficient methods for the synthesis of nitriles and a-arylated ketones has attracted considerable attention. Conventional procedures for their synthesis often suffer from drawbacks, such as multistep reactions, the use of stoichiometric amounts of toxic reagents, harsh reaction conditions and low atom economy.In the first part, the cyanation of aryl/heteroaryl bromides with K4[Fe(CN)6] were achieved by using palladium catalyst and P,N-ligand. Under the optimized conditions, the cyanation of aryl/heteroaryl bromides with K4[Fe(CN)6] proceeded smoothly, and the desired products were obtained in 72%-95% yields. The newly formed P,N-ligands was highly effective in inhibiting contact between the transition metal center and the cyanide ions, thus enhancing the activity of the catalyst at relatively low temperature. This protocol shows good functional group tolerance, such as formyl, amide, halide (F and Cl), acetyl, nitryl, trifluoromethyl, cyano, ester, methyl, methoxyl, n-butyl, hydroxyl, and amino groups.In the second part, azides that contained a-hydrogens were efficiently oxidized by acetone and Pd(OAc)2 into their corresponding nitriles. This strategy turned out to be useful methods to synthesize nitriles from the corresponding azides. Under the optimized conditions, one-pot two steps transformation of primary halides into corresponding nitriles was successfully achieved in the presence of the sterically bulky ligand, and the nitriles were obtained in 38%-88% yields. In this novel protocol, inexpensive and widely available acetone functioned both as a solvent and a hydrogen acceptor. The poisoning of palladdium catalyst by the azido anion (N3-) was observed, and could be avoided by using Xphos ligand. This protocol shows good functional group tolerance, such as methyl, methoxyl, halide (F and Cl), nitryl, formyl, C-C triple bond, and C-C double bond groups. The mechanism study shows that the transformation of primary azides to nitriles proceeds via palladium benzylideneamide intermediate.In the last part, palladium-catalyzed a-arylation of ketones was studied, this was a novel method to synthesize a-arylated ketones. Under the optimized conditions, the nucleophilic substitution reaction of chloromethylnaphthalene and its derivatives with ketones occured selectively in the para position of the aromatic ring to produce a-arylated ketones, the yield was up to 83%. The mechanism study shows that the a-arylation proceeded via the nucleophilic-substitution dearomatization of ?-benzyl palladium intermediates with ketones and 1,5-prototropic shift aromatization. This protocol shows good tolerance for alkyl ketones, and aryl ketones. Aryl ketones bearing electron-donating groups exhibits higher reactivities than aryl ketones bearing electron-withdrawing groups.