Ni(I)–X Complexes Bearing a Bulky α‑Diimine Ligand: Synthesis, Structure, and Superior Catalytic Performance in the Hydrogen Isotope Exchange in Pharmaceuticals

The synthesis and spectroscopic characterization of a family of Ni–X (X = Cl, Br, I, H) complexes supported by the bulky α-diimine chelate N,N′-bis­(1R,2R,3R,5S)-(−)-isopinocampheyl-2,3-butanediimine (^ipcADI) are described. Diimine-supported, three-coordinate nickel­(I)–X complexes have been proposed as key intermediates in a host of catalytic transformations such as C–C and C–heteroatom cross-coupling and C–H functionalization but have until now remained synthetically elusive. A combination of structural, spectroscopic, electrochemical, and computational studies were used to establish the electronic structure of each monomeric [(^ipcADI)­NiX] (X = Cl, Br, I) complex as a nickel­(I) derivative supported by a redox-neutral α-diimine chelate. The dimeric nickel hydride, [(^ipcADI)­Ni­(μ₂-H)]₂, was prepared and characterized by X-ray diffraction; however, magnetic measurements and ¹H NMR spectroscopy support monomer formation at ambient temperature in THF solution. This nickel hydride was used as a precatalyst for the hydrogen isotope exchange (HIE) of C–H bonds in arenes and pharmaceuticals. By virtue of the multisite reactivity and high efficiency, the new nickel precatalyst provided unprecedented high specific activities (50–99 Ci/mmol) in radiolabeling, meeting the threshold required for radioligand binding assays. Use of air-stable and readily synthesized nickel precursor, [(^ipcADI)­NiBr₂], broad functional group tolerance, and compatibility with polar protic solvents are additional assets of the nickel-catalyzed HIE method.