Highly stereoselective asymmetric hydrogenation of 2-benzamidomethyl-3-oxobutanoate catalysed by cationic binap–ruthenium(II) complexes

Abstract

Highly diastereoselective hydrogenation of methyl 2-benzamidomethyl-3-oxobutanoate has been accomplished by using [Rul{ (R)-binap}(p-cymene)]I and corresponding complexes of derivatives of binap as catalyst, giving methyl (2S,3R)-2-benzarnidomethyl-3-hydroxybutanoater a versatile intermediate for the synthesis of @-lactam antibiotics, in up to 98% diastereoisomeric excess and 99% enantiomeric excess.

Substituent electronic effects in chiral ligands for asymmetric catalysis

“…Mashima and co-workers developed catalysts of the type [RuX(BINAP)(arene)]Y (X = halides, Y = anions), which promoted the asymmetric hydrogenation of both olefins and ketones [46]. They identified the importance of reaction conditions, the halide bound to Ru and phenyl-ring substitution patterns on the reaction outcome [47]. In a further investigation of the influence of the electronic and steric properties of the substituents on the phenyl rings of BINAP, the derivatives 73 were synthesised and applied in the hydrogenation of olefinic and ketonic substrates, Scheme 38 [48].…”

Conformationally Flexible Biphenyl-phosphane Ligands for Ru-Catalyzed Enantioselective Hydrogenation

“…H NMR spectrum that is quite similar to that of the racemic DM-BINAP/RuCl 2 /(S,S)-DPEN complex. [8,9] This indicated the initial formation of an equimolar mixture of S-and R-fixed DM-BIPHEP/RuCl 2 /(S,S)-DPEN diastereomers in this solvent ( (1/2). In each case, the R and S configuration is fixed.…”

Stereoselective determination of 2-benzamidomethyl-3-oxobutanoate and methyl-2-benzoylamide-3-hydroxybutanoate by chiral high-performance liquid chromatography in biotransformation

“…Several chromatographic methods for the diastereo-and enantioselective separation of MBHB isomers have been reported [7,16,19,20]. Schneider and co-workers firstly described the diastereoselective resolution of (2S, 3S)-MBHB and (2R, 3S)-MBHB isomers by thin-layer chromatography (TLC) using toluene/ethyl acetate (1:2, v/v) as eluent [19].…”

“…Schneider and co-workers firstly described the diastereoselective resolution of (2S, 3S)-MBHB and (2R, 3S)-MBHB isomers by thin-layer chromatography (TLC) using toluene/ethyl acetate (1:2, v/v) as eluent [19]. Then indirect HPLC using sample derivatization with (+)-(R)-␣-methoxy-␣-(trifluoromethyl) phenylacetic acid (MTPA) esters of MBHB prior to injection onto achiral chromatography columns, Nucleosil 100-3 and Deverosil 100-3 [16,20], has been described for the enantioselective separation of MBHB; however, it is inconvenient and time consuming thus not suitable for screening biocatalysts. Subsequently, direct HPLC methods have been developed for the enantioselective separation of MBHB [7] and structural analogs involved ethyl-2-benzoylamide-3-hydroxybutanoate [15,21,22], ethyl-2-benzamidomethyl-4-fluoro-3-hydrobutanoate [6] and ethyl-2-(benzamidomethyl)-3-oxo-phenyl propanoate [15], using Chiralcel OD column, Chiralpak AD column or Chiralpak IA column.…”