Total Synthesis of the Macrolide (+)-Aspicilin by an Asymmetrically Catalyzed Macrocyclization of an ω-Alkynal Ester

Article abstract of DOI:10.1016/0040-4039(95)00351-C

ω-Alkynal ester 3, prepared from (S)-propylene oxide 4, yields the macrocyclic (6R)-allylic alcohol 2 (60percent yield, 83percent d.e.) in one operation via monohydroboration, boron/zinc-transmetalation and (-)-DAIB "catalyzed" intramolecular alkenylzinc/aldehyde addition.Introduction of the C(2)-C(3) double bond by selenoxide elimination (2 -> 8), hydroxy-directed epoxidation (8 -> 9), acetate assisted α-epoxide opening (10 -> 12) and acidic methanolysis provides pure (+)-aspicilin (1) in 22percent yield from 4.