Dienophiles in Diels-Alder reaction

Butenediol is a weak dienophile in Diels-Alder reactions. Adducts have been described with anthracene (108) and with hexachlorocyclopentadiene... 

Acrolein a.s Dienophile. The participation of acrolein as the dienophile in Diels-Alder reactions is, in general, an exothermic process. Dienes such as cyclopentadiene and l-dieth5laniino-l,3-butadiene react rapidly with acrolein at room temperature. 

Maleic anhydride has been used in many Diels-Alder reactions (29), and the kinetics of its reaction with isoprene have been taken as proof of the essentially transoid stmcture of isoprene monomer (30). The Diels-Alder reaction of isoprene with chloromaleic anhydride has been analy2ed using gas chromatography (31). Reactions with other reactive hydrocarbons have been studied, eg, the reaction with cyclopentadiene yields 2-isopropenylbicyclo[2.2.1]hept-5-ene (32). Isoprene may function both as diene and dienophile in Diels-Alder reactions to form dimers. 

Cycloaddition Reactions. Methacrylates have been widely used as dienophiles in Diels-Alder reactions (22—24). 

The following compounds have been obtained from thiete 1,1-dioxide Substituted cycloheptatrienes, benzyl o-toluenethiosulfinate, pyrazoles, - naphthothiete 1,1-dioxides, and 3-subst1tuted thietane 1,1-dioxides.It is a dienophile in Diels-Alder reactions and undergoes cycloadditions with enamines, dienamines, and ynamines. Thiete 1,1-dioxide is a source of the novel intermediate, vinylsulfene (CH2=CHCH=SQ2). which undergoes cyclo-additions to strained olefinic double bonds, reacts with phenol to give allyl sulfonate derivatives or cyclizes unimolecularly to give an unsaturated sultene. - Platinum and iron complexes of thiete 1,1-dioxide have been reported. 

The 5-methylene-2(5//)-furanone 216 was found to be a good dienophile in Diels-Alder reactions with acyclic dienes (R = H, 2-Me, 2,3-di-Me, 1-Me, 1,3-di-Me). The reaction took place specifically at the cxo-cyclic double bond to give the corresponding spiro adducts 217 in good yields (Scheme 59) (90JOC3060). 

Amino-subsdnued dienes are also important dienophiles in Diels-Alder reactions Recently, chiral and achiral 2-amino-l,3-dienes have been prepared to snidy their reactivity Csee also asymmetric Diels-Alder reaction Section 8 1 2 The reaction of 2,3-diamino-l,3-butadienes v/ith nitrostyrene gives unusual [3t-2 carbocyclization products, 2-aminocyclopentanones, which are not formed by the direct cycloaddidon but derived from the Michael addidon products fsee secdon discussing the Michael addidon Secdon 4 1 3 "... 

Trifluoromethyl-l,3-dioxin-4-ones can act as the enone component in [2 + 2] or as dienophiles in Diels-Alder reactions and are potential synthons for enantiomerically pure trifluoromethyl aliphatics [92JCS-(Pl)1393). 

It has been established that alkoxy alkenylcarbene complexes participate as dienophiles in Diels-Alder reactions not only with higher rates but also with better regio- and stereoselectivities than the corresponding esters [95]. This is clearly illustrated in Scheme 51 for the reactions of an unsubstituted vinyl complex with isoprene. This complex reacts to completion at 25 °C in 3 h whereas the cycloaddition reaction of methyl acrylate with isoprene requires 7 months at the same temperature. The rate enhancement observed for this complex is comparable to that for the corresponding aluminium chloride-catalysed reactions of methyl acrylate and isoprene (Scheme 51). 

It was also well established that silenes could take part as the dienophile in Diels-Alder reactions. In many cases, particularly with unsymmetric dienes such as isoprene, the reactions were not clean because, in addition to formation of the [2+4] cycloadduct 61, the possibility exists for the formation of it regioisomer 62, products of an ene reaction 63, and conceivably the [2+2] cycloaddition product 64, as shown in Eq. (23). Wiberg... 

It has been known that aromatic heterocycles such as furan, thiophene, and pyrrole undergo Diels-Alder reactions despite their aromaticity and hence expected inertness. Furans have been especially used efficiently as dienes due to their electron-rich properties. Thiophenes and pyrroles are less reactive as dienes than furans. But pyrroles with A-elecIron-withdrawing substituents are efficient dienes. There exists a limited number of examples of five-membered, aromatic heterocycles acting as dienophiles in Diels-Alder reactions. Some nitro heteroaromatics serve as dienophiles in the Diels-Alder reactions. Heating a mixture of l-(phenylsulfonyl)-3-nitropyrrole and isoprene at 175 °C followed by oxidation results in the formation of indoles (see Eq. 8.22).35a A-Tosyl-3-nitroindole undergoes high-yielding Diels-Alder reactions with... 

Isoxazole ring systems play an important role in organic synthesis, and 4-nitroisoxazoles have been used as dienophiles in Diels-Alder reactions, as shown in Eq. 8.23.36... 

Kerth etal. have investigated the reactions of 1,2-thiaphospholes as dienophiles in Diels-Alder reactions (see Sections 12.12.6.1.3 and 12.12.6.2.4). The reaction of compound 281 with cyclopentadiene only proceeded at high temperature (120 °C) and produced two products that could be separated chromatographically. The major product, compound 282, was a crystalline solid, and the minor product, compound 283, was isolated as a viscous oil <2003EJ01894>. 

Hetero substituted 2-cyclopropylideneacetates are ring-strain activated acrylates, highly reactive dienophiles in Diels-Alder reactions, but also powerful Michael acceptors. The reactivity of these compounds is enhanced by the same strain release in the Diels-Alder cycloadditions as well as in the 1,4-additions, and indeed the borderline between tandem Michael-cyclization and Diels-Alder-type cycloaddition is not well defined in many cases. 

As mentioned already in CHEC-II(1996) <1996CHEC-II(8)411>, some tetrazolo[l,5- ]pyridines can react with their C(5)-C(6) and C(7)-C(8) double bonds as dienophiles in Diels-Alder reactions. A novel study again supported this recognition Goumont et al. described that 6,8-dinitrotetrazolo[l,5- ]pyridine 11 easily react with some 2,3-disub-stituted butadienes to give bis-cycloadducts 48 <2002T3249>. These products when treated with potassium /-butoxide undergo base catalyzed elimination of nitric acid followed by oxidation reaction to yield the fully aromatic tetracyclic compounds 49 (Scheme 14). 

Simple dienes react readily with good dienophiles in Diels-Alder reactions. Functionalized dienes are also important in organic synthesis. One example which illustrates the versatility of such reagents is l-methoxy-3-trimethylsilyloxy-1,3-butadiene (.Danishefsky s diene) 1 Its Diels-Alder adducts are trimethylsilyl enol ethers which can be readily hydrolyzed to ketones. The /j-mcthoxy group is often eliminated during hydrolysis. 

L in Scheme 11.3) departs. Nucleophilic addition to the intermediate benzyne (step D) is readily explained by perturbative MO arguments. The extra and orbitals of benzyne are compared to those of ethylene in Figure 11.7. The aromatic n system is not involved in the special properties of benzyne. The third benzyne n bond is due to the overlap in fashion of the two sp2 hybrid orbitals which lie in the nodal plane of the intact 6 electron system. Two factors contribute to a very low LUMO for benzyne. First, the sp2 hybrid orbitals are lower in energy than the 2p orbitals from which the ethylene orbitals are constructed. Second, the intrinsic interaction between the two sp2 orbitals is less than the normal / cc since the orbitals have less p character and are tipped away from each other. The low LUMO of benzyne makes the molecule a strong Lewis acid, susceptible to attack by bases, and a reactive dienophile in Diels-Alder reactions, as we shall see later. 

Reduced furan rings occur in many important anhydrides, lactones, hemiacetals and ethers. Maleic anhydride is frequently used as a dienophile in Diels-Alder reactions and it is a component of alkyd resins. Several unsaturated y-lactones are natural products, while the furanose sugars are cyclic hemiacetals. 

Triazines usually react with dienophiles in Diels-Alder reactions to afford pyrimidine derivatives (Equation 7). 

Although a,/8-unsaturated thio- and selenoaldehyde complexes also seemed to behave as dienophiles in Diels-Alder reactions with cyclopentadiene, the products were too unstable for characterization. Therefore, it remains unknown which double bond (E=C or C=C) was involved in the cycloaddition.64... 

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