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Department of Chemistry

Prof. Andrew Whiting, BSc Hns, PhD, MRSC CChem

Personal web page

Professor in the Department of Chemistry
Telephone: +44 (0) 191 33 42081
Director, Centre for Sustainable Chemical Processes

(email at andy.whiting@durham.ac.uk)

Director of the Center for Sustainable Chemistry and Catalysis (CSCP)

Biography

PhD (1981-’84): University of Newcastle upon Tyne, working on beta-lactam chemistry. Post-doctoral research (1984-’86): Boston College, MA, USA, working on natural product synthesis and asymmetric synthesis and developing chiral Diels-Alder Lewis-acid catalysts. Industrial experience (1986-’88): Ciba-Geigy plc., Central Research UK, working on varied topics, including developing new methodology for the preparation of novel amino-acid analogues and asymmetric synthesis. Academic experience: Chemistry Department, UMIST (1989-2001), moved to Readership at Durham (2001) and promoted to Professor in 2009.

Current Research Interests

Bifunctional catalysis: synthesis and applications of aminoboronic acids

We are interested in developing new methods for the synthesis of organoboron compounds for a number of reasons (see below) and one major ongoing project in this area involves the design, synthesis and development of new bifunctional catalysts based on amino-boronic acids. For example, homoboroproline is an excellent enamine-based organic/bifunctional catalyst especially when the boron Lewis acidity is tuned in situ by esterification, as show in the following reaction:1

We have also recently developed an efficient highly enantioselective synthesis of the enantiomeric catalyst using an Sn2-like borylation route from natural proline, i.e.:2

Direct amide formation

Despite what we are told at undergraduate level, direct amide formation from amines and carboxylic acids works, and without the need to use atom uneconomic methods. We have been working on the development of catalysts to accomplish this reaction under increasingly lower temperature conditions, especially by using organoboron bifunctional catalysts.3 Recently, we have also delved into the heavily misunderstood uncatalysed reaction which is much more facile than many working in the area realise!  We have proposed, backed up by theoretical calculations, that hydrogen-bonded dimeric carboxylic acid complexes could well be involved in such reactions, as outlined below:4

Nitroso- and imino-dienophile based formal aza-Diels-Alder reactions: novel approaches to nitrogen heterocycles

Our interest in developing novel routes to nitrogen heterocycles using clean catalytic methods goes back many years, particularly involving imino dienophiles.5 Recently, we have developed a novel copper-based air oxidative formation of acyl nitroso species from hydroxamic acids, which are then efficiently trapped out as Diels-Alder adducts, as follows:6

Borylation of unsaturated imines

We are interested in developing new, catalytic, asymmetric routes to gamma-amino alcohols and beta-amino acids etc, and together with Prof Elena Fernández' group at the Universitat Rovira i Virgili in Tarragona, a rapid and efficient entry to such systems is being developed using borylation of unsaturated imines, i.e. as summarised below:7

Stereocontrolled polyene natural product synthesis

We have pioneered the use of vinylboronate esters which undergo Heck-Mizoroki coupling to derive dienyl and polyenyl-boronates systems. This is a powerful technology when coupled with highly efficient iodo-deboronation methods, which can be carried out with either inversion or retention of stereochemistry. The additional use of Suzuki-Miyaura cross-coupling completes the technology to access highly sensitive polyene systems, particularly with cis-alkene geometries present and we are currently part-way through the total synthesis of the anti-leukemic agent viridenomycin and stable analogues using this technology, i.e. as outlined here:8

 

Design and synthesis of organic compounds for controlled cellular development

In collaboration with colleagues in Biology (Prof Stefan Przyborski), here in Chemistry (Professor Todd Marder) and the Northern Centre for Cancer Research, Newcastle (Dr Chris Redfern), we have been designing, preparing and applying new structures based on analogues of retinoic acids (for example, all-trans-retinoic acid, ATRA) as molecular trigger molecules and studying their effect on cell development processes. For example, we have been developing light and heat stable analogues (such as EC239) of ATRA which are still capable of inducing cell differentiation in stem cell systems deriving neural cells.

 

New materials directed synthesis: novel, environmentally benign approaches to crosslinked polymers

We have an ongoing project involving patented technology developed jointly with the Materials Science department at Manchester, which has involved the design and synthesis of bifunctional crosslinking polymer monomers for application in water-borne latex coating systems. For example, HydroxyEthylSulfonylStyrene (HESS)10 is a reactive monomer species which was developed by us to demonstrate the concept in a new entirely-water based crosslinking system.

Acknowledgements

We would like to thank the following for support over the years (not all of which still exist!): EPSRC, BBSRC, MRC, Royal Society, RSC, GSK, Merck, Schering-Plough, Syngenta, Pfizer, Knoll Pharmaceuticals, Johnson-Matthey, Holliday Dyes & Chemicals, ICI Surfactants, Chiroscience, Schlumberger Cambridge Research and Ciba-Geigy.

Recent relevant references

1. I. Georgiou, A. Whiting, Org. Biomol. Chem., 2012, 10, 2422-2430, DOI:10.1039/C2OB06872A and references therein.

2. I. Georgiou, A. Whiting, Eur. J. Org. Chem., 2012, 4110–4113, DOI: 10.1002/ejoc.201200652

3. K. Arnold, A. S. Batsanov, B. Davies, A. Whiting, Green Chem., 2008, 10, 124-134, DOI: 10.1039/b712008g

4. H. Charville, D. Jackson, G. Hodges, A. Whiting, M. R. Wilson, Eur. J. Org. Chem., 2011, 5981–5990, DOI: 10.1002/ejoc.201100714

5. L. Di Bari, S. Guillarme, J. Hanan, A. P. Henderson, J. A. K. Howard, G. Pescitelli, M. R. Probert, P. Salvadori, A. Whiting, Eur. J. Org. Chem., 2007, 5771-5779, DOI: 10.1002/ejoc.200700731

6. D. Chaiyaveij, L. Cleary, A. S. Batsanov, T. B. Marder, K. J. Shea, A. Whiting, Org. Lett., 2011, 13, 3442-3445, DOI: 10.1021/ol201188d

7. C. Solé, A. Tatla, J. Mata, A. Whiting, H. Gulyás, E. Fernandez, Chem. Eur. J., 2011, 17, 14248-14257, DOI: 10.1002/chem.201102081

8. J. P. Knowles, V. E. O’Connor, A. Whiting, Org. Biomol. Chem., 2011, 9, 1876-1886, DOI: 10.1039/c0ob00977f

9. D. J. Maltman, V. B. Christie, J. C. Collings, S. Fenyk, T. B Marder, A. Whiting, S. A Przyborski, Mol. BioSyst., 2009,5, 458-471, DOI: 10.1039/b817912c

10. D. J. Berrisford, P. A. Lovell, N. R. Suliman, A. Whiting, Chem. Commun, 2005, 5904-5906.