Gram scale synthesis of the C(1)-C(9) fragment of amphidinolide C

Abstract

An allylic cis-epoxide prepared by Sharpless asymmetric epoxidation was transformed in nine steps and 41% overall yield to the cyclization precursor 4 via a key one carbon homologation. Cobalt-catalyzed aerobic oxidative cyclization of 4 gave the trans-THF in 94% yield at gram scale. Subsequent manipulations, including a Still-Gennari olefination, Sharpless asymmetric dihydroxylation, Corey-Fuchs alkynylation, and Kazmaier hydrostannylation provided the fully functionalized C(1)-C(9) fragment 2 suitable for cross-coupling. The sequence is readily scalable and provides gram quantities of 2. © 2013 Elsevier Ltd. All rights reserved.