Studies and Applications of Intramolecular (4+3) Cycloadditions of Pyrroles

Abstract

While (4+3) cycloadditions commonly proceed with furans and cyclopentadienes, the corresponding reaction with pyrroles is far less reported, since pyrroles tend to undergo Friedel-Crafts type of reactions, resulting in the restoration of aromaticity instead of cycloadditions. So far, there have been no examples of intramolecular (4+3) cycloadditions of pyrroles that afford polycyclic tropanoid scaffolds as products. We have been studying the inter- and intramolecular (4+3) cycloadditions of furans and other dienes using epoxy and aziridinyl enolsilanes as the dienophiles. We have recently found that pyrroles also engage readily in intramolecular (4+3) cycloadditions with epoxy enolsilanes, resulting in optically active polycyclic cycloadducts harboring the tropane nucleus. Based on these results, we are applying this reaction as the key strategy for the construction of the BCDEF core of the Type II galbulimima alkaloid, himandrine.