Enantiomers of (2R∗,3R∗)-1-methyl-5-oxo-2-phenyltetrahydro-1H-pyrrolidine-3-carboxylic acid as novel chiral resolving agents

A series of (2R∗,3R∗)-1-methyl-5-oxo-2-aryltetrahydro-1H-pyrrolidine-3-carboxylic acids were prepared and their structures were proven with X-ray crystallography. Racemic acid 5 has been resolved into enantiomers (2S,3S)-5 and (2R,3R)-5 by the formation of diastereomeric salts with brucine 9 and strychnidine 10, respectively. The ability of these enantiomers to serve as chiral discriminating agents was demonstrated by the chromatographic separation of diastereomeric amides and esters. Also, some preliminary results on the enantioselective reduction of prochiral imines with sodium borohydride modified by (2R,3R)-5 were collected.

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(2S,3S)-1-Methyl-5-oxo-2-phenyltetrahydro-1H-pyrrolidine-3-carboxylic acidC12H13NO3[α]D23=+112.0 (c 0.9, CHCl3)Source of chirality: resolution with brucineAbsolute configuration: (2S,3S)

(2S,3S)-1-Methyl-5-oxo-2-phenyl-N-[(1R)-1-phenylethyl]tetrahydro-1H-pyrrolidine-3-carboxoamideC20H22N2O2[α]D23=+71.7 (c 1.0, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (2S,3S)-[(1R)]

(2S,3S)-1-Methyl-5-oxo-2-phenyl-N-[(1S)-1-phenylethyl]tetrahydro-1H-pyrrolidine-3-carboxoamideC20H22N2O2[α]D23=-10.3 (c 1.0, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (2S,3S)-[(1S)]

(1R)-2-Oxo-1,2-diphenyl-ethyl (2S,3S)-1-methyl-5-oxo-2-phenyltetrahydro-1H-pyrrolidine-3-carboxylateC26H23NO4[α]D23=-34.2 (c 1.1, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (2S,3S)-[(1R)]

(1S)-2-Oxo-1,2-diphenyl-ethyl (2S,3S)-1-methyl-5-oxo-2-phenyltetrahydro-1H-pyrrolidine-3-carboxylateC26H23NO4[α]D23=+150.8 (c 1.0, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (2S,3S)-[(1S)]

(1R)-1-(2,3,4-Trichlorophenyl)ethanolC8H7Cl3O[α]D23=+62.0 (c 1.0, CHCl3)Source of chirality: resolution by the formation of diastereomeric estersAbsolute configuration: (1R)

(1S)-1-(2,3,4-Trichlorophenyl)ethyl (2S,3S)-1-methyl-5-oxo-2-phenyltetrahydro-1H-pyrrolidine-3-carboxylateC20H18Cl3NO3[α]D23=+49.5 (c 1.0, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (2S,3S)-[(1S)]

(1R)-1-(2,3,4-Trichlorophenyl)ethyl (2S,3S)-1-methyl-5-oxo-2-phenyltetrahydro-1H-pyrrolidine-3-carboxylateC20H18Cl3NO3[α]D23=+36.7 (c 1.0, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (2S,3S)-[(1R)]