Palladium-Catalyzed Direct Conversion of Carboxylic Acids into Ketones with Organoboronic Acids Promoted by Anhydride Activators

Abstract

Various carboxylic acids are catalytically converted into ketones on treatment with organoboron compounds in the presence of activators and palladium catalysts. Detailed examination of factors influencing the yield of ketone formation revealed the following characteristics of the reactions: (a) Palladium complexes containing tertiary phosphine ligands, particularly triphenylphosphine and tricyclohexylphosphine, are most effective among the palladium complexes; (b) Dioxane and THF are suitable as the solvent; (c) Dimethyl dicarbonate is required as the activator to obtain ketones in high yields. The process provides a general, versatile, synthetic method to produce various symmetrical and unsymmetrical ketones with aromatic, aliphatic, and heterocyclic groups. The mechanism proposed for the catalytic process involves (i) exchange reaction of the carboxylic acid employed with dimethyl dicarbonate added as the activator to form a mixed anhydride of the carboxylic acid and mono methyl ester of carbonic acid; (ii) oxidative addition of the mixed anhydride to zerovalent palladium species to give an (acyl)(methyl carbonato)palladium species; (iii) decarboxylation of the methyl carbonato ligand to give (acyl)(methoxo)palladium species; (iv) transmetallation of the (acyl)(methoxo)palladium species with an arylboronic acid to give an (acyl)(aryl)palladium species; and (v) reductive elimination of the (acyl)(aryl)palladium species to liberate the coupling product of the acyl and aryl ligands with regeneration of the Pd(0) species. Not only homogeneous catalyst systems but also heterogeneous systems were found to give ketones under mild conditions. On the basis of the present study involving the acyl(methoxo)palladium complexes generated in the reaction mixture of carboxylic acids with dimethyl dicarbonate on reaction with Pd(0) complexes, we also developed a new catalytic process to convert carboxylic acids with terminal alkynes into α, β-alkynyl ketones under similar conditions.

Recent Development about the Use of Pyrocarbonates as Activator in Organic Synthesis: A Review

“…Therefore, activation of carboxylic acids would be an important improvement. Actually, independently both Gooßen [56] and Yamamoto [57] found that carboxylic acids can be converted in the corresponding ketones, usually in good yields on treatment with pyrocarbonates and palladium catalysis. Gooßen put first the conditions to convert anhydrides to ketones [58] and then extended the reaction to carboxylic acid via in situ conversion into anhydrides [56].…”

Synthesis of benzylpalladium complexes through C–O bond cleavage of benzylic carboxylates: Development of a novel palladium-catalyzed benzylation of olefins

“…doi:10.1016/j.jorganchem.2007. 10.051 processes using the cleavage of the C-O bond in carboxylic esters and carboxylic anhydrides [4][5][6][7][8].…”

“…As another application of the concept of the C-O bond cleavage to give acylpalladium complexes, we have developed a new process to prepare ketones and perfluoroketones by combination of the C-O bond cleavage in carboxylic anhydride with transmetallation with arylboronic acids as arylation reagents, providing with further examples of utility of the process involving the Pd-promoted C-O bond cleavage [9,10].…”

Novel Substrates for Palladium‐Catalyzed Coupling Reactions of Arenes

“…(5)] 22. 24 Under these conditions, the addition of a small amount of water was found to enhance the reaction rate strongly. …”

“…An activating agent that leaves just readily separable residues would thus be of some advantage. Di‐( N ‐succinimidyl) carbonate25a as well as dimethyl dicarbonate24, 25b, 26 fulfill this requirement. The former coupling reagent is successful in the presence of electron‐rich trialkyl phosphanes and a base such as sodium carbonate.…”