Mechanism and Origin of Enantioselectivity in Nickel-CatalyzedAlkyl–Alkyl Suzuki Coupling Reaction

Enantioselective Suzuki coupling reactions are a widely used method in asymmetric synthesis of chiral compounds. In an important extension of this protocol, 1-bromo-1-fluoroalkanes were coupled with alkyl-9-BBN using chiral NiCl2L* as the catalyst (where L* = bis-pyrrolidine ligand) under Suzuki conditions to obtain a product with a stereogenic center bearing a fluorine. In view of the current interest in chiral fluorine containing compounds as well as lack of clarity on the mechanism of Ni-catalyzed asymmetric Suzuki coupling reactions, we decided to examine various mechanistic pathways of the title reaction. The (U)M06 density functional theory computations have been employed to identify the energetically preferred pathway first, and then to probe the origin of high enantioselectivity. In particular, we have compared the likely involvement of different redox couples such as Ni(0)/Ni(II) and Ni(I)/Ni(III) in the catalytic cycle. For Ni(0)/Ni(II) pathway, both singlet and triplet spin states have been con...