The stereoselectivities of tributyltin hydride-mediated reductions of 5-bromo-d-glucuronides to l-iduronides are dependent on the anomeric substituent: syntheses and DFT calculations?

Organic & Biomolecular Chemistry Pub Date: 2016-02-09 DOI: 10.1039/C6OB00283H

Abstract

One of the shortest synthetic routes to L-iduronic acid derivatives is via free radical reduction of the C-5 bromide of the corresponding protected D-glucuronic acid derivative. The epimerization of such C-5 bromides to the L-ido derivatives via reaction with tributyltin hydride was investigated. It was found that the stereoselectivity of the reaction was dependent on the anomeric substituent. If the substituent was fluoride the L-ido product was obtained exclusively in 65–72% yield whereas the O-methyl or O-acetyl derivatives led to isomeric mixtures of both the L-ido and D-gluco products in different ratios depending on the reaction conditions. DFT calculations were performed to determine the stereoelectronic factors that favour formation of the L-ido isomer from the fluoride and suggest the selectivity is due to a transition state gauche effect and an Sn–F interaction.

Graphical abstract: The stereoselectivities of tributyltin hydride-mediated reductions of 5-bromo-d-glucuronides to l-iduronides are dependent on the anomeric substituent: syntheses and DFT calculations
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