The Library
Asymmetric transfer hydrogenation of aromatic and heterocyclic ketones
Tools
Zheng, Ye (2022) Asymmetric transfer hydrogenation of aromatic and heterocyclic ketones. PhD thesis, University of Warwick.
PDF
WRAP_Zheng_Y_2022.pdf - Submitted Version Embargoed item. Restricted access to Repository staff only until 3 August 2024. Contact author directly, specifying your specific needs. - Requires a PDF viewer. Download (7Mb) |
|
PDF
WRAP_Zheng_Y_2022_Appendix.pdf - Submitted Version Embargoed item. Restricted access to Repository staff only until 3 August 2024. Contact author directly, specifying your specific needs. - Requires a PDF viewer. Download (123Mb) |
Official URL: http://webcat.warwick.ac.uk/record=b3861530~S15
Abstract
Asymmetric transfer hydrogenation (ATH) of ketones using ([(arene)Ru(TsDPEN)Cl]-type catalysts is now a well-established method for the enantioselective synthesis of alcohols. ATH of simple acetophenone and benzophenone derivatives, using Noyori-Ikariya catalysts has been reported and often gives the corresponding alcohol products with high enantioselectivities. But the ATH of hindered and challenging ketones is less well studied.
In this thesis, the ATH of a series of challenging ketone and imine
substrates and their applications has been investigated. ATH of substrates containing the ortho-hydroxyphenyl group was carried out using various [(arene)Ru(TsDPEN)Cl] precatalysts out of which (R,R)-3C-tethered catalyst c1 was found to be the most active. The enantioselectivity is influenced by a combination of steric and electronic factors. The correct choice of substituents can be used to deliver products with very high enantiomeric excess, including examples that would otherwise be very difficult to access by other methods. The directing effect of the ortho-OH group can provide the products with high enantioselectivity. The methodology was applied to the synthesis of challenging targets, including a sphingosine 1-phosphate receptor inhibitor.
Furthermore, the ATH of a range of hindered aromatic/heterocyclic (furan, thiophene, N-methylimidazole) ketones was also studied. The reduction enantioselectivity was high (up to 99% ee) in cases where the aromatic ring contained an ortho-substituent. For the furan and thiophene containing ketones, the enantioselectivity was influenced by a combination of steric and electronic factors, following literature precedents. In the case of the ketones containing N-methylimidazole, an unexpected switch in enantioselectivity took place upon variation of the opposing aromatic group. Pyrrole-containing ketones were resistant to the reduction.
Moreover, ATH of Bpin-containing acetophenone derivatives afforded alcohols in high enantiomeric excess (up to 98% ee) when the Bpin is in the para- or meta- positions. The highly enantioselective alcohol products were converted to substituted derivatives using Pd-catalyzed coupling reactions.
Item Type: | Thesis (PhD) | ||||
---|---|---|---|---|---|
Subjects: | Q Science > QD Chemistry | ||||
Library of Congress Subject Headings (LCSH): | Ketones, Hydrogenation, Heterocyclic compounds | ||||
Official Date: | June 2022 | ||||
Dates: |
|
||||
Institution: | University of Warwick | ||||
Theses Department: | Department of Chemistry | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Wills, Martin | ||||
Format of File: | |||||
Extent: | viii, 282 pages : illustrations, charts ; appendix (964 pages) | ||||
Language: | eng |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |