Abstract
The concepts of nucleophilicity and protophilicity are fundamental and ubiquitous in chemistry. A case in point is bimolecular nucleophilic substitution (SN2) and base‐induced elimination (E2). A Lewis base acting as a strong nucleophile is needed for SN2 reactions, whereas a Lewis base acting as a strong protophile (i.e., base) is required for E2 reactions. A complicating factor is, however, the fact that a good nucleophile is often a strong protophile. Nevertheless, a sound, physical model that explains, in a transparent manner, when an electron‐rich Lewis base acts as a protophile or a nucleophile, which is not just phenomenological, is currently lacking in the literature. To address this fundamental question, the potential energy surfaces of the SN2 and E2 reactions of X−+C2H5Y model systems with X, Y = F, Cl, Br, I, and At, are explored by using relativistic density functional theory at ZORA‐OLYP/TZ2P. These explorations have yielded a consistent overview of reactivity trends over a wide range in reactivity and pathways. Activation strain analyses of these reactions reveal the factors that determine the shape of the potential energy surfaces and hence govern the propensity of the Lewis base to act as a nucleophile or protophile. The concepts of “characteristic distortivity” and “transition state acidity” of a reaction are introduced, which have the potential to enable chemists to better understand and design reactions for synthesis.
Highlights
The ability to rationally design chemical reactions is one of the fundamental challenges in chemistry
The SN2, anti-E2, and syn-E2 model reactions proceed via a reactant complex (RC) and a transition state (TS) towards a product complex (PC), which may eventually dissociate into products; exceptions are discussed later on
The acid–base, that is, highest occupied molecular orbital (HOMO)–LUMO, interaction between the Lewis base and substrate goes from a stronger interaction, for example, in the case of FÀ (Figure 7 c), to a weaker interaction (Figure 7 d) and, changes the preferred reaction pathway from E2 in the gas phase to SN2 in solution.[3m,4b,j,6a,e] In addition, for weaker Lewis bases (XÀ = ClÀ, BrÀ, IÀ, AtÀ), solvation will enhance the apparent nucleophilicity as it increases the E2 reaction barrier to a larger extent than the SN2 reaction barrier
Summary
The ability to rationally design chemical reactions is one of the fundamental challenges in chemistry. We develop, based on quantum chemical analyses, a unified model that provides chemists with the tools to readily understand the duality of Lewis bases, that is their nucleophilic or protophilic character To this end, we have explored and analyzed the potential energy surfaces along the reaction coordinates of the SN2 substitution, anti-E2 elimination (E2-a), and syn-E2 elimination (E2-s) reactions of XÀ + C2H5Y, with X, Y = F, Cl, Br, I, and At, by using relativistic density functional theory (DFT) at ZORA-OLYP/TZ2P.[9] The C2H5Y substrate allows us to probe the direct competition between SN2 and E2, and our findings can be extended to any substrate where the acidic hydrogen and the leaving group are electronically coupled. These concepts will provide chemists with rational design principles that will enable the design of selective synthetic routes to targeted products
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