Isotope Effects Reveal the Catalytic Mechanism of the Archetypical Suzuki-Miyaura Reaction.

Experimental and theoretical 13 C kinetic isotope effects (KIEs) are utilized to obtain atomistic insight into the catalytic mechanism of the Pd(PPh 3 ) 4 -catalyzed Suzuki-Miyaura reaction of aryl halides and aryl boronic acids. Under catalytic conditions, we establish that oxidative addition of aryl bromides occurs to a 12-electron monoligated palladium complex (Pd-(PPh 3 )). This is based on the congruence of the experimental KIE for the carbon attached to bromine (KIE C-Br = 1.020) and predicted KIE C-Br for the transition state for oxidative addition to the Pd(PPh 3 ) complex (1.021). For aryl iodides, the near-unity KIE C-I of ~1.003 suggests that the first irreversible step in the catalytic cycle precedes oxidative addition and is likely the binding of the iodoarene to Pd(PPh 3 ). Our results suggest that the commonly proposed oxidative addition to the 14-electron Pd(PPh 3 ) 2 complex can occur only in the presence of excess added ligand or under stoichiometric conditions; in both cases, experimental KIE C-Br of 1.031 is measured, which is identical to the predicted KIE C-Br for the transition state for oxidative addition to the Pd(PPh 3 ) 2 complex (1.031). The transmetalation step, under catalytic conditions, is shown to proceed via a tetracoordinate boronate (8B4) intermediate with a Pd-O-B linkage based on the agreement between an experimental KIE for the carbon atom involved in transmetalation (KIE C-Boron = 1.035) and a predicted KIE C-Boron for the 8B4 transmetalation transition state (1.034).