This thesis describes the application of novel and existing cinchona-alkaloid catalyzed Interrupted Feist Bènary (IFB) reactions towards the total synthesis of two biologically active targets: the anticancer compound (-)-rocaglamide and the benzo[b]indeno[2,1-d]furanone Picornavirus inhibitor tetracyclic antiviral-1 (TA-1).
Part I presents our progress towards both targets via the classic highly enantioselective and diastereoselective IFB reaction. Towards rocaglamide, we activated the relatively unreactive ester moiety of the IFB product and perform side chain extension, required to close the cyclopentanone ring of the natural product. We also accomplished the activation of the IFB¿s benzylic C-H bond by Hartwig¿s mild C-H azidation. Towards TA-1, we constructed the tetracyclic core of the target via a required tertiary alcohol protection followed by tin-mediated cyclization.
Part II describes the discovery and optimization of the asymmetric IFB-like reaction between 1,2,3-indanetriones and substituted phenols. We found that the introduction of a substituted aryl ester at the ortho position of the 1,2,3-indanetriones leads to moderate enantioselectivities (up to 79% ee). The introduction of stoichiometric benzoic acid additive was key for obtaining excellent enantioselectivity (up to 93% ee). This new acid-assisted asymmetric IFB-like reaction was used to prepare a number of chiral cyclic hemiacetals, which are useful precursors towards TA-1 and its analogs., In Copyright – Non-Commercial Use Permitted (InC-NC)