Cyclohexenes cycloaddition with

Fig. 11.9. Symmetry properties of ethylene, butadiene, and cyclohexene orbitals with respect to cycloaddition.

Enamines have been observed to act both as dienophiles (46-48) and dienes (47,49) (dienamines in this case) in one-step, Diels-Alder type of 1,4 cycloadditions with acrylate esters and their vinylogs. This is illustrated by the reaction between l-(N-pyrrolidino)cyclohexene (34) and methyl t/-a i-2,4-pentadienoate (35), where the enamine acts as the dienophile to give the adduct 36 (47). In a competitive type of reaction, however, the... 

One of the most useful features of the Diels-Alder reaction is that it isstaeo-specific, meaning that a single product stereoisomer is formed. Furthermore, the stereochemistry of the reactant is maintained. If we carry out the cycloaddition with a cis dienophile, such as methyl ds-2-butenoate, only the cis-substituted cyclohexene product is formed. With methyl tmtts-2-butenoate, only thetrans-substituted cyclohexene product is formed. 

Cyclohexadiene derivatives are less reactive than butadiene derivatives, thus only a few examples of cycloadditions with these compoimds are known (Figure 4.3) [37 0]. The cyclohexadiene bicychc derivative 32 was synthesized by rhodium-catalyzed reaction of toluene with tert-butyldiazoacetate and cycloadds in about 40% yield to Cjq [39]. The product has anti-cyclopropane orientation relative to the entering dienophile Cjq. Valence isomerization of 33 (Scheme 4.4) leads to the cyclobutene-fused cyclohexene 35 that adds in good yields (50%) at moderate temperatures (110 °C) to Cjq [40]. The reaction of with the electron-deficient cyclohexene 34 is also possible in moderate yields [38]. 

In addition, phenylsufonylallene (110), a,(3-unsaturated phosphonates (111), and alkenes with perfluorinated substituents (112) are all useful dipolarophiles. The yields observed with methyl 2-propenoate are significantly lower than those with the corresponding acrylate (entries 7 and 9), because of the additional substituent. On the other hand, the dipolar cycloadditions with either ethyl vinyl ether, 1-hexene, cyclohexene, or a trisubstituted dipolarophile provide the corresponding isoxazolidines in either low yields or not at all (18). 

A special case involves the thermal decomposition of 3,4-dinitrofuroxan (104). The cycloreversion is already observed at room temperature and the nitroformo-nitrile oxide could be trapped with electron-deficient nitriles. The cycloadditions with styrene, phenylacetylene, frani-stilbene, and cyclohexene, however, led to complex mixtures of products that could not be separated (104). In the related case of a furoxan with an a-hydrogen adjacent to the sulfonyl group, the reaction was proposed to proceed according to course (b) (Scheme 6.7). 

Diazoacetaldehyde dimethylacetal (12) has been used as a substitute for diazoacetaldehyde in 1,3-dipolar cycloadditions with l-benzopyran-2(//)-ones (40), styrene, methyl methacrylate, 1-cyanocyclopentene, and methyl cyclohexene-1-carboxylate (41). The resulting A -pyrazolines were readily transformed in two steps into cyclopropanecarbaldehydes [e.g., 13 —> 14 (Scheme 8.4)]. In a similar manner, 3-phenylcyclopropane-l,2-dicarbaldehyde was obtained from the reaction of 12 with dimethyleneketal of cinnamic aldehyde. 

Bromo-2-pyrone is not only a valuable precursor for the synthesis of various 3-substituted 2-pyrones,7 but it is also a reactive unsymmetrical diene.8 3-Bromo-2-pyrone undergoes Diels-Alder cycloadditions with a regioselectivity and stereoselectivity that is superior to that of 2-pyrone. Furthermore, 3-bromo-2-pyrone is a chameleon (i.e., ambiphilic) dienophile, undergoing cycloaddition to both electron deficient and electron rich dienophiles. The cycloadducts of bromopyrone with dienophiles are isolable and are useful in the synthesis of diastereomerically pure cyclohexene carboxylates (Scheme 2).8... 

Nonetheless, there are a small number of systems that do mediate such [2 -i- 2 -t- 2] cycloadditions. With allenes as the alkene , cycloaddition with both acetylene and terminal alkynes proceeds regio-selectively to give 3,5-dimethylenecyclohexenes using Ni catalysts, and mostly 3,6-dimethylenecyclo-hexenes using Ni° catalyst precursors (equation 19). Norbomadiene undergoes so-called homo-Diels-Alder cycloaddition with both alkenes and a ynes in the presence of nickel catalysts. Further elaboration of this chemistry with alkynes but not alkenes has been described using a Co/Al catalyst system (equation 20). Attempts to produce cyclohexenes via all-intramolecular [2 + 2 + 2] cycloaddition of l,13-dien-7-ynes or 1,1 l-dien-6-ynes have been unsuccessful. ... 

Knoevenagel products of aliphatic aldehydes do not undergo photochemically induced [2 + 2] cycloaddition with alkenes, but are isomerized instead to the 3,7-unsaturated isomers. On the other hand, benzylidene-Meldrum s acids give two isomeric cycloadducts upon irradiation in the presence of cyclohexene. Unsymmetrical Knoevenagel products such as the benzylidenepyrazolones undergo cisitrans isomerization on irradiation. The photostationary state of (231) is = 2 1, whereas the thermo-... 

Contrary to earlier reports,1 3a,4,5,6,7,7a-hexahydroindoxazenes can be prepared by cycloaddition of nitrile oxides to cyclohexene.102,103 Similar cycloadditions with 1,2-dihydronaphthalene produce a mixture of the regioisomers 91a and 91b, and with cyclohex-2-en-l-one a mixture of 3-aryl-4-oxo- and 3-aryl-7-oxo-3a,4,5,6,7,7a-hexahydroindoxazenes, the former predominating.104... 

Formation of the acetal-tethered triene 34 was achieved by selective nucleophilic displacement of the secondary alkyl bromide in 35 with hydroxydiene 36. Subsequent thermolysis at 145 °C for 70 h resulted in completely regiospecific cycloaddition with the formation of two out of the possible four diastereoisomers 37 and 38 in a 2.5-3 1 ratio (Scheme 10-11). The presence of a stereogenic center in the tether provides the source of stereocontrol - the products derive from exo and endo T. S.s in which the bromomethyl group in the tether occupies a pseudo-equatorial position (Scheme 10-11). Small differences in non-bonding interactions between the tether and pyruvate ester most probably account for the slight exo. selectivity. The separated major product was further elaborated, and finally the tether was cleaved under reductive conditions to provide the advanced cyclohexene intermediate 39. 

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