Unexpected Substituent Effects in Aryl-Aryl Negishi Cross-Coupling Reactions Rationalized by Density Functional Theory and Natural Charges

While numerous studies
consider substitution effects at the aromatic
system in the arylzinc reactant during the transmetalation step in
palladium-catalyzed Negishi cross-coupling reactions, the effects
caused by varying substituents at the arylpalladium complex have not
been the center of attention so far. Herein, we present results from
competition experiments providing the counterintuitive observation
that electron-withdrawing (donating) groups in the para position to the palladium center inhibit (accelerate) the transmetalation
step in aryl-aryl Negishi cross-coupling reactions. Quantum-chemical
calculations based on density functional theory provide mechanistic
insights and show that an associative transmetalation mechanism is
favored over a dissociative one. Foster–Boys localized orbitals
and Mayer bond orders aid in rationalizing molecular and electronic
structural features. Natural population analysis reveals that charge
accumulation at the palladium center causes a destabilization of the
transition state, which clearly correlates with the electronic properties
of the substituents represented by their Hammett parameters.