Iron-Catalysed Transformations for Sustainable Catalysis in Organic Synthesis
Iron-catalysed cross-coupling methods are highly attractive metal for sustainable organic synthesis, yet these remain underdeveloped and uncompetitive with respect to existing palladium systems. Bespoke ligand and catalyst design has remained largely insurmountable in these systems due to a general lack of mechanistic understanding of the active iron species and reaction pathways that lead to selective product formation. This limitation is in stark contrast to palladium chemistry, where detailed studies of active catalyst structure and mechanism have provided the foundation for the continued design and development of catalysts with novel and/or improved catalytic performance to meet the synthetic needs of the academic and industrial communities.
To address these challenges, our group utilizes an innovative experimental approach combining inorganic spectroscopic methods (e.g. Mössbauer, electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD)), density functional theory (DFT), synthetic/catalytic and kinetic studies to define the key parameters required for high catalytic activity. Our prior work with this approach has revolutionized our understanding of iron cross- coupling in areas including elucidation of Kochi’s S = 1/2 species and the role of NMP in cross-coupling with simple ferric salts2 (both decades long mysteries), the importance of iron(II)-ligand species in cross-coupling, and the role of TMEDA and alkoxide additives in catalysis, and three-component radical cross-couplings. These studies have provided the foundation for improvements in catalyst activity by defining the roles of ligands, additives and reaction conditions in generating specific active iron species in situ, as well as enabling hypothesis driven ligand and pre-catalyst development.
Selected Publications
- Neidig, M. L.; Carpenter, S. H.; Curran, D. J.; DeMuth, J. C.; Fleischauer, V. E.; Iannuzzi, T. E.; Neate, P. G. N.; Sears, J. D.; Wolford, N. J. Acc. Chem. Res. 2019, 52, 140-150.
- Liu, L.; Aguilera, M. C.; Lee, W.; Youshaw, C. R.; Neidig, M. L.; Gutierrez, O. Science 2021, 374, 432-439.
- Bakas, N. J.; Sears, J. D.; Brennessel, W. W.; Neidig, M. L. Angew. Chem. Int. Ed. 2022, e202114986.
- Aguilera, M. C.; Gogoi, A. R.; Lee, W.; Liu, L.; Brennessel, W. W.; Gutierrez, O., Neidig, M. L. ACS Catal. 2023, 12, 8987-8996.
Beyond cross-coupling, our group is interested in the development of iron-based methods for the broader set of organic transformations central to modern organic synthesis. Areas of continuing interest included olefin funationalisation and carbon-heteroatom (e.g. C-N, C-B) with iron catalysis. Some examples of recent contributions by our group in this area have included studies of active iron species in mechanism in hydromagnesiation reactions of styrene derivatives, alkene aminoboration, olefin amino-oxygenation and cycloadditions.
Selected Publications
- Neate, P. G. N.; Greenhalgh, M. D.; Brennessel, W. W.; Thomas, S. P.; Neidig, M. L. J. Am. Chem. Soc. 2019, 141, 10099-10108.
- Neate, P. G. N.; Greenhalgh M. D.; Brennessel, W. W.; Thomas, S. P.; Neidig, M. L. Angew. Chem. Int. Ed. 2020, 59, 17070-17076.
- Feo, M.; Bakas, N. J.; Radovic, A.; Parisot, W.; Clisson, A.; Chamoreau, L. -M.; Haddad, M.; Ratovelomanana-Vidal; Neidig, M. L., Lefevre, G. ACS Catal. 2023, 13, 4882-4893.
- Gay, B.; Wang, Y.-N.; Bhatt, S.; Tarasewicz, A.; Cooke, D.; Milem, E.; Zhang, B.; Gary, J.; Neidig, M. L.; Hull, K. J. Am. Chem. Soc. 2023, 145, 18939-18947.
