Diels-Alder reactions furan

Keywords alkadienes, intramol Diels-Alder reaction, furan dienes, epoxydecalin systems... 

Wenkert, E., Moeller, P.D., Piettre, S.R. (1988). Five-membered aromatic heterocycles as dienophiles in Diels-Alder reactions. Furan, pyrrole and indole Journal of the American Chemical Society, 110, 21, 7188-7194, ISSN 0002-7863 Wenkert, E., Piettre, S.R. (1988). Reaction of a-and 3-acylated furans with conjugated dienes. Journal of Organic Chemistry, 53,5850-5853, ISSN 0022-3263 Wilkes, J.S. (2002). A short history of ionic liquids - From molten salts to neoteric solvents. Green Chemistry, 4, 73-80, ISSN 1463-9270... 

The balance between aromatic and aUphatic reactivity is affected by the type of substituents on the ring. Furan functions as a diene in the Diels-Alder reaction. With maleic anhydride, furan readily forms 7-oxabicyclo [2.2.1]hept-5-ene-2,3-dicarboxyhc anhydride in excellent yield [5426-09-5] (4). 

Furan and maleic anhydride undergo the Diels-Alder reaction to form the tricycHc 1 1 adduct, 7-oxabicyclo [2.2.1]hept-5-ene-2,3-dicarboxyHc anhydride (4) in exceUent yield. Other strong dienophiles also add to furan (88). Although both endo and exo isomers are formed initially, the former rapidly isomerize to the latter in solution, even at room temperature. The existence of a charge-transfer complex in the system has been demonstrated (89,90). 

Aqueous ring-opening metathesis polymerization (ROMP) was first described in 1989 (90) and it has been appHed to maleic anhydride (91). Furan [110-00-9] reacts in a Diels-Alder reaction with maleic anhydride to give exo-7-oxabicyclo[2.2.1]hept-5-ene-2,3—dicarboxylate anhydride [6118-51 -0] (24). The condensed product is treated with a soluble mthenium(Ill) [7440-18-8] catalyst in water to give upon acidification the polymer (25). Several apphcations for this new copolymer have been suggested (91). 

Benzo[Z)]furans and indoles do not take part in Diels-Alder reactions but 2-vinyl-benzo[Z)]furan and 2- and 3-vinylindoles give adducts involving the exocyclic double bond. In contrast, the benzo[c]-fused heterocycles function as highly reactive dienes in [4 + 2] cycloaddition reactions. Thus benzo[c]furan, isoindole (benzo[c]pyrrole) and benzo[c]thiophene all yield Diels-Alder adducts (137) with maleic anhydride. Adducts of this type are used to characterize these unstable molecules and in a similar way benzo[c]selenophene, which polymerizes on attempted isolation, was characterized by formation of an adduct with tetracyanoethylene (76JA867). 

Furan, 2,5-bis(trimethylsilyloxy)-cycloaddition reactions, 4, 625 Diels-Alder reactions, 4, 77 synthesis, 1, 417 Furan, bromo-dipole moments, 4, 553 Furan, 2-bromo-electron diffraction, 4, 537 reactions, 4, 78 synthesis, 4, 604 Furan, 3-bromo-electron diffraction, 4, 537 Furan, 2-bromomethyl-5-nitro-reactions... 

Knunyants showed that such perfluoroalkenes, under forcing conditions, undergo Diels-Alder reactions with cyclic dienes such as cyclohexadiene [72] (equation 65) or furan [7J] (equation 66). 

Alkynes substituted with one or two trifluoromethyl groups are also highly reactive dienophiles [9] Indeed, hexafluoro-2-butyne is used increasingly as a definitive acetylenic dienophile in "difficult Diels-Alder reactions. It was used, for example, to prepare novel inside-outside bicycloalkanes via its reaction with cir,trnns -l,3-undecadiene [74] (equation 67) and to do a tandem Diels-Alder reaction with a l,l-bis(pyrrole)methane [75] (equation 68) Indeed, its reactions with pyrrole derivatives and furan have been used in the syntheses of 3,4-bis(tri-fluoromethyl)pyrrole [76, 77] (equation 69) and ],4-bis(trifluoromethyl)benzene-2,3-oxide [78] (equation 70), respectively. 

On the other hand, Chambers found that the related perfluorobiscyclobut-yhdene undergoes Diels-Alder reactions with butadiene, cyclopentadiene, and furan [79, 56] (equation 71) Such enhanced reactivity may be due to strain in the substrate... 

Allenes carrying trifluoromethyl groups, such as l,l-dichloro-3,3-bis(tn fluoromethyl)allene, undergo facile, room-temperature Diels-Alder reactions with cyclopentadiene (87%) and furan (95%) [94]... 

Soon after the discovery of the addition reaction between diene-ophiles and dienes which now bears their names, Diels and Alder extended their investigations to include potential heterocyclic dienes. In 1929 the first compound investigated, furan, was observed to combine with maleic anhydride, like butadiene in a typical Diels-Alder reaction, across the 2,5-positions yielding a 1 1 molar adduct... 

Diels-Alder reactions of benzo[d]furan-4,5-diones and benzo[d]furan-4,7-diones 99H(50)1137. 

The borane catalyst 4 is also effective in the Diels-Alder reaction of furan (Scheme 1.11). In the presence of a catalytic amount of this reagent a-bromoacro-lein or a-chloroacrolein reacts with furan to give the cycloadduct in very good chemical yield with high optical purity [6d]. 

Although furan is usually a poor diene in the Diels-Alder reaction, the chiral copper reagent 24b promotes its asymmetric addition to acryloyloxazolidinone to afford the 7-oxabicyclo[2.2.1]hept-2-ene derivative in high optical purity (Scheme 1.40). Because a retro-Diels-Alder reaction occurs above -20 °C, the reaction must be performed at low temperature (-78 °C) to obtain a high optical yield. The bicy-... 

Further mechanistic evidence comes from trapping experiments. When bromobenzene is treated with KNH2 in the presence of a diene such as furan, a Diels-Alder reaction (Section 14.5) occurs, implying that the symmetrical intermediate is a benzyne, formed by elimination of HBr from bromobenzene. Ben-zyne is too reactive to be isolated as a pure compound but, in the presence of water, addition occurs to give the phenol, in the presence of a diene, Diels-Alder cycloaddition takes place. 

The reactivity of heterocyclic dienes is determined by the nature and number of heteroatoms and, in the case of heteroaromatic compounds, also by the aromatic character. Furans undergo Diels-Alder reactions with strong dienophiles and generally afford cxo-cycloadducts which are thermodynamically more stable than the kinetically favoured c z/o-adducts. 

An example of the Diels Alder reaction of furans is the cycloaddition of 31 with 4,4-diethoxybut-2-ynal (32) which acts as an acetylenedicarbaldehyde synthon to afford 7-oxabicyclo [2.2.1]heptene derivatives [29] which were then converted into substituted cyclohex-l-ene-l,6-dicarbaldehydes by a four-step procedure (Scheme 2.14). 

As vinylbenzofurans allow a large variety of substituted dibenzofurans to be synthesized, 2- and 3-vinylbenzo[b]thiophenes allow an easy entry, by Diels Alder reaction with the appropriate dienophiles, to substituted dibenzo-thiophenes which are not easily accessible by other methods. Vinylbenzo-[bjthiophenes are less reactive than the corresponding vinylbenzo[b]furans. Some cycloaddition reactions of 2-vinylbenzo[b]thiophene (82) with various dienophiles are reported [83] in Scheme 2.34. 

Good yields and high diastereoselectivities were obtained by using zeolites in combination with Lewis-acid catalyst [21]. Table 4.7 illustrates some examples of Diels-Alder reactions of cyclopentadiene, cyclohexadiene and furan with methyl acrylate. Na-Y and Ce-Y zeolites gave excellent results for the cycloadditions of carbocyclic dienes, and combining these zeolites with anhydrous ZnBr2 further enhanced the endo diastereoselectivity of the reaction. An exception is the cycloaddition of furan that occurred considerably faster and with better yield, in comparison with the classic procedure [22], when performed in the presence of sole zeolites. 

Intramolecular Diels-Alder reactions employing furan as the diene component are an effective step in the synthesis of many natural products, but difficulties are sometimes encountered due to the poor dienic character of the aromatic ring. Using CDs can help to overcome this problem. Thus, when 73 is heated in water at 89 °C for only 6h a 20% epimeric 1 2 mixture of 74 and 75 is... 

Stereoseiective synthesis of decaiines via tandem photooxidation-intramolecular Diels-Alder reactions of bis-furan [104]... 

Intramolecular Diels-Alder reactions of the furan diene (IMDAF) rapid construction of highly functionalized isoquinoline skeletons [65i]... 

The more reactive furan (139a) undergoes thermal Diels-Alder reaction [52] with reactive dienophiles such as maleic anhydride and maleimide (Scheme 5.21). Whereas the cycloaddition with the maleic anhydride afforded the exoadduct at room temperature, the stereochemistry of the reaction of maleimide depends on the reaction temperature. 

Diels-Alder reactions of furans are markedly reversible because of the aromatic character of the furan nucleus [la]. The lability of the cycloadducts, even at relatively low temperatures, as well as the sensitivity to acidic conditions of both furans and cycloadducts, preclude the use of strong Lewis acids and have therefore given importance to the high pressure technique. 

Whereas maleic anhydride can react with furan (139a) at ambient pressure, citraconic anhydride (140) reacts only at high pressures due to the strong deactivating effect of the methyl group (Schemes 5.21 and 5.22). The two-step synthesis [53] of the palasonin (141), in an overall yield of 96 %, is a good example of the acceleration of the Diels-Alder by high pressure (Scheme 5.21). Previous synthesis [54] based on the thermal Diels-Alder reaction of furan with methoxy carbonyl maleic anhydride required 12 steps. 

Diels-Alder reaction of the furan derivative 148 with homochiral bicyclic enone 149 is the key step [56] in the total synthesis of the diterpenes jatropho-lone A and B, 151 and 152, respectively, isolated from Jatropha gossypiifolia L [57], Initial efforts to carry out the cycloaddition between 148 and 149 under thermal or Lewis-acid conditions failed due to diene instability. Application of 5kbar of pressure to a neat 1 1 mixture of diene and dienophile afforded crystalline 150 with the desired regiochemistry (Scheme 5.23). Subsequent aromatization, introduction of the methylene group, oxidation and methylation afforded (-l-)-jatropholones 151 and 152. 

The cycloaddition between furan and maleic anhydride was the first uncatalyzed aqueous Diels-Alder reaction reported in the literature and was studied by Diels and Alder themselves [11]. This cycloaddition was successfully revised by Woodward and Baer [12] and some years later by De Koning and coworkers [13]. The aqueous medium was also used in the cycloaddition of aromatic diazonium salts with methylsubstituted 1,3-butadienes [14]. 

The Diels-Alder reaction can be greatly enhanced by high pressure (Chapter 5) but the effect of pressure is generally weaker in aqueous medium than in organic solvent. Results of high pressure-mediated Diels-Alder reactions of furans and acrylates in water and dichloromethane are reported in Table 6.6 [32]. In aqueous medium the cycloadditions occur with lower yields and less diastereoselectivity than in dichloromethane and, in some cases, addition-substitution reactions were observed. 

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