Furan 4 + 4 cycloadduct with benzene

The treatment of 23 with methyllithium in the presence of furan gave rise to the tetracyclic product 26, which is obviously a [4 + 2]-cycloadduct of furan to the 1,2-cyclopentadiene derivative 25 [27]. The feature that the oxanorbornene system of 26 carries its saturated substituent in the endo-position is analogous to the [4 + 2]-cycloadducts of furan to all six-membered cyclic allenes (see Section 6.3). Balci et al. [36] also provided evidence for the generation of l-phenyl-l,2-cyclopentadiene. They postulated this species to be an intermediate in the reaction of l-phenyl-2-iodocydo-pentene with potassium tert-butoxide in benzene at 240 °C, which resulted in the formation of 1-phenyl- and 1,2-diphenylcyclopentene. Both products were considered as evidence in favor of the diradical nature rather than the allene structure of 1-phe-nyl-1,2 -cyclopentadiene. 

However, what is most remarkable about this work is that during attempts to form the diazadicyclo[5.3.0]decane 238, trace quantities of 241 were isolated, rationalized by cycloaddition with the benzene ring. Although cycloadditions with reactive aromatics such as furans are known, this represents the first example of a phenyl ring undergoing a [2 + 3] cycloaddition. Improvements to this novel cycloaddition were attempted by removal of the competing alkene functionality and treatment of the dibenzylamine 242 under the standard FVT conditions, furnishing the cycloadduct 243 in 67% yield (Scheme 3.82). 

Cumulenes, generally regarded as difficult to prepare, can be obtained readily via rDA methods. Al-lenes, the most basic cumulenes, with a wide range of substituents on the allenic carlxm, can be obtained by FVP of anthracenic DA adducts as shown in equation (114). Butatriene (258), the next in the series of cumulenes, has been produced by FVP of a variety of adducts that includes 9,10-ethano-9,10-dihy-droanthracene, " cyclohexyne and fulvene, furan and benzene cycloadducts. Pentatetraene (260), a compound that is stable enough to be purified by GLC at room temperature, has also been obtained by the FVP of vinylallene (259). ... 

The dehydrogenation of bis(a-bromobenzyl) sulfide (41) with Fe2(CO)9 in the presence of furan affords (43). The iron-stabilized sulfur ylide (42) has been proposed as intermediate. Reaction of C -di-phenylnitrone (44) with l,2-bis(methylene)-3,3.4,4,5,5-hexamethylcyclopentane (45) in benzene at 80 C gives a [4 -I- 3] cycloadduct (46 18%), along with some other products. Landor et al. have shown that the dehydrobromination of allenyl bromide (47) in the presence of furan affords bicyclic ketone (49) in 9% yield. Apparently, a strain alkyne intermediate reacts with r-butyl alcohol to afford an enol ether (48), which is then converted to (49) (Scheme 11). 

Furans give 2,5-cycloadducts on irradiation with alkynes (equation 75) . Thiophens probably behave similarly , but the product isolated is a substituted benzene which arises by extrusion of sulphur from the adduct (equation 76). The photochemical reaction with thiophen involves a triplet excited state of the thiophen, but both furan and thiophen cycloadditions can also be brought about thermally , (compare the pyrrole reaction in equation 74). 

In regard to transformation of the benzyne cycloadduct product between benzyne and furan into benzo[c]furan, the direct transformation by elimination of acetylene will not occur because computed activation barriers for this reaction were to high. The AMI computed activation barrier for acetylene elimination was 57.0 kcal/mol, while the activation barriers for the addition of a-pyrone (30.4 kcal/mol) and the elimination of carbon dioxides and benzene (29.9 kcal/mol) were much more energetically favorable (Scheme 1). These computational results are in full agreement with experimental evidence [38]. 

Arynes, such as benzyne (1,2-dehydrobenzene), also undergo Diels-Alder cycloaddition reactions. Benzyne, CelTj, is a highly reactive species and can be prepared by elimination of a suitably substituted benzene derivative. It reacts in situ with various dienes such as furan, cyclopentadiene, cyclohexadiene and even benzene and naphthalene to give bicyclic or polycyclic cycloadducts (3.15). Analogous addition reactions are shown by dehydroaromatics in the pyridine and thiophene series. 

Five-Component Synthesis of Hexasubstituted Benzene Cycloaddition of oxazole with olefin afforded functionalized pyridine after fragmentation of the oxa-bridged cycloadduct (Eq. (1), Scheme 15.19). Logically, if an alkyne were used as a partner of oxazole, the cycloaddition would give an oxa-bridged cyclohexadiene that could undergo the retro-DA reaction to provide a substituted furan (Eq. (2), Scheme 15.19). 

More unusual IMDAF reactions involve 2-vinylfuran as an extra-annular diene in which vinyl and furan C4-C5 double bond act as a diene. This synthetic approach was employed by Harwood in the synthesis toward colletofraga-rone A1 (Scheme 18) [31]. The intramolecular reaction showed that the use of a 2-vinylfuran substrate 73 with the dienophile connected by a tether chain at C-4 of the furan nucleus, formed a single tricyclic adduct 74 with a similar skeleton to that of the tricyclic core of colletofragarones. In this instance, the mildness of the high-pressure conditions permits the cycloadducts to be isolated without subsequent isomerization of the double bond to reform the furan, and in greatly superior yields to the thermal conditions (benzene 80 °C, 24 h, 28%). 

The three-component reaction between ethyl 3-(4,5,6,7-tetrahydroindol-2-yl)pro-pynoate, DDQ, and methanol affords furan-2-on-4,5,6,7-tetrahydroindolecyclobu-tene ensemble 23 in 53% yield (Scheme 2.63) [531]. As minor products, furan-2-one isomer 24 along with bicycloheptadienone 22 has been either isolated or identified. Like in the case of benzene or acetone, the corresponding [2+2]-cycloadduct 21 is the intermediate of this reaction. 

Coyle has summarized the photochemistry of carboxylic acid derivatives. For arene carboxylic acid esters it has been shown that [2-1-2]-cycloaddition competes with hydrogen abstraction by the excited ester from an allylic position of the alkene. The addition of methyl benzoate 17 to 2-methyl-2-butene gave a 1 1 mixture of the Paterno-Bilchi adduct 18 and the coupling product 19. Less electron-rich alkenes (e.g., cyclopentene) did add preferentially toward the benzene ring of 17 in an ortho- and metacycloaddition manner. Furans could also be added photochemically to methyl benzoate and other aren-ecarboxylic acid esters. The resulting bicyclic oxetanes could be transformed into a series of synthetically valuable products. [2-1-2]-Cycloadducts and/or their cleavage or rearrangement products have also been described for photoreactions of alkenes with diethyl oxalate,benzoic acid, " and carbamates. ... 

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