Dr Alison M Stuart

Alison Stuart

Senior Lecturer 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 methods 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 ten of the top thirty best-selling pharmaceutical products in 2008 contained at least one fluorine atom. We are also interested in using fluorous chemistry in order to develop “clean” organic synthesis

Awards received

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

Publications

  1. “Separation, recovery and recycling of a fluorous-tagged nickel catalyst using fluorous solid-phase extraction.” B. Croxtall, E. G. Hope and A. M. Stuart, Chem. Commun., 2003, 2430-2431.
  2. “A recyclable perfluoroalkylated PCP pincer palladium complex.” D. Duncan, E. G. Hope, K. Singh and A. M. Stuart, Dalton Trans., 2011, 40, 1998-2005.
  3. “Novel insoluble perfluoroalkylated polymers: new solid supports for supported fluorous catalysis.” N. Audic, P. W. Dyer, E. G. Hope, A. M. Stuart and S. Suhard, Adv. Synth. Catal., 2010, 352, 2241-50. (Highlighted in Synfacts, 2010, 12, 1432)
  4. “Di(1H,1H,2H,2H-perfluorooctyl)-dibenzo-18-crown-6: A “light fluorous” recyclable phase transfer catalyst.” B. Gourdet, K. Singh, A. M. Stuart and J. A. Vidal, J. Fluorine Chem., 2010, 131, 1133-1143.
  5. “Perfluoroalkylated 4,13-diaza-18-crown-6 ethers: Synthesis, phase-transfer catalysis, and recycling studies.” A. M. Stuart and J. A. Vidal, J. Org. Chem., 2007, 72, 3735-3740.
  6. “Syntheses and properties of fluorous quaternary phosphonium salts that bear four ponytails; new candidates for phase transfer catalysts and ionic liquids.” C. Emnet, K. M. Weber, J. A. Vidal, C. S. Consorti, A. M. Stuart and J. A. Gladysz, Adv. Synth.  Catal., 2006, 348, 1625-1634.
  7. “Enantioselective Reformatsky reaction of ethyl iododifluoroacetate with aromatic ketones.” M. Fornalczyk, K. Singh and A. M. Stuart, Org. Biomol. Chem., 2012, 10, 3332-3342.
  8. “Syntheses of a-fluoro-b-hydroxy esters by an enantioselective Reformatsky-type reaction." M. Fornalczyk, K. Singh and A. M. Stuart, Chem. Commun., 2012, 48, 3500-3502. (Highlighted in Synfacts, 2012, 8, 656)
  9. “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, DOI: 10.1039/C3CC44792H.

Research

Electrophilic Fluorination Using Hypervalent Iodine Reagents

In late 2011, Ritter reported the first example of a formal umpolung of fluoride by the clever design of a palladium-based electrophilic fluorination reagent derived from fluoride and used to synthesise aromatic 18F-labelled molecules.

As part of a  research program my aim is to develop an alternative, non-metal based strategy using cyclic hypervalent iodine(III) compounds. To this end, in collaboration with Professor Eric Hope, we have synthesised the electrophilic hypervalent iodine reagent 2 by the nucleophilic fluorination of the hydroxyiodane 1 with triethylamine tris(hydrogenfluoride) (TREAT-HF).

AMS 1

Preliminary reactivity studies have revealed that the air and moisture stable fluoroiodane 2 can be used for the electrophilic fluorination of 1,3-dicarbonyl compounds (Scheme 1) and we are currently investigating further applications of 2 as an electrophilic fluorinating reagent with a range of different organic substrates.

Fluorinated Reformatsky Reaction

One of the most challenging topics in organofluorine chemistry is the enantioselective introduction of fluorine atoms, difluoromethyl and trifluoromethyl groups.  We have 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).  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.

AMS 2

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

AMS 3

Fluorous Catalysis

Fluorous chemistry is a powerful separation technology for recycling catalysts and reagents that contain long perfluoroalkyl groups.  We reported, in collaboration with Prof Eric Hope, the first example of recycling a perfluoroalkylated transition metal catalyst using fluorous solid-phase extraction.

AMS 4Fluorous solid-phase extraction is essentially a filtration that separates the organic products from the fluorous catalyst by flash chromatography on fluorous reverse phase silica gel.  Recently, we have demonstrated that a perfluoroalkylated PCP pincer palladium complex (Figure 1) can be recovered intact by fluorous solid-phase extraction and was reused four times in the Heck reaction between methyl acrylate and 4-bromoacetophenone without loss in catalytic activity.

We have also synthesised a range of phase transfer catalysts derivatised with long perfluoroalkyl groups and demonstrated their straightforward recovery and recycling using fluorous solid-phase extraction.

Furthermore, we have prepared new perfluoroalkylated polystyrene resins and evaluated these highly fluorinated insoluble materials as catalyst supports for rhodium-catalysed hydrogenation and palladium-mediated Suzuki-Miyaura carbon-carbon bond forming reactions.

Supervision

Current postgraduate opportunities.

Current postdoctoral opportunities.

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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

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