jo971521g_si_002.pdf (560.66 kB)
Chiral Pyridines: Optical Resolution of 1-(2-Pyridyl)- and 1-[6-(2,2‘-Bipyridyl)]ethanols by Lipase-Catalyzed Enantioselective Acetylation
journal contribution
posted on 1998-03-24, 00:00 authored by Jun'ichi Uenishi, Takao Hiraoka, Shinichiro Hata, Kenji Nishiwaki, Osamu Yonemitsu, Kaoru Nakamura, Hiroshi TsukubeThe 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
°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
sp3-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 °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 °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.