E. V. Larina

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.

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.

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.

Measuring the kinetic isotope effect at natural isotopic abundances for discriminating between the homogeneous and heterogeneous catalytic mechanisms in the Heck and Suzuki reactions

The kinetic isotope effect (KIE) at the natural abundances of bromine and carbon isotopes in the substrates of the Heck and Suzuki reactions have been investigated to determine the true nature of catalyst in these reactions. Data processing has demonstrated that statistically significant differences between KIE values for the Suzuki reaction of nonactivated bromobenzene are observed upon the replacement of the soluble catalyst precursor with the insoluble one. This finding unambiguously indicates that the reaction takes place on heterogeneous palladium species. Similar experiments on the Heck reaction have demonstrated that the KIE values are insensitive to the nature of the catalyst precursor, which is consistent with the true homogeneous mechanism of catalysis.