Decoding Transmetalation in Miyaura Borylation: The Hidden Chemistry of Bis(pinacolato) Diboron and Base Effects

We present a comprehensive mechanistic investigation of the well-defined precatalyst [Pd(IMesMe )(cin)Cl], which has exhibitedhigh catalytic efficiency in the Miyaura borylation of various aryl chlorides. Despite its proven catalytic performance, key aspectsof the mechanism, particularly the transmetalation step, remained elusive. In this study, we addressed these mechanistic aspectsthrough detailed density functional theory (DFT) calculations. Our results elucidate the role of the second equivalent of base,pinpointing its specific involvement within the catalytic cycle. Furthermore, we unraveled the activation pathway of bis(pinacolato)diboron (B2 Pin2 ), determining whether base-mediated cleavage occurs independently or requires direct coordinationto the palladium center. The mechanism reveals a surprising concerted fusion of the oxidative addition and transmetalation steps,paving the way not only for a new avenue in the Miyaura reaction, but potentially for other cross-coupling processes. This synergy may prompt a re-evaluation of previous studies, suggesting that similar pathways could enable milder reaction conditions.