2.3- Disubstituted furans synthesis

Cyclotrithiazyl chloride is also a useful reagent in organic chemistry in the fusion of 1,2,5-thiadiazoles to quinones as well as the synthesis of (a) isothiazoles from 2,5-disubstituted furans and (b) bis-1,2,5-thiadiazoles from A-alkylpyrroles (Scheme 8.4). Alkenes and alkynes react readily with (NSC1)3 to give 1,2,5-thiadiazoles, while 1,4-diphenyl-1,3-butadiene gives a variety of heterocyclic products including a bis(l, 2,5-thiadiazole). ... 

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. 

A multitude of 2,3,5-trisubstituted furans are available via the Paal-Knorr condensation. As with the synthesis of disubstituted furans, the scope of this version of the reaction is broad and includes incorporation of aryl, alkyl, ester, and phosphonate substituents. 

A eommon approaeh starts with a proteeted 1,4-diearbonyl and unmasks the requisite earbonyl using aeid, thus faeilitating the Paal-Knorr reaetion immediately upon deproteetion. For example, Nagai used sulfurie aeid to eonvert aeetal 77 into 2,4-disubstituted furan 78 albeit in low yield.Molander produeed a different 2,4-disubstituted furan by a similar strategy. Thioketal aeetal 79 was treated with mereury(II) ehloride and furnished furan 80 in 71% yield. Thus this strategy provides a useful approaeh for the synthesis of a variety of 2,4-disubsituted furans. 

Regiospecific synthesis of 3,4-disubstituted furans and thiophenes 97LA459. 

A convenient synthesis of 33 -difurans was presented. Treating alkynones with Pd(PPh3>4 (THF, EtaN) at room temperature gave 2,5-disubstituted furans, but under similar conditions with Pda2(PPh3)z by a tandem dimerization and cyclization 33 -difurans were obtained predominantly <99TL4841>. 

A flexible entry into 2,4-disubstituted furan derivatives through condensation of the sulfur ylide derived from 20 with aldehydes, Pd-catalyzed opening of the vinyl oxirane thus formed, and a final oxidative cyclization of the furan ring was reported. Its utility was exemplified by the first total synthesis of the marine natural product ircinin-4 (21) <99SL29>. 

Furans generally react with alkynic dienophiles under mild conditions affording oxanor-bornadienes in high yield (Scheme 59). The products have found a variety of uses in synthesis. The unsubstituted double bond may be hydrogenated and the product, on thermolysis, undergoes cycloreversion, thus providing a convenient synthesis of 3,4-disubstituted furans... 

Furan synthesis.1 The original synthesis of 3,4-disubstituted furans by Garst using dimethylsulfonium methylide (4, 196-197) can be improved by use of 1 under phase-transfer conditions. 

As shown below, allene derivatives have been adopted as starting materials in the synthesis of furans. Palladium(II)-catalyzed cyclization of a-allenic ketones afforded 2,3-disubstituted furans in good yields <07EJO2844>. The substituent at the a-position of a carbonyl group influences the reaction pathway. Cyclization products were provided when the substituent was a methyl group or a phenyl group, while dimerization products were produced when the substituent was a hydrogen atom. 

The oxidation of 2,5-disubstituted furans by NBS <20050L27> and singlet oxygen <20060L1945> was adopted for the synthesis of [5,5,5]- and [6,5,6]-bis(spiroketals). An interesting example is depicted in Scheme 18. 

The retro-Diels-Alder reaction is a valuable tool for the synthesis of heterocycles <2003COR1423>. The Diels-Alder/ retro-Diels-Alder reaction of oxazoles with acetylenedicarboxylates has been extensively applied for the synthesis of 3,4-disubstituted furans. In a total synthesis of the alkaloid colchicine, such a reaction has been carried out in an intramolecular mode to yield a [ ]-annulated furan, which served as a synthetic key intermediate (Equation 30) <2000T10175>. 

The first total synthesis of cristatic acid, a compound of considerable cytotoxic activity, was reported by A. Furstner et al." The disubstituted furan moiety was constructed by the Tsuji-Trost allylation of a vinyl epoxide intermediate by b/s(phenylsulfonyl)methane. The resulting 1,4-diol was obtained in an almost quantitative yield. 

Bisagni, E., Marquet, J. P., Andre-Louisfert, J., Cheutin, A., Feinte, F. 2,3-Disubstituted furans and pyrroies. i. Extension of the Feist-Benary reaction to P-diketones. New synthesis of 3-acyiated furans and pyrroies. Bull. Soc. Chim. Fr. 1967, 2796-2780. 

Ji, J., Lu, X. Facile synthesis of 2,5-disubstituted furans via palladium complex and perfluorinated resin sulfonic acid catalyzed isomerization-dehydration of alkynediols. J. Chem. Soc., Chem. Common. 1993, 764-765. 

An impressive alternate approach to the synthesis of furans beginning with alkynols was developed by Balme [160, 161] and subsequently applied in a total synthesis by Morimoto [162]. Balme discovered that a three-component coupling reaction between a propargylic alkoxide, a conjugate addition acceptor, and an unsaturated halide yields a variety of di- and trisubstituted furans. In one example, propargyl alcohol, diethyl ethoxymethylene malonate (193), and iodobenzene combine to furnish disubstituted furan 194 in... 

The early synthetic endeavors in this area focused mainly on the synthesis of various nonactic acid derivatives. The scenario utilized in almost all of these early studies involved the hydrogenation of a 2,5-disubstituted furan ring to give a cis-disubstituted tetrahydrofuran. 

A full paper describing the synthesis of 2,4-disubstituted furans in high yields through a novel oxidative cyclization-dimerization reaction between two different allenes was provided <05JOC6291>. 

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