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Abstract
The development of a titanium(III)-mediated cascade electrocyclisation/rearrangement for the
enantioselective total synthesis of indole alkaloids (+)-condyfoline and (-)-tubifoline serve as the basis
of the first chapter of this thesis. An introduction will focus on the use of domino sequences
incorporating a 1,2-shift in the context of complex natural product synthesis. The design of such a
domino process is then presented, along with preliminary results originating from our research group
concerning the titanium(III)-mediated Cadogan cyclisation. This novel domino sequence enabled the
first enantioselective total synthesis of (+)-condyfoline. These results provided insights into the
mechanistic nature of the formal 1,2-shift, indicating that the formal 1,2-migration most likely
proceeds via 1,5-sigmatropic rearrangement rather than retro-Mannich/Mannich sequence. The
isolation of (+)-condyfoline enabled a re-investigation of its isomerisation process to Strychnos isomer
(-)-tubifoline. The chapter concludes with synthetic studies towards (+)-tronoharine and (+)-
tubotaiwine.
The second chapter of this thesis deals with the development of an integrated
Oxidation/Reduction/Cyclisation (iORC) sequence for the enantioselective total synthesis of the Uleine
family of monoterpene indole alkaloids. A brief introduction will review our group's previous efforts
to implement iORC sequences for the total synthesis of alkaloids. The step-by-step development of the
iORC sequence is described, along with the endgame strategy for the synthesis of (+)-
nordasycarpidone, (+)-dasycarpidone, (-)-dasycarpidol and (+)-uleine. The chapter ends with the
attempted titanium(III)-mediated cyclisation/rearrangement sequence towards (+)-uleine, and
attempted iORC sequence towards (+)-condyfoline.
The third chapter of this thesis reports a novel synthesis of benzofuro[3,2-b]indolines from onitrostylbene precursors using a titanium(III)-mediated interrupted Cadogan reaction. A rapid
investigation of the substrate scope is presented. The remaining of the chapter reports our efforts to
apply this newly developed transformation for the total synthesis of bis-indole alkaloid phalarine.
The last chapter is dedicated to our synthetic studies towards (+)-pestalustaine A, a recently isolated
sesquiterpene possessing a unique 5/6/7-fused tricyclic system. A designed formal [3+2] reaction was
envisioned to provide access to this novel sesquiterpene, but resulted in the isolation of a Wilson-Cloke
rearrangement product.