Methylenetetrahydrofurans, formation

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>. 

Annulation to carbonyl functions has also been achieved with Trost s bifunctional reagents. Whereas the parent silyl acetate (97) yields only simple alkylation products with aldehydes under normal conditions, addition of only a few mole % of trimethyltin acetate to the reaction mixture results in facile formation of methylenetetrahydrofurans Furthermore, excellent diastereoselectivity is observed in the cycloaddition to a galactose-derived aldehyde (125) (equation 136). The tin acetate co-catalyst also promotes addition to relatively unreactive ketone carbonyls, such as in the case of benzofuran (126) and the acetylenic ketone (127) (equations 137, 138). It is remarkable that even the sterically hindered enone (128) reacts preferentially at the ketone function (equation 139). A tributyltin analog (129) of (97) has been used in the stepwise formation of a methylenetetrahydrofuran from aldehydes. Similarly, pyrrolidines can be prepared from the corresponding imines in two steps via a Lewis acid-catalyzed 1,2-addition of the tin reagent, which is then followed by a Pd-catalyzed cyclization (equation 140). Direct formation of pyrrolidine from the imine is possible if one uses a mesylate analog of (97) and a nickel(O) catalyst (equation 141). ... 

Besides carbon — carbon multiple bonds, carbon —heteroatom double bonds (C = 0 C = NR) are also capable of undergoing metal-catalyzed [3 4- 2] cycloadditions. However, the simplest class of substrates, i.e. ketones and imines, respectively, could so far only be employed when 2-(trimethylsilylmethyl)prop-2-enyl acetate (1) was used as a TMM synthon. These reactions, which additionally require the presence of cocatalysts such as tin or indium compounds when ketones are used as substrates, lead to the selective formation of 3-methylenetetrahydrofurans and 3-methylenepyrrolidines (3, X = O, N), respectively. ... 

Stereoselective formation of 3-methylenetetrahydrofuran such as 180 by intramolecular allylation of alcohol with allyl benzoate in 179 was utilized in synthetic studies of the core of amphidinolide [70]. Thus treatment of 179 with Pd(OAc)2 and PPh3 in the presence of Me3SnCl (1 equiv.) and NaH in THF afforded the cA-tetrahydrofuran 180 stereoselectively in 77 % yield. In this reaction, the less reactive hydroxy group was converted to the more reactive tin alkoxide by the reaction of Me3SnCl (1 equiv.) and NaH. 

Genet et al. reported an interesting cyclization of 1,6-enynes in an aqueous solution. Treatment of the 1,6-enyne 177 with PdCF in aqueous dioxane afforded the methylenetetrahydrofuran 178 in 85 % yield. The reaction is explained by involvement of H-Pd-OH species, namely, formation of 179 by insertion of the alkyne to H-Pd-OH, followed by cyclization, and reductive elimination [53]. 

The strategy used for the formation of methylenecyclopentanes was applied to the one-pot synthesis of various 3-methylenetetrahydrofurans. The methodology was based on an oxygen nucleophile initiated Michael addition of propargyl alcohols to alkylidene or arylidenemalonates followed in situ by a Pd-mediated cyclization. ° ... 

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