The interplay of thermodynamics and kinetics in dictating organocatalytic reactivity and selectivity

Burés, Jordi; Armstrong, Alan; Blackmond, Donna G.

doi:10.1351/PAC-CON-13-01-14

Pure Appl. Chem., 2013, Vol. 85, No. 10, pp. 1919-1934

http://dx.doi.org/10.1351/PAC-CON-13-01-14

Published online 2013-07-29

The interplay of thermodynamics and kinetics in dictating organocatalytic reactivity and selectivity

Jordi Burés^1,2, Alan Armstrong¹ and Donna G. Blackmond^1,2*

¹ Department of Chemistry, Imperial College London, London SW7 2AZ, UK
² Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA

Abstract: Recent reports of the real-time identification of intermediates in organocatalytic reactions by NMR spectroscopy coupled with detailed kinetic studies highlight a potential role for stable intermediates reversibly formed downstream from what is generally considered to be the enantioselectivity-determining step. In this work, we employ kinetic modeling to explore these concepts further. We demonstrate that when an intermediate is common to multiple reaction pathways, the relative reactivity of these pathways dictates the ultimate outcome, regardless of the relative stability of other intermediates connected to these pathways. Kinetic modeling also illustrates important implications for enantioselectivity depending on whether such intermediates lie on or off the catalytic cycle.