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 (1) has been constructed from an 1,2-acetonide containing aldehyde 5 via a Julia-Kocienski olefination with the C16-C23 segment 6. 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 alpha,beta-unsaturated ester.