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

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-N-acyloxazolidin-2-ones results in formation of triols that
undergo spontaneous intramolecular 5-exo-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,
(E)-1,2-disubstituted, (Z)-1,2-disubstituted,
and 1,1,2-trisubstituted alkenes undergo dihydroxylation with anti-diastereoselectivity, while 1,2,2-trisubstituted systems
afford syn-diastereoisomers. The synthetic utility
of this methodology has been demonstrated for the asymmetric synthesis
of the natural product 2-deoxy-d-ribonolactone.