Synthesis of the C1-C17 fragment of the archazolids by complex cis-homodimer cross metathesis.

A synthesis of the C1-C17 fragment of the archazolids is described featuring a complex cross-metathesis coupling reaction between a cis-homodimer (prepared by silyl-tethered ring-closing metathesis) and the Z,Z-terminal triene containing "eastern domain" of the archazolid natural products. This cross-metathesis was only successful when using the cis- as opposed to the monomer or trans-homodimer, with the cis-dimer added batchwise to minimize cis/trans-isomerization. The product was obtained in an optimized 78% yield using the Hoveyda-Grubbs catalyst at 50 °C in toluene.