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

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

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 Tf2O 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.

Citation

Evans, S. T., Tizzard, G. J., Field, R. A., & Miller, G. J. (2024). 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. Carbohydrate Research, 545, Article 109275. https://doi.org/10.1016/j.carres.2024.109275

• Journal Article Type: Article
• Acceptance Date: Sep 12, 2024
• Publication Date: 2024-11
• Deposit Date: Oct 18, 2024
• Journal: Carbohydrate Research
• Print ISSN: 0008-6215
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 545
• Article Number: 109275
• DOI: https://doi.org/10.1016/j.carres.2024.109275
• Public URL: https://keele-repository.worktribe.com/output/952087
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0008621524002544?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: 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; Journal Title: Carbohydrate Research; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.carres.2024.109275; Content Type: article; Copyright: © 2024 The Authors. Published by Elsevier Ltd.