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Title: Dearomatising cyclisations of pyridine derivatives
Author: Senczyszyn, Jemma Louise
ISNI:       0000 0004 2729 8919
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2012
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Pyridines react with N-acylating agents to create extremely electrophilic pyridinium ions, which are susceptible to dearomatising attack of various nucleophiles. The use of anionic nucleophiles in these cyclisations has been well documented in the literature. Recently within the Clayden group, tethered neutral π-nucleophiles have also been shown to be suitable nucleophiles in this reaction. Dearomatising cyclisations of neutral nucleophiles can occur if the pyridine is first activated by a powerful electrophile (EX). 1,4-Dihydropyridines are generated upon spirocyclisation of N-vinylisonicotinamides. This thesis begins with routes towards enamides used as cyclisation precursors in this dearomatising spirocyclisation. It will go on to discuss the suitability of various electrophilic activation reagents in this reaction as well as the nature of the enamide, and the importance of the base. The optimised conditions for the hydrogenation of dihydropyridines to give stable, pharmaceutically-interesting piperidines and deprotections of the electrophilic activating reagents will also be discussed. Spirocyclisations of sterically encumbered chloropyridines and quinolines will also be included in this section.Dearomatising cyclisations of N-vinylnicotinamides and N-vinylpicolinamides will also be investigated. This section will contain routes to synthetically challenging N-vinylpicolinamides as well as quinoline-2-amides. The regioselectivity of additions to activated N-activated nicotinamides as well as attempted methods of achieving high regioselectivities in these reactions will be discussed.Finally, the feasibility of performing dearomatising cyclisation chemistry on other N-containing heterocycles such as pyrimidine and pyrazinecarboxamides will be investigated.
Supervisor: Clayden, Jonathan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available