Electrochemically Deprotonated Chiral Nickel(II) Glycinate in Stereoselective Nucleophilic Addition to Michael Acceptors: Advantages and Limitations

Abstract

A Ni(II) glycine/Schiff base complex containing (S)-o-[N-(N-benzylprolyl)amino]benzophenone as an auxiliary chiral moiety was deprotonated using electrochemically generated azobenzene radical anion and used in nucleophilic addition to Michael acceptors, terminal 2,2-and 1,2-disubstituted alkenes ((2E)-1,3-diphenylprop-2-en-1-one, (E)-2-nitroethenylbenzene, 2-methylprop-2-enenitrile, Ni(II) dehydroalanine complex), creating a preparatively convenient path for asymmetric functionalization of the α-glycine carbon in the Ni(II) coordination environment, yielding new chiral Ni(II) complexes. The main advantage of the application of electrochemical techniques is the possibility of precise control of the concentration of a base and its in situ reaction with the complex. This opens up the possibility to carry out further functionalization of the anionic adduct formed in Michael addition via a successive one-pot reaction with the other electrophile. A one-pot cascade reaction of electrochemically deprotonated Ni(II) glycinate with (E)-2-nitroethenylbenzene and the successive interaction with benzyl chloride or dimethyl sulfate allowed a new oxime-containing Ni(II) complex to be obtained, which might be considered as an important synthon. All complexes were reliably characterized using HRMS and 1 H and 13 C NMR (including 2D techniques); an adduct with (2E)-1,3-diphenylprop-2en-1-one was also characterized by X-ray diffraction studies and CD spectrum. The manner of stereocontrol in the Michael addition of electrochemically deprotonated Ni(II) glycinate was shown to be different for terminal 2,2-and for 1,2-disubstituted alkenes. In the case of the 1,2-disubstituted alkene both stereocenters are already formed in the first reaction step, which is reversible and thermodynamically controlled. The second step (protonation of the anion) is fast and irreversible, and it does not influence the stereochemical result of the reaction. In contrast to the previous case, only one stereocenter is formed in the first thermodynamically controlled step for terminal alkenes, whereas the configuration of the second stereocenter is determined by a kinetically controlled protonation step.

Which Stereoinductor Is Better for Asymmetric Functionalization of α‐Amino Acids in a Nickel(II) Coordination Environment? Experimental and DFT Considerations

“…Various types of reactions are compatible with this methodological platform, as represented by alkyl halide alkylations; Michael, Mannich, and aldol addition reactions; as well as multistep transformations, affording a wide range of practically important α‐ and β‐amino acids . Recently, asymmetric synthesis via metal Schiff base complexes was combined with the electrochemical activation approach, which disclosed a virtually unexplored methodological facet of this area of research.…”

Stereoselective Electrosynthesis of β‐Hydroxy‐α‐Amino Acids in the Form of NiII‐Schiff‐Base Complexes

“…Elaboration of new stereoselective synthetic approaches to organic molecules is a topical problem nowadays since the configuration of stereocenters often determines properties of diastereomers and possibilities for their practical applications . Recently, we started an extensive research on the application of electrochemical activation in stereoselective synthesis in a coordination environment of chiral metal complexes . Wide capabilities provided by electrochemical techniques open new horizons in stereoselective synthesis.…”

“…New compounds which were not available using common approaches were obtained when cathodic or anodic activation of the starting compounds was applied . The other possible approach – deprotonation with electrochemically generated base – provides the possibility of a precise control on the concentration of a base and its in situ reaction with the complex, thus opening up the possibility of carrying out multistep stereoselective one‐pot transformations . Here we report a new electrochemical route for the stereoselective oxyalkylation of glycine in a Ni II coordination environment (Scheme ) using in situ electrogenerated active species.…”

Individual (f,tA)‐ and (f,tC)‐Fullerene‐Based Nickel(II) Glycinates: Protected Chiral Amino Acids Directly Linked to a Chiral π‐Electron System

“…It also ensures precise control on the concentration of the base and its in situ reaction with the complex, thus opening ar oute for multistep one-pot stereoselective transformations. [15,16] Electrochemical deprotonation of GlyNi was performed with azobenzene radical-anions (at the potential of their formation, À1.32 Vv s. Ag/AgCl/KCl). [16] NiGly -H formation was monitored using voltammetry (by detecting the characteristic oxidation peak, À0.23 Vi no-DCB) and spectroelectrochemical methods (UV/Vis, l = 458 nm).…”

“…[15,16] Electrochemical deprotonation of GlyNi was performed with azobenzene radical-anions (at the potential of their formation, À1.32 Vv s. Ag/AgCl/KCl). [16] NiGly -H formation was monitored using voltammetry (by detecting the characteristic oxidation peak, À0.23 Vi no-DCB) and spectroelectrochemical methods (UV/Vis, l = 458 nm). After complete deprotonation of GlyNi an equimolar amount of C 60 was added and the solution became dark-green, thus indicating formation of the carbanionic fullerene derivative,w hich underwent consecutive S N 2r eaction with two different alkyl halides (allyl or benzyl bromides).…”