Tom Bettens1, Mercedes Alonso1, Frank De Proft1, Trevor A Hamlin2, F Matthias Bickelhaupt2,3. 1. Eenheid Algemene Chemie (ALGC), Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium. 2. Department of Theoretical Chemistry, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Amsterdam Center for Multiscale Modeling (ACMM), Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081, HV, Amsterdam, The Netherlands. 3. Institute for Molecules and Materials (IMM), Radboud University Nijmegen, Heyendaalseweg 135, 6525, AJ, Nijmegen, The Netherlands.
Abstract
The ability to understand and predict ambident reactivity is key to the rational design of organic syntheses. An approach to understand trends in ambident reactivity is the hard and soft acids and bases (HSAB) principle. The recent controversy over the general validity of this principle prompted us to investigate the competing gas-phase SN 2 reaction channels of archetypal ambident nucleophiles CN- , OCN- , and SCN- with CH3 Cl (SN 2@C) and SiH3 Cl (SN 2@Si), using DFT calculations. Our combined analyses highlight the inability of the HSAB principle to correctly predict the reactivity trends of these simple, model reactions. Instead, we have successfully traced reactivity trends to the canonical orbital-interaction mechanism and the resulting nucleophile-substrate interaction energy. The HOMO-LUMO orbital interactions set the trend in both SN 2@C and SN 2@Si reactions. We provide simple rules for predicting the ambident reactivity of nucleophiles based on our Kohn-Sham molecular orbital analysis.
The ability to understand and predict ambident reactivity is key to the rational design of organic syntheses. An approan class="Chemical">ch to understand trends in ambident reactivity is the hard and soft acids and bases (HSAB) principle. The recent controversy over the general validity of this principle prompted us to investigate the competing gas-phase SN 2 reaction channels of archetypal ambident nucleophiles CN- , OCN- , and SCN- with CH3 Cl (SN 2@C) and SiH3 Cl (SN 2@Si), using DFT calculations. Our combined analyses highlight the inability of the HSAB principle to correctly predict the reactivity trends of these simple, model reactions. Instead, we have successfully traced reactivity trends to the canonical orbital-interaction mechanism and the resulting nucleophile-substrate interaction energy. The HOMO-LUMO orbital interactions set the trend in both SN 2@C and SN 2@Si reactions. We provide simple rules for predicting the ambident reactivity of nucleophiles based on our Kohn-Sham molecular orbital analysis.