2-Methoxyfuran, Diels-Alder reactions

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. 

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]. 

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 Diels-Alder reaction of 3-methoxyfuran with octyl vinyl ketone took place at room temperature in quantitative yield to afford exclusively the endo cycloadduct (27) (81CC221). Reduction of the carbonyl group with lithium tri-r-butoxyaluminum hydride produced a single alcohol (28). Ozonolysis of the double bond followed by Jones oxidation yielded the lactone ester (29). Hydrolysis of the ester and lead tetraacetate oxidation gave the lactone acetate. This was converted by further hydrolysis and Jones oxidation to the bis-lactone (30), a known intermediate in the synthesis of ( )-isoavenaciolide (Scheme 6). 

Dimethoxyfuran is readily available from the enolic dimethyl 3,4-dihydroxyfuran-2,5-dicarboxylate. This intermediate, like a phenol, can be readily O-methylated or O-benzy-lated. Hydrolysis and decarboxylation then furnishes the 3,4-dialkoxy compounds (78HCA430). The dimethoxy compound readily enters into Diels-Alder reactions, the Man-nich reaction, and may be lithiated. On mild acid hydrolysis it supplies, in poor yield, 4-methoxyfuran-3(2/f)-one and not tetrahydrofuran-3,4-dione, which is not produced by attempted hydrogenolysis of 3,4-dibenzyloxyfuran either. The dione, however, is known, and surprisingly exists in the diketo form (60JA3219). 

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]... 

An intramolecular Diels-Alder reaction of a furan with a strained and sterically hindered bicyclopropylidene that proceeded under high pressure to provide the acid-labile cycloadduct is shown in Equation (43) <1996T12185>. An apparent increase in the reaction rate was observed with the 5-methoxyfuran 58 compared to the 5-unsubstituted analog 59. 

The introduction of a nitro or trifluoromethyl group at the C-3 position on the pyridine ring in 3-(2-pyridylsulfinyl)acrylates has been shown to enhance the reactivity and diastereoselectivity of the dienophile in the Diels-Alder reaction with furan and its derivatives [171]. Such a modification of the dienophile renders the addition of diethylaluminium chloride unnecessary in order to achieve the desired asymmetric cycloaddition. The cycloadduct (207), prepared with high stereoselectivity from the asymmetric Diels-Alder reaction between (5)-menthyl 3-(3-trifluoromethylpyrid-2-ylsulfinyl)acrylate (194) and 2-methoxyfuran (208), was converted in seven steps to the glyoxalase I inhibitor (209) [171] (Scheme 5.67). 

When the dichloro diaryl ether 112 was treated with x-BuIi, a dibenzyne was generated and subsequently trapped by 2-methoxyfuran, affording dinaphthyl ethers 113 and 114 after aromatization (Scheme 12.34) [64]. The monocycloadducts 115 and 116 were also present in the reaction mixture. With carefijl control of the stoichiometry of the butyl lithium, an iterative double benzyne-furan Diels-Alder reaction was achieved between benzyne precursor l,4-difluoro-2,5-dime-thoxybenzene and two different furans. 

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