A six-step synthesis of （-）-clausenamide is described. Optically pure （R,E）-1,3-diphenylallylic alcohol was ac-etylated and then subjected to an Ireland-Claisen rearrangement, giving the γ,δ-unsaturated acid, wh...A six-step synthesis of （-）-clausenamide is described. Optically pure （R,E）-1,3-diphenylallylic alcohol was ac-etylated and then subjected to an Ireland-Claisen rearrangement, giving the γ,δ-unsaturated acid, which underwent a substrate-induced stereoselective bromolactonization to afford the expected all-equatorial substituted bromo-δ-lac-one. An unusual chemo-selective aminolysis of the lactone resulted in the formation of a γ,δ-epoxy-amide in stereospecific manner. Base-promoted cyclization of this intermediate and the subsequent Davis oxidation furnished the synthesis, delivering the final product in 〉99% ee and up to 34% overall yield.展开更多
文摘A six-step synthesis of （-）-clausenamide is described. Optically pure （R,E）-1,3-diphenylallylic alcohol was ac-etylated and then subjected to an Ireland-Claisen rearrangement, giving the γ,δ-unsaturated acid, which underwent a substrate-induced stereoselective bromolactonization to afford the expected all-equatorial substituted bromo-δ-lac-one. An unusual chemo-selective aminolysis of the lactone resulted in the formation of a γ,δ-epoxy-amide in stereospecific manner. Base-promoted cyclization of this intermediate and the subsequent Davis oxidation furnished the synthesis, delivering the final product in 〉99% ee and up to 34% overall yield.
