Total synthesis of (+)-acutiphycin.
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.
Moslin
Ryan M
RM
Massachusetts Institute of Technology, Department of Chemistry, Cambridge, Massachusetts 02139, USA.
Jamison
Timothy F
TF
D002384:Catalysis; D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry; D013237:Stereoisomerism
D006571:Heterocyclic Compounds; D018942:Macrolides; C515767:acutiphycin; D009532:Nickel