Butyrolactone, hydroxyalkylation

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. 

A complementary entry to hydroxyalkylated products has been opened by deprotonation, carbonyl compound addition and ring-opening as outlined in equation 100 . The resulting y-lactols are precursors to y-butyrolactones or tetrahydrofuran derivatives. 

S-Benzyl-y-butyrolactones (44) for which convenient preparative procedures are available, and improved techniques for their a-alkylation and a-hydroxyalkylation, provide the most common synthetic route for these lignan sub-classes (39). The Stobbe condensation (40) of aryl aldehyde with dimethyl succinate (Scheme 9) leads to the half-ester (42) which can be catalytically hydrogenated at atmospheric pressure to give the dihydro half-ester (43). Selective reduction of the potassium salt of the latter can be effectively achieved by calcium borohydride (41)... 

The addition of a carbonyl compound to methyl 2-siloxycyclopropanecarboxylate (113 equation 47) in the presence of a stoichiometric amount of TiCU affords a mixture of hydroxyalkylation products (114) and (115), which are versatile starting materials for highly substituted tetrahydrofurans, dihydrofu-rans, and y-butyrolactones. ... 

An annulation of a y-butyrolactone ring to naphthols recruits CO and an aldehyde to become the carbonyl group and the substituted a-carbon. Trifluoroacetic acid is a highly effective cocatalyst for this reaction, but HO Ac, PhCOOH, and TsOH are not. The acid apparently promotes the formation of 2-(l-hydroxyalkyl)naphthols, which undergo carbonylation. That phenols are unreactive may be due to the difficulty in achieving this first step under the conditions employed. 

The aUylation of aldehydes with ethyl a-(a-hydroxymethyl)acrylate and ethyl a-(a-hydroxyalkyl)acrylates is successfully preformed under the conditions shown in Scheme 12. The primary product, a-methylene-y-stannyloxycarboxylate, spontaneously undergoes an intramolecular transesterification to provide a-methylene-y-butyrolactone in moderate yield. The high yn-selectivity may be rationalized on the basis of an anti-periplanar transition state. 

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