Diels-Alder cycloadditions with cyclopentadiene

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. 

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. 

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. 

Esterification of 19 with acrylic acid chloride made diene 20 available. Subsequent stereoselective Diels-Alder cycloaddition with cyclopentadiene proceeded with complete diastereoselectivity in 55% yield. The asymmetric product 21 was cleaved from the polymer by exposure to light (Scheme 12.11). 

In the presence of a 1,3-diene this species produces [4 + 2] cycloadducts. The exact nature of this reactive intermediate has not yet been determined. It was found that a boron imide undergoes a Diels-Alder cycloaddition with cyclopentadiene under mild conditions [Eq. (25)].75... 

The bisiodonium ethyne 24 is even more reactive than 18 and readily undergoes Diels-Alder cycloaddition with cyclopentadiene and furans as shown in equation 41. The remarkable fact of the cycloaddition of 24 is that, unlike the usual Diels-Alder reactions that require extensive heating and/or pressure, these reactions occur in a matter of minutes at -35 °C. 

Low-temperature trapping experiments of the photolysis products of disilacycloheptene (75), which was prepared by insertion of ethyne into the Si—Si bond of l,l,2,2-tetramethyl-l,2-disilacyclopentane <75JA931>, provided evidence for the trans isomer of (75) <90JA6601>. GC-MS analyses indicated that, as the decay of trans-(75) progressed, a mixture of six dimers of mjz 368 was formed. Only one of the dimeric products was successfully isolated in pure form by preparative GC this dimer was assigned the unsymmetrical c/s,fra 5-fused cyclobutene structure (76) on the basis of NMR data. Trapping experiments of metastable trans-(75) by Diels-Alder cycloadditions with cyclopentadiene and 9,10-dihydro-l l,12-dimethylene-9,10-ethanoanthracene afforded (77) and (78), respectively. The crystal and molecular structures of (78) were determined. 

Carretero and colleagues have recently reported a systematic study on the use of enantiomerically pme 2-p-tolylsulfinylmaleates as dienophiles in asymmetric Diels-Alder cycloadditions with cyclopentadiene over a wide range of catalysed and uncatalysed conditions [164]. High diastereofacial selectivities were observed in some cases, and the stereochemical results have been interpreted using a sterically controlled approach. 

Another type of reaction that has been developed in order to resolve nitrogen-containing compounds is the Diels-Alder cycloaddition. As a rare example, Sibi et al. [235] have recently reported the KR of pyrazohdinones that could not be obtained in high enantioselectivities from direct methods on the basis of a Diels-Alder cycloaddition with cyclopentadiene catalysed by a combination of Cu(OTf)2 with a chiral aminoindanol-derived bisoxazohne hgand. The recovered almost enantiopure (98% ee) substrate was isolated with a selectivity factor of 34. Excellent results were also reported by Fu et al. [236] for the KR of azomethine imines via copper-catalysed [3-1-2] cycloadditions with aUcynes performed in the presence of a chiral phosphaferrocene-oxazoline ligand, which furnished the chiral recovered substrates with high selectivity factors of up to 76, as shown in Scheme 3.15. 

Direct Wittig reaction of Ph PCHCOn,Me with the four unsubstituted D-aldopentoses followed by acetylation provides convenient preparative access to acyclic seven-carbon trans-2.3-unsaturated sugar derivatives. These products served as dienophiles for a detailed comparative study in Diels—Alder cycloaddition with cyclopentadiene. Related syntheses afforded analogous cis-dienophiles. Cycloaddition under uncatalyzed thermal conditions gave mixtures of the four possible stereoisomeric norbornene adducts. The endo, exo ratios, and diastereofacial selectivities of the adducts were determined by NMR spectroscopy and by chemical transformations, supplemented by selected X-ray crystallographic analyses. Different distributions of isomers were encountered when a Lewis acid was used to catalyze the cycloaddition. The reaction can be controlled to provide preparative access to selected isomers and thus constitutes a versatile method for chirality transfer from the precursor sugar to four new asymmetric centers in a carbocyclic framework. 

Norbornene-2-carboxylic acid (8) was obtained in acceptable ee by the use of a chiral auxiliary. Optically active tetrahydropyrimidones 6 underwent Diels-Alder cycloadditions with cyclopentadiene (5) in water at room temperature. Subsequent removal of the auxiliary was achieved by boiling the carboxamide 7 in water (Scheme 5.2). The cycloaddition conversions were at least 90% and the endo adduct was the prevalent diastereoisomer. Using 70% aqueous ethanol as reaction medium, both the endo/exo ratio and ee were lower than in pure water. Since tetrahydropyrimidones 6 can be prepared in water from L-asparagine and a suitable aldehyde and subsequent acylation with acryloyl chloride, the entire synthesis of 8 was performed in water by one-pot procedure. The yield was fair, but the ee of norbornene carboxylic acid 8 was lower than that obtained by using a step-by-step procedure. This result was probably due to some acryloyl chloride being hydrolyzed to acrylic acid, which then reacted with 5 in a non-stereo-biased manner. 

The furanoside-based dienophiles 3 and 4 undergo stereoselective Diels-Alder cycloaddition with cyclopentadiene and 1,3-cyclohexadiene to give exclusively the exo-adducts 5 and 6 respectively adduct 5 (n=l) has been converted to the complex cyclopentane 7 (Scheme 2).5 A lengthy synthesis of PGF2a from D-mannitol has been described with the carbohydrate unit contributing stereochemical centres in both the cyclopentane ring and the side chain. ... 

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]. 

Bolm et al. [106] have carefully studied the synthesis and the hganding ability of salen-like bis(sulfoximines). The chirahty which is indeed generally introduced via the use of chiral diamines in the salen series, is in sulfoximines present via the sulfur atom. They investigated the Diels-Alder cycloaddition between cyclopentadiene and acryloyl-2-oxazolidinones with various bis(sulfoximines) (see Scheme 42) and Cu(OTf)2 as the copper source [107]. 

An unusual Diels-Alder cycloaddition involving the Cp=Cy bond has been described. The reaction took place by treatment of the electron-deficient allenylidene moiety in complex [RuCp(=C=C=CPh2)(CO)(P -Pr3)][BF4] (46) with a 20-fold excess of isoprene at room temperature affording the cycloadduct 90 (Scheme 33) [287]. This Diels-Alder cycloaddition in which the allenylidene moiety acts as a dienophile was completely regioselective, only the Cp=Cy bond of the allenylidene skeleton being implicated. Furthermore, it was also regioselective with regard to the orientation of the diene with the exclusive attack of C(l) and C(4) carbons at the Cp and Cy positions, respectively. Allenylidene 46 also underwent Diels-Alder reactions with cyclopentadiene and cyclohexadiene to afford the... 

Individual activation energies from BP, BLYP, EDFl and B3LYP density functional models are similar (and different from those of Hartree-Fock and local density models). They are both smaller and larger than standard values, but typically deviate by only a few kcal/mol. The most conspicuous exception is for Diels-Alder cycloaddition of cyclopentadiene and ethylene. Density functional models show activation energies around 20 kcaPmol, consistent with the experimental estimate for the reaction but significantly larger than the 9 kcal/mol value obtained from MP2/6-311+G calculations. Overall, density functional models appear to provide an acceptable account of activation energies, and are recommended for use. Results from 6-3IG and 6-311+G basis sets are very similar, and it is difficult to justify use of the latter. 

Consider, for example, endolexo selectivity in the Diels-Alder cycloaddition of cyclopentadiene and 2-butanone. In cyclopentadiene as a solvent, the observed endolexo product ratio is 80 20 (endo preferred), corresponding to a transition state energy difference on the order of 0.5 kcal/mol. With water as the solvent, this ratio increases to 95 5, corresponding to an energy difference on the order of 2 kcal/ mol. Hartree-Fock 6-3IG caleulations on the respective endo and exo transition states are largely in accord. Uncorrected for solvent, they show a very slight (0.3 kcal/mol) preference for endo in accord with the data in (non-polar) cyclopentadiene. This preference increases to 1.5 kcal/mol when the solvent is added (according to the Cramer/... 

Figures 15-1 and 15-2 provide evidence for the extent to which transition states for closely-related reactions are very similar. Figure 15-1 compares the transition state for pyrolysis of ethyl formate (leading to formic acid and ethylene) with that for pyrolysis of cyclohexyl formate (leading to formic acid and cyclohexene). Figure 15-2 compares the transition state for Diels-Alder cycloaddition of cyclopentadiene and acrylonitrile with both syn and anti transition states for cycloaddition of...

Table 15-4 Effect of Choice of Geometry on Relative Activation Energies of Diels-Alder Cycloadditions of Cyclopentadiene with... 

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... 

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... 

The facially perturbed enantiopure (.S, .S )-2-(p-tolylsulfinyl)norborncno-/7-bcnzoquin-ones (119), undergo asymmetric Diels-Alder additions with cyclopentadiene to yield the four possible adducts (120) and (121). The endo-syn cycloadducts (121) can be used in the synthesis of the cage compound garudane (122) (Scheme 44).234 The antiaromatic compound 1,4-biphenylenequinone (123) has been synthesized and trapped by Diels-Alder reaction with cyclopentadiene (Scheme 45).235 The 4 + 2-cycloadditions of 4-methylene-5-(bromomethylene)-4,5-dihydrothiazole with 2- and 3-bromonaphtha-quinones are highly regiospecific.236... 

Diels-Alder reaction with cyclopentadienes. An improved synthesis of a key intermediate (6) to gibberellic acid (7) begins with the cycloaddition of 1 to a 2 1 mixture of 2- and l-(2-bromoallyl)cyclopentadiene (2) to give the adduct 3 in which the acetyl group has the enr/o-orientation. The silyl enol ether of 3 when heated undergoes a Cope rearrangement to give a eis-hydrindene (4), which was converted... 

The intermolecular Diels-Alder reaction between the dibromoenone (111) and dienes (112) provides access to bicyclo[5.4.0]undecane systems (113) that are common core structures of many natural products (Scheme 32).118 The alio-threonine-derived O-(/ -biphenyl carbonyl oxy)-/i-phenyloxazaborolidi none catalyses the enan-tioselective Diels-Alder reaction of acyclic enones with dienes.119 The reversal of facial selectivity in the Diels-Alder cycloaddition of a semicyclic diene with a bro-moenone was induced by the presence of the bromo substituent in the dienophile.120 Mixed Lewis acid catalyst (AlBr3/AIMe3) catalyses the Diels-Alder reaction of hindered silyloxydienes with substituted enones to produce highly substituted cyclohexenes.121 Chiral /V-enoyl sultams have been used as chiral auxiliaries in the asymmetric Diels-Alder reactions with cyclopentadiene.122... 

Analogously to the oxidation of A -alkoxycarbonylhydroxylamines, the oxidation of A -hydrox-yureas, performed with tetraalkylammonium periodate, gives nitrosocarbonyl compounds which undergo hetero-Diels-Alder cycloaddition with 1,3-dienes. A number of adducts 10 have been prepared and the reaction proceeds with total diastereoselectivity, although the yield has only been reported for cyclopentadiene and Ar-hydroxy-A"-phenylurea33. 

Diels-Alder Cycloadditions (AUcene -+ Six-Membered Cycloadduct). lV-Acryloyl-a-methyltoluene-2,a-sultam (3a) participates in highly endo and C(a)-re ir-face selective Lewis acid promoted Diels-Alder reactions with Cyclopentadiene, 1,3-Butadiene, and Isoprene (eq 2 and Table 1). These levels of induction compare favorably with most alternative auxiliaries, including the 10,2-camphorsultam. However, V-crotonyl-a-methyltoluene-2,a-sultam (ent-3b) reacts with cyclopentadiene with only mod-... 

EtO)PS ) give 3-0- or 3-S- substituted thietanes, respectively. Thiirane structures reported as the products of several reactions have been shown to be thietanes. The acrylate adducts undergo Diels-Alder cycloadditions with butadiene, isoprene, and cyclopentadiene. ... 

In contrast to the unreactive dienes that can t achieve an s-cis con formation, other dienes are fixed only in the correct s-cis geometry and are therefore highly reactive in the Diels-Alder cycloaddition reaction. Cyclopentadiene, for example, is so reactive that it reacts with itself. At room temperature, cyclopentadiene dimerizes One molecule acts as diene and another acts as dienophile in a self Diels-Alder reaction. 

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