engleski

On the Way to a-Alkyl-a-Amino Acids; Unusual Elimination-Addition in 3,3-Disubstituted 1,4-Benzodiazepines-2-ones

(–)-3-Methanesulfoxymethyl-3-acetoxoymethyl-7-chloro-5-phenyl-1,4-benzodiazepin-2-one, (–)-2, reacts with ethanethiol in the presence of a strong base affording racemic elimination-addition product 3-ethylthiomethyl-7-chloro-5-phenyl-1,4-benzodiazepin-2-one (4). Intermediary 3-methylene-7-chloro-5-phenyl-1,4-benzodiazepin-2-one (3) is formed by pericyclic C–C bond breaking during elimination of both acyloxy groups. The second approach to a-methyl-a-amino acids comprises kinetic resolution of racemic 3-hydroxymethyl-3-benzyl7-chloro-5-phenyl-1,4-benzodiazepin-2-one (7) via acetylation by Novozym 435 lipase; enantiomeric excess (e.e.) for alcohol (3S)-(+)-7 33.2%; e.e. for acetate (3R)-(–)-8 30.2%. Opposite direction of enantioselectivity during acetylation of 7 and the recently studied 9 (Ref. 3) was established by determination of absolute conformation and relative configuration at C(3) (pseudoaxial/pseudoequatorial) by combining CD and 1H NMR spectroscopy.

1,4-Benzodiazepin-2-ones; kinetic resolution; absolute configuration

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