Synthesis of C13-C22 of Amphidinolide T2 via Nickel-Catalyzed Reductive Coupling of an Alkyne and a Terminal Epoxide

Tetrahedron 61(26), 6243-6248, DOI: 10.1016/j.tet.2005.03.116

Several stereoselective routes to the synthesis of (1S,3R)-t-butyldimethyl-(1-methyl-3-oxiranyl-propoxy)-silane (13a) were explored, and the use of Jacobsen’s hydrolytic kinetic resolution to separate a mixture of diastereomeric epoxides was a key step in the shortest of these. As part of an approach to the total synthesis of amphidinolide T2 (2), this epoxide, corresponding to C17–C22 of the natural product, was successfully joined with an alkyne (C13–C16) by way of a nickel-catalyzed reductive coupling reaction.