Massachusetts Institute of Technology, Department of Chemistry, Cambridge, Massachusetts 02139
tfj@mit.edu
Received August 30, 2007
Abstract:
Synthetic studies toward the total synthesis of (+)-acutiphycin (1) resulted in the discovery of additive-free, highly regioselective nickel-catalyzed reductive coupling reactions of aldehydes and 1,6-enynes
and the construction of an advanced intermediate in studies directed toward the synthesis of 1. Ultimately,
although not employing the nickel-catalyzed reaction, a highly convergent total synthesis of (+)-acutiphycin
featuring an intermolecular SmI2-mediated Reformatsky coupling reaction and macrolactonization initiated
by a retro-ene reaction of an alkoxyalkyne was achieved. The resulting synthesis was 18 steps in the
longest linear sequence from either methyl acetoacetate or isobutyraldehyde.
