ENANTIOSELECTIVE PHOSPHINE-CATALYZED ANNULATION TO CONSTRUCT SPIROOXINDOLES AND COMPLEX INDOLE ALKALOIDS THEREOF

Abstract

The tachytelic evolution of asymmetric phosphine catalysis, over the past few decades, has forged a novel synthetic platform to access highly functionalized chiral molecular frameworks, leading an impetus to contemporary medicinal and pharmaceutical research. However, demonstrations of such methodology in target-oriented asymmetric syntheses of privileged scaffolds and bioactive natural products are still exiguous, if not elusive. This thesis is principally concerned with the strategic exploitations of underdeveloped sterically-congested substrates (e.g. isatin-derived ketimines & isoindigo-based tetrasubstituted alkenes as new 2-equivalent annulation synthons) in highly enantioselective, diastereoselective and even regioselective phosphine-catalyzed formal [3+2] spirocyclizations in general, and with the practical and creative transformations of the enantioenriched spiro-products towards the core structures of bioactive multi-substituted (5’-alkyl) 3,2’-pyrrolidinyl spirooxindoles and complex dimeric hexahydropyrroloindole alkaloids possessing vicinal quaternary stereogenic centers in particular. An unpublished work on the potential discovery of the first enantioselective phosphine-triggered intramolecular Diels–Alder reaction of bis(divinyl) ketones is also finally detailed.