Synthesis and characterization of chiral 1,2-diamines from 5-oxo-pyrrolidine-(S)-2-carboxylic acid

Unsymmetrical chiral secondary vicinal diamines were synthesized by applying a modified three-step reaction. The key step in this sequence is a primary amine mediated ring opening reaction of a diastereomeric oxazolidinone derivative. A possible mechanism for this step is described.

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N-Phenyl-5-oxo-pyrrolidine-(S)-2-carboxamideC11H12N2O2[α]D20=+14.1 (c 2.27, DMSO)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

N-Tolyl-5-oxo-pyrrolidine-(S)-2-carboxamideC12H14N2O2[α]Drt=+16.1 (c 2.11, DMSO)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

N-Mesityl-5-oxo-pyrrolidine-(S)-2-carboxamideC14H18N2O2[α]Drt=+23.4 (c 2.22, DMSO)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

N-(4-Chlorophenyl)-5-oxo-pyrrolidine-(S)-2-carboxamideC11H11N2O2Cl[α]Drt=+13.8 (c 2.18, DMSO)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

N-(1-Naphthyl)-5-oxo-pyrrolidine-(S)-2-carboxamideC15H14N2O2[α]Drt=+34.65 (c 2.02, DMSO)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

N-Benzyl-5-oxo-pyrrolidine-(S)-2-carboxamideC12H14N2O2[α]Drt=+13.7 (c 2.04, DMSO)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

N-(4-Methylbenzyl)-5-oxo-pyrrolidine-(S)-2-carboxamideC13H16N2O2[α]Drt=+7.8 (c 2.04, DMSO)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

N-(R)-1-Phenylethyl-5-oxo-pyrrolidine-(S)-2-carboxamideC13H16N2O2[α]Drt=+84.85 (c 1.98, DMSO)Source of chirality: 5-oxo-l-proline (R)-2-phenylethylamineAbsolute configuration: (S,R)

N-(S)-1-Phenylethyl-5-oxo-pyrrolidine-(S)-2-carboxamideC13H16N2O2[α]Drt=-89.6 (c 2.21, DMSO)Source of chirality: 5-oxo-l-proline (S)-2-phenylethylamineAbsolute configuration: (S,S)

N-(Pyrrolidin-2-ylmethyl)-anilineC11H16N2[α]Drt=+31.0 (c 4.77, CHCl3)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

4-Methyl-N-(pyrrolidin-2-ylmethyl)-anilineC12H18N2[α]Drt=+29.5 (c 2.85, CHCl3)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

2,4,6-Trimethyl-N-(pyrrolidin-2-ylmethyl)-anilineC14H22N2[α]Drt=+23.25 (c 5.85, CHCl3)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

4-Chloro-N-(pyrrolidin-2- ylmethyl)-anilineC11H15N2Cl[α]Drt=+27.1 (c 2.58, CHCl3)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

N-(Pyrrolidin-2-ylmethyl)-naphthalene-1-amineC15H18N2[α]Drt=+52.0 (c 3.27, CHCl3)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

Benzyl-(pyrrolidin-2-ylmethyl)-amineC12H18N2[α]Drt=+15.15 (c 5.81, CHCl3)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

4-Methylbenzyl-(pyrrolidin-(S)-2-ylmethyl)-amineC13H21N2[α]Drt=+14.95 (c 3.88, CHCl3)Source of chirality: 5-oxo-l-prolineAbsolute configuration: (2S)

(R)-1-Phenylethyl-(pyrrolidin-(S)-2-ylmethyl)-amineC13H20N2[α]Drt=+27.1 (c 2.58, CHCl3)Source of chirality: 5-oxo-l-proline (R)-2-phenylethylamineAbsolute configuration: (S,R)

(S)-1-Phenylethyl-(pyrrolidin-(S)-2-ylmethyl)-amineC13H20N2[α]Drt=-15.3 (c 3.40, CHCl3)Source of chirality: 5-oxo-l-proline (S)-2-phenylethylamineAbsolute configuration: (S,S)