My group is interested in the development of new methods for the synthesis of functionalised, complex molecules with applications.
Current Research Interests: Macrocycle Synthesis, Direct Imine Acylation, spirocyclisation, C–H activation, alkyne activation, copper catalysis, rhodium catalysis, asymmetric synthesis, target synthesis. More deatils on current projects are included below:
Important applications across the physical sciences rely on the synthesis of functionalised macrocycles. At present, macrocycles are typically made via the end-to-end cyclisation of a linear precursor, a notoriously difficult and unpredictable transformation; in particular, achieving macrocyclisation (1 → 2, Figure 1a) rather than dimerisation (1 → 3) is a major challenge. The most common strategy used to combat this is to perform the reactions at high-dilution but while successful in many cases, such protocols are generally highly substrate dependent and impractical for large scale synthesis.
Successive Ring Expansion (SuRE for short) is designed to improve the efficiency of macrocycle synthesis by completely avoiding end-to-end macrocyclisation. It is based on the sequential insertion of linear fragments into existing cyclic systems, by coupling a cyclic compound (4) to a linear fragment 5, which can thenrearrange (6), initiating ring expansion, forming a ring enlarged product 7. A key design feature is the replication of the functionality in the cyclic starter unit in the ring-expanded product (circled), as this means that the same coupling/ring expansion sequence can be repeated, allowing further iterations to be performed in the same way (7 → 9; 9 → 11). SuRE can incorporate a range of linear fragments and can theoretically be repeated indefinitely, meaning macrocycles of virtually any ring size and composition are potentially accessible.
More deatils on this concept can be found in our first publication arising from this project, see: Angew. Chem. Int. Ed. 2015, 54, 15794 –15798. In this paper, the SuRE concept is validated using a telescoped two-step sequence, to generate macrocyclic lactams and lactones from cyclic β-keto esters (Figure 1c).
See also: Ring expansion approach to medium-sized lactams and analysis of their medicinal lead-like properties
L. G. Baud, M. A. Manning, H. L. Arkless, T. C. Stephens, W. P. Unsworth, Chem. Eur. J. 2017, 23, 2225.
Synthesis of Cyclic Peptide Mimetics by the Successive Ring Expansion of Lactams
T. C. Stephens, M. Lodi, A. Steer, Y. Lin, M. Gill, W. P. Unsworth, Chem. Eur. J. 2017 doi: 10.1002/chem.201703316
We are interested in the development of new catalytic processes in which multiple products can be generated from a common precursor through catalyst variation. This work has two major benefits: 1) by generating multiple products from a single starting material, the synthesis of potentially valuable compounds can be signifricantly streamlined; 2) we believe that challenging ourselves to uncover new catalyst selective synthetic methods is an effective way to inspire the discovery of new reactions and deliver new insight in catalytic processes.
The best illustration of this can be found in our 2016 publication entitled: Selective Synthesis of Six Products from a Single Indolyl α-Diazocarbonyl Precursor. The essence of work is in illustrated in the art work below; much as a single light source can be split into an array of colours with different visible properties, for example in a rainbow, we have been able to apply this concept chemically, to generate an array of 6 products with diverse chemical properties from a single precursor.
We are interested in the development of new dearomatising spirocyclisation methods, especially those involving alkyne activation with π-acids and metal carbenoid intermedaites.
For selected publications, see:
J. T. R. Liddon, M. J. James, A. K. Clarke, P. O'Brien, R. J. K. Taylor, W. P. Unsworth, Chem. Eur. J. 2016, 22, 8777–8780.
M. J. James, R. E. Clubley, K. Y. Palate, T. J. Procter, A. C. Wyton, P. O’Brien, R. J. K. Taylor, W. P. Unsworth, Org. Lett. 2015, 17, 4372.
M. J. James, J. Cuthbertson, P. O’Brien, R. J. K. Taylor, W. P. Unsworth, Angew. Chem. Int. Ed. 2015, 54, 7640.
D. S. Gkotsi, H. Ludewig, S. V. Sharma, W. P. Unsworth, R. J. K. Taylor, M. M. W. McLachlan, S. Shanahan, J. H. Naismith, R. J. M. Goss, Nature Chem. 2019 doi: 10.1038/s41557-019-0349-z
A. Lawer; J. A. Rossi-Ashton; T. C. Stephens; B. J. Challis; R. G. Epton; J. M Lynam; W. P. Unsworth, Angew. Chem., Int. Ed. 2019, 58, 13942–13947
H. E. Ho, T. C. Stephens, T. J. Payne, P. O’Brien, R. J. K. Taylor, W. P. Unsworth, ACS Catal. 2019, 9, 504–510
A. K. Clarke, J. M. Lynam, R. J. K. Taylor, W. P. Unsworth, ACS Catal. 2018, 8, 6844
H. E. Ho, M. J. James, P. O’Brien, R. J. K. Taylor, W. P. Unsworth, Org. Lett. 2018, 20, 1439
J. T. R. Liddon, J. A. Rossi-Ashton, R. J. K. Taylor, W. P. Unsworth, Org. Lett. 2018, 20, 3349
T. C. Stephens, M. Lodi, A. Steer, Y. Lin, M. Gill, W. P. Unsworth, Chem. Eur. J. 2017, 23, 13314
W. P. Unsworth, J. R. Donald, Chem. Eur. J. 2017, 23, 8780
Ring expansion approach to medium-sized lactams and analysis of their medicinal lead-like properties
L. G. Baud, M. A. Manning, H. L. Arkless, T. C. Stephens, W. P. Unsworth, Chem. Eur. J. 2017, 23, 2225.Selective Synthesis of Six Products from a Single Indolyl α-Diazocarbonyl Precursor
M. J. James, P. O’Brien, R. J. K. Taylor, W. P. Unsworth, Angew. Chem. Int. Ed. 2016,
J. T. R. Liddon, M. J. James, A. K. Clarke, P. O'Brien, R. J. K. Taylor, W. P. Unsworth, Chem. Eur. J. 2016, 22, 8777–8780.
S.J. Chambers, G. Coulthard, W. P. Unsworth, P. O’Brien, R. J. K. Taylor, Chem. Eur. J. 2016, 22, 6496–6500.
Synthesis of Spirocyclic Indolenines
M. J. James, P. O’Brien, R. J. K. Taylor, W. P. Unsworth, Chem. Eur. J. 2016 22, 2856–2881.
The Synthesis of Structurally Diverse Macrocycles By Successive Ring Expansion
C. Kitsiou, J. J. Hindes, P. I’Anson, P. Jackson, T. C. Wilson, E. K. Daly, H. R. Felstead, P. Hearnshaw, W. P. Unsworth, Angew. Chem. Int. Ed. 2015, 54, 15794 –15798.
M. J. James, R. E. Clubley, K. Y. Palate, T. J. Procter, A. C. Wyton, P. O’Brien, R. J. K. Taylor, W. P. Unsworth, Org. Lett. 2015, 17, 4372.
M. J. James, J. Cuthbertson, P. O’Brien, R. J. K. Taylor, W. P. Unsworth, Angew. Chem. Int. Ed. 2015, 54, 7640.
Direct Imine Acylation for Molecular Diversity in Heterocyclic Synthesis.
W P Unsworth, G Coulthard, C Kitsiou, and R J K Taylor, J. Org. Chem., 2014, 79, 1368.
Dearomatizing Spiroannulation Reagents: Direct Access to Spirocycles from Indoles and Dihalides
Current Group Members
Dr Aimee Clarke (EPSRC funded PDRA)
Dr. Hon Eong Ho (EPSRC funded PDRA, co-supervised with Richard Taylor and Peter O'Brien)
James Rossi-Ashton (4th year PhD, co-supervised with Richard Taylor)
Wendy Robinson (3rd year PhD student, co-supervised with Gideon Grogan and Alison Parkin)
Kleopas Palate (3rd year PhD student, co-supervised with Peter O'Brien)
Ryan Epton (2nd year PhD student, co-supervised with Jason Lynam)
Rebecca Donovan (2nd year PhD student, co-supervised with Tom Farmer and Rob McElroy)
Balazs Pogranyi (2nd year PhD student, co-supervised with Gideon Grogan)
Zhongzhen Yang (1st year PhD student)
Nantachai Inprung (1st year PhD student, co-supervised with Richard Taylor and Michael James)
Verity Barber (1st year PhD student, co-supervised with Gideon Grogan)
Dominic Spurling (MRes)
James Clegg (MChem)
Ruben Godwin-Suttie (MChem)
Farhaan Dobah (visiting student from University of Cape Town)
Youstena Hana (Erasmus)
Former Group Members
Thomas Stephens (PhD student, co-supervised with Martin Fascione)
Chris Baldwin (MChem 2018-19)
Jess Hine (MChem 2018-19)
Angela Pagano (Erasmus+ student)
Dr Aggie Lawer (EPSRC funded PDRA, 2018)
Yun Lin (MRes)
Michelle Yeung (MRes)
Emilie Marotte (Erasmus student)
Emma Wright (MChem 2017-18)
Brad Challis (MChem 2017-18)
Dr. Mahendar Lodi (Indian-SERB funded PDRA 2016-17)
Jade Sangha (MChem 2016-17)
James Pitts (MChem 2016-17)
Andrew Steer (Research Associate, 2017, co-supervised with Alison Parkin and Gideon Grogan)
Leonard Himmel (Erasmus student 2017)
Laetitia Baud (Erasmus student 2016)
Morgan Manning (MChem 2015-16)
Helen Arkless (MChem 2015-16)
Christiana Kitsiou (PDRA, 2015)
Phil I'Anson (MChem 2014-15)
Jordan Hindes (MChem 2014-15)
Paula Jackson (MChem 2013-14)
Thomas Wilson (MChem 2013-14)
Visitors/placement students
Somchai Noppawan (2017-18)
Matthew Gill (2016)
Darius Stankevicius (2016)
Hannah Felstead (2015)
Eleanor Daly (2014)
Peter Hearnshaw (2013)
For more recent news, follow the Unsworth group on Twitter @UnsworthChem
Biography
Will is originally from Coppull, near Chorley in Lancashire (UK). He studied chemistry at the University of Oxford, and remained there to complete his Ph.D. studies in the group of Prof. Jeremy Robertson. He completed his Ph.D. in 2010 and then began work at the University of York, first as a postdoctoral research associate in the group of Prof. Richard J. K. Taylor, before being appointed to a Research and Teaching Fellowship in 2013. In 2016 Will took up a Leverhulme Trust Early Career Fellowship to develop new procedures to synthesise functionalised macrocycles and is now the holder of the inaugrual Eleanor Dodson Fellowship at the University of York. His current research interests include ring expansion approaches for the synthesis of medium-sized rings and macrocycles, the construction of diverse spirocyclic scaffolds, cascade reactions and total synthesis. He now lives in York with his wife Hayley and two children Billy and Catherine.
Invited Talks/Seminars
2019
2018
2017
2016
2015
2014
Awards
For current PhD opportunities, see main York Chemistry pages.
Applications from self-funded PhD/PDRA level researchers and Erasmus students are welcomed; contact Will directly for advice and details of current projects (william.unsworth@york.ac.uk)
Group photo 2017
Group Christmas meal 2016
Group Photo 2016 (Left to Right: Lin, Ton, James P, Leo, Will, Jade, James R, Michelle)
Gregynog Synthesis Meeting 2016
Will presenting his SuRE methodlogy at the BMOS meeting, Buzios, Rio de Janeiro, Brazil