Representative dienophiles

Substituted Alkynes 7 Esters of acetylenedicar-boxylic acid 

6 Vinyl ketones, acrolein, acrylate esters, acrylonitrile, nitroalkenes, etc. 

Functionalized dienophiles have long played a prominent role in synthetic organic chemistry. Cycloaddition of a substituted benzoquinone to 1,3-butadiene, for example, was the first step in one of the early syntheses of steroids and served to introduce the required angular methyl group in a molecule containing appropriate functionality for further elaboration. 

The synthetic utility of the Diels-Alder reaction has been significantly expanded in recent years by development of dienophiles which contain masked functionalities and are the synthetic equivalents of unreactive or inaccessible species. For example, a-chloroacrylonitrile shows satisfactory reactivity as a dienophile. The a-chloronitrile function in the adduct can be hydrolyzed to a carbonyl group. Thus, a-chloroacrylonitrile is serving as a ketene (CH2=C=0) equivalent. Ketene itself is not suitable as a dienophile since it has a tendency to react with dienes in a [2 -f 2]-cycloaddition rather than the desired [4 + 2] fashion. 

The variety of transformations available to a nitro group permits Diels-Alder adducts of nitroethylene to serve as precursors to a number of useful structural types. 

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Diels-Alder Reaction General Remarks Table 1.2 Representative dienophiles... 

The reactivity of the dienophile depends on the electron demand of the reaction. Electron-withdrawing groups in the dienophile will accelerate the reaction rate. Simple alkenes and alkynes such as ethylene and acetylene are poor dienophiles. In the following table some representative dienophiles have been tabulated along with their reaction with cyclopentadiene. 

Table 4.5. Reactivity of some representative dienophiles towards cyclopentadiene...

Scheme 6.1. Diels-Alder Reactions of Some Representative Dienophiles... 

Diels-Alder reactions. Investigation of use of the sodium salt of 1 in aqueous Diels-Alder reactions was prompted by reports rom two laboratories that water can function as a catalyst in this reaction. In fact, re.iction of the sodium salt in water with representative dienophiles proceeds at lower tempi ratures than those required in reactions of the corresponding methyl ester in benzene. Moioover, the sensitive dienol ether system in 1 is stable to long reaction times (72 hours) an 1 temperatures of 80°. 

The in situ generation of the <, /3-unsaturated sulfine 24 via thermolytic retro Diels-Alder reaction of its dimer and subsequent reactions with the representative dienophiles, acrylonitrile and styrene, provided a regioiso-meric mixture of Diels-Alder products in modest yields [Eq. (19)]. 

Conjugated dienes possessing the 2,3-diaza-1,3-butadiene system rarely participate in effective [4 + 2] cycloadditions. Typical efforts to promote the Diels-Alder cycloadditions of such systems with representative dienophiles afford 2 1 adducts or [3 + 2] criss-cross products.11... 

In efforts to increase the reactivity of simple 1-aza-1,3-butadienes toward typical electron-deficient dienophiles, Ghosez and co-workers found that the a,/3-unsaturated hydrazone 1 behaves as a well-defined electron-rich diene in regioselective, normal (HOMOd,ene controlled) Diels-Alder reactions with a number of representative dienophiles. Reductive cleavage of the nitrogen-nitrogen bond concurrent with reduction of the carbon-carbon double bond has provided substituted piperidines, and aro-matization with elimination of dimethylamine has provided substituted pyridines (Scheme 9-1). Similar reactions of simple or functionalized a, -unsaturated oximes failed to provide an observable [4 -t- 2] cycloaddition. It remains to be determined whether this process is general for a,/3-unsaturated hydrazones capable of tautomerization. 

Diels-Alder reactions of some representative dienophiles... 

On the example of 3,3-dimethyl-2-phenyl- and 3,3-dimethyl-2-(2-thienyl)-3//-pyrroles, a peculiar Diels-Alder condensation has been observed (Scheme 1.149). This is dimerization of 3//-pyrroles where one molecule of 3/f-pyrrole acts as azadi-ene component and the second one represents dienophile [325]. 

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