Synthesis of the hamigeran skeleton through an electro-oxidative coupling reaction

The tricyclic core of the hamigerans has been prepared through the use of a two-step electrochemical benzannulation reaction. The annulation proceeds through an initial conjugate addition of a phenethyl cuprate to 3-methylcyclopentenone with in situ silylation of the resulting enolate. Anodic oxidation effectively couples the pendant arene and the silyl enolether to produce a key intermediate for the synthesis of the natural products. Careful optimization revealed that the use of ‘alcohol-free’ conditions during the electrolysis was critical to obtain high yields of the annulated product. This method allowed the preparation of the tricyclic core of hamigeran A and B in just four steps from commercially available starting materials.