Synthesis of Two Diastereomeric C1–C7 Acid Fragments of Amphidinolactone B Using B-Alkyl Suzuki–Miyaura Cross-Coupling as the Modular Assembly Step

The proposed structure of amphidinolactone B has an oxygenated stereogenic center at C6 whose absolute configuration remains unassigned. As part of our total synthesis program, two diastereomeric C1-C7 acid fragments have been synthesized from a common C6, C7-diol intermediate. The latter was obtained from the two readily available chiral alkenyl/alkyl iodides using the "9-MeO-9-BBN variant" of the B-alkyl Suzuki-Miyaura cross-coupling reaction under the Pd(OAc)(2)-Aphos-Y-catalyzed reaction conditions (K3PO4 center dot 3H(2)O, H2O, THF, r.t., 12 h, 75%). The C6, C7-diol was then transformed into two diastereomeric C6, C7-epoxides through manipulation of the epoxide ring closure process. Finally, the epoxides reacted with dimethylsulfonium methylide (Me2S+CH2-) to form, respectively, the corresponding allylic alcohols with the defined absolute configuration at C6.