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Catalyst Diversity from Chiral Palladacycles

Lead Research Organisation: University of East Anglia
Department Name: Chemistry

Abstract

Catalytic methodologies have a very major impact on improving the efficiency and cost effectiveness of synthesis, a key (usually the key) technology for the development of new medicines, agrochemicals, materials, fragrances and, in turn, further catalysts. This programme will generate a platform for the discovery of chiral palladium catalysts for use in asymmetric synthesis based upon a new method of catalyst formation. This will allow numerous catalysts to be generated in just one step from palladium-based complexes, the synthesis of which has been pioneered within the Richards group. Access to a diverse array of palladium catalysts will enable the optimisation of selectivity and the minimisation of the quantity of catalyst required in a host of reactions. In addition, the new catalyst generation protocol will enable facile immobilisation, boosting further the sustainability of the chemistry through catalyst recovery and reuse. The new platform will be applied to the selective synthesis of novel and varied chiral (i.e. handed) structures, diversity generation lying at the heart of the process of discovering new bioactive compounds for application in drug discovery programmes.

Planned Impact

Beyond academia, beneficiaries will include the pharmaceutical industry, the agrochemical industry, and more specialist companies focused on the synthesis of fine chemicals and compound libraries. Novel catalysts may exploited for wealth creation through the discovery and manufacture of high value products. These include new medicines, and also related compounds that enable a full scientific understanding of a disease and its treatment. Other ways in which this work will directly benefit society by addressing global challenges is through potential application to the discovery and manufacture of new materials and agrochemicals, and through the specialist expertise to be garnered by the PDRA and PI. Interwoven with these societal benefits is the economic impact through the support of sectors of UK industry that are vital for employment and the UK balance of payments.

Publications

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Arthurs R (2021) Copper(I) Complexes of P -Stereogenic Josiphos and Related Ligands in European Journal of Organic Chemistry

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Arthurs RA (2020) Planar chiral palladacycle precatalysts for asymmetric synthesis. in Organic & biomolecular chemistry

 
Description The central objective of this programme was the utilisation of planar chiral palladacycles as precursors for the generation of new catalysts for use in asymmetric synthesis. To this end, in the early stages of the programme, we developed methods for the efficient asymmetric synthesis of planar chiral palladacycles. In addition, this was extended to the synthesis of related iridacycles as potential precursors to iridium-based catalysts for use in asymmetric catalysis. As part of this methodology we developed a practical method to control planar chirality formation using deuterium as a stereochemically invisible blocking group. Further to this a detailed review of the literature revealed the significance of chiral cooperativity by chiral element addition as a method for improving the enantioselectivity of a catalyst. To explore the potential of this as a catalyst optimisation technique we developed methodology to synthesise all four possible diastereoisomers of a bidentate ligand containing three elements of chirality, and obtained preliminary evidence that these elements may be combined iteratively and cooperatively to improve the enantioselctivity of a catalysed reaction. Returning to the central objective we then demonstrated the application of chiral non-racemic palladacycles as precatalysts for the in situ generation of chiral bidentate ligand coordinated Pd(0) species. These in turn were applied as catalysts for asymmetric allylic alkylation (up to 97% ee) and asymmetric aryl-aryl cross-coupling (ca. 80% ee). These are the first time palladacycles has been used in this way, key outcomes demonstrating the central objective of this work.
Exploitation Route A new way of thinking about chiral cooperativity for catalyst development in asymmetric synthesis. The efficient generation of planar chiral diastereoisomers as the basis of exploiting chiral cooperativity. Novel planar chiral palladacycles, iridacycles and related ligands are now available for cooperative projects in asymmetric synthesis. Planar chiral palladacycles are precatalysts for the in situ generation of chiral ligand ligated Pd(0) complexes, active catalysts for use in asymmetric synthesis.
Sectors Chemicals

Pharmaceuticals and Medical Biotechnology

 
Title CCDC 1578881: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, Peter N. Horton, Simon J. Coles, Christopher J. Richards|2018|Chem.-Eur.J.|24|4310|doi:10.1002/chem.201705113 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc1pzyn8&sid=DataCite
 
Title CCDC 1578882: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, Peter N. Horton, Simon J. Coles, Christopher J. Richards|2018|Chem.-Eur.J.|24|4310|doi:10.1002/chem.201705113 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc1pzyp9&sid=DataCite
 
Title CCDC 1578883: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, Peter N. Horton, Simon J. Coles, Christopher J. Richards|2018|Chem.-Eur.J.|24|4310|doi:10.1002/chem.201705113 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc1pzyqb&sid=DataCite
 
Title CCDC 1578884: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, Peter N. Horton, Simon J. Coles, Christopher J. Richards|2018|Chem.-Eur.J.|24|4310|doi:10.1002/chem.201705113 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc1pzyrc&sid=DataCite
 
Title CCDC 1578885: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, Peter N. Horton, Simon J. Coles, Christopher J. Richards|2018|Chem.-Eur.J.|24|4310|doi:10.1002/chem.201705113 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc1pzysd&sid=DataCite
 
Title CCDC 1855096: Experimental Crystal Structure Determination 
Description Related Article: Ross A Arthurs, Christopher Prior, David L. Hughes, Vasily S. Oganesyan, Christopher John Richards|2018|Organometallics|37|4204|doi:10.1021/acs.organomet.8b00495 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc208cth&sid=DataCite
 
Title CCDC 1855097: Experimental Crystal Structure Determination 
Description Related Article: Ross A Arthurs, Christopher Prior, David L. Hughes, Vasily S. Oganesyan, Christopher John Richards|2018|Organometallics|37|4204|doi:10.1021/acs.organomet.8b00495 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc208cvj&sid=DataCite
 
Title CCDC 1855133: Experimental Crystal Structure Determination 
Description Related Article: Ross A Arthurs, Christopher Prior, David L. Hughes, Vasily S. Oganesyan, Christopher John Richards|2018|Organometallics|37|4204|doi:10.1021/acs.organomet.8b00495 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc208f0r&sid=DataCite
 
Title CCDC 1916753: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, David L. Hughes, Christopher J. Richards|2020|J.Org.Chem.|85|4838|doi:10.1021/acs.joc.9b03342 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc22bjrq&sid=DataCite
 
Title CCDC 1938231: Experimental Crystal Structure Determination 
Description Related Article: Ross A Arthurs, David L. Hughes, Christopher John Richards|2019|Organometallics|38|4271|doi:10.1021/acs.organomet.9b00551 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc231wln&sid=DataCite
 
Title CCDC 1938232: Experimental Crystal Structure Determination 
Description Related Article: Ross A Arthurs, David L. Hughes, Christopher John Richards|2019|Organometallics|38|4271|doi:10.1021/acs.organomet.9b00551 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc231wmp&sid=DataCite
 
Title CCDC 1938233: Experimental Crystal Structure Determination 
Description Related Article: Ross A Arthurs, David L. Hughes, Christopher John Richards|2019|Organometallics|38|4271|doi:10.1021/acs.organomet.9b00551 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc231wnq&sid=DataCite
 
Title CCDC 1938234: Experimental Crystal Structure Determination 
Description Related Article: Ross A Arthurs, David L. Hughes, Christopher John Richards|2019|Organometallics|38|4271|doi:10.1021/acs.organomet.9b00551 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc231wpr&sid=DataCite
 
Title CCDC 1956990: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, Alice C. Dean, David L. Hughes, Christopher John Richards|2021|Eur.J.Org.Chem.|2021|2719|doi:10.1002/ejoc.202100146 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc23pdqy&sid=DataCite
 
Title CCDC 1956991: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, Alice C. Dean, David L. Hughes, Christopher John Richards|2021|Eur.J.Org.Chem.|2021|2719|doi:10.1002/ejoc.202100146 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc23pdrz&sid=DataCite
 
Title CCDC 1982092: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, David L. Hughes, Christopher J. Richards|2022|Eur.J.Inorg.Chem.|2022||doi:10.1002/ejic.202101077 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc24jjgp&sid=DataCite
 
Title CCDC 1983850: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, David L. Hughes, Christopher J. Richards|2020|Org.Biomol.Chem.|18|5466|doi:10.1039/D0OB01331E 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc24lc59&sid=DataCite
 
Title CCDC 2033033: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, Alice C. Dean, David L. Hughes, Christopher John Richards|2021|Eur.J.Org.Chem.|2021|2719|doi:10.1002/ejoc.202100146 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc267jqq&sid=DataCite
 
Title CCDC 2033034: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, Alice C. Dean, David L. Hughes, Christopher John Richards|2021|Eur.J.Org.Chem.|2021|2719|doi:10.1002/ejoc.202100146 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc267jrr&sid=DataCite
 
Title CCDC 2033035: Experimental Crystal Structure Determination 
Description Related Article: Ross A. Arthurs, Alice C. Dean, David L. Hughes, Christopher John Richards|2021|Eur.J.Org.Chem.|2021|2719|doi:10.1002/ejoc.202100146 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc267jss&sid=DataCite