The Synthesis of Functionalised beta-Lactams

Nugent, Mark James (1988) The Synthesis of Functionalised beta-Lactams. PhD thesis, University of Glasgow.

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N-t-Butyldimethylsilyl imines were prepared readily by oxidation of the corresponding primary amines. The application of N-t-butyl-dimethylsilyl imines to the synthesis of monocyclic beta-lactams was examined via the ester-imine condensation reaction with silyl ketene acetals. Initial choice of Znl2 as Lewis acid for this reaction proved fruitful in certain instances. This reaction, performed in the presence of t-BuOH to suppress reaction of the initially formed N-metallo beta-amino ester with a further molecule of activated imine, followed by treatment with Grignard reagent, displays a modest trans selectivity in the product beta-lactams. However, difficulties were encountered during utilization of more highly functionalised N-t-butyldimethylsilyl imines. As a result, a second Lewis acid system was investigated. Utilization of trimethylsilyl trifluoromethanesulphonate (TMSOTf) as the Lewis acid component produced, in a one-pot process, a range of beta-lactams in a trans-selective manner. Chemical yields resulting from this approach were comparable to those achieved using Znl2 as Lewis acid and the diastereoselectivities found showed a modest increase over those induced in the earlier approach. Low temperature quenching of the derived from treatment of a non-enolisable aldehyde with lithium hexamethyldisilazide resulted in formation of the corresponding N,N,O-tris(trimethylsilyl) amine acetal. Treatment of these compounds with TMSOTf provides access to the same reactive iminium species as found in the reaction between N-silyl imines and TMSOTf and, as such, provides an alternative route to beta-lactam synthesis. Two functionalised silyl ketene acetals were prepared. Attempts to incorporate these substrates into the ester-imine condensation process met with only partial success. The cyclic silyl ketene acetal derived from delta-valerolactone was incorporated into a beta-lactam nucleus, although some atypical characteristics were observed in this system. As an alternative source of the electrophilic iminium species generated in the reaction between an imine or amine acetal with a Lewis acid, the reactivity of enamines was examined. Lewis acid catalysis did allow access to beta-amino esters from enamines, although certain aspects of this process are, as yet, unexplained.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry
Date of Award: 1988
Depositing User: Enlighten Team
Unique ID: glathesis:1988-77753
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53

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