Carboxylic esters with ketones

Ketones can also be obtained by treatment of the lithium salt of a carboxylic acid with an alkyllithium reagent (16-31). For an indirect way to convert carboxylic esters to ketones, see 16-33. 

Ketones from esters. Methylselenol esters, readily available by reaction of carboxylic esters with (CHdiAlSeCH, (8, 182), react with organocuprates to give ketones in generally high yield... 

The a-arylation of ketones, such as cyclohexanone, can be achieved using different methods. A convenient route by Pinhey et al.89), reacts cyclohexanone-2-carboxylic esters with aryllead triacetates in pyridine. The protection of the P-carboxylic ester prevents a,a-di- or even higher arylations in a -positions. The ester group can be removed by basic hydrolysis and mild thermal decarboxylation or by heating in wet dimethylsulfoxide with sodium chloride (120-180 °C)90). Barton et al. 91) have found a similar a-arylation route using the less electrophilic triphenylbismuth carbonate. In both cases probably the lead- or bismuth-enolates, respectively, are the first inter-... 

Addition of aldehydes to activated double bonds Aldehydes (I) react with a,0-unsaturated carboxylic esters (2a), ketones (2b), or nitriles under the catalytic influence of sodium cyanide to give y-kelocarboxylic esters (3a), y-diketones (3b). or y-ketonitriles... 

Palladium complexes also catalyze the carbonylation of halides. " Aryl (see 13-15), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex.Similar reactivity was reported with vinyl triflates. a-Halo ketones are converted to (3-keto esters with CO, an alcohol, NBU3 and a palladium catalyst at 110°C. Use of an amine instead of the alcohol or alkoxide leads to an amide. 

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. " ... 

Corey and Chaykovsky described the reduction of carboxylic esters to ketones by way of / -keto sulfoxides. The ester is treated in tetrahydrofuran with a solution of methylsulfinyl carbanions in a mixture of dimethyl sulfoxide and tetrahydrofuran at 0°. This yields a j8-keto sulfoxide which is reduced with aluminum amalgam in 90% aqueous tetrahydrofuran.527 The methylsulfinyl carbanions are formed by the action of sodium hydride on dimethyl sulfoxide under nitrogen at 65-70°. 

The addition of acyl hydrazides to (l,2-alkadiene)phosphonic diamides (325) yields the 1,2,3-diazaphospholidine 3-oxides (326). Interaction of the phospho-nite esters (327) (X = Cl or Br) with a,P-unsaturated carboxylic esters, nitriles, ketones, or related compounds, gives quaternary products which decompose in boiling benzene to produce the dihydrophospholes (328). ... 

The very acidic (in the region of pK 10) 1,3-dicarbonyl compounds (—CO—CH— CO—), diketones, and ketoesters are readily converted into the enolates by reaction with alkali hydrides in polar as well as in apolar solvents [1]. Also some acidic mono-ketones, e.g., PhCH2COCH3, react smoothly with sodium hydride [4], Potassium hydride has been used to convert aldehydes into the enolates [2, compare 3]. A serious drawback of this method is the handling of the commercially available potassium hydride, which inter alia involves removal of the protecting mineral oil. Reaction of kinetically less acidic ketones and carboxylic esters with alkali hydrides, in general, gives rise to extensive formation of self-condensation products [3,6],... 

Proline-derived phosphines (254) produced efficient catalysts in situ with [Ir(cod)]2BArp for the asymmetric hydrogenation of olefins in CH2CI2. These ligands gave high enantioselectivities with several classes of alkenes, most notably a,p unsaturated carboxylic esters and ketones. ... 

Acyl azoliums generated from enals have been converted to cyclopropyl carboxylic esters with ee < 99% by reaction with sulfur ylides. Some FLPs have been found to i react by conjugate P/B addition to unsaturated ketones and esters, whereas 1,2-addition to corresponding aldehydes is usual. ... 

The reductive coupling of aldehydes or ketones with 01, -unsaturated carboxylic esters by > 2 mol samarium(II) iodide (J.A. Soderquist, 1991) provides a convenient route to y-lactones (K. Otsubo, 1986). Intramolecular coupling of this type may produce trans-2-hy-droxycycloalkaneacetic esters with high stereoselectivity, if the educt is an ( )-isomer (E.J. Enholm, 1989 A, B). 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Oxygen-Gontaining Organics. Neutral and anionic oxygen-containing organic molecules form a wide variety of complexes with uranium. Much work has focused on alkoxides (222), aryloxides and carboxylates complexes with alcohols, ethers, esters, ketones, aldehydes, ketoenolates, and carbamates are also well known. 

Upon heating of a carboxylic ester 1 with sodium in an inert solvent, a condensation reaction can take place to yield a a-hydroxy ketone 2 after hydrolytic workup. " This reaction is called Acyloin condensation, named after the products thus obtained. It works well with alkanoic acid esters. For the synthesis of the corresponding products with aryl substituents (R = aryl), the Benzoin condensation of aromatic aldehydes is usually applied. 

When a ketone 1 is treated with hydrogen peroxyde or a peracid, a formal insertion of oxygen can take place to yield a carboxylic ester 2. This process is called the Baeyer-Villiger oxidation ... 

The prototype of a Knoevenagel reaction shown in the scheme above is the condensation of an aldehyde or ketone 1 with a malonic ester 2, to yield an a ,/3-unsaturated carboxylic ester 4. 

Alpha hydrogen atoms of carbonyl compounds are weakly acidic and can be removed by strong bases, such as lithium diisopropylamide (LDA), to yield nucleophilic enolate ions. The most important reaction of enolate ions is their Sn2 alkylation with alkyl halides. The malonic ester synthesis converts an alkyl halide into a carboxylic acid with the addition of two carbon atoms. Similarly, the acetoacetic ester synthesis converts an alkyl halide into a methyl ketone. In addition, many carbonyl compounds, including ketones, esters, and nitriles, can be directly alkylated by treatment with LDA and an alkyl halide. 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

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