5-aryl-substituted furans

Arylation of furan and thiophene with arylhydrazine (40) and Mn(OAc)3 gives 2-aryl substituted furan and thiophene (41) as shown in eq. 5.22. 

The arylation of furan by the Gomberg reaction has been carried out using a number of differently substituted diazonium salts. In... 

Synthesis of 2-alkyl- or 2-aryl-substituted benzo[b]furans has been reported, involving a CuITMEDA complex which catalyzes the transformation of readily available ketone derivatives into the corresponding benzofurans in good-to-excellent yields in water (Eq. 6.13).29... 

A palladium-catalyzed one-step synthesis of dihydrobenzo[fc]furan-based fused aromatic heterocycles from bifunctional bromoenoates or bromoalkyl indoles and iodoarenes was reported, and an example is provided in the scheme below <060L3601>. 2-Alkyl- or 2-aryl-substituted benzo[ >]furans were synthesized by a copper-TMEDA catalyzed intramolecular annulation from the corresponding ketones <06OL1467>. 

Acetyl-l-aryl-2-pentene-l,4-diones 65 formed from the reaction of arylglyoxal with 2,4-pentanedione in the presence of BF3 Et20 are converted to tri- and tetra-substituted furans <00TL3149>. 

When furan or substituted furans were subjected to the classic oxidative coupling conditions [Pd(OAc)2 in refluxing HOAc], 2,2 -bifuran was the major product, whereas 2,3 -bifuran was a minor product [12,13]. Similar results were observed for the arylation of furans using Pd(OAc)2 [14]. The oxidative couplings of furan or benzo[i]furan with olefins also suffered from inefficiency [15]. These reactions consume at least one equivalent of palladium acetate, and therefore have limited synthetic utility. 

A similar substituted furan synthesis was realized via a Pd-catalyzed tandem carbonylation-arylation using an a,p-acetylenic ketone, carbon monoxide, and bromothiophene [104],... 

The direction of MCR involving pyruvic acid, aldehyde, and l-aryl substituted l,2,4-triazole-3,5-diamine was different from the directions of all other processes that were discussed earher. It was established [53] that this treatment yielded 3-(5-ammo-lH-l,2,4-triazol-3-ylamino)furan-2(5H)-one 39 instead of triazolopyri-midine carboxylic acids 38 (Scheme 16). 

The main types of substrates investigated so far are polycyclic aromatic compounds, aryl substituted carbo- and heterocyclic pentadienes, cyclic 1,3-dienes, furans, and olefins. It has turned out that type II photooxygenation of these compounds in solution occurs via the oxygen-activation mechanism. 

Cyclopentadienes, 1,3-cyclohexadienes, 1,3-cycloheptadienes, as well as furan and aklyl-substituted furans, have been investigated as substrates of photosensitized oxygenation reactions, while aromatic compounds such as anthracenes and tetracenes as well as aryl-substituted carbo-and heterocyclic pentadienes were studied in direct and indirect (photosensitized) photooxygenation reactions. 

In addition to this latter work, a silver-catalyzed 1,2-alkyl/aryl shift is also possible with allenyl ketones (16), giving, as before, highly substituted furans (17, Scheme 5.9).44 Not surprisingly, Gevorgyan et al. observed that the migratory aptitude... 

The synthesis of furo[3,4-<7]pyridazines is most conveniently accomplished by treating a suitably substituted furan with hydrazine. Thus, the furan dicarboxylic ester (195 R = substituted phenyl) yields the aryl-substituted furopyridazine (196) when so treated (Equation (67)) <83KFZ683>. 

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]. 

Non-aryl substituted isomiinchnones also undergo the same transformation but under less rigorous conditions. Thus, when acyclic diazoimides 19 and 20 were subjected to Rh2(OAc)4-catalyzed decomposition in the presence of DMAD, cycloaddition followed by extrusion of methyl isocyanate occurred to give the substituted furans 94 and 95 [35]. 

The [4+1] cycloadducts formed from 4,4-bis(trifluoromethyl)-l-oxa-buta-1,3-dienes (92JPR219) and tin(II )-chloride are transformed on heating into 4,4-difluoro-3-trifluoromethylbut-3-en-l-ones, which on treatment with sodium hydride yield 2-fluoro-3-trifluoromethylfurans (92CC348). When heated with phosphorus pentasulfide, l-aryl-4,4-difluoro-3-trifluor-omethylbut-3-en-l-ones give 2-fluoro-3-trifluoromethylthiophenes. The fluorine atom at C—2 of the furans and thiophenes can readily be substituted by a wide variety of nucleophiles (92JPR3II). This reaction sequence represents a preparatively useful method for the selective introduction of biologically relevant substituents into the C—2 position of 3-trifluoro-methyl-substituted furans and thiophenes (Scheme 87). 

The reaction of thioenol aryl ethers with 1,3-diketones mediated by Ag2C03 on Celite leads to a facile construction of medium- and large-sized ring-substituted furans (Equation 36) <20000L1387>. This method has been exploited in syntheses of dibenzofurans, coumestans, and 4-pyrones. 

The addition of vinyl and aryl Grignard reagents to propargyl alcohols followed by reaction with a nitrile provides access to furans and butenolides in a one-pot procedure. These reactions are believed to involve a magnesium-chelate intermediate. Highly substituted furans can be prepared with control over the substitution pattern by the judicious choice of substrates and reagents (Scheme 26) <2000TL17>. 

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