Periodic Reporting for period 2 - EARTHCAM (Earth-Abundant Metals with Exclusively Achiral Ligands for Sustainable Chiral-at-Metal Catalysis)
Período documentado: 2022-07-01 hasta 2023-12-31
Asymmetric catalysis relies on the design of chiral catalysts and is dedicated to the economical generation of non-racemic chiral compounds, which are building blocks for the production of drugs, agricultural chemicals, flavors, fragrances, and materials. Chiral transition metal complexes constitute an important class of chiral catalysts and are typically synthesized by combining metal salts or organometallic precursors with chiral ligands. A neglected approach follows a different direction and exploits the generation of metal-centered chirality in the course of the assembly of achiral ligands around a central metal. Our group has pioneered the general use of such chiral-at-metal catalysts from noble metals, with the metal center both serving as the exclusive stereogenic center and at the same time acting as the reactive center for catalysis. The design of reactive chiral-at-metal catalysts based on earth-abundant metals, which have economical and environmental benefits, is the focus of this proposal. The design strategy appeals for its combination of sustainability (earth-abundant metals) and simplicity (achiral ligands). Furthermore, without the requirement for chiral motifs in the ligand sphere, untapped opportunities emerge for the design of chiral 3d metal complexes with distinct electronic properties and unique architectures. This unexplored chemical space for chiral catalysts will be applied to the challenging enantioselective functionalization of C-H bonds with inexpensive and sustainable 3d metal catalysts.
The implementation of chiral-at-metal catalysts from earth-abundant metals relies on taming the high lability of coordinative bonds of 3d metals to warrant a satisfactory configuration stability. This is addressed by exploiting the chelate effect of tailored multidentate ligands in combination with strong-field ligands and attractive weak interactions between coordinated ligands.
The implementation of chiral-at-metal catalysts from earth-abundant metals relies on taming the high lability of coordinative bonds of 3d metals to warrant a satisfactory configuration stability. This is addressed by exploiting the chelate effect of tailored multidentate ligands in combination with strong-field ligands and attractive weak interactions between coordinated ligands.
In order to achieve the development of chiral-at-metal catalysts from earth-abundant metals, this project has investigated a variety of structural architectures and topologies which generate an overall chirality with 3d transition metals while at the same time retaining a reactive metal center for transition metal catalysis, and explores catalytic properties of such chiral-at-metal complexes.
Employing meridional tridentate ligands:
We developed a stereogenic-at-iron(II) catalyst scaffold which contains one coordinated meridional tridentate imidazolidin-2-ylidene-functionalized 2,2'-bipyridine, one bidentate pyrazolylpyridine, and one monodentate acetonitrile ligand (D. Baran, L. Hinterlang, S. I. Ivlev, E. Meggers, Eur. J. Inorg. Chem. 2023, doi.org/10.1002/ejic.202300148). This (3+2+1)-coordination sphere implements a stereogenic iron center. A carbon stereocenter in the N-heterocyclic carbene moiety controls the absolute metal-centered configuration. The obtained enantiopure complexes were applied as chiral catalysts in the ring contraction of an isoxazole to a chiral 2H-azirine.
Employing linear tetradentate ligands:
We investigated stereogenic-at-iron(II) complexes containing linear tetradentate ligands. For example, non-C2-symmetric stereogenic-at-iron complexes were synthesized, analyzed and investigated for asymmetric catalysis (P. S. Steinlandt, M. Hemming, X. Xie, S. I. Ivlev, E. Meggers, Chem. Eur. J. 2023, e202300267). Related C2-symmetric stereogenic-at-iron complexes with linear tetradentate ligands were successfully applied to nitrene-mediated C-H insertion chemistry. This led to the discovery of a novel 1,3-migratory nitrene C-H insertion (C.-X. Ye, X. Shen, S. Chen, E. Meggers, Nat. Chem. 2022, 14, 566; B. Zhou, C.-X. Ye, E. Meggers, Eur. J. Org. Chem. 2023, e202300296), a directed nitrene-mediated C-H amination (C.-X. Ye, D. R. Dansby, S. Chen, E. Meggers, Nat. Synth. 2023, doi.org/10.1038/s44160-023-00267-w) and an iron-catalyzed enantioselective ring-closing C-H amination to chiral 2-imidazolidinones (T. Cui, C.-X. Ye, J. Thelemann, D. Jenisch, E. Meggers, Chin. J. Chem. 2023, doi.org/10.1002/cjoc.202300162).
Employing tripodal ligands:
We investigated stereogenic-at-iron(II) complexes containing tripodal pentadentate ligands. The properties of such complexes were investigated and the complexes applied to asymmetric catalysis (P. S. Steinlandt, X. Xie, S. Ivlev, E. Meggers, ACS Catal. 2021, 11, 7467).
Furthermore, we spent significant efforts to understand the factors that provide sufficient configurational stability for stereogenic metal centers of 3d metals. This allowed us to succeed in improving the configurational stabilty of chiral-at-iron catalysts containing two N-(2-pyridyl)-substituted N-heterocyclic carbene ligands by carefully tuning the sigma-donor and pi-acceptor properties of the bidentate ligands (N. Demirel, J. Haber, S. I. Ivlev, E. Meggers, Organometallics 2022, 41, 3852). Remarkably, the developed chiral-at-iron complex is completely configurational stable, even in the presence of water and air. The complex was demonstrated to be an excellent catalyst for an asymmetric hetero-Diels-Alder reaction.
Employing meridional tridentate ligands:
We developed a stereogenic-at-iron(II) catalyst scaffold which contains one coordinated meridional tridentate imidazolidin-2-ylidene-functionalized 2,2'-bipyridine, one bidentate pyrazolylpyridine, and one monodentate acetonitrile ligand (D. Baran, L. Hinterlang, S. I. Ivlev, E. Meggers, Eur. J. Inorg. Chem. 2023, doi.org/10.1002/ejic.202300148). This (3+2+1)-coordination sphere implements a stereogenic iron center. A carbon stereocenter in the N-heterocyclic carbene moiety controls the absolute metal-centered configuration. The obtained enantiopure complexes were applied as chiral catalysts in the ring contraction of an isoxazole to a chiral 2H-azirine.
Employing linear tetradentate ligands:
We investigated stereogenic-at-iron(II) complexes containing linear tetradentate ligands. For example, non-C2-symmetric stereogenic-at-iron complexes were synthesized, analyzed and investigated for asymmetric catalysis (P. S. Steinlandt, M. Hemming, X. Xie, S. I. Ivlev, E. Meggers, Chem. Eur. J. 2023, e202300267). Related C2-symmetric stereogenic-at-iron complexes with linear tetradentate ligands were successfully applied to nitrene-mediated C-H insertion chemistry. This led to the discovery of a novel 1,3-migratory nitrene C-H insertion (C.-X. Ye, X. Shen, S. Chen, E. Meggers, Nat. Chem. 2022, 14, 566; B. Zhou, C.-X. Ye, E. Meggers, Eur. J. Org. Chem. 2023, e202300296), a directed nitrene-mediated C-H amination (C.-X. Ye, D. R. Dansby, S. Chen, E. Meggers, Nat. Synth. 2023, doi.org/10.1038/s44160-023-00267-w) and an iron-catalyzed enantioselective ring-closing C-H amination to chiral 2-imidazolidinones (T. Cui, C.-X. Ye, J. Thelemann, D. Jenisch, E. Meggers, Chin. J. Chem. 2023, doi.org/10.1002/cjoc.202300162).
Employing tripodal ligands:
We investigated stereogenic-at-iron(II) complexes containing tripodal pentadentate ligands. The properties of such complexes were investigated and the complexes applied to asymmetric catalysis (P. S. Steinlandt, X. Xie, S. Ivlev, E. Meggers, ACS Catal. 2021, 11, 7467).
Furthermore, we spent significant efforts to understand the factors that provide sufficient configurational stability for stereogenic metal centers of 3d metals. This allowed us to succeed in improving the configurational stabilty of chiral-at-iron catalysts containing two N-(2-pyridyl)-substituted N-heterocyclic carbene ligands by carefully tuning the sigma-donor and pi-acceptor properties of the bidentate ligands (N. Demirel, J. Haber, S. I. Ivlev, E. Meggers, Organometallics 2022, 41, 3852). Remarkably, the developed chiral-at-iron complex is completely configurational stable, even in the presence of water and air. The complex was demonstrated to be an excellent catalyst for an asymmetric hetero-Diels-Alder reaction.
Knowledge gained on the design of stereogenic-at-iron catalysts will be applied to the development of configurationally more robust earth-abundant Fe(II), Co(III), Cr(III), Mn(II), and Ni(II) catalysts. It has become clear that the electronic tuning of the coordinated multidentate ligands is crucial for a configurational inertness of the ligand sphere. We expect to develop novel catalysts and discover unprecedente catalytic transformations.