Dr Alison M Stuart

Alison Stuart

Associate Professor in Organic Chemistry

BSc (St Andrews), PhD (Birmingham), AFHEA

Tel : +44 (0)116 252 2136
Email : alison.stuart@le.ac.uk

Personal details

My research group is interested in designing new synthetic methodology for introducing fluorine into organic molecules because of the importance of incorporating fluorine into drug candidate molecules. Over the last 60 years fluorinated molecules have proved crucial in the development of new pharmaceuticals and there are approximately 200 current pharmaceuticals that contain fluorine. Consequently, the chemical industry still needs more efficient and cheaper methods for fluorination and new fluorinated motifs, particularly fluorinated heterocycles.

Awards received

  • Royal Society University Research Fellow, October 2000 to April 2010

Publications

  1. “Fluorinations of unsymmetrical diaryliodonium salts containing ortho-sidearms; influence of sidearm on selectivity” A. M. H. Abudken, E. G. Hope, K. Singh and A. M. Stuart, Org. Biomol. Chem., 2020, 18, 6140-6146.

  2. “Activation of the hypervalent fluoroiodane reagent by hydrogen bonding to hexafluoroisopropanol” H. K. Minhas, W. Riley, A. M. Stuart and M. Urbonaite, Org. Biomol. Chem., 2018, 16, 7170-7173.

  3. “Intramolecular fluorocyclizations of unsaturated carboxylic acids with a stable hypervalent fluoroiodane reagent.” G. C. Geary, E. G. Hope and A. M. Stuart, Angew. Chem. Int. Ed. Engl., 2015, 54, 14911-14914.

  4. “Preparation of iodonium ylides: Probing the fluorination of 1,3-dicarbonyl compounds with a fluoroiodane.” G. C. Geary, E. G. Hope, K. Singh and A. M. Stuart, RSC Adv., 2015, 5, 16501-16506.

  5. “Electrophilic fluorination using a hypervalent iodine reagent derived from fluoride.” G. C. Geary, E. G. Hope, K. Singh and A. M. Stuart, Chem. Commun., 2013, 49, 9263-9265.

  6. “Enantioselective Reformatsky reaction of ethyl iododifluoroacetate with aromatic ketones.” M. Fornalczyk, K. Singh and A. M. Stuart, Org. Biomol. Chem., 2012, 10, 3332-3342.

  7. "Syntheses of α-fluoro-β-hydroxy esters by an enantioselective Reformatsky-type reaction." M. Fornalczyk, K. Singh and A. M. Stuart, Chem. Commun., 2012, 48, 3500-3502.

Research

Fluoroiodane: A New Fluorinating Reagent

In 2013 we reported the preparation of the air- and moisture-stable fluoroiodane reagent 1 from cheap sources of nucleophilic fluoride and its application as a new fluorinating reagent with a series of 1,3-dicarbonyl substrates.4 Since then, the reaction scope of fluoroiodane 1 has extended significantly to other electron-rich substrates such as diazocarbonyl compounds, cyclopropanes, styrenes and alkenes. Most of these reactions, however, required a transition metal catalyst to activate fluoroiodane reagent 1 by coordinating to the fluorine atom. We have now established that 1 can be activated by hydrogen bonding to hexafluoroisopropanol and crucially, it removed the need for transition metals (Scheme 1).1

Scheme 1

Scheme 1

One of the advantages of fluoroiodane 1 is that it offers new regioselectivity and access to novel fluorinated heterocycles.1,2 For example, the unsaturated carboxylic acid underwent a cyclisation, aryl migration and fluorination cascade to deliver the novel lactone containing a tertiary alkyl fluoride, whereas the same reaction with SelectfluorTM provided lactones containing a primary alkyl fluoride (Scheme 1). The disparity arises from the aryl migration occurring during the cascade, which is not possible with Selectfluor.

Enantioselective Fluorinations

One of the most challenging topics in organofluorine chemistry is the enantioselective introduction of fluorine atoms, difluoromethyl and trifluoromethyl groups. We developed a convenient one-pot enantioselective Reformatsky-type reaction of ethyl iododifluoroacetate with ketones using diethylzinc to generate the Reformatsky reagent homogeneously and (1R,2S)-1-phenyl-2-(1-pyrrolidinyl)-1-propanol as the chiral ligand (Scheme 2).5 Good yields (60-90%) and excellent enantiomeric excesses (81-91%) were obtained with a broad range of alkyl aryl ketones that contain enolisable protons as well as functional groups.

Scheme 2

Scheme 2

We also extended this methodology to the preparation of α-fluoro-β-hydroxy esters by an enantioselective Reformatsky-type reaction of ethyl iodofluoroacetate with alkyl aryl ketones (Scheme 3).6 For small alkyl groups the diastereoselectivities were moderate and excellent enantioselectivities were obtained for both diastereomers (74-94% ee). High diastereoselectivities and excellent enantioselectivities for the major diastereomer (93-95% ee) were achieved with larger alkyl groups.

Scheme 3

Scheme 3

Supervision

Current postgraduate opportunities.

Current postdoctoral opportunities.

Share this page:

Contact Details

Department of Chemistry
University of Leicester
Leicester, LE1 7RH, UK

Email: chemistry@le.ac.uk

Tel: [+44] (0)116 252 2100

Fax: [+44] (0)116 252 3789

RSS Logo Subscribe to our news

Facebook logo Like us on Facebook

Twitter @leicesterchemistry Follow us on Twitter

Just click on the logos to keep up to date with our activities!

Department Video