The development of more efficient syntheses of polycyclic diterpenes through intramolecular cyclopropanation of aryl rings in diazomethyl ketones

Abstract

Several approaches to the total synthesis of the troponoid diterpene lactone 1 have been undertaken. The most successful approach to date has afforded secoharringtonolide 26. The intramolecular cyclopropanation reaction of an aryl ring by means of the transition metal catalysed reaction of a diazoacetyl function was used to assemble the 5/7 ring system and to provide a cycloheptatrienyl precursor to the tropone moiety. In a cognate study, the intramolecular cyclopropanation reactions of the aromatic ring in a wide range of tetralin 2-diazomethyl ketones afforded norcaradiene products which, because of geometric constraints, were energetically more favoured than the tautomeric cycloheptatrienes. The [4+2] cycloaddition of selected dienophiles to some of these products, e.g. the vinyl analogue 34, allowed the rapid stereocontrolled assembly of advanced intermediates for the synthesis of diterpenoids 2 and 3.