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The development of one-pot tandem reactions for the synthesis of polycyclic y-lactams

McGonagle, Fiona I. (2012) The development of one-pot tandem reactions for the synthesis of polycyclic y-lactams. PhD thesis, University of Glasgow.

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Abstract

A novel tandem process has been developed for the stereoselective synthesis of bicyclic γ-lactams. Treatment of an allylic alcohol with trichloroacetonitrile, in the presence of DBU, affords the corresponding allylic trichloroacetimidate. This is then subjected to a tandem Overman rearrangement/RCM/Kharasch cyclisation, forming the desired bicyclic lactam in high yield and high enantiomeric excess. Overall, the one-pot tandem process involves three mechanistically distinct processes catalysed by palladium(II) (step 1) and Grubbs 1st generation catalyst (steps 2 and 3). The use of a thermal Overman rearrangement in tandem with the Grubbs catalysed RCM/Kharasch cyclisation was also investigated. Furthermore, a microwave-assisted tandem process was developed which resulted in the accelerated synthesis of the desired bicyclic γ-lactams. A two-step tandem process was then developed for the synthesis of bicyclic allylic amides, a closely related core unit to that found in a number of important commercially available drugs. Finally, progress has been made towards the total synthesis of (±)-deethylibophyllidine, which will utilise a tandem RCM/Kharasch cyclisation to construct the C and D rings of the natural product.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Tandem reactions, N-heterocycles, organic synthesis
Subjects: Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Supervisor's Name: Sutherland, Dr. Andrew
Date of Award: 2012
Depositing User: Ms Fiona I. McGonagle
Unique ID: glathesis:2012-3684
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Oct 2012
Last Modified: 10 Dec 2012 14:09
URI: http://theses.gla.ac.uk/id/eprint/3684

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