2- Methylene-2,3-dihydrofuran

The ene reaction of fuUerene (C o) with 3-methylene-2,3-dihydrofuran gives an easily isolated addition product in good yield <96JOC2559>. There is a continuous need for chiral acrylate esters for asymmetric Diels-Alder reactions with high diastereoselectivity. Lewis acid promoted Diels-Alder reactions of acrylate esters from monobenzylated isosorbide 28 (or isomannide) and cyclopentadiene provided exclusively e db-adducts with good yields and high diastereoselectivity <96TL7023>. 

The Lewis acid-catalyzed ene reaction of 3-methylene-2,3-dihydrofuran (available by Wolflf-Kishner reduction of 3-furaldehyde <93TL5221>) with aldehydes gives the corre onding alcohols in good to excellent yields <96TL7893>. 5- >ttto-dig iodocyclizations of alk-3-yn-l,2-diols. 

An extensive study was undertaken to optimize the carbonyl-ene reaction between benzaldehyde (143, Scheme 30) and 3-methylene-2,3-dihydrofuran 144, which was utilized in the enantioselective synthesis of fluoxetine hydrochloride, a selective seratonin reuptake inhibitor.89 The degree of hydration of the molecular sieves proved important in the stereoselectivity of the reaction, with lower enantioselectivities reported both with highly active... 

The Huang-Minlon reduction of 3-formylfuran surprisingly gave 3-methylene-2,3-dihydrofuran. The product undergoes ene reactions with a number of electron depleted alkenes and provides a route to functionalize the 3-position in furan as shown in Scheme 66 (93TL5221). 

In contrast to facile Pd(0)-catalyzed reactions of allyl esters with soft carbon nucleophiles via r-allylpalladium intermediate, propargyl esters such as acetate are less reactive toward soft carbon nucleophiles. However, /3-keto esters and malonates react under neutral conditions with propargyl carbonates using DPPE as a ligand [37], Acetoacetate reacts with meAyl propargyl carbonate (119) in THF at room temperature to afford 4-(methoxycarbonyl)-5-methyl-3-methylene-2,3-dihydrofuran (120) in 88 % yield. The furan 121 was obtained by isomerization of the methylenefuran 120 under slightly acidic conditions. 

Reacting with the methylene dihydrofuran derivative 192 as trapping reagent, 34d gave rise to a mixture of [4 + 2] cycloadduct 193 and furan 194, which could be separated and obtained in 25% and 37% yields, respectively. Upon further heating, 193, whose configuration has not been determined, isomerized completely to the more stable 194 (Scheme 31) [47]. 

These two aspects of furan chemistry are placed together since neither is particularly extensive and since they often have points in common, especially in reactions leading to methylene dihydrofurans, these being regarded as tautomers of alkylfurans which often rearrange to true furans. Some methylene furans have already been seen as intermediates in various furan syntheses and reactions. 

The Cu(I)-catalyzed cyclization for the formation of ethyl ( )-tetrahydro-4-methylene-2-phenyl-3-(phenylsulfonyl)furan-3-carboxylate 82 has been accomplished starting from propargyl alcohol and ethyl 2-phenylsulfonyl cinnamate. Upon treatment with Pd(0) and phenylvinyl zinc chloride as shown in the following scheme, the methylenetetrahydrofuran 82 can be converted to a 2,3,4-trisubstituted 2,5-dihydrofuran. In this manner, a number of substituents (aryl, vinyl and alkyl) can be introduced to C4 <00EJO1711>. Moderate yields of 2-(a-substituted N-tosyIaminomethyl)-2,5-dihydrofurans can be realized when N-tosylimines are treated with a 4-hydroxy-cis-butenyl arsonium salt or a sulfonium salt in the presence of KOH in acetonitrile. The mechanism is believed to involve a new ylide cyclization process <00T2967>. 

Dibromoethane normally reacts with activated methylene groups to produce cyclopropyl derivatives [e.g. 25, 27], but not with 1,3-diphenylpropanone. Unlike the corresponding reaction of 1,3-dibromopropane with the ketone to form 2,6-diphenylcyclohexanone, 1,2-dibromoethane produces 2-benzylidene-3-phenyl-tetrahydrofuran and the isomeric 2-benzyl-3-phenyl-4,5-dihydrofuran via initial C-alkylation followed by ring closure onto the carbonyl oxygen atom (Scheme 6.2) [28],... 

Dimethylene-2,3-dihydrofuran derivatives, which are produced by fluoride-induced 1,4-conjugative elimination of trimethylsilyl acetate from the [(trimethylsilyl)methyl]-3-furan precursor 207, undergo subsequent [4-1-4] dimerization reactions to produce cycloocta[l,2-3 6,5-. ]difuran derivatives as a mixture of isomers (Equation 137) <1995JA841 >. A methyl substituent at the 3-methylene position was found to retard the rate of dimerization, an observation which is consistent with the proposed two-step mechanism involving the initial formation of a diradical intermediate in the rate-determining step (Table 16). 

Anodic oxidation of Mn(OAc)2 (catalytic amounts) in the presence of nonacti-vated alkenes and ethyl acetoacetate provides a route to dihydrofurans (cf, 6, 356). This electrooxidation of Mn(OAc)2 has been extended to coupling of activated methylene compounds with alkenes and dienes. 

The stereoselectivity of this reaction rises when more bulky nucleophiles are employed (compare entries 7, 3,1, and 5). This is most impressively demonstrated by comparison of the y-lactol reduction with its allylation leading to 205 or 206, respectively (Scheme 10). Formation of tetrahydrofuran derivative 208, dihydrofuran 209, or unsaturated a-methylen-y-butyrolactone 207 illustrate that various modes of straightforward work-up procedures provide two different five membered heterocycles 93 b-96). A second example without the geminal dialkyl substitution at C-3 of the siloxy-cyclopropane depicted in Eq. 86 making available the annulated tetrahydrofuran-3-carboxylate 210 underlines the generality of the C-C-bond forming hydroxyalkylation reaction via ester enolates. 

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