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Review
Farewell to the HSAB Treatment of Ambident Reactivity
Article first published online: 1 JUL 2011
DOI: 10.1002/anie.201007100
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Mayr, H., Breugst, M. and Ofial, A. R. (2011), Farewell to the HSAB Treatment of Ambident Reactivity. Angew. Chem. Int. Ed., 50: 6470–6505. doi: 10.1002/anie.201007100
Publication History
- Issue published online: 5 JUL 2011
- Article first published online: 1 JUL 2011
- Manuscript Received: 11 NOV 2010
Keywords:
- intrinsic barriers;
- linear free-energy relationships;
- Marcus theory;
- nucleophilic substitution;
- regioselectivity
Abstract
The concept of hard and soft acids and bases (HSAB) proved to be useful for rationalizing stability constants of metal complexes. Its application to organic reactions, particularly ambident reactivity, has led to exotic blossoms. By attempting to rationalize all the observed regioselectivities by favorable soft–soft and hard–hard as well as unfavorable hard–soft interactions, older treatments of ambident reactivity, which correctly differentiated between thermodynamic and kinetic control as well as between different coordination states of ionic substrates, have been replaced. By ignoring conflicting experimental results and even referring to untraceable experimental data, the HSAB treatment of ambident reactivity has gained undeserved popularity. In this Review we demonstrate that the HSAB as well as the related Klopman–Salem model do not even correctly predict the behavior of the prototypes of ambident nucleophiles and, therefore, are rather misleading instead of useful guides. An alternative treatment of ambident reactivity based on Marcus theory will be presented.