Understanding reactivity with Kohn-Sham molecular orbital theory: E2-S(N)2mechanistic spectrum and other concepts

On the basis of Kohn-Sham density functional (DFT) investigations on elemen tary organic and organometallic reactions, we show how a detailed understan ding of the electronic structure of a reaction system can help recognize ce rtain characteristics of the process, yielding valuable mechanistic concept s. 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. Fu rthermore, electronic structure considerations provide the so-called E2-S(N )2 mechanistic spectrum, in terms of which one can interpret and understand the competition between elimination and substitution reactions and the shi ft, on solvation, of the reactivity from E2 to S(N)2. in addition, mechanis tic concepts from organometallic and organic chemistry are Linked as we arg ue that oxidative addition may be conceived, in some respect, as the organo metallic analog of the frontside S(N)2 substitution. Finally, we introduce the ideas of "activation strain" of and "transition state interaction" betw een the deformed reactants in the activated complex, which together determi ne the activation energy Delta E* = Delta E-strain* + Delta E-int*. They pr ove to be helpful conceptual tools for understanding in detail how activati on barriers and relative efficiencies of competing reaction mechanisms aris e and how they may be affected (e.g., by changing reactants or by solvation ). (C) 1999 John Wiley & Sons, Inc.