Benzofuran quinones

The first total synthesis of the marine furanosesquiterpenoid tubipofuran was accomplished in the laboratory of K. Kanematsu. The c/s-fused furanodecalin system was constructed by the regioselective Diels-Alder cycloaddition reaction of benzofuran quinone and Danishefsky s diene in refluxing toluene. The reaction gave an 11 1 mixture of the desired ortho-endo adduct versus the undesired para-endo product in 98% isolated yield. The major isomer then was subjected to sequential radical deoxygenation reactions before it was finally converted to the natural product. 

MOORE Cyclobutenone Rearrangement Thermal rearrangement of alkyl or alkenylcyclobutanones to benzofurans, quinones,... 

The reactions of enamines with positively activated olefins have been extended to arylations with />-quinones (350,362-369) and quinone sulfoni-mides (365-368,370). Thus a new pathway for the facile formation of benzofurans and indoles became available. 

This review of furan chemistry is meant to continue the earlier survey by Bosshard and Eugster1 and concentrates upon the period 1968 to the end of 1979. Like the earlier review, this one is limited to the chemistry of the monocyclic furan nucleus and does not deal, except incidentally, with fused rings such as benzofuran or its quinones. Nor does it deal in detail with dihydro- or tetrahydrofurans, nor with compounds like furylpyridine that contain some other heterocyclic nucleus as well. Some butenolides and tetronic acids are admitted to consideration since they are the carbonyl equivalents of hydroxyfurans regarded as enols, but side-chain reactions are wholly excluded unless the furan nucleus clearly affects them in some important way. 

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>. 

Michael additions to quinones. In the presence of TrC104, enol silyl ethers undergo 1,4-addition to benzoquinone to give adducts that cyclize to benzofurans.1 A similar reaction with diimidoquinones produces indole derivatives. 

The nature of the substituents on the allene can have an impact on the outcome of a [2 + 2] cycloaddition reaction, as was illustrated by the Lewis acid catalyzed cycloadditions of l-thioaryl-3,3-dimethylallene (24) and 1 -methyl- 1-trimethylsilylallene to various 2-alkoxy-p-benzoquinones 25 (e.g. equation 8)17. The reactions were considered to proceed via carbocation intermediates formed by nucleophilic attack of the thioallene on the Lewis acid activated quinone. At lower temperatures, these carbocations closed to cyclobutanes 26, whereas at higher temperatures, the thermodynamically more stable benzofurans 27 were formed. 

Cycloaddition Reactions with Other Nucleophiles The anodic two-electron oxidation of catechol affords o-quinone that may react with the enolates of 4-hydroxycoumarine or 5,5-dimethyl-1,3-cyclohexanedione (dimedone). The resulting adducts undergo a second anodic oxidation leading to benzofuran derivatives in good yields (90-95%) (Scheme 53) [75, 76]. 

Anodic oxidation of catechols enables the unstable quinones to be prepared and reacted in situ. Reaction of the 1,2-quinone with a 1,3-dicarbonyi compound gives a high yield of a benzofuran [123, 124]. Both 1,2- and 1,4-quinones, prepared electrochemically in nitromethane, are efficiently topped in Diels-Alder reactions with butadienes [125]. 

Methoxy-6-propyl-l,4-benzoquinone (170, Scheme 43) with hydrogen chloride undergoes dimerization and yields the biquinone 171 and the di-benzofuran 172. 2-Hydroxy-3,6-dimethyl-1,4-benzoquinone (173, Scheme 44), however, on treatment with boron trifluoride etherate in ether, or with concentrated sulfuric acid in acetic acid at room temperature, yields the extended quinone 174, which on reductive acetylation affords the dibenzo-furan 175. 

Acetonyl p-quinones by reduction give 2-acetonyl phenols, which undergo ring closure to the corresponding 2-methylbenzofurans an instance is the synthesis of 2,4,6,7-tetramethylbenzofuran.333 Heterocyclic ring closure with a-substituted o-hydroxyphenylacetones seems easier 334 reduction of 2-(a-acetopropyl)-5-methoxybenzoquinone, in an acidic medium leads directly to the benzofuran (132). 

Oxidative degradation of the o-quinone (429), obtained by chromic acid oxidation of the corresponding benzofuran (extracted from coal... 

The phenolics include anthocyanins, anthraquinones, benzofurans, chromones, chromenes, coumarins, flavonoids, isoflavonoids, lignans, phenolic acids, phenylpropanoids, quinones, stilbenes and xanthones. Some phenolics can be very complex in structure through additional substitution or polymerization of simpler entities. Thus xanthones can be prenylated and flavonoids, lignans and other phenolics can be glycosylated. Condensed tannins involve the polymerization of procyaninidin or prodelphinidin monomers and hydrolysable tannins involve gallic acid residues esterified with monosaccharides. As detailed in this review, representatives of some major classes of plant-derived phenolics are potent protein kinase inhibitors. 

Complex polyfunctional molecules can often be assembled efficiently by short, spectacular sequences of reactions, an example of which is the preparation of the pentasubstituted benzofuran 1. Thus, addition of l-lithio-l-methoxy-3-(trimethylsilyl)-l,2-hexadiene to 3,4-dimethoxycyclobut-3-ene-l,2-dione gave the expected keto alcohol in 70% yield. This alcohol was heated at reflux temperature in toluene for 4 hours to give a 2,3,5,6-tetrasubstituted hydroquinone in 90% yield. Oxidation of the hydroquinone with silver oxide and potassium carbonate in anhydrous benzene (90%) followed by reaction of the quinone thus obtained with TFA in methylene chloride at 0°C then at room temperature for two days gave 1 in 75% yield. 

Aromatization to furanes. The dihydrofurane group in 1 can be aromatized with the quinone to form the benzofurane 2 in 48% yield. 

A formal iron-catalyzed [3 + 2]-cycloaddition of styrene derivatives with benzoqui-none was reported by Itoh s group [96]. The process is believed to proceed via electron-transfer reactions mediated by a proposed Fe3+/Fe2+ couple, which generates a styrene radical cation and a semiquinone. These intermediates undergo stepwise addition to yield the benzofuran product 51 (Scheme 9.38). The reaction seems to be limited to electron-rich alkoxy-functionalized styrenes, as the Fe3+/Fe2+ redox couple is otherwise unable to transfer the electrons from the styrene to the quinone. 

Pyrolysis of o-hydroxybenzyl alcohol at 550 °C resulted in the formation of simple o-quinone methide, which was directly observed using low-temperature IR spectroscopy.122 Pyrolysis of chroman (Scheme 33) at 400-600 °C gives the simple o-quinone methide and ethene along with o-cresol, benzofuran, and styrene.123,124 The o-quinone methide was trapped with alkenes to form Diels Adler adducts, with hydrogen gas or hydrogen atom to form o-cresol, or underwent a further pyrolysis to CO and fulvene. 

The compounds studied were 2-methoxyhydroquinone A, 4-methylcatechol B, 2-hydroxy-2,3,3,-trimethoxy-5,5 -di-n-propylbiphenyl C, methoxy-p-benzoquinone D, 4,4 -dimethoxybiphenyl-2,5,2,5,-bisquinone E, 8-hydroxy-3,7-dimethoxydi-benzofuran-l,4-quinone F, 2,5-dihydroxy-2, 3,3 -trimethoxy-5 -hydroxymethyl-biphenyl G, and the related p-quinone H (scheme 1). Compounds A, D, E, and F were synthesized according to ref. [9], and compound Q, was prepared from 2-hydroxy-2,3,3,-trimethoxy-5-formyl-5,-hydroxymethyldiphenyl by Dakin reaction using the same procedure as for compound A. Compound G was isolated in presence of the corresponding p-quinone H. Titration of H was performed by... 

While both 2- and 3-furylcarbene complexes 99 and 103 gave [fo -annulated benzofurans (100 and 104), only the 2-pyrrolyl carbene complex 105 afforded the aromatic indole skeleton (106). In contrast, annulation of the 2,5-dimethylated 3-pyrrolylcarbene complex 107 occurred at the 4-position to give isoindole quinone 108 after oxidative work-up [82g]. 

The use of tertiary enaminones in the reaction with quinones to give benzofurans is a long known reaction140. If acetylbenzoquinone is used as the starting material, the resulting benzofuran141 (whose structure had to be corrected)142 (equation 93) can be transformed to furanobenzopyrans. 

There are only few representatives of 79. When 2,3-diphenyl-7-hydroxy-benzofuran was oxidized with Fremy s salt, a mixture of the 6,7- and 4,7-dione was obtained (70MI2). Similarly, nitric acid oxidation of the dihydroxy precursor afforded the quinone 82 or the related 5,6-dione, corresponding to the system 81 (12LA384). 

From Cyperaceae, many quinones with the 407 skeleton (scabequinones) were isolated, among others (73TL3 78P263). Total synthesis of racemic scabequinone (407), a major component of Cyperus scaber, from a benzofuran derivative has been described (73CC718). 

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