3.5- Dibromo-4- ester

To obtain the pure dibromo ester, recrystallise from light petroleum, b.p. (60-80°) the recovery of the pure ester, m.p. 75°, is 85 per cent. 

A naphthalene-catalyzed (<10%) lithiation of a,a-dibromo esters 152 in THF at —78°C was used to generate ester dianions 153, which by warming at 0°C gave lithium ynolates 154. These intermediates were trapped by carbonyl compounds, for instance benzophenone, to give, after final hydrolysis with water, a,/3-unsaturated acids 155 (Scheme 55)" ... 

After standing for one hour, the solution is poured into a large dish and the carbon tetrachloride and unused bromine allowed to evaporate spontaneously (Note 3). The dibromo ester separates in large crystals which form a solid cake in the bottom of the dish (Note 4). This cake is broken up and spread in a thin layer on a large Buchner funnel and subjected to suction until all traces of bromine have disappeared. The white crystals are then dried by pressing between large filter papers. The yield of crude dibromo ester is 280-285 g. (83-87 per cent of the theoretical amount). It melts 65-71 °. 

To avoid the effect of the strong base and to simplify the protocol, a,a-dibromo esters 43 are used as the starting materials, which are treated with 4 equiv of t-BuLi or s-BuLi at —78 °C. The reaction mixture is then warmed to 0 °C to produce the ynoiates 44 in excellent yield (equation 13) . This improved facile method can be carried out without the use of lithium amides. If compouds 43 with R = Ph are used as the starting materials. 

Although this method is convenient in the laboratory, t- and i-BnLi are somewhat expensive and shonld be handled carefnlly, especially in a large scale. A more practical method for the synthesis of ynolates is the rednctive lithiation method. The dibromo esters 43 are treated with lithinm naphthalenide to give the ynolates 44 in good yield. Naphthalene-catalyzed reductive lithiation of the dibromo esters can also be performed, providing the ynolates more efficiently (equation 17) . 

Synthesis of maerolides. The intramolecular coupling reaction of allylic halides (I, 722-723 2, 290-292 3, 211) has now been shown to be applicable to the synthesis of maCrocyclic lactones. Thus addition of the dibromo ester (1) to 6 eq. of nickel carbonyl in N-methylpyrrolidone effects cyclization to the macrolide (2) as the major product. 

The procedure for the elimination of HBr from the dibromo ester is a modification of the method of Lawton and co-workers for sui generis generation of the methyl or ethyl ester during a reaction. Methyl a-(bromomethyl)acrylate has also been prepared by bromination of methyl methacrylate in 700°C steam and by dehydrohalogenation with sodium acetate in acetic acid. Ethyl a-(bromomethyl)acrylate has been prepared by dehydrohalogenation with the monosodium salt of ethylene glycoP and ethyl diisopropylamine." The latter reaction was reported by Ohler et al. with no experimental details for the elimination reaction. The use of triethylamine as reported in this procedure appears to be the most efficient and convenient method for dehydrobromination to these acrylate esters. 

Crocetin dimethyl ester (143) was prepared from each of the isomeric dibromo esters (140-142) with DBU in different solvents at ambient temperature (77CB3582). 

Methyl 9-octadecynoate (174) was obtained in 95% yield from the 9,10-dibromo ester 173 with DBU at 140°C in a nitrogen atmosphere (84JMC94). ... 

Diethyl 1-(ethoxycarbonyl)methylphosphonate, on treatment with freshly prepared sodium hypochlorite or hypobromite solution at 0°C or with chlorine under UV irradiation at 28-30°C 4 and at 50-70°C in CCI4 or with SO.CI, at 40 70"C in CIK b is converted, respectively, into the dichloro or dibromo derivatives in excellent yields. A subsequent selective reduction converts the dichloro products into the monohalo esters. Sodium sulfite is highly selective in the reduction of diethyl 1,1-dichloro-1-(ethoxycarbonyl)methylphosphonate to diethyl 1-chloro-l-(ethoxycarbonyl)methylphosphonate in high yield (90-98%). However, the dibromo ester is completely debrominated on treatment with sodium sulfite, so this method is not useful for the preparation of monobromo ester. Reduction of the dibromoester with SnCl2 (1 eq) in EtOH/H2O gives the monobromo ester in 70-85% isolated yields. ... 

Intramolecular allylic coupling (1, 722-723 2, 290-292). The key step in a total synthesis of the sesquiterpene elemol (3) involves reaction of the dibromo ester (1) with nickel carbonyl (7 equiv.) in N-methylpyrrolidone to form the monocyclic ester (2). Several other products are obtained, separable by chromatography. Significantly none of the c/ -adduct is formed. Reaction of (2) with... 

In 1999, Shindo and Sato reported an interesting one-pot tandem [2 + 2]-cycloaddition-Dieckmann condensation. The condensation is a unique approach for the synthesis of functionalized 5- and 6-membered rings. The reaction proceeds by first treating the 3molate anions of structure 41, which is formed readily in situ from its corresponding o,a-dibromo esters with 4 equiv of tert-BoLi at -78 C. The reaction is warmed up to 0 °C, followed by the addition of y-keto-esters of structure 40 in THF, after which the temperature is then lowered to -78 C, and the reaction then proceeds at that temperature. After workup and with no purification, acid-catalyzed decarboxylation in benzene follows to give compounds of structure 42 in good yields. 

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