Benzofurans isomeric

The 2a,7b-dihydrocyclobuta[7>]benzofuran structure, obtained by addition of activated acetylenes to benzofurans (see Houben-Weyl, Vol.E6b, p 148), isomerizes thermally to a 1-benz-oxepin182 184 185 which reacts further to 1-naphthol derivatives at higher temperature182,185 (see Section 1.2 ). Under photochemical conditions, the 1-benzoxepins undergo ring contraction to the starting material.182 184... 

From the copper-catalyzed reaction of methyl 2-diazo-3-oxobutyrate 57 a with Z-3-methoxystyrene, dihydrofuran 59 (formed with retention of olefin configuration) and butadienol 60 result130). Such an acyclic by-product also occurs when benzofuran is the cycloaddition partner. In that case, however, regioisomers 61 and 62, arising from the connection of the former diazo carbon with either the 2- or 3-position of the heterocycle, are obtained similarly, two isomeric dihydrofurans 63 and 64 are formed under Cu(hfacac)2 catalysis130). 

Rawal s group developed an intramolecular aryl Heck cyclization method to synthesize benzofurans, indoles, and benzopyrans [83], The rate of cyclization was significantly accelerated in the presence of bases, presumably because the phenolate anion formed under the reaction conditions was much more reactive as a soft nucleophile than phenol. In the presence of a catalytic amount of Herrmann s dimeric palladacyclic catalyst (101) [84], and 3 equivalents of CS2CO3 in DMA, vinyl iodide 100 was transformed into ortho and para benzofuran 102 and 103. In the mechanism proposed by Rawal, oxidative addition of phenolate 104 to Pd(0) is followed by nucleophilic attack of the ambident phenolate anion on o-palladium intermediate 105 to afford aryl-vinyl palladium species 106 after rearomatization of the presumed cyclohexadienone intermediate. Reductive elimination of palladium followed by isomerization of the exocyclic double bond furnishes 102. 

Intramolecular [4+2]-cycloaddition reactions, which involve base-induced isomerization of a propargyl ether to an allenyl ether, have been extensively studied. Treatment of 157 with a base caused an intramolecular Diels-Alder reaction of the intermediate allenyl ether to give tricyclic compounds 158 [131]. An asymmetric synthesis of benzofuran lactone 159 was achieved by an analogous procedure [132],... 

Svoboda and co-workers studied substitution reactivity of thieno[3,2- ][l]benzofuran 61 <1997CCG1468> in comparison with the isomeric [l]benzothieno[3,2-. ]furan 60, which was already described <1993CCC2983>. They discovered that under electrophilic substitution conditions, the system 61 is more stable than 60. 

Methyl-o-benzyloxyphenylglyoxylate (32) cyclizes on irradiation to give an isomeric mixture of 2-phenyl-3-carboxymethyl-3-hydroxyl-2,3-dihydro-benzofurans (33), apparently by an internal hydrogen abstraction-cyclization mechanism.103 This abstraction must take place through a seven-membered... 

Furanones having an exocyclic double bond at position 3 follow a different course of isomerization. Thus, the furanones 13 and 14 isomerize in acidic medium to give the corresponding benzofuran and benzothio-phene carboxylic acids 15 and 16, respectively (Scheme 3) (90JPR414). 

Benzamido-cinnamic acid, 20, 38, 353 Benzofuran polymerization, 181 Benzoin condensation, 326 Benzomorphans, 37 Benzycinchoninium bromide, 334 Benzycinchoninium chloride, 334, 338 Bifiinctional catalysts, 328 Bifiinctional ketones, enantioselectivity, 66 BINAP allylation, 194 allylic alcohols, 46 axial chirality, 18 complex catalysts, 47 cyclic substrates, 115, 117 double hydrogenation, 72 Heck reaction, 191 hydrogen incorporation, 51 hydrogen shift, 100 hydrogenation, 18, 28, 57, 309 hydrosilylation, 126 inclusion complexes, oxides, 97 ligands, 19, 105 molecular structure, 50, 115 mono- and bis-complexes, 106 NMR spectra, 105 olefin isomerization, 96... 

Although the isomeric chromenes (48) and (49) obtained from the isoflavanone (47) and 3-chloro-3-methylbut-l-yne could not be separated by chromatography, a chemical separation was achieved. Ring contraction of the 7-methoxy isomer (49) to the benzofuran (50) occurred on reaction with thallium(III) nitrate in methanol the 5-methoxy compound was unaffected. The resulting mixture was readily separated <8iG2li). 

From benzofurans. Russian workers have reported several examples of the isomerization of 2,3-dihydrobenzo[6]furans into chromans. Triphenylmethyl perchlorate in acidic media converts the 2-ethyl derivative into 2-methylchroman, whilst the same chroman results when the 2,3-dimethylbenzofuran is treated with aluminosilicates at high temperature (72DOK(204)879, 75CHE278). 

Finally it has been found28 that from a mixture of 2-(/>-tolyl)benzo-furano[3,2-/]- and [3,2-e]benzofuran, the two isomeric stilbene derivatives (42) and (43) can be obtained. 

The reaction of 2-vinylfuran la with methyl propiolate (MP) did not proceed at room temperature owing to the lower reactivity of this dieno-phile and at 80°C, although two isomeric benzofurans are possible, only methyl benzofuran-4-carboxylate 6a was obtained. This regioselectivity is not unexpected, considering electronic and substituent effects (67AG 16). 

The industrial synthesis of vinyl acetate [14] via palladium-catalyzed oxidative coupling of acetic acid and ethene using direct 02 reoxidation has already been mentioned (Scheme 3, d). Some NaOAc is required in the reaction medium, and catalysis by Pd clusters, as alternative to Pd(II) salts, was proposed to proceed with altered reaction characteristics [14]. Similarly, the alkenyl ester 37 (Table 5) containing an isolated vinyl group yields the expected enol acetate 38 [55] whereas allylphenol 39 cyclizes to benzofuran 40 with double bond isomerization [56]. 

In contrast with benzofuran (and with thiophene itself), benzothiophene is substituted preferentially at the )3 position. Bromina-tion,77, 226, 227 formylation,228, 229 acylation,77, 221, 230-232 chlorination,233 chloromethylation,234 sulfonation,235 mercuration,236 and iodination237 give exclusively or prevalently the 3-substituted isomers. Anomalous orientation (in position 2) has been observed in iso-propylation,238 but it is possible that isomerization occurs under the conditions reported. 

Another intramolecular substitution has been used for the synthesis of an intermediate in a proposed route to 3-substituted benzofurans. A / -methylene-dihydrobenzofuran complex was obtained upon fluoride-induced removal of the SiR3 protecting group from complex 37 (Scheme 16) in an ipso SnAr process. Desilylation resulted in spontaneous cyclization to the stable methylene complex 38 in 89 % yield. No isomerization occurred and the 3-methyl benzofuran complex was not detected [21]. 

Recently, Minkin and coworkers31 have reported on thermal and photoinitiated E-Z isomerizations in a series of bicyclic N-monosubstituted 2-acylenamines (6). The E-Z equilibrium was found to be strongly dependent on the heteroatom X. While the indole derivative 6a exists only in the hydrogen-bonded E form both in solution and in the crystalline state, the benzofuran analogue 6b adopts the Z form in the crystal and in polar solvents. In chloroform and in hydrocarbon solvents, a slow transformation to the E form occurs, accelerated by heat and by catalytic amounts of acids and bases. The benzothiophene analogue 6c behaves similarly, and on irradiation a photostationary mixture of E and Z forms is established, which returns to the initial form in the dark. 

Highly substituted benzofurans have been synthesized from their corresponding substituted l-allyl-2-allyloxy-benzenes using a ruthenium-mediated C- and 0-allyl isomerization followed by RGM (Scheme 84) <2005T7746>. 

Benzohydrofuranes. 2-Allylphenols are cyclized oxidatively by Pd(OAc)2 (1 equiv.) to isomeric benzofuranes. In the presence of oxygen, the Pd(II) salt can be used in catalytic amounts. An example is formulated in equation (I). ... 

Z)-2-Butenyl]phenol, on the other hand, gives only 0.7 % ee of the (R)-2,3-dihydro-2-vinyl-benzofuran. The difference in optical yields between the (E)- and (Z)-isomeric substrates must be due to the geometric difference, since no Z-> isomerization of the double bond occurs during the reaction. 

Sauter and Adam have applied DMDO lb for the epoxidation of benzofurans in their study of the DNA-damaging activity of benzofuran epoxides 70 and their valence-isomeric compounds 71 and 72 <1995ACR289>. 

Palladium salts also promote the addition of nucleophiles to alkenes and alkynes. The Pd-catalyzed additions of nucleophiles to alkynes, which is useful for intramolecular cyclizations such as the isomerization of 2-alkynylphenols to benzofurans, proceeds by exactly the same mechanism as does the Hg-catalyzed reaction. However, the Pd-catalyzed additions of nucleophiles to alkenes takes the course of substitution rather than addition because alkylpalladium complexes are unstable toward /3-hydride elimination. The Pd-catalyzed nucleophilic substitutions of alkenes are discussed later in this chapter (Section 6.3.6). 

The hydroformylation of the orf/zo-prop-2-enylphenol 81 which contains no benzylic hydroxy group gives a mixture of the open-chain aldehyde 82 and the seven-membered cyclic hemiacetal 83 in a 82 83 ratio of approximately 40 60 (equation 34) °. The ben-zofuran epoxide 85 and its valence-isomeric quinone methide 86, both readily obtainable from benzofuran 84, rearrange thermally above —20°C to form the allylic alcohol 87 and the tautomeric phenol 88 (equation 35) . ... 

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