Chirality Transfer and Oxazolidine Formation in Reaction of L and D Enantiomers of β-Hydroxy Amino Acids with Nitrogenous Carboxaldehydes and Nickel(II).

The reaction of either the L (2S3R) or D (2R3S) enantiomers of H2N-C*H(R)CO2- (R = -C*H(OH)CH3 or -C*H(OH)CH(CH3)2) and the L (2S) or D (2R) enantiomers of H2N-C*H(C(CH3)2OH)CO2- with imidazole-4-carboxaldehyde and nickel(II) acetate in methanol yields a single stereoisomer of an oxazolidine. There is retention of chirality on ring positions 4 and 5 (if Cβ is chiral) of the oxazolidine, Cα and Cβ of the parent amino acid, and transfer of chirality to the newly generated stereogenic centers, ring positions 3, the amino acid nitrogen atom, NAA, and 2, the aldehyde carbon atom, Cald. Specifically, when Cα has an S configuration, both NAA and Cald are formed as R. Likewise, a Cα which is R results in both NAA and Cald being formed as S. For example, the reaction of L threonine (Cα is S and Cβ is R) with 4-imidazolecarboxaldehyde in the presence of nickel(II) gives the facial Λ NiL2, where L is (2R, 3R, 4S, 5R) 4-carboxylato-5-methyl-2-(4-imidazolyl)-1,3-oxazolidine. The same reaction with D threonine produces the enantiomeric Δ complex of (2S, 3S, 4R, 5S) 4-carboxylato-5-methyl-2-(4-imidazoyl)-1,3-oxazolidine. The high stereospecificity is thought to be based on the fused three-ring structure of the characterized nickel complexes in which the hydrogen atoms of Cα, NAA, and Cald must be cis to one another. Identical reactions occur with 2-pyridine carboxaldehyde and LT or DT. In contrast, the reactions of L allo threonine (2S3S) and the primary alcohols, L or D serine, give the conventional meridionally coordinated aldimine product.