Formyl esters

Reactions using 2-formyl esters have also been reported. The anilines reacted smoothly with 40 to give 41 which was cyclized without purification to give the desired quinolines 42 and 43 in 50 and 37% overall yield, respectively. 

The addition of dibutylcupratc to the a-substituted /1-formyl esters 1 preferentially affords, via chelation control, the cw-disubstituted y-lactone 241. These results are in agreement with those found with a-unsubstituted /1-esters39-41 (vide supra), assuming a seven-membered chelate as transition state of the addition reaction. The diastercosclectivity is somewhat lower with esters 1 as the stereogenic center is one carbon atom further removed from the reaction center and therefore the steric influence of the substituent R1 is less pronounced. 

A strikingly different behavior was found with formyl ester 3 which bears two additional methyl groups a to the aldehyde functionality. In this case, addition of dibutylcuprate leads to the predominant formation of the /ranv-disubstituted y-lactone 441. 

The formyl ester and hydroxylamine were allowed to react in ethanol, which was then removed by vacuum evaporation at 40°C. The dry residue decomposed violently 5 min later. Analysis of the residue suggested that the oxime had undergone an exothermic Beckmann rearrangement, possibly catalysed by traces of hydrogen chloride in the reaction residue. 

An alternative method to prepare (Mormyl esters uses different building blocks to assemble the 1,4-dicarbonyl system and is complementary in many cases.10 Base-catalyzed addition of nitromefhane to a, J-unsaturated esters, followed by a variation of the Nef reaction, provides y-dialkoxy-substituted esters. The scope of this sequence has not yet been explored. Another approach involves cuprate additions to norephedrine-derived 2-alkenyloxazolidines this process allows small-scale synthesis of several p-formyl esters in optically active form (ee up to 95%).11... 

A major advantage of the sequence presented here is that the aldehyde group is protected at the siloxycyclopropane stage, which allows convenient storage of this stable intermediate. Of equal importance is the valuable carbanion chemistry that can be carried out a to the ester function. Efficient substitution can be achieved by deprotonation with LDA and subsequent reaction with electrophiles.12-13-6 This process makes several a-substituted [1-formyl esters available. Other ring opening variants of siloxycyclopropanes - mostly as one-pot-procedures - are contained in Scheme I. They underscore the high versatility of these intermediates for the synthesis of valuable compounds.6 Chiral formyl esters (see Table, entries 2-5) are of special... 

An early, qualitative observation of the exceptional reactivity of phenyl and naphthyl acetates having proximate formyl groups was made in 1946 (Vavon and Scandel, 1946). A quantitative study of the alkaline hydrolysis of the 2-, 3- and 4-formylphenyl acetates was made by Holleck et al. (1958). The 2-formyl ester [39] was very rapidly hydrolysed compared with the 3- and... 

The study of both carbonyl and carbon acid participation in ester hydrolysis has been used by Bowden and Last (1971) to evaluate certain of the factors suggested for important roles in enzymic catalysis. A first model concerns a comparison of the three formyl esters and shows that the proximity of the formyl to the ester group and internal strain increase in passing along the series, 1,2-benzoate, 1,8-naphthoate and 4,5-phenanthroate. The very large rate enhancements result from the proximity of the internal nucleophile once formed and from internal strain. Strain is increased or induced by the primary... 

Early studies of the cobalt hydroformylation (4) included vinyl acetate as the olefinic reactant. A mixture of a- and /3-formyl esters was reported. 

The stereoselective total synthesis of both ( )-corynantheidine (61) (170,171) (alio stereoisomer) and ( )-dihydrocorynantheine (172) (normal stereoisomer) has been elaborated by Szdntay and co-workers. The key intermediate leading to both alkaloids was the alio cyanoacetic ester derivative 315, which was obtained from the previously prepared ketone 312 (173) by the Knoevenagel condensation accompanied by complete epimerization at C-20 and by subsequent stereoselective sodium borohydride reduction. ( )-Corynantheidine was prepared by modification of the cyanoacetate side chain esterification furnished diester 316, which underwent selective lithium aluminum hydride reduction. The resulting sodium enolate of the a-formyl ester was finally methylated to racemic corynantheidine (171). 

The formyl esters of acetamidoxime and benzamidoxime have been synthesized and were immediately dehydrated into the corresponding oxadiazoles. 

Oxasteroids. Hydroxy steroids are converted by this system into hypoiodites, which on irradiation are cleaved to formyl esters. These products are cyclized to oxasteroids with sodium borohydride. 

The reaction ofimines such as 33 with ethyl diazoacetates yields complex product mixtures consisting ofaziridines and P-enamino esters. When phenyldiazomethane is used as the nucleophilic component in this iron-catalyzed reaction, aziridines such as 34 are obtained in high yield and as single diastereoisomers (Scheme 8.11) [42]. The catalyst is the same Fe(II)-complex that was applied for the preparation of a-formyl ester 23 (cf. Scheme 8.6). 

Resonance form B identifies it as a formylated ester- or lactone enolate and resonance form... 

Fig. 13.50. a-Methylenation of an ester (in this special case of a lactone) via aldol condensation of the resulting a-formylated ester enolate (in this special case a lactone enolate) B <- B with paraformaldehyde. Here, the migration of the formyl groups E —> C is considered to proceed intramolecularly, but an inter-molecular process is equally conceivable. 

Enantioselective alkylation ofta-formyl esters. In the presence of a catalytic amount of the N,N-dibutyl derivative (2) of 1, dialkylzincs add to the formyl group of esters such as 3 or 4 to form (S)-4- or -5-hydroxyalkanoic esters. These esters cyclize to optically active alkyl-substituted lactones. 

Although alkylations of enolates with a-halo ester compounds are quite effective in singular cases, these reactions often proceed with poor yield and selectivity. Therefore the siloxycyclopropane route is to be considered even for large scale preparations of relatively simple y-oxoesters. Synthesis of rather sensitive formyl esters (entries 9, 13, 16, 17) or the stereoselective generation of /ranj-substituted cyclic y-oxoesters as mentioned above can hardly be achieved with comparable efficiency by other methods. 

Photochemical Fe(CO)5-induced rearrangement of silylated allyl amine 9 gave N-silylated enamine 1015, which on subsequent Cu-catalyzed cyclopropanation by methyl diazoacetate afforded cyclopropane derivative 11. The use of an optically active catalyst gave an asymmetric induction of 56% ee for the cis isomer and 20% ee for the trans isomer. Further acid-induced ring cleavage afforded the -formyl ester 12, whereas reduction and desilylation produced aminocyclopropane carboxylic acid 13 (equation 2). 

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