2- Substituted furans, formation

Substituted furan formation by an indirect cyclization of 1,4-dicarbonyl derivatives has also been adopted as a key step in the synthesis of 3-oxa-guaianolides. Although 1,4-dicarbonyl compounds have been traditionally considered as the direct precursors for furans, treatment of 1,4-dicarbonyl compounds having a tertiary acetoxy group with p-toluenesulfonic acid leads to only 11% yield of an alkenylfurans as derived from a cyclization/acetoxy-elimination route. The following scheme shows an alternative multi-step conversion of the 1,4-dicarbonyl that leads to a more acceptable yield of the acetoxyfuran . 

Friedrichsen and co-workers (135), along with Padwa, has utilized the carbonyl ylide cycloaddition to generate reactive furan moieties that can be further used in inter- or intramolecular Diels-Alder reactions to prepare aza- and carbocyclic compounds. Friedrichsen conducted a number of synthetic and theoretical studies on the reactivity, regioselectivity, and stereoselectivity of substituted furan formation and subsequent Diels-Alder reaction (Scheme 4.69). 

Directive effects on lithiation have also been studied. The regiospecific /3-metallation of A-methylpyrrole derivatives and 2-substituted furans has been effected by employing the directive effect of the oxazolino group (82JCs(Pl)1343). 2-Substituted furans and thiophenes are metallated in the 5-position. The formation of 2-lithio-3-bromofuran on treatment of... 

Tandem reaction of aromatic aldehydes with electron-deficient acetylenes and dialkyl acetylenedicarboxylates in the presence of I it iN led to the formation of fully substituted furans in moderate yields. One appropriate example is shown below <06EJOC5174>. 

Diaryl- and tetraaryl-substituted furans such as tetraphenylfuran (384) for example, yield generally cw-diaroylethylenes such as 380, probably via intermediate ozonide formation.257 Secondary reactions seem to depend very much on the nature of the solvents. Thus, cis-dibenzoylstilbene (380) has been observed by direct photooxygenation of 384 in CS2 as well as by methylene blue-sensitized photooxygenation of 384 in methanol.257,258 However, when the latter reaction was carried out in acetone, epoxide 386 and the enolbenzoate 387 were obtained.258... 

The preparation of 5-arylfurfurals (and arylthiophene-2-carboxaldehydes) via Pd-catalyzed C-C bond formation in aqueous media was carried out <990L965>. Full details have been reported for the Pd-catalyzed cycloisomerization of (Z)-2-en-4-yn-l-ols (a facile synthesis of a variety of substituted furans) <99JOC7687>... 

The intramolecular addition of hydroxyl groups to triple bonds might be utilised in the formation of furane derivatives. Enynols, having the appropriate double bond geometry, underwent ring closure and subsequent double bond isomerisation in the presence of both palladium and ruthenium catalysts to give substituted furans (3.52.),66... 

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. 

Many examples of natural furans are recorded as having been prepared from five-membered heterocycles such as 2(5H)-furanones (butenolides), which are reduced to furans with diisobutylaluminum hydride. The facile elimination of selenoxides derived from a-phenylseleneyl-y-lactones with formation of endocyclic a,/3-unsaturated butenolides is reported (75JOC542) as a useful route to 2,4- and 2,3,4-substituted furans via their corresponding butenolides. The mixture of dihydrofurans obtained from the tosylhydrazone of tetrahydro-2-furanone (Scheme 88) was oxidized to furans by 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (66CJC1083). 

The intensity of undesirable sensory notes has been positively correlated with the content of carbonyl compounds formed through lipid autoxidation reactions. In general, the carbonyl compounds present have the greatest impact on flavor owing to their low flavor thresholds in comparison with hydrocarbons, substituted furans, and alcohols. Aldehydes are major contributors to the loss of desirable flavor in meats because of their rate of formation during lipid oxidation and low flavor threshold. Thus, an alternative approach for monitoring the extent of lipid oxidation in fats and oils is to measure... 

A recent study of proton transfer from rhenium Fisher-type carbine complexes (13) shows that the reactions lead to the formation of an aromatic product (14), following the same rules as reactions that lead to the formation of products stabilized by simple resonance. The conjugate bases of these carbine complexes represent aromatic heterocycles, i.e., substituted furan, selenophene, and thiophene derivatives, respectively. The aromatic stabilization of these heterocycles is known to follow the order furan < selenophene < thiophene (Scheme 1) [43],... 

On the contrary, Lewis acids catalyzed a different behavior. Treatment with BF3 Et20 gave only 3-substituted furan in THF and 89% of 2-substituted furan in acetonitrile (Scheme 3.21) [51]. This behavior is in agreement with the formation of a carbocation 17, which can be stabilized by splitting off a proton to... 

In the PB reaction of unsymmetrically substituted furans with aldehydes, the site-selectivity was reported as quite difficult to control (Scheme 7.13). Thus, a 1.3 1 mixture of oxetanes was formed in the PB reaction of 2-methylfuran with benzalde-hyde. Schreiber and coworkers found that the site-selectivity could be controlled by using bulky substituents at the furan ring [29a], and consequently the less-substituted oxetanes were selectively prepared in the PB reaction (Scheme 7.13). On the other hand, a highly site-selective formation of the more-substituted oxetanes was reported in the PB reaction ofacetylfurans with aromatic aldehydes (Scheme 7.13) [29b]. A high exo-selectivity was also observed in the PB reaction with aldehydes (vide infra). 

Recently, a notable temperature-related effect was reported for site-selectivity (double-bond selectivity or chemoselectivity) in the PB reaction of unsymmetrically substituted furans (Scheme 7.14) [30]. For example, the selective formation of the more substituted oxetane, OX1, was observed during the PB reaction of 2-methyl-furan with benzophenone at a high temperature (61 °C). However, a 58 42 mixture of the oxetanes, 0X1 and 0X2, was reported at low temperature (—77 °C). This notable effect of temperature could be explained by the relative population of conformers of the intermediary triplet 1,4-biradicals, T-BR1 andT-BR2. The excited benzophenone was considered to attack the double bonds equally so as to produce a mixture of the conformers of T-BR1 and T-BR2 however, at low temperature the conformational change was suppressed. Thus, the site-random formation of oxetanes 0X1 and 0X2 was observed after the ISC process. Nonetheless, at high... 

The cycloaddition of isomiinchnones with acetylenic dipolarophiles followed by the extrusion of an alkyl or aryl isocyanate (RNCO) has proven to be an effective method for the synthesis of substituted furans. The Ibata group investigated the bimolecular 1,3-dipolar-cycloaddition of aryl-substituted isomiinchnones with a number of acetylenic dipolarophiles [50]. Aryl diazoimides of type 1 were heated in the presence of a catalytic amount of Cu(acac)2 and the appropriate acetylenic dipolarophile. Formation of the substituted furan was found to be temperature-dependent higher temperatures (ca. 120°C) were needed for complete conversion to the furan. It was reasoned that the extrusion of methyl isocyanate was not as facile as the loss of carbon dioxide from sydnones and miinchnones [50]. 

Formation of the difurylalkane skeleton has been accomplished by condensation of a 2-substituted furan derivative with a carbonyl compound under acidic conditions in other words, difurfuryl propane (18) has been produced by the condensation of furan with acetone (60). 

Via Elimination of A kohol or W alter from Dihydrofurans Pyrolysis of 2,5-dialkoxy- or -diacetoxy-2,5-dihydrofurans results in a smooth reaction with the formation of 2-substituted furans.39 40... 

Carbonyl compounds also react with allenes and, in fact, the first example of a gold-catalyzed addition of a nucleophile to allenes was the formation of lurans from allenones. The reaction was applied by Gevorgyan to the synthesis of substituted furans and in the case of bromide-substituted allenes halide migration was observed. Similar additions of... 

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