Allyl fluorides : new syntheses and enantioselective manipulations

Awarding institution
  • University of Strathclyde
Date of award
  • 2011
Thesis identifier
  • T12887
Qualification Level
Qualification Name
Department, School or Faculty
  • Selectively mono-fluorinated sugars have been acknowledged as useful molecular tools for the study of sugar processing enzymes. The small steric size of the fluorine atom coupled with its high electronegativity make fluorinated sugars ideal candidates to study structure relationships in carbohydrate architecture. We have identified the, as yet, under researched de novo route to fluorinated sugars, whereby the modern tools of asymmetric synthesis are applied to small highly functionalised fluorinated building blocks allowing the possibility of entire libraries of fluorinated sugar analogues to be generated in high enantiomeric excess from a single versatile fluorinated building block. We believe the allylic fluoride moiety represents one of the most versatile and useful functional groups for fluorinated building blocks of this nature. As such, ready access to compounds of this nature is required. Firstly, this work describes the comparison of a new nucleophilic fluorination methodology developed within our laboratory using TBAF.3H₂O and KHF₂, against a recently reported fluorination reaction by Hou on a small selection of simple allylic bromides. A potential fluorinated building block is then prepared and its compatability with a number of asymmetric dihydroxylation techniques assessed. Secondly, the stereodivergent and stereoselective synthesis of all four diastereoisomers of a versatile C4 fluorinated building block is described. The development and optimisation of a new and facile method for the determination of ee's for these and other fluorinated substrates is also described. Thirdly, a stereodivergent route to an analogous C4 fluorinated building block, via an unusual alkene inversion, developed within our laboratory, is examined in detail. Finally, the development, scope and limitations of a novel methodology for the generation of allylic fluorides using cross metathesis is described. A potentially versatile fluorinated building block is prepared via this method and its suitability as a fluorinated pentose precursor explored.
Resource Type
Date Created
  • 2011
Former identifier
  • 833318