New synthetic routes to (.+-.)-perhydrohistrionicotoxin. Stereoselective synthesis of (6S*, 7S*, 8S*)-7-butyl-8-hydroxy-1-azaspiro(5.5)-undecan-2-one and its (6R*)-isomer.

Abstract

A highly stereoselective synthesis of (6S*, 7S*, 8S*)-7-butyl-8-hydroxy-1-azaspiro [5.5]-undecan-2-one (6), a key intermediate for (±)-perhydrohistrionicotoxin synthesis, from the Diels-Alder cycloadduct of 1, 3-bis (trimethylsiloxy)-2-methyl-1, 3-butadiene (15) and ethyl 3-acetoxy-1-cyclohexene-1-carboxylate is described. This key intermediate and its stereoisomer, (6R*, 7S*, 8S*)-7-butyl-8-hydroxy-1-azaspiro [5.5] undecan-2-one (7), were stereoselectively synthesized by means of a conjugate addition reaction using 1-(3-tert-butyldimethylsiloxy-1-cyclohexen-1-yl)-ethanone and BuCu·AlCl3 as the key step.