Core-Structure-Motivated Design of Iminium-Enolate Organocascade Reactions: Enantioselective Syntheses of 5,6-Dihydroindolizines

摘要

Bioactive natural products are a key source of inspiration for syntheses of biological tools and potential therapeutic compounds. The indolizine core is a privileged heterocyclic ring system found in a large number of bioactive natural alkaloids and clinically useful pharmaceuticals. The 5,6,7,8-tetra- and 5,6-dihydroindolizine frameworks (Figure 1) have recently drawn tremendous interest from both synthetic and medicinal chemists because of their properties as anti-tumor, anti-leukemia, anti-cholinergic agents and other important biological activities. In addition, 5,6,7,8-tetra- and 5,6-dihydroindolizine alkaloids are common secondary metabolites in plants, invertebrates, fungi, and bacteria. Thus, the design of new synthetic methods to provide molecules in this class of compounds is of interest, and intramolecular cycliza-tion of intermediates using metal-catalyzed,radical, and base-induced processes have been reported.