Esters arylation carboxylic acid

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

ROCOR" RNH ROAr" ROH ROR RH RNH2 RAr RR X X (anhydrides) X (aryl esters) X (carboxylic acids) X (alkyl esters) X (amides)... 

Carbanions derived from optically active sulfoxides react with esters, affording generally optically active )S-ketoesters ° . Kunieda and coworkers revealed that treatment of (-t-)-(R)-methyl p-tolyl sulfoxide 107 with n-butyllithium or dimethy-lamine afforded the corresponding carbanion, which upon further reaction with ethyl benzoate gave (-l-)-(R)-a-(p-tolylsulfinyl)acetophenone 108. They also found that the reaction between chiral esters of carboxylic acids (R COOR ) and a-lithio aryl methyl sulfoxides gave optically active 3-ketosulfoxides The stereoselectivity was found to be markedly influenced by the size of the R group of the esters and the optical purity reached to 70.3% when R was a t-butyl group. 

The palladium-catalyzed Heck carbonylation reaction is a powerful means of generating amides, esters, and carboxylic acids from aryl halides or pseudohalides [28]. The development of rapid, reliable, and convenient procedures for the introduction of carbonyl groups is important for the development of high throughput chemistry in general and high-speed microwave-mediated chemistry in particular. Unfortunately, the traditional method of introducing carbon monoxide into a reaction mixture via a balloon or gas tube is not practical because of the special requirements of microwave synthesis. 

An additional stabilization of the negative charge provided by the adjacent aryl group in aryllithiomethyl intermediates 400 makes l-(arylmethyl)benzotriazoles 399 attractive starting materials for many syntheses. Thus, reaction of anions 400 with esters of carboxylic acids leads to a-(benzotriazole-l-yl) ketones 401, which can be easily reduced to carbinols 402... 

Selection of appropriate hydroxamic esters and carboxylic acid salts has enabled synthesis of a wide range of A-acyloxy-Af-alkoxyamides in which and can be alkyl or aryl but, to date, only aUcoxyl or arylalkoxyl groups have been present at R". ... 

Aryl esters of carboxylic acids (X in general formula 1 = —COR,—COOR or —CONHR Section II). 

Palladium-catalyzed carbonylation reactions with aryl halides are powerful methods of generating aromatic amides, hydrazides, esters and carboxylic acids [25]. We have previously reported the exploitation of Mo(CO)6 as a robust carbon monoxide-releasing reagent in palladium-catalyzed carbonylation reactions [26-29]. This stable and inexpensive solid delivers a fixed amount of carbon monoxide upon heating or by the addition of a competing molybdenum coordinating ligand (for example DBU). This allows for direct liberation of carbon monoxide in the reaction mixture without the need for external devices. 

Other methods that can be used to prepare thiol esters from carboxylic acids include the use of aryl thiocyanates,12 thiopyridyl chloroformate,13 2-fIuoro- V-methylpyridinium tosylate,14 1-hydroxybenzotriazole, 5 and boron thiolate.16 Direct conversion of 0-esters to 5-esters can also be effected via aluminum and boron reagents.17 However, the applicability of these 1217 and other more recent methods18 to the selective thiol ester formation discussed above has not been clearly defined. 

Phenvalera te)] (chlorinated aryl carboxylic acid ester) analogue of Pyrethrin I sensitive TTX-resistant) activator (persistent open state depolarization, block, paralysis) [insecticide, proconvulsant, toxic]... 

In the presence of a catalytic amount of the chiral titanium reagent (8) prepared from titanium tetraisopropoxide and the (/ )-1,4-diol, kinetic resolution of 5 -(2-pyridyl) thioesters of a-aryl carboxylic acids is achieved with high relative rate of both the enantiomers to give the (f )-isopropyl esters with high optical purity (eq 17). ... 

Ketones can also be obtained by treatment of the lithium salt of a carboxylic acid with an alkyllithium reagent (16-28). For an indirect way to convert carboxylic esters to ketones, see 16-82. A similar reaction with hindered aryl carboxylic acids has been reported. " Treatment of a p-amido acid with two equivalents of M-butyllithium, followed by reaction with an acid chloride leads to a p-keto amide.Carboxylic acids can be treated with 2-chloro-4,6-dimethoxy[l,3,5]-triazine and the RMgX/Cul to give ketones. " ... 

Titanocene dichloride catalyzes the reduction of alkyl, aryl, and vinyl bromides, aryl chlorides, alkoxy- and halosilanes ketones, esters, and carboxylic acids with alkyl Grignard reagents. This Cp2TiCl2/RMgX system can also be used for the hydromagnesation of alkynes, dienes, and alkenes (Section 3.2.5). Kambe et al. have reported a new type of titanocene-catalyzed transformation with vinyl Grignard reagents and chlorosilanes to furnish l,4-disilyl-2-butenes, as shown in Scheme 3.43 [31]. 

In these reactions, hydrolysis of diphenyl and triaryl phosphites to monoaryl phosphites and phenol was coupled by dehydration between carboxylic acids and amines or alcohols to the corresponding amides and esters. Therefore, the reaction can be generalized as a hydrolysis-dehydration reaction (Scheme 2). The concept of the hydrolysis-dehydration reaction using phosphites has been drown to be applicable also to reactions with other phosphorus compounds such as phosphinites, phos-phonites and phosphorates s Aryl esters of these phosphorus compounds are effective as condensing agents in the production of carboxylic amides and esters (from carboxylic acids and amines or alcohols, respectively) whereas alkyl esters are ineffective (Eqs. (1-3)) ... 

Aminopyrimidine-5-carboxamidcs can also be condensed with diethyl carbonate leading to pyrimido[4,5-r/]pyrimidine-2,4-diols, by treatment with sodium ethoxide/ethanol at reflux for 1 -6 hours.109 The analogous reaction with alkyl or aryl carboxylic acid esters gives alkyl- or arylpyrimido[4,5-t/]pyrimidin-4-ols 23.130... 

Phosphine oxides [73] icc-Benzylic alcohols [77,78] A -Phthalimido amino acids [80] 2-(Aryl)carboxylic acids [83,84] Hydroxy esters [85]... 

The palladium-catalyzed carbonylation reaction with aryl halides is a powerful method for generating aromatic amides, hydrazides, esters, and carboxylic acids... 

Olofsson and coworkers have developed a general and high-yielding synthesis of various diaryl ethers 681 using the reaction of diaryliodonium salts with phenols under basic conditions (Scheme 3.273) [874]. The scope of products includes bulky orf/io-substituted diaryl ethers, which are difficult to obtain by metal-catalyzed protocols. A similar procedure has been used for the metal-free synthesis of aryl esters from carboxylic acids and diaryliodonium salts [875]. 

In contrast to facile a-alkylation of carbonyl compounds, a-arylation or alkenylation of carbonyl compounds has been considered to be a difficult reaction. Recently, a big breakthrough has occurred, and methods for the smooth a-arylation or alkenylation of carbonyl compounds have been developed [1]. Active methylene compounds, ketones, aldehydes, esters, amides and nitriles are now a-arylated easily not only with aryl iodides, but also with bromides and even chlorides. These reactions will lead to wide-ranging applications. A typical example of a synthetic application of the innovative reactions is a new preparative method for a-arylated carboxylic acids, such as ibuprofen (1) and naproxen, by direct a-arylation of acetate or propionate. 

Carboxylic acid aryl esters from carboxylic acids and phenols Azeotropic water entrainment... 

---