Understanding reactivity with Kohn-Sham molecular orbital theory: E2-SN2 mechanistic spectrum and other concepts

On the basis of Kohn–Sham density functional (DFT) investigations on elementary organic and organometallic reactions, we show how a detailed understanding of the electronic structure of a reaction system can help recognize certain characteristics of the process, yielding valuable mechanistic concepts. The concept of the base as a selective catalyst in E2 eliminations, for example, leads to a straightforward explanation for the general preference for anti over syn stereochemistry in base-induced elimination reactions. Furthermore, electronic structure considerations provide the so-called E2–SN2 mechanistic spectrum, in terms of which one can interpret and understand the competition between elimination and substitution reactions and the shift, on solvation, of the reactivity from E2 to SN2. In addition, mechanistic concepts from organometallic and organic chemistry are linked as we argue that oxidative addition may be conceived, in some respect, as the organometallic analog of the frontside SN2 substitution. Finally, we introduce the ideas of "activation strain" of and "transition state interaction" between the deformed reactants in the activated complex, which together determine the activation energy, ΔE*=ΔE+ΔE. They prove to be helpful conceptual tools for understanding in detail how activation barriers and relative efficiencies of competing reaction mechanisms arise and how they may be affected (e.g., by changing reactants or by solvation). © 1999 John Wiley & Sons, Inc. J Comput Chem 20: 114–128, 1999