Benzo furans Diels-Alder reaction

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). 

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

Nebois P., Pillion H. Diels-Alder Reactions of Benzo[h Furan-4,5-Diones and Benzo[h Fnran-4,7-Diones Heterocydes 1999 50 1137 1156... 

Condensed benzo[i>]furan molecules can be prepared by inter- or intra-molecular Diels-Alder reactions from furo[3,4-b]benzofurans, and some interesting intermolecular examples are listed below. As can be seen, the furo[3,4-i>]benzofuran 60 underegoes Diels-Alder reactions with naphtho-l,4-quinone in the presence of Znl2 as a Lewis acid to form the aromatized cycloadduct. When the diene precursor reacts with benzo-l,4-quinone in the absence of Znl2, the product is obtained as an endo-exo mixture <00JCS(P1)1387>. 

Benzo[c]furans (isobenzofurans) are reactive molecules usually employed as reactive dienes in the synthesis of more complex molecules. In the synthesis of spiro compounds related to fredericamycin A, Kumar generated the trimethylsiloxytrimethylsilylbenzo[c]furan 125 from phthalide via two consecutive deprotonations and silylations of the resulting anions. Diels-Alder reaction of the isobenzofuran as shown below with a spiroenedione leads to the formation of an endo-exo mixtures that can be smoothly converted to the dihydroxydione <00IJC(B)738>. 

Diels-Alder reactions of benzo[fc]furan-43-diones and benzo[b]furan-4,7-diones have been reported <99H(50)1137>. The activation of a C-0 bond in a Mn(C0>3 complexed benzo[i>]furan was examined <99AG2343>. The enzyme-catalyzed dealkylation of (+)-marmesin to the phototoxic psoralene (and acetone) has been investigated <99AG413>. A hi yielding synthesis of bidentate bisoxazoline DBFOX/Ph [(R,R)-4,6-dibenzofutandiyl-2 2 -bis(4-phenyloxazoline)] was developed. DBFOX/Ph was subsequently tested in enantio-selective conjugate radical additions onto 3-(3-phenyl-2-propenoyl)-2-oxazolidinone <99TA2417>. 

The furo[3,4- ]pyrroles 132, 133 <2002TL6983>, thieno[2,3-f]furan 134, <1996JOC6166>, and furo[2,3-f]pyrrole 135 <1995T193>, which are mostly less stable than the benzo-fused analogues, were trapped by Diels-Alder reactions with dienophiles followed by elimination of water to give the corresponding indoles 136-139, 140, 141, and benzothiephenes 142, 143, and 144 with good to excellent yields (Scheme 13). 

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>. 

The retro Diels Alder reaction has also been proved of value in a number of related cases benzo[c]indoles, isobenzofulvenes, furans, and ful-venes have been prepared by the tetrazine route, white the Wiersum-Mijs method has been used for the preparation of benzo[c]indole itself. ... 

A useful synthesis of benzo[c]furans, based on experiments described by Ried, has been published by White et It consists of the Diels-Alder reaction of an acyclic diene with dibenzoylacetylene (146) and subsequent ring closure of the resulting 1,2-diaroylcyclohexadiene with /j-toluenesulfonic acid in benzene there has, however, been one report where this... 

The Diels Alder reaction of the acyclic diene and 146 may result in unexpected products, however. As reported by Ried, the reaction of 1,4-diphenylbutadiene and 146 may, under drastic conditions, give the aromatized compound (148) and l,3,4,7-tetraphenylbenzo[c]furan (149) in varying amounts, depending on the conditions. In methylglycol/propanol (6 hr reflux) a substance was isolated (mp 147-148°C, 59%) which has tentatively been formulated as 150. One final goal of the sequence described seems to be unaffected by these anomalous reactions, however Diels-Alder adducts of benzo[c]furans can be obtained in a one-step reaction from a diene, 146, and an appropriate olefinic compound in acetic acid/acetic anhydride as shown in Eq. (7). ° ... 

By far the most important property of benzo[c] furans is their capacity to act as 471-components in cycloaddition reactions. Whereas the reactions described before 1969 were almost always of the Diels-Alder type, more recent investigations have shown that they can also participate in [7 4 + 714]-and [714 + TCgj-addition (Section IV,C). In this chapter Diels-Alder reactions will be discussed. Benzo[c]furans have been used for two main purposes. First, Diels-Alder adducts with olefinic compounds can conveniently be dehydrated to naphthalene derivatives or higher condensed hydrocarbons not easily accessible by other methods second, benzo[c]furans are excellent... 

The question may arise as to whether the diene moiety of the benzene ring of benzo[c]furan may participate in a Diels-Alder reaction (Eq. 11). Such a reaction seems not to be known in the simple benzo[c]furan series, but... 

Synthesis of benzo[c]furans and isoindoles (181) is also possible by the addition of benzyne to the respective monocycles (178), followed by reduction (179 — 180) and pyrolysis. In an alternative procedure, (179) is reacted with 3,6-bis(2-pyridyl)-l,2,4,5-tetrazine, which affords (181) under far less vigorous conditions via a retro Diels-Alder reaction of the intermediate (182). 4-Phenyl-1,2,4-triazoles pyrolyze to form isoindoles (Section 3.4.3.12.2). 

Diaroylcyclohexadienes, which can be prepared from acyclic dienes and dibenzoylacetylene, undergo ring closure with p-toluenesulfonic acid in benzene to afford benzo[c]furans (Scheme 67) (71JOC1048). 1,4-Diphenylbutadiene and dibenzoylacetylene undergo Diels-Alder reaction to give the o-diaroylbenzene (237) and 1,3,4,7-tetraphenyl-benzo[c]furan (238) the ratio of each product obtained depends on the reaction conditions. 

The generation of benzo[c]furan in a retro Diels-Alder reaction was first reported in 1956 (56CB1334). When (402) was treated with diazomethane the adduct (403) was obtained which, when heated in the presence of copper powder to 180-200 °C, gave a polymer of benzo[c]furan (Scheme 108). 

The generation of benzo[c]furan as a transient species by retro Diels-Alder reactions has been used for synthetic purposes. When the adduct (414) was decomposed in the presence of dimethyl fumarate the product (415) was obtained decomposition of (414) with dimethyl maleate yielded the adducts (416) and (417) in the ratio 2 1 (Scheme 110) (69TL5231). 

As 2-vinylfuran rapidly polymerizes even in a nitrogen atmosphere in the presence of a stabilizer, yields obtained for these Diels-Alder reactions were very low. In fact, when the more stable 5-(4-nitrophenyl)-2-vinylfuran lb reacted with DMAD, the yield of the aromatized cycloadduct, dimethyl 2-(4-nitrophenyl)benzofuran-4,5-dicarboxylate 4b, was 50%. The 4-nitrophenyl group not only deactivated the vinylfuran for oxidation and polymerization, but also deactivated the diene system toward cycloadditions, and the reaction was successful only when conducted in boiling xylene. The decrease in reactivity of the reactive diene may account for the relatively low yield of methyl 2-(4-nitrophenyl)benzo-furan-4-carboxylate 6b obtained in a similar reaction with MP (73-AJC1059). 

A domino process for the construction of a tetracyclic ring was achieved by the gold-catalyzed formation of an isobenzopyrylium derived from a phenylacetylene-based benzaldehyde. This was followed by reaction with electron-rich benzo[ ]furan as a dienophile in a Diels-Alder reaction with inverse electron demand (Equation 102) <2003AGE4399>. 

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