Reverse-electron-demand

In the case of the reverse-electron-demand Diels-Alder reactions, the secondary orbital interaction between the Jt-HOMO of dienophile and the LUMO of 114 or the effect of the orbital phase enviromnents (Chapter Orbital Phase Enviromnents and Stereoselectivities by Ohwada in this volume) cannot be ruled out as the factor controlling the selectivity (Scheme 55). 

Diels-Alder reactions are one of the most fundamental and useful reactions in synthetic organic chemistry. Various dienes and dienophiles have been employed for this useful reaction.1 Nitroalkenes take part in a host of Diels-Alder reactions in various ways, as outlined in Scheme 8.1. Various substituted nitroalkenes and dienes have been employed for this reaction without any substantial improvement in the original discovery of Alder and coworkers.2 Nitrodienes can also serve as 4ti-components for reverse electron demand in Diels-Alder reactions. Because the nitro group is converted into various functional groups, as discussed in Chapters 6 and 7, the Diels-Alder reaction of nitroalkenes has been frequently used in synthesis of complex natural products. Recently, Denmark and coworkers have developed [4+2] cycloaddition using nitroalkenes as heterodienes it provides an excellent method for the preparation of heterocyclic compounds, including pyrrolizidine alkaloids. This is discussed in Section 8.3. 

The quinolizinium ring can behave as the diene component in reverse electron demand Diels-Alder reactions. For example (Equation 1), the reaction between a dienophile generated in situ by acid-catalyzed dehydration of precursor 72 and quinolizinium 73 gave the l,4-ethanobenzo[A]quinolizinium derivative 74 <2001BML519>. 

An AMI semiempirical method was used to investigate the Diels-Alder cycloaddition reactions of vinyl sulfenes with buta-1,3-dienes.156 The reactivity and stereoselectivity of vinyl boranes have been reviewed.157 Aromatic methyleneamines undergo reverse-electron-demand Diels-Alder reactions with cyclopentadiene, norbom-ene, and vinyl sulfides.158... 

Thus the reaction of 3,4-bis(methoxycarbonyl)-l,2-dithiete 19f with alkenes and alkynes gave the corresponding dihydrodithiins or thiophenes 120-126, respectively (Scheme 14). This reaction was considered as a reverse electron-demand hetero-Diels-Alder process (see Section 2.18.2) <2000JOM(611)106, 1999JOC8489>. 

A novel reverse electron demand hetero-cycloaddition of glycals 538 with diacylthione 537 has been reported, an example of which is shown in Equation (37) giving products 539 and 540 <1998JOC6673>. It is suggested that this [4+2] cycloaddition may occur in stepwise fashion. 

A rarer type is the reverse electron demand Diels-Alder reaction in which the dienophile has electron-donating groups and the diene has a conjugated electron-withdrawing group. 

The reaction is clearly a cycloaddition but at first sight the regioselectivity is all wrong. The answ comes from a realization that this is a reverse electron demand Diels-Alder reaction. The diene very electron-deficient with two conjugated carhonyl groups so the dienophile needs to be electro." rich. The enone is not electron-rich enough but its enol is. The enone could be prepared by Eire reduction... 

When l,8-bis(dimethylamino)-4-vinylnaphthalene (121) is heated with 3,6-diphenyl-s-tetrazine (DFT), a [4 + 2]-cycloaddition reaction with reverse electron demands takes place to give the 1,4-dihydropyridazine derivative 208 (Scheme 37). The latter could be oxidized with chloranil or with excess of DFT to pyridazine 209118. A similar reaction with acenaphthylene proton sponge 107 gives directly the annelated pyridazine 139, since the intermediate dihydropyridazine is readily oxidized in air. It was established that the reactivity ratio of compounds 107, 121, 5-dimethylaminoacenaphthylene and acenaphthylene in the reaction with DFT is equal to 32 17 14 1, respectively. These data are in... 

The double bond of unsubstituted benzvalene is considered to be an electron-rich system which reacts with electron-deficient 1,3-dienes namely the Diels-Alder reaction is reverse electron demanding. Two Diels-Alder reactions of benzvalene are described in the following. Benzvalene does not react with usual 1,3-diene but with electron-deficient 1,3-dienes like 1,2,4,5-tetrazine (80) or hexachlorocyclopentadiene (81)74). Dihalogenocarbene also adds to the double bond (82) 75). The obtained... 

Among the few examples of simple 1-azadiene Diels-Alder reactions is a dihydropyridine synthesis using the stable azadiene 39 (prepared from cinnamaldehyde and aniline) with the dienophile 38 prepared from the isoxazole 35 by elimination. This is a reverse-electron-demand cycloaddition, the HOMO of the dienophile 38 combining with the LUMO of the azadiene 39 to give the cycloadduct 40 and hence the dihydropyridine 41 with complete regioselectivity and in very high yield.3... 

Sulfonamides are the most widely used electrophilic 1-azadienes, e.g. 51, and they react with electron-rich dienophiles such as enol ethers in reverse electron demand Diels-Alder reactions.6... 

For a reverse electron-demand Diels-Alder with azadienes, Barluenga8 reacted stable silylated imines 65 of unenolisable aldehydes (R = Ar or cinnamyl) with acetylene dicarboxylic esters to give the 2-azadienes 67. 

L. F. Tietze, K. H. GlUsenkamp, K. Harms, G. Remberg, and G. M. Sheldiick, Diels-Alder reactions of malondialdehyde derivatives with reversed electron demand, Tetrahedron Lett., 1147 (1982). 

Experimental protocol for Staudinger-Bertozzi, Cu(l)-catalyzed Huisgen alkyne-azide cycloaddition, and reverse-electron-demand Diels-Alder ligation to distinguish between pi, p2,and p5. 

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