Density Functional Theory Studies of Negishi Alkyl–Alkyl Cross-Coupling Reactions Catalyzed by a Methylterpyridyl-Ni(I) Complex

Density functional theory calculations were done to examine the potential energy surfaces of Ni(I)-catalyzed Negishi alkyl–alkyl cross-coupling reactions by using propyl iodide and isopropyl iodide as model alkyl electrophiles and CH₃ZnI as a model alkyl nucleophile. A four-step catalytic cycle involving iodine transfer, radical addition, reductive elimination, and transmetalation steps were characterized structurally and energetically. The reaction mechanism for this catalytic cycle appears feasible based on the calculated free energy profiles for the reactions. The iodine transfer step is the rate-determining step for the Ni(tpy)-CH₃ (tpy = 2,2′6′,2″-terpyridine) reactions with alkyl iodides. For secondary alkyl electrophiles, the oxidative addition intermediate, Ni(III), prefers to undergo decomposition over reductive elimination, whereas for the primary alkyl electrophiles, Ni(III) prefers to undergo reductive elimination over decomposition based on comparison of the relative reaction rates for these two types of steps. In addition, thermodynamic data were employed to help explain why the yield of the coupled product is very low from the Ni(II)-alkyl halide reactions with organozinc reagents.