Combining two-directional synthesis and tandem reactions, part 11: second generation syntheses of (±)-hippodamine and (±)-epi-hippodamine

Abstract

BackgroundHippodamine is a volatile defence alkaloid isolated from ladybird beetles which holds potential as an agrochemical agent and was the subject of a synthesis by our group in 2005.ResultsTwo enhancements to our previous syntheses of (±)-hippodamine and (±)-epi-hippodamine are presented which are able to shorten the syntheses by up to two steps.ConclusionsKey advances include a two-directional homologation by cross metathesis and a new tandem reductive amination / double intramolecular Michael addition which generates 6 new bonds, 2 stereogenic centres and two rings, giving a single diastereomer in 74% yield.