Asymmetric synthesis of anti-diastereoisomers of β-heterocycle substituted (S)-α-aminobutyric acids

A new efficient method for the asymmetric synthesis of β-heterocycle substituted (2S,3S)-α-aminobutyric acids through the diastereoselective addition of 5-thioxo-4-allyl-1,2,4-triazoles, containing various substituents at the 3-position, to the CC double bond of (E)- and (Z)-dehydroaminobutyric acid in the NiII complexes of their Schiff base with chiral auxiliaries (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide [(S)-BPB], (S)-N-(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)pyrrolidine-2-carboxamide [(S)-3,4-DCBPB], (S)-N-(2-benzoylphenyl)-1-(3,4-dimethylbenzyl)pyrrolidine-2-carboxamide [(S)-3,4-DMBPB], and (S)-N-(2-benzoylphenyl)-1-(2-chlorobenzyl)pyrrolidine-2-carboxamide [(S)-2-CBPB] has been elaborated upon. The nucleophilic addition proceeds with high diastereoselectivity with a preferential formation of (S,S,S)-diastereoisomers. After decomposition of a mixture of diastereomeric complexes, optically active β-heterocycle substituted (2S,3S)-α-aminobutyric acids with high diastereomeric purity (de >98%) were isolated.

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(2S,3S)-3-(4′-Allyl-3′-hydroxypropyl-5′-thioxo-1,2,4-triazol-1′-yl)-2-aminobutyric acidC12H20N4O3SEe pure[α]D20=-30 (c 0.1, 6 M HCl)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

(2S,3S)-3-(4′-Allyl-3′-hydroxyisoamyloxybutyl-5′-thioxo-1,2,4-triazol-1′-yl)-2-aminobutyric acidC18H32N4O4SEe pure[α]D20=-22.5 (c 0.04; 4.9 M HCl)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

(2S,3S)-3-(4′-Allyl-3′-o-methoxyphenyl-5′-thioxo-1,2,4-triazol-1′-yl)-2-aminobutyric acidC16H20N4O3SEe pure[α]D20=-33.3 (c 0.1, 4.9 M HCl)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

(2S,3S)-3-(4′-Allyl-3′-o-chlorophenyl-5′-thioxo-1,2,4-triazol-1′-yl)-2-aminobutyric acidC15H17N4ClO2SEe pure[α]D20=-25.6 (c 0.1, 4.9 M HCl)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

(2S,3S)-3-(4′-Allyl-3′-hydroxyoctyl-5′-thioxo-1,2,4-triazol-1′-yl)-2-aminobutyric acidC17H30N4O3SEe pure[α]D20=-5.0 (c 0.1, 4.9 M HCl)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)