New Sulfone-Assisted Strategies for Alkaloid Synthesis
Author(s)
Tholen, Niels T.H.
Type
Thesis
Abstract
This thesis is divided into three chapters.
Chapter 1 provides brief reviews on the subjects of previous total syntheses of suaveoline,
alstonerine and cytisine. In addition, a review concerning the Pictet–Spengler reaction
mechanism and its application to the total syntheses of isoquinoline containing natural
products has been included as well.
Chapter 2 focuses on the research findings in the past three years. Two routes were
investigated towards the total synthesis of (±)-suaveoline involving the decarboxylative
Claisen rearrangement (dCr), N-sulfonylaziridine chemistry and subsequent nucleophilic ringopening
of the latter by various sulfone-anions. Route A focused on the use of oxo-lithio
chelation during aziridine ring-opening while route B employed selective weakening of the
aziridine C–N bond proximal to the olefin by PiC–C→Sigma*
C–N overlap (Scheme 0.1).
Attempts towards total synthesis of (±)-alstonerine involved the preparation and subsequent
screening of various sulfone-anions against the indolic hydroxy aziridine, followed by an
interesting E1cB / Michael addition, cis-Pictet–Spengler cyclization and an ambitious global
reduction step.
Furthermore progress towards total synthesis of (–)-cytisine involved investigation towards
the application of regioselective sulfone-anion hydroxy-aziridine opening mediated by oxolithio-
chelation.
Chapter 3 provides the experimental details and characterization data.
Chapter 1 provides brief reviews on the subjects of previous total syntheses of suaveoline,
alstonerine and cytisine. In addition, a review concerning the Pictet–Spengler reaction
mechanism and its application to the total syntheses of isoquinoline containing natural
products has been included as well.
Chapter 2 focuses on the research findings in the past three years. Two routes were
investigated towards the total synthesis of (±)-suaveoline involving the decarboxylative
Claisen rearrangement (dCr), N-sulfonylaziridine chemistry and subsequent nucleophilic ringopening
of the latter by various sulfone-anions. Route A focused on the use of oxo-lithio
chelation during aziridine ring-opening while route B employed selective weakening of the
aziridine C–N bond proximal to the olefin by PiC–C→Sigma*
C–N overlap (Scheme 0.1).
Attempts towards total synthesis of (±)-alstonerine involved the preparation and subsequent
screening of various sulfone-anions against the indolic hydroxy aziridine, followed by an
interesting E1cB / Michael addition, cis-Pictet–Spengler cyclization and an ambitious global
reduction step.
Furthermore progress towards total synthesis of (–)-cytisine involved investigation towards
the application of regioselective sulfone-anion hydroxy-aziridine opening mediated by oxolithio-
chelation.
Chapter 3 provides the experimental details and characterization data.
Date Issued
2010-07
Date Awarded
2010-11
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Craig, Donald
Creator
Tholen, Niels T.H.
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)