Theoretical Study on the Mechanism of Ni‐Catalyzed Alkyl–Alkyl Suzuki Cross‐Coupling

Ni-catalyzed cross-coupling of unactivated secondary alkyl halides with alkylboranes provides an efficient way to construct alkyl-alkyl bonds. The mechanism of this reaction with the Ni/L1 (L1=trans-N,N'-dimethyl-1,2-cyclohexanediamine) system was examined for the first time by using theoretical calculations. The feasible mechanism was found to involve a Ni(I)-Ni(III) catalytic cycle with three main steps: transmetalation of Ni(I)(L1)X (X=Cl, Br) with 9-borabicyclo3.3.1nonane (9-BBN)R(1) to produce Ni(I)(L1)(R(1)), oxidative addition of R(2) X with Ni(I)(L1)(R(1)) to produce Ni(III)(L1)(R(1))(R(2))X through a radical pathway, and C-C reductive elimination to generate the product and Ni(I)(L1)X. The transmetalation step is rate-determining for both primary and secondary alkyl bromides. KOiBu decreases the activation barrier of the transmetalation step by forming a potassium alkyl boronate salt with alkyl borane. Tertiary alkyl halides are not reactive because the activation barrier of reductive elimination is too high (+34.7 kcal mol(-1)). On the other hand, the cross-coupling of alkyl chlorides can be catalyzed by Ni/L2 (L2=trans-N,N'-dimethyl-1,2-diphenylethane-1,2-diamine) because the activation barrier of transmetalation with L2 is lower than that with L1. Importantly, the Ni(0)-Ni(II) catalytic cycle is not favored in the present systems because reductive elimination from both singlet and triplet Ni(II)(L1)(R(1))(R(2)) is very difficult.