Some Other Dienophiles

PhSOCH=CHCChR PhS0CH=CHN02 PhS02CH=CHNOi vinylic sulfones 

E- or Z-PhS02CH=CHS02Ph H2C=C(S02Ph)2 PhS02CH=CHC0R H2C==CHN02 

PhSOCH=CHC02R PhSOCH=CHN02 PhS02CH=CHN02 vinylic sulfones 

PhC=CTs PhSeC=CTs t-BuS02C=CS02-f-Bu ArS02C=CS02Ar 5-membered aromatic het 

PhS0CH=CHC02R PhSOCH—CHNOj PhS02CH=CHN02 vinylic sulfones 

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Although 1,1-disubstituted-l,3-dienes are quite unreactive in the Diels-Alder reaction, allylidenecyclopropanes exhibit a good reactivity especially toward activated dienophiles. The strain present in the alkylidenecyclopropane moiety is responsible for the reactivity enhancement observed in these compounds. The literature concerning the parent diene and few analogs until 1984 has been thoroughly reviewed by Krief [31]. Since then, some other examples of variously-substituted allylidenecyclopropane reacting as dienes in [4 + 2] cycloadditions were published. 

Although pyrroles do not generally participate in Diels-Alder reactions with olefinic dienophiles, the very reactive hexafluoro-Dewar benzene with pyrrole gives the 1 1 and 1 2 adducts, 27 and 28, both of which probably have all-ea o stereochemistry. Some other 7-azabicyclo-heptene derivatives have been obtained via cycloaddition reactions of 7-azaquadricyclanes (see Section II, F). 

Trapping of l-azetin-4-one as a dienophile was attempted by using some polymers functionalized with dienic groups, such as the 2-(polymeric carb-oxymethyl)-3-methyl-1,3-butadiene of the polymeric ester of 2-furoic acid, which have been good trapping agents for other dienophilic systems. Under several experimental conditions, both dienic polymers were recovered unchanged. 

Furo[3,4-(/]pyrimidines are ideally suited for participation in Diels-Alder reactions. The reaction of the derivatives (47) with dienophiles leads to tricyclic compounds of the type (48) <9iJOC245>. There is some selectivity, since methyl acrylate forms only two regioisomeric endo products whilst other dienophiles yield both endo and exo adducts (Equation (13)). 

Now for some real examples. Most ene reactions with simple alkenes are with maleic anhydride. Other dienophiles—or enophiles as we should call them in this context—do not work very well. However, with one particular alkene, the natural terpene P-pinene from pine trees, reaction does occur with enophiles such as acrylates. 

Phenylazo-l-alkenes dimerize (a (4+2)-cycloaddition) in the absence of solvent to give pyridazines, or they may react with dienophiles. Some other cycloadditions of this type are reported. 

The (4+2)-cycloaddition reactions are theoretically and experimentally well founded for electron-rich dienes. However, those reactions with electron-rich dienophiles are less investigated. An early application of the inverse type of (4+2)-cycloaddition to pyridazine synthesis, i.e., from electron-deficient azoalkenes and alkenes, was reported by Sommer in 1977, [Eq. (4)]. A mixture of regioisomeric products 22 and 23 was obtained.107 108 However, in the presence of diphenylketene, products of either (2 + 2)- and/or (4+2)-cycloaddition (i.e., pyridazines) are formed arylazoalkenes thus behave similarly to a,/ -unsaturated carbonyl compounds in cycloadditions.109 2-Phenylazo-l-alkenes dimerize (a (4+2)-cycloaddition) in the absence of solvent to give pyridazines, or they may react with dienophiles.110-115 Some other cycloadditions of this type are reported.116-120... 

Some other electron-deficient ketones have been used as dienophiles in Diels-Alder reactions. Various types of 1,2,3-tricarbonyl compounds seem to be quite reactive in this type of process, and some selected examples are listed in Table 4-III.26-28... 

The lack of a strong chromophore has hampered use of LC-UV techniques for isolation or analysis of YTXs. The formation of a fluorescent derivative with the dienophile reagent DMEQ-TAD is the basis for a useful LC-FL method for analysis of YTX and homo YTX in shellfish and algal concentrates. The method can also detect some other analogues of YTX including 45-OHYTX,... 

Phenylphosphole and 3-methyl-1-phenylphosphole also gave such adducts, but they were difficult to separate from some accompanying P-oxides. Other dienophiles (maleic anhydride, tetra-cyanoethylene, benzoquinone) were not useful in this process. 

Another pioneer in the Diels-Alder reactions of vinylpyrroles was Noland, who also developed the reactions of vinylindoles to yield carbazoles. Some examples of the former are shown in Scheme 2 (equations 1 and 2) [4-7], Jones and his colleagues were equally active in this cycloaddition chemistry of vinylpyrroles (equations 3 and 4) [8-12], These workers measured the rates of the reaction between 1-methyl-2-vinylpyrrole and seven dienophiles, with maleic anhydride being 4800 to 50,000 times more reactive than the other dienophiles (DMAD, maleonitrile, fumaronitrile, dimethyl maleate, methyl acrylate, and acrylonitrile) [8], In a clever tactic to thwart the formation of dihydroindoles, Jones used an excess of methyl propio-late to convert the initial adduct to a second Diels-Alder cycloadduct that subsequently loses ethene by a retro-Diels-Alder reaction to afford the dimethyl 1-methyl (phenyl)-4,7-dicarboxylates (equation 4). The reactions are concerted and were consistent with FMO calculations (HOMO[vinylpyrrole]-LUMO[alkene]). The yields are 54% to 81%, but attempts to dehydrogenate the tetrahydroindole products to indoles were unsuccessful. 2-Vinylpyrrole itself undergoes Michael additions and polymerization with these dienophiles. Domingo, Jones, and coworkers subsequently... 

The conclusion as to the nonconcerted character of the [4 -h 2]-cycloaddition reactions and sharp asynchronization of the process of formation of the -bonds in the course of the reaction has been borne out by a careful kinetical analysis, performed by Dewar, of reactions of typical dienophile maleic anhydride with a number of furane derivatives as well as by critical examination of other experimental data on the Diels-Alder reactions [29,35]. A similar conclusion has also been drawn for the [4 + l]-cycloaddition reaction [31], for some other... 

Another consideration is the formation of a charge-transfer complex as an intermediate. It is not difficult to think that some charge transfer occurs on the way to the transition state. A number of dienes form charge-transfer complexes with MA as well as other dienophiles. This is often evidenced by formation of transient colors. Experimentally, this can be determined spectroscopically. A detailed argument about this possibility would be difficult to entertain. Suffice it to say that according to Andrews and Keefer it is impossible to distinguish kinetically between the following two mechanisms ... 

The cycloaddition between norbornadiene (23 in Scheme 1.12) and maleic anhydride was the first example of a /mmo-Diels-Alder reaction [55]. Other venerable examples are reported in Scheme 1.12 [56]. Under thermal conditions, the reaction is generally poorly diastereoselective and occurs in low yield, and therefore several research groups have studied the utility of transition metal catalysts [57]. Tautens and coworkers [57c] investigated the cycloaddition of norbornadiene and some of its monosubstituted derivatives with electron-deficient dienophiles in the presence of nickel-cyclo-octadiene Ni(COD)2 and PPhs. Some results are illustrated in Tables 1.4 and 1.5. 

As vinylbenzofurans allow a large variety of substituted dibenzofurans to be synthesized, 2- and 3-vinylbenzo[b]thiophenes allow an easy entry, by Diels Alder reaction with the appropriate dienophiles, to substituted dibenzo-thiophenes which are not easily accessible by other methods. Vinylbenzo-[bjthiophenes are less reactive than the corresponding vinylbenzo[b]furans. Some cycloaddition reactions of 2-vinylbenzo[b]thiophene (82) with various dienophiles are reported [83] in Scheme 2.34. 

The photo-induced exo selectivity was observed in other classic Diels-Alder reactions. Data relating to some exo adducts obtained by reacting cyclopentadiene or cyclohexadiene with 2-methyl-1,4-benzoquinone, 5-hydroxynaphtho-quinone, 4-cyclopentene-l,3-dione and maleic anhydride are given in Scheme 4.13. The presence and amount of EtsN plays a decisive role in reversing the endo selectivity. The possibility that the prevalence of exo adduct is due to isomerization of endo adduct under photolytic conditions was rejected by control experiments, at least for less reactive dienophiles. 

The study was extended to other dienes and dienophiles [16d, e]. Some examples and comparisons are reported in Scheme 6.2. With respect to the organic solvent, the aqueous reaction requires milder conditions and the reactio-nis faster and more selective. It is significant that the use of cosolvents such as methanol, dioxane and tetrahydrofuran results in a reduction of reaction rate. 

Although there have been many experimental and theoretical studies on the behavior of facially perturbed dienes (see below), only a few systematic experiments have been carried out to characterize facially perturbed dienophiles. Dienophiles embedded in the norbomane or norbomene motif have been rather intensively studied [146-150]. In most cases, steric effect controls selectivity, but in some cases the reactions are considered to be free from steric bias, and the selectivity has been explained in terms of other factors, such as orbital effects [151, 152]. 

Cyclic ADC compounds are similarly prepared by oxidation of the corresponding cyclic hydrazine derivatives. The most commonly encountered compounds are the 3//-l,2,4-triazole-3,5(4//)-diones (5), and in particular the 4-phenyl derivative (5, R = Ph), usually abbreviated as PTAD. Similarly, the abbreviation MTAD is used for the 4-methyl derivative. First prepared by Thiele,18 PTAD remained unused in organic synthesis until Cookson reported its powerful dienophilic properties some 70 years later.19 PTAD is an isolable, red, crystalline compound, prepared by r-butyl hypochlorite oxidation of 4-phenylurazole.20 Other oxidants which have been successfully... 

At the other extreme of diene reactivity, some dienes are so unreactive that only powerful dienophiles such as PTAD will undergo Diels-Alder reactions with them. Thus, 4,5-dimethylene-l,3-dioxolan-2-one fails to react with TCNE or maleic anhydride, but gives the required Diels-Alder adduct (63%) with PTAD.232 The powerful dienophilic properties of PTAD have... 

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