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Distinguishing between true homogeneous and heterogeneous catalytic mechanisms in cross-coupling reactions is not well-understood. The main reason for this is the numerous interconversions of different Pd species during the reaction progress that can potentially provide the catalytic activity. Catalytic experiments with the determination of the differential selectivity were performed on pairs of competing aryl halides or alkenes in the Mizoroki–Heck mono- and following double arylations in order to determine if the nature of active species would be affected by varying the Pd precursors. No differences in the differential selectivity values were observed for the products of both mono- and double arylations. The selectivity patterns indicated an identical active catalyst in all experiments. As the characteristics of Pd interconversions are well described, the active Pd species of mono- and double Mizoroki–Heck arylations with nonreactive aryl chlorides were identified as dissolved Pd molecular complexes.

Hammett correlation is one of the widely applied tools in the mechanistic studies of catalytic processes. From the beginning, it was applied for measuring reaction rates with various substituted substrates, particularly benzoic acid derivatives (under competitive or noncompetitive modes), to construct a two-dimensional plot of the relative reactivity vs the σ-constant of the substituents. In this study, we use time-resolved fundamental Hammett correlation to obtain a three-dimensional plot for a catalytic reaction using experimental data of cross-coupling reactions. Using this approach, possible variations of the Hammett correlation parameter ρ during the catalytic reaction can be easily monitored. Importantly, the suggested approach does not require differentiation of primary experimental kinetic data on the concentrations of substrates and products. The study was conducted for the Suzuki–Miyaura reaction, and demonstrative data were obtained for different behaviors of the Pd species activating aryl iodides, aryl bromides, or aryl chlorides under “ligand-free” catalytic conditions. The proposed approach was tested for other reactions of aryl halides and related substrates to confirm its validity for the monitoring of possible changes in active catalyst species during the reactions.

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).

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.

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 heterogenized Pd compounds. To date, hypotheses that concern whether the reaction proceeds in the solution phase or on the surface of solid particles, including nanosized ones, have been based on experimental results obtained under different reaction conditions. Moreover, convincing evidence was obtained for reactions proceeding simultaneously through homogeneous and heterogeneous catalytic mechanisms. However, most of the experimental evidence was obtained for relatively reactive aryl bromides and aryl iodides, while insufficient data exists for nonreactive aryl chlorides to make any well-grounded conclusions regarding the homogeneous or heterogeneous nature of the active species. Here, we report the use of “ligand-free” conditions, which excludes the need to add strong organic ligands, such as phosphines, amines, and carbenes, for the activation of aryl chlorides in the Suzuki-Miyaura reaction. The results suggest that the reaction proceeds in the solution phase through a homogeneous mechanism even when heterogeneous precursors are used. The main reason for this conclusion is the independence of the reaction differential selectivity under the competition of two aryl chlorides or two arylboronic acids, which is based on numerous parameters that only influence the nature of the possible heterogeneous Pd forms when the homogeneous mechanism is realized.