On the way to alpha-methyl-alpha-amino acids; Unusual elimination-additionin 3,3-disubstituted 1,4-benzodiazepin-2-ones and inversion of enantioselectivity in the lipase catalyzed acetylation

(-)-3-Methanesulfoxymethyl-3-acetoxoymethyl-7-chloro-5-phenyl-1, 4-benzodia zepin-2-one, (-)-2, reacts with ethanethiol in the presence of a strong bas e 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 breakin g during elimination of both acyloxy groups. The second approach to a-methy l-cl-amino acids comprises kinetic resolution of racemic 3-hydroxymethyl-3- benzyl-7-chloro-5-phenyl-1,4-benzodiazepin-2-one (7) via acetylation by Nov ozym 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 H-1 NMR spectroscopy.