Role of dppf Monoxide in the Transmetalation Step of the Suzuki–Miyaura Coupling Reaction
Pierre‐Adrien Payard, Antoine Bohn, Damien Tocqueville, Khaoula Jaouadi, Émile Escoudé, Sanaa Ajig, Annie Dethoor, Geoffrey Gontard, Luca Alessandro Perego, Maxime R. Vitale, Ilaria Ciofini, Simon Wagschal, Laurence Grimaud
Abstract
Diphosphine ligands are frequently used in palladium-catalyzed Suzuki–Miyaura (S-M) reactions. Despite their widespread application in both academic and industrial settings, their role in the B-to-Pd transmetalation has not been firmly established. We combined electrochemistry, NMR spectroscopy, and DFT calculations to elucidate the role of dppf (1,1′-bis(diphenylphosphino)ferrocene) in this key elementary step of the S-M reaction. We observed that excess dppf inhibits transmetalation involving PhB(OH)2 and dppf-ligated arylpalladium(II) complexes, while an optimal [base]/[PhB(OH)2] ratio maximizes the concentration of a [Pd–O–B] key intermediate. In situ oxidation of dppf to the diphosphine monoxide dppfO can take place in the presence of base, leading to dppfO-ligated arylpalladium(II) complexes, which readily undergo transmetalation at room temperature. These findings suggest guidelines for the rational optimization of diphosphine-promoted S-M reactions.