Thesis
New iridium catalysed methods for enantioselective imine hydrogenation
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2024
- Thesis identifier
- T17096
- Person Identifier (Local)
- 202060378
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Over the last two decades, research within the Kerr laboratories has focused on the development of highly active iridium catalysts for use in hydrogen isotope exchange (HIE) methodologies. Furthermore, these catalysts have also shown appreciable activity in the realm of hydrogenation transformations and can facilitate the reduction of C-C bonds under mild reaction conditions and low catalyst loadings. The work disclosed in this thesis highlights the expansion of these highly active iridium species’ applicability to the reduction of C=N bonds, namely the reduction of imines to amines. Through a series of optimisation studies and catalyst screening, twenty-nine aldimine substrates were successfully reduced to their corresponding amines in high isolated yields up to 99%. This was achieved using a bidentate iridium-NHC-phosphine catalyst, employed it at just 1 mol% catalyst loading and under mild conditions, including atmospheric pressures of hydrogen gas. The methodology also benefits from a broad solvent applicability, including notable green solvents. The methodology was then expanded to more challenging ketimine substrates, with a small substrate scope established alongside the requirement for moderately more forcing conditions, utilising 2.5 mol% catalyst loading to obtain high yields of products, up to 98%. The successful reduction of ketimines using this system led to the expansion of the protocol to facilitate enantioselective hydrogenation. Initially, two novel chiral iridium catalysts were synthesised and tested in the key reduction transformation but provided only low level s of enantioselectivity with a maximum enantiomeric ratio of 61:39. Due to the synthetic challenges associated with preparing chiral catalysts, it was decided no further resources would be spent on design and synthesis of new chiral iridium complexes. Through an understanding of the mechanism, as well as key intermediates within the reaction, an alternative approach was adopted in order to embed chirality into the emerging reaction system, avoiding the requirement for more prolonged and demanding synthetic routes towards chiral catalysts. Through the addition of a simple chiral additive, high enantioselectivities were generated when used in conjunction with an achiral iridium complex. It was discovered that a chiral oxazoline additive could be employed in equimolar amounts to the iridium catalyst at 5 mol%, forming a chiral iridacycle species in situ through cyclometallation of the oxazoline to the iridium. Through a combination of experimental and DFT calculations, levels of up to 96:4 er have been generated from a series of imines across nine substrates.
- Advisor / supervisor
- Lindsay, David
- Taylor, Jonathan
- Kerr, Billy
- Paterson, Laura
- Resource Type
- DOI
- Funder
- Embargo Note
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File | 2024-10-08 | Embargo |