General method for the asymmetric synthesis of anti-diastereoisomers of β-substituted L-2-aminobutanoic acids via chiral nickel(II) Schiff's base complexes of dehydroaminobutanoic acid. X-Ray crystal and molecular structure of the nickel(II) complex of the Schiff's base from [(benzylprolyl)amino]benzophenone and dehydroaminobutanoic acid

Abstract

An efficient approach to the asymmetric synthesis of (L)-allo-isomers of β-substituted α-aminobutanoic acid is described. The chiral Ni^II complex of a Schiff's base derived from (S)-o-[N-(N-benzylprolyl)amino]benzophenone (BBP) and glycine was treated with acetaldehyde in MeOH. The addition proceeds with high diastereoselectivity to give, if catalysed by MeONa, the corresponding complex of (R)-threonine, and, if catalysed by Et₃N, the corresponding complex of (S)-allo-threonine. The (R)-threonine complex was converted into the chiral Ni^II complex of dehydroaminobutanoic acid, and a X-ray diffraction structural study of its major isomer showed that the dehydroaminobutanoic acid moiety was in the E-configuration. The complex, in turn, entered into Michael addition reactions with nucleophiles, including MeOH, EtOH, PhSH, and PhCH₂SH. The reaction proceeded with high diastereoselectivity, producing predominantly complexes of the allo-threonine derivatives (d.e. > 90%). Diastereoisomerically and enantiomerically pure α-amino acids were obtained after chromatographic purification, decomposition of the complexes, and recovery of the initial chiral auxiliary, BBP. The thiol addition reaction is accompanied by a side reaction leading to the formation of sizeable amounts of the vinylglycine complex. An approach to the synthesis of optically active vinylglycine starting with racemic methionine is described.