Ni(I)-X complexes bearing a bulky alpha-diimine ligand
Synthesis, structure, and superior catalytic performance in the hydrogen isotope exchange in pharmaceuticals
Zarate, C., Yang, H., Bezdek, M. J., Hesk, D., & Chirik, P. J. (2019). Ni(I)-X complexes bearing a bulky alpha-diimine ligand: Synthesis, structure, and superior catalytic performance in the hydrogen isotope exchange in pharmaceuticals. Journal of the American Chemical Society, 141(12), 5034-5044. https://doi.org/10.1021/jacs.9b00939
The synthesis and spectroscopic characterization of a family of Ni X (X = Cl, Br, I, H) complexes supported by the bulky alpha-diimine chelate N,N'-bis(1R,2R,3R,5S)-(-)-iso-pinocampheyl-2,3-butanediimine ((ipc)ADI) 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 [((ipc)ADI)NiX] (X = Cl, Br, I) complex as a nickel(I) derivative supported by a redox-neutral alpha-diimine chelate. The dimeric nickel hydride, [((ipc)ADI)Ni(mu(2)-H)](2), was prepared and characterized by X-ray diffraction; however, magnetic measurements and 'H NMR spectroscopy support monomer formation at ambient temperature in THE 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 C-i/mmol) in radiolabeling, meeting the threshold required for radioligand binding assays. Use of air-stable and readily synthesized nickel precursor, [((ipc)ADI)NiBr2], broad functional group tolerance, and compatibility with polar protic solvents are additional assets of the nickel-catalyzed HIE method.