Trans dienophile-cyclopentadiene reaction

In the presence of a more reactive dienophile, a retro Diels-Alder reaction can be carried out at or below room temperature when catalyzed by a Lewis acid.78 In fact, this process can be regarded as a trans-Diels-Alder reaction in which the C C bond is replaced by another more reactive functionality. Thus, when treated with fumaronitrile in the presence of EtAlCl2 at ambient temperature for 2 hours, compound 159 can easily be converted to compound 160 with the removal of cyclopentadiene (Scheme 5-48). 

The Diels-Alder reaction is stereo specific. The stereochemistry of the dienophile is retained in the product i.e., cis and trans dienophiles produce different diastereoisomers in the product. For example, freshly distilled cyclopentadiene, having s-cis configuration, reacts with maleic anhydride to give c/ -norbornene-Sjh-endo-dicarboxylic anhydride. 

Diels-Alder reactions are stereospecific with respect to the E- and Z-relationships in both the dienophile and the diene. For example, addition of dimethyl fumarate and dimethyl maleate with cyclopentadiene is completely stereospecific with respect to the cis or trans orientation of the ester substituents. 

Cyclopentadiene (6) reacted with 105 at 0°C to give 108 (entry 1). At 100°C, butadiene (12) afforded 109 (entry 2). No [2 + 2] cycloadduct was formed in either reaction. Perfluoromethylenecyclopropane (105) failed to react with cis,cis- or cis,trans-2,4-hexadiene at 100 °C, although 110 was readily formed from trans,frans-2,4-hexadiene (106) under these conditions [29] (entry 3). Anthracene (107) added to 105 at 100 °C. The dienophilicity of 105 is exceptional when compared with the reactivity of simple fluoroolefins, such as perfluoro-isobutylene, which require 150 and 200 °C to undergo cycloaddition to cyclopentadiene [30] and anthracene, respectively. 

Phenyl-l,2,4-triazoline-3,5-dione acts as a dienophile by in situ reaction with butadiene, cyclopentadiene, cycloheptatriene, and bicyclohepta-diene (62TL615). Thus, it is possible to compare the reactivity of the cis-azo dienophile (110) with trans-azo dienophiles, such as ethyl azodicar-boxylate, which has been observed to undergo alternate modes of reaction when used with less reactive or hindered dienes. Treatment of (110) with several dienes resulted in exclusively Diels-Alder addition. The results are summarized in Table III. 

Complete stereoselectivity occurs in the Diels-Alder reaction through syn addition of the dienophile to the diene. Hence, the reaction of dimethyl fumarate and dimethyl maleate with cyclopentadiene yields the trans and cis adducts, respectively (Scheme 26.1).29... 

In the presence of 10 mol % Sc(OTf)3, A-benzylideneaniline reacts with 2-trans-l-methoxy-3-trimethylsiloxy-l, 3-butadiene (Danishefsky s diene) [23] to afford the corresponding aza Diels-Alder adduct, a tetrahydropyridine derivative, quantitatively (Eq. 7) [24]. In the reaction of A -benzylideneaniline with cyclopentadiene under the same conditions, on the other hand, the reaction course ehanged and a tetrahydroqui-noline derivative was obtained (Eq. 8). In this reaction, the imine aeted as an azadiene toward one of the double bonds of cyclopentadiene as a dienophile [25]. In the reaction with 2,3-dimethylbutadiene a mixture of tetrahydropyridine and tetrahydroqui-noline derivatives was obtained. A vinyl sulfide, a vinyl ether, and a silyl enol ether worked well as dienophiles to afford the tetrahydroquinoline derivatives in high yields [26,27]. 

The uncatalyzed Diels-Alder reaction is well known to be highly stereospecific, preferentially occurring via syn addition to both the diene and dienophilic components. Stereochemical studies of the cation radical Diels-Alder reaction have confirmed an analogous stereospecificity in two distinctly different systems. The initial study was carried out using the cycloaddition of the three geometric isomers of 2,4-hexadiene as dienophilic components and 1,3-cyclohexadiene as the diene component [39]. Each of the three isomers of the acyclic diene was found to add stereo-specifically to cyclohexadiene. In a more recent study, the cis and trans isomers of 1,2-diaryloxyethenes were found to add stereospecifically to 1,3-cyclopentadiene (Scheme 17) and also to 2,3-dimethyl-l,3-butadiene [46]. 

In 1964, J. Sauer et al.43 reported the reactivity of cyclopentadiene (26) with the cyanoethylene series in the DA reaction (see Scheme 1 and Table 3). An analysis of the relative rates shows that the rate increases with the cyano substitution on ethylene. However, it is easy to see that the successive substitution on the Cl and C2 carbon atoms has a different incidence. For instance, while 1,1-dicyanoethylene (6) reacts more than 10.000 times faster than acrylonitrile (12), cis and trans 1,2-dicyanoethylene (37 and 38) are only ca. 100 times faster. In addition, tetracyanoethylene (2), the most reactive dienophile within the series, reacts only 100 times faster than tricyanoethylene (36) (see Table 3). These results indicate that the symmetric substitution at the Cl and C2 carbon atom of ethylene produces a loss of effectiveness of the EW effect of the substitution. 

The preceding discussion is not meant to imply that stereo electronic effects alone are responsible for determining diastereoselection in the Diels-Alder reaction. Indeed, examples of reactions that do not conform to the endo rule abound, and these cases are not easily explained without invoking alternative hypotheses. For instance, it has been demonstrated that 1,1-disubstituted dien-ophiles can favor formation of the exo product with cyclopentadiene, sometimes to the complete exclusion of the electronically favored endo isomer [19]. There appears to be subtle interplay between steric and electronic factors, as simply switching the diene to cyclohexadiene or an acyclic diene results in a turnover in selectivity to favor the endo isomer. While the exact source of stereocontrol for a given cycloaddition is still a source of debate, this review will emphasize the practical ramifications of diastereoselection, namely, prototypical dienophiles such as a-methacrolein and a-bromoacrolein can be relied on to deliver exo cycloadducts preferentially with cyclopentadiene endo otherwise), while acrylate, crotonate, and cinnamate-derived dienophiles will generally favor the endo tran-... 

In order to obtain an insight into the diastereoselectivity in the Diels-Alder reaction of acetylenic sulfinates, chiral (+)-trans-2-phenylcyclohexanol [35] was used in place of cyclohexanol in the synthesis of the dienophile. A 1 1 dia-stereoisomeric mixture of acetylenic sulfinates 69 and 70 was obtained. After separation, each diastereoisomer was subjected to a Diels-Alder reaction with cyclopentadiene. Although the reaction once again occurred readily at room temperature, to our disappointment an inseparable mixture of diastereomeric adducts (3 2 by NMR) was obtained for each sulfinate. Apparently, a more spatially demanding chiral auxiliary needs to be incorporated into the dienophile in order to generate chiral sulfinates which cycloadd with prominent diastereoselectivity. 

Section IV,A,2,a Pentachloro-2H-pyrrole (21) behaves as a diene via the rearranged 3f/-pyrrole form 133 in its reaction with trans-1,3-pentadiene, giving a product 132 having R = trans-l-propenyl. However, the mode of cycloaddition is reversed with cyclopentadiene, the 2i/-pyrrole (21) reacting directly as a dienophile at the 3-4 C=C bond. With 1,3-cyclohexadiene, both modes of cycloaddition occur simultaneously. Steric factors rather than relative HOMO and LUMO energies are thought to determine the reaction course.147... 

The stereochemistry of the adduct obtained in many Diels-Alder reactions can be selected on the basis of two empirical rules formulated by Alder and Stein in 1937. According to the cis principle , the relative stereochentistry of substituents in both the dienophile and the diene is retained in the adduct. That is, a dienophile with trans substituents will give an adduct in which the trans configuration of the substituents is retained, while a cis disubstituted dienophile will form an adduct in which the substituents are cis to each other. This aspect is often referred to as the stereospecific nature of the Diels-Alder reaction. For example, in the reaction of cyclopentadiene with dimethyl maleate, the cis adducts 74 and 75 are formed, while in the reaction with dimethyl fumarate, the trans configuration of the ester groups is retained in the adduct 76 (3.64). 

The interesting olefin perfluoromethylenecyclopropane (see p. 59) fails to undergo the familiar [2 + 2] additions of fluoro-olefins possibly for steric reasons, but it is a reactive dienophile in the Diels-Alder reaction. Cyclopentadienc yields adduct (106) at 0 °C buta-1,3-diene and fra s,fra/i,y-hcxa-2,4-diene (but not the CIS,CIS- or cis,trans-isomsrs) react at 100 °C anthracene gives the expected adduct at 100 °C and quadricyclane yields adduct (107) at 25 °C. The isomeric perfluoro-1-methylcyclopropene forms Diels-Alder adducts with cyclopentadiene and buta-1,3-diene with equal facility. ... 

Diels-Alder reactions continue to be of value for the interception of highly reactive dienes or dienophiles. Thus, irradiation of 2-cyclo-octen-l-one or of 2-cyclohepten-l-one in the presence of excess cyclopentadiene affords the norbornene derivatives (173 n = 5 or 4 respectively), which undergo retro-[4 -I- 2] addition on distillation. Presumably the trans-2-cycloalken-l-ones are reactive intermediates in these processes. Elimination of acetic acid from bis(trifluoromethyl)cyclopentadienylcarbinyl acetate yields the reactive 6,6-bis(trifluoromethyl)fulvene, which rapidly dimerizes by [4 + 2] cycloaddition the fulvene intermediate can be intercepted by similar addition to cyclopentadiene. The adduct (174) is formed on reaction of cyclopentadiene with the imine produced by iodine-catalysed rearrangement of NN-... 

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