A novel synthetic route to rac-(Z)-recifeiolide from cyclooctanone and acetaldehyde

A novel synthetic approach to (±)-Z-recifeiolide 6, a 12-membered-ring lactone which can be selectively isomerized into (E)-recifeiolide, a natural antibiotic product isolated from fungus (Cephalosporium recifei) is reported. The synthesis is accomplished in five steps starting from readily available cyclooctanone and acetaldehyde based on the Lewis acid-catalyzed TMS-directed oxy-2-oxonia-Cope rearrangement. The work represents a novel strategy to assemble related macrolides.

An efficient diastereoselective synthesis of rac-(Z)-recifeiolide from cyclooctanone and acetaldehyde was developed. The key step features the Lewis acid mediated electrocyclic oxy-2-oxonia-Cope rearrangement of the β,γ-unsaturated ketone with acetaldehyde. The β-trimethylsilyl group functions as masked proton as well as electronic activator group and was cleaved off by in situ proto desilylation.Figure optionsDownload as PowerPoint slide