Structural and Reactivity Comparisons of JosiPhos CyPF-Cy and a Simplified Variant (“CyPBn-Cy”) in Nickel-Catalyzed C(sp2)-N Cross-Couplings

The synthesis and characterization of the new complexes (CyPBn-Cy)NiCl2 and (CyPBn-Cy)Ni(o-tol)Cl are reported (CyPBn-Cy = o-di(cyclohexyl)phosphino-benzyl-di(cyclohexyl)phosphine), along with a head-to-head structural and reactivity comparison of (L)Ni(o-tol)Cl precatalyst complexes (L = JosiPhos CyPF-Cy and CyPBn-Cy) in the Ni-catalyzed cross-couplings of (hetero)aryl chlorides or phenol-derived electrophiles with ammonia or furfurylamine. The structures of these precatalysts were found not to differ significantly (e.g., coordination geometry and % buried volume), and these similarities were, generally speaking, reflected in the observed catalytic behavior of these precatalysts, with notable exceptions including reactions involving the hindered electrophile 2-chloro-m-xylene, where (CyPBn-Cy)Ni(o-tol)Cl proved superior; the N-arylation of furfurylamine by use of 1-(N,N-diethylcarbamoyl)-naphthalene, where CyPF-Cy proved to be the preferred ligand; and monoarylation (CyPBn-Cy) versus diarylation (CyPF-Cy) selectivity in the cross-coupling of furfurylamine with 2-chloro-6-methoxypyridine. In studying the time-course of the cross-coupling of furfurylamine and 1-chloronaphthalene, significantly faster conversion to product and higher overall yield were noted when using CyPBn-Cy. These results confirm that CyPBn-Cy can be viewed as being competitive with, and complementary to, the well-established JosiPhos ligand CyPF-Cy in this class of Ni-catalyzed cross-couplings.