Yasuyuki Kita

Facile and efficient macrolactonization of hydroxycarboxylic acid via ethoxyvinyl esters (EVEs), which can give 9‐ to 14‐membered macrolactones in good yields, has been developed (see scheme; DCE = 1,2‐dichloroethane). The method is useful for acid‐/base‐sensitive substrates and applicable to the compound with many functional groups. magnified image We present the highly efficient reaction procedure of the macrolactonization method via ethoxyvinyl esters (EVEs). The following procedure was performed: 1) The EVE was prepared from hydroxycarboxylic acid and ethoxyacetylene in the presence of the Ru catalyst [RuCl₂(p‐cymene)]₂ in acetone; 2) after filtration of the Ru catalyst through a short‐neutral SiO₂ pad and evaporation of acetone, the EVE formed was diluted in 1,2‐dichloroethane (DCE) and the solution was slowly added by a syringe pump to the highly diluted DCE solution of pTsOH (10 mol %) at 80 °C. Various‐sized lactones could be produced by the method described here. It is noteworthy that the method can give 9‐ to 14‐membered macrolactones in good yields. This macrolactonization method via EVEs is useful for acid‐/base‐sensitive substrates. Furthermore, it was found that EVE formation was possible without loosing activity of the Ru catalyst even for the compounds with nucleophilic amine functions. The characteristic feature of the method was exemplified by the reaction of the compound 14 with many functional groups.

A novel method to prepare 2-H-imidazolines from glyoxylic acid monohydrate and 1,2-diamines is described; the key reaction of this method is the oxidative decarboxylation of the 2-carboxy imidazolidines by NBS.

The concise asymmetric total synthesis of scyphostatin has been achieved by condensation of the optically active cyclohexane unit, prepared from the commercially available 1,4‐cyclohexadiene by our own method, and the side chain, prepared by the method developed by Hoye and Tennakoon (T. R. Hoye, M. A. Tennakoon, Org. Lett. 2000, 2, 1481–1483). The modification of the epoxy cyclohexenone unit was achieved in a late stage of the total synthesis, and deprotection of the primary alcohol was conducted in the final step. During the synthesis several key reactions were attained: 1) intramolecular bromoetherification of the cyclohexadiene acetal; 2) stereoselective introduction of the tertiary alcohol, 3) deprotection of the acetal function to the aldehyde by combination with silyl triflate/2,4,6‐collidine and the one‐pot synthesis of the disilyl aldehyde compounds, with different types of silyl groups, from the dihydroxy acetal compounds; and 4) facile deprotection of the 2,4‐dimethoxyphenylmethyl (^2,4DMPM) protecting group of the primary alcohol.