Showing papers by "Donna G. Blackmond published in 2003"

Insights into the Origin of High Activity and Stability of Catalysts Derived from Bulky, Electron-Rich Monophosphinobiaryl Ligands in the Pd-Catalyzed C-N Bond Formation

Abstract: A comparative kinetic examination of catalyst systems based on several monophosphinobiaryl ligands is reported. The bulk of the phosphine ligand controls the catalytic activity and the rate of catalyst activation with the catalyst based on 2-dicyclohexylphosphino-2‘,4‘,6‘-triisopropylbiphenyl providing the greatest activity and fastest activation. In the case where catalyst activation is slow (i.e., use of the smaller ligands such as 2-dicyclohexylphosphino-2‘-methylbiphenyl in combination with Pd(OAc)2) stirring the amine with the catalyst/base mixture prior to the commencement of the reaction increases the reaction rate along with the rate of catalyst activation. Kinetic isotope effects established that the catalyst activation process occurs through a β-hydride elimination pathway.

Kinetic Evidence for a Tetrameric Transition State in the Asymmetric Autocatalytic Alkylation of Pyrimidyl Aldehydes

Abstract: Experimental kinetic data coupled with kinetic modeling implicates a tetrameric transition state in the Soai autocatalytic alkylation of pyrimidyl aldehydes. The kinetic model accurately predicts both the reaction rate and the amplification in enantiomeric excess observed in reactions carried out under a wide range of conditions. These studies reveal the Soai reaction to be an example of true autocatalytic efficiency in a template-directed “minimal system” for self-replication.

Erratum: Requiem for the Reaction-Rate Equation?

Abstract: In a Perspectives in Catalysis article that appeared recently in Catalysis Letters, Professor Michel Boudart hailed a coming revolution in catalytic kinetics [1]. He predicts that the twenty-first century will be dominated by the rate constant, which will be determined by a combination of microkinetic analysis, computational chemistry, and surface science techniques. By contrast, the twentieth century belonged to the rate equation, elucidated using a mechanistic approach to kinetic modeling and supported by discrete experimental data sets arising from a large number of reactions carried out over a range of reaction conditions. Boudart argues that by perfecting the methodology of microkinetic analysis over the next few decades, kinetics-assisted design of catalysts will become predictive, obviating the need for rate equations. Since catalysis is a kinetic phenomenon [2], an approach advocating a prominent role for kinetics in the future development of protocols for discovery, design, and rapid screening of catalysts holds great promise. However, it is perhaps premature to hold a requiem for the rate equation in catalytic reaction kinetics. Indeed, I would argue that the role of the rate equation is currently in ascendance in one area of growing importance, that of research involving the complex organic catalytic reactions common to pharmaceutical applications. In this field, kinetic analysis and the determination of rate constants via the rate equation presents exciting opportunities for future research, aimed at increasing fundamental mechanistic understanding, aiding future catalyst design, and streamlining pharmaceutical process research and development in an ever more competitive environment. The key to this ‘‘back-to-the-future’’ approach to reaction kinetics in liquid-phase organic reactions lies in the recent development of accurate in situ experimental methods for the continuous monitoring of reaction rate as a function of reaction progress. These tools now insure that the fastest way to obtain information about these reactions is simply to run them—and by that I mean to run them just as one would in the commercial application, without resorting to experiments that measure initial rates using distorted reactant concentrations. Monitoring reactions using such in situ methods, we may obtain the equivalent of thousands of separate ‘‘initial-rate’’ measurements at different reactant concentrations in one reaction—typically over the course of an hour or less. What would Langmuir, Rideal, or Michaelis and Menten have given for access to such plentiful data for use in their rate equations? The attraction in pharmaceuticals of an approach based on the rate equation may be stronger than in petrochemical applications. The reasons for this become more clear when we compare key characteristics of typical pharmaceutical reactions with those of the petrochemical or basic chemicals industry, where the methodology of microkinetic analysis [3] described by Boudart has been most successfully applied (table 1). Petrochemical reactions are conventionally carried out at relatively high temperatures over fixed beds of heterogeneous catalysts that maintain a constant level of conversion of the flowing gaseous reactants. The reactants are small molecules, and the products may be many. Networks describing the global reactions can be extremely complex, with parallel and consecutive elementary steps often numbering in the dozens. Incorporating all of these into an explicit rate equation may prove to be intractable. The aim of the microkinetic treatment is to identify the unior bimolecular rate constants for all of these steps, culminating in the presentation of a mechanism-based macroscopic picture of the reaction. For such an approach to be successful, the assembling of the data required entails extensive experimental work, including various ex situ adsorption and surface chemistry experiments in addition to the The publisher regrets that this article first published in Vol. 83, Nos. 3–4 November 2002, pp. 133–136, appeared without any of the equations. Since the author originally supplied the complete article, the publisher accepts full responsibility for this grievous error. This version of the article, now published correctly and in its entirety, is the true representation of the author’s intent. Please contact the author directly regarding reprints. Catalysis Letters Vol. 89, Nos. 3–4, September 2003 (# 2003) 281