Asymmetric synthesis of the perhydroepoxyethanoindole core via sequential [4 + 2]-addition/reduction/fluoroannulation reactions

Abstract

Herein, we present the sequential aminocatalytic [4 + 2]-addition/reduction and fluoroannulation reactions to afford a novel class of bridged fluoro-perhydroepoxyethanoindole spiropyrazolone and fluoro-perhydroepoxyethanoindole spirooxindole moieties with six contiguous stereocenters. An array of perhydroepoxyethanoindole core derivatives (up to 31 examples) mimicking aspidosperma alkaloids were obtained with moderate to good yields and excellent enantio- and diastereo-selectivities (up to 69% overall yield, up to 99.9% ee and up to >20 : 1 dr). Furthermore, we have also disclosed the synthesis of the unexpected tribromo derivative of hexahydroepoxyethanoindole spiropyrazolone in a moderate yield with excellent selectivity by employing the developed protocol in sequential bromoannulation reactions.