Syntheses of Hydroxy Ketones from Lactones

Article abstract of DOI:10.1021/jo00181a022

γ-Hydroxy ketones (4, n=2) are cleanly obtained by the addition of 1.1 equiv of n-butyllithium to γ-lactones dissolved in ether at -90 deg C, since in these conditions the formation of diols by double organometallic attack is avoided, especially in the case of substituted lactones.The corresponding reactions performed in tetrahydrofuran are less satisfactory.The method cannot be applied to δ-valerolactone and ε-caprolactone, as well as to β-lactones, from which extremely complex mixtures are obtained in low yields.Furthermore the reactions of Grignard reagentswith lactones in ether or in tetrahydrofuran are quite poor.From those lactones which behave unsatisfactorily toward n-butyllithium in ether, the corresponding β-, δ-, and ε-hydroxy ketones (4, n=1, 3, 4) are prepared in two steps.The reactions with α,α-dilithioalkyl phenyl sulfones in tetrahydrofuran at low temperatures afford the ω-hydroxy-β-keto sulfones (12), which are successively cleaved with aluminum amalgam to afford 4 in satisfactory overall yields.