Distinguishing Between Pathways for Transmetalation in Suzuki−Miyaura Reactions

Abstract

We report a systematic study of the stoichiometric reactions of isolated arylpalladium hydroxo and halide complexes with arylboronic acids and aryltrihydroxyborates to evaluate the relative rates of the two reaction pathways commonly proposed to account for transmetallation in the SuzukiMiyaura reaction. Based on the relative populations of the palladium and organoboron species generated under conditions common for the catalytic process and the observed rate constants for the stoichiometric reactions between the two classes of reaction components, we conclude that the reaction of a palladium hydroxo complex with boronic acid, not the reaction of a palladium halide complex with trihydroxyborate, accounts for transmetallation in catalytic Suzuki-Miyaura reactions conducted with weak base and aqueous solvent mixturesThe Suzuki-Miyaura reaction is one of the most practiced classes of catalytic C-C bond formation. Although this reaction is established to occur by oxidative addition, transmetallation and reductive elimination, the mechanism of the transmetallation step has been widely debated. Two pathways are typically considered for transmetallation: conversion of an organoboron compound by base to form a nucleophilic boronate, followed by attack on a palladium halide complex (Scheme 1, Path A) or conversion of a palladium halide to a nucleophilic palladium hydroxo complex that subsequently reacts with a neutral organoboron compound (Scheme 1, Path B). 1 A number of studies have led to the conclusion that transmetallation occurs between the palladium halide and boronate, but data that indicate transmetallation could occur between the boronic acid and palladium hydroxo species have also been reported. 2,3 Because transmetallation is often proposed to be turnover limiting and to dictate the choice of reaction conditions, a firm understanding of the mechanism of this step is important for the use of this common catalytic process. 4 We report a systematic study involving the reactions of isolated arylpalladium hydroxo complexes and arylpalladium halide complexes containing the same ancillary ligands with arylboronic acids and aryltrihydroxyborates. Equilibrium data for the interconversion of boronic acid and trihydroxyborate, as well as equilibrium constants for the interconversion of palladium hydroxo and halide complexes containing PPh 3 and PCy 3 (Cy=cyclohexyl) as ligands have also been gained. Together, these data provide strong evidence that, in the typical mixtures of water and organic solvent, transmetallation between a palladium center that is ligated by common phosphines, such as PPh 3 or PCy 3 , occurs between the palladium hydroxo complex and a boronic acid, not between the palladium halide complex and a trihydroxyborate, as often proposed.* jhartwig@illinois.edu . Our experimental design to assess the different proposed pathways focused on comparing the relative rates of the different stoichiometric reactions between isolated arylpalladium complexes and arylboron species. We studied the stoichiometr...

Speciation of Pd(OAc)2in ligandless Suzuki–Miyaura reactions

“…In previous reports, water was found to accelerate the reduction of tertiary phosphine (PR 3 ) complexes of palladium(II) acetate to L n Pd(0), but at elevated temperatures. 51,52 Recently, two independent studies of the transmetalation of arylboronic acids to phosphine-ligated palladium complexes were reported, 53,54 which implicated the involvement of a hydroxylpalladium intermediate for the transfer of an aryl group from ArB(OH) 2 . The formation of Pd(0) species was not observed by the introduction of water, under the reaction conditions adopted by the stopped-flow experiments described above.…”

Palladium catalysed sequential imine arylation/Suzuki–Miyaura coupling: synthesis of α-(biarylyl)benzylamines

“…18,19 On the other hand, recent kinetic studies and extensive computational data suggest that the boronic acid should be activated by the base (forming a boronate) in order for the transmetalation to occur. 20,21 In our case, we experimentally used a variety of conditions, which included boronic acid reagents (together with a base), or NaPh 4 B (see Tables 1, 3 and 4).…”

Palladium-Catalyzed Cross-Coupling Reactions of Perfluoro Organic Compounds

“…Most of the reported Suzuki-Miyaura type cross-coupling reactions via C-F bond cleavage, employing either highly electron-deficient organofluorine compounds or those bearing a directing group, have traditionally been conducted in the presence of a base [59,[75][76][77][78][79][80][81][82][83][84][85], whereas fluoride anion itself is regarded as a good activator for neutral organoboron reagents. The role of a base in a Suzuki-Miyaura coupling reaction is generally considered to follow one of two patterns; either converting a neutral organoboron compound into a nucleophilic boronate, or converting a palladium halide intermediate into an active palladium species via a ligand exchange reaction by the base [86,87]. In fact, Widdowson pointed out the possibility that the use of an extraneous base should be, in principle, catalytic [75].…”