Open Access Te Herenga Waka-Victoria University of Wellington
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A Palladium-Catalysed Allylic Alkylation Cascade: Towards the Total Synthesis of Thromboxanes A₂ and B₂

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posted on 2021-11-13, 23:13 authored by Turner, Claire Alison

The design and development of new chemical reactions is crucial to the ongoing success of organic synthesis research. In this work the scope and utility of a recently discovered regioselective palladium-catalysed allylic alkylation (Pd-AA) cascade was explored through increasing the range of non-symmetric pyran-based biselectrophiles and β-dicarbonyl bis-nucleophiles that can be used in this reaction.  Four differentially protected tri-substituted dihydropyrans based on glucose were synthesised, including 2,3-unsaturated silyl glycosides and α,β-unsaturated lactones. These substrates were assessed as bis-electrophiles in the Pd-AA cascade. One silyl glycoside bis-electrophile, possessing a carbonate leaving group, was shown to be an excellent substrate for reaction with a number of cyclic bis-nucleophiles. Furthermore, a series of regioisomeric methylated 4-hydroxycoumarins were synthesised, tested and found to be equally effective as bis-nucleophiles in the Pd-AA cascade with both acyclic and cyclic bis-electrophiles.  Advances made during this research include a novel Ferrier reaction with silanol nucleophiles, which was found to produce silyl glycosides, albeit in low yields. Additionally, several Perlin aldehydes were generated by the Ferrier-type hydrolysis of 3,4,6-tri-O-acetyl-D-glucal and led to the discovery of discrepant structural assignments in the literature. Furthermore, a ¹³C NMR shielding template was generated as a tool for the stereochemical assignment of tri-substituted dihydropyrans.  An extended variant of the Pd-AA cascade was achieved by employment of the bisnucleophile Meldrum’s acid with the optimal tri-substituted bis-electrophile in the presence of H₂O. The reaction afforded a γ-butyrolactone that could serve as a potential intermediate en route to the synthesis of the biologically interesting compounds thromboxanes A₂ and B₂. This extended Pd-AA cascade, although currently unoptimised, is capable of performing five synthetic transformations in one-pot and holds the potential to improve on the current syntheses of the thromboxanes.


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Date of Award



Te Herenga Waka—Victoria University of Wellington

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Author Retains Copyright

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Degree Grantor

Te Herenga Waka—Victoria University of Wellington

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Degree Name

Master of Science

ANZSRC Type Of Activity code

970103 Expanding Knowledge in the Chemical Sciences

Victoria University of Wellington Item Type

Awarded Research Masters Thesis



Victoria University of Wellington School

School of Chemical and Physical Sciences


Harvey, Joanne