3- -1 -alkene furan

Furans may be formed in the reaction with metal carbenoids derived from diazocarbonyl compounds, if alkynes are used instead of alkenes. Furan formation is particularly favored when the carbenoid is a 3-diazo-2-oxopropionate (e. g., 8.110, Wenkert et al., 1983) or contains two electron-withdrawing groups (see Davies and Romines, 1988) and when electron-donating groups are present in the alkyne. Davies... 

Chloro-4-fluorothiophene-1,1-dioxide 234, a new synthetically useful fluoro-diene was prepared from commercially available 3-sulfolene. This compound reacts with different types of dienophiles acetylenes, alkenes, furans quinine, and antracene giving the 3-fluoro-4-chloro-substituted arenes or cyclic chlorofluorodienes. " ... 

Anhydrides (R C0)20 + H2O 2R COOH Conductimetric, polarimetric, thermometric, or UV Alkenes, furans, aromatic, ketones, formic acid, aldehydes, amides, and oximes range 0.2-10% water depending upon the sample... 

The Pd—C cr-bond can be prepared from simple, unoxidized alkenes and aromatic compounds by the reaction of Pd(II) compounds. The following are typical examples. The first step of the reaction of a simple alkene with Pd(ll) and a nucleophile X or Y to form 19 is called palladation. Depending on the nucleophile, it is called oxypalladation, aminopalladation, carbopalladation, etc. The subsequent elimination of b-hydrogen produces the nucleophilic substitution product 20. The displacement of Pd with another nucleophile (X) affords the nucleophilic addition product 21 (see Chapter 3, Section 2). As an example, the oxypalladation of 4-pentenol with PdXi to afford furan 22 or 23 is shown. 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

In addition to benzene and naphthalene derivatives, heteroaromatic compounds such as ferrocene[232, furan, thiophene, selenophene[233,234], and cyclobutadiene iron carbonyl complexpSS] react with alkenes to give vinyl heterocydes. The ease of the reaction of styrene with sub.stituted benzenes to give stilbene derivatives 260 increases in the order benzene < naphthalene < ferrocene < furan. The effect of substituents in this reaction is similar to that in the electrophilic aromatic substitution reactions[236]. 

Heteroaromatics such as furan, thiophene, and even the 2-pyridone 280 react with acrylate to form 281(244-246]. Benzene and heteroaromatic rings are introduced into naphthoquinone (282) as an alkene component[247]. The pyrrole ring is more reactive than the benzene ring in indole. 

Electron-deficient alkenes add stereospecifically to 4-hydroxy-THISs with formation of endo-cycloadducts. Only with methylvinyl-ketone considerable amounts of the exo isomer are produced (Scheme 8) (16). The adducts (6) may extrude hydrogen sulfide on heating with methoxide producing 2-pyridones. The base is unnecessary with fumaronitrile adducts. The alternative elimination of isocyanate Or sulfur may be controlled using 7 as the dipolarenOphile. The cycloaddition produces two products, 8a (R = H, R = COOMe) and 8b (R = COOMe, R =H) (Scheme 9) (17). Pyrolysis of 8b leads to extrusion of furan and isocyanate to give a thiophene. The alternative S-elimi-nation can be effected by oxidation of the adduct and subsequent pyrolysis. 

Hydroxy-THISs react with electron-deficient alkynes to give nonisol-able adducts that extrude carbonyl sulfide, affording pyrroles (23). Compound 16 (X = 0) seems particularly reactive (Scheme 16) (25). The cycloaddition to benzyne yields isoindoles in low- yield. Further cyclo-addition between isoindole and benzyne leads to an iminoanthracene as the main product (Scheme 17). The cycloadducts derived from electron-deficient alkenes are stable (23, 25) unless highly strained. Thus the two adducts, 18a (R = H, R = COOMe) and 18b (R = COOMe, R = H), formed from 7, both extrude furan and COS under the reaction conditions producing the pyrroles (19. R = H or COOMe) (Scheme 18). Similarly, the cycloadduct formed between 16 (X = 0) and dimethylfumarate... 

Cyclic compounds that contain at least one atom other than carbon within their ring are called heterocyclic compounds, and those that possess aromatic stability are called het erocyclic aromatic compounds Some representative heterocyclic aromatic compounds are pyridine pyrrole furan and thiophene The structures and the lUPAC numbering system used m naming their derivatives are shown In their stability and chemical behav lor all these compounds resemble benzene more than they resemble alkenes... 

Alkylation of furan and thiophene has been effected with alkenes and catalysts such as phosphoric acid and boron trifluoride. In general, Friedel-Crafts alkylation of furans or thiophenes is not preparatively useful, partly because of polymerization by the catalyst and partly because of polyalkylation. 

Pyrroles, furans and thiophenes undergo photoinduced alkylation with diarylalkenes provided that the alkene and the heteroaromatic compound have similar oxidation potentials, indicating that alkylation can occur by a non-ionic mechanism (Scheme 20) (81JA5570). 

Aromatic ethers and furans undergo alkoxylation by addition upon electrolysis in an alcohol containing a suitable electrolyte.Other compounds such as aromatic hydrocarbons, alkenes, A -alkyl amides, and ethers lead to alkoxylated products by substitution. Two mechanisms for these electrochemical alkoxylations are currently discussed. The first one consists of direct oxidation of the substrate to give the radical cation which reacts with the alcohol, followed by reoxidation of the intermediate radical and either alcoholysis or elimination of a proton to the final product. In the second mechanism the primary step is the oxidation of the alcoholate to give an alkoxyl radical which then reacts with the substrate, the consequent steps then being the same as above. The formation of quinone acetals in particular seems to proceed via the second mechanism. ... 

In the chemical shift range for alkenes and aromatic and heteroaromatic compounds enol ether fragments (furan, pyrone, isoflavone, 195-200 Hz) ... 

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). ... 

With respect to aromatic substrates, the Vilsmeier formylation reaction works well with electron-rich derivatives like phenols, aromatic amines and aromatic heterocycles like furans, pyrroles and indoles. However various alkenes are also formylated under Vilsmeier conditions. For example the substituted hexatriene 6 is converted to the terminal hexatrienyl aldehyde 7 in 70% yield ... 

Nonstabilized carbonyl ylides (41) prepared by reaction of a-iodosilyl ethers with Smlj, can be trapped with various alkenes, alkynes and allenes to form furans of type 42, 43, and 44... 

Intramolecular cycloadditions between cyclobutadiene and an oxygen-tethered unactivated alkene (alkyne) offers an attractive route to benzo[c]furans (Scheme 26, <96JA9196>). 

Note that hydrozirconation of 2-vinylfuran gives only the internal product [86] (Scheme 8-16) which probably is the result of the combination of the effects described in this section (i) O-coordination, (ii) aromatic stabihzation, (iii) reduced steric effect of the flat furan ring, which favors the reverse expected regiochemistry in the hydrozirconation reaction of alkenes with [Cp2Zr(H)Cl] (1). 

The thermo- and photocycloaddition of alkenes will be discussed in Chapter 12, on pericyclic reactions. On the other hand, transition-metals have effectively catalyzed some synthetically useful cycloaddition reactions in water. For example, Lubineau and co-worker reported a [4 + 3] cycloaddition by reacting a,a-dibromo ketones with furan or cyclopen-tadiene mediated by iron or copper, or a-chloro ketones in the presence of triethylamine (Eq. 3.48).185... 

Diterpenoids related to lambertianic acid were prepared by intramolecular cyclization of either an alkene or an alkyne with a furan ring <2005RJ01145>. On heating amine 101 with allyl bromide, the intermediate ammonium ion 102 was formed which then underwent [4+2] cycloadditions in situ to give the spiroazonium bromides 103 and 104 (Scheme 13). These isomers arose from either endo- or co-transition states. The analogous reaction was also carried out with the same amine 101 and propargyl bromide. The products 105 and 106 contain an additional double bond and were isolated in 58% yield. The product ratios of 103 104 and 105 106 were not presented. 

Simple acetylenic allylic alcohols can be cyclized easily by tarf-butoxide, and since this base initiates prototropic shifts the vinylic link may.be E or Z such cyclizations proceed via exomethylene furans similar to 15.65 If necessary, UV irradiation can effect both the isomerization of an to a Z-alkene and the cyclization, leaving only the final adjustments to be made chemically.66 In a variation, methoxide plays the role of leaving group allowing very good yields to be attained (Scheme 10).67... 

Photoproducts arising by a [3 + 2] cycloaddition of s-triazolo[4,3-b]-pyridazine (269) to alkenes have been described.222 Addition to cyclohexene, for example, led to the formation of adducts 270 and 271, and the proposed mechanism is outlined in Scheme 8. The reaction has been extended to include addition to cis- and rans-hex-3-ene,223 cyclooctene,224 and furan.225... 

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... 

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