Hiroshi Iwamura

Thermodynamic control of asymmetric amplification in amino acid catalysis.

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.

Asymmetric synthesis of allylsilanes by palladium-catalyzed asymmetric reduction of allylic carbonates with formic acid☆

Abstract Reduction of 3-alkyl-3-trialkylsilyl-2-propenyl methyl carbonates with formic acid and 1,8-bis(dimethylamino)naphthalene in the presence of a palladium catalyst (3 mol %) coordinated with (R)-3-diphenylphosphino-3′-methoxy-4,4′-biphenanthryl (MOP-phen) gave optically active allylsilanes (3-alkyl-3-trialkylsilyl-1-propenes) of up to 91 % ee.

A mechanistic rationalization of unusual kinetic behavior in proline-mediated C–O and C–N bond-forming reactions

Kinetic evidence supports the role of the reaction product in the catalytic cycle of proline-mediated alpha-aminoxylation and alpha-amination reactions, providing both design principles as well as a model for the evolution of efficiency in catalysis.

Catalytic asymmetric synthesis of optically active alkenes by palladium-catalysed asymmetric reduction of racemic allylic esters with formic acid

Asymmetric reduction of racemic allyl ester, e.g. methyl 1-vinyl-1,2,3,4-tetrahydronaphth-1-yl carbonate, which contain two different alkyl groups at the α-position, with formic acid in the presence of 1 mol% of palladium catalyst coordinated with (R)-3-diphenylphosphino-3′-methoxy-4,4′-biphenanthryl [(R)-MOP-phen] ligand gives optically active terminal alkenes in up to 93% ee.