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1,4] O f C and [1,4] C f O rearrangements are described for a variety of furans and thiophenes. Treatment of 3-((silyloxy)methyl)furans and -thiophenes with n-BuLi in HMPA provided 2-silylated-3-(hydroxymethyl)furans and -thiophenes in good to excellent yields. The reaction was shown by crossover studies to proceed via an intramolecular [1,4] O f C silyl migration. Silyl esters of 3-furoic acids also underwent an intramolecular [1,4] O f C silyl migration to provide 2-silylated-3-furoic acids in moderate to good yield when treated with a mixture of LDA and HMPA. Finally, the above silyl migrations were shown to be reversible. Treatment of 2-silylated-3-(hydroxymethyl)furans and -thiophenes with NaH in DMF provided 3-((silyloxy)methyl)furans and -thiophenes in excellent yields via a [1,4] C f O silyl migration. The [1,4] C f O silyl migration was also shown to be an intramolecular process by a crossover study.

Rates of reaction are reported for the title compounds in aqueous solution. The influence of added salts on the rate of reaction is recorded: alkali-metal salts advance the rate, while tetraethylammonium chloride retards it. Sodium dodecyl sulphate and cetyltrimethylammonium bromide also retard the reaction, while the effect of cyclodextrins depends on their cavity size. The explanation of these phenomena in terms of the hydrophobic effect is considered and extended by measurement of AHS and AS* parameters for the reaction.The use of Diels-Alder reactions in water for organic synthesis has received much attention over the last decade.' Such processes are often, although not always, carried out in suspension," although it seems likely that even in these cases the reaction proceeds via the small amounts of dissolved reactants. In solution,2 the acceleration observed over reactions in organic solvents has been attributed to the hydrophobic effect,' a factor which may also influence their ~electivity.~**~ We have carried out an investigation of the aqueous Diels-Alder reaction of fumaronitrile (FN) and cyclopentadiene (CPD), Scheme 1, to seek further evidence for the hydrophobic effect in these types of bimolecular reaction. Scheme 1This particular reaction was chosen because it can be considered in many ways to constitute the quintessential normal 4 + 2 cycloaddition, particularly for study in aqueous solution. First, facilitating substituent effects exist in the components. The diene is activated by the methylene group at both C-1 and C-4, raising the HOMO energy, the methylene group further serving to hold it in the reactive cisoid configuration, while the dienophile is activated by the two electron-withdrawing cyano groups, lowering the LUMO. Secondly, both participants are sufficiently soluble to allow study by UV spectrometry, under pseudo-first-order conditions, with FN being in large excess. Thirdly, only one product, or, at least, a racemic mixture, is formed, which removes the complexity involved in consideration of the variation of exolendo ratios, as well as reaction rate, as conditions are varied. For example, exo-and endo-transition states would have different AHt and ASt values, as shown by the change in the exolendo ratio as temperature is varied.' Paper 0/04055J

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A new method for the preparation of 3,4-and 2,5-disubstituted furan rings is described. A variety of 2-silylated-3-(hydroxymethyl)furans and 2-silylated-3-furoic acids lithiate exclusively at C-4 when treated with 2.2 equivs of BuLi. The resulting dianions were quenched with a variety of electrophiles to provide 2-silylated-3-(hydroxymethyl)-4-substituted furans and 2-silylated-4-substituted 3-furoic acids in good to excellent yields. Removal of the silyl group (n-Bu 4 NF) provided a variety of 4-substituted-3-(hydroxymethyl)furans and methyl 4-substituted-3-furoates, respectively. The latter esters were prepared due to difficulties encountered in isolating 4-substituted-3-furoic acids. The site of lithiation was altered by protecting the 3-hydroxyl group with a triethylsilane. Lithiation of 2-silylated-3-(((triethylsilyl)oxy)methyl)furan with 1.2 equivs of BuLi followed by the addition of electrophiles provided 2-silylated-3-(((triethylsilyl)oxy)methyl)-5-substituted furan rings. Subsequent removal of both silyl groups provided 2,4-disubstituted furan rings in moderate to good yields. A rationale is provided to explain why protection of the hydroxyl group at C-3 leads to a change in lithiation from the C-4 to the C-5 position of the furan ring. In addition, an explanation for the observed effect of adding HMPA or LiCl to the solution during the lithiation of 2-(tertbutyldimethylsilyl)-3-(hydroxymethyl)furan is provided.In the preceding paper, 1 the difficulty in preparing 3,4and 2,4-disubstituted furan rings due to the preference for furan rings to lithiate 2 and add electrophiles 3 in the C-2 or C-5 positions was discussed. New synthetic routes toward the preparation of furan rings which contain groups in the 3 and/or 4 positions are useful, since many natural products incorporate furan rings with either a 3,4-or 2,4-disubstituted or 2,3,4-trisubstituted pattern. 4 This paper describes a full account of our work in this area.Some previous reports on the preparation of 3,4disubstituted furans have involved using Diels-Alder/ retro-Diels-Alder chemistry, 5 chemical modifications of 3,4-furandicarboxylic acid, 6 and the synthetic modification of acyclic precursors. 7 An alternative approach to the preparation of 3,4-disubstituted furans is the direct lithiation of substituted furan rings. The C-4 lithiation of a 3-substituted furan, however, has not been successful