Prof. Andrew Whiting, BSc Hns, PhD, FRSC CChem
(email at email@example.com)
Director of the Center for Sustainable Chemistry and Catalysis (CSCP)
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.
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.
Journal papers: academic
- G. Ilyashenko, R. Al-Safadi, R. Donnan, R. Dubrovka, J. Pancholi, M. Watkinson & A. Whiting (Published). Facile synthesis of a 1,1’-desymmetrised ferrocene backbone and its one-pot double-“click” functionalisation. RSC Advances 3(38): 17081.
- Girling, P.R., Batsanov, A.S., Calow, A.D.J., Shen, H.C. & Whiting, A. (2016). Alternative tandem cyclisation pathways in the reaction between imines and enones,. Tetrahedron 72(8): 1105-1113.
- Liu, S., Zhang, Q., Li, H., Yang, Y., Tiana, X. & Whiting, A. (2015). A visible light induced α-H chlorination of alkylarenes with inorganic chloride under nanoAg@AgCl. Chemistry: A European Journal 21(27): 9671-9675.
- Chaiyaveij, D., Batsanov, A.S., Fox, M.A., Marder, T.B. & Whiting, A. (2015). An experimental and computational approach to understanding the reactions of acyl nitroso compounds in [4+2]-cycloadditions. The Journal of Organic Chemistry 80(19): 9518-9534.
- Whiting, Andrew, Madden, Katrina S., David, Sylvain & Knowles, Jonathan P. (2015). Heck-Mizoroki Coupling of Vinyliodide and Applications in The Synthesis of Dienes and Trienes. Chemical Communications 51(57): 11409-11412.
- Pujol, A., Calow, A. D. J., Batsanov, A. S. & Whiting, A. (2015). One-pot catalytic asymmetric borylation of unsaturated aldehyde-derived imines; functionalisation to homoallylic boronate carboxylate ester derivatives. Organic & Biomolecular Chemistry 13(18): 5122-5130.
- Eberlin, Ludovic, Carboni, Bertrand & Whiting, Andrew (2015). Regioisomeric and substituent effects upon the outcome of the reaction of 1-borodienes with nitrosoarene compounds. The Journal of Organic Chemistry 80(13): 6574-6583.
- La Cascia, E., Sanz, X., Bo, C., Whiting, A. & Fernandez, E. (2014). Asymmetric metal free β-boration of α,β-unsaturated imines assisted by (S)-MeBoPhoz. Organic and Biomolecular Chemistry 13(5): 1328-1332.
- Batsanov, A. S., Georgiou, I., Girling, P. R., Pommier, L., Shen, H. C. & Whiting, A. (2014). Asymmetric synthesis and application of homologous pyrroline-2-alkylboronic acids: Identification of the B-N distance for eliciting bifunctional catalysis of an asymmetric aldol reaction. Asian Journal of Organic Chemistry 3(4): 470-479.
- Madden, K. S., Mosa, F. A. & Whiting, A. (2014). Non-isoprenoid polyene natural products - structures and synthetic strategies. Org. Biomol. Chem 12: 7877-7899.
- Calow, A. D. J. Carbó, J. J. Cid, J. Fernández, E. & Whiting, A. (2014). Understanding α,β-unsaturated imine formation from amine additions to α,β-unsaturated aldehydes and ketones: an analytical and theoretical investigation. The Journal of Organic Chemistry 79(11): 5163-5172.
- Tripoteau, F., Eberlin, L., Fox, M. A., Carboni, B. & Whiting, A. (2013). A novel, efficient synthesis of N-aryl pyrroles via reaction of 1-boronodienes with arylnitroso compounds. Chemical Communications 49(47): 5414-5416.
- Calow, A. D. J., Batsanov, A. S., Pujol, A., Solé, C., Fernández, E. & Whiting, A. (2013). A selective transformation of enals into chiral γ-amino alcohols. Organic Letters 15(18): 4810-4813.
- Calow, A. D. J., Solé, C., Whiting. A. & Fernández, E. (2013). Base-free β-boration of α,β-unsaturated imines catalysed by Cu2O with concurrent enhancement of asymmetric induction. ChemCatChem 5(8): 2233-2239.
- Clemens, G., Flower, K.R., Gardner, P., Henderson, A. P., Knowles, J. P., Marder, T. B., Whiting, A. & Przyborski, S. A. (2013). Design and biological evaluation of synthetic retinoids: Probing length vs. stability vs. activity. Molecular BioSystems 9(12): 3124-3134.
- Liu, S., Yang, Y., Liu, X., Ferdousi, F. K., Batsanov, A. S. & Whiting, A. (2013). Direct Amidation of Amino Acid Derivatives Catalyzed by Arylboronic Acids: Applications in Dipeptide Synthesis. European Journal of Organic Chemistry 2013(25): 5692-5700.
- Zhou, G.-L., Tams, D. M., Marder, T. B., Valentine, R., Whiting, A. & Przyborski, S. A. (2013). Synthesis and applications of 2,4-disubstituted thiazoles derivatives as small molecule modulators of cellular development. Organic & Biomolecular Chemistry 11(14): 2323-2334.
- Clemens, G., Flower, K. R., Henderson, A. P., Whiting, A., Przyborski, S. A., Jimenez-Hernandez, M., Ball, F., Bassan, P., Cinque, G. & Gardner, P. (2013). The action of all-trans-retinoic acid (ATRA) and synthetic retinoid analogues (EC19 and EC23) on human pluripotent stem cells differentiation investigated using single cell infrared microspectroscopy. Molecular BioSystems 9(4): 677-692.
- Girling, P.R., Batsanov, A.S., Shen, H.C. & Whiting, A. (2012). A multicomponent formal [1+2+2+1]-cycloaddition for the synthesis of dihydropyridines. Chemical Communications 48(40): 4893-4895.
- I. Georgiou; & A. Whiting; (2012). An efficient enantioselective (R)-homoboroproline from (S)-proline using borylation approach. European Journal of Organic Chemistry 2012(22): 4110-4113.
- A. D. J. Calow;, C. Solé;, E. Fernandez; & A. Whiting; (2012). Novel transformation of α,β-unsaturated aldehydes and ketones to γ-amino alcohols or 1,3-oxazines via a 4 or 5 step, one-pot sequence. Chemical Communications 48(93): 11401.
- W. Na;, A. Messinis;, A. S. Batsanov;, Y. Zhen;, A. Whiting; & T. B. Marder; (2012). Palladium(II)-catalysed tandem cyclisation of electron-deficient aromatic enynes. Chemical Communications 48(80): 9986-9988.
- S. Liu;, Y. Yang;, X. Zhen;, J. Li;, H. He; J. Feng; & A. Whiting; (2012). Stereoselective synthesis and rearrangement-fragmentation of arylidene N-alkoxydiketopiperazines. Organic & Biomolecular Chemistry 10(3): 663-670.
- C. Solé;, A. Tatla;, J. Mata;, A. Whiting;, H. Gulyás; & E. Fernandez; (2011). Catalytic 1,3-difunctionalization of organic backbones via a highly stereoselective, one-pot, boron conjugate-addition/reduction/oxidation process,. Chemistry - A European Journal 17(50): 14248.
- J. P. Knowles;, V. E. O’Connor; & A. Whiting; (2011). Studies towards the synthesis of the northern polyene of viridenomycin and synthesis of Z-double bond analogues. Organic & Biomolecular Chemistry 9(6): 1876-1886.
- R.J. Mears, H.E. Sailes, J.P. Watts & A. Whiting (2006). A stereoselective remote homochiral boronate ester-mediated aldol reaction. 95-103.
- Batsanov, A.S., Lightfoot, A.P., Twiddle, S.J.R. & Whiting, A. (2006). Bis(2,6-dimethylpyridyl)iodonium dibromoiodate. Acta crystallographica section E structure reports online E62: o901-o902.
- H.C. Greenwell, A.A. Bowden, B.Q. Chen, P. Boulet, J.R.G. Evans, P.V. Coveney & A. Whiting (2006). Intercalation and in situ polymerization of poly(alkylene oxide) derivatives within M+-montmorillonite (M = Li, Na, K). 16(11): 1082-1094.
- Blatch, A.J., Howard, J.A.K., Probert, M.R. & Whiting, A. (2006). N-(diphenylphosphinoyl)hydroxylamine. Acta crystallographica section E structure reports online 62(11): o5343-o5345.
- Blatch, A.J., Howard, J.A.K., Probert, M.R., Smethurst, C.A. & Whiting, A. (2006). Potassium 4-nitrophenylsulfonate monohydrate. Acta crystallographica section E structure reports online 62(4): m741-m743.
- A.J. Blatch, O.V. Chetina, J.A.K. Howard, L.G.F. Patrick, C.A. Smethurst & A. Whiting (2006). Synthesis and structure of bifunctional N-alkylbenzimidazole phenylboronate derivatives. Organic & Biomolecular Chemistry 4(17): 3297-3302.
- Blatch, A.J., Howard, J.A.K., Probert, M.R., Smethurst, C.A. & Whiting, A. (2006). tert-Butyl N-(phosphinoyloxy)carbamate. Acta crystallographica section E structure reports online 62(11): o5346-o5348.
- K. Arnold, B. DavieS, R.L. Giles, C. Grosjean, G.E. Smith & A. Whiting (2006). To catalyze or not to catalyze? Insight into direct amide bond formation from amines and carboxylic acids under thermal and catalyzed conditions. 348(7-8): 813-820.
- A. Whiting & S. Walton (2006). Unexpected exothermic reaction between thioacetic acid and DMSO. 10(4): 846-846.