Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.557459
Title: Asymmetric synthesis of amines using modular heterocyclic catalysts
Author: Li, Xianfu
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2011
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Abstract:
Catalyst 117 was previously reported in the Jones group and demonstrated to a very good catalyst at 1 mol% catalyst load. With the optimized conditions, a wide range of N-arylimines can be reduced in good yield and enantioselectivity by trichlorosilane. Followed this previous discovery, the project now is extending the application this methodology, investigating the mechanism and designing more efficient catalysts. A chromatography process for the synthesis of catalyst 117 was developed. Asymmetric reduction of both N-aryl and N-alkyl ketimines can be performed using trichlorosilane catalyzed by 117 at 1 mol% catalyst loading. The scalability of this process was demonstrated. This catalyst can also facilitate the reduction of β-enamino esters by trichlorosilane with good yield and high enantioselectivity albeit with the necessity of a high catalyst loading and benzoic acid as an additive. An asymmetric reductive amination of ketones with both aromatic and aliphatic amines was achieved in good yield and high enantioselectivity at 1 mol% catalyst loading. Sterically hindered ketones also undergo reductive amination in good yield and enantioselectivity by a two-step one-pot procedure. The asymmetric synthesis of (+)-NPS R-568 in good yield and high enantioselectivity using the two-step one-pot procedure demonstrated the potential utility of this catalyst to the pharmaceutical industry. Lewis acidic TMSOTf can improve the yield in direct reductive amination, but showed a negative effect on the enantioselectivity. Initial investigations into the mechanism have resulted in unprecedented discoveries. Both the NMR study of catalyst 117 and the discovery of a new highly active catalyst 263 place the Matsumura transition state model into doubt. Although no signals were detectable to support the hypercoordinate silane species by NMR experiments, in-situ ReactIR data showed that there might be some interactions between trichlorosilane and catalysts. A new tentative transition state model was proposed according to the study of structure/activity of catalysts and the preliminary in-situ IR data.
Supervisor: Jones, Simon Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.557459  DOI: Not available
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