Role of dppf Monoxide in the Transmetalation Step of the Suzuki–Miyaura Coupling Reaction

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.

Mechanistic Studies and Data Science-Guided Exploration of Bromotetrazine Cross-Coupling

“…The coupling observed in 31 P NMR for both pairs of signals is typical for dppf-type Pd complexes with two different additional ligands. This suggests the absence of any phosphine oxide species resembling 9 , since similar J -coupling has not been observed for in situ generated Pd­(dppfO) species . Repetition of this experiment in the presence of H 2 O, which should favor the formation of the phosphine oxide species, resulted in a complex mixture from which no identifiable species could be isolated.…”

“…As Amatore and co-workers have demonstrated, reduction of Pd­(II) by coordinated phosphine ligands in the presence of H 2 O and amines is rather efficient. Furthermore, mono-oxidation of bidentate phosphine ligands, such as dppf, by this or similar mechanisms has since been suggested as crucial for the formation of catalytically active Pd(0) species. , To commence our investigation of the involvement of dppf oxidation in the generation of Pd(0), we performed the standard cross-coupling reaction in the presence of 2 and 5% H 2 O, respectively (compared to the amount of solvent). This afforded the cross-coupling product 4 in yields of 61 and 48%, respectively, which is significantly lower than the 82% yield obtained in the absence of H 2 O.…”

“…This hypothetical 9 -ligated Pd(0) could arise from the stoichiometric reaction between Pd­(dppf-CF 3 )­Cl 2 and Ag 2 CO 3 . Additionally, the resulting species should be competent to undergo oxidative addition of tetrazine 1 and engage in the transmetalation of boronate species . Hence, to probe the formation of 9 under the conditions present in our method and to see whether such species can undergo transmetalation from boronates, we performed a cross-coupling reaction in the presence of tetrazine 1 , boronate 7 , and catalytic amounts of Ag 2 CO 3 and Pd­(dppf-CF 3 )­Cl 2 (Scheme ).…”

The Coordination and Catalytic Chemistry of Phosphanylferrocene Chalcogenides

“…[64] Another recent study pointed to possible involvement of dppfO in Suzuki-Miyaura cross-coupling reactions mediated by Pd-dppf complexes. [65] Conversely, studies focused on the properties of dppfS 2 and dppfSe 2 remain scarce. Both ligands have been studied primarily in complexes containing coinage metals, and the collected data reveal generally similar coordination behaviors for these symmetrical bis-chalcogenides.…”

“…When applied as a supporting ligand in Pd‐catalyzed telomerization of 1,3‐butadiene with methanol, dppfO showed similar selectivity but lower turnovers than dppf and (diphenylphosphanyl)ferrocene [64] . Another recent study pointed to possible involvement of dppfO in Suzuki‐Miyaura cross‐coupling reactions mediated by Pd‐dppf complexes [65] …”