Furans vinyl-substituted

Vinyl-substituted benzo[c]furans can be prepared by reaction of n-alkynylbenzaldehydes with chromium Fischer carbene complexes. Initially a benzo[c]furan chromiumtricarbonyl complex is believed to be formed which is converted into an alkylidenephthalan derivative or can be trapped with electron-deficient dienophiles with excellent ( 3 ti-selectivity (Equation 128) <20000L1267>. More elaborate vinylidene Fischer carbene complexes yield dienyl benzo[c]furans that undergo [8-1-2] cycloaddition with DMAD to furnish furanophane derivatives <2003JA12720>. An equilibrium between 7] -(o-ethynylbenzoyl)rhenium complexes and rhenium benzo[f]furyl carbene complexes has been observed. These species behave like other benzo[< ]furans in the reaction with DMAD <20040M4121>. 

Aryl halides which are rather inert in usual organic reactions can undergo reactions by means of palladium catalysts. Thus, styrene and stilbene derivatives are obtained by reaction of olefins with aryl bromides at 125 °C using Pd(0Ac)2 (1 mol%) and tri-(o-tolyl)phosphine (2 mol%)83. The palladium-catalyzed vinylic substitution reaction is applicable to a variety of heterocyclic bromides including pyridine, thiophene, indole, furan, quinoline and isoquinoline84. Thus, reaction of 3-bromopyri-dine with l-(3-butenyl)phthalimide at 100 °C gives l-[4-(3 -pyridyl)-3-butenyl]-phthalimide (yield of mixed amine 57%, selectivity 68%) at 100 °C. This phthalimide is subsequently converted to nornicotine (188) (Scheme 59). The reaction of acrylic... 

Studies relating to the stereoselective hydroboration of polyfunctional alkenes continue to appear. Various vinyl substituted pyridines, thiophenes and furans have been reacted with representative hydroborating agents,11" and further aspects of the hydroboration of cyclic dienes have been disclosed.11 The asymmetric hydroboration of cyclic enol ethers and enamines (heterocyclic alkenes) provides access... 

Beginning in 1998, Ma has developed a series of cascade cross-coupling cycliza-tion reactions of functionalized allenes with organic hahde in the presence of palladium species, leading to various highly substituted carbocycles or heterocycles, such as y-butenolides, y-lactams, y-iminolactones, vinylic epoxides, 2,5-dihydrofurans, 2,3-dihydropyrroles, furans, vinylic cyclopropanes, and cyclopentenes, which depend on the nature of the functional groups and the substituents on the allenes. This has been well summarized by the author [102] (Scheme 6.76). 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

In addition to benzene and naphthalene derivatives, heteroaromatic compounds such as ferrocene[232, furan, thiophene, selenophene[233,234], and cyclobutadiene iron carbonyl complexpSS] react with alkenes to give vinyl heterocydes. The ease of the reaction of styrene with sub.stituted benzenes to give stilbene derivatives 260 increases in the order benzene < naphthalene < ferrocene < furan. The effect of substituents in this reaction is similar to that in the electrophilic aromatic substitution reactions[236]. 

The high reactivity of pyrroles to electrophiles is similar to that of arylamines and is a reflection of the mesomeric release of electrons from nitrogen to ring carbons. Reactions with electrophilic reagents may result in addition rather than substitution. Thus furan reacts with acetyl nitrate to give a 2,5-adduct (33) and in a similar fashion an adduct (34) is obtained from the reaction of ethyl vinyl ether with hydrogen bromide. 

Elementary considerations indicate that with appropriate substitutions some of the reactions mentioned above can be eliminated. Indeed, when 5-methyl-2-vinyl-furan was used, no alkylation was observed, the positions C-3 and C-4 being rather unreactive16, and the polymer was a mixture of linear chains with polyunsaturations and linear saturated chains, i.e. only structures like 21, 23 and 26 were present, with a 5-methyl ring instead of the 5-unsubstituted one. When 2-isopropenylfuran was used, no hydride transfer took place since this requires a hydrogen atom in the a-position to the ring, which this monomer does not have the polymers were white and gave electronic spectra transparent down to 280 nm. Alkylation at C-5, how-... 

There are several reports scattered in the literature of the retarding effect of simple furan derivatives in the polymerization of a specific monomer. Hardy69, U6 found that furan, 2-furoic acid and its esters, and 5-substituted-2-furoie acids were strong retarders in the radical polymerization of vinyl acetate, but did not act likewise with styrene. He proposed that as a result of the reactions of the free radicals with the furan derivatives, dihydro- and tetrahydrofurans would form, but he did not produce any evidence to support these speculations. Clarke, Howard and Stock-... 

The nitrofuran group of drugs (Fig. 5.18) is based on the finding over 40 years ago that a nitro group in the 5 position of 2-substituted furans endowed these eompounds with antibacterial activity. Many hundreds of such compounds have been synthesized, but only a few are in current therapeutic use. In the most important nitrofurans, an azomethine group, —CH=N—, is attached at C-2 and a nitro group at C-5. Less "important nitrofurans have a vinyl group, —CH=CH—, at C-2. 

Such nucleophilic displacements are likely to be addition-elimination reactions, whether or not radical anions are also interposed as intermediates. The addition of methoxide ion to 2-nitrofuran in methanol or dimethyl sulfoxide affords a deep red salt of the anion 69 PMR shows the 5-proton has the greatest upfield shift, the 3- and 4-protons remaining vinylic in type.18 7 The similar additions in the thiophene series are less complete, presumably because oxygen is relatively electronegative and the furan aromaticity relatively low. Additional electronegative substituents increase the rate of addition and a second nitro group makes it necessary to use stopped flow techniques of rate measurement.141 In contrast, one acyl group (benzoyl or carboxy) does not stabilize an addition product and seldom promotes nucleophilic substitution by weaker nucleophiles such as ammonia. Whereas... 

Negishi coupling of 2-furylzinc chloride with vinyl telluride provided 2-substituted furan with (Z)-double bond in a stereoselective manner, which was used in the total synthesis of l-(Z)-atractylodinol, a biologically active natural product as depicted in the following scheme <06TL8183>... 

JOC6503>, and new pyridazino-psoralens 15 were prepared via a furan ring expansion reaction <05T4805>. The reaction of 3-acetylcoumarins with alloxan followed by NH2NH2 easily produced 3-(2-oxo-2//-chromen-3-yl)-6//,8//-pyrimido[4,5-c]pyridazine-5,7-diones <05JHC1223>. Furano- and pyrano[2,3-c]pyridazines 17 and 18a,b as well as substituted quinolines were conveniently prepared from pyridazinone 16 and vinyl- and allyltriphenyl-phosphonium salts <05HAC56>. 

Reactions of furan (5) under solvent-free conditions, catalyzed by Montmorillonite K10, have been described by Cintas [27]. The reaction with methyl vinyl ketone (32) produced Michael addition in positions 2 and 5, whereas reaction with symmetrically substituted cyclic dienophiles produced a mixture of the endo and exo adducts with the kinetically favored endo adduct predominating, except when maleic anhydride (39) was used as the dienophile (Scheme 9.2). 

An efficient access to 3-carboxy-2,5-disubstituted furans 64 has been developed. p-Keto esters are found to undergo an acid- or a base-catalyzed enolization and a subsequent intramolecular 1,4-addition to afford the desired furans in excellent yields. The carbonyl substituent can be further transformed to a vinylic substituent with a desired substitution pattern <00TL1347>... 

Reaction of 1,3-dicarbonyl compounds with vinyl sulfides gives the corresponding medium- and large-sized ring substituted furans 78 in moderate to good yields. In addition to cyclohexane-1,3-diones, 4-hydroxycoumarins and 4-hydroxyquinone can also be used as 1,3-dicarbonyl components . 

The Cu(I)-catalyzed cyclization for the formation of ethyl ( )-tetrahydro-4-methylene-2-phenyl-3-(phenylsulfonyl)furan-3-carboxylate 82 has been accomplished starting from propargyl alcohol and ethyl 2-phenylsulfonyl cinnamate. Upon treatment with Pd(0) and phenylvinyl zinc chloride as shown in the following scheme, the methylenetetrahydrofuran 82 can be converted to a 2,3,4-trisubstituted 2,5-dihydrofuran. In this manner, a number of substituents (aryl, vinyl and alkyl) can be introduced to C4 <00EJO1711>. Moderate yields of 2-(a-substituted N-tosyIaminomethyl)-2,5-dihydrofurans can be realized when N-tosylimines are treated with a 4-hydroxy-cis-butenyl arsonium salt or a sulfonium salt in the presence of KOH in acetonitrile. The mechanism is believed to involve a new ylide cyclization process <00T2967>. 

Thus, 2-furfuryl vinyl ether 6a is extremely sensitive to cationic activation (16) because of its very pronounced nucleophilic character, but the polymerization is accompanied by some gel formation due to abundant alkylation of the furan rings pendant to the macromolecules. This structural anomaly is not encountered with the 5-methylated monomer 6b (16) precisely because electrophilic substitutions take place predominantly at C5 and are therefore impossible with this monomer. A similar difference of phenomenolo was observed with the 2-fiiryl oxiranes 4a and 4b (17). 

The propensity of the C5 site towards electrophilic substitution has been exploited to prepare functionalized oligomers by cationic polymerization. Thus monomers like isobutene, s ene, the vinyl ethers, etc. polymerize in the presence of simple furan derivatives such as 2-methyl furan to give essentially short chains (DP between 2 and 100 depending on the specific experimental conditions) with a terminal furan ring as a result of predominant transfer onto the C5 position of the added furan compound (20). 

An example of the first type of study is the cationic pol erization of alkenes and heterocyclic monomers in the presence of 2-alWlfurans. As discussed above, electrophilic substitution at C5 is quite facile with these compounds and one can therefore prepare monofunctional oligomers bearing a furanic end-group. By a judicious choice of experimental conditions this transfer reaction will predominate over all other chain-breaking events and virtually all the chains will have the same terminal structure, i.e. a 5-oligomer-2-al lfuran. Structure 32 illustrates this principle with isobutyl vinyl ether oligomers capped by 2-methylfuran ... 

It was shown <1998CCC681> that [l]benzothieno[3,2-3]furan 60, due to its low furan aromaticity, possesses dienophilic behavior and reacts with electron-rich dienes with the formation of a new heterocyclic system [l]ben-zothieno[3,2-3][l]benzofuran 93. Furthermore, it was reported <1999CCC389> that introduction of a vinyl moiety at C-2 of 57 created a reactive diene 94, which reacted with various dienophiles. Thus, both cycloaddition reactions led to new derivatives of heterocycle 93 substituted in the benzofuran part of the heterocyclic system (Scheme 10). 

Vinyl ethers and amines disclose little tendency to revert to type thus, the intermediate formed by reaction with an electrophilic reagent reacts further by adding a nucleophilic species to yield an addition compound cf the sequence (8) — (11). Thiophene and pyrrole have a high degree of aromatic character consequently the initial product formed by reaction of thiophene or pyrrole with an electrophilic species subsequently loses a proton to give a substituted compound cf the reaction sequence (12) — (15). Furan has less aromatic character and often reacts by overall addition as well as by substitution. In electrophilic addition, the first step is the same as for substitution, i.e. the formation of a tr-complex (e.g. 13), but instead of losing a proton this now adds a nucleophile. 

Treatment of lithiated (41) with aldehydes (42a-c) at -78 °C and then at room temperature gives the corresponding alcohols (43a-c) in yields up to 80%. When (43a-c) were refluxed in benzene containing a catalytic amount of p-toluenesulfonic acid the 2-substituted furans (44a-c) were formed in good yields. Various 2,3-disubstituted furans were readily prepared by combination of the synthetic methods for 2- and 3-substituted furans (Scheme 9). The synthetic utility of this route is illustrated by the preparation of 2-(3,7-dimethyl-2,6-heptadienyl-3-methylfuran (47), which is a typical 2,3-disubstituted furan occurring in nature, starting from the aldehyde (46) and the acetal (45) (Scheme 10). Table 1 summarizes the 2,3-disubstituted furans synthesized by this route. However, attempts to extend the method to the preparation of 3-acylfurans (48) was unsuccessful because of the formation of the vinyl sulfone (49) via deacylation. 

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