Alkoxy esters

The first report of oxidative carbonylation is the reaction of alkenes with CO in benzene in the presence of PdCh to afford the /3-chloroacyl chloride 224[12,206]. The oxidative carbonylation of alkene in alcohol gives the q, f3-unsaturated ester 225 and /3-alkoxy ester 226 by monocarbonylation, and succinate 111 by dicarbonylation depending on the reaction conditions[207-209]. The scope of the reaction has been studied[210]. Succinate formation takes... 

Blooming is the phenomenon of the formation of a white residue of cured adhesive near a bond line. It is the result of the evaporation of a small amount of the adhesive monomer from where it was applied onto the adjoining surfaee and its subsequent polymerization. The use of higher molecular weight monomers, such as the alkoxy esters, eliminates this problem. 

The lithium enolates of a-alkoxy esters exhibit high stereoselectivity, which is consistent with involvement of a chelated enolate.374 39 The chelated ester enolate is approached by the aldehyde in such a manner that the aldehyde R group avoids being between the a-alkoxy and methyl groups in the ester enolate. A syn product is favored for most ester groups, but this shifts to anti with extremely bulky groups. 

The stereoselectivity of silyl ketene acetal Claisen rearrangements can also be controlled by specific intramolecular interactions.246 The enolates of a-alkoxy esters adopt the Z-configuration because of chelation by the alkoxy substituent. 

A slightly more complex Scheme is required for preparation of an antihistaminic agent bearing a secondary amine, e. g., tofenacin (32). In the synthesis of tofenacin, alkylation of the benzhydrol (29) with ethyl bromoacetate affords the alkoxy ester (30) saponification followed by conversion to the methylamide gives (31), which is reduced with lithium aluminum hydride to complete the synthesis of 32. 10... 

The ft -hydroxy ester resulting from the reaction of the tert-butyldimethylsilyl ketene acetal of ethyl acetate with a lactone under acid conditions can be reduced to the /3-alkoxy ester.306 The overall yields are excellent (Eq. 149). 

For the primary and secondary a-alkoxy radicals 24 and 29, the rate constants for reaction with Bu3SnH are about an order of magnitude smaller than those for reactions of the tin hydride with alkyl radicals, whereas for the secondary a-ester radical 30 and a-amide radicals 28 and 31, the tin hydride reaction rate constants are similar to those of alkyl radicals. Because the reductions in C-H BDE due to alkoxy, ester, and amide groups are comparable, the exothermicities of the H-atom transfer reactions will be similar for these types of radicals and cannot be the major factor resulting in the difference in rates. Alternatively, some polarization in the transition states for the H-atom transfer reactions would explain the kinetic results. The electron-rich tin hydride reacts more rapidly with the electron-deficient a-ester and a-amide radicals than with the electron-rich a-alkoxy radicals. 

The lithium enolates of a-alkoxy esters have been extensively explored, and several cases in which high stereoselectivity is observed have been documented.14 This stereoselectivity can be explained in terms of a chelated ester enolate which is approached by the... 

A wide range of carbon-carbon double bonds undergo chain polymerization. Table 3-1 shows monomers with alkyl, alkenyl, aryl, halogen, alkoxy, ester, amide, nitrile, and heterocyclic substituents on the alkene double bond. 

The discovery, by Purdie and his collaborators, that the reaction between a lower alkyl iodide and the silver salt of a simple hydroxy acid yielded a proportion of the corresponding alkoxy ester, led to the silver... 

Around 1970, Heck found that olefins reacted with alcohols under a CO atmosphere in the presence of oxidants such as Pd(ii) and Gu(ii) salts to give /3-alkoxy esters 94, 1,2-diesters 95, and a,/ -unsaturated esters 96, as described in Equation Intensive studies have been carried out, aiming at (i) seeking an oxidation catalyst using... 

Ba-hexaaluminate Sol-gel hydrolysis of organic precursors A1 alkoxy-ester and Ba acetate 1200-1300 Ba-P-Al203, no surface area Ceramic meterials 19... 

To prepare hexaaluminates for ceramic applications a slightly different sol-gel process was proposed by Debsikbar.19 Ba-hexaaluminates were prepared via hydrolysis of Al di(isopropoxide) acetoacetic ester chelate and anhydrous Ba acetate obtained by reaction between BaC03 and glacial acetic acid. The substitution of Al(i-OC3H7)3 with the alkoxy ester was intended to control the chemical polymerization during gel formation. The reaction was performed in 1-butanol. The formation of the gel slowly occurred at room temperature in about 10 h. To obtain the final phase the gel precursor was dried at 70 °C for about 2 weeks, ground and calcined at 1200°C for 2 h. However no data on the morphology of the final materials were reported by the author. 

The synthesis of succinic acid derivatives, /3-alkoxy esters, and a,j3-unsaturated esters from olefins by palladium catalyzed carbonylation reactions in alcohol have been reported (24, 25, 26, 27), but full experimental details of the syntheses are incomplete and in most cases the yields of yS-alkoxy ester and diester products are low. A similar reaction employing stoichiometric amounts of palladium (II) has also been reported (28). In order to explore the scope of this reaction for the syntheses of yS-alkoxy esters and succinic acid derivatives, representative cyclic and acyclic olefins were carbonylated under these same conditions (Table I). The reactions were carried out in methanol at room temperature using catalytic amounts of palladium (II) chloride and stoichiometric amounts of copper (II) chloride under 2 atm of carbon monoxide. The methoxypalladation reaction of 1-pentene affords a good conversion (55% ) of olefin to methyl 3-methoxyhexanoate, the product of Markov-nikov addition. In the carbonylation of other 1-olefins, f3-methoxy methyl esters were obtained in high yields however, substitution of a methyl group on the double bond reduced the yield of ester markedly. For example, the carbonylation of 2-methyl-l-butene afforded < 10% yield of methyl 3-methyl-3-methoxypentanoate. This suggests that unsubstituted 1-olefins may be preferentially carbonylated in the presence of substituted 1-olefins or internal olefins. The reactivities of the olefins fall in the order RCH =CHo ]> ci -RCH=CHR > trans-RCH =CHR >... 

The oxycarbonylation of propene under the same conditions results in the formation of crotonic acid as the major product instead of the more valuable methacrylic acid.439 When the oxycarbonylation of ethylene or terminal alkenes is carried out in anhydrous alcoholic solvents instead of acetic acid, dialkyl succinates and /3-alkoxy esters are the major products (equation 173).441,442... 

C-H insertion a to oxygen would generate p-hydroxy or p-alkoxy esters. Thus, the reaction could be considered as a surrogate of the aldol reaction. In Vol. II, Chap. 16 of this series, the preliminary studies on C-H activation of tet-rahydrofuran were summarized [3]. Since then this reaction has been optimized such that the major C-H activation product 22a can be obtained in 97% ee [17]. The optimum reaction conditions (2 equivalents of THF in hexane at -50 °C) demonstrate the regioselectivity that is possible with this chemistry because no reaction with the solvent was observed under these mild conditions. 

The /f-alkoxy ester 111 is formed by nucleophilic substitution of 114 with alkoxide. Formation of 109, the esters 111, and 112 can be regarded as the nucleophilic addition to alkenes promoted by Pd(II). 

The Claisen ester enolate reaction has proved to be extremely useful in the synthesis of a large number of natural products.3 In addition, the rearrangement has been extended to allow the preparation of useful intermediates such as a-alkoxy esters,88 329 33 336 343 a-phenylthio esters,339344-345 a- and [3-amino acids,340 346-350 a-fluoro esters,351 cycloalkenes,352353 tetronic acids,354 and dihydro-pyrans.355-357... 

In the presence of CO, terminal alkenes are oxidized by PdCl2 to RCH(C1)CH2C0C1. When the reaction is made catalytic in palladium by the addition of CuCl2 and oxygen, and carried out in alcohols, the products are a, /3-unsaturated esters, /3-alkoxy esters, and, under some conditions, succinate derivatives (equation 87). Two mechanisms are possible for this reaction. In the first, an oxypalladation can produce a Pd-CH2-CH2-X species, which can undergo CO insertion into the Pd-C bond. Alternatively, an XCOPd species can form and add across the double bond. Loss of Pd-H can generate the a, /3-unsaturated ester, or a second carbonylation step can lead to succinate derivatives. 

Conjugate addition of alcohols to conjugated esters, using ceric ammonium nitrate and LiBr, gave the corresponding a-bromo-p-alkoxy ester. ... 

It is, in fact, likely that Eq. (112) may explain the j3-alkoxy ester formation, whereas Eq. (113) may be the route to methyl acrylate. Thus, preparation of carboalkoxypalladium(II) in situ by exchange with the stable ROOCHgCl in the presence of ethylene gives only acrylate esters (90) ... 

The reduction of esters to aldehydes generally works best when alkoxy or amino functionality is in close proximity to the ester group, as in a- or -alkoxy esters. A neighboring alkoxy group will stabilize the tetrahedral intermediate through chelation and prevent overreduction. DIBAL-H-mediated mono-reduction of lactones delivers the corresponding lactols (hemiacetals). ... 

Step 2. Chemoselective reduction of the a-alkoxy ester Step 4. Ester enolate alkylation (5-exo-tet cyclization)... 

Summarizing the different results from the literature, under the conditions of oxidative carbonylation in the presence of alcohols and catalytic amounts of PdCl2, esters of a,)0-unsaturated carboxylic acids, j0-alkoxy-esters and 2-sub-stituted dialkyl succinates are generally obtained, or mixtures of all of these compounds. Preferably CuCl2, but also other transition metal salts, can be used as co-catalysts (eq. (2)). 

Depending on the oxidative reaction conditions, besides dicarboxylated products, unsaturated carboxylic acid derivatives or in the case of hydroesterification ff-alkoxy esters could be formed [32]. Thus, linear 1-alkenes afford in principle /9-alkoxy esters under neutral oxidative conditions, but under more basic conditions, e.g., sodium butyrate buffer, 1,2-diesters predominate [36]. 

The first step of the Stobbe condensation is the deprotonation of the succinate at the a-carbon to afford an ester enolate that in situ undergoes an aldol reaction with the carbonyl compound to form a 3-alkoxy ester intermediate. The following intramolecular acyl substitution gives rise to a y-lactone intermediate which undergoes ring-opening and concomittant double bond formation upon deprotonation by the alkoxide ion. Under certain conditions the lactone intermediate can be isolated. 

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