A highly efficient macrolactonization method via ethoxyvinyl ester.
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 [RuCl(2)(p-cymene)](2) in acetone; 2) after filtration of the Ru catalyst through a short-neutral SiO(2) 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 degrees 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.
Ohba
Yusuke
Y
Graduate School of Pharmaceutical Sciences, Osaka University 1-6, Yamada-oka, Suita, Osaka, Japan.
Takatsuji
Mayuko
M
Nakahara
Kenji
K
Fujioka
Hiromichi
H
Kita
Yasuyuki
Y
D002384:Catalysis; D003500:Cyclization; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D004952:Esters; D007783:Lactones; D012997:Solvents; D014753:Vinyl Compounds; D012428:Ruthenium