Hiroshi Iwamura

Bio: Hiroshi Iwamura is an academic researcher from Mitsubishi. The author has contributed to research in topics: Reaction progress kinetic analysis & Enantiomeric excess. The author has an hindex of 5, co-authored 8 publications receiving 725 citations. Previous affiliations of Hiroshi Iwamura include University of Calgary & Imperial College London.

Thermodynamic control of asymmetric amplification in amino acid catalysis

Abstract: Ever since Pasteur noticed that tartrate crystals exist in two non-superimposable forms that are mirror images of one another--as are left and right hands--the phenomenon of chirality has intrigued scientists. On the molecular level, chirality often has a profound impact on recognition and interaction events and is thus important to biochemistry and pharmacology. In chemical synthesis, much effort has been directed towards developing asymmetric synthesis strategies that yield product molecules with a significant excess of either the left-handed or right-handed enantiomer. This is usually achieved by making use of chiral auxiliaries or catalysts that influence the course of a reaction, with the enantiomeric excess (ee) of the product linearly related to the ee of the auxiliary or catalyst used. In recent years, however, an increasing number of asymmetric reactions have been documented where this relationship is nonlinear, an effect that can lead to asymmetric amplification. Theoretical models have long suggested that autocatalytic processes can result in kinetically controlled asymmetric amplification, a prediction that has now been verified experimentally and rationalized mechanistically for an autocatalytic alkylation reaction. Here we show an alternative mechanism that gives rise to asymmetric amplification based on the equilibrium solid-liquid phase behaviour of amino acids in solution. This amplification mechanism is robust and can operate in aqueous systems, making it an appealing proposition for explaining one of the most tantalizing examples of asymmetric amplification-the development of high enantiomeric excess in biomolecules from a presumably racemic prebiotic world.

Investigations of Pd-catalyzed ArX coupling reactions informed by reaction progress kinetic analysis.

Abstract: 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.

Kinetic Studies Prove High Catalytic Activity of a Diene–Rhodium Complex in 1,4‐Addition of Phenylboronic Acid to α,β‐Unsaturated Ketones

Abstract: In the 1,4-addition of phenylboronic acid to alpha,beta-unsaturated ketones, [Rh(OH)(cod)]2 has a much higher catalytic activity than [Rh(OH)(binap)]2 (cod = 1,5-cyclooctadiene, binap = 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl). Kinetic studies revealed that the rate-determining transmetalation step in the catalytic cycle has a large rate constant when [Rh(OH)(cod)]2 is used.

Asymmetric catalysis by chiral hydrogen-bond donors.

Abstract: Hydrogen bonding is responsible for the structure of much of the world around us. The unusual and complex properties of bulk water, the ability of proteins to fold into stable three-dimensional structures, the fidelity of DNA base pairing, and the binding of ligands to receptors are among the manifestations of this ubiquitous noncovalent interaction. In addition to its primacy as a structural determinant, hydrogen bonding plays a crucial functional role in catalysis. Hydrogen bonding to an electrophile serves to decrease the electron density of this species, activating it toward nucleophilic attack. This principle is employed frequently by Nature's catalysts, enzymes, for the acceleration of a wide range of chemical processes. Recently, organic chemists have begun to appreciate the tremendous potential offered by hydrogen bonding as a mechanism for electrophile activation in small-molecule, synthetic catalyst systems. In particular, chiral hydrogen-bond donors have emerged as a broadly applicable class of catalysts for enantioselective synthesis. This review documents these advances, emphasizing the structural and mechanistic features that contribute to high enantioselectivity in hydrogen-bond-mediated catalytic processes.

Organocatalysis--after the gold rush.

Abstract: The use of secondary amines as asymmetric catalysts in transformations of carbonyl compounds has seen tremendous development in recent years. Going from sporadic reports of selected reactions, aminocatalysis can now be considered as one of the methods of choice for many asymmetric functionalizations of carbonyl compounds—primarily of aldehydes and ketones. These functionalizations have been published at a breathtaking pace over the last few years—during the “golden age” and “gold rush” of organocatalysis. This tutorial review will firstly sketch the basic developments in organocatalysis, focussing especially on the use of secondary amines as catalysts for the functionalization of aldehydes and α,β-unsaturated aldehydes, with emphasis on the mechanisms of the transformations and, secondly, outline recent trends within central areas of this research topic. Lastly, we will present our guesses as to where new developments might take organocatalysis in the years to come.

Asymmetric aminocatalysis--gold rush in organic chemistry.

Abstract: Catalysis with chiral secondary amines (asymmetric aminocatalysis) has become a well-established and powerful synthetic tool for the chemo- and enantioselective functionalization of carbonyl compounds. In the last eight years alone, this field has grown at such an extraordinary pace that it is now recognized as an independent area of synthetic chemistry, where the goal is the preparation of any chiral molecule in an efficient, rapid, and stereoselective manner. This has been made possible by the impressive level of scientific competition and high quality research generated in this area. This Review describes this "Asymmetric Aminocatalysis Gold Rush" and charts the milestones in its development. As in all areas of science, progress depends on human effort.