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.