Substituted furan synthesis

As can be seen in the scheme below, the catalytic activity of gold species was also shown in a multi-substituted furan synthesis. Cyclization of allenones in the presence of Au(III)-porphyrin gave rise to the corresponding substituted furan in good to high yields. The catalyst can be recycled several times and still maintain the same catalytic activity <06OL325>. 

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 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]. 

An efficient and atom-economical Au-catalyzed poly substituted furan synthesis was reported <04JA11164>. As can be seen, Au-catalyzed cyclization of 2-(l-alkynyl)-2-alken-l-ones in the presence of MeOH as a nucleophile afforded 2,3,5-trisubstituted furans with high regioselectivity and high yields. A variety of alcohols, 1,3-diketones, some indoles, and amines can serve as nucleophiles. 

Another cycloaddition, in which this time the silyl enol ether functions as a dienophile, is the SnCl4-catalysed addition of butadiene to (180 R = Me) giving (181). If R = H in the starting material a 4 + 3 reaction takes place, producing the seven-membered ring (182). Flash-vacuum thermolysis of P-keto-trimethylsilyl enol ethers has been used in a substituted furan synthesis, and the same process has been used to prepare a-allenic acids (183) from siloxy-dienes. ... 

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. ... 

The add-catalyzed cyclodehydration of (Z)- and ( )-6-hydroxy-a,p-unsaturared ketones offers a mild synthesis of substituted furans. In the case of ( )-olefins, photochemical isomerisation was found to accelerate the reaction <96TL6065>. Reaction of alkynyl(phenyl)iodonium tetrafluoroborates with tropolone in the presence of a base yields 2-substituted furotropones (Scheme 16, <96TL5539>). 

An intramolecular radical cyclization gives the cxo-cyclic compounds, which has been extensively used in the synthesis of cyclic compounds. Michael additions of allyl alcohols or propargy 1 alcohols to nitroalkenes and the subsequent treatment with tin radicals provide a useful method for the preparation of substituted furans (Eqs. 7.83 and 7.84).126... 

Finally, Scharf and Wolters report a method said to be superior to both the Paal-Knorr synthesis (starting materials more easily accessible) and the Feist-Benary synthesis (freer choice for 3-substituent). Thermal rearrangement-elimination by alkylated dioxolanes at 230 C gives alkyl substituted furans. Yields can be nearly quantitive since the only serious by-products also give the furans under proton-catalyzed thermolysis (Scheme 25).124 Photochemical methods are outlined in Section VII. 

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... 

Negishi coupling of 2-furylzinc chloride with vinyl telluride provided 2-substituted furan with (Z)-double bond in a stereoselective manner, which was used in the total synthesis of l-(Z)-atractylodinol, a biologically active natural product as depicted in the following scheme <06TL8183>... 

These cycloadducts, at their most elementary level, are excellent intermediates for the synthesis of 3-substituted furan derivatives. For example, Kawanisi and coworkers reported a synthesis of perillaketone 174 in which the critical step was a Paterno-BUchi photocycloaddition between furan and 4-methylpentanal in the presence of methanesul-fonic acid (Scheme 39)82. This reaction furnished two initial photoadducts, 172 and 173. The unexpected product 173 presumably arises from a Norrish Type II cleavage of 4-methylpentanal to give acetaldehyde, and subsequent cycloaddition with furan. The desired cycloadduct 172 was then converted uneventfully to 174 via acid-catalyzed aromatization and oxidation. 

Cycloaddition reactions of furans are still widely used as key steps in the construction of complex molecules including natural products. As an example, the intramolecular Diels-Alder cycloaddition of 2-amido substituted furans provides a useful tool for the synthesis of fused, nitrogen-containing poly-heterocycles. Thus, thermolysis of 3-substituted amidofuran produces tricyclic indolinone 39 as a 2 1 mixture of diastereomers via amidofuran cycloaddition-rearrangement methodology, which serves as a key intermediate in the total synthesis of ( )-dendrobine, a major component of the Chinese ornamental orchid Dendrobium nobile . 

The cycloaddition-isomerization strategy has also been applied to the synthesis of hydrindanone. Thus, by using a modified Kanematsu s procedure, the keto aldehyde 40, a hydrindanone of the steroid C-D ring type, can be synthesized from a substituted furan via a cycloaddition-isomerization procedure and is followed by subsequent transformations . 

Substituted furan formation by an indirect cyclization of 1,4-dicarbonyl derivatives has also been adopted as a key step in the synthesis of 3-oxa-guaianolides. Although 1,4-dicarbonyl compounds have been traditionally considered as the direct precursors for furans, treatment of 1,4-dicarbonyl compounds having a tertiary acetoxy group with p-toluenesulfonic acid leads to only 11% yield of an alkenylfurans as derived from a cyclization/acetoxy-elimination route. The following scheme shows an alternative multi-step conversion of the 1,4-dicarbonyl that leads to a more acceptable yield of the acetoxyfuran . 

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 photoinduced-addition of alcohols to cycloalkenones has been investigated by Fraser-Reid and co-workers,4 by Paquette,5 and was used as the key step in the synthesis of the prostaglandin endoperoxide analogue (15S)-hydroxy-9a,11a-epoxymethanoprosta-(52,13E)-dienoic acid,6 and for the recent synthesis of 2, 3 -dideoxy-3 -hydroxymethyl-5 -carbanucleosides.7 No work (other than our own) has been reported on the photoinduced-addition of alcohols to 5-substituted furan-2(5H)-ones. 

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. 

Scheme 1 Synthesis of trihydroxyalkyl-substituted furans derivatives 3 or 4 from D-pentose and C-furyl glycosides 5 or 6 from D-hexoses...

The preparation of 5-arylfurfurals (and arylthiophene-2-carboxaldehydes) via Pd-catalyzed C-C bond formation in aqueous media was carried out <990L965>. Full details have been reported for the Pd-catalyzed cycloisomerization of (Z)-2-en-4-yn-l-ols (a facile synthesis of a variety of substituted furans) <99JOC7687>... 

Keto esters such as acetoacetate without a substituent at the a-carbon. namely with two acidic protons, first attack the central carbon of the allenylpal-ladium to form the zr-allyl complex 89. Then intramolecular attack of the enolate oxygen of the 0-keto ester at the rr-ully l system takes place to form the nieihv-lenedihydrofuran 90 as a primary product, which is easily isomerized to the turn 91. The /3-diketone 92 reacts similarly to give the furan 93[40], The reaction can be applied to the synthesis of the phenyIthiomethyl-substituted furan 94. which is useful for the synthesis of natural products such as neoliacine. [41]... 

Substituted furan can be prepared by using the Feist-Binary synthesis, which is similar to the Hantszch synthesis of the pyrrole ring. In this reaction, a-haloketones react with 1,3-dicarbonyl compounds in the presence of pyridine to yield substituted furan. 

A related synthesis of highly substituted furans was reported by Schmalz and Zhang from cyclopropyl alkynyl ketones. The reaction scope included a great variety of nucleophiles such as several alcohols, indole or even acetic acid [140]. 

The development of intramolecular Diels-Alder (IMDA) reactions for the synthesis of natural products (80CR63) and the facility with which substituted furans can be assembled have been reviewed 840R(32)1, 86CRV795, 87CSR187, 90SL186). Thus, IMDA product from the propargyl sulfone shown in Scheme 43 proceeds via the allene and was converted subsequently into the benzenoid sulfone under base catalysis (92CC735). 

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