How Lewis Acids Catalyze Ring-Openings of Cyclohexene Oxide

Abstract

We have quantum chemically studied the Lewis acid-catalyzed epoxide ring-opening reaction of cyclohexene epoxide by MeZH (Z = O, S, and NH) using relativistic dispersion-corrected density functional theory. We found that the reaction barrier of the Lewis acid-catalyzed epoxide ring-opening reactions decreases upon ascending in group 1 along the series Cs + > Rb + > K + > Na + > Li + > H + . Our activation strain and Kohn–Sham molecular orbital analyses reveal that the enhanced reactivity of the Lewis acid-catalyzed ring-opening reaction is caused by the reduced steric (Pauli) repulsion between the filled orbitals of the epoxide and the nucleophile, as the Lewis acid polarizes the filled orbitals of the epoxide more efficiently away from the incoming nucleophile. Furthermore, we established that the regioselectivity of these ring-opening reactions is, aside from the “classical” strain control, also dictated by a hitherto unknown mechanism, namely, the steric (Pauli) repulsion between the nucleophile and the substrate, which could be traced back to the asymmetric orbital density on the epoxide. In all, this work again demonstrates that the concept of Pauli-lowering catalysis is a general phenomenon.

Rational Tuning of the Reactivity of Three‐Membered Heterocycle Ring Openings via SN2 Reactions

“…shows that the substrate gradually evolves from a half chair to a chair. Of note, we also computed the skew boat-like transition state (b-attack) of all substrates (see Table S5), and found, in line with our previous work, [8] that this pathway is substantially higher in energy and thus not relevant.…”

C(spn)−X (n=1–3) Bond Activation by Palladium

“…Note that these EDA plots should be interpreted with caution. We previously found,[ 7c , 7d , 7e ] as one would expect, that the EDA results are strongly dependent on the distance between the reactants, in this case, the catalyst and substrate. The Pd⋅⋅⋅C distance is more than 0.2 Å longer for the Pd+H 3 C−CH 2 −H than Pd+HC≡C−H, i.e., 2.14 Å and 1.92 Å, respectively, at the same consistent TS‐like geometries (C⋅⋅⋅H bond stretch of 0.50 Å), as obtained from the IRC.…”

The Pauli Repulsion-Lowering Concept in Catalysis

“…This is the ultimate physical factor responsible for the acceleration of the process as compared to the analogous uncatalyzed reaction. This concept seems general and applicable to rather different transformations, spanning from nucleophilic additions to cycloaddition reactions . For this reason, we envisage that the insights emerging from the ASM-EDA method will guide future experimental developments toward the design of more efficient catalytic transformations.…”