Reaction Progress Kinetic Analysis Research Articles

Kinetics of the Chiral Disulfonimide‐Catalyzed Mukaiyama Aldol Reaction

Making progress: The kinetics of the disulfonimide-catalyzed Mukaiyama aldol reaction have been established by using the reaction progress kinetic analysis (RPKA) method. The reaction is first order with respect to catalyst and silyl ketene acetal, and has an order of 0.55 with respect to the aldehyde, which suggests the reversibility of the binding between the aldehyde and the actual catalyst.

Scope and mechanism of the Pt-catalyzed enantioselective diboration of monosubstituted alkenes.

The Pt-catalyzed enantioselective diboration of terminal alkenes can be accomplished in an enantioselective fashion in the presence of chiral phosphonite ligands. Optimal procedures and the substrate scope of this transformation are fully investigated. Reaction progress kinetic analysis and kinetic isotope effects suggest that the stereodefining step in the catalytic cycle is olefin migratory insertion into a Pt-B bond. Density functional theory analysis, combined with other experimental data, suggests that the insertion reaction positions platinum at the internal carbon of the substrate. A stereochemical model for this reaction is advanced that is in line both with these features and with the crystal structure of a Pt-ligand complex.

A Combined Kinetic and Thermodynamic Approach for the Interpretation of Continuous‐Flow Heterogeneous Catalytic Processes

The heterogeneous proline-catalyzed aldol reaction was investigated under continuous-flow conditions by means of a packed-bed microreactor. Reaction-progress kinetic analysis (RPKA) was used in combination with nonlinear chromatography for the interpretation, under synthetically relevant conditions, of important mechanistic aspects of the heterogeneous catalytic process at a molecular level. The information gathered by RPKA and nonlinear chromatography proved to be highly complementary and allowed for the assessment of optimal operating variables. In particular, the determination of the rate-determining step was pivotal for optimizing the feed composition. On the other hand, the competitive product inhibition was responsible for the unexpected decrease in the reaction yield following an apparently obvious variation in the feed composition. The study was facilitated by a suitable 2D instrumental arrangement for simultaneous flow reaction and online flow-injection analysis.

Mechanistic Investigation of Chiral Phosphoric Acid Catalyzed Asymmetric Baeyer–Villiger Reaction of 3‐Substituted Cyclobutanones with H2O2 as the Oxidant

The mechanism of the chiral phosphoric acid catalyzed Baeyer-Villiger (B-V) reaction of cyclobutanones with hydrogen peroxide was investigated by using a combination of experimental and theoretical methods. Of the two pathways that have been proposed for the present reaction, the pathway involving a peroxyphosphate intermediate is not viable. The reaction progress kinetic analysis indicates that the reaction is partially inhibited by the gamma-lactone product. Initial rate measurements suggest that the reaction follows Michaelis-Menten-type kinetics consistent with a bifunctional mechanism in which the catalyst is actively involved in both carbonyl addition and the subsequent rearrangement steps through hydrogen-bonding interactions with the reactants or the intermediate. High-level quantum chemical calculations strongly support a two-step concerted mechanism in which the phosphoric acid activates the reactants or the intermediate in a synergistic manner through partial proton transfer. The catalyst simultaneously acts as a general acid, by increasing the electrophilicity of the carbonyl carbon, increases the nucleophilicity of hydrogen peroxide as a Lewis base in the addition step, and facilitates the dissociation of the OH group from the Criegee intermediate in the rearrangement step. The overall reaction is highly exothermic, and the rearrangement of the Criegee intermediate is the rate-determining step. The observed reactivity of this catalytic B-V reaction also results, in part, from the ring strain in cyclobutanones. The sense of chiral induction is rationalized by the analysis of the relative energies of the competing diastereomeric transition states, in which the steric repulsion between the 3-substituent of the cyclobutanone and the 3- and 3'-substituents of the catalyst, as well as the entropy and solvent effects, are found to be critically important.

Kinetic and mechanistic studies of proline-mediated direct intermolecular aldol reactions

Reaction progress kinetic analysis of the proline-mediated intermolecular aldol reaction shows that the rate depends on the concentrations of both the donor ketone 1 and the electrophilic aldehyde 2, implying that enamine formation cannot be rate-determining. The observed kinetics and deuterium isotope effects are consistent with formation of the product iminium species as the rate-determining step.

Regioselectivity and Diasteroselectivity in Pt(II)-Mediated “Green” Catalytic Epoxidation of Terminal Alkenes with Hydrogen Peroxide: Mechanistic Insight into a Peculiar Substrate Selectivity

Recently developed electron-poor Pt(II) catalyst 1 with the "green" oxidant 35% hydrogen peroxide displays high activity and complete substrate selectivity in the epoxidation of terminal alkenes because of stringent steric and electronic requirements. In the presence of isolated dienes bearing terminal and internal double bonds, epoxidation is completely regioselective toward the production of terminal epoxides. Insight into the mechanism is gained by means of a reaction progress kinetic analysis approach that underlines the peculiar role of 1 in activating both the alkene and H2O2 in the rate-determining step providing a rare example of nucleophilic oxidation of alkenes by H2O2.

Reaction Calorimetry as a Tool for Understanding Reaction Mechanisms: Application to Pd-Catalyzed Reactions

Reaction calorimetry can be employed for kinetic studies of complex catalytic reactions. In the calorimeter, the enthalpy balance around the reactor is continuously monitored and gives a profile of reaction heat vs time, which can be easily expressed in terms of reaction rate, conversion, and concentration of reactants/products. The data can be further analyzed using a methodology called reaction progress kinetic analysis, where the rate is expressed in terms of the concentration of substrates and a graphical expression is used to analyze the order in each substrate and in the catalyst. When studying a catalytic cycle, we can obtain useful information on catalyst activation/deactivation, substrate or product activation/deactivation, and the rate-limiting step. Thus, a detailed mechanistic picture can be obtained. In the present work we show an example of the role of reaction calorimetry in both fingerprinting and detailed study of some Pd-catalyzed aminations of aryl halides. These reactions are considere...

Investigations of Pd-Catalyzed ArX Coupling Reactions Informed by Reaction Progress Kinetic Analysis

This Perspective highlights how the methodology of reaction progress kinetic analysis can provide a rapid and comprehensive kinetic profile of complex catalytic reaction networks under synthetically relevant conditions in a fraction of the number of experiments required by classical kinetic analysis. This approach relies on graphical manipulation of the extensive data sets available from accurate in situ monitoring of reaction progress under conditions where two concentration variables are changing simultaneously. A series of examples from Pd-catalyzed coupling reactions of aryl halides demonstrates how a wealth of kinetic information may be extracted from just three experiments in each case. Even before proposing a reaction mechanism, we can determine reaction orders in substrates, propose a resting state for the catalyst, and probe catalyst stability. Carrying out this kinetic analysis at the outset of a mechanistic investigation provides a framework for further work aimed at seeking a molecular-level understanding of the nature of the species within the catalytic cycle. To be considered plausible, any independent mechanistic proposal must be shown to be consistent with this global kinetic analysis.

Mechanistic Insights from Reaction Progress Kinetic Analysis of the Polypeptide-Catalyzed Epoxidation of Chalcone

[reaction: see text] Reaction progress kinetic analysis of the poly(L)-leucine (PLL)-catalyzed epoxidation of substituted chalcones 1a-1c helps to refine an earlier mechanistic proposal by demonstrating that the reaction proceeds via reversible addition of chalcone to a PLL-bound hydroperoxide, forming a fleeting hydroperoxy enolate species. Observation of an induction period offers an alternate rationalization for effects formerly attributed to substrate inhibition. Previous clues about the origin of enantioselectivity in this system are supported by this work.

Reaction Progress Kinetic Analysis: A Powerful Methodology for Mechanistic Studies of Complex Catalytic Reactions

AbstractFor Abstract see ChemInform Abstract in Full Text.