Photoreductive decarboxylation of carboxylic acids via their benzophenone oxime esters

Decarboxylation of various carboxylic acids, including ∝β- andamino acids, is performed by the photolysis of their benzophenoneoxime esters in isopropanol in the presence of t-butyl mercaptane,and corresponding decarboxylated products are obtained in goodyields under mild photolytic conditions.     

Copper-catalyzed decarboxylation/cycloaddition cascade of alkynyl carboxylic acids with azide

A copper-catalyzed decarboxylation/cycloaddition cascade of alkynyl carboxylic acids with azide has been developed. This reaction exhibits good functional group tolerance and wide substrate scope, provides an efficient way to construct 1,4-disubstituted 1,2,3-triazoles.     

Cyanocuprates convert carboxylic acids directly into ketones

Carboxylic acids were converted directly in 56-99% yields into methyl, n-butyl, and isopropyl ketones using excess cyanocuprates R(2)CuLi·LiCN. A substrate with a stereocenter α to the carboxylic acid was converted into ketones with very little loss of enantiomeric purity. A variety of functional groups were tolerated including aryl bromides. This direct transformation of a carboxylic acid into ketone with minimal tertiary alcohol formation is proposed to involve a relatively stable copper ketal tetrahedral intermediate.     

Oxidative decarboxylation of α-keto carboxylic acids by carbonyl oxides

Photosensitized oxygenation of α-keto carboxylic acids in the presence of diazo compounds afforded the corresponding carboxylic acids and carbon dioxide in high yields; oxidative decarboxylation by carbonyl oxides occurred.     

Mechanism of silver- and copper-catalyzed decarboxylation reactions of aryl carboxylic acids

Silver- and copper-catalyzed decarboxylation reactions of aryl carboxylic acids were investigated with the aid of density functional theory calculations. The reaction mechanism starts with a carboxylate complex of silver or copper. Decarboxylation occurs via ejecting CO(2) from the carboxylate complex followed by protodemetallation with an aryl carboxylic acid molecule to regenerate the starting complex. Our results indicated that the primary factor to affect the overall reaction barriers is the ortho steric destabilization effect on the starting carboxylate complexes for most cases. Certain ortho substituents that are capable of coordinating with the catalyst metal center without causing significant ring strain stabilize the decarboxylation transition states and reduce the overall reaction barriers. However, the coordination effect is found to be the secondary factor when compared with the ortho effect.     

Pd/PR3-catalyzed cross-coupling of aromatic carboxylic acids with electron-deficient polyfluoroarenes via combination of decarboxylation with sp2 C-H cleavage

By using Pd(TFA)(2)/PCy(3) as a catalyst, a broad range of aromatic carboxylic acids, including heteroaromatic carboxylic acids, efficiently underwent decarboxylative coupling with an array of polyfluoroarenes in the presence of stoichiometric amount of silver salts to generate biaryls. Silver salts were adjusted to the reactivity of aromatic carboxylic acids to efficiently suppress the protodecarboxylation and therefore improve decarboxylative cross-couplings. It was established that the palladium complex containing the PCy(3) ligand was capable of catalyzing the decarboxylation of electron-rich aromatic carboxylic acids, and silver salts promoted the decarboxylation of both electron-rich and -deficient ones. To explain the two different decarboxylation processes, two possible reaction pathways are proposed, which were further supported by the facts that the stoichiometric arylpalladium complex can directly arylate pentafluorobenzene in the presence of PCy(3) and the arylpalladium complex can catalyze the decarboxylative coupling of 2,4-dimethoxybenzoic acid with pentafluorobenzene. The kinetic isotope effect of 4.0 clearly showed that the C-H bond cleavage of polyfluoroarenes is involved in the rate-determining step.     

One-pot synthesis of aldehydes or ketones from carboxylic acids via in situ generation of Weinreb amides using the Deoxo-Fluor reagent

A one-pot, high yield conversion of carboxylic acids to the corresponding aldehydes and ketones is described. The highlight of this methodology is the in situ generation of Weinreb amides with the Deoxo-Fluor reagent, which undergo nucleophilic reaction with DIBAL-H and Grignard reagents.     

The nature of the fragmentation step for decarboxylation in heterocyclic carboxylic acids

A mechanism of fragmentation for five membered heterocyclic-substituted acids is proposed. The suggested four centered transition state for the CO₂ elimination is based on the resulting deuterium-labelled ions.     

Free-radical decarboxylation of carboxylic acids as a concerted abstraction and fragmentation reaction

Two variants of the reaction of radicals with the carboxyl group of carboxylic acids, namely, RO ₂ ^? + R _i COOH → ROOH + R _i CO ₂ ^? and RO _i ^? + R _j COOH → ROOH + R _i ^? + CO₂ are theoretically analyzed. It is demonstrated by the intersecting-parabolas method that if the reaction proceeded via the formation of an intermediate carboxyl radical, it would be much slower than is actually observed. Quantum-chemical calculations carried out by the density functional method using the nonempirical functional PBE have shown that the reactions of the methyl radical with the carboxyl group of acetic, butyric and vinylacetic acids include concerted H atom abstraction and C-C bond breaking. In the framework of the intersecting-parabolas model, an algorithm has been developed to calculate the activation energy and rate constant for X^? + R _i COOH → XH + CO₂ + R _i ^? reactions, where X = R^?, RO^?, HO^?, ArO^?, Ar₂N^? or H^?     

An improved preparation and a new application of trichloromethylcarbinols from enolizable ketones

We report an improved method for the preparation of trichloromethylcarbinols from enolizable ketones. Trichloromethylcarbinols were obtained in good to excellent yields by using of a combination of CHCl₃, n-BuLi, and chlorotitanium (IV) triisopropoxide. Hydrolysis of the trichloromethylcarbinol to an α,β-unsaturated ester was also explored.     

Direct conversion of primary and secondary carboxylic acids to trifluoromethyl ketones

Primary and secondary carboxylic acids were converted in one step to the corresponding trifluoromethyl ketones by treatment with trifluoroacetic anhydride (TFAA) and pyridine in toluene at 60-100 °C followed by hydrolysis/decarboxylation with water at 45 °C.     

Base-catalyzed three-component direct Mannich reaction of enolizable ketones with high syn-selectivities

The three-component direct Mannich reaction between aldehydes, p-toluenesulfonamide, and enolizable ketones was achieved for the first time with organic bases as the catalysts. The corresponding N-tosylated β-aminoketones were obtained in high yields and good to excellent diastereoselectivities using TMG as the catalyst. Through reduction of the ketone group, the reaction product may be converted into β-aminol with excellent diastereoselectivity.     

One-pot synthesis of ketones from carboxylic acids and grignard reagents using N,N-Diphenyl-p-methoxyphenylchloromethyleniminium chloride

N,N-Diphenyl-p-methoxyphenylchloromethyleniminium chloride is found to be an effective condensation reagent of carboxylic acids and Grignard reagents under mild conditions to afford the corresponding ketones in high yields.     

1,2-Dibromoethane and KI mediated α-acyloxylation of ketones with carboxylic acids

The 1,2-dibromoethane-and Kl-mediatedα-acyloxylation of ketones is reported in moderate to good yield without the use of transition metals and strong oxidants.Various acids are well tolerated with wide functional group compatibility.An 1,2-dibromoethane-and Kl-catalysed reaction mechanism is proposed based on the results of control experiments.     

Oxidative decarboxylation of arylacetic acids in water: One-pot transition-metal-free synthesis of aldehydes and ketones

One-pot transition-metal-free synthesis of aromatic aldehydes and ketones via oxidative decarboxylation of arylacetic acids in water is developed. Protocol relies on the direct decarboxylation of sp³-hybridized carbon in water without any over oxidation into carboxylic acids with minimal waste. Reaction mechanism is investigated and application of this protocol is demonstrated on a gram scale.     

Highly syn-diastereoselective Michael addition of enolizable ketones to 3-(diethoxyphosphoryl)coumarin

A new approach to 3-(diethoxyphosphoryl)-4-(2-oxoalkyl)-3,4-dihydrocoumarins by base promoted conjugate addition of enolizable ketones to 3-(diethoxyphosphoryl)coumarin is described. The resulting products were transformed into the corresponding α-methylene-δ-lactones. A transition state model rationalizing stereochemical outcome of the reaction is proposed.