Novel ferrocene-based phosphine ligands for earth-abundant metal-catalysed asymmetric hydrogenation

Zeng, Liyao ORCID: 0000-0001-5136-2042 (2022). Novel ferrocene-based phosphine ligands for earth-abundant metal-catalysed asymmetric hydrogenation. University of Birmingham. Ph.D.

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Abstract

Transition metal-catalysed homogeneous asymmetric hydrogenation has been developed as one of the most efficient and atom economical methods for the synthesis of chiral molecules. In this field, thousands of chiral phosphine ligands have been reported, with ferrocene as one of privileged ligand scaffolds because of its unique electronic and steric properties. In recent years, earth-abundant metal-catalysed asymmetric hydrogenation has attracted much attention in order to handle the high supply risk of precious metals, however, with slow progress due to the lack of effective chiral ligands. This thesis mainly aims to contribute to the development in asymmetric hydrogenation catalysed by earth-abundant first-row metals (e.g. manganese, iron, cobalt, nickel, copper etc), by designing and synthesizing novel ferrocene-based chiral multidentate phosphine ligands. As a result, a series of highly reactive and enantioselective multidentate phosphine ligands have been developed, including novel ferrocene-based tridentate PNP ligands for manganese catalysis, novel ferrocene-based secondary phosphine oxide ligands Fc-SPO for cobalt catalysis and others. The PNP ligands have been proven highly efficient for manganese-catalysed asymmetric hydrogenation of simple ketones, giving excellent enantioselectivities (92%∼99% ee for aryl alkyl ketones) as well as high efficiencies (TON up to 2000). The Fc-SPO ligands have been successfully applied for cobalt-catalysed asymmetric hydrogenation of diaryl ketones, providing high yields (up to 99%) and good enantioselectivities (up to 92% ee). In addition to multidentate phosphine ligands, this thesis briefly introduces another ligand design strategy towards transition metal-catalysed asymmetric hydrogenation, involving noncovalent interaction-assisted ferrocenyl phosphine ligands.
The second aim of the Mn-PNP complex mentioned above is used as a novel redox-switchable catalyst for the asymmetric hydrogenation of acetophenone. Switching between two iron oxidation states of the ferrocene unit was found to have a significant effect on the catalytic reactivity, with the process chemically reversible. Furthermore, an attempt on the development of novel DNA-organometallic hybrid phosphine ligands for DNA-based asymmetric catalysis has been performed by incorporating a small ferrocenyl phosphine molecule into the DNA backbone. Despite phosphine oxidation issue, the resulting ferrocenyl phosphine oxide-modified strands could still successfully form DNA duplexes, which widens the range of bio-organometallic nucleic acid systems that can be made.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):