Studies directed towards the synthesis of (-)-Ebelactone-A

This thesis describes work concerning the total synthesis of ebelactone-a 16, and in particular the synthesis of one of the retrosynthetic fragments (fragment A 20) and its coupling to the combined fragment BC 115 formed from the other two. We repeated the synthesis of enantiomerically enriched 20 devised by Williams, employing a Mukaiyama aldol reaction directed by Oppolzer's sultam to establish the anti-anti stereotriad of the fragment. We modelled the coupling of this to 115 using isobutyraldehyde in place of 20 and vinyl iodide 133 in place of 115, and verified that the Nozaki-Kishi method using chromium(II) chloride and catalytic nickel(II) chloride was effective. By this method, we successfully coupled 133 to 20. Model work was unsuccessful in establishing a methodology for removing the hydroxy group from alcohols 188/189 without disrupting either the position or geometry of the adjacent C=C bond. We also established a completely new route to fragment A, utilising the features of organosilicon chemistry to control the stereochemistry. An intermediate 213 containing two different silyl groups, in which we hoped to transform one selectively into a hydroxy group with retention of configuration by Fleming's method, proved too unstable for synthesis, but we were able to modify the route and produce alcohol 254 in enantiomerically pure form (Oppolzer's sultam was once again used as the chiral auxiliary), and we expect future workers to be able to take this through to fragment A. See attached file abstract.pdf for related images of the the molecular structures

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

1999

Author dc:creator

• Foster, Colin Frederick

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/e7dd2c9b-16d4-4aeb-b4c1-a5e65a12d039/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

en

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.16278

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/236311