Furans syntheses with

Several modifications of the Feist-Benary furan synthesis have been reported and fall into two general classes 1) reactions that yield furan products 2) reactions that yield dihydrofuran products. One variant that furnishes dihydrofiirans uses substrates identical to the traditional Feist-Benary furan synthesis with a slight modification of the reaction conditions. The other transformations covered in this section involve the combination of P-dicarbonyls with reagents that are not simple a-halocarbonyls. Several reactions incorporate a-halocarbonyl derivatives while others rely on completely different compounds. 

Scheme 6 Furan synthesis with subsequent hydrogenation of the side-chain double bond.

FEIST - SENARY Furan Synthesis Synthesis ol lurans by condensation ol an a-halocarbonyl compound with an enol. 

The Feist-Benary furan synthesis occurs when an a-halocarbonyl (1) reacts with a P-dicarbonyl (2) in the presence of a base. The resulting product (3) is a 3-furoate that incorporates substituents present in the two starting materials. ... 

Chatteijea showed that cyclic ot-halocarbonyls are acceptable substrates for the Feist-Benary furan synthesis by combining 1-chlorocyclohexanone (34) with 1,3-cyclohexanedione (30) to yield octahydrodibenzofuran 35. ... 

The final variation of the Feist-Benary furan synthesis encompasses reactions of 1,3-dicarbonyls with 1,2-dibromoethyl acetate (52). For example, treatment of ethyl acetoacetate (9) with sodium hydride followed by addition of 52 at 50°C yields dihydrofuran 53. The product can be easily converted into the corresponding 2-methyl-3-furoate upon acid catalyzed elimination of the acetate, thus providing another strategy for the synthesis of 2,3-disubstituted furans. 

Treatment of 1,4-dicarbonyls (1) with catalytic acid yields substituted furans (2) and is called the Paal-Knorr furan synthesis. This method is used extensively to produce a variety of mono-, di-, tri-, and tetrasubstituted furans. ... 

As depicted in the following scheme, in the presence of sodium iodate and pyridine, several 5,6-dihydroxylated benzofuran derivatives were synthesized via an oxidation-Michael addition of P-dicarbonyl compounds to catechols in a one-pot procedure <06TL2615 06JHC1673>. A novel additive Pummerer reaction of 2-benzo[fc]furan sulfilimines with carbon nucleophiles derived from P-dicarbonyl compounds was also employed to the synthesis of 2,3-disubstituted benzo[b]furans <06TL595>. 

Zamojski and coworkers have explored the use of the furan-carbonyl photocycloaddition in asymmetric synthesis, with somewhat limited success88. Irradiation of chiral glyoxylate derivative 196 [R = (R)(—)-menthyl and (R)(—)-8-phenylmenthyl] afforded... 

The most unique feature of furan synthesis using palladium chemistry is heteroannulation. Enones, ynones and ynols all have been annulated into furans and benzofurans. More importantly, trapping the reactive Pd(II) intermediates at different stages with electrophiles offers unique opportunities to synthesize substituted furans and benzofurans. 

The reaction appears to be general and the additions are regiospecific and stereoselective. The product from the reaction with 2-propanol has been used for the synthesis of cis-chrysanthemic acid,8 and the product with methanol has been used for the construction of novel 2, 3 -dideoxy-3 -hydroxymethylnucleosides.9 In addition, ethane-1,2-diol provides the expected photoadduct as a 1 1 mixture of the two possible diastereoisomers, and these can be easily separated as their acetonides, to provide compounds with three contiguous chiral centers emanating from furan-ones with only one chiral center.9 More recently, we have shown that photoinduced-... 

One of the earliest uses for rhodium(II)-catalyzed dipoles was demonstrated in Davies furan synthesis [22]. Isomiinchnones were also shown to produce substituted furans [115]. Additional furan syntheses have been described using silylacetates [116], unsaturated esters [117], and fluoroalkyl diazo acetates [118]. The synthesis of furofuranones and indenofuranones 35 from a-diazo ketones having pendant alkynes has also been reported (Eq. 6) [119]. Other fused heterocyclic systems include furo[3,4-c]furans [120, 121] furo[2,3-b]furans [122] as well as thiobenzofurans [123], and benzoxazoles[124] have also been synthesized with this methodology. 

Racemic analogs of showdomycin have been synthesized from adducts (352 and 353) of methyl 2-nitroacrylate with furan. Synthesis of DL-2-ept-showdomycin involved treatment of the adducts with m-chloroperoxybenzoic acid, followed by nitrous acid elimination, to give the alkenic epoxide 379. Opening of the oxirane ring, and a sub-... 

Pyrroles and furans also undergo the Gattermann aldehyde synthesis with HC1 and HCN, furan gives furfuraldehyde and 2-methylindole gives 2-methylindole-3-carboxaldehyde. The Houben-Hoesch ketone synthesis is also applicable to the preparation of acyl derivatives of furans and pyrroles, e.g. ethyl 2,4-dimethylpyrrole-3-carboxylate with MeCN and HC1 yields (81). 

A novel synthesis of the sesquiterpene ( )-cinnamodial (148) utilizes the furan ring as a latent 1,4-dialdehyde synthon (81JA3226). The triol (141) was thus oxidized to the ketofuran (142). Oxidation of the furan moiety with lead tetraacetate afforded a 90% yield of epimeric diacetates (143) which when exposed briefly to DBU gave dienone (144). Epoxidation of (144) and exposure of the epoxide (145) to p-toluenesulfonic acid gave the bis-acetal (146). Reduction of this intermediate to a diol and hydrolysis of the bis-acetal furnished dialdehyde (147). Acetylation of the secondary hydroxyl group completed the synthesis of cinnamodial (Scheme 32). 

Among the more recent examples of furan synthesis is the cyclization of the unsaturated 1,4-diketone (9) in acetic anhydride to afford 3-acetoxy-2,4,5-triphenylfuran (10). Treatment of l,2,3,4-tetrapheny but-2-ene-l,4-dione (PhCOCPh==CPhCOPh) with triethyl phosphite yields 2,3,4,5-tetraphenylfuran (79JOC494). 1,2-Diaroylethylenes have been converted to 2,5-diarylfurans with tin(II) chloride and hydrochloric acid (62ZOB1195). 

The method described has some features in common with the well-known, but apparently little-used, Feist-Benary furan synthesis,1 which uses an a-haloketone in place of the sulfonium salt. Acetylenic bromides suitable for preparing the sulfonium salts are readily available by well-documented procedures involving acetylenic organometallic compounds. 

A six-step synthesis of hexahydrofuro[3,2-3]oxepin-2(3/7)-one involves cyclization with the formation of an ethereal C-0 bond (Scheme 13). However, its specific peculiarities are that the product skeleton is built from tetrahydrofuran (THF) and furan, the key reactions being the oxidation of a furan ring with singlet oxygen, followed by an intramolecular Michael addition to 2(5/7)-furanone C=C bond <2003TL4467, 2004TL5207>. 

A phenolic oxygen participates in facile oxypalladation. 2-Allylphenol (55) undergoes clean cyclization to 2H-l-benzopyran (56) in DMSO under air with a catalytic amount of Pd(OAc)2 without a reoxidant. 2-Methylbenzofuran (57) is obtained when PdCl2 is used [50]. But different chemoselectivity with the Pd(II) salts was also reported [51]. Catalytic asymmetric cyclization of the tetrasubstituted 2-allylic phenol 58 using the binaphthyl-type chiral ligand 60, called (.S, .S )-ip-borax, afforded the furan 59 with 96% ee. Use of Pd(CF3 002)2 as a catalyst is essential in the presence of benzoquinone [52]. Formation of the benzofuran 62 from 61 has been utilized in the synthesis of aklavinione [53]. The intramolecular reaction of 2-hydroxychalcone (63) produces the flavone 64 [54]. 

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