Enyne metathesis of norbornene derivatives: a facile approach to polycyclic heterocycles

A concise synthesis of the ten-membered lactone 26 is described which constitutes the key intermediate of a previous total synthesis of the marine natural product ascidiatrienolide 1 and can also be elaborated into the closely related didemnilactones 2 - 4. The E/Z-ratio obtained in the ring-closing metathesis (RCM) reaction forging such non-enolide structures is found to be dependent on the relative configuration of the cyclization precursor as well as on the chosen catalyst. Specifically, it is shown that the ruthenium indenylidene complex 12 and the "second generation" Grubbs type catalyst 13 bearing an N- heterocyclic carbene ligand lead to opposite stereochemical results when applied to the synconfigured diene 21, but to the identical outcome with the anti-configured analogue 10