Issue 5, 2014

The Houk–List transition states for organocatalytic mechanisms revisited


The ten year old Houk–List model for rationalising the origin of stereoselectivity in the organocatalysed intermolecular aldol addition is revisited, using a variety of computational techniques that have been introduced or improved since the original study. Even for such a relatively small system, the role of dispersion interactions is shown to be crucial, along with the use of basis sets where the superposition errors are low. An NCI (non-covalent interactions) analysis of the transition states is able to identify the noncovalent interactions that influence the selectivity of the reaction, confirming the role of the electrostatic NCHδ+⋯Oδ interactions. Simple visual inspection of the NCI surfaces is shown to be a useful tool for the design of alternative reactants. Alternative mechanisms, such as proton-relays involving a water molecule or the Hajos–Parrish alternative, are shown to be higher in energy and for which computed kinetic isotope effects are incompatible with experiment. The Amsterdam manifesto, which espouses the principle that scientific data should be citable, is followed here by using interactive data tables assembled via calls to the data DOI (digital-object-identifiers) for calculations held on a digital data repository and themselves assigned a DOI.

Graphical abstract: The Houk–List transition states for organocatalytic mechanisms revisited

Supplementary files

Article information

Article type
Edge Article
12 Dec 2013
24 Feb 2014
First published
24 Feb 2014
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2014,5, 2057-2071

Author version available

The Houk–List transition states for organocatalytic mechanisms revisited

A. Armstrong, R. A. Boto, P. Dingwall, J. Contreras-García, M. J. Harvey, N. J. Mason and H. S. Rzepa, Chem. Sci., 2014, 5, 2057 DOI: 10.1039/C3SC53416B

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