Chemistry

Richard J Whitby

Primary position:
Professor of Organic Chemistry

Background

The University of Southampton
Professor Richard J Whitby's photo

ResearcherID

ORCID

Richard Whitby graduated with a BA in Natural Sciences from Trinity College, Cambridge University in 1982. After a PhD with Professor P. G. Sammes at the University of Leeds and a fellowship with Professor P. J. Kocienski at the University of Southampton he was appointed to a lectureship at Southampton in 1988. In 1995 he was awarded the Society of the Chemical Industry 'Young Chemists' award, the Zeneca Research Award in Organic Chemistry and the Pfizer Research Award in Chemistry. In 1996, Richard Whitby became a Reader and was also awarded the GlaxoWelcome 'Innovative Chemistry' Research Award. He was promoted to Professor of Organic Chemistry in 1999, the year in which he received the Royal Society of Chemistry Bader award.

He has published chapters in two books on zirconium chemistry, contributed to special issues of Tetrahedron and Synthesis dedicated to Organotransition metal chemistry applied to organic synthesis and presented his work at many international conferences.

He originated and leads the ‘Dial-a-Molecule’ Grand Challenge (www.dial-a-molecule.org) which has the 20-40 year aim of making the synthesis of new molecules as quick and easy as it currently is to order a commercial compound.

His research interests include total synthesis, particularly using transition metal chemistry to rapidly assemble structures; Novel polyaromatic and heteroaromatic compounds for applications in molecular and organic electronics, photovoltaics, and Organic Light Emitting Diodes; The synthesis and properties of endohedral fullerenes (such as H2O@C60) using molecular surgery; The development of flow and automated chemistry, particularly using in-situ analysis to allow rapid optimization and mechanistic investigation; The synthesis and evaluation of biologically active molecules including agonists and antagonists of the orphan nuclear receptors LRH-1 and SF-1; Development of cheminformatics in synthesis, particularly developing ways of capturing, sharing and using detailed data on reaction execution and outcomes.

He is currently a member of the Organic Division Council of the Royal Society of Chemistry and on the advisory board of the national Chemical Database Service.

Links to

Organic synthesis using early transition metal chemistry

Novel polyaromatic and heteroaromatic compounds for Organic and Molecular Electronics, Organic Light Emitting Diodes and Organic Photovoltaic devices.

Synthesis and properties of endohedral fullerenes

Investigation and optimization of reactions using automated and flow chemistry.

The orphan nuclear receptors LRH-1 and SF-1.

Publications

The University of Southampton's electronic library (e-prints)

Key Publications

Martin, Santiago, Giustiniano, Francesco, Haiss, Wolfgang, Higgins, Simon J., Whitby, Richard J. and Nichols, Richard J. (2009) Influence of conformational flexibility on single-molecule conductance in nano-electrical junctions. Journal of Physical Chemistry C, 113, (43), 18884-18890. (doi:10.1021/jp906763p).
Henderson, Alan R., Stec, Jozef, Owen, David R. and Whitby, Richard J. (2012) The first total synthesis of (+)-mucosin. Chemical Communications, 48, (28), 3409-3411. (doi:10.1039/c2cc17915f). (PMID:22358150).
Whitby, Richard J., Stec, Jozef, Blind, Raymond D., Dixon, Sally, Leesnitzer, Lisa M., Orband-Miller, Lisa A., Williams, Shawn P., Willson, Timothy M., Xu, Robert, Zuercher, William J., Cai, Fang and Ingraham, Holly A. (2011) Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2). Journal of Medicinal Chemistry, 54, (7), 2266-2281. (doi:10.1021/jm1014296).
Thomas, Emma, Dixon, Sally and Whitby, Richard J. (2007) The regiochemistry of zirconacycle elaboration. Tetrahedron, 63, (47), 11686-11701. (doi:10.1016/j.tet.2007.08.105).
Harrowven, David C., Mohamed, Mubina, Gonçalves, Théo P., Whitby, Richard J., Bolien, David and Sneddon, Helen F. (2012) An efficient flow-photochemical synthesis of 5H-furanones leads to an understanding of torquoselectivity in cyclobutenone rearrangements. Angewandte Chemie International Edition, 51, (18), 4405-4408. (doi:10.1002/anie.201200281).

Article

Krachmalnicoff, Andrea, Bounds, Richard, Mamone, Salvatore, Levitt, Malcolm H., Carravetta, Marina and Whitby, Richard (2015) Synthesis and characterisation of an open-cage fullerene encapsulating hydrogen fluoride. Chemical Communications, 1-4. (doi:10.1039/C5CC00499C).
Henry, Cyril, Bolien, David, Ibanescu, Bogdan, Bloodworth, Sally, Harrowven, David C., Zhang, Xunli, Craven, Andy, Sneddon, Helen F. and Whitby, Richard J. (2015) Generation and trapping of ketenes in flow. European Journal of Organic Chemistry, 2015, (7), 1491-1499. (doi:10.1002/ejoc.201403603).
Krachmalnicoff, A., Levitt, M. and Whitby, R. (2014) An optimised scalable synthesis of H2O@C60and a new synthesis of H2@C60. Chemical Communications (doi:10.1039/C4CC06198E).
Mamone, Salvatore, Concistrè, Maria, Carignani, Elisa, Meier, Benno, Krachmalnicoff, Andrea, Johannessen, Ole G., Lei, Xuegong, Li, Yongjun, Denning, Mark, Carravetta, Marina, Goh, Kelvin, Horsewill, Anthony J., Whitby, Richard J. and Levitt, Malcolm H. (2014) Nuclear spin conversion of water inside fullerene cages detected by low-temperature nuclear magnetic resonance. The Journal of Chemical Physics, 140, (19), 194306. (doi:10.1063/1.4873343).
Mamrosh, Jennifer L., Lee, Jae M., Wagner, Martin, Stambrook, Peter J., Whitby, Richard J., Sifers, Richard N., Wu, San-pin, Tsai, Ming-jer, DeMayo, Fransesco J. and Moore, David D. (2014) Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic reticulum stress resolution. eLife, 1-24. (doi:10.7554/eLife.01694).
Coles, Simon J., Frey, Jeremy G., Bird, Colin L., Whitby, Richard J. and Day, Aileen E. (2013) First steps towards semantic descriptions of electronic laboratory notebook records. Journal of Cheminformatics, 5, (52), 1-10. (doi:10.1186/1758-2946-5-52).
Richard, Vincent, Ipouck, Melinda, Gaillard, Sylvain, Whitby, Richard J., Witulski, Bernhard and Renaud, Jean-Luc (2013) Iron(II)-catalysed [2+2+2] cycloaddition for pyridine ring construction. Chemical Communications, 50, 593-595. (doi:10.1039/C3CC47700B).
Coles, Simon J., Whitby, Richard J., Day, A., Willoughby, Cerys, Tkachenko, V., Frey, Jeremy G. and Williams, A.J. (2013) Tablets in the lab: enabling the flow of chemical synthesis data into a chemistry repository. Abstracts of Papers of the American Chemical Society
Harrowven, David C., Mohamed, Mubina, Gonçalves, Théo P., Whitby, Richard J., Bolien, David and Sneddon, Helen F. (2012) An efficient flow-photochemical synthesis of 5H-furanones leads to an understanding of torquoselectivity in cyclobutenone rearrangements. Angewandte Chemie, 124, (18), 4481-4484. (doi:10.1002/ange.201200281). (PMID:22441937).
Stec, Jozef, Henderson, Alan R. and Whitby, Richard J. (2012) Synthesis of homopropargyl alcohols via insertion of allenyl carbenoids into acyclic organozirconium bonds. Tetrahedron Letters, 53, (9), 1112-1115. (doi:10.1016/j.tetlet.2011.12.081).
Zhang, Yuxia, Yang, Zhihong, Whitby, Richard and Wang, Li (2011) Regulation of miR-200c by nuclear receptors PPARα, LRH-1 and SHP. Biochemical and Biophysical Research Communications, 416, (1-2), 135-139. (doi:10.1016/j.bbrc.2011.11.011). (PMID:22100809).
Mohamed, Mubina, Gonçalves, Théo P., Whitby, Richard J., Sneddon, Helen F. and Harrowven, David C. (2011) New insights into cyclobutenone rearrangements: a total synthesis of the natural ROS-generating anti-cancer agent cribrostatin 6. Chemistry - A European Journal, 17, (49), 13698-13705. (doi:10.1002/chem.201102263).
Parfenova, Lyudmila V., Berestova, Tatyana V., Tyumkina, Tatyana V., Kovyazin, Pavel V., Khalilov, Leonard M., Whitby, Richard J. and Dzhemilev, Usein M. (2010) Enantioselectivity of chiral zirconocenes as catalysts in alkene hydro-, carbo- and cycloalumination reactions. Tetrahedron: Asymmetry, 21, (3), 299-310. (doi:10.1016/j.tetasy.2010.01.001).
Thiruchelvam, Paul T. R., Lai, Chun-Fui, Hua, Hui, Thomas, Ross S., Hurtado, Antoni, Hudson, William, Bayly, Andrew R., Kyle, Fiona J., Periyasamy, Manikandan, Photiou, Andrew, Spivey, Alan C., Ortlund, Eric A., Whitby, Richard J., Carroll, Jason S., Coombes, R. Charles, Buluwela, Laki and Ali, Simak (2010) The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells. Breast Cancer Research and Treatment (doi:10.1007/s10549-010-0994-9). (PMID:20607599).
Marsh, Dan H., Rance, Graham A., Whitby, Richard J., Giustiniano, Francesco and Khlobystov, Andrei N. (2008) Assembly, structure and electrical conductance of carbon nanotube-gold nanoparticle 2D heterostructures. Journal of Materials Chemistry, 18, (19), 2249-2256. (doi:10.1039/b801334a).
Marsh, Dan H., Rance, Graham A., Zaka, Mujtaba H., Whitby, Richard J. and Khlobystov, Andrei N. (2007) Comparison of the stability of multiwalled carbon nanotube dispersions in water. Physical Chemistry Chemical Physics, 9, (40), 5490-5496. (doi:10.1039/b708460a).
Macfarlane, Donald P.S., Norton, David, Whitby, Richard J. and Tupper, David (2006) Zirconium-mediated synthesis of azepanes and benzazepanes. Synlett, (20), 3439-3442. (doi:10.1055/s-2006-956477).
Thomas, Emma, Kasatkin, Alexander N. and Whitby, Richard J. (2006) Cyclopropyl carbenoid insertion into alkenylzirconocenes: a convergent synthesis of alkenylcyclopropanes and alkylidenecyclopropanes. Tetrahedron Letters, 47, (52), 9181-9185. (doi:10.1016/j.tetlet.2006.10.132).
Whitby, Richard J., Dixon, Sally, Maloney, Patrick R., Delerive, Philippe, Goodwin, Bryan J., Parks, Derek J. and Willson, Timothy M. (2006) Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1. Journal of Medicinal Chemistry, 49, (23), 6652-6655. (doi:10.1021/jm060990k).
Thomas, Emma, Dixon, Sally and Whitby, Richard J. (2006) A rearrangement to a zirconium-alkenylidene in the insertion of dihalocarbenoids and acetylides into zirconacycles. Angewandte Chemie International Edition, 45, (42), 7070-7072. (doi:10.1002/anie.200602822).
Dixon, Sally and Whitby, Richard J. (2006) Efficient synthesis of thioamide terminated molecular wires. Tetrahedron Letters, 47, (46), 8147-8150. (doi:10.1016/j.tetlet.2006.09.032).
Hunter, Rupert A., Macfarlane, Donald P.S. and Whitby, Richard J. (2006) Organozirconium-mediated solution- and solid-phase synthesis of 3-benzyl pyrrolidines and other potentially neuroactive amines. Synlett, (19), 3314-3318. (doi:10.1055/s-2006-951553).
Kishore, K., Tetala, R., Whitby, R. J., Light, M. E. and Hursthouse, M. B. (2004) Corrigendum to Palladium-catalysed three component synthesis of α, β-unsaturated amidines and imidates [Tetrahedron Lett. 45 (2004) 6991]. Tetrahedron Letters, 45, (45), 8427-8427. (doi:10.1016/j.tetlet.2004.09.077).
Hunter, R. A., Whitby, R. J., Light, M. E. and Hursthouse, M. B. (2004) Synthesis of phosphinines and phosphinanes using zirconium chemistry. Tetrahedron Letters, 45, (41), 7633-7636. (doi:10.1016/j.tetlet.2004.08.098).
Kishore, K., Tetala, R., Whitby, R. J., Light, M. E. and Hurtshouse, M. B. (2004) Palladium-catalysed three component synthesis of α, β-unsaturated amidines and imidates. Tetrahedron Letters, 45, (38), 6991-6994. (doi:10.1016/j.tetlet.2004.07.150).
Saluste, C. Gustaf, Crumpler, S.imon, Furber, Mark and Whitby, Richard J. (2004) Palladium catalysed synthesis of cyclic amidines and imidates. Tetrahedron Letters, 45, (38), 6995-6996. (doi:10.1016/j.tetlet.2004.07.151).
Norton, David, Whitby, Richard J. and Griffen, Ed (2004) Insertion of (E)-(1,2-dihalovinyl)lithium and (2-haloethynyl)lithium into zirconacycles. Chemical Communications, (10), 1214-1215. (doi:10.1039/b403337j).
Whitby, R.J. (2004) Carbenoid insertion into organozirconocenes. Abstracts of Papers of the American Chemical Society, 227, U129-U129.
Dixon, S., Fillery, S. M., Kasatkin, A., Norton, D., Thomas, E. and Whitby, R. J. (2004) Ring expansion of 5-to 6-member zirconacycles by carbenoid insertion. Tetrahedron, 60, (6), 1401-1416. (doi:10.1016/j.tet.2003.09.056).
Whitby, Richard J., Saluste, C.Gustaf and Furber, Mark (2004) Synthesis of α-iminoimidates by palladium catalysed double isonitrile insertion. Organic & Biomolecular Chemistry, 2, (14), 1974-1976. (doi:10.1039/b408673m).
Kasatkin, A. and Whitby, R. J. (2003) A convergent regiospecific synthesis of zirconium enolates. Tetrahedron, 59, (49), 9857-9864. (doi:10.1016/j.tet.2003.09.022).
Baldwin, I.R. and Whitby, R.J. (2003) Total synthesis of (+/-)-acetoxyodontoschismenol using zirconium chemistry. Chemical Communications, 2003, (22), 2786-2787. (doi:10.1039/b309848f).
Saluste, C. Gustaf, Whitby, Richard J. and Furber, Mark (2001) Palladium-catalysed synthesis of imidates, thioimidates and amidines from aryl halides. Tetrahedron Letters, 42, (35), 6191-6194. (doi:10.1016/S0040-4039(01)01201-1).

Book Section

Dixon, Sally and Whitby, Richard J. (2002) Elaboration of organozirconium species by insertion of carbenoids. In, Marek, IIan (ed.) Titanium and Zirconium in Organic Synthesis. Chichester, GB, Wiley, 86-109. (doi:10.1002/3527600671.ch3).

Conference or Workshop Item

Bird, Colin, Coles, Simon J., Day, Aileen, Frey, Jeremy G. and Whitby, Richard J. (2014) Extracting data, information, and knowledge from an ELN. In, 247th ACS National Meeting & Exposition , Dallas, US, 16 - 20 Mar 2014.
 

Research

Research Interests

Prof. Whitby’s research interests span a wide range from using synthetic chemistry to tackle important scientific and societal problems, to developing the technology and informatics of synthesis itself. Current research interests include:

New synthetic methods using transition metals and application to organic synthesis. Our work focuses on various tandem processes using zirconocene templates to rapidly assemble complex organic structures. Particularly powerful has been methods based on the insertion of carbenoids into organozirconocene chlorides or zirconacycles. We have applied zirconium mediated key steps to the synthesis of several natural products. We have also developed a novel approach to chiral zirconocene complexes and applied them to catalytic carbomagnesiation and carboalumination reactions.

Ligands for Orphan Nuclear Receptors. We developed the first small molecule agonists for the important nuclear receptors SF-1 and LRH-1 with potential for application in a variety of biological and therapeutic areas including Stem Cell research and several cancers. Our molecules have been used in 20 laboratories worldwide to investigate the biology of these receptors. We are currently working on targets with better bioavailability, and aiming for antagonist activity.

Endohedral Fullerenes. We perform molecular surgery on fullerenes such as C60. The procedure involves opening a hole in the fullerene cage so that a small molecule such as H2 or H2O can be inserted, then suturing the opening to reform the pristine cage thus making endohedral fullerenes such as H2O@C60 and H2@C60. The molecules have fascinating quantum properties as a result of the presence or ortho- and para- spin isomers of the ‘H2’ systems. We recently ‘caged’ HF for the first time.

Flow chemistry. We are developing new synthetic methods which take advantage of flow chemistry (continuous processing) techniques. Currently we are working mostly on ‘reagentless’ methods such as using very high temperatures or photochemistry to achieve conversions. We also us flow techniques, particularly with the use of in-line IR, UV, and HPLC-MS, to allow rapid kinetic characterisation and optimisation of reactions.

Automated Chemistry and Closed Loop Optimisation. As part of a multi-disciplinary effort we are developing systems which will automatically and efficiently establish the scope and optimum conditions for reactions. The systems analyse the composition of reactions in real time and use the results to design and execute more experiments in an iterative process which should end with a complete reaction model. The work uses both flow and automated parallel batch reactors.

Organic electronics. We are designing and synthesising molecules with useful optoelectronic properties for application in organic electronics and photovoltaics. The work is lead by high level ab-inito calculations on properties. The current focus is on polyaromatic and heteroaromatic systems. Closely related is work on Molecular Electronics. We are designing and synthesising molecules which could form components of molecular circuits as well as working with colleagues from other disciplines on their electrical characterisation.

“Dial-a-Molecule” (http://www.dial-a-molecule.org) is an EPSRC funded Grand Challenge network which I lead. It is aimed at making the synthesis of novel molecules as quick as it currently is to order a stock chemical. A key to Dial-a-Molecule is to be able to predict the outcome of novel reactions, and hence the best way to do them and the best synthetic route. One requirement is high quality data on both successful and less successful reactions. We are working to facilitate the adoption of Electronic Laboratory Notebooks by academia as a way of ensuring that in the future such data is collected in a potentially usable form. We are also working on common data formats to enable sharing of such data and are looking forward to new ways to use the data.

Primary research group:  Organic Chemistry: Synthesis, Catalysis and Flow

Research projects

Whitby: Organic synthesis using transition metal chemistry

Innovative Synthesis, Culture and Entrepreneurship in Chemistry (ISCE-Chem)

Whitby: Insertion of carbenoids into organozirconocene chlorides

Whitby: Natural product synthesis using zirconium chemistry

Whitby: Insertion of carbenoids into zirconacycles

Whitby: Synthesis of Bioactive compounds: Ligands for Nuclear Receptors and Neuroactive amines

Whitby: Invention of new transition metal catalysed reactions

Whitby: Asymmetric Synthesis - Novel chiral transition metal complexes

Nandhakumar & Whitby: Molecular Electronics and Neural Networks

Contact

Professor Richard J Whitby
Chemistry University of Southampton Highfield Southampton SO17 1BJ

Room Number: 30/3035

Telephone: (023) 8059 2777
Facsimile: (023) 8059 3781
Email: R.J.Whitby@soton.ac.uk