Total Synthesis of Pumiliotoxins 209F and 251D
via Late-Stage, Nickel-Catalyzed Epoxide-Alkyne
Reductive Cyclization
Katrina S. Woodin andTimothy F. Jamison*
Department of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139
tfj@mit.edu
Received June 6, 2007
Abstract:
Pumiliotoxins 209F and 251D were synthesized using highly
selective nickel-catalyzed epoxide-alkyne reductive cyclizations as the final step. The exocyclic (Z)-alkene found in
the majority of the pumiliotoxins was formed stereospecifically and regioselectively, without the use of a directing
group on the alkyne, and the epoxide underwent ring opening
exclusively at the less hindered carbon to provide the
requisite tertiary alcohol. The epoxides were prepared using
diastereoselective addition of a sulfoxonium anion to a
proline-derived methyl ketone.
