| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1347980 | Tetrahedron: Asymmetry | 2007 | 7 Pages |
This paper concentrates on studies of the acylation of alcohols with 3,3-difluoro-4-phenylazetidin-2-one rac-1, trans-3-fluoro-4-phenylazetidin-2-one rac-2 and 4-phenylazetidin-2-one rac-3 in the presence of immobilized lipase PS from Burkholderia cepacia in dry tert-butyl methyl ether (TBME). Fluorine activation in the compounds studied was essential in order to split the β-lactam ring with lipase PS. The highly enantioselective ring opening of rac-1 and rac-2 with methanol (1-butanol was also studied) allowed the preparation of the (R/(3R,4R))-β-lactams as the unreacted enantiomers and (S/(2S,3S))-β-amino esters as the product enantiomers with an ee >99%. Under the same conditions, rac-3 was totally unreactive. The possibility for a competing hydrolysis caused by water in the enzyme preparations is also discussed.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
(R)-3,3-Difluoro-4-phenyl-2-azetidinoneC9H7F2NOEe >99%[α]D22=-76.6 (c 1.0, CHCl3)Source of chirality: lipase PS-catalyzed resolutionAbsolute configuration: (R)
(3R,4R)-3-Fluoro-4-phenyl-2-azetidinoneC9H8FNOEe >99%[α]D22=-19.1 (c 1.0, CHCl3)Source of chirality: lipase PS-catalyzed resolutionAbsolute configuration: (3R,4R)
(2S,3S)-Methyl 2-fluoro-3-amino-3-phenyl-propanoateC10H12FNO2Ee >99%[α]D22=+10.1 (c 1.0, CHCl3)Source of chirality: lipase PS-catalyzed methanolysisAbsolute configuration: (2S,3S)
(2S,3S)-2-Fluoro-3-amino-3-phenyl-propanoic acidC9H10FNO2Ee >99%[α]D22=-42.8 (c 0.4, CH3OH)Source of chirality: derivative of the product from lipase PS-catalyzed methanolysisAbsolute configuration: (2S,3S)
(S)-Methyl 2,2-difluoro-3-amino-3-phenyl-propanoateC10H11F2NO2Ee >99%[α]D22=-5.8 (c 1.0, CHCl3)Source of chirality: lipase PS-catalyzed methanolysisAbsolute configuration: (S)
