Unsaturated carboxylic esters with aldehydes

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 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. 

In 2006, Zeitler demonstrated the use of alkynyl aldehydes in redox esterification [114]. As in previous examples, the author proposes the formation of an activated carboxylate that acts as an acylating agent Eq. 19. A variety of a,P-unsaturated carboxylic esters 199 are formed in moderate yields with E-selectivity up to >95 5. 

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... 

Some typical reactions of 1,1 -difluoroethene with nucleophiles are summarized in Scheme 2.18. Alkoxides [3], trialkylsilyl anion [4], ester enolates [5], and diphenylphosphinyl anion [6] attack the gem-difluorinated carbon of 5. However, it is noteworthy that nucleophilic substitution and proton abstraction are in some cases competitive, and thus s -butyl lithium abstracts the (3 -vinylic proton predominantly to generate vinyllithium. The lithium species can be trapped with an aldehyde, providing difluoroallyl alcohol, which is then hydrolyzed to a, (3-unsaturated carboxylic ester (11) [ 7 ] (Scheme 2.19). Some synthetically useful examples are shown in Schemes 2.20 and 2.21. Tetrathiafulvalene derivative (14) is prepared from difluorinated derivative (13) [8]. An elegant intramolecular version was demonstrated by Ichikawa, which provided a range of cyclized compounds (17), including dihydrofurans, thiophenes, pyrroles, and cyclopentenes, and also corresponding benzo derivatives (20) [2]. 

Finally, a different type of coupling reaction is achieved by molybdenum 0x0 complexes as catalysts. Aldehydes react with diazoacetate in the presence of PPhs to give a,jS-unsaturated carboxylic esters and Ph3P=0. Molybdenum carbene intermediates have been suggested (Scheme... 

The addition of alkoxyacetylides to aldehydes and ketones has emerged as a powerful olefination strategy for the production of a,p unsaturated carboxylic esters. This technique was first reported in the synthesis of an antifungal mold metabolite isolated from the fermentation of an acrostalagmus species. Addition of the acetylide anion to 28 and subsequent Meyer-Schuster rearrangement completed the synthesis of the metabolite 29 along with its anomer 30. 

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. ... 

In the presence of a strong base, the ot carbon of a carboxylic ester can condense with the carbonyl carbon of an aldehyde or ketone to give a P-hydroxy ester, which may or may not be dehydrated to the a,P-unsaturated ester. This reaction is sometimes called the Claisen reaction,an unfortunate usage since that name is more firmly connected to 10-118. In a modem example of how the reaction is used, addition of tert-butyl acetate to LDA in hexane at -78°C gives the lithium salt of ferf-butyl acetate, " (12-21) an enolate anion. Subsequent reaction a ketone provides a simple rapid alternative to the Reformatsky reaction (16-31) as a means of preparing P-hydroxy erf-butyl esters. It is also possible for the a carbon of an aldehyde or ketone to add to the carbonyl carbon of a carboxylic ester, but this is a different reaction (10-119) involving nucleophilic substitution and not addition to a C=0 bond. It can, however, be a side reaction if the aldehyde or ketone has an a hydrogen. 

The benzotriazolyl derivative of acrolein acetal, compound 882, is lithiated, treated with chlorodiphenylphosphine, and the obtained intermediate is oxidized with hydrogen peroxide to phosphine oxide 883 (Scheme 145). The relatively acidic proton in derivative 883 is easily removed by a base, and the obtained anion adds to a carbonyl group of aldehyde or ketone. Subsequent rearrangement and elimination of the phosphorane group generates diene 884. For the derivatives of aldehydes (884, R2 = H), (E)-(E) stereoselectivity of the elimination is observed. Acidic alcoholysis of dienes 884 affords esters of P,y-unsaturated carboxylic acids 885 < 1997JOC4131>. 

Composition. Shellac is primarily a mixture of aliphatic polyhydroxy acids in the form of lactones and esters. It has an acid number of ca 70, a saponification number of ca 230, a hydroxyl number of ca 260, and an iodine number of ca 15. Its average molecular weight is ca 1000. Shellac is a complex mixture, but some of its constituents have been identified. Aleuritic acid, an optically inactive 9,10,16-trihydroxypalmitic acid, has been isolated by saponification. Related carboxylic acids such as 16-hydroxy- and 9,10-dihydroxypalmitic acids, also have been identified after saponification. These acids may not be primary products of hydrolysis, but may have been produced by the treatment. Studies show that shellac contains carboxylic acids with long methylene chains, unsaturated esters, probably an aliphatic aldehyde, a saturated aliphatic ester, a primary alcohol, and isolated or unconjugated double bonds. 

DSM jointly with Du Pont de Nemours308 have patented platinum catalysts generated from the water soluble sulfonated ligand 30 (Table 2 m=0, n=0, m=l, n=2 m=l, n=l, Ar=nBu-S03Li) and used in the aqueous phase hydroformylation of internally unsaturated carboxylic acids, esters or nitriles to their corresponding formyl derivatives which are useful intermediates for the preparation of di-carboxylic acids (e.g. adipic acid). For example, TOFs up to 105 h-1 were achieved in the hydroformylation of 3-pentenoic acid catalysed by Pt/30 (m=0, n=0) at 100°C and 80 bar CO/H2 to give aldehydes with a selectivity of 83% (n/i=3.4), valeric acid (4.6%) and adipic acid (8.1%).308 The products were separated from the aqueous catalyst solution by extraction with ether. Five recycles of the aqueous catalyst solution showed that the Pt/30 (m=0, n=0) catalyst retains its activity. 

Heterosubstituted cyclopropanes can be synthesized from appropriate olefins and car-benes. Since cyclopropane resembles olefins in its reactivity and is thus an electron-rich car bo-cycle (p. 76ft). it forms complexes with Lewis acids, e.g. TiCL, and is thereby destabilized This effect is even more pronounced in cydopropanone ketals. If one of the alcohols forming the ketal is a silanol, the ketal is stable and distillable. The O—Si-bond is cleaved by TiCl4 and a d3-reagent is formed. This reacts with a -reagents, e.g. aldehydes or ketals. Various 4-substituted carboxylic esters are available from 1-alkoxy-l-siloxycyclopropanes in this way (E. Nakamura, 1977). If one starts with l-bromo-2-methoxycyclopropanes, the bromine can be selectively substituted by lithium. Subsequent treatment of this reagent with carbonyl compounds yields (2-methoxycyclopropyl)methanols, which can be transformed to /7,y-unsaturated aldehydes (E.J. Corey, 1975B). 

Aromatic carboxylic acids, a,/f-unsaturated carboxylic acids, their esters, amides, aldehydes and ketones, are prepared by the carbonylation of aryl halides and alkenyl halides. Pd, Rh, Fe, Ni and Co catalysts are used under different conditions. Among them, the Pd-catalysed carbonylations proceed conveniently under mild conditions in the presence of bases such as K2CO3 and Et3N. The extremely high toxicity of Ni(CO)4 almost prohibits the use of Ni catalysts in laboratories. The Pd-catalysed carbonylations are summarized in Scheme 3.9 [215], The reaction is explained by the oxidative addition of halides, and insertion of CO to form acylpalladium halides 440. Acids, esters, and amides are formed by the nucleophilic attack of water, alcohols and amines to 440. Transmetallation with hydrides and reductive elimination afford aldehydes 441. Ketones 442 are produced by transmetallation with alkylmetal reagents and reductive elimination. 

Diisobutylaluminum benzenetellurolate, prepared from diphenyl ditellurium and diisobutylaluminum hydride, adds in a 1,4-fashion to a,/i-unsaturated aldehydes, ketones, and carboxylic acid esters to give as intermediates /i-phenyltelluro-substituted aluminum enolates that can be hydrolyzed to the carbonyl compounds or reacted with aldehydes to produce aldol adducts2. 

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