0,7-Unsaturated esters

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  

Yields of largely (E)-isomers are usually above 70% and the method works equally well with lactones to give -hydroxy unsaturated esters. Both phosphoranes and phosphonates derived from long-chain 

Wittig-type reactions but the former phosphoranes give greater 207 

An alternative strategy for this type of olefination is the Reformatsky reaction, which, when mediated by tri-n-butyl stibine, directly gives excellent yields of (E)-a,B-unsaturated esters with or 

However, these are only effective with non-enolisable 

Unsaturated Esters. - Following on from a recent report that the ionization of triethyl phosphonoacetate can be promoted by lithium chloride to such an extent that only DBU or Hunig s base 

3- chloropropanal for acrolein the initial adducts (181) undergo smooth and rapid elimination of the elements of HCl when treated with DBN to give esters (182) in ca. 80% yields. 

A useful polystyrene-bound palladium catalyst has been developed for use in Heck-type coupling reactions [(193)— (195)  

Peterson olefination reactions between lactones (196) and a-silylacetates have been used to obtain isomeric mixtures of the 

N-alkyl-lactams with lithium t-butyl acetate. 

Most unsaturated esters are hydroformylated in good yield (table 18). The conjugation in a,p-unsaturated esters is weaker than in unsaturated aldehydes (the resonance energy of crotonaldehyde, for example, is 2.4 Kcal/mole higher than for ethyl crotonate [7]). Thus, conjugated unsaturated esters such as acrylates and crotonates, in contrast to acrolein and crotonaldehyde, can be converted to aldehyde products with synthesis gas. 

Even unsaturated esters having the double bond in conjugation with another unsaturated system, such as maleinates, fumarates and cinnamates, are hydroformylated (see table 18). Rhodium catalysts frequently give better yields than cobalt catalysts [175]. With catalytic amounts of cobalt, cinnamate gave only an 8% yield of hydroformylation product together with 91% hydrocinnamate [60]. Even with stoichiometric amounts of cobalt, only 34% underwent hydroformylation with 49 % being hydrogenated to the hydrocinnamate. In contrast, with catalytic amounts of rhodium, the yield of hydroformylation product was 73 % [175], 

Reactant Pressure (atm) Temp. CQ Products Yield (%) Reference 

Methyl oleate 600-750a 140-145 Mixed aldehyde esters 72 [269-271] 

In analogy with olefins, the hydroformylation of unsymmetrical unsaturated esters gives a mixture of isomeric products. a,p-Unsaturated esters differ from olefins in that the a-carbon atom carries the highest negative charge. At low temperatures and high pressures, the a-formyl compound is formed, while the -formyl ester is produced at higher temperatures and lower pressures [59, 60]. 

A synthesis of unsaturated o-acetylenic vinyl esters has been reported that uses the elimination of trimethylsilyl acetate as a key step. Yields are good for a range of examples, but vinyl-3-butynoate was not accessible by this route. 

The synthesis of ene-sulphides derived from 2-methoxycarbonyIcyclo-pentanone has been described along with their interconversion to other enesulphides via the corresponding S-oxides. A convenient route to the prostaglandin intermediates butyl-5-oxocyclopentene-1-acetate and heptano-ate involves the condensation between 1-morpholinocyclopentene and an appropriate aldehydo ester. 

Takamura, S. D. Young, and B. Ganem, Tetrahedron Lett., 1981, 22, 4163. T. Kitazume and N. Ishikawa, Chem. Lett., 1981, 1259. 

The conversion of acetylenes into olefinic esters by use of addition reactions has been illustrated by the following two examples, (i) 1-Alkenyl boranes, which are readily prepared by the hydroboration of alkynes, are converted into a,fi-unsaturated carboxylic esters in good yield by reaction with carbon monoxide in the presence of palladium chloride and sodium acetate in methanol the process is carried out at atmospheric pressure and occurs with retention of configuration with respect to the alkenyl borane. (ii) Carboxylic acids add to acetylenes in the presence of silver carbonate to provide a novel synthesis of enol esters, which are formed in an 8 2 mixture of isomers.  

Reagents i, trioctylmethylammonium chloride-NaOH-HjO-toluene ii, H2O2-CH3CO2H ui, HCI-MeOH 

Trost has described in full yet another method for the introduction of a double bond adjacent to an ester function. Treatment of the ester enolate with diphenyl-(or dimethyl-) disulphide affords the a-thioester which may be smoothly converted to the a/3-unsaturated ester following oxidation (Nal04 or w-ClC H CO3H) to the sulphoxide and thermal elimination at 110 C (for an alternative, cf. ref. 98) the method gives acceptable yields. 

A ready route to j8-acylacrylic esters has been described, entailing alkylation of jS-keto-sulphoxides with bromoacetate followed by thermal sulphoxide elimination. The intermediate j8-ketosulphoxide esters may be reduced with sodium borohydride to the corresponding -hydroxysulphoxide esters which in turn may be converted into both y-hydroxy-ajS-unsaturated esters or a -butenolides. 

Alkylation of dianion (127) derived from 2-butynoic acid and lithium di-isopro-pylamide, with neryl bromide shows a propensity for 1,4- addition producing a mixture of (128) and (129) in a ratio of 3 1. By contrast, the dianion of 3-methyl-crotonic acid similarly generated, suffers alkylation predominantly at the a-position, although, in the presence of copper(i) iodide, this is altered in favour of attack at the y-position. 

A further example of the synthetic potential of ir-allylpalladium complexes in the formation of carbon—carbon bonds (c/. refs. 152, 189) is the coupling of malonate enolates to complexes (135) to give the unsaturated triesters (136) in virtually quantitative yield.Treatment of diketene with the Grignard reagent 

Miyaura, N. Sasaki, M. Itoh, and A. Suzuki, Tetrahedron Letters, 1977, 3369. 

Tanaka, N. Yamagishi, R. Tanikaga, and A. Kaji, Chem. Letters, 1977, 471. 

The synthetic utility of the Wittig reaction in the preparation of c/s-olefins is further illustrated in the reactions between ( )-ethyl 4-oxobutenoate and alkyl phosphorylides (generated from the parent phosphonium salt using sodamide) 

Methyl 3,6-dihydrobenzoate forms an enolate on treatment with lithium di-isopropylamide which, with primary halides, undergoes a high-yielding alkylation leading to cyclohexa-1,3-diene derivatives (143) such coupling reactions unfortunately fail, however, with secondary halides, aldehydes, and diphenyl disulphide. 

Chiral auxiliaries are very often applied for induction of asymmetry in 1,3-dipolar cycloadditions. For most of the reactions described in this section, recovery of the chiral auxiliary has been demonstrated, but for some reactions the chiral moiety has the potential to be recovered, although it was not performed. Most frequently, the chiral auxiliary is connected to the dipolarophile, very often as a,p-unsaturated esters or amides. In a few cases, auxiliaries have been attached to the 1,3-dipole. 

Brandi and co-workers (271) applied the familiar a,p-unsaturated esters 158 and 159 in reactions with cychc nitrones. In these reactions, the isoxazolidine products were formed as intermediates, which immediately underwent N-alkylation to give tricyclic compounds. The reactions proceeded in both cases with moderate selectivities of 39% de for 158 and 57% de for 159. Most remarkably, the reactions proceeded with opposite face selectivity. 

Humphries, Herling and Dobriner, J. Amer. Chem, Soc., 1951, 73, 

Jones and Dobriner, Vitamins and Hormones (N.Y. Academic Press,) 1949, 

Barnes, Gore, Liddel and Williams, Infra-red Spectroscopy (Reinhold, 

Randall, Fowler, Fuson and Dangl, Infra-red Determination of Organic 

Rasmussen and Brattain, The Chemistry of Penicillin (Princeton Univ. Press, 

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Reformatski reaction Aldehydes and ketones react with a-bromo- fatty acid esters in the presence of zinc powder to give -hydroxy-esters which may be dehydrated to give a-, 0-unsaturated esters. a-Chloroesters will react if copper powder is used in conjunction with the zinc. 

Unsaturated esters decolourise a solution of bromine in carbon tetrachloride and also neutral potassium permanganate solution. 

Clalsen aldol condensation. This consists in the condensation of an aromatic aldehyde and an ester R—CHjCOOCjHj in the presence of finely divided sodium and a trace of alcohol at a low temperature. The catalyst is the alkoxide ion aqueous alkalis caimot be employed since they will hydrolyse the resulting ester. The product is an ap-unsaturated ester, for example ... 

It may be pointed out that dehydration of p hydroxy esters with fused potassium hydrogen sulphate, acetic anhydride, phosphoric oxide or with tliionyl chloride in benzeue solution leads to ap unsiiturated esters containing some PY-unsaturated ester the proportion of the latter depends not only upon the structure of the ester but also upon the dehydrating agent used. Elehydration occasionally occurs during the reaction itself or upon attempted distillation. 

Electrolysis, under similar conditions, of a mixture of two carboxylic acids RCOOH and R COOH leads, in addition to normal coupling products R—R and R —R, to cross coupling R—R. If a mixture of a saturated carboxylic acid and a half ester of an ato-dicarboxylic acid is electrolysed, there are three main products, viz., a hydrocarbon (I), a mono-ester (II), and a di-ester (HI) and these are readily separable by distillation. Some unsaturated ester (IV) is often present in small quantity. 

There s still no helpful C-S disconnection, so let s do the a,p-unsaturated ester next. 

Aryl and vinylic bromides and iodides react with the least substituted and most electrophilic carbon atoms of activated olefins, e.g., styrenes, allylic alcohols, a,p-unsaturated esters and nitriles. 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

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... 

Treatment of 7r-allylpalladium chloride with CO in EtOH affords ethyl 3-butenoate (321)[284]., 3, y-Unsaturated esters, obtained by the carbonylation of TT-allylpalladium complexes, are reactive compounds for 7r-allyl complex formation and undergo further facile transformation via 7r-allylpalladium complex formation. For example, ethyl 3-butenoate (321) is easily converted into 1-carboethoxy-TT-allylpalladium chloride (322) by the treatment with Na PdCL in ethanol. Then the repeated carbonylation of the complex 322 gives ethyl 2-... 

Organotelluriumfll and IV) compounds undergo transmetallation with Pd(II)[414], The carbonylation of the alkenylphenyltellurium(II) 459 gives the a,/3-Unsaturated ester 460 and benzoate, 460 being the main product[415], Reductive coupling of diaryl, dialkyl, and aryl alkyltellurides 461 to give 462 proceeds by treatment with Pd(OAc)2[416,417],... 

Synthesis of camptothecin (163) is another example[133]. The iboga alkaloid analog 164 has been synthesized smoothly by the intramolecular coupling of iodoindole and unsaturated ester to form an eight-membered ring. Af-Methyl protection of the indole is important for a smooth reaction[134]. An efficient construction of the multifunctionalized skeleton 165 of congeners of FR900482 has been achieved[135]. 

Carbonylation of enol triflates derived from ketones and aldehydes affords Q,/)-unsaturated esters[332]. Steroidal esters are produced via their aryl and enol triflates[328]. The enol triflate in 477 is more reactive than the aryl tritlate and the carbonylation proceeds stepwise. First, carbonylation of the enol triflate affords the amide 478 and then the ester 479 is obtained in DMSO using dppp[333]. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

The Q. j-unsaturated ester and amide 942 is prepared by the Pd-catalyzed Wittig-type reaction of the bromoacetate or bromoacetamide 941 with aldehydes and BU(Asf785],... 

A key intermediate, 163, which possesses all but one chiral center of (+ )-brefeldin, has been prepared by the enantiocontrolled cycloaddition of the chiral fi,/3-unsaturated ester 162 to 154[107], Synthesis of phyllocladane skeleton 165 has been carried out by the Pd-catalyzed cycloaddition of the unsaturated diester 164 and cobalt-catalyzed cycloaddition of alkynes as key reactions[108]. Intramolecular cycloaddition to the vinylsulfone in 166 proceeds smoothly to give a mixture of the trans and cis isomers in a ratio of 2.4 1[109], Diastereocontrolled cycloaddition of the hindered vinylsulfone 167 affords a single stereoisomeric adduct, 168, which is used for the synthesis of the spirocarbocyclic ring of ginkgolide[l 10],... 

Unusual cyclocarbonylation of allylic acetates proceeds in the presence of acetic anhydride and an amine to afford acetates of phenol derivatives. The cinnamyl acetate derivative 408 undergoes carbonylation and Friedel-Crafts-type cyclization to form the a-naphthyl acetate 410 under severe condi-tions[263,264]. The reaction proceeds at 140-170 under 50-70 atm of CO in the presence of acetic anhydride and Et N. Addition of acetic anhydride is essential for the cyclization. The key step seems to be the Friedel-Crafts-type cyclization of an acylpalladium complex as shown by 409. When MeOH is added instead of acetic anhydride, /3,7-unsaturated esters such as 388 are... 

The reaction can be applied to the synthesis of q, /3-unsaturated esters and lactones by treatment of the ketene silyl acetal 551 with an allyl carbonate in boiling MeCN[356]. The preparation of the q,, 3-unsaturated lactone 552 by this method has been used in the total synthesis of lauthisan[357]. 

The allyl cyanoacetate 731 can be converted into an a, /3-unsaturated nitrile by the decarboxylation-elimination reaction[460], but allyl malonates cannot be converted into unsaturated esters, the protonation and allylation products being formed instead. 

J-unsaturated ester is formed from a terminal alkyne by the reaction of alkyl formate and oxalate. The linear a, /J-unsaturated ester 5 is obtained from the terminal alkyne using dppb as a ligand by the reaction of alkyl formate under CO pressure. On the other hand, a branehed ester, t-butyl atropate (6), is obtained exclusively by the carbonylation of phenylacetylene in t-BuOH even by using dppb[10]. Reaction of alkynes and oxalate under CO pressure also gives linear a, /J-unsaturated esters 7 and dialkynes. The use of dppb is essen-tial[l 1]. Carbonylation of 1-octyne in the presence of oxalic acid or formic acid using PhiP-dppb (2 I) and Pd on carbon affords the branched q, /J-unsatu-rated acid 8 as the main product. Formic acid is regarded as a source of H and OH in the carboxylic acids[l2]. 

Using a catalyst system of PdCl2, CuCH, HCl, and O2, the internal alkyne 20 is carbonylated at room temperature and 1 atm to give unsaturated esters[19]. This apparently oxidizing system leads to non-oxidative cu-hydroesterilica-tion. With terminal alkynes, however, oxidative carbonylation is observed. 

The intermediate m hydrogenation formed by reaction of the unsaturated ester with the hydrogenated surface of the metal catalyst not only can proceed to the saturated fatty acid ester but also can dissociate to the original ester having a cis double bond or to its trans stereoisomer Unlike polyunsaturated vegetable oils which tend to reduce serum cholesterol levels the trans fats produced by partial hydrogenation have cholesterol raising effects similar to those of saturated fats... 

Olefins add anhydrous acetic acid to give esters, usually of secondary or tertiary alcohols propjiene [115-07-1] yields isopropyl acetate [108-21-4], isobutjiene [115-11-7] gives tert-huty acetate [540-88-5]. Minute amounts of water inhibit the reaction. Unsaturated esters can be prepared by a combined oxidative esterification over a platinum group metal catalyst. Eor example, ethylene-air-acetic acid passed over a palladium—Hthium acetate catalyst yields vinyl acetate. 

Other reactions similar to the aldol addition include the Claisen and Perkin reactions. The Claisen reaction, carried out by combining an aromatic aldehyde and an ester in the presence of metallic sodium, is useful for obtaining a,P-unsaturated esters. 

Esters. The monoisobutyrate ester of 2,2,4-trimethyl-1,3-pentanediol is prepared from isobutyraldehyde ia a Tishchenko reaction (58,59). Diesters, such as trimethylpentane dipelargonate (2,2,4-trimethylpentane 1,3-dinonanoate), are prepared by the reaction of 2 mol of the monocarboxyhc acid with 1 mol of the glycol at 150—200°C (60,61). The lower aUphatic carboxyHc acid diesters of trimethylpentanediol undergo pyrolysis to the corresponding ester of 2,2,4-trimethyl-3-penten-l-ol (62). These unsaturated esters reportedly can be epoxidized by peroxyacetic acid (63). 

Heteroatom functionalized terpene resins are also utilized in hot melt adhesive and ink appHcations. Diels-Alder reaction of terpenic dienes or trienes with acrylates, methacrylates, or other a, P-unsaturated esters of polyhydric alcohols has been shown to yield resins with superior pressure sensitive adhesive properties relative to petroleum and unmodified polyterpene resins (107). Limonene—phenol resins, produced by the BF etherate-catalyzed condensation of 1.4—2.0 moles of limonene with 1.0 mole of phenol have been shown to impart improved tack, elongation, and tensile strength to ethylene—vinyl acetate and ethylene—methyl acrylate-based hot melt adhesive systems (108). Terpene polyol ethers have been shown to be particularly effective tackifiers in pressure sensitive adhesive appHcations (109). 

The starting amino acid for nylon-11 is produced from methyl ricinoleate [141 -24-2] which is obtained from castor oil (qv). The methyl ricinoleate is pyrolized to methyl 10-undecylenate [25339-67-7] and heptanal [111-71-7]. The unsaturated ester is hydroly2ed and then converted to the amino acid by hydrobromination, followed by ammoniation and acidification. The CO-amino acid product is a soft paste containing water, which is dried in the first step of the polymeri2ation process. 

DADC may be polymerised industrially with small amounts of other miscible Hquid monomers. Some acryflc ester monomers and maleic anhydride may accelerate polymerisation. Copolymerisation with methacrylates, diaHyl phthalates, triaHyl isocyanurate, maleates, maleimides, and unsaturated polyesters are among the examples in the early Hterature. Copolymers of DADC with poly-functional unsaturated esters give castings of high clarity for eyeglass lenses and other optical appHcations (20). 

From Diazo Compounds via 1,3-Dipolar Cycloaddition. This method has been utilized widely in heterocychc chemistry. Pyrazohne (57) has been synthesized by reaction of ethyl diazoacetate (58) with a,P-unsaturated ester in the presence of pyridine (eq. 12) (42). 

Composition. Shellac is primarily a mixture of aUphatic 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 carboxyflc 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 carboxyflc acids with long methylene chains, unsaturated esters, probably an aliphatic aldehyde, a saturated aliphatic ester, a primary alcohol, and isolated or unconjugated double bonds. 

The i -alkoxycarbonyhnethylxanthate esters treated with lithium diisopropylamide (LDA) and an aldehyde or ketone give excellent yields of a,P-unsaturated esters (56) ... 

Garboxylation Reaction. The carboxylation reaction represents the conversion of acetylene and olefins into carboxyHc acids (qv) or their derivatives. The industrially important Reppe process is used in the synthesis of P-unsaturated esters from acetylene. Nickel carbonyl is the catalyst of choice (134). 

Unsaturated esters can be prepared from the corresponding acetylenic ethers with yields in most cases of >50% (91) as in the following example ... 

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