Furans, with

The oxidative reaction of furan with bromine in methanol solution or an electrochemical process using sodium bromide produces 2,5-dimethoxy-2,5-dihydrofuran (19), which is a cycHc acetal of maleic dialdehyde. The double bond in (19) can be easily hydrogenated to produce the corresponding succindialdehyde derivative. Both products find appHcation in photography and as embalming materials, as well as other uses. 

Pyrrohdine [123-75-1] (tetrahydropyrrole) (19) is a water-soluble strong base with the usual properties of a secondary amine. An important synthesis of pyrrohdines is the reaction of reduced furans with excess amine or ammonia over an alumina catalyst in the vapor phase at 400°C. However, if labde substituents are present on the tetrahydrofurans, pyrroles may form (30). 

The chemical consequences of /3-protonation are illustrated further by the ring-opening reactions of furans with methanolic hydrogen chloride and of (V-substituted pyrroles with hydroxylamine hydrochloride (Scheme 11) (82CC800). 

Furan reacts vigorously with chlorine and bromine at room temperature to give poly-halogenated products. Low temperature (-40 °C) reaction of furan with chlorine in dichloromethane yields mainly 2-chlorofuran and reaction of furan with dioxane dibromide at 0 °C affords 2-bromofuran in good yield. 2-Iodofuran is obtained by treatment of 2-furoic acid with iodine and potassium iodide in aqueous sodium hydroxide. 

Competitive metallation experiments with IV-methylpyrrole and thiophene and with IV-methylindole and benzo[6]thiophene indicate that the sulfur-containing heterocycles react more rapidly with H-butyllithium in ether. The comparative reactivity of thiophene and furan with butyllithium depends on the metallation conditions. In hexane, furan reacts more rapidly than thiophene but in ether, in the presence of tetramethylethylenediamine (TMEDA), the order of reactivity is reversed (77JCS(P1)887). Competitive metallation experiments have established that dibenzofuran is more easily lithiated than dibenzothiophene, which in turn is more easily lithiated than A-ethylcarbazole. These compounds lose the proton bound to carbon 4 in dibenzofuran and dibenzothiophene and the equivalent proton (bound to carbon 1) in the carbazole (64JOM(2)304). 

Among the less widely exploited interconversion processes are those involving thermal reactions with ethyl azidoformate, which convert furan into A-ethoxycarbonyl-A -pyrrolin-2-one, and thiophenes into A-ethoxycarbonylpyrroles (Scheme 96a) (64TL2185). The boron trifluoride catalyzed reaction of l,3-diphenylbenzo[c]furan with A-sulfinylaniline results in the replacement of the oxygen by an iV-phenyl group (Scheme 96b) 63JOC2464). 

The unsaturated tetraoxaquaterene (accompanied by linear condensation products) was first synthesized in 18.5% yield by the acid-catalyzed condensation of furan with acetone in the absence of added lithium salts. Other ketones also condensed with furan to give analogous products in 6-12% yield.A corresponding macrocycle was also prepared in 9% yield from pyrrole and cyclohexanone. The macrocyclic ether products have also been obtained by condensation of short linear condensation products having 2, 3, or 4 furan rings with a carbonyl compound. ... 

Given the relatively rare appearance of oxetanes in natural products, the more powerful functionality of the Patemo-Biichi reaction is the ability to set the relative stereochemistry of multiple centers by cracking or otherwise derivitizing the oxetane ring. Schreiber noted that Patemo—Btlchi reactions of furans with aldehydes followed by acidic hydrolysis generated product 37, tantamount to a threo selective Aldol reaction. This process is referred to as photochemical Aldolization . Schreiber uses this selectivity to establish the absolute stereochemistry of the fused tetrahydrofuran core 44 of the natural product asteltoxin. ... 

The only known reaction of a furan with a dihalocarbene is that recently reported between benzofuran and dichlorocarbene in hexane at 0°. The initial adduct (7) could not be isolated but on hydrolysis gave the ring-expanded product 8, possibly via 9, in 15% yield. Benzothiophene was recovered in 92% yield under the same conditions. 2,5-Dihydrofuran reacted with dichloro- and dibromo-carbene to give the products of allylic insertion, 2-dihalogenomethyl-2,5-dihydrofuran, as well as the normal addition products. ... 

Angular annulation of benzo[h]furan with a benzene ring leads to naph-tho[2,l-h]furan and naphtho[l,2-h]furan. 

DinitrQ-ll-Qxatricyclo[6 2 1 0 undec-9-ene has been prepared by an intramolecular Diels-Alder reacdon of the furan with a idtroalkene group as shown in Eq 8 26 This tricyclic compound is a versatile synthedc tool for the preparadon of ergot alkaloids... 

Pyrrole, the simplest five-membered unsaturated heterocyclic amine, is obtained commercially by treatment of furan with ammonia over an alumina catalyst at 400 °C. Furan, the oxygen-containing analog of pyrrole, is obtained by acid-catalyzed dehydration of the five-carbon sugars found in oat hulls and... 

Diels-Alder cycloaddition of 3,4-bis(trifluoromethyl)furan with ethyl propynoate involved addition of two a,/3-unsaturated esters followed by acid-catalyzed ring opening, rearrangement, and elimination of ethanol to give a 6,7-bis(trifluoromethyl)isocoumarin-3-carboxylate [92JFC(56)359]. 

The results of these four groups of investigators present, at least for the present author, a bewildering and scarcely understandable diversity in the interactions of furan with arenediazonium ions. Where is the physical organic or theoretical chemist who will accept the challenge to unravel this entanglement It is not surprising to... 

Good yields and high diastereoselectivities were obtained by using zeolites in combination with Lewis-acid catalyst [21]. Table 4.7 illustrates some examples of Diels-Alder reactions of cyclopentadiene, cyclohexadiene and furan with methyl acrylate. Na-Y and Ce-Y zeolites gave excellent results for the cycloadditions of carbocyclic dienes, and combining these zeolites with anhydrous ZnBr2 further enhanced the endo diastereoselectivity of the reaction. An exception is the cycloaddition of furan that occurred considerably faster and with better yield, in comparison with the classic procedure [22], when performed in the presence of sole zeolites. 

Whereas maleic anhydride can react with furan (139a) at ambient pressure, citraconic anhydride (140) reacts only at high pressures due to the strong deactivating effect of the methyl group (Schemes 5.21 and 5.22). The two-step synthesis [53] of the palasonin (141), in an overall yield of 96 %, is a good example of the acceleration of the Diels-Alder by high pressure (Scheme 5.21). Previous synthesis [54] based on the thermal Diels-Alder reaction of furan with methoxy carbonyl maleic anhydride required 12 steps. 

Table 6.6 Diels-Alder reactions of furans with acrylates in water and dichloromethane under high pressure...

The reaction of furan with 2,5-dihydrothiophene-3,4-dicarboxylic anhydride is remarkable (Scheme 6.19). Furan is a poor diene and requires high pressure to affect cycloadditions [39]. On the other hand, high temperatures are forbidden because cycloaddition products derived from furan undergo cycloreversion under these conditions. In 5.0m LP-DE, the Diels-Alder reaction of furan with 2,5-dihydrothiophene-3,4-dicarboxylic anhydride proceeds at room temperature and atmospheric pressure in 9.5 h with 70 % yield and with the same diastereos-electivity found when the reaction is carried out under high pressure [40]. 

A review on fliran and its derivatives in the synthesis of other heterocycles was published <95CHE1034>. Furan decomposes on Pd(lll) at 300 K to form H, CO and CjH, which can dimerize to benzene at 350 K <96JA907>. Again, a considerable number of Diels-Alder reactions with furan and fiiran derivatives was reported. The synthesis of 2-pyridinyl-7-oxabicyclo[2.2.1]heptanes (e.g., 3, 4) was accomphshed via zinc chloride-mediated Diels-Alder reaction of furan with 2-vinylpyridines <96SL703>. 

Reactions of tc-excessive heteroaromatic compounds such as pyrroles, thiophenes and furans with carbenoids have been known for several years 6-10>u>. Recent activities were directed towards further synthetic applications of already known reactions, evaluation of the efficacy of novel catalysts and towards mechanistic insights. 

Furans and some of its derivatives have been cyclopropanated with the ketocarbenoids derived from ethyl diazoacetate and copper catalysts. The 2-oxabicyclo[3.1.0]hex-3-enes thus formed are easily ring-opened to 1,4-diacylbutadienes thermally, thermo-catalytically or by proton catalysis 14,136). The method has been put to good use by Rh2(OAc)4-catalyzed cyclopropanation of furan with diazoketones 275 to bicyclic products 276. Even at room temperature, they undergo electrocyclic ring-opening and cis, trans-dienes 277a are obtained with fair selectivity 257,258). These compounds served as starting materials in the total syntheses 257 259) of some HETE s (mono-... 

The cyclopropanation of furan with methyl 4-bromophenyldizoacetate using the chiral dirhodium tetraprolinate was further studied, showing the initial bond formation occurred at the... 

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>... 

As can be seen below, a retro-Diels-Alder strategy was used to prepare 2,3- and 2,4-disubstituted furans with a SF5 group as one of the substituents, which was introduced into furan ring for the first time <06OL5573>. 

Diastereoselective Friedel-Crafts reaction of a 2-substituted furan with chiral glyoxylate regiospecifically gave chiral 2,5-disubstituted furans in high yields, and an example is shown in the scheme below <060L5045>. 

Functionalized hexanofuran shown below was provided as a 5.1 1 mixture of the desired diastereomer and its epimer by Pd-catalyzed cyclization of 3-iodo-4-substituted furan prepared from 3,4-diiodofuran through I-Li exchange, and was followed by trapping of the lithiated furan with an aldehyde. The modification of this procedure to produce diiodofuran using 1-methyl-2-pyrrolidinone as co-solvent was also reported <06JA17057>. 

Furan can be used as a source for malealdehyde. McKervey and coworkers found that oxidation of furan with dimethyldioxirane results in malealdehyde, which can be trapped in situ with a variety of Wittig reagents to generate dienes and polyenes (equation 174)295. The same sequence with substituted furans gives ketodienealdehydes and ketodieneesters295. 

Reaction of furan with a modified vinyl sulfoxide type dieneophile, namely (Z)-3-p-tolylsulfinylacrylonitriles, has been carried out with high reactivity and stereoselectivity . 

---