Aldehydes with carboxylic esters

Although solutions of molybdenum complexes A in methylcyclohexane or benzene are stable for several weeks at room temperature [416], these complexes are sensitive towards oxygen and protic solvents [813,814]. Aldehydes are quickly olefinated by complexes A, whereas variable reactivity is observed towards ketones [416,736]. With carboxylic esters usually no reaction occurs. 

When the same reaction is carried out with carboxylic esters R COOR", ot-diketones RCOCOR are obtained.410 Another way to add RCO to aldehydes and ketones is to treat the substrate with ArCOLi, generated by treating ArCOTeBu with BuLi.411... 

Aldehydes, ketones, carboxylic esters, carboxylic amides, imines and N,A-disubstiluted hydrazones react as electrophiles at their s/ 2-hybridized carbon atoms. These compounds also become nucleophiles, if they contain an H atom in the a-position relative to their C=0 or C=N bonds. This is because they can undergo tautomerization to the corresponding enol as seen in Chapter 12. They are also C,H-acidic at this position, i.e., the H atom in the a-position can be removed with a base (Figure 13.1). The deprotonation forms the conjugate bases of these substrates, which are called enolates. The conjugate bases of imines and hydrazones are called aza enolates. The reactions discussed in this chapter all proceed via enolates. 

Multiple bonds between the atoms in the molecules of conventional monomers may possess a relative excess or deficiency of electrons. In principle, only a few of these bond types exist nitrile, aldehyde, carbonyl, carboxyl, ester, vinyl and acetylene. In macromolecular chemistry, the reactions of anions with oxiranes, the amide and ester (in rings) and the siloxane bond are also of importance. 

The alkoxytitanium propene compound Ti(T] -propene)(OTr)2 (46) [153], which is believed to be generated from Ti(0 Pr)4 and two equivalents of /-PrMgCl, reacts with internal alkynes to give titanium-alkyne compounds Ti(ri-alkyne) (0 Pr)2 (47) in quantitative yield (Scheme 6.9) [154,155]. 46 reacts with carboxylic esters to produce cyclo-propan- 1 -ols in modest yields [ 156,157]. Oxidative addition of allyllic halides or allyllic alcohols to 46 proceeds readily to form allyl titanium compounds 48, whose reaction with aldehyde provides a stereoselective synthesis of homoallylic alcohols [153]. 

The condensation of aldehydes with thiocyanoacetic esters, catalysed by potassium fluoride or potassium carbonate, gave as minor products yV-carbamoyl-2-imino-5-alkyl(or aryl)-l, 3-oxathiolan-4-carboxylic esters, in which the 4,5-c/j-isomers predominated according to n.m.r. spectroscopy. l,3-Oxathiolan-2-thione was converted into dimethyl 1,3-dithiol-2-one-4,5-dicarboxylate and ethylene on treatment with dimethyl acetylene-dicarboxylate, and the transformation of methyl 2-methoxycarbonyl-methyl-1,3-oxathiolan-2-carboxylate into dimethyl-5,6-dihydro-l, 4-oxa-thiin-2,3-dicarboxylate by chlorination at low temperatures found analogy in the reactions of 2,2-dialkyl-l,3-oxathiolans. Thiomethoxymethyl hexachloroantimonate reacted with potassium t-butoxide to give mainly 3,5,5-trimethyl-l,3-oxathiolanium hexachloroantimonate the mechanism of this remarkable reaction was not settled. ... 

The formation of Mannich bases 25 results from the reaction of (C5C)N)2 with enolizable ketones, aldehydes, and carboxylic esters (26-29) (Scheme 9.22) [42, 48, 49]. The reaction is reasonably interpreted in terms of the electrophilic addition of C59N+ intermediate to the enol form of the carbonyl compound. Dicarbonyl... 

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). 

The conversion of primary alcohols and aldehydes into carboxylic acids is generally possible with all strong oxidants. Silver(II) oxide in THF/water is particularly useful as a neutral oxidant (E.J. Corey, 1968 A). The direct conversion of primary alcohols into carboxylic esters is achieved with MnOj in the presence of hydrogen cyanide and alcohols (E.J. Corey, 1968 A,D). The remarkably smooth oxidation of ethers to esters by ruthenium tetroxide has been employed quite often (D.G. Lee, 1973). Dibutyl ether affords butyl butanoate, and tetra-hydrofuran yields butyrolactone almost quantitatively. More complex educts also give acceptable yields (M.E. Wolff, 1963). 

The main example of a category I indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from ot-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3]. 

We ve seen how Grignard reagents add to the carbonyl group of aldehydes ketones and esters Grignard reagents react m much the same way with carbon dioxide to yield mag nesium salts of carboxylic acids Acidification converts these magnesium salts to the desired carboxylic acids... 

Isothiazole-3-carboxylic acid and its 4-bromo derivative have been obtained by oxidation of the corresponding aldehydes with silver oxide. They form acid chlorides, esters, and amides. The amides may be dehydrated to give the corresponding nitriles. ... 

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. 

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. 

Anhydrides are reduced with relative ease. McAlees and McCrindle 20) established the following increasing order of difficulty for various carbonyls acid chlorides > aldehydes, ketones > anhydrides > esters > carboxylic acids > amides. Reduction may proceed by 1,2-addilion of hydrogen or by cleavage of an oxygen-carbonyl bond. If 1,2-addition to the carbonyl occurs, as in the presence of strong protic acids over palladium, 1,1-diesters are formed by acylation 26). 

For acyclic systems, the anti diastereoselectivity of the (i )-enolates is lower than the syn diastereoselectivity of comparable (Z)-enolates. For example, carboxylic acid esters, which form predominantly ( )-enolates, react with aldehydes with high anti selectivity only in those cases where bulky aromatic substituents are in the alcoholic part of the ester22 25. 

When the related saccharin derived sultam (R)-29 is converted into the (Z)-boron enolate and subsequently treated with aldehydes,. vy -diastereomers 30 result almost exclusively. Thus, the diasteromeric ratios, defined as the ratio of the major product to the sum of all other stereoisomers, surpass 99 1. Hydroperoxide assisted saponification followed by esterification provides carboxylic esters 31 with recovery of sultam 32106a. 

Carboxylic esters have been reduced to aldehydes with DIBALH at — 70°C, with... 

Carboxylic esters can be treated with ketones to give p-diketones in a reaction that is essentially the same as 10-118. The reaction is so similar that it is sometimes also called the Claisen condensation, though this usage is unfortunate. A fairly strong base, such as sodium amide or sodium hydride, is required. Yields can be increased by the catalytic addition of crown ethers. Esters of formic acid (R H) give P-keto aldehydes. Ethyl carbonate gives P-keto esters. 

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

Both alcohols and phenols add to ketenes to give carboxylic esters (R2C=C= O+ROH —> R2CHC02R). This has been done intramolecularly (with the ketene end of the molecule generated and used in situ) to form medium- and large-ring lactones. In the presence of a strong acid, ketene reacts with aldehydes or ketones (in their enol forms) to give enol acetates. 

Similar additions have been successfully carried out with carboxylic acids, anhydrides, acyl halides, carboxylic esters, nitriles, and other types of compounds. These reactions are not successful when the alkene contains electron-withdrawing groups such as halo or carbonyl groups. A free-radical initiator is required, usually peroxides or UV light. The mechanism is illustrated for aldehydes but is similar for the other compounds ... 

Aldehydes and ketones can be converted to ethers by treatment with an alcohol and triethylsilane in the presence of a strong acid or by hydrogenation in alcoholic acid in the presence of platinum oxide. The process can formally be regarded as addition of ROH to give a hemiacetal RR C(OH)OR", followed by reduction of the OH. In this respect, it is similar to 16-14. In a similar reaction, ketones can be converted to carboxylic esters (reductive acylation of ketones) by treatment with an acyl chloride and triphenyltin hydride. " ... 

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