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

## TL;DR

This paper studies how the chirality of amino acids is transferred during a chemical reaction involving nitrogenous carboxaldehydes and nickel(II), forming specific oxazolidine stereoisomers.

## Contribution

The study reveals a high stereospecificity in chirality transfer during oxazolidine formation from enantiomers of β-hydroxy amino acids.

## Key findings

- The reaction preserves chirality at specific ring positions and transfers it to new stereogenic centers.
- L and D enantiomers of threonine produce enantiomeric nickel complexes with distinct configurations.
- The stereospecificity is attributed to the fused three-ring structure of nickel complexes.

## Abstract

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.