Methoxyfurans

The sensitized irradiation of 2-methoxyfuran gave a product (34) deriving from a transposition reaction of the methyl group (Scheme 13) (69TL2767). The 5-methyl derivative 35 was obtained starting from 2-acetoxyfuran (Scheme 13). 

Acid chloride 5 is readily available from the known benzylic alcohol 6,4e but intermediate 4 is still rather complex. It was recognized that compound 4 could conceivably be formed in one step from 2-methoxyfuran (9)10 and iodotriflate 10. The latter compound was designed with the expectation that it could be converted to benzyne 8," a highly reactive species that could be intercepted in an intermolecular Diels-Alder reaction with 2-methoxyfuran (9) to give 7. The intermediacy of 7 is expected to be brief, for it should undergo facile conversion to the aromatized isomer 4 either in situ or during workup. 

Danishefsky and coworkers using the same approach have synthesized substituted cyclohexadienones 563s65,666 (equation 361). A highly stereoselective (96%) cycloaddition of diastereoisomerically pure (Ss)-menthyl 3-(3-trifluoromethylpyrid-2-ylsulphinyl)acrylate 564 to 2-methoxyfuran 565 leads to the cycloadduct 566 which was elaborated by Koizumi and coworkers to glyoxalase I inhibitor 567667 (equation 362). 

Methoxyfurans reacted with ruthenium and platinum carbenoids, derived from tertiary propargyl carboxylates, regioselectively, leading to interesting triene systems, as represented by the example below <06OL1741>. 

Bicyclopropylidene (1) does not undergo an intermolecular Diels-Alder reaction with furan and 2-methoxyfuran even under high pressure. Intramolecular cycloadditions of compounds 160 with a furan tethered to bicyclopropylidene, however, were easily brought about under high pressure (10 kbar) and gave cycloadducts 161 stereoselectively in yields ranging from 32 to 95% (Scheme 35) [58]. 

The nature of the dipolar intermediate is crucial in the reaction with furans, since the product distribution is greatly influenced by the substituents present on the furan and vinylcarbenoid (Tab. 14.10) [84—86]. Electron-rich 2-methoxyfuran leads to exclusive formation of triene 89 with vinyldiazoacetate 42, whereas the corresponding reaction with 2,5-dimethylfuran affords only the [3+4] cycloaddition product 88 in 70% yield. 

The oxaziridine ring system has been formed by the oxidation of C=N double bond . The two-step synthesis of iV-phosphinoyloxaziridines 16 from oximes 15 was described (equation 7) . Irradiation of hydroperoxynitrones 18, prepared by dye-sensitized photooxygenation of 2-methoxyfuran in the presence of oximes 17, led to fraw -oxaziridines 19 in yields up to 89% (equation 8) ". ... 

Diels-Alder reactions with furans constitute a major class of cycloaddition reactions, which have been used for the preparation of a variety of new compounds. Some examples will be given in this section. A one-pot stereoselective synthesis of tricyclic -y-lactones was achieved via Diels-Alder reactions of 2-methoxyfuran with masked o-benzoquinones, which are in turn available from the corresponding 2-methoxyphenols <99CC713>. 

The presence of functional groups in the heterocycle frequently determines the nature of the photoreaction observed. The major product of irradiation of 2-methoxyfuran (191) in the gas phase or in solution is the lactone (192).157 Similarly, 2-nitrofuran (193) undergoes a photoreaction typical of a,f -unsaturated nitro compounds to give the oxime (194) by the pathway shown in Scheme 13.158 A different process is observed, however, on irradiation of thenitrovinylbenzo[6]furan(195) to give the 6-hydroxy-l,2-oxazine(196)159 this transformation is viewed as proceeding via an electrocyclization pathway (Scheme 14) for which there is a precedent in the known photochromism of nitrostyrenes. 

By using tetraphenylporphyrin as sensitizer at — 80 °C, the . 

Table 6.26 1,2-Aza-Friedel-Craft reactions of 2-methoxyfuran and aldimines.

A dry test tube containing catalyst (1.95 mg, 2 pmol, 2 mol%) was purged with nitrogen and charged with 1,2-dichloroethane (1 mL). The solution was cooled to —35 °C prior to sequential addition of neat imine (24.0 mg, 0.1 mmol, 1 equiv) and 2-methoxyfuran (11.1 pL, 0.12 mmol, 1.2 equiv). The resulting solution was stirred at —35 °C for 24 h prior to loading directly onto a column for purification by FC on silica gel (ethyl acetate hexanes, 4 1) to give the product (29.7 mg, 0.09 mmol, 88% yield, 97% ee) as a solid. 

An example of the simplicity and potential of the photo-oxygenation reaction is described for the preparation of (Z)-l-hydroperoxy-A-[(Z)-3-methoxycarbonyl)-2-propenylidene]cyclohexylamine A-oxide (P) starting from 2-methoxyfuran and cyclohexanone oxime, which both can be purchased and used without further purification. 

Recently, Koizumi et al. reported that the use of high pressures allows exclusion of Lewis acids (which are not compatible with many dienes and/or adducts) in the cycloadditions of acrylates [43]. Thus, methyl 3-alkylsulfinyl acrylate 29 is able to react with cyclopentadiene, furan, and 2-methoxyfuran at 12.6 Kbar (Scheme 14). Both 7r-facial and endo/exo selectivities are very high in reactions with cyclopentadiene (only one adduct was obtained), whereas with furan derivatives the endo/exo selectivity is clearly lower. In reactions with cyclopentadiene it could be established that high pressures do not have a significant influence on the diastereoselectivity. The transformation into (-)-COTC of the major adduct obtained from 2-methoxyfuran was carried out in order to confirm its absolute configuration. 

The most recent report in this field is related to the use of optically pure 3-(2-exo-hydroxy-10-bornyl)propenamide 56 [43]. This compound reacted with cyclopentadiene under both atmospheric and high pressure conditions in CH2Cl2/methanol to give similar mixtures of endo and exo cycloadducts (de 80-88%). Reactions with furan and 2-methoxyfuran took place only under high pressure (12.6 kbar). With furan, the endo-adduct was obtained as a single diastereoisomer (82% yield), whereas with 2-methoxyfuran a 92 8 mixture of endo-57 and exo-57 adducts was obtained (Scheme 30). 

Yamakoshi, Y.N. et al. High Pressure Mediated Asymmetric Diels-Alder Reaction of Chiral Sulfinylacrylale Derivatives with Furan and 2-Methoxyfuran. 3.3 1996 [188]... 

Regioselective addition of 2-methoxyfuran and 2-trimethylsilyloxyfuran to chromium(O) alkynylcarbene complexes furnished interesting dienyne and dienediyne carboxylates <07AGE2610>. The reaction likely proceeded through a formal vinylogous Michael addition adduct, as illustrated in the following example. 

The corresponding reaction of 2-methoxyfuran with chiral tungsten(O) alkenylcarbene complexes also proceeded via a similar Michael intermediates which collapsed to provide trisubstituted cyclopropanes, as shown below <07CEJ1326>. 

Methoxyfuran also reacted with vinylcarbenes that were derived from sec-O-propargyl thiocarbamates in a transition metal-catalyzed ring opening to give a mixture of geometrical isomers, as depicted below <07TL6651>. 

Furfurylamine derivatives could be prepared, via an in j tV -generated aldimine intermediate, by treatment of an aldehyde and A-sulfinyl-/)-toluenesulfonamide with furan in the presence of ZnCl2 <2003T4939>. As shown in Equation (8), enantioselective addition of 2-methoxyfuran to aldimines was achieved using the chiral C -symmetric phosphoric acid 6 as an organocatalyst <2004JA11804>. This reaction uniformly provided >94% ee irrespective of the substitution pattern on the aldimine phenyl ring. 

An enantiopure Fischer carbene complex was able to react with 2-methoxyfuran in an intriguing manner that led to the formation of trisubstituted cyclopropane molecules in excellent diastereoselectivities. The relevant mechanism for the formation of a cyclopropane is depicted in Scheme 88 <2007CEJ1326>. 

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