Synthesis of Iriomoteolide-1a C13−C23 Fragment via Asymmetric Conjugate Addition and Julia−Kocienski Coupling Reaction

The key C13−C23 fragment toward the total synthesis of iriomoteolide-1a (<b>1</b>) has been constructed from an 1,2-acetonide containing aldehyde <b>5</b> via a Julia−Kocienski olefination with the C16−C23 segment <b>6</b>. The key step involves stereoselective introduction of the C29 methyl group by a highly efficient CuI-Tol-BINAP-catalyzed asymmetric conjugate addition of methylmagnesium bromide to an α,β-unsaturated ester.