3-(Hydroxy(phenyl)methyl)azetidin-2-ones obtained via catalytic asymmetric hydrogenation or by biotransformation

The catalytic asymmetric reduction of ethyl-2-(benzamidomethyl)-3-oxo-phenylpropanoate was realized with high enantiomeric and diastereoisomeric excesses via biotransformation using whole cells of different yeasts and asymmetric hydrogenation with Ru(II) complexes prepared from different chiral diphosphine ligands.With these combined approaches it was possible to prepare both enantiomers of the syn-stereoisomers in almost enantiomerically pure form; one of the enantiomers of the anti-stereoisomer was obtained in high ee with selected yeast while the other enantiomer of the anti was prepared in low ee and de. With three of the four epimers we were able to prepare the corresponding azetidinones.

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(2R,3R)-Ethyl 2-(benzamidomethyl)-3-hydroxy-3-phenylpropanoateC19H21NO4[α]D20=+33.2 (c 0.15, CHCl3)Source of chirality: [RuCl2(DMF)n((−)-tetraMe-BITIOP)] or by Kluyveromyces marxianus CBS 1553Absolute configuration: (2R,3R)

(2S,3R)-Ethyl 2-(benzamidomethyl)-3-hydroxy-3-phenylpropanoateC19H21NO4[α]D20=-11.3 (c 0.12,CHCl3)Source of chirality: Pichia glucozyma CBS 5766Absolute configuration: (2R,3S)

(2S,3S)-Ethyl 2-(benzamidomethyl)-3-hydroxy-3-phenylpropanoateC19H21NO4[α]D20=-11.0 (c 0.18, CHCl3)Source of chirality: [RuCl2(DMF)n((+)-tetraMe-BITIOP)]Absolute configuration: (2S,3S)