Furan ozonolysis

A number of the bicyclic ozonides 12 were prepared in good yield (45-65 %) by diimide reduction of furan singlet oxygenates (Eq. 9) 23>. Again, low temperature were essential because the furan endoperoxides readily transform into 1,2-diacyl-ethylenes. Of course, the bicyclic ozonides 12 can alternatively be prepared via ozonolysis of the appropriate 1,2-disubstituted cyclobutene 24). 

Hydrolysis of 20 with the aid of butanol followed by syn-selective reduction of jS-keto ester 21 and protection as the isopropylidene acetal was accomplished in 87% yield. L1A1H4 reduction and TBS protection of the primary alcohol gave 22 in very good yields. In this strategy, the furan residue serves as an aldehyde synthon and ozonolysis followed by esterification gave the corresponding methyl ester. Reduction and consecutive oxidation established aldehyde 23 in 71% yield. 

In their pioneering work. Just and co-workers have described many interesting transformations of the Diels-Alder adducts of furan to methyl nitroacrylate (77 + 77 ) and to dimethyl acetylenedicarboxylate (53). The mixture of racemic adducts 77 + 77 was hydroxylated into the exo-cis-diols 125 + 125 , separable by crystallization. Treatment of the isopropylidene acetal obtained from 125 with diazabicyclo[5.4.0]undec-5-ene (DBU) gave a high yield of alkene 126. Ozonolysis followed by a reductive work-up with dimethylsulfide, then with NaBH4, gave a mixture of epimeric triols 127. Cleavage with sodium periodate afforded 2,5-anhydro-3,4-0-isopropylidene-DL-allose (128) in 15 % yield, based on methyl 2-nitroacrylate used. TTie same allose derivative was obtained from adduct 53. ... 

Mass spectrometry has been used to investigate the mechanism of ozonolysis <79JOC3i85,80JA4763) and to study the gas-phase reaction of furans with singlet oxygen in which endoperoxides are intermediates. 

Alternatively, lactone 392 was condensed with 2-furaldehyde, and the aldol adduct was dehydrated to give 394. Treatment of 394 with methanolic sodium methoxide afforded the methyl ester 395, which, after (trialkylsilyl)ation, was transformed by ozonolysis into the unstable keto ester 396. Compound 396 was converted into showdomycin, as well as into some 6-azapseudouridines.261 A number of a,a -dibro-moketones react262 with furan, to give substituted analogs of the bicy-elic ketone 390. Appropriately substituted substrates have been converted,263 by way of Baeyer-Villiger oxidation and treatment of the resulting lactone with tcrt-butoxybis(dimethylamino)methane, into pseudouridines 397 modified at C-5. 

On treatment of furan at low temperature with hydrogen peroxide the peroxide (53) is obtained which may be partially hydrogenated to malealdehyde. 2,5-DimethyIfuran with acidic hydrogen peroxide yields the hydroperoxide (54) and the cyclic peroxides (55) and (56) mechanisms have been proposed. Ozonolysis of furan at -60 °C in chloroform with reductive work up affords glyoxal and formic acid. Methylfurans behave similarly thus... 

The furanoid ring in benzo[6 ]furan is susceptible to attack by oxidants. Permanganate and chromic acid give derivatives of 2-hydroxybenzoic acid with compounds unsubstituted at the 3-position, but compounds with a 3-methyl or a 3-aryl substituent give derivatives of 2-hydroxyacetophenone or 2-hydroxybenzophenone. Ozonolysis of benzo[6]furan affords 2-hydroxybenzoic acid, 2-hydroxybenzaldehyde and some catechol produced via its diformate. Before the advent of NMR spectroscopy these methods were used in structural elucidation of benzofuranoid natural products, as in the case of O-methyleuparin (Scheme 26). 

Bailey and Colomb278 described an ozonolysis of 2,5-diphenylfuran in methanol-acetone, with two equivalents of ozone, which gave 14% phenylglyoxal and 81% benzoic acid. Abnormal ozonizations such as this can be explained if we consider that the initial step is the normal 2,5-addition of ozone on the furan ring. Then 26 or the primary ozonides 27 or 28 could give the resulting ketonic product ... 

The asymmetric total synthesis of the natural enantiomer (—)-nakadomarin A was completed by Nishida et al. in 2004 (Scheme 8.12) [82]. Diels-Alder reaction between siloxydiene 173 and chiral dienophile 172 (prepared from L-serine in 10 steps [83]) gave the highly functionalized key intermediate hydroisoquinoline 174, which was subjected to Luche reduction, cyclization, and HCl treatment to furnish the tricyclic intermediate 175. Compound 175 was converted to 177 via ozonolysis cleavage of ring B followed by recyclization of the unstable bisaldehyde to a five-membered ring by aldol condensation. The Z-olefin 178 was obtained from Wittig reaction of 177, and was further converted to furan 180 via peroxide 179. The... 

The copper(l)-catalyzed asymmetric cyclopropanation of methyl furan-2-carboxylate with ethyl diazoacetate was achieved by the use of the bisoxazoline ligand 12 to provide the o o-isomer of 2-oxa[3.0.1 ]bicyclohexene 13, as shown in Scheme 5 <2003CEJ260>. The product was transformed into 1,2,3-trisubstituted cyclopropane by ozonolysis... 

The ozonolysis of furan itself yields glyoxal (about 46% by weight) and formic acid. Interesting results, however, have been obtained in the ozonolysis of methyl furans. 

Among the scission products formed in the ozonolysis of 2,5-dimethylfuran were found glyoxal and methylglyoxal in a molecular ratio of 1 to 1.4 and a total yield of 48%. Formic acid and acetic acid were also formed. This means that in the cleaving of the furan ring a linking between an and a yg-carbon atom may remain intact. 

Two other approaches to the furan derivative 67 have been described (a) from perfluoro-2-butyne and involving the novel cyclopropenyl ketone derivative 74154 and (b) by ozonolysis of hexakistrifluoromethylbenzvalene (75), followed by treatment of the ozonide (76) with triphenylphosphine and... 

In this case the trityl-protected lactaldehyde 882 is prepared from trityl lactate 463 by reduction of the ester with lithium aluminum hydride followed by oxidation under Swem conditions. An aldol-type addition of titanated furan produces a 6 1 mixture of anti and syn adducts from which the pure anti diastereomer 883 is isolated by column chromatography (55% yield, >95% de). Treatment of 883 with bromine in methanol followed by acidic hydrolysis gives the ulose 885. A 1,4-reduction to 886, acetylation to 887, and ozonolysis affords the unstable aldehyde 888, which is immediately coupled with 2,5,6-triamino-4-pyrimidinol (889) to afford 890 [237]. 

The annelation of phenols with 2,3-epoxycycloalkanones via a Lewis acid-promoted intramolecular acylation-rearrangement of a lactone intermediate, e.g. (184), has been shown to give tricyclic benzofurans, e.g. (183), in excellent yields (Scheme 38). The methyl-substituted furan double bond in (183) is effectively a masked ketone carbonyl that is easily liberated by ozonolysis, producing the diketone (182). 

The intramolecular cyclization of a stabilized phosphonate carbanion onto an aldehyde has proved to be an effective method for the synthesis of brefeldin polyene macrolides, and in a formal synthesis of carbomycin Pyrenophorin has been synthesized using a pent-3-enoic acid d reagent two other routes to the racemic compound have also appeared. Macrocyclic polyether macrolides have been prepared by cyclization, and by ozonolysis of a furan crown-ether compound. 

Ozonolysis causes usually in other furan containing natural compounds the loss of C H 0 unit from the molecule and a carboxylic group is formed. It can be assumed that in the NTBN molecule the positively charged nitrogen atom withdraws the electrons from the furan ring so the C4 - Cll bond bears some olefinic character. This bond could be attacked by ozone molecule in the subsequent reaction step and quinolizidone derivatives are formed. X-ray analysis of NTBN bromohydride shows that C4 - Cll bond is really shortened. In the next reaction step lactam rings could be cleaved by acid in ethanol and corresponding esters are formed. The C-15 compounds are presumably formed via sulfenic acid intermediate. 

The results of the NTBN ozonolysis are comparable with that of ipomeamarone. The NTBN and ipomeamarone molecules are formally similar, having an electronegative heteroatoms in the -position to the furan ring. 

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