Synthetic studies on the salicylihalamides: macrolactone formation via ring closing metathesis versus macrolactonization

Two routes to the unusual 12-membered unsaturated benzolactone of the highly cytotoxic marine metabolites the salicylihalamides are presented. The first involves an RCM step to construct the C9C10 alkene bond and this provided the model macrolactones 9 and 10 in a ratio of 77:23, respectively. An alternative route involved a Stille coupling to construct the C8C9 bond followed by a macrolactonization to give the lactones 9 and 10 in a ratio of 96:4.