Stereoselective Electrosynthesis of -Hydroxy--Amino Acids in the Form of NiII-Schiff-Base Complexes

A new electrochemical method for stereoselective hydroxyalkylation of glycine in the form of a chiral Ni-II complex of the Schiff base derived from (S)-2-[N-(N-benzylprolyl)amino] benzophenone (GlyNi) is elaborated. The method is technologically simple: galvanostatic electrolysis of GlyNi is performed in a one-compartment electrochemical cell in an alcohol solution (which serves as a reactant and a solvent simultaneously) in the presence of KOH. High chemical yields of -amino--hydroxy acids (in the form of Ni-II Schiff base complexes) were obtained for the C1-C3 primary alcohols; for the higher alcohols yields were low. The stereochemical outcome of the process is dependent on the pH of the solution and the reaction time between the end of the electrolysis and the work-up procedure. Thermodynamically more stable (2R) product (for methanol) and (2R,28S)-diastereomer (for the homologues) are formed at high pH with high diastereselectivity (de up to 94%). In the media with low basicity, under kinetic control, the (2S) complex (for methanol) and (2S,28R)-diastereomer (for higher alcohols) can be obtained (de = 100%). The correlation between the chemical shift of the H8 proton in the H-1 NMR spectra and the configuration of the amino acid -stereocenter in the Ni-II Schiff-base complexes was established providing a new tool for determination of the absolute configuration of the -carbon stereocenter.