Oxidative coupling furans

The oxidative coupling of thiophene, furan[338] and pyrrole[339,340] is also possible. The following order of reactivity was observed in the coupling of substituted furans[338] R = H > Me > CHO > CO Me > CH(OAc)i > CO2H. The cross-coupling of furans and thiophenes with arene is possible, and 4-phenylfurfural (397) is the main product of the cross-coupling of furfural and benzene[341]. 

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. 

Racemic yatein 43 was obtained by Michael addition of the anion of piperonaldehyde dithiomethyl acetal to 5/7-furan-2-one (butenolide), followed by trapping of the resulting enolate with 3,4,5-trimethoxybenzyl bromide (see section 3.2.2). This process gave 43 with the desired trans stereochemistry at the butyrolactone. Oxidative coupling of the two... 

As can be seen in the scheme below, a series of substituted 2-(2-aminothiazol-4-yl)-benzo[ ]furans with inhibitory activity for leukotriene B4 were made from benzofurans via acylation, followed by Hantzsch thiazole formation <070BC3083>. 2-Substituted benzo[ ]furans could also be generated via an aerobic oxidative coupling of 2-unsubstituted benzo[ ]furans with arenes through the palladium-catalyzed double C-H activation <07OL3137>. In addition, 2,3-diarylbenzo h I uran could be constructed by a palladium-catalyzed arylation of benzo[6]furan with an aryl chloride in the presence of a bulky, and electron-rich phosphine <07OL1449>. 

A series of dibenzofuran-l,4-diones illustrated in the following scheme were constructed via a DDQ-mediated intramolecular oxidative cyclization of quinone-arenols <070L2807>. Dibenzo[b] furans were also found to be made from 2//-pyran-2-ones and 6,7-dihydro-577-benzo[Z>]furan-4-one <07T1610>. The asymmetric synthesis of chiral furo-fused BINOL derivatives was achieved via copper(II)-mediated oxidative coupling from naphthofuranol in the presence of chiral phenylethylamine <07TL317>. 

The stmcturally interesting bis(benzo[4,5]-furo)[2,3-< 3, 2 -g][l,2,3,4]tetrathiocine was obtained by an oxidative coupling reaction of 2-lithiated benzo[/)]furan with elemental sulfur (Equation 80) <2002JOC6220>. 

Scheme 7.2 The active site for the oxidative coupling of acetylene to furan over UO. The unit bulk structure of P-UO contains five U atoms (three are sixfold coordinated) only one is represented in the scheme for simplicity. U atoms can accommodate up to eight hgands and the adsorption of two acetylene molecules can occur on a single sixfold coordinated U atom. Oxidative coupling proceeds with the following reaction stoichiometry 2C2H2-rU03 C H O-rUO. The square indicates an O vacancy. The out-of-plane oxygen (represented by O) is incorporated into the C. intermediate to form furan...

The first furan-isoannelated [14]annulene was prepared by Y.-H. Lai et al. The furan moiety was installed by the Paai-Knorr furan synthesis. The 1,4-diketone substrate was synthesized via an oxidative coupling using Mn02/AcOH. The dehydration to the furan was effected by phosphorous pentoxide in ethanol. 

C.S. Cooper and co-workers synthesized several quinolones containing five- and six-membered heterocyclic substituents at the 7-position and tested their antibacterial activities. The 1,4-diketone substrate was prepared via the oxidative coupling of isopropenyl acetate and an acetophenone derivative. The Paai-Knorr furan synthesis was conducted in the presence of p-TsOH. 

Oxidative coupling of furanes with quinones. Furanes do not react with mtphlhoquinone under usual conditions. However, Bridson and co-workers1 have effected this addition in the presence of a high-potential quinone to oxidize the Initial adduct to a 2-fury 1-1,4-naphthoquinone and displace the equilibrium. The reliction with 2-methoxyfurane is particularly interesting because the adduct can be Converted to a naphthacenequinone (equation I). 

A small amount of bisthiophene was isolated when thiophene was treated with Pd(OAc), [35]. The oxidative couplings of a thiophene with thiophene, furan, or substituted arenes were achieved in poor to moderate yields using PdfOAc), in HOAc [36-38]. The oxidative couplings of thiophene or benzo[Z ]thiophene with olefins also suffer from inefficiency [39]. 

Intramolecular Diels-Alder reactions of furan derivatives 86YGK109. Oxidative coupling of furans under the action of transition metal catalysts ... 

An efficient manganese(III)-mediated oxidative coupling reaction between a-aryl enamides and 1,3-dicarbonyl compounds was developed, giving a series of dihydrofurans and dicarbonyl enamides in moderate-to-good yields. Moreover, these dihydrofurans could be readily transformed into the corresponding furans and pyrroles via the Paal—Knorr reaction (140L5992). 

The arene substrates are not limited to simple benzene derivatives. A variety of het-eroarenes can also participate in alkene arylations to generate the desired coupling products. Stoichiometric oxidative coupling of aromatic heterocycles such as furan, thiophene, selenophene, A-methylpyrrole, benzofiiran and benzothiophene with a variety of alkenes, including acrylonitrile, styrene and methyl acrylate, have been extensively studied by Fu-jiwara and coworkers [8]. Furan, thiophene, selenophene and A-methylpyrrole are easily alkenylated with alkenes to give 2-alkenylated and 2,5-dialkenylated heterocycles in relatively low yields (3 6%) [8a], while the reactions of benzofuran and benzothiophene with alkenes produced a mixture of 2- and 3-alkenylated products [8b]. 

The palladium(II)-catalysed alkenylation of heterocycles has also been studied extensively. Fujiwara and coworkers [8b, 26] reported that the reactions of furan and thiophene with alkenes such as methyl acrylate and acrylonitrile in the presence of 2 mol% Pd(OAc)2 and 2 equiv of Cu(OAc)2 under atmospheric oxygen or air produced both 2-alkenylated and 2,5-dialkenylated products. This method, however, was not particularly synthetically useful due to the low yields of the reactions (0.3-39%). Tsuji and Nagashima [21] also observed that furans 31a-c reacted with acrylates 4b and 4c to produce monoalkenylated compounds 32a-c, where the furan has been functionalized solely at the 2-position (or the 5-position if the 2-position is substituted) in moderate to good yields. Even a furan with an electron-withdrawing substituent (2-furaldehyde, 31c) participated in the oxidative coupling to yield a moderate 34% yield of the arylation... 

The catalytic oxidative coupling of furans with acrylonitrile to yield 2-alkenenitriles proceeds in good yield. ... 

The structure of grayanic acid (351) has been confirmed by synthesis 101). It co-occurs with the ring-opened diphenyl ether congrayanic acid (352) in the lichen Gymnoderma melacarpum 47). Interestingly the dibenzo-furan melacarpic acid (353), a product of carbon-carbon oxidative coupling, also occurs in this lichen. 

An oxidative coupling between indoles and allylic alcohols was developed (eq 157). The palladium-catalyzed reaction used O2 as the oxidant and was amenable to both primary and secondary alcohols to give the corresponding /3-aldehydes or ketones. Thiophene and furan could also react to form the corresponding alkylated products. 

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