Synthesis of β,β-Disubstituted γ-Butyrolactones by Chemo­selective Oxidation of 1,4-Diols and γ-Hydroxy Olefins with RuCl3/NaIO4

Substituted γ-butyrolactones represent an important group of structural fragments commonly found in natural products, receptor ligands, and drug molecules. Interest in preparing a library of substituted γ-butyrolactones and finding that limited routes to β-substituted lactones exist, led to the development of an efficient approach for the synthesis of β,β-disubstituted γ-butyrolactones. Readily prepared substituted 1,4-diols and γ-hydroxy olefins were treated with the ­RuCl 3 /NaIO 4 oxidation system to provide the target β,β-disubstituted γ-butyrolactones in modest to good yields. The reaction goes through a lactol intermediate that was isolated and characterized for selected compounds. The approach supplies an efficient and versatile method for the synthesis of these important heterocyclic structures. Importantly, the present work is the first report that demonstrates the ability of RuCl 3 /NaIO 4 to selectively oxidize primary hydroxyl groups in the presence of secondary alcohols to prepare lactones in good yields.