Dienophiles diethyl maleate

More recently, Cheeseman and coworkers have investigated cycloaddition reactions of 2,6-dioxypyrazines (80jCS(Pl)1603). 2,6-Dihydroxy-3,5-diphenylpyrazine (77) reacts with electron deficient dienophiles such as iV-phenylmaleimide, diethyl maleate and diethyl fumarate (Scheme 26) to yield adducts of the 3,8-diazabicyclo[3.2.1]octane class such as (78). This reaction is believed to proceed by way of the betaine (79) and has precedent (69AG(E)604) in that photolysis of the bicyclic aziridine (80) generates analogous betaines which have been trapped in cycloaddition reactions. 

The Diels-Alder cycloaddition reaction (Section 14.4) is a pericvclic process that takes place between a diene (four tt electrons) and a dienophile (two tr electrons) to yield a cyclohexene product. Many thousands of examples of Diels-Alder reactions are known. They often take place easily at room temperature or slightly above, and they are stereospecific with respect to substituents. For example, room-temperature reaction between 1,3-butadiene and diethyl maleate (cis) yields exclusively the cis-disubstituted cyclohexene product. A similar reaction between 1,3-butadiene and diethyl fumarate (trans) yields exclusively the trans-disubstituted product. 

In contrast, addition of dimethyl acetylenedicarboxylate to cyclopent[6]azepine (6) is slow and furnishes, in 53% yield, a mixture of the dimeric 1 2 adduct 7 (red crystals), the 1 3 adduct 8 (yellow oil), and an unidentified purple oil.2 Surprisingly, cyclopent[6]azcpine fails to react with other common dienophiles such as ethenetetracarbonitrile, diethyl maleate and chlorosulfonyl isocyanate. 

The same authors also presented a completely selective three-component cascade reaction but of a slightly different type. By reacting 26 with a vinyl-stannane 27 (R = SnBus) in the presence of methyl acrylate or diethyl maleate, a sequential Stille-type [31] cross-coupling-Diels-Alder reaction took place, which only gave the desired products [30]. Since the Stille coupling proceeds without a base present, the dienophile does not participate in a Heck reaction, but only in a [4 + 2] cycloaddition with the initially formed electron-rich diene. 

These methods stiU show limitations. The reduction of (550a) with activated nickel in the presence of diethyl maleate gave a 50 50 mixture of cis and trans adducts (entry 4), probably due to a nickel-promoted cisitrans isomerization of the dienophile prior to cycloaddition. Homogeneous reduction using (ZrCh failed with a dibromide precursor containing a quinone moiety. ... 

Unfortunately the Diels-Alder reaction of vinylketene Ihioacetals is limited to reactive dienophiles thus (3) does not react with diethyl maleate or diphenylacetylene. Also several vinylketene thioacctals were found tobcunrcactivc toward malcicanhydridc. 

The cyclopentadienyltin(IV) compounds undergo Diels-Alder cycloadditions with reactive dienophiles such as maleic anhydride, diethyl maleate, and diethyl acetylenedi-carboxylate," and an endoperoxide has been identified from the reaction with singlet oxygen.123... 

Experiments with 3-oxaquadricyclane 28 and diethyl fumarate or diethyl maleate indicate that the configuration of the dienophile is retained in the product. 

Pindur and Haber explored the chemistry shown in equation 2 and synthesized several new cycloadducts (Scheme 7, 6-12) from IQD 4 [52], The observed regiochemistry with unsymmetrical dienophiles (methyl acrylate, nitrosoben-zene, l,l-bis(phenylsulfonyl)ethane, methyl vinyl sulfone, and methyl vinyl ketone) was low to modest, with the major isomer as predicted by simple FMO theory. However, dienophiles acrolein, propynoates, and diethyl maleate were unreactive relative to dimerization of IQD 4. Pindur and Meyer prepared several bis(tetrahydropyrrolo[3,4- ] carbazoles) by exposing IQDs (generated as shown in equation 2) to alkane-tethered bismaleimides [53]. In two... 

A variety of electron-deficient olefins were shown to be effective dienophiles, giving the expected cycloaddition products (Table 7.9). Reaction ofthe o-xylylene species 2 with maleic anhydride yielded only the cis product, while cis olefins (e.g., dimethyl or diethyl maleate) yielded a mixture of cis and tram cycloaddition products. Tram esters (diethyl fumarate and methyl crotonate) yielded tram adducts however, fumaronitrile gave a mixture of cis and tram adducts. In a separate experiment, it was discovered that upon exposure to the activated nickel, dimethyl maleate was isomerized to dimethyl fumarate. The exact mechanism of the isomerization is at this point unexplained. Noncyclic cis olefins appear to give mixtures of cis and tram cycloadducts, while tram olefins may yield tram products or mixtures of cis and tram products. In cases where mixtures are produced, the tram isomer is the major adduct isomer with the ratio of cis tram isomers apparently being affected by the nature of the olefin. Thus, although the cycloaddition reaction itself is still not proven to be a concerted rather than a stepwise process, the mixture of cis and tram cycloadducts could arise from isomerization of the olefin prior to the cycloaddition process. 

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