Electrochemical Transformations of Chiral Ni(II) Schiff Base Derivative of Serine: A Route to Novel Structures

Abstract

Electrochemical oxidative functionalization of (R)‐ and (S)‐SerNi complexes performed in a biphasic H2O, NaBr, NaHCO3/CH2Cl2 system using TEMPO as a mediator results in the formation of a new glycine derivative brominated at the α‐amino acid carbon as well as at the para‐position of the aminophenylene ring in 70 % yield. The reaction is stereoselective; only the (S)‐diastereomer is formed, regardless of the stereo configuration of the starting complex, which can be either (S)‐ or (R)‐SerNi. The lability of the Cα‐−Cβ bond in SerNi precludes targeted oxidation of the hydroxy group in the carbonyl derivative even under the mild conditions. Meanwhile, a new dibrominated complex with a labile Cα‐Br bond (BDE is 27 kcal/mol) is a convenient precursor for further modification of the amino acid fragment, for example via nucleophilic reactions. The new α‐sulfanyl complex was obtained in 63 % yield. The mechanism of the electrochemical processes is discussed.

Electrochemical Approaches for Preparation of Tailor-Made Amino Acids

“…, respectively. [32] Recently in 2020, Magdesieva and co-authors [33] developed an electrochemical bromination and sulfanylation reaction of serine-derived chiral Ni(II)-complex by using TEMPO (2,2,6,6-tetrame-thylpiperidinooxy) as a mediator (Scheme 10). This electrochemical transformation was performed in an undivided cell in a biphase H 2 O, NaBr, NaHCO 3 /CH 2 Cl 2 system with current density of 20 mA/cm 2 under argon, affording a new glycine derivative brominated at the α-amino acid carbon as well as at the para-position of the aminophenylene ring in 70% yield.…”

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

“…Recently, we elaborated a versatile electrochemical approach for the stereoselective functionalization of a side chain of amino acids involved in the Ni(II) chiral coordination environment [9][10][11][12][13][14][15]. A combination of redox-activity and chirality provided by the Ni-Schiff base template, supported with the protection from redox-destruction of the amino acid skeleton, makes the suggested approach a convenient route to various types of nonproteinogenic amino acids [9,10,12,13]. Recently, several practical approaches to α,α-cyclopropanated amino acids in the form of Ni(II)-Schiff base complexes were suggested [16][17][18][19], including electrochemical ones [15].…”

Ni(II) Schiff‐Base Complexes as Chiral Electroauxiliaries and Methodological Platform for Stereoselective Electrochemical Functionalization of Amino Acids

“…Redox‐active platform containing a chirality source will be able to provide a stereoselectivity control, in addition to activation using electron transfer. To the best of our knowledge, such “combined” approach was first actualized in our publications which concerned electrochemically activated reactions in the chiral coordination environment of the stable Ni(II) Schiff base complexes [30–39] …”

“…In particular, Schiff base complexes was suggested by Prof. Belokon and coworkers [45] as a platform for chiral modification of the amino acids; recent publications are reviewed in [46–49] . However, the combination of the synthesis in the chiral coordination environment with electrochemical activation has not been probed prior to our publications [30–35] . Meanwhile, electrochemistry creates a possibility to develop new modes of reactivity for well‐known compounds, thus increasing the functionality of a molecule.…”