Application of a tandem electrocyclic [3,3]sigmatropic reaction of o-quinodimethane to the synthesis of calabar bean alkaloids. Part 2. First total synthesis of (±)-geneserine

Abstract

The first total synthesis of the Calabar bean alkaloid geneserine (1) starting with 1-cyano-5-methoxybenzocyclobutene (7) has been accomplished via a 16-step sequence in 27% overall yield. The key step in the synthetic strategy involves the tandem electrocyclic [3,3]sigmatropic reaction of the o-quinodimethane generated in situ by thermolysis of the benzocyclobutene (4), which affords quantitatively the isochroman-3-one (5). After the conversion of (5) into the oxindole (6), the pivotal intermediate for our strategy, differential functionalisation of this system provides the hydroxylamine (19) which has finally been converted into (±)-geneserine by treatment with di-isobutylaluminium hydride.