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The generally accepted mechanism of the Suzuki—Miyaura reaction suggests a sequential activation of the substrate (aryl halide) and the reagent (arylboronic acid) by a palladium catalyst with the formation of unsymmetric biaryl as a result of a single turnover of the catalytic cycle, i.e., it is linear from the kinetic point of view. At the same time, the use of an unconventional kinetic approach based on the analysis of the differential selectivity of the reaction, rather than the regularities of catalytic activity, indicates the inadequacy of the linear mechanism, that is consistent with the hypothesis of a nonlinear (the so-called cooperative) mechanism of catalysis, in which the product is formed as a result of the substrate and reagent activation by two different palladium-containing intermediates in two parallel catalytic cycles. The experimentally observed low kinetic orders of the Suzuki—Miyaura reaction with respect to the concentration of the palladium catalyst precursor under the ligand-free conditions of catalysis are also consistent with the cooperative mechanism and can be due to the changes in the relative amount of the catalyst in two parallel catalytic cycles and/or to the process of catalyst deactivation.

A distinction between the homogeneous and heterogeneous catalytic mechanisms of a myriad of Pd catalytic systems for the Suzuki-Miyaura reaction has been made based on soluble metal complexes or he...

The results of a kinetic study on the character (fast or slow) of a step of alkene activation in the catalytic cycle of the Mizoroki–Heck reaction with unreactive aryl chlorides in the presence of a so-called ligand-free catalytic system based on palladium are presented. An analysis of integral kinetic curves of the consumption of two competing alkenes in the reaction with aryl chloride showed that alkenes participate in a fast step of the catalytic cycle.

Three-component cross-coupling in the system aryl halide–arylacetylene–alkene in the presence of simplest ligand-free palladium catalysts gave products of both 1+1+1-coupling and cross-dimerization of arylacetylene with alkene. The possibility of controlling the reaction selectivity has been demonstrated.

The aryl halide-arylacetylene-arylboronic acid three-component coupling in the presence of a Pd catalyst containing no organic ligands is described. The reaction routes that take place in the reaction system are shown to include the consecutive carbopalladation of two arylacetylene molecules, leading to unsaturated polyaromatic compounds. The possibility of controlling the alternative reaction routes is demonstrated.

This paper presents the results of a kinetic study on the step of activation of aryl iodides and aryl bromides under conditions of ligand-free catalysis in the direct arylation of indole at a C–H bond performed using an analysis of the integral kinetic curves of consumption of the competing aryl halides. In the course of an experiment under the conditions of competition between a pair of aryl halides having different reactivity, an acceleration in the consumption of a less active substrate was observed, which coincided in time with the almost complete consumption of a more active one. The experimental data unambiguously indicated a rapid character of the stage of oxidative addition with the participation of not only reactive aryl iodides but also nonactivated aryl bromides.

The kinetic approach for distinguishing between homogeneous and heterogeneous catalysis mechanisms by the analysis of differential selectivity was applied for direct C–H arylation of an indole with aryl halides under “ligandless” conditions. The differential selectivity of competing arylation of an indole with two aryl iodides or bromides and the differential regioselectivity of a parallel formation of C2- and C3-regioisomers of arylated indoles were studied by the simple method of phase trajectories needed for raw kinetic data only. The results obtained indicated that the selectivities strongly depended on the type (soluble or insoluble) and concentration of the Pd precursor. Considering the pathways of Pd transformations under the reaction conditions, this indicates a substantial contribution of catalysis occurring on the surface of metallic Pd (including nanoparticles).

The results of a comparative study of phosphine-containing and phosphine-free catalytic systems of the Heck reaction using aromatic carboxylic anhydrides as arylating agents are presented. It was demonstrated that the patterns of diff erential selectivity of the reaction under competition of two aromatic anhydrides or two alkenes are independent of the presence of a tertiary phosphine additive in the system. It was established that palladium complexes with no phosphine ligands in their coordination sphere are catalytically active at the step of activation of aromatic carboxylic anhydride and alkene. The patterns of diff erential selectivity for regioisomers of arylated products provide the evidence of the participation of phosphine-containing anionic palladium complexes in the regioselectivity-determining step of the catalytic cycle. The data obtained are in agreement with the phosphine involvement in the catalyst transformations proceeding outside the main catalytic cycle.

A kinetic study of reaction of alkene arylation by anhydrides of aromatic acids (modified Mizoroki–Heck reaction) was carried out using differential selectivity as the main measured parameter. The results obtained under conditions of competition between a pair of alkenes or a pair of aromatic anhydrides point to the occurrence of the reaction via a homogeneous mechanism of catalysis analogously to a conventional variant of reaction with aryl halides as arylating reagents. The hypothesis that the active catalyst is homogeneous agrees with the results of kinetic studies of processes of catalyst formation and deactivation.

Differential selectivity of the direct arylation of indole with aryl halides under competing and noncompeting conditions with a varying set of reaction parameters was determined using phase trajectories. The results described herein allow for conclusions to be drawn regarding the character of active complexes (cationic, neutral, or anionic) as well as realization of the indole electrophilic substitution in the catalytic cycle using the ligand-free catalytic system.

The role of ionic Pd species in the catalytic systems used for cross-coupling reactions has been revised in recent years, mainly utilizing in situ analytical techniques to detect catalyst species in the reaction mixture. The possible inclusion of phosphine molecules in the active Pd complexes is still debated. We have carried out a comparative study on the differential selectivity of the Mizoroki–Heck reaction with competition between two aryl halides or two alkenes to elucidate the active Pd species in different types of catalytic systems, including those favoring the formation of ionic complexes. The sensitivity of the reaction differential selectivity of two competing aryl halides to the additives of tertiary phosphine and halide salts points to the catalytic activity of anionic Pd(0) complexes containing at least one phosphine ligand when the phosphine-containing catalytic systems are used. The changes of the reaction differential selectivity of two competing alkenes to phosphine and halide salt allow to propose the entrance of both phosphine and halide ions into the coordination sphere of active Pd(II) complexes possessing anionic character. In addition, evidence for the effect of phosphine ligand and salt additives on the composition of the active Pd complexes that determine the regioselectivity of the reaction is presented. The data obtained indicate the decisive role of anionic Pd species in the Mizoroki–Heck reaction using both phosphine-free and phosphine-containing catalytic systems.

Differential selectivity in the competitive Heck reaction with aromatic carboxylic anhydrides has been found to depend on the nature of both the cation and anion of a salt used as an additive for the catalytic system. This fact indicates that the anions present in the system are involved in active anionic species.

Distinguishing between several probable mechanistic hypotheses for complex catalytic reactions is a very complicated task. The main cause of such complication is the simultaneous realization of several consecutive-parallel processes under the reactions proceeding including side reactions with the participation of a catalyst. Under these circumstances, using kinetic studies of the reactions can provide unique possibilities to discriminate alternative mechanistic proposals. To achieve the goal, we offer to use the studies of the differential selectivity of such complex reactions by analysing possible correspondence of its patterns to different mathematical models describing alternative mechanistic hypotheses. Using this approach the fine mechanistic details of the catalytic cycles of two-component cross-coupling Suzuki-Miyaura and Mizoroki-Heck reactions as well as of three-component Sonogashira-type reaction coupling have been established.

Herein, the independent differential selectivity in the Suzuki-Miyaura reaction of two competing arylboronic acids with regard to the nature of the aryl halide (both halide and aryl moieties) was established. This pattern cannot be realized via the “textbook” mechanism of the reaction, which suggests the interaction of boron-containing species with an ArPdX intermediate (product of the aryl halide catalytic activation). The data obtained indicate the participation of two distinct palladium species in the aryl halide and arylboronic acid activations in the catalytic cycle of biaryl formation, which are in accordance with the so-called cooperative mechanism.

The retarded oxidative addition of aryl chloride to Pd(0) is believed, by most scientists, to be the main hindrance in achieving effective conversion in the Suzuki–Miyaura reaction and other cross-coupling reactions of aryl chlorides. Herein, we have demonstrated by competing experiments, using two aryl chlorides under “ligand-free” catalytic conditions (absence of strong ligands; high ratio of substrate to catalyst), that the elementary step of oxidative addition is substantially reversible. This implies that the hypothesis on the rate-determining character of the oxidative addition step is incorrect, and the existing problems with aryl chloride conversion in the Suzuki–Miyaura reaction are caused by some other reasons that need to be investigated.