A. A. Kurokhtina

Distinguishing between the homogeneous and heterogeneous mechanisms of catalysis in the Mizoroki-Heck and Suzuki-Miyaura reactions: Problems and prospects

This review presents a critical analysis of experimental methods used in distinguishing between the homogeneous and heterogeneous catalytic mechanisms in the Mizoroki-Heck and Suzuki-Miyaura reactions. The main problems arising in the interpretation of data obtained by these methods are discussed. It is demonstrated that it is necessary to take into account the dynamics of the interconversion of molecular, nanosized, and larger palladium species that is independent of the catalyst precursor type (dissolved or solid). The role of the in situ formation of colloidal palladium particles in the case of a supported catalyst precursor is considered.

Role of a base in Suzuki-Miyaura reaction

The existing hypotheses about the base role are limited to two possible versions of the transmetallation stage in the catalytic Suzuki–Miyaura reaction. According to the first hypothesis, the transmetallation is possible only when the palladium compound I reacts with borate anions II formed in situ starting from arylboronic acid III and the base. The second version postulates that the transmetallation is possible only if the palladium intermediate IV involves the basic counterion originating from the present base.

Simple kinetic method for distinguishing between homogeneous and heterogeneous mechanisms of catalysis, illustrated by the example of “ligand-free” Suzuki and Heck reactions of aryl iodides and aryl bromides

Using a simple method based on an analysis of the phase trajectories of competing reactions of several substrates, it has been established that the selectivity of catalytically active species in the Suzuki reaction of aryl bromides depends on the nature of the catalyst precursor. This indicates that there is a considerable contribution from heterogeneous catalysis. At the same time, in the reaction involving aryl iodides, when the catalyst concentration in the solution is much higher, the selectivity of the catalyst is precursor-independent, suggesting that homogeneous catalysis is dominant. In the Heck reaction of both aryl bromides and aryl iodides, pure homogeneous catalysis takes place.

Differential selectivity measurements and competitive reaction methods as effective means for mechanistic studies of complex catalytic reactions

In most kinetic investigations of catalytic reactions, catalytic activity is a traditionally measured kinetic parameter. However, differential selectivity measurements have many advantages for mechanistic studies. This Perspective gives an overview of the basic principles and practices of mechanistic studies based on differential selectivity measurements, including the use of artificially created competitive reactions.

State of palladium in ligandless catalytic systems for the Heck reaction of nonactivated bromobenzene

In the Heck reaction of bromobenzene catalyzed by the palladium salts (PdX2) without phosphine ligands, a considerable amount of palladium (up to 70%) is not involved in the catalytic cycle and exists as the catalytically inactive anionic complex [PdX4]2−.

competing reaction method for identification of fast and slow steps of catalytic cycles: Application to heck and Suzuki reactions

A method for identification of fast and slow steps of catalytic cycles is suggested. This method provides reliable data for reactions conducted at an unsteady-state catalyst concentration. It has been used in the determination of the rate-determining step in the Heck reaction of aryl bromides and in the Suzuki reaction of aryl bromides and aryl iodides. The data obtained by this method are in agreement with the data obtained by other methods, including kinetic isotope effect measurements.

Study of the differential selectivity of cross-coupling reactions for elucidating the nature of the true catalyst

A phase trajectory analysis has demonstrated that, in the Mizoroki-Heck reaction involving competing aryl bromides, variation of reaction parameters (nature and concentration of the catalyst precursor and the presence/absence of a reductant and a stabilizer of colloid particles) does not change the phase trajectories. This indicates that the reaction proceeds solely via a homogeneous mechanism. A similar situation is observed when benzoic anhydride is used as the arylating agent. This suggests that the homogeneous mechanism takes place in this case as well. When the arylating agent is benzoyl chloride, the phase trajectory of the competitive reaction depends on the nature of the catalyst precursor; therefore, this process occurs at least partially via a heterogeneous mechanism.

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

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 monitoring data for the catalytic reaction involving aryl iodides that a considerable part of palladium during the process is in the form of Pd2+ acid complexes with endogenous anions and does not participate in the main catalytic cycle.

Problems of distinguishing the homogeneous and heterogeneous mechanisms of the Suzuki reaction

The results of comparative kinetic experiments, homogeneity/heterogeneity testing data, and the relative substrate reactivity data for the Suzuki and Heck reactions are consistent with the participation of heterogeneous forms of the catalyst (colloidal palladium and larger palladium aggregates) in the Suzuki reaction. This is the reason why the Suzuki reaction occurs more readily than the Heck reaction. The data obtained in this study indicate that these reactions differ in the nature of catalyst deactivation processes.

Formation of polyaromatic compounds by coupling of aryl iodides with arylacetylenes in the presence of palladium-based ligand-free catalytic systems

Cross-coupling of aryl, hetaryl, and vinyl halides with acetylenes with formation of substituted alkynes (Sonogashira reaction) is catalyzed by Pd(II) complexes in the presence of a base, copper(I) compound, and organic ligand [1]. Many examples have been reported for the formation of analogous products in high yield in the absence of copper(I) compound but in the presence of organic ligands (see, e.g., pioneering publication [2]). If neither copper compound nor organic ligand is added, the yield of the Sonogashira reaction sharply decreases. For example, the yield of diphenylacetylene in the reaction of equimolar amounts of iodobenzene and phenylacetylene catalyzed by Pd(OAc)2–2 PPh3 was quantitative, but it decreased to less than 3% in the absence of triphenylphosphine. Nevertheless, the conversion of both phenylacetylene and iodobenzene was complete. At first glance, this result may be rationalized by the fact that in the absence of Cu(I) and ligand the major reaction pathway is carbopalladation of acetylene (c) rather than nucleophilic substitution of halogen (b) in the product of oxidative addition (a) of organic halide to Pd(0) by acetylide ion (Scheme 1). Carbopalladation of acetylene gives σ-alkenyl palladium complex analogous to products of oxidative addition of vinyl halides to Pd(0). It is known that the stability of such complexes (even when β-hydrogen atoms are present therein) allows catalytic coupling of vinyl halides with various nucleophiles to be accomplished (e.g., Heck [3], Suzuki [4], Kumada [5], and Buchwald–Hartwig reactions [6]). Thus, in the absence of Cu(I) and strong ligands it becomes possible to efficiently generate arylated σ-alkenyl palladium complexes from aryl halides and acetylenes, and these complexes are capable of reacting with various nucleophiles. However, this approach has not been implemented so far in cross-coupling reactions (Scheme 1). In fact, the only example of such transformations is the three-component reaction of aryl halides with acetylene and arylboronic acid [7, 8]. This reaction conforms to the following path: oxidative addition (a), carbopalladation (c) , and transmetalation (e) (Scheme 1). The feasibility of the above approach was indirectly confirmed by the formation of enynes as ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 9, pp. 1356–1358.