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The synthesis of enantiomerically-pure alcohols using ruthenium-catalysed asymmetric transfer hydrogenation
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Gediya, Shweta K. (2022) The synthesis of enantiomerically-pure alcohols using ruthenium-catalysed asymmetric transfer hydrogenation. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3884088
Abstract
A series of α-amino ketones were reduced using asymmetric transfer hydrogenation (ATH) through a dynamic kinetic resolution (DKR). A preliminary investigation including racemization kinetics and catalyst screening was carried out to find the best combination of N-protecting group and reducing agent, and following optimization, a series of substrates were investigated, giving products in high diastereoselectivity, over 99% ee in several cases and full conversion. The methodology was applied to the enantioselective synthesis of a MDM2–p53 inhibitor precursor which had previously been prepared in an asymmetric form through a chiral resolution.
The asymmetric transfer hydrogenation (ATH) of α-keto-1,4-diamides using a tethered Ru/TsDPEN catalyst was achieved in high ee. Functional groups modification e.g., amide, thioamide, ester, alkyl chains on the proximal and distal end of the ketones were investigated which helped to understand the necessary structural features that are required for the highest enantioselectivities. The products were transformed to a -amino amide derivative via a Curtius rearrangement, and partial and full reduction of the amide with NaBH4 and LiAlH4 led to a synthesis of corresponding diamine without loss of ee. The products and their derivatives are valuable targets in themselves and useful intermediates for other pharmaceutical target molecules.
The novel tethered ruthenium complexes with modified arene ring were successfully synthesised and screened for asymmetric transfer hydrogenation against various ketone substrates. The synthesised catalysts were found to be active and generated the corresponding alcohol products in high enantioselectivities and obtained results were compared to the non-tethered ruthenium derivatives.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QD Chemistry | ||||
Library of Congress Subject Headings (LCSH): | Alcohols -- Synthesis, Enantiomers, Ketones, Asymmetric synthesis, Hydrogenation, Ruthenium catalysts | ||||
Official Date: | July 2022 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Department of Chemistry | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Wills, Martin | ||||
Format of File: | |||||
Extent: | iii, 331 pages : illustrations | ||||
Language: | eng |
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