Dihydroxylation-based approach for the asymmetric syntheses of hydroxy-gamma-butyrolactones

Jennifer Peed, Iwan R Davies, Lucy R Peacock, James E Taylor, Gabriele Kociok-Kohn, Steven D Bull

OAI: oai:purehost.bath.ac.uk:openaire_cris_publications/a29bb3ad-89d3-4b3a-8d90-44cd4d01aff8 • DOI: https://doi.org/10.1021/jo2021289

A method of preparing enantiopure hydroxy-gamma-butyrolactones containing multiple contiguous stereocenters in high yield with good diastereoselectivity has been developed. Osmium tetroxide mediated dihydroxylation of a range of beta-alkenyl-beta-hydroxy-N-acyloxazolidin-2-ones results in formation of triols that undergo spontaneous intramolecular 5-exo-trig cyclization reactions to provide hydroxy-gamma-butyrolactones. The stereochemistry of these hydroxy-gamma-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.