jo301066p_si_001.pdf (2.41 MB)
Study of the Total Synthesis of (−)-Exiguolide
journal contribution
posted on 2012-08-17, 00:00 authored by Cyril Cook, Frédéric Liron, Xavier Guinchard, Emmanuel RoullandIn this article, we disclose the various routes and strategies
we had to explore before finally achieving the total synthesis of
(−)-exiguolide ((−)-1). Two first types
of approaches were set, both relying on the Trost’s domino
ene–yne coupling/oxa-Michael reaction that we choose for its
ability to control the geometry of the methylacrylate-bearing tetrahydropyrane
ring B. In our first approach, we expected to assemble
the two main fragments (C14–C21 and C1–C13) by creating
the C13–C14 bond through a palladium(0)-catalyzed cross-coupling,
but this step failed, unfortunately. In the second approach, which
was more linear, we created the C16–C17 bond through condensation
of a lithium acetylide on a Weinreb amide, and we assembled the C1–C5
and C6–C21 subunits through Trost’s domino ene–yne
coupling/oxa-Michael reaction. These two approaches served us to design
an ameliorated third strategy, which finally led to the total synthesis
of (−)-exiguolide.