Homologation, of esters

It has been reported ( ) that homogeneous ruthenium- or cobalt-iodide-based complexes catalyze the homologation of esters of carboxylic acid to their next higher homologues, for instance ... 

We will here report on homogeneous catalyst systems which allow the homologation of esters to proceed under very mild reaction conditions, i.e. 20-60 bar and 150-160 C, and according to two alternative stoichiometries ... 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

An alternative to the double deprotonation consists in a cleavage, then lithium-bromine exchange on a-bromoenol acetates induced by the sequential use of methyllithium and t-butyllithium (Scheme 28)122. Obviously, the latter enol acetate can result from a conjugate addition on an enone123. Note that an extension of this reaction to the homologation of esters has been described by the same group124. 

Propionic acid is also formed as a co-product when methyl acetate is treated with carbon monoxide in the presence of hydrogen [28]. Rhodium-based homogeneous catalyst systems have been described which permit the homologation of esters according to two alternative stoichiometries. The reactions proceed under mild conditions according to eqs. (17) and (18) [31] ... 

The homologation of esters via a DIBAL reduction and phosphonate extension sequence is a commonly desired transformation. The DIBAL reduction to give an aldehyde suitable for homologation is often plagued by over-reaction problems,so that a reduction-reoxidation procedure is often required. These... 

Unsaturated Esters. - An efficient, single step procedure for two carbon homologation of esters (224) into a,8-unsaturated esters (225) consists of reduction using diisobutylaluminum hydride at low temperature in the presence of a lithiated phosphonoacetate.20 ... 

A number of new methods for the homologation of esters have been reported. Methyl bis(ethylthio)acetate, derived from dichloroacetate and the sodium salt of ethanethiol, can be smoothly alkylated under standard conditions to the corresponding a-alkyl (or alkenyl) derivatives, in excellent yield. The use of DBU as base to effect high yield dialkylations of Knoevenagel type substrates with alkyl bromides has been described. Directed additions of a-substituted ester enolates to cyclohexenone can be achieved by careful control of temperature. Conjugate addition of diphenylmethide to acrylate esters has been achieved after much trial and error substituted acrylates lead to the best yields. 

A protocol for the two-carbon homologation of esters (350) to o,jS-un-saturated esters (352) has been described by Jamison and Webb. Application of multireactor allowed to cany out three-operations procedure involving the ester (350) reduction, phosphonate (351) deprotonation, and the Homer-Wadsworth-Emmons olefination (Scheme 119). ... 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

One of the most sensitive tests of the dependence of chemical reactivity on the size of the reacting molecules is the comparison of the rates of reaction for compounds which are members of a homologous series with different chain lengths. Studies by Flory and others on the rates of esterification and saponification of esters were the first investigations conducted to clarify the dependence of reactivity on molecular size. The rate constants for these reactions are observed to converge quite rapidly to a constant value which is independent of molecular size, after an initial dependence on molecular size for small molecules. The effect is reminiscent of the discussion on the uniqueness of end groups in connection with Example 1.1. In the esterification of carboxylic acids, for example, the rate constants are different for acetic, propionic, and butyric acids, but constant for carboxyUc acids with 4-18 carbon atoms. This observation on nonpolymeric compounds has been generalized to apply to polymerization reactions as well. The latter are subject to several complications which are not involved in the study of simple model compounds, but when these complications are properly considered, the independence of reactivity on molecular size has been repeatedly verified. 

Coumarin formation proceeds via an intramolecular attack by enol ester 9 on the ketone to give 10. Dehydration of 10 then affords coumarin 11. It has been observed that coumarins are favored when higher order homologs of acetic anhydride and their corresponding salts such as propionic anhydride/sodium propionate and butyric anhydride/ sodium butyrate are used. 

Instead of a-halo esters, related reactants can be used e.g. the a-halo derivatives of ketones, nitriles, sulfones and A,A-disubstituted amides. The Darzens condensation is also of some importance as a synthetic method because a glycidic acid can be converted into the next higher homolog of the original aldehyde, or into a branched aldehyde (e.g. 5) if the original carbonyl substrate was a ketone ... 

The effects of structure and temperature on the densities of a homologous series of esters were investigated. In all, five different series of esters were considered. 

Mixtures of two neighboring homologous ester sulfonates and two neighboring disalts (e.g., mixtures of C16 and C18) have different effects on the solubility compared with the pure components. Suitable mixtures of ester sulfonates are more soluble in water than their pure components. The disalts, however, behave in the opposite way (Figs. 2 and 3) [58]. 

For a homologation of carboxylic esters RCOOEt —> RCH2COOEt, which goes by an entirely different pathway, see Kowalski, CJ. Haque, M.S. Fields, K.W. J. Am. Chem. 

Various cyclic phosphonate esters 36 and 37 have been described previously as products from the HHT reaction of 25 with the appropriate cyclic phosphite. A complementary method has also been developed from the V-protected phosphonyl chloride 84, which was readily prepared from the corresponding phosphonic acid 83. Subsequent reaction of 84 with the appropriate diol produced the cyclic phosphonate esters 85 (63). Higher homologs of 85 have also been prepared from the analogous propane or butane diols. 

The main synthetic application of the Wolff rearrangement is for the one-carbon homologation of carboxylic acids.242 In this procedure, a diazomethyl ketone is synthesized from an acyl chloride. The rearrangement is then carried out in a nucleophilic solvent that traps the ketene to form a carboxylic acid (in water) or an ester (in alcohols). Silver oxide is often used as a catalyst, since it seems to promote the rearrangement over carbene formation.243... 

The DIBAL reduction of esters to aldehydes in the presence of phosphonate anions appears to solve problems of overreduction to alcohol and provides a good general method of 2-carbon homologation... 

In addition to the enzymatic hydrolysis of esters, there also ample examples where an epoxide has been cleaved using a biocatalyst. As described by the Faber group [19], reaction of the ( )-2,3-disubstituted ds-chloroalkyl epoxide roc-8-40 with a bacterial epoxide hydrolase (BEH), led to the formation of vie-diol (2 ,3S)-8-41 (Scheme 8.11). The latter underwent a spontaneous cydization to give the desired product (2i ,3i )-8-42 in 92 % ee and 76 % yield. The same strategy was used with the homologous molecule rac-8-43, which afforded the THF derivative (2R,3R)-S-4S in 86% ee and 79% yield. 

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