Approaches to the synthesis of non-natural carbohydrates via silicon tethered ene and allyl transfer reaction

Thesis



The efficiency of an intermolecular synthetic transformation can be improved by temporarily linking reaction components together. The addition of a tether leads to enhanced regio- and stereocontrol by restraining the mobility of the reacting partners, effectively transforming an intermolecular reaction into its intramolecular counterpart. Silicon tethers are associated with an expanding range of applications, including hydrosilylations, cycloadditions and radical reactions. This project has continued work pioneered by the Robertson group into silicon tethered Type I ene cyclisations, extending the methodology to incorporate O-linked ene precursors with the intention of applying this chemistry to the stereoselective synthesis of non-natural carbohydrates.

This investigation encompassed advances in the area made concurrently within the Robertson group and extended the scope of the ene protocol by successfully incorporating latent functionality into the R-group side chain. In addition, a new route to the O-linked ene precursors was established employing silylcyanohydrin chemistry. In general, the ene reactions proceeded stereoselectively to generate the expected oxasilacyclohexanols, which could be cleaved oxidatively to afford 1,2,4-triols. The formation of the major diastereomer was consistent with ene cyclisation proceeding through a trans-decalin type transition state (e.g. leading to compound 1).

During our attempts to effect ene cyclisation in the O-linked prenyl systems we observed an unexpected side reaction, resulting from intramolecular allylic transfer. Further studies revealed that this novel process could be initiated thermally to generate 1,2-homoallylic diols with excellent levels of stereoselectivity. Tethered E- and Z-crotylsilanes were found to be equally receptive to this process.

Although attempts to apply the silicon tethered allyl transfer chemistry to aldimines and glycosides failed, an extension of the methodology to incorporate cyclohexadienylsilanes was successful and provided interesting synthetic intermediates for elaboration to carbasugars.

Authors: Stafford, P

• Publication date: 2004
• DOI: 10.5287/ora-6qkkxnepz
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Subjects: Carbohydrates; Stereochemistry; Research; Aldehydes; Synthesis