CHIRAL PYRIDINES - OPTICAL RESOLUTION OF 1-(2-PYRIDYL)ETHANOL AND 1-[6-(2,2'-BIPYRIDYL)]ETHANOL 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 asymmetr ic acetylation with vinyl acetate is reported. The reactions were carr ied out in diisopropyl ether at either room temperature or 60 degrees C using Candida antarctica lipase (CAL) to give (R)-acetate and unreac ted (S)-alcohol with excellent enantiomeric purities in good yields. T he reaction rate was relatively slow at room temperature for substrate s 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 all yl groups at the 2-position on the pyridine ring, such as 2l and 2m. I n such cases, a higher temperature was required. Thus, when the reacti on was conducted at 60 degrees C, it was accelerated 3- to 7-fold with out losing the high enantiospecificity. However, the reaction of homoa llylic alcohol 2n was not complete, even when the reaction was continu ed for a longer period of time at 60 degrees C. This enzymatic resolut ion 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.