Synthesis of furans

Furfural and thence, by vapour phase decarbonylation, furan are available in bulk and represent the starting points for many furan syntheses. The aldehyde is manufactured from xylose, obtained in turn from pentosans, which are polysaccharides extracted from many plants, e.g. com cobs and rice husks. Acid catalyses the overall loss of three moles of water in very good yield. The precise order of events in the multistep process is not known for certain, however a reasonable sequence is shown. Comparable dehydrative ring closure of fructose produces 5-hydroxymethylfurfural. 

Many routes to furans have been described, but the majority are variants on the first general method - the dehydrating ring closure of a 1,4-dicarbonyl substrate. 

4-Dicarbonyl compounds can be dehydrated, with acids, to form furans. 

The most widely used approach to furans is the cyclising dehydration of 1,4-dicarbonyl compounds, which provide all of the carbon atoms and the oxygen necessary for the nucleus. Usually, non-aqueous acidic conditions are employed to encourage the loss of water. The process involves addition of the 

Access to a 1,4-dicarbonyl substrate has been realised in several ways alkylation of imines with 2-alkoxy-allyl halides (equivalents of 2-haloketones), addition of P-ketoester anions to nitroalkenes, followed by Nef reaction, and rhodium-catalysed carbonylation of 2-substituted acrolein acetals are just three routes by which such precursors can be obtained. The dialdehyde (as a mono-acetal) necessary for a synthesis of diethyl furan-3,4-dicarboxylate was obtained by two successive Claisen condensations between diethyl succinate and ethyl formate. 

More controlled processes can be carried out using milder catalysts such as indium(in) chloride when enantiopure furan alcohols can be obtained.  

Reagents and conditions ) DIC, DMAP, DMF ii) 188, benzene, 60°C iii) TsNj, EtjN, CHjClj, 18h 

Resin-bound diazoimides 190 were subsequently reacted with different electron deficient acetylenes 191 in benzene at 80°C for 2 hours in the presence of Rh2(OAc)4 as a catalyst. Analysis of the crude products showed exclusively the presence of the desired furans 192 and excess unreacted acetylene, which, when sufficiently volatile (e.g propiolate esters), were eliminated in vacuo to provide furans of high purity. To avoid contamination of the desired furan product with residual, non-volatile acetylene, a two step sequence was implemented for the cycloaddition reaction. Thus, C-labelled diazoimide 193 was allowed to react with a large excess (10 eq) of dimethyl acetylenedicarboxylate (DMAD) 194 in the presence of Rhj(OAc)4 at room temperature in anticipation of trapping the bicyclic intermediate 196 on the polymeric support. After washing the 

The stepwise (room temperature/thermal) cycloreversion sequence failed to provide furans from acetylene derivatives activated by just a single electron withdrawing moiety (e.g. propiolate esters). These derivatives, less reactive than DMAD, did not undergo cycloadditions to the immobilised dipoles at an appreciable rate at room temperature. 

To further illustrate the utility of this solid-phase synthesis, a small (32 member) combinatorial library of furans was generated via split synthesis by using the stepwise cycloaddition sequence. From eight carboxylic acids, two malonyl chlorides and two acetylenes, a library of four pools comprising eight compounds each was synthesised. 

Diarylnitrilimine on cyclocondensation with alkynes and disubstitued alkenes gave the corresponding pyrazoles when irradiated with microwaves. The 

---

The parallel synthesis of furans from a-hydroxycarbonyl compounds is frequently conducted using aldoses or ketoses as readily available sources of this functional grouping, especially as the resulting polyhydroxyalkyl side-chain can be removed easily by oxidative degradation (Schemes 67d and 67e) 56MI30300). 

Fischer-type carbene complexes in the synthesis of furan, pyrrole, 5//-furanone, and 5//-pyrrolone derivatives 98YGK413. 

Scheme 12 Synthesis of furans via reductive Paal-Knorr reaction...

The approach also allows the synthesis of furans by employing ethoxymethylene malonate, followed by an eliminative decarboxylation. This method was used by Balme for a formal synthesis of the antitumor lignan burseran (6/1-294), starting from 6/1-290,6/1-291 and 6/1-292 via the furan 6/1-293 (Scheme 6/1.78) [139], Furans as 6/1-298 can also be obtained by Pd-catalyzed reaction of 2-propynyl-l,3-dicarbonyls 6/1-295 with aryl halides 6/1-296 in DMF, using potassium carbonate as base, as shown by Arcadi, Cacchi and coworkers (Scheme 6/1.79) [140]. 

Yosikoshi reported the synthesis of furan derivatives by the reaction of 1,3-diketones with nitroalkenes, in which the Michael addition of the anions of 1,3-diketones and the subsequent intramolecular displacement of the nitro group by enolate oxygen are involved as key steps (Eq. 7.40).42... 

The reaction can also be used for synthesis of furans by a [2 + 3]annelation. Example ... 

Table 9.41 Synthesis of furans from acyl chlorides and allenylsilanes.

Dibromo-1-(phenylsulfonyl)-1-propene as a Versatile Reagent for the Synthesis of Furans and Cyclopentenones. 

In an extension of traditional Stetter methodology, Miiller and co-workers have used the Stetter reaction in a one-pot multicomponent reaction for the synthesis of furans and pyrroles (Scheme 19) [85,86], The ot,P-unsaturated ketone XXVI is formed in situ and undergoes a Stetter reaction followed by a Paal-Knorr condensation. 

A great deal of work has been reported on the synthesis of furans, benzofurans, and related compounds. For the sake of clarity, the subject matter covered in this section has been divided into four parts that are based on different synthetic approaches as presented in Section II.A. 

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... 

Marcaccini S, Pepino R, Marcos CF, Polo C, Torroba T (2000) Studies on isocyanides and related compounds. Synthesis of furan derivatives and their transformation into indole derivatives. J Heterocycl Chem 37 1501-1503... 

FIGURE 4.10 Synthesis of furan resins from furfuryl alcohol. 

Diketones can be used as the common precursor for the synthesis of furan, pyrrole, and thiophenes. The treatment of 1,4-diketones with aryl amines under similar conditions results in the formation of the corresponding pyrrole derivatives. 

Table 7 Synthesis of furan, pyrrole, and thiophene derivatives...

Gowravaram and Gallop (169) adapted the rhodium-catalyzed generation of isomiinchnones from diazo imides to the solid-phase synthesis of furans, following a 1,3-dipolar cycloaddition reaction with alkynes. A variety of furans were prepared in this fashion. With unsymmetrical electron-deficient alkynes (e.g., methyl... 

The synthesis of furan-(thiophene-, benzo[b]thiophene-)bridged macrocycles of 4,4 -bipyri-dine was reported <99T4709>. 

Azetidin-2-ones have found application in a synthesis of furan derivatives (82JCS(P1)257). Condensation of 4-methyl-l-phenylazetidin-2-one (156) with cyclohexanone afforded 3-cyclohexylidene-4-methyl-l-phenylazetidin-2-one (157). Treatment of (157) with lithium... 

The preceding sections described the newer methods for the synthesis of furan and its derivatives. This section snmmariy.es the best practical methods for the synthesis of the parent furan and benzofuran ring structures and their substituted derivatives. It is from furfural that furan itself is prepared industrially by the catalytic decarbonylation in steam. 

---