Total synthesis of the proposed structure of iriomoteolide-1a

Full details of the total synthesis of the proposed structure of iriomoteolide-1a (1) are described. The key steps include (i) a Sakurai reaction between allylsilane 11 and aldehyde 10 that bears both a tertiary chiral center and vinyl iodide moiety (ii) an anti-aldol reaction to construct the C18/C19 chiral centers (iii) a B-alkyl Suzuki-Miyaura coupling reaction to assemble the C7-C23 fragment, and (iv) a macrocyclic ring-closing metathesis to complete the construction of the target molecule. Two different approaches to access penultimate precursor 2 are delineated. The NMR spectra of the synthetic iriomoteolide-1a (1) were found not to match those reported for the natural product bringing into question its true structural identity.