Work

Towards the synthesis of a 2-deoxy-2-fluoro-d-mannose building block and characterisation of an unusual 2-S-phenyl anomeric pyridinium triflate salt via 1 → 2 S-migration

Year: 2024

Type: article

Abstract: Regio- and stereo-selective synthetic routes to 2-deoxy-2-fluoro- d -mannose building blocks are often experimentally challenging when using Selectfluor with the corresponding glycal. We targeted a late-stage method to introduce fluorine in a stereospecific manner using inversion via a triflate. Accordingly, synthesis of a conventionally protected 2-deoxy-2-fluoro- d -mannose β-thioglycoside donor, directly applicable to oligosaccharide synthesis, was attempted using C2-triflate inversion of the corresponding d -glucoside with TBAF. Unexpectedly, an anomeric pyridinium salt was isolated when attempting to form the C2-triflate using Tf 2 O in pyridine. Indicatively, this proceeds via a 1 → 2 S -migration delivering a 1,2- trans product with α- d -manno configuration and the anomeric pyridinium in a pseudo-equatorial position. The structure of this unexpected intermediate was confirmed in the solid-state using X-ray crystallography. Omission of the pyridine solvent led to dimer formation. Switching the aglycone to an O - para -methoxyphenyl enabled smooth C2 inversion to the desired 2-deoxy-2-fluoro d -mannose system, suitably equipped for further anomeric manipulation. • Synthesis of a 2-deoxy-2-fluoro- d -mannose building block. • Characterisation of an unusual 2- S -phenyl anomeric pyridinium triflate salt formed via 1. → 2 S -migration.

Source: Carbohydrate Research

DOI: 10.1016/j.carres.2024.109275

Authors: Sean T. Evans, Graham J. Tizzard, Robert A. Field, Gavin J. Miller

Institutions: Keele University, University of Southampton, University of Manchester

Language: English

Topic: Carbohydrate Chemistry and Synthesis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $3,550