C-5 Epimerisation of d-Mannopyranosyl Fluorides: The Influence of Anomeric Configuration on Radical Reactivity

Abstract

The fluorine-directing effect has so far been exploited to provide short and efficient synthetic routes to rare L-ido sugars. However, the importance of anomeric configuration to its success has remained experimentally unverified. We now report on the synthesis of α- and β-configured per-O-benzoylated mannopyranosyl fluorides and initially show that their reactivity towards photo-bromination is strongly dependent on the anomeric configuration. The stereochemical basis of the fluorine-directing effect is then validated by revealing the striking difference in stereoselectivity observed for the free radical reductions of the isolated 5-C-bromo sugars. This work importantly provides a synthetic route to a donor-functionalised derivative of L-gulose and reveals new insights into the behaviour of glycosyl radicals.

Synthetic Access to L-Guluronic Acid via Fluorine-Directed C-5 Epimerization

“…12a Conveniently, compound 3 is endowed with glycosyl donor capability 29 and is conceivably amenable to protecting group substitutions. In accordance with our previous studies, 14 we have also shown that and -configured mannosyl fluorides demonstrate different reactivities towards Ferrier photo-bromination. This enabled the isolation of both 2 and 3 from their appropriate stereoisomeric mixtures via a photochemical resolution.…”

“…The X-ray crystal structures of With a view to harnessing the Ferrier photo-bromination 22 to complete the synthesis of 2, we postulated that compared to 4, -D-mannosyl fluoride 4 would demonstrate poorer reactivity towards these conditions. 14 This can be understood by examining the ratedetermining step of the Ferrier photo-bromination which features the reversible brominemediated abstraction of a hydrogen atom from C-5 (Figure 5a). 22b The associated forward and reverse processes are respectively characterised by rate constants k1 and k-1.…”

“…The optimizations were conducted in implicit toluene, as modelled with the SMD implicit solvent model. 14 Harmonic vibrational frequency calculations were performed to confirm that the stationary points were indeed transition states (one imaginary frequency), and also to compute zero-point energies and thermochemical corrections. Truhlar's quasiharmonic approximation was used to correct errors in computed entropies.…”