Furan endoperoxides

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). 

Several 1,2,4-trioxolanes are known which contain a double bond linked in some way to the ring, with interest focusing on furan endoperoxides. The alkene moiety of 2,5-dimethylfuran endoperoxide (41) can be selectively functionalized in the presence of the 1,2,4-trioxolane ring. Reaction with diimide gives the saturated ozonide <81TL3509> and a single addition product was obtained with p-nitrophenylazide, although the stereochemistry of the reaction was not determined. 

The reactions of a number of ozonides and alkenes in the presence of BF3 Et20 resulted in the formation of E- and Z-l,2-dioxolanes in 12-70% yields (Scheme 30) <83JA6279>. 2,5-Dimethyl-thiophene endoperoxide can act as a sulfur- or oxygen-atom transfer agent in analogous reactions to those shown by furan endoperoxides <86JA2775>. 

Furans. Scarpati showed that the presence of an electron-withdrawing group at the ft position enhances the thermal stability of furan endoperoxides, which prove sufficiently stable to be isolated and characterized spectroscopically and chemically (Sch. 37) [58],... 

The p-peroxide 84 was obtained by methylene blue-sensitized photooxygenation of diene 83 together with its a-isomer (2 1 9,13-a p) and was separated by silica gel chromatography. Diepoxides are the thermally rearranged products of a.a -unsubstituted or alkylsubstituted furan endoperoxides [59,60d,g]. 

Results have been presented that show that furan endoperoxides such as (51)... 

The rate constants of singlet oxygen reactions have been determined for a series of substituted furans by Koch, Clennan et al., and Gollnick and Griesbeck. ° Only a moderate solvent dependence was observed, which implies a concerted (possibly asynchronous) [4 -i- 2]-cycloaddition. More thermally persistent endoperoxides were obtained from alkyl-substituted furans, e.g., 2,5-dimethylfuran or furans with electron-withdrawing substituents. A few representative examples of furan endoperoxides together with their thermal stability are given in Table 25.3. 

These furan endoperoxides are valuable building blocks for the synthesis of di- and tetrahydrofuran derivatives, e.g., bis-epoxides, epoxy lactones, ene diones, cis-diacyloxiranes, enol esters, butenolides, and others. Furthermore, the primary [4 + 2]-cycloadducts may rearrange into 1,2-dioxetanes or 1,2-dioxolenes. ... 

The thiophene endoperoxides ate considerably more labile than the furan endo-peroxides 26), but diimide is sufficiently reactive even at —30 to —50 °C to trap them in the form of thiaozonides 13. 

The oxidation of 2,5-disubstuted furans by singlet oxygen was exploited for the synthesis of [5,5,5] and [6,5,6] bis-spiroketals <06OL1945>. An unusual regioselective photooxidation of 3-bromofuran to 2- and 3-bromo- hydroxybutenolides, as depicted below, was reported. The mechanism for the observed base-dependent regioselective deprotonation of the endoperoxide intermediate was not determined <06OL4831>. 

The corresponding endoperoxides of furans usually ring-open to afford 1,4-diketones. Such a sequence, followed by an intramolecular Diels Alder reaction was utilized in the synthesis of the tts-indacenyl dianion (6.7) 613>. 

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. 

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. 

When solutions of 2,2-dimethyl-1,3-diphenylisoindene (467) were exposed to air at ambient temperature the products formed included l,3-diphenylbenzo[c]furan, acetone, an endoperoxide (468) and 1,2-dibenzoylbenzene (Scheme 120) (81JOC3752). The formation of l,3-diphenylbenzo[c]furan and acetone from the endoperoxide (468) may occur via the diether (469). 

Photosensitized oxidation offurans.3 The endoperoxide (2) formed in photosensitized (methylene blue) oxidation of 3-substituted or 3,4-disubstituted furans in acetone at -40° rearranges at 20° to 4-hydroxy-2-butenolides in 30-97% yield. Example ... 

It is known that thiophenes react with singlet oxygen forming endoperoxides, which are thiaozonides, and whose thermal reactions have been investigated. A novel reaction of acylthiophene endoperoxides 213 (photosensitized oxidation with tetraphenylporphyrine at —30 °C) involves their treatment with triphenylphosphine. The nucleophilic attack finally leads to a furan derivative 214 by elimination of O and S atoms bound to phosphorus (Scheme 71) <1995TL7431, 1998JA8914>. 

Quantitative rearrangement of monocyclic endoperoxides to furans catalyzed by cobalt(II). Journal of Organic Chemistry, 54 (14), 3475-3477. 

Fig. 87 Furans by cobalt-catalyzed cleavage/recyclization of endoperoxides...

The oxidation of furans has often been used to express the latent functionality present within this heterocyclic framework, and it results particularly attractive for the synthesis of the widespread butenolides [8c,56]. Dye-sensitized photo-oxygenation of furfural, furoic acid and a- or a,a -unsubstituted furans leads directly to butenolides [8c,56,60d,63]. The presence of a silyl group in a-position enhances the rate of endoperoxide formation and controls the regiochemical outcome of the second-step leading to the related butenolide via a rapid intramolecular silatropic shift [64]. An application of this reaction is shown in Sch. 39 as a step in the synthesis of spongianolide A, an antitumoral natural sestertepenoid [65],... 

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