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

Background: Hippodamine 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. Results: Two enhancements to our previous syntheses of (+/-)-hippodamine and (+/-)-epi-hippodamine are presented which are able to shorten the syntheses by up to two steps. Conclusion: Key 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.