Work in the group results in new catalysts that enable the stereoselective synthesis of novel bioactive compounds with the potential to treat disease.
This is underpinned by investigations into the influence of structure and stereochemistry on catalyst activity and selectivity, with the aim of improving these key measures of efficiency.
Ongoing areas of research are summerised as follows:
Ligand Design and Stereochemical Evolution
Identifying a suitable ligand is central to achieving high enantioselectivity in a metal catalysed asymmetric reaction. The group has developed several new classes of ligand based principally on ferrocene and a related cobalt sandwich complex.1 Our ongoing work in this area focuses on the synthesis of ligands containing multiple chirality elements and additional functionality, together with the systematic optimisation of these to achieve high activity and selectivity in metal catalysed reactions.2
1. (a) R. A. Arthurs, P. N. Horton, S. J. Coles and C. J. Richards Chem. Eur. J. 2018, 24, 4310. (b) R. A. Arthurs and C. J. Richards Synlett 2018, 29, 585.
2. (a) R. A. Arthurs, D. L. Hughes and C. J. Richards, J. Org. Chem. 2020, 85, 4838. (b) C. J. Richards and R. A. Arthurs, Chem. Eur. J. 2017, 48, 11460.
Metallacycles in Catalyst Discovery
Metallacycles are typically bidentate ligand-metal complexes synthesised by C-H activation. Use of ferrocene or a related cobalt sandwich complex precursor results in a new element of planar chirality, and the group has developed several stereoselective methods to control this reaction.3
Planar chiral metallacycles, notably palladacycles, have been used widely as catalysts in asymmetric synthesis.4 In addition, our group recently demonstrated the first example of asymmetric catalysis following precatalyst activation by simultaneous ligand synthesis and metal capture.5 This is anticipated to be applicable to high-throughput catalyst generation and screening for application to many reactions.
3. (a) R. A. Arthurs, D. L. Hughes and C. J. Richards, Organometallics, 2019, 38, 4271. (b) R. A. Arthurs, D. L. Hughes, P. N. Horton, S. J. Coles and C. J. Richards, Organometallics, 2019, 38, 1099.
4. D. J. Cassar, G. Ilyashenko, M. Ismail, J. Woods, D. L. Hughes and C. J. Richards, Chem. Eur. J.2013, 19, 17951-17962.
5. R. A. Arthurs, D. L. Hughes and C. J. Richards, Org. Biomol. Chem. 2020, 18, 5466.
Catalysis and Sequential Asymmetric Synthesis
Catalysts and ligands, including those generated in-house, are applied to the enantioselective synthesis of important building-blocks for the synthesis of natural products and other potentially bioactive compounds. For example, we have recently developed procedures for the synthesis and highly enantioselective reduction of unsaturated γ-lactones and lactams, and extended this chemistry to the synthesis of Lucidulactone A.6
The products of asymmetric catalysis may be further diversified by linking to a second catalysed process where orthogonal reactivity is exploited to give additional structural, functional group and stereochemical complexity.7 In this way simple prochiral starting materials are converted quickly into novel fragment and lead-like compounds, starting points for the discovery of bioactive compounds.
6. O. S. Ojo, D. L. Hughes and C. J. Richards, 2021, in preparation.
7. C. J. Richards and O. S. Ojo, 2021, in preparation.