Synthesis of Cyclopentane-Macrolides Based on Lewis Acid Mediated Cyclization of Chiral Epoxy-Alcohols

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In the course of investigation concerning intramolecular Lewis acid mediated nucleophilic opening of epoxy-alcohols, we have developed an enantioselective route to a substituted cyclopentane 2 from an allyl alcohol 1 through four manipulations ; i)Sharpless asymmetric epoxidation, ii)Lewis acid mediated cyclization ; iii)protection as acetonide ; iv)ozonolysis followed by base-catalyzed epimerization. The generality of this method was proved by the fact that regardless of the stereo- and regio-chemistry of pre-exsisting substituents(R^1 and/or R^2)of 1, tri- or four-substituted cyclopentanes 2 with 1, 2-trans configuration were obtained in high enantiomeric excess(>90% ee). The synthetic utility of this method was demonstrated by the achievement of enantiocontrolled syntheses of(+)-brefeldin A(3)and(+)-brefeldin C(4)from 2(R^1=H, R^2=OBn or R^1=R^2=H).brefeldin C(4)from 2(R'=H, R2=OBn or RI=R2=H).