Chiral Pyridines:  Optical Resolution of 1-(2-Pyridyl)- and 1-[6-(2,2‘-Bipyridyl)]ethanols by Lipase-Catalyzed Enantioselective Acetylation

Abstract

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.

Chiral pyridyl phosphinites with large aryl substituents as efficient ligands for the asymmetric iridium-catalyzed hydrogenation of difficult substrates

“…Uenishi et al 36,37 reported the kinetic resolution of simple tetrahydroquinoline-8-ols with lipase, which we later used and optimized in the preparation of enantiopure alcohols en route to catalysts 6a,b, and 8.…”

Purification and characterization of rat liver enzyme catalyzing stereoselective reduction of acetylpyridines

“…From 301 mg (2.48 mmol) of 2-acetylpyridine (3), 83.7 mg (27.8%) of alcohol (6) 28 93.0% ee by HPLC analysis: Chiralcel OD-H columun (4.6 Â 250 mm, 5 mm; Daicel Chemical Industries, Ltd.) eluted with hexane/2-propanol (49:1 v/v) at 0.5 ml/min; t R = 30.5 min for (R)-6 and t R = 34.2 min for (S)-6. The absolute stereochemistry of the product was determined by comparing the HPLC retention time with authentic samples synthesized by the method of Uenishi et al 29 (R/S:1.5/98.5)-1-Phenylethanol (10). From 301 mg (2.51 mmol) of acetophenone (7), 27 mg (9.0%) of alcohol (10) 30 ; 96.9% ee by HPLC analysis: Chiralcel OD-H columun (4.6 Â 250 mm, 5 mm; Daicel Chemical Industries, Ltd.) eluted with hexane/2-propanol (49:1 v/v) at 1.0 ml/min; t R = 16.9 min for (R)-10 and t R = 21.1 min for (S)-10.…”

Asymmetric Reduction of Heteroaryl Methyl Ketones Using <i>Daucus carota</i>

“…UV detector at 210 nm, varying the mobile phase conditions depending on the specific substrate/product. The structures of the products were determined by mass, infrared spectra, 1 H and 13 C NMR spectroscopic studies and also confirmed by the spectral data of the products obtained through chemical synthesis of the compounds (1a -1g) by NaBH 4 reduction and compared with literature values [33][34][35][36][37][38][39][40]. The enantiomeric excess (ee) and absolute configuration of chiral compounds 2a -2j were determined by the sign of specific rotation or by HPLC using chiral columns.…”