Dihydroxylation-Based Approach for the Asymmetric Syntheses of Hydroxy-γ-butyrolactones

Abstract

A method of preparing enantiopure hydroxy-γ-butyrolactones containing multiple contiguous stereocenters in high yield with good diastereoselectivity has been developed. Osmium tetroxide mediated dihydroxylation of a range of β-alkenyl-β-hydroxy-<i>N</i>-acyloxazolidin-2-ones results in formation of triols that undergo spontaneous intramolecular 5-<i>exo</i>-trig cyclization reactions to provide hydroxy-γ-butyrolactones. The stereochemistry of these hydroxy-γ-butyrolactones has been established using NOE spectroscopy, which revealed that 1-substituted, 1,1-disubstituted, (<i>E</i>)-1,2-disubstituted, (<i>Z</i>)-1,2-disubstituted, and 1,1,2-trisubstituted alkenes undergo dihydroxylation with <i>anti</i>-diastereoselectivity, while 1,2,2-trisubstituted systems afford <i>syn</i>-diastereoisomers. The synthetic utility of this methodology has been demonstrated for the asymmetric synthesis of the natural product 2-deoxy-d-ribonolactone