Soloshonok Nucleophilic Glycine Equivalents for Synthesis of alpha-Amino Acids

Recently, Soloshonok et al. have developed Ni(II) complexes of glycine Schiff base 1, 2 and 3 that is used as nucleophilic glycine equivalents for reparation of structurally varied tailor-made α-amino acids. They have found a unique combination of 1 and N-(E-enoyl)oxazolidin-2-ones 4 as α,β-unsaturated carboxylic acid derivatives allowing the corresponding Michael addition reactions to proceed at room temperature in the presence of a catalytic amount of organic non-chelating base with virtually complete diastereoselective and quantitative chemical yield.¹⁾ Also, with simple workup conditions such as acidic decomposition of adduct followed by aqueous ammonium hydroxide treatment to afford β-substituted pyroglutamic acids 5 in enantio- and diastereomerically pure form.

With the same success, in terms of virtually complete chemical (>95% yield) and stereochemical (>95% ee and de) outcome, derivatives 2 and 3 can be applied in these Michael addition reactions.

In particular, complex 1 has been successfully used for large-scale (kg) production of several enantiomerically pure β-substituted pyroglutamic acids.

Moreover, they have demonstrated that complexes 2 and 3 easily undergo complete bis-alkylation with various alkyl halides in the presence of sodium tert-butoxide to give a practical access to the corresponding sym-α,α-dialkylated α-amino acids²⁾ and cyclic α,α-disubstituted α-amino acids.³⁾

Application of these complexes in bis-alkylation reactions can be conducted under operationally convenient conditions (ambient temperature) and allows for preparation of highly sterically constrained bis-amino acids in high chemical yields.

Besides, these complexes, 2 and 3, have a potential to be used under phase transfers conditions (PTC), using chiral phase transfer catalysts for asymmetric synthesis of α-amino acids.⁴⁾