Chiral Pyridines: Optical Resolution of 1-(2-Pyridyl)- and 1-[6-(2,2'-Bipyridyl)]ethanols by Lipase-Catalyzed Enantioselective Acetylation.
The resolution of racemic 1-(2-pyridyl)ethanols 2a-n, including the 2,2'-bipyridyl and isoquinolyl derivatives, by lipase-catalyzed asymmetric acetylation with vinyl acetate is reported. The reactions were carried out in diisopropyl ether at either room temperature or 60 degrees C using Candida antarctica lipase (CAL) to give (R)-acetate and unreacted (S)-alcohol with excellent enantiomeric purities in good yields. The reaction rate was relatively slow at room temperature for substrates bearing an sp(3)-type carbon at the 6-position on the pyridine ring, such as 2c, 2d, and 2e, and for those bearing 1-hydroxypropyl and allyl groups at the 2-position on the pyridine ring, such as 2l and 2m. In such cases, a higher temperature was required. Thus, when the reaction was conducted at 60 degrees C, it was accelerated 3- to 7-fold without losing the high enantiospecificity. However, the reaction of homoallylic alcohol 2n was not complete, even when the reaction was continued for a longer period of time at 60 degrees C. This enzymatic resolution can be used practically in a wide range of reaction scales from 10 mg to 10 g or more. This catalyst can be used repeatedly with a 5-10% loss of the initial activity with each use.
Uenishi
Jun'ichi
J
Department of Chemistry, Faculty of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558, Japan.
Hiraoka
Takao
T
Hata
Shinichiro
S
Nishiwaki
Kenji
K
Yonemitsu
Osamu
O
Nakamura
Kaoru
K
Tsukube
Hiroshi
H