Seemingly Simple Stereoelectronic Effects in Alkane Isomers and the Implications for Kohn–Sham Density Functional Theory

✍ Scribed by Stefan Grimme

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 112 KB
• Volume: 45
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.200600448

✦ Synopsis

The concept of stereoelectronic (SE) effects is widely applied especially in organic chemistry. [1] Substituents are typically described as electron-density-donating or -withdrawing or responsible for sterically interacting with, for example, reagents. The rational application of SE design rules is of utmost importance in synthetic chemistry where target structures are often kinetically or thermodynamically favored. Important SE effects can be introduced by alkylation (methylation in the following discussion for simplicity) of strategic positions in a molecule. The resulting energetic changes can be qualitatively separated into so-called electronic (bonding) and nonbonding (through-space, i.e., attractive van der Waals (vdW) and electrostatic, and repulsive Pauli) interactions. While a meaningful definition and separation of these individual terms is quite difficult at a rigorous quantum mechanical level, it is generally believed that modern quantum chemical methods are at least able to describe the overall energetic effects quantitatively. It is shown in this Communication that this does not hold for the widely used Kohn-Sham density functional theory (DFT) [2] with all state-of-the-art density functionals; this approach does not provide even a qualitatively correct picture for an important class of chemical problems.

The problem has become evident in recent years since larger molecular systems have been studied more routinely. In general it appears when a first-row atom or group X (X = B, C, N) is successively alkylated. Gilbert [3] found increasing errors of the B3LYP functional (up to 20 kcal mol À1 ) for the dissociation reaction (1) when R = H is replaced by CH 3 .

Similar results were reported later [4,5] for the CÀC bond dissociation reaction (2) and [2+2] cycloadditions and CH 2 -

[*] Prof.