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Title: Towards the asymmetric total synthesis of (-)-lycorine
Author: Nieh, Ling-Fu
ISNI:       0000 0004 6061 5015
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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The application of organocatalysis has expanded significantly in recent years. Organocatalysts can give good enantioselectitvity and hence provide an efficient access to chiral building blocks for organic synthesis. The first chapter in this thesis discusses the possibility to improve the enantioselectivity of the asymmetric Kornblum-DeLaMare (KDLM) rearrangement on a six-membered cyclic endoperoxide. Toste has developed efficient bifunctional catalysts derived from quinine and quinidine for the asymmetric KDLM rearrangement on eight- and seven-membered cyclic endoperoxides, but these catalysts can only provide moderate enantioselectivity for six-membered cyclic endoperoxides. We successfully developed an efficient Bucherer reaction to introduce an amine group on the quinoline ring of quinine and then synthesised various quinine derived catalysts with different hydrogen bond donors. We then examine these compounds as catalysts for the KDLM rearrangement of six-membered cyclic endoperoxides. In the second chapter, we attempted to achieve the total synthesis of (-)-lycorine. The total synthesis started with TBS-protected 4-hydroxycyclohexenone. Our synthesis features a stereoselective Michael addition to establish the cis-relative stereochemistry between the C3 and C3a stereocentres on the six-membered ring. The 1,3-benzodioxole group is introduced by an efficient Suzuki coupling. Then, a highly stereoselective Cope-type hydroamination is performed to introduce the two stereogenic centres of the (-)-lycorine core. Various conditions were examined in order to optimise the Cope-type hydroamination. The double bond between C2 and C3 was constructed by an efficient anti-elimination. We therefore have developed an efficient method to construct the stereocentres and the double bond in (-)-lycorine, which were difficult to construct previously.
Supervisor: Spivey, Alan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral