Maleic anhydride-furan Diels-Alder

It has previously been proposed that the saturated products from the homopolymerization of norbornene (17) and the CPD-MAH Diels-Alder adduct (12-15), and probably from the furan-maleic anhydride Diels-Alder adduct (11), have rearranged structures. An analogous structure would arise from the homopolymerization of the cyclopentadiene-N-phenylmaleimide CPD-NPMI adduct, as follows ... 

Development of synthetic routes to the anthracycline antibiotics is important because of the cytotoxic properties of many of these compounds. A short route " to possible intermediates proceeds via double Diels-Alder addition to (16). The problem of the availability of (16) has been overcome " by efficient palladium-catalysed carbomethoxylation of the furan-maleic anhydride Diels-Alder adduct to give (122) in 92% yield. Elaboration of Diels-Alder adducts of (16) to anthracyclines requires rupture of the ether bridge. Acid-catalysed ringopening " in simple 7-oxabicyclo[2.2.1]heptanes has been studied. 

Furan is readily hydrogenated, hence it is a source of commercial tetrahydrofuran (THF). Reaction with hydrogen sulfide over alumina produces thiophene. A recent patent describes a catalyst based on cobalt and molybdenum oxides supported on alumina for this reaction (105). Furan undergoes the Diels-Alder reaction with strong dienophiles. Hydrogenation of the product resulting from reaction with maleic anhydride, followed by hydrolysis and neutralization gives a herbicide, Endothall. 

The radical catalyzed homopolymerization of the furan-maleic anhydride (F-MAH) Diels-Alder adduct yields a saturated homopoly-mer at temperatures below 60 C, and an unsaturated equimolar alternating copolymer at elevated temperatures, due to retrograde dissociation of the adduct (10, 11). The copolymerization of monomeric furan and maleic anhydride yields the same unsaturated alternating copolymer, independent of temperature (1C)). 

The analogy of the reactivity of furan with that of butadiene is further underlined by the fact that furan undergoes a Diels-Alder reaction with dienophiles such as maleic anhydride ... 

Sol 15. The majority of Diels—Alder reactions yield endo products. In most of the cases, the exo product is thermodynamically more stable, but the endo adduct forms much more rapidly (kinetic control). However, [4 + 2] cycloaddition of furan and maleic anhydride gives predominantly exo adduct. Such a stereochemistry of the furan-maleic anhydride adduct is due to the fact that the initially formed endo compound readily reverses into the reactants whereas the exo cycloaddition gives a relatively stable adduct that is the product of the thermodynamic control. 

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). 

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... 

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. 

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. 

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 student is recommended to carry out the Diels and Alder diene synthesis when making preparations from the original literature. For example, he should condense cyclo-hexadiene with quinone (Annalen. 1933, 507, 288) or furane with maleic anhydride (Ber., 1929, 62, 554). 

As a result of its reduced aromaticity, relative to pyrrole, furan undergoes [4 + 2] cycloaddition reactions much more readily. It combines as a diene with electron-poor dienophiles to yield Diels-Alder-type adducts. Maleic [(Z)-butenedioic acid] anhydride, for example, reacts at room temperature, and the only isolated adduct is the exo isomer (the more thermodynamically favoured adduct) (Scheme 6.27a). 

Substituted benzo[ ]thiophene derivatives have been prepared in excellent yields by a tandem Pummer rearrange-ment/Diels-Alder reaction of the intermediate furan with maleic anhydride or A -phenylmaleimide (Equation 87) <1996JOC6166>. 

Problem 20.14 Give the Diels-Alder product for the reaction of furan and maleic anhydride. ... 

The parent compound (4), a derivative of o-quinodimethane, is unstable in solution it reacts almost instantaneously with typical dienophiles like maleic anhydride and methyl vinyl ketone to give the corresponding Diels-Alder adducts (Section III). Simple HMO calculations show that the total ji-electron energy of 4 is smaller than that of benzo[h]furan (8). It can be... 

Reduced furan rings occur in many important anhydrides, lactones, hemiacetals and ethers. Maleic anhydride is frequently used as a dienophile in Diels-Alder reactions and it is a component of alkyd resins. Several unsaturated y-lactones are natural products, while the furanose sugars are cyclic hemiacetals. 

Conversely, furans with electron-withdrawing groups e.g. CHO, CN, C02Me) in the 2-position show reduced Diels-Alder reactivity. Although furan-2-carboxaldehyde is a poor diene the related N,N-dimethylhydrazones do take part in reactions with a range of dienophiles including maleic anhydride, maleimides, and fumaronitrile (88JOC1199). 

The Diels-Alder cycloadduct of furan and maleic anhydride has played a key role in a new synthesis of butenolides (79S607). Treatment of the cycloadduct (24) with methanol affords a half acid ester which is reacted in turn with an excess of a Grignard reagent to produce the lactone (25) on acidic work-up. On heating this lactone at 150-180 °C, thermal fragmentation takes place to yield the 4,4-dialkylbutenolide (26) in high overall yield (Scheme 5). 

A new stereoselective synthesis of 1,2,3-trisubstituted cyclopentanes based on the Wag-ner-Meerwein rearrangement of a 7-oxabicyclo[2.2.1]heptyl 2-cation starts with the Diels-Alder product of maleic anhydride and a furan (78TL2165, 79TL1691). The cycloadduct was hydrogenated and subjected to methanolysis. The half acid ester (47) was then electrolyzed at 0 °C to generate a cationic intermediate via the abnormal Kolbe reaction (Hofer-Moest reaction). Work-up under the usual conditions provided the 2-oxabicyclo[2.2.1]heptane (48) in 83% yield. Treatment of this compound in turn with perchloric acid effected hydrolysis of the ketal with formation of the trisubstituted cyclopentane (49) in nearly quantitative yield (Scheme 11). Cyclopentanes available from this route constitute useful... 

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