Kinetic, mechanistic, and theoretical studies of proline-mediated transformations

ORGN 547

Donna G Blackmond, D.BLACKMOND@IMPERIAL.AC.UK1, Hiroshi Iwamura2, Suju P Mathew2, David H Wells Jr.2, Natalia Zotova2, Martin Klussmann2, Emma Emanuelsson2, and Alan Armstrong2. (1) Department of Chemistry, Imperial College London, London, SW7 2AZ, United Kingdom, (2) Department of Chemistry, Imperial College, London, SW7 2AZ, United Kingdom
Asymmetric aminocatalysis has emerged as a successful vehicle for accomplishing a wide variety of highly enantioselective organic transformations. Mechanistic analogies to enzymes, including the importance of hydrogen bonding, have recently been highlighted in a number of cases. We recently proposed a novel variation of these hydrogen bonding themes in recent kinetic, mechanistic and computational studies of the proline-mediated alpha-aminoxylation and alpha-amination of aldehydes. Observation of an accelerating rate that is proportional to product concentration led us to propose that the active catalyst is a product-proline adduct exhibiting multi-dentate hydrogen bonding. The product-proline adduct helps to stabilize a key proton transfer transition state in the addition of aldehyde to proline, relative to the same reaction unassisted by product. The example of a reaction product enabling higher efficiency in its own catalytic production may help us understand how small molecule amino acid catalysts evolved into highly efficient enzymes.
 

Asymmetric Reactions and Syntheses
1:00 PM-5:00 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- 201, Oral

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005