Use this URL to cite or link to this record in EThOS: | https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.723525 |
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Title: | Palladium(II)-catalysed sp 3 C–H functionalisation of hindered amines and its application in synthesis of astemizole analogues | ||||||
Author: | Ho, Danny Ka Hei |
ISNI:
0000 0004 6425 5272
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Awarding Body: | University of Cambridge | ||||||
Current Institution: | University of Cambridge | ||||||
Date of Award: | 2016 | ||||||
Availability of Full Text: |
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Abstract: | |||||||
The development of a palladium-catalysed C–H carbonylation of hindered secondary amines is described. Central to this strategy is the temporary conversion of simple ketones into hindered secondary amines that facilitates a sterically promoted palladium-catalysed C–H activation. A range of functional groups are shown to be compatible with this catalytic process, and with exclusive regioselectivity for the terminal ethyl sp 3 C–H in most cases. This method allows an overall incorporation of a carboxyl group to the b-position of terminal ketones, generating 1,4- dicarbonyl moieties which are important synthetic building blocks. The sterically promoted C–H functionalisation strategy has been employed as the key step in the synthesis of a functionalised analogue of astemizole, a pharmaceutical agent which suffers from undesired hERG activity. The increased steric bulk around the tertiary amine, coupled with introduction of a polar hydroxyl group via the C–H acetoxylation reaction, is proposed to reduce binding to the hERG channel. The hERG profile of this analogue is not yet established.
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Supervisor: | Gaunt, Matthew J. | Sponsor: | EPSRC | ||||
Qualification Name: | Thesis (Ph.D.) | Qualification Level: | Doctoral | ||||
EThOS ID: | uk.bl.ethos.723525 | DOI: | |||||
Keywords: | CH activation ; Palladium ; functionalisation of ketones ; hindered secondary amines ; Catalysis | ||||||
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