The Interplay between Steric and Electronic Effects in S_N2 Reactions

Abstract

Myths of steric hindrance: In contrast with current opinion, energy decomposition analysis shows that the presence of bulky substituents at carbon leads to the release of steric repulsion in the transition state shown in the graphic. It is rather the weakening of the electrostatic attraction, and in particular the loss of attractive orbital interactions, that are responsible for the activation barrier. Quantum chemical calculations for S(N)2 reactions of H(3)EX/X(-) systems, in which E=C or Si and X=F or Cl, are reported. In the case of the carbon system we also report on bulkier species in which the hydrogen atoms are substituted by methyl groups. It is shown how the variation in the individual energy terms of the Morokuma/Ziegler energy decomposition analysis (EDA) scheme along the reaction coordinate from reactants to products provides valuable insight into the essential changes that occur in the bond-breaking/bond-forming process during S(N)2 reactions. The EDA results for the prototypical S(N)2 reaction of the systems [X...R(3)E...X](-), in which the interacting fragments are [X...X](2-) and [R(3)E](+), have given rise to a new interpretation of the factors governing the reaction course. The EDA results for the carbon system (E=C) show that there is less steric repulsion and stronger electrostatic attraction in the transition structure than in the precursor complex and that the energy increase comes mainly from weaker orbital interactions. The larger barriers for systems in which R(3) is bulkier also do not arise from increased steric repulsion, which is actually released in the transition structure. It is rather the weakening of the electrostatic attraction, and in particular the loss of attractive orbital interactions, that are responsible for the activation barrier. The D(3h) energy minima of the silicon homologues [XH(3)SiX](-) is driven by the large increase in the electrostatic attractions and also of stronger orbital interactions, while the steric interactions is destabilizing.

Response to the Comment on “The Interplay between Steric and Electronic Effects in SN2 Reactions”

“…The curves of the EDA values that are shown in Figure 1 b in their Correspondence [1] support the conclusion that the steric repulsion, which is identified with the DE Pauli term of the EDA, decreases along the reaction path and that the DE Pauli value for the transition structure is smaller than for the reactants. The small hump in the curve for F À + Me 3 CÀ F, which was already observed by us in our previous study, [3] is interesting but not relevant for the present topic. Zeist and Bickelhaupt then introduce a new scenario where they consider a hypothetical system in which they suppress the geometric relaxation of the substrate when the nucleophile approaches.…”

“…This term is named DE strain by Zeist and Bickelhaupt. Essential to this discussion, is the fact that the unfavorable DE prep term of the R 3 C moiety within the tetrahedral R 3 CX species is almost fully released in passing from reactants to transition structure, since the R 3 C unit within [X···R 3 C···X] À for all practical reasons has the same planar geometry as in the reference state. If DE prep (or DE strain ) becomes further partitioned into the energy terms given in Equation (1), which is the approach applied by Zeist and Bickelhaupt in the preceding Correspondence, it would mean that the EDA results refer to a geometry that does not represent the actual structure of the investigated species.…”

“…[3] Unlike previous work, in which the S N 2 reaction often is analyzed in terms of interactions between an attacking nucleophile and a substrate, we also considered the effect of the leaving group on the energy terms of the EDA along the reaction path. We think this is a particularly reasonable approach for an identity reaction such as X À + R 3 C À X, where in the transition structure [X···R 3 …”

Double Group Transfer Reactions: Role of Activation Strain and Aromaticity in Reaction Barriers

“…[9] They showed, for instance, how the activation barrier of S N 2 reactions originates from steric congestion around the carbon atom that is nucleophilically attacked, and how electronic factors modulate the barrier height. [9,10] Not much later, Houk et al [11] were the first to successfully apply the activation strain model (or distortion/interaction model) to pericyclic reactions, in particular to [3+2] cycloaddition reactions. The latter, curiously, are concerted and occur through highly synchronous and in-plane aromatic transition states, very similar to the situation for DGT reactions.…”

Anions coordinating anions: analysis of the interaction between anionic Keplerate nanocapsules and their anionic ligands

“…61 In most of these examples, a non-charged system was divided into neutral fragments, and the analysis did not take into consideration any sort of solvent effects. 60 Other examples can be found in which charged fragments interact to form either a neutral 62,63 or a charged system, 64,65 but in these cases solvent effects were not included in the analysis either. De Jong and Bickelhaupt 66 introduced for the first time the EDA analysis in solvent, thus we followed an equivalent protocol.…”