Role of the base and endogenous anions in “ligand-free” catalytic systems for the Suzuki–Miyaura reaction

Abstract

UV spectroscopic studies combined with kinetic measurements for the Suzuki-Miyaura reaction catalyzed by "ligand free" catalytic systems have demonstrated that the base is involved in the formation of the palladium complexes ensuring the occurrence of the transmetalation stage. It follows from UV monitor ing data for the catalytic reaction involving aryl iodides that a considerable part of palladium during the pro cess is in the form of Pd 2+ acid complexes with endogenous anions and does not participate in the main cat alytic cycle.

Overcoming Halide Inhibition of Suzuki–Miyaura Couplings with Biaryl Monophosphine-Based Catalysts

“…Notably, this reaction did not proceed to full conversion even after 24 h (Table S11). This finding suggests that the sluggish reactivity of aryl iodides is due in part to catalyst decomposition or inhibition of the desired reaction by KI. ,,, …”

“…This finding suggests that the sluggish reactivity of aryl iodides is due in part to catalyst decomposition 38 or inhibition of the desired reaction by KI. 10,31,39,40 To evaluate any potential inhibition by the halide salts generated during Suzuki−Miyaura reactions, we examined the coupling of PhCl and phenylboronic acid in the presence of KX salts (Table 2; see SI section 7 for details). Under the standard reaction conditions, the desired reaction proceeds to 33% conversion within 60 min at room temperature.…”

“…A similar inhibitory effect was also observed for the faster Suzuki–Miyaura coupling of 3-chloroanisole with 2,6-difluorophenylboronic acid, which led to poor conversions in the presence of added KI due to competing protodeborylation (Figure S9). Notably, Jutand and Amatore previously observed that exogenous Br – has an inhibitory effect on the rate of Suzuki–Miyaura couplings with PPh 3 -based catalysts, and Schmidt demonstrated that exogenous halide binds to Pd under ligand-free conditions . This unexpected reaction inhibition by halide salts contributes to the slow couplings of aryl iodides and should also retard reactions involving multiple cross-couplings of polyhalogenated substrates.…”

“… ,− In Pathway I, exhaustive reaction of the organoboron precursor with OH – produces an arylboronate (R–B­(OH) 3 – ), which then reacts directly with the L n ·Pd­(Ar)­X (X = Cl, Br, I) intermediate formed after oxidative addition . Consistent with this mechanistic hypothesis, most arylboron species undergo rapid partial conversion to arylboronates under basic biphasic conditions, ,− and preformed arylboronates are competent reaction partners. , In Pathway II, the L n ·Pd­(Ar)­X intermediate instead reacts with OH – to form an L n ·Pd­(Ar)­OH species, ,,, which in turn reacts with the boronic acid nucleophile. , Indeed, previous stoichiometric studies have shown that isolated L n ·Pd­(Ar)­OH complexes undergo rapid transmetalation with boronic acids. ,, Elegant studies by Hartwig, Jutand and Amatore, , Schmidt, , and Denmark − favor reaction via Pd–OH intermediates (Pathway II) with simple supporting ligands under biphasic conditions.…”

“…10,12 Indeed, previous stoichiometric studies have shown that isolated L n •Pd(Ar)OH complexes undergo rapid transmetalation with boronic acids. 10,11,14 Elegant studies by Hartwig, 11 Jutand and Amatore, 10,15 Schmidt, 30,31 and Denmark 32−34 favor reaction via Pd−OH intermediates (Pathway II) with simple supporting ligands under biphasic conditions.…”