Applications furan syntheses

The palladium-catalyzed arylation of alkenes by haloarenes, and applications in furan synthesis have been described earlier (see Eq. 14 in Section IV,B, 1). By employing o-aminoiodoarenes and appropriately substituted (Z)-alkenes it has proved possible to develop an efficient synthetic route to quinolin-2-ones (Scheme 140).213... 

The isorniinchnone cyclization/isocyanate cycloreversion process for substituted furan synthesis has been well studied, as exemplified by the conversion of 104 to 106 (Scheme 19.19). In a solid-phase adaptation of this transformation, two groups independently utilized this reaction to estabhsh a traceless self-cleaving method for the synthesis of substituted furans [176, 177]. Further investigation of the thermal requirements of this cycloreversion led to its application in the split-pool synthesis of a small library of amides [178]. 

B-74MI31200 A. Williams Furans, Synthesis and Applications , Noyes Data Corporation,... 

The widely applicable acid-catalyzed cyclization of 1,4-dicarbonyl compounds and their surrogates, known as the Paal-Knorr furan synthesis, is frequently used in the synthesis of furan-containing compounds (Equation 1). 

A. Williams, Furans, Synthesis and Applications, pp. 1-303. Noyes Data Corp., London, 1973. 

Similar oxidants can be used as above for the preparation of open-chain compounds. The addition of singlet oxygen to the furan ring has found wide application in synthesis (Scheme 7). 

Obviously, the majority of the efficient methods for fluorinated furans synthesis has been described over the last 20 years. The development of modem fluorinating agents, organometallic chemistry, and homogeneous catalysis provided new possibilities for the preparation of flnoro- and perfluoroalkylfurans, which find then-application in pharmacology, agriculture, and material science. 

Therapeutics. Compounds containing the furan or tetrahydrofuran ring are biologically active and are present in a number of pharmaceutical products. Eurfurjdamine [617-89-0] is an intermediate in the diuretic, furosemide. Tetrahydrofurfurylamine [4795-29-3] may also have pharmaceutical applications. 5-(E)imethyiaininomethyi)furfuryi alcohol [15433-79-17 is an intermediate in the preparation of ranitidine, which is used for treating ulcers. 2-Acet5dfuran [1192-62-7] prepared from acetic anhydride and furan is an intermediate in the synthesis of cefuroxime, a penicillin derivative. 2-Euroic acid is prepared by the oxidation of furfural. Both furoic acid [88-14-2] and furoyl chloride [527-69-5] are used as pharmaceutical intermediates. 

Benzo[b]furan, 2-alkyl-2,3-dihydro-synthesis, 4, 680 Benzo[b]furan, 2-amino-synthesis, 4, 710 Benzo[b]furan, 3-amino-tautomerism, 4, 38 Benzo[b]furan, 2-amino-2,3-dihydro-applications, 4, 708... 

Benzo[b]furan, 2,3-dihydro-2-phenyl-synthesis, 4, 697 Benzo[b]furan, 2,3-dihydroxy-tautomerism, 4, 37 Benzo[6]furan, 4,6-dimethoxy-acylation, 4, 606 Benzo[6]furan, 2,3-dimethyl-acetylation, 4, 606 bromination, 4, 605 photooxygenation, 4, 642 Benzo[b]furan, 5,6-dimethyl-2,3-diphenyl-applications, 4, 709 Benzo[b]furan, 1,3-diphenyl-vertical ionization potential, 4, 587 Benzo[b]furan, 2-ethoxy-5-hydroxy-synthesis, 4, 127... 

Synthesis of multisubstituted furan rings using silyl protection 99CSR209. Synthetic applications of furan Diels-Alder chemistry 97T14179. Transformation of furans to N-heterocycles by aza-Achmatovicz reaction 98SL105. 

Diels-Alder reaction of the furan derivative 148 with homochiral bicyclic enone 149 is the key step [56] in the total synthesis of the diterpenes jatropho-lone A and B, 151 and 152, respectively, isolated from Jatropha gossypiifolia L [57], Initial efforts to carry out the cycloaddition between 148 and 149 under thermal or Lewis-acid conditions failed due to diene instability. Application of 5kbar of pressure to a neat 1 1 mixture of diene and dienophile afforded crystalline 150 with the desired regiochemistry (Scheme 5.23). Subsequent aromatization, introduction of the methylene group, oxidation and methylation afforded (-l-)-jatropholones 151 and 152. 

Wong HNC Regiospecific Synthesis of Polysubstituted Furans and Their Application in Organic Synthesis Pure Appl. Chem. 1996 68 335 344... 

Ring-closing reactions promoted by mercuric salts are valuable transformations which find an increasing use in the total synthesis of various natural products.130-140 Several examples of solvomercurations demonstrating the applicability of these transformations to the synthesis of natural product precursors are presented in Table 2. Piperidines (entry a), 141 pyrans (entries b-d), 142-144 and furans (entries e, f)14S>146 have been obtained in good yields and diastereoselectivity. These derivatives serve as starting materials for various natural products and can be demercu-rated under reducing conditions.147... 

Pure xylan is not employed in industry. but crude xylan or pentosans are of industrial importance. Xylan has been proposed as a textile size but is not employed as yet for this purpose.130 Perhaps the largest use of pentosans is in their conversion to furfural, which has many applications and serves as the source of other furan derivatives. At the present time, large quantities of furfural are used in the extractive purification of petroleum products, and recently a large plant has been constructed to convert furfural by a series of reactions to adipic acid and hexamethylene-diamine, basic ingredients in the synthesis of nylon. In commercial furfural manufacture, rough ground corn cobs are subjected to steam distillation in the presence of hydrochloric acid. As mentioned above, direct preferential hydrolysis of the pentosan in cobs or other pentosan-bearing products could be used for the commercial manufacture of D-xylose. 

Challenging applications in the field of macrocyclic furans have been investigated. The major synthetic advantage is the cyclization to the furan after the macro-cyclization. This will avoid a problematic ring closure to macrocycles (to 1,3-furano-phanes) with a furan substrate ( furan latest strategy ). Test substrates demonstrated the viability of this concept [50], as shown below for the synthesis of the [8]furano-phane 91 from the macrocyclic ketone 90 (Scheme 15.22) [39]. 

Oxidation of silyl enol ethers leading to carbon-carbon bond formation [85JCS(CC)420 87JCS(P1)559] finds an interesting application in the synthesis of furans. For example, l,4-di(3-thienyl)-l,4-butanedione (65), which... 

An elegant application of the [3 + 4] cycloaddition methodology was showcased in model studies directed toward the synthesis of the core skeleton of CP-263114 115 (Scheme 14.12) [103]. The key step is the intramolecular [3 + 4] cycloaddition of furan with the siloxy-substituted vinyldiazoacetate in 112. The oxabicychc system 113 was obtained in 68% yield and was converted in eight steps to furnish the core structure 114 [103]. 

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). 

Two approaches, based on furan, have found wide application in carbohydrate synthesis. Cycloaddition reactions of furan with 2-substituted acrylonitrile or acrolein lead to oxabicycloheptanes which, in tnm, can be transformed to monosaccharides. On the other hand, furfuryl alcohols can be converted—either by the Clauson-Kaas reaction or by mild oxidation—into 5,6-dihydro-4-pyrones, suitable for easy functionalization to sugars. 

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