Nickel-catalyzed reductive coupling reactions of 1,6-enynes and the total synthesis of (+)-acutiphycin

Abstract

Nickel-Catalyzed Reductive Coupling Reactions of Aldehydes and Chiral 1,6-Enynes. A study of nickel-catalyzed reductive coupling reactions of aldehydes and chiral 1,6-enynes has provided evidence for stereospecific ligand substitution from a planar three-coordinate nickel species as a plausible explanation of regioselectivity in the nickel-catalyzed reductive coupling of aldehydes and 1,6-enynes. In the absence of a phosphine additive, high regioselectivity and high diastereoselectivity are obtained as a direct result of coordination of both the alkyne and the olefin to the metal center during the C-C bond-forming step. ... Total Synthesis of (+)-Acutiphycin. Synthetic studies toward the total synthesis of (+)-acutiphycin led to, and were in turn further developed by, the study of nickel-catalyzed reductive coupling reactions of 1,6-enynes and aldehydes. ... Ultimately, though 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 developed. The resulting synthesis was 18 steps in the longest linear sequence from either methyl acetoacetate or isobutyraldehyde. ...