Furan with maleic anhydride

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). 

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>. 

In the fused compounds (241) and (242) the furan ring fails to react as a diene and Diels-Alder reaction with dienophiles occurs on the terminal carbocyclic rings. However, (243) and (244) afford monoadducts with dimethyl fumarate by addition to the furan rings (70JA972). The rates of reaction (Table 2) of a number of dehydroannuleno[c]furans with maleic anhydride, which yield fully conjugated dehydroannulenes of the exo type (247), have been correlated with the aromaticity or antiaromaticity of the products (76JA6052). It was assumed that the transition state for the reactions resembled products to some extent, and the relative rates therefore are a measure of the resonance energy of the products. The reaction of the open-chain compound (250), which yields the adduct (251), was taken as a model. Hence the dehydro[4 + 2]annulenes from (246) and (249) are stabilized compared to (251), and the dehydro[4 ]annulenes from (245) and (248) are destabilized (Scheme 84). 

Table 2 Relative Rates of Reaction of Dehydroannuleno[c]furans with Maleic Anhydride...

As the focus of this chapter is on the synthetic utility of the rDA reaction, an overview of mechanism is beyond the scope of this review however, the subject has beoi reviewed previously. Structural and medium effects on the rate of the rDA reaction are of prime importance to their synthetic utility, and therefore warrant discussion here. A study of steric effects cm the rate of cycloreversicHi was the focus of early work by Bachmann and later by Vaughan. The effect of both diene and dioiophile substituticHi on Ae rate of the rDA reaction in anthracene cycloadducts has been reported in a study employing 45 different adducts. If both cycloaddition and cycloreversion processes are fast on the time scde of a given experiment, reversibility in the DA reaction is observed. Reversible cycloaddition reactions involving anthracenes, furans, fulvenes and cyclopentadienes are known. Herndon has shown that the well-known exception to the endo rule in tiie DA reaction of furan with maleic anhydride (equation 2) occurs not because exo addition is faster than endo addition (it is not), but because cycloreversion of the endo adduct is about 10 000 times faster than that of the exo adduct. ... 

However, establishment of an equilibrium between the higher energy endo and lower energy exo results in the predominant formation of the exo product (thermodynamic control) (Scheme 4.13). Cycloaddition of furan with maleic anhydride, for instance, provides only the exo product. This may be ascribed to... 

The addition of the nitrile oxide (142) to furan is regiospecific, giving solely compound (143) with benzofuran, on the other hand, both possible adducts, (144) and (145), are obtained. The Diels-Alder reaction of furan with maleic anhydride has been re-investigated. Both endo- and exo-adducts are formed the... 

Scheme 20 Diels-Alder reaction of furan with maleic anhydride kinetic (endo Alder rule) and thermodynamic control...

The reaction of furans with ethyl 2,2-difluoro-l-diethylamino-carboxyacrylate generates fluorinated 7-oxanorbomenes [163]. These cycloadducts undergo alkene catalytic hydrogenation (or other reactions) into the corresponding 7-oxabicyclo[2.2.1]heptanes. Examples have been presented with the synthesis of norcantharidin, 5, with the synthesis of the 2-epimer of rac-3, 6 -epoxyauraptene, 32 (Scheme 3), and with the synthesis of thromboxane mimetics (Scheme 8). In 1929, Diels and Alder first reported the reaction of furan with maleic anhydride that produces at room temperature the exo-adduct 132 [164]. In 1962, Anet found that at low temperature, the reaction produces first the ew fo-adduct 133 in agreement with the endo Alder rule [165]. At 25 °C and in MeCN, the exo-adduct 132 is more stable by 1.9 kcal/mol compared with 133 [166] (Scheme 20). 

Bur and coworkers examined the dynamics of the cycloaddition by varying the silyl group and the dienophile. Surprisingly, reaction of the furans with maleic anhydride gave only cycloadducts 221a-c with exo stereochemistry... 

The [4-1-2] cycloaddition of 2-(benzoyloxy)furan with maleic anhydride was used as the first step in a short synthesis of dihydroxyperhydroisobenzofuranone 400, a natural... 

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). 

NH2)50s(2,3-T -L)], where L = furan, pyrrole, and thiophene. Although neither the furan nor thiophene complexes react with maleic anhydride over a period of 10 days, the pyrrole complex (15) reacts rapidly at room temperature and 101.3 kPa to form a mixture of endo (17) and exo (16) complexes. An a2omethine ylide intermediate was postulated as the key intermediate through which maleic anhydride added to the 2- and 5-positions of the coordinated pyrrole ring. 

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... 

Vinyl- and 3-vinylthiophene (73b and 77) are less reactive than the corresponding furans and show a notable preference for extra-annular addition due to the higher reactivity of the diene system, including the side-chain double bond. 2-Vinylthiophene is less reactive than 3-vinylthiophene. Whereas 2-vinylthiophene (73b) reacted with maleic anhydride and 1,4-benzoquinone to give cycloadducts in reasonable yield, 3-vinylthiophene (77) gave a higher yield of the cycloadduct [76, 77] (Scheme 2.31). 

The investigation on the use of K-10 montmorillonite under free solvent conditions was then extended to inner ring dienes such as furan and its 2,5-dimethyl derivative [9] (Table 4.3). The cycloadditions generally proceed slowly, and Zn(II)-doped clay and microwave irradiation were used to accelerate the reactions. The reaction with maleic anhydride preferentially affords the thermodynamically favored exo adduct. 

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]. 

Arylidine-furan-2-ones 439 undergo [4+2] cycloaddition with maleic anhydride 440 to give the tricyclic adducts 441 (Equation 119) <1997CHE910>. 

Novitskii, Khachaturova and Yur ev obtained 4i/,6/f-thieno[3,4-c]-furan (128) from 3,4-bischloromethylfuran (127) and sodium sulfide. The thienofuran (128) was converted into an adduct (129) with maleic anhydride and into 3,4-dimethylfuran (130) by desulfurization with Raney nickel [Eq. (40)]. 

Preparation of addition polymers having the oxolene (dihydrofuran) functionality can be envisioned to occur in two possible ways (Scheme 13). Both, in fact, have been observed (77MI11102). Whereas furan (53) or its derivatives do not homopolymerize under free radical conditions, 1 1 alternating copolymers possessing the 1,4-structure are produced with maleic anhydride (50). Intermediate formation of a CT complex between monomers (50) and (53) is believed to be necessary before polymerization can occur. On the other hand, cationic polymerization is quite facile. The outcome is straightforward with benzo[f>]furan derivatives, producing 1,2-polymers. Optically active poly(benzofurans) are formed when the cationic polymerizations are conducted in the presence of a chiral anion. 

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). 

As expected from Alder s endo rule, and justified by consideration of maximum accumulation of unsaturation in the transition state, secondary orbital interactions and dispersion forces, furan reacts with maleic anhydride in acetonitrile at 40 °C (78JOC518) to give initially... 

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