Ethyl bromoacetate coupling reactions

Indium enolates, prepared conveniently by transmetalation of hfhium enolates with IriCl j, react wifh aldehydes to give fhe corresponding -hydroxy esters [80]. Ultrasound irradiation promotes fhe Reformatsky reaction of aldehydes and ethyl bromoacetate wifh indium [81]. Indium-mediated Reformatsky reaction of phenyl a-bromoalkanoates wifh ketones or aldehydes gives di-, tri-, and tetrasubstituted -lactones (Scheme 8.57) [82]. Indium-mediated reaction of imines with ethyl bromoacetate gives 3-unsubstituted -lactams (Scheme 8.58) [83]. An indium-Refor-matsky reagent prepared from 2-(chlorodifluoroacetyl)furan couples with aldehydes (Scheme 8.59) [84]. 

The starting material 6-methylhept-5-en-2-one (170) was converted, with methanol, into the methoxy compound 171 which was condensed with ethyl bromoacetate (172) in a Reformatsky reaction to give the ester 173. Reaction of 173 with NBS and then dehydrobromination led to the ester 174 which was reduced with LiAIH4 and transformed with triphenylphosphine hydrobromide to the Cio-phosphonium salt 175 and then coupled with crocetindialdehyde (27) in the presence of sodium methoxide as base in a Wittig reaction to give spirilloxanthin (169) in an overall yield of 2% referred to 170 [87] (Scheme 40). 

Within the framework of studies of the mechanism of fragmentation of 2-phenyl-oxetane by electron bombardment in the ion source of a mass spectrometer 2-phenyloxetanes labelled with stable isotopes were needed104. 2-Phenyloxetanes, 157, labelled with fH (and 13C) in different positions have been synthesized according to four-step reaction schemes shown in equations 68 and 69105. In the first step, isotopically (D- or 13C) labelled benzaldehyde has been coupled with ethyl bromoacetate in the presence of Zn and dimethoxymethane. The deuterated 3-phenyl-3-hydroxypropionate obtained has been reduced with lithium aluminium hydride. In the next step the primary alcohol group of the deuterated phenyl propanediol 158 has been tosylated. Cyclization of the monotosylates 159 yielded 13C- or deuterium-labelled 2-phenyloxe-oxtanes 157. 

Reformatsky reaction. The Reformatsky reaction of ethyl bromoacetate with several aldehydes and ketones proceeds in improved yields when the zinc is replaced by Le Goff s zinc-copper couple (1, 1020). THF is usually superior to ether as solvent. ... 

Asym. synthesis. A stirred soln. of startg. optically pure dioxane (prepared from (S)-( + )-butane-l,3-diol) and 4 eqs. of ethyl bromozinc-acetate (prepared from ethyl bromoacetate and Zn-Cu couple) in methylene chloride at —78° treated with 3 eqs. TiCl4, and quenched with 10% NaHC03 when reaction complete ca. 1 h) - product. Y 82% (diastereomer ratio 3.0 1). F.e. with racemic acetals s. T. Basile et al., J. Chem. Soc. Chem. Commun. 1989, 596-7 chiral a-alkoxynitriles with Me3SiCN/TiCl4 s. A. Solladie-Cavallo et al.. Tetrahedron Letters 29, 2955-8 (1988). 

The zinc-mediated Reformatsky reaction is one of the classical methods for carbon-carbon bond formation. To date, various main group metals and transition metals have been used for this reaction. Rieke s activated indium powder mediates readily the coupling of ethyl a-bromoacetate and a variety of carbonyl compounds yielding /3-hydroxy esters in good yields (Scheme 87).3 Later, commercially available indium powder has been found to be equally effective for the indium-based Reformatsky reaction in THF.28 This indium Reformatsky reaction is accelerated by ultrasound irradiation (Scheme 88).322,323 Indium(i) iodide also mediates the Reformatsky reaction of aldehydes and ketones to give /3-hydroxy esters, presumably via organoindium(m) diiodide (Scheme 89).27... 

Hii reported an aminophosphine ligand similar to Amphos [118]. This ligand is prepared in four steps, starting from N-methylaniline and bromoacetic acid ethyl ester. An elevated temperature of 110°C was required to achieve aminations of aryl bromides with secondary amines. Surprisingly, the order of reactivity is reported to be reversed to that usually encountered for palladium-catalyzed couplings, and consequently electron-deficient aryl bromides were aminated in lower yields than the corresponding electron-rich electrophiles. The ligand metal ratio was identified as one of the key parameters for the reaction. 

Bromoacetyl-p-aminobemylsuccinic Acid. Bromoacetic acid, 1.5 mmoles, and 1.5 mmoles of AT-hydroxysuccinimide dissolved in 6 ml of dioxane are coupled with 1.5 mmoles of dicyclohexylcarbodiimide for 2 hr at 0°. The urea derivative is removed by filtration, and the active ester in the dioxane solution is coupled with 1.2 mmoles of p-aminobenzyl-succinic acid dissolved in 4 ml of 80% dioxane. The reaction mixture is kept at room temperature for 6 hr and then evaporated to dryness. The oily residue is dissolved in ethyl acetate. The organic phase is washed twice with H2O, dried over NagSO, and evaporated to dryness. The compound crystallizes from ethyl acetate-petroleum ether m.p. 126°. 

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