Cyclopentadiene, cycloaddition with

Evans s bis(oxazolinyl)pyridine (pybox) complex 17, which is effective for the Diels-Alder reaction of a-bromoacrolein and methacrolein (Section 2.1), is also a suitable catalyst for the Diels-Alder reaction of acrylate dienophiles [23] (Scheme 1.33). In the presence of 5 mol% of the Cu((l )-pybox)(SbF5)2 catalyst with a benzyl substituent, tert-butyl acrylate reacts with cyclopentadiene to give the adduct in good optical purity (92% ee). Methyl acrylate and phenyl acrylate underwent cycloadditions with lower selectivities. 

The enantiomerically pure, doubly activated a, /j-olefinic sulfoxides 46-5095 98 undergo highly diastereoselective Diels-Alder cycloadditions with cyclopentadiene, and pyridyl vinylic sulfoxide 5199 reacts diastereoselectively with furan. It is noteworthy that olefins singly-activated by only a sulfinyl group are not effective partners in Diels-Alder cycloadditions, as we have found after many attempts and as has been reported recently98. 

Furanones are a class of chiral dienophiles very reactive in thermal cycloadditions. For example, (5R)-5-(/-menthyloxy)-2-(5H)-furanone (28) underwent Diels Alder reaction with cyclopentadiene (21) with complete re-face-selectivity (Equation 2.10), affording a cycloadduct which was used as a key intermediate in the synthesis of dehydro aspidospermidine [27]. 

Selenoaldehydes 104, like thioaldehydes, have also been generated in situ from acetals and then directly trapped with dienes, thus offering a useful one-pot procedure for preparing cyclic seleno-compounds [103,104], The construction of a carbon-selenium double bond was achieved by reacting acetal derivatives with dimethylaluminum selenide (Equation 2.30). Cycloadditions of seleno aldehydes occur even at 0 °C. In these reactions, however, the carbon-selenium bond formed by the nucleophilic attack of the electronegative selenium atom in 105 to the aluminum-coordinated acetal carbon, may require a high reaction temperature [103], The cycloaddition with cyclopentadiene preferentially gave the kinetically favorable endo isomer. 

It is believed that clay minerals promote organic reactions via an acid catalysis [2a]. They are often activated by doping with transition metals to enrich the number of Lewis-acid sites by cationic exchange [4]. Alternative radical pathways have also been proposed [5] in agreement with the observation that clay-catalyzed Diels-Alder reactions are accelerated in the presence of radical sources [6], Montmorillonite K-10 doped with Fe(III) efficiently catalyzes the Diels-Alder reaction of cyclopentadiene (1) with methyl vinyl ketone at room temperature [7] (Table 4.1). In water the diastereoselectivity is higher than in organic media in the absence of clay the cycloaddition proceeds at a much slower rate. 

Clay-catalyzed asymmetric Diels-Alder reactions were investigated by using chiral acrylates [10]. Zn(II)- and Ti(IV)-K-10 montmorillonite, calcined at 55 °C, did not efficiently catalyze the cycloadditions of cyclopentadiene (1) with acrylates that incorporate large-size chiral auxiliaries such as cA-3-neopentoxyisobornyl acrylate (2) and (-)-menthyl acrylate (3, R = H) (Figure 4.1). This result was probably due to diffusion problems. 

Tropone (125) and the 2-substituted tropones showed a different reactivity in the cycloaddition with 2-cyclopentenone (28). Whereas tropone itself (125) and the 2-methoxytropone (126) reacted at lOkbar, giving a mixture of four and three products, respectively (Scheme 5.18), 2-hydroxy- and 2-chloro-tropone failed to react at all [43b]. Compound 127 does not have the expected dihydro-homobarrelenone framework it is probably derived from the cycloaddition of 125 and 1,4-cyclopentadien-l-ol, the enol form of 28. 

Engberts [3e, 9] has extensively investigated the Diels Alder reaction in aqueous medium. Recently Engberts and colleagues reported [9c] a kinetic study of a Diels Alder reaction of N-alkyl maleimides with cyclopentadiene, 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene in different solvents. The reaction rates of the cycloadditions with the open-chain diene relative to w-hexane are reported in Table 6.3. The aqueous medium greatly accelerates the Diels Alder reaction and the acceleration increases as the hydrophobic character of the alkyl group of the dienophile increases. These and other kinetic data [3e, 9], along with the observation that the intramolecular Diels-Alder reaction is also accelerated in... 

The N-silylated aminomethylcyclopropenecarboxylic ester underwent a smooth highly endo- and anti-selective [4+2]-cycloaddition with cyclopentadiene [2]. The novel GABA analogue 5 can be liberated in good yield by acid treatment [6]. 

MCP (1) is not known to undergo [4 + 2] cycloadditions. The substitution of two, or more, ring protons with fluorine atoms, however, seems to improve dramatically the dienophilic reactivity of the exocyclic double bond. 2,2-Di-fluoromethylenecyclopropane (5) is a quite reactive dienophile in Diels-Alder cycloadditions. With cyclopentadiene (6) and furan (7), it formed two isomeric adducts (Scheme 1) [9]. In both cases the adduct with the endo CF2 group is the major isomer. 

C(sp2)=C(sp2) bond imparts properties which more closely resemble those of the central double bond in butatriene than of the one in a simple tetrasub-stituted ethylene [12]. For this reason, bicyclopropylidene (3) undergoes cycloadditions with 1,3-dienes, and these showed an interesting dependence on the structure of the diene. Whereas cyclopentadiene (6) gave the [4 + 2] cycloadduct 28 exclusively, 1,3-cyclohexadiene (26) and 1,3-butadiene (12) led to mixtures of the [4 + 2] and [2 + 2] cycloadducts, with the proportion of the [2 + 2] adduct increasing respectively [13] (Table 3). 

Various substituted unsaturated acylphosphonates participate in highly dias-tereoselective and enantioselective cycloadditions with vinyl ethers, Eqs. 177 and 178. It is intriguing to note that catalysts [(.V,.Y)-f-Bu-box]Cu (OTf)2 (269c) and [(.V,.S )-Ph-box]Cu (OTf>2 (269d) possessing the same sense of chirality afford opposite antipodes of the cycloadduct in comparable selectivities. Cyclopentadiene was found to react with acylphosphonates to give a mixture of the normal Diels-Alder adduct and the inverse electron demand hetero-Diels-Alder adduct (35 65), Eq. 179. This result may be contrasted with crotonylimide, which furnishes the normal demand Diels-Alder adduct exclusively. 

The cycloaddition of allenes carrying an electron-withdrawing phosphorus substituent has also been studied [118]. Allenyl phosphine oxide 138 is prepared in a manner analogous to allenyl sulfoxide. The [4+ 2]-cycloaddition reaction of 138 with cyclopentadiene proceeded with a high endo selectivity. 

Although allene itself is reluctant to react with ordinary 1,3-dienes, it underwent successful [4+2]-cycloadditions with relatively reactive cyclopentadienes to afford 5-methylenebicyclo[2.2.1]hept-2-ene derivatives [145]. 

An extensive review of 4 - - 3-cycloaddition reactions has been presented. The 1,3-difluorooxyallyl intermediate obtained from l-bromo-l,3-difluoropropan-2-one undergoes 4 + 3-cycloaddition with cyclopentadiene and ftiran to give difluorobicyclo[3.2.1]octenones. The use of 4 + 3-cycloaddition reactions of cyclic oxyallyls in the synthesis of natural products has been extensively studied. The intramolecular 4 + 3-cycloaddition of allylic sulfones (111) possessing a diene in the side-chain in the presence of Lewis acids yield cycloadducts (112) in good to excellent yields (Scheme 43). ... 

In the presence of water the tropylium ion (50) has been found to undergo polar cycloaddition of the 4 + 2 type. Ito and Itoh found that cyclopentadiene reacted with the tropylium ion to afford a 90% yield of a complex mixture of alcohols, all of which could be derived from the allylic cation (51). 

Chinese chemists have reported the synthesis of pentacyclo[4.3.0.0 , 0 ]nonane-2,4-bis(trinitroethyl ester) (88). This compound may find potential use as an energetic plastisizer in futuristic explosive and propellant formulations. The synthesis of (88) uses widely available hydroquinone (81) as a starting material. Thus, bromination of (81), followed by oxidation, Diels-Alder cycloaddition with cyclopentadiene, and photochemical [2 - - 2] cycloaddition, yields the dione (85) as a mixture of diastereoisomers, (85a) and (85b). Favorskii rearrangement of this mixture yields the dicarboxylic acid as a mixture of isomers, (86a) and (86b), which on further reaction with thionyl chloride, followed by treating the resulting acid chlorides with 2,2,2-trinitroethanol, gives the energetic plastisizer (88) as a mixture of isomers, (88a) and (88b). Improvements in the synthesis of nitroform, and hence 2,2,2-trinitroethanol, makes the future application of this product attractive. 

The asymmetric [3 + 4] cycloaddition is readily achieved using chiral auxiliaries or catalysts [16]. The efficiency of the chiral auxiliary approach is illustrated in the [3-1-4] cycloaddition with cyclopentadiene. The vinyldiazoacetate 6, with (T)-pantolactone as the chiral auxiliary, generated the bicyclo[3.2.1]octadiene 75 in 87% yield and 76% dia-stereomeric excess (Eq. 10) [82]. Alternatively, the chiral rhodium prolinate Rh2(S-DOSP)4-catalyzed reaction of 4 generated the bicyclo[3.2.1]octadiene 76 in 77% yield and with 93% enantiomeric excess (Eq. 11) [83]. 

A series of a,a-dimethoxysilyl enol ethers has been prepared and shown to undergo diastereoselective [4+3]-cycloaddition with furan and cyclopentadiene in the presence of catalytic amounts of trimethylsilyl triflate <99SL213>. Furo[3,4-d]oxazoles and furo[3,4-d]thiazo-les react with 13-dimethyloxyallyl to give [4+3]-cycloadducts. The ring opening reaction of these compounds with H2S04Mt20 yields armulated hydroxytropones <99H(51)1225>. 

Since the energy of D+A- is governed by the magnitude of /D — Aa, D + A" will be stabilized when the diene is substituted by electron-releasing substituents (/ is lowered) and the ene by electron-withdrawing ones (Aa is increased). Indeed, cycloadditions proceed more rapidly in such cases. For example, 1,2-dicyanoethylene undergoes cycloaddition with cyclopentadiene c. 80 times faster than cyanoethylene (Sauer, 1967). In the former case / — Aa is 7.8 eV while in the latter case it is 8.6 eV. 

Given a typical diene, an increased reactivity is expected of the reaction with en-hanciftg polarity alternation of the dienophile. This is easily appreciated in view of an ionic reaction being more exothermic. Thus, acryloxyboranes [172] undergo cycloaddition with cyclopentadiene even at —78 °C. The same principle underlies dienophile activation by replacing an enone with an alkoxyallyl cation [173] or allylidene-metalcarbonyl [174],... 

Diels-Alder catalyst, Bicyclo[2.2.1]hept-2-ene-2,3 dicarboxylic anhydride (1) does not undergo cycloaddition with cyclopentadiene (2) in the absence of a catalyst. AlClj in this case does not function as a catalyst. However the two compounds undergo cycloaddition at room temperature when slurried on silica gel. The anti- (3) and syn- (4) anhydrides are formed in a ratio of about 3 2. The mixture can be separated readily because 3 is hydrolyzed by KOH in ethanol-water (3 1), whereas 4 is not hydrolyzed under any known conditions. 

As with the alkyl and aryl derivatives of the pyrrolenines and indolenines, a tautomeric equilibrium has also been noted between the pentachloro-2//- and -3H- pyrroles, such that when the 2//-pyrrole, produced by chlorination of 2,3,4,5-tetrachloropyrrole or of 3,4-dichloromaleimide, is allowed to react with dienophiles, the adducts are those formed by cycloaddition with the 3H-pyrrole tautomer (Scheme 84) (80JOC435, 80JA7862, 81JOC3036). Cycloaddition with cyclopentadiene occurs on the 2H-pyrrole, which behaves as the dienophile. 

The reactions of a,a -dibromoketones with iron carbonyls generate oxyallyliron complexes (75). These undergo cycloaddition with cyclopentadiene and furan, but with thiophene only products of electrophilic attack are obtained (78JA1765). Thus the oxyallyliron complex (75 R = Me R = H) reacts with thiophene to produce (76) in 37% yield. 

Maleic thioanhydride and its dichloro derivative function as dienophiles. Cycloaddition with cyclopentadiene and butadiene has been reported (Scheme 155) (72AHC(14)33l). Succinic thioanhydride undergoes bis-Wittig condensations (Scheme 156) the product from ethoxycarbonylmethylenetriphenylphosphorane aromatizes to the thiophene-2,5-bis-acetic ester (454) (75LA1967). 

Benzo[6]thiophene 1,1-dioxides undergo [2+4] cycloaddition with 1,3-dienes such as cyclopentadiene, anthracene, etc. (70AHC(11)177>. Cycloaddition with dipolar species such as diazoalkanes (74M550), nitrilimines (74M869) and nitrile oxides (79TL4845) have also been described (Scheme 192). 

A large number of metal-coordinated chalcogenacycles were prepared from the heteroaldehyde and -ketone complexes [M(CO)5 E=C(Ph)R ] (M = Cr, Mo, W E = S, Se, Te R = H, Aryl) and 1,3-dienes. The cycloadditions proceeded rapidly, even at low temperatures.179180,228-233 As dienes 2,3-dimethyl-l,3-butadiene [for an example see Eq. (27)], isoprene, transA, 3-pentadiene, cyclopentadiene, pentamethylcyclopentadiene, and 1,3-cyclohexadiene were used. Decomplexation with pyridine/THF yielded the free heterocycles. Although the tellurobenzaldehyde complex [W(CO)5 Te = C(Ph)H ] (99c) proved too unstable for isolation, it could be generated and employed in subsequent cycloadditions with dienes.180... 

The more reactive bicyclopropylidene (19) displays even greater tendency to undergo [2+2] cycloadditions37. For example, only 1,3-cyclopentadiene reacts with this olefin in the [4+2] mode, while 1,3-butadiene and 1,3-cyclohexadiene give products resulting mainly from [2+2] cycloaddition (equation 16)37. 

There are a few reports in the literature in which the carbonyl group has been formally replaced by another unsaturated function. Thio-benzophenone (268) undergoes photochemical 1,2-cycloaddition to a-phellandrene (269) to give the thietane (270), together with the sulfur heterocycles (271 and 272) formed by 1,4-cycloaddition.298 Isoprene, cyclopentadiene, and 1,4-diphenylbutadiene also undergo 1,4-cycloaddition with thiobenzophenone, but 1,3-cyclooctadiene... 

Zinconacyclopentadienes (141), substituted with alkyl groups, undergo 1,1-cycloaddition with propynoates to yield cyclopentadienes (142) as outlined in Scheme 53.270... 

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