Bromomalonic Ester

The regioselecdve cross-coupling between anions of bromomalonate esters or bromoacetate esters and m-dirutrobenzene proceeds in the presence of copper tfirr-bntoxide to give the 3-snbsdtiited product Without the copper salt, the4-snbsritiited isomer is the only product fEq 9 35,... 

Finally, Scheme 3.14 presents the Michael addition of bromomalonic ester to conjugated nitro olefins 10. This approach allows one to synthesize five-membered cyclic nitronates (5) doubly functionalized at the C-5 atom (Scheme 3.14, Eq. 5). 

Ethoxycarbonyl-l,2,3,4-tetrahydroquinoxalin-2-ones (86) are obtained either by sodium dithionite reduction of the corresponding quin-oxalinone esters or by direct synthesis from o-phenylenediamines and bromomalonic ester (85).102... 

Cyclopropanation of olefins using bromomalonic ester and l,8-diazabicyclo[5.4.0]-undec-7-ene (DUB) in the presence of a catalytic amount of copper(II) bromide gives 1,1-bis(alkoxycarbonyl)cyclopropane derivatives135. An example is shown in equation 90. 

The 1,4-conjugate addition of ester enolates to a, 3-enones was first reported by Kohler in 1910,138a c as an anomalous Reformatsky reaction, but chemoselectivity was dependent on the structure of the a,(3-enone and restricted to bromozinc enolates obtained from either a-bromoisobutyrate or bromomalonate esters (Scheme 66).138d,e Further evaluation, with lithio ester enolates and lithio amide enolate additions, has resulted in identification of four factors that affect the chemoselectivity and diastereoselectivity of additions to a, 3-enones.139 These factors are (a) enolate geometry, (b) acceptor geometry, (c) steric bulk of the -substituent on the acceptor enone and (d) reaction conditions. In general, under kinetic reaction conditions (-78 °C), ( )-ester enolates afford preferential 1,2-addition products while (Z)-ester enolates afford substantial amounts of 1,4-addition products however, 1,2 to 1,4 equilibration occurs at 25 C in the presence of HMPA. The stereostructure of the 1,4-adducts is dependent on the initial enolate structure for example, with ( )-enones, (Z)-ester enolates afford anti adducts, while (E)-ester enolates afford syn adducts (Scheme 54). In contrast, amide enolates show a modest preference for anti diastereomer formation. 

In 1902, Wheeler and Johnson (63) obtained 5-substituted rhodanines (54) by condensing substituted bromomalonic esters with postassium thiocyanate, then thiolacetic acid, the cyclization resulting from an alkaline treatment. 

Reactions which may at first glance appear to involve ylides may not in fact do so. For example, a bromomalonic ester reacted with a variety of aldehydes in the presence of tributylarsine to form alkylidene- or arylidene-malonic esters, but no base was required and it was suggested that reaction proceeded not via an ylide but via an arsonium salt formed by extraction of a bromonium ion from the malonic ester The malonate anion... 

Although there is no reaction directly related to the Breckpot )0-actam synthesis, other methods of preparing )0-lactams include the cycloaddition of imino compound with ketene, the reaction between diazomethane and isocyanate and the use of bromomalonic ester and primary amine. ... 

FIGURE 23.11 The Gabriel synthesis uses bromomalonic ester in the first step. 

WORKED PROBLEM 23.10 In a simpler version of the Gabriel synthesis, acetamidomalonic ester is used rather than bromomalonic ester. Sketch out the steps in this related amino acid synthesis. 

A simple one-pot strategy for the synthesis of differently substituted quinoxalines from 1,2-aryl diamines and 2-bromomalonic ester at room temperature (Scheme 65) xmder solvent- and catalyst-free conditions has been investigated by Haidar et al. [95]. The mechanism followed is nucleophilic substitution, amide formation, followed by in situ oxidative aromatization. The compoxmd 54a, a key synthetic intermediate for the synthesis of a 5-HT3 receptor antagonist, could be effectively synthesized by this reaction protocol. 

SCHEME 65 Quinoxaline synthesis from 1,2-aryl diamines and 2-bromomalonic ester at room temperature. 

Chloroacetone reacts similarly. Bromomalonic ester gives [29 R = Me X = C(C02Et)2] the intermediate in this case cannot lose a proton, but loses hydrogen bromide instead. Secondary a-halogeno-ketones CHBr(COR)2 react analogously. ... 

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