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 1H and 13C NMR (including 2D techniques); an adduct with (2E)-1,3-diphenylprop-2-en-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.