Asymmetric Total Synthesis of Indole Alkaloids (+)-Condyfoline, (-)-Tubifoline, (+)-Dasycarpidone and (+)-Uleine

The development of a titanium(III)-mediated cascade electrocyclisation/rearrangement for theenantioselective total synthesis of indole alkaloids (+)-condyfoline and (-)-tubifoline serve as the basisof the first chapter of this thesis. An introduction will focus on the use of domino sequencesincorporating a 1,2-shift in the context of complex natural product synthesis. The design of such adomino process is then presented, along with preliminary results originating from our research groupconcerning the titanium(III)-mediated Cadogan cyclisation. This novel domino sequence enabled thefirst enantioselective total synthesis of (+)-condyfoline. These results provided insights into themechanistic nature of the formal 1,2-shift, indicating that the formal 1,2-migration most likelyproceeds via 1,5-sigmatropic rearrangement rather than retro-Mannich/Mannich sequence. Theisolation 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 integratedOxidation/Reduction/Cyclisation (iORC) sequence for the enantioselective total synthesis of the Uleinefamily of monoterpene indole alkaloids. A brief introduction will review our group's previous effortsto implement iORC sequences for the total synthesis of alkaloids. The step-by-step development of theiORC sequence is described, along with the endgame strategy for the synthesis of (+)-nordasycarpidone, (+)-dasycarpidone, (-)-dasycarpidol and (+)-uleine. The chapter ends with theattempted titanium(III)-mediated cyclisation/rearrangement sequence towards (+)-uleine, andattempted 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 rapidinvestigation of the substrate scope is presented. The remaining of the chapter reports our efforts toapply 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 isolatedsesquiterpene possessing a unique 5/6/7-fused tricyclic system. A designed formal [3+2] reaction wasenvisioned to provide access to this novel sesquiterpene, but resulted in the isolation of a Wilson-Clokerearrangement product.