Understanding the role of noncovalent interactions on the rate of some Diels‐Alder reactions in different solvents

Abstract

In this article, the role of noncovalent interactions (NCI) on four types of cycloaddition reactions in different solvents was investigated by employing quantum chemistry calculations. For this purpose, explicit and implicit solvation models were applied in the experimental conditions of temperature and pressure. NCI analysis indicates that van der Waals (vdW) interactions, as a part of NCI, change the stability and Gibbs energy of the transition states (TSs), which in turn affects the rate of the reaction. On the basis of NCI analysis, a partial covalent nature of the forming CC bonds at the TSs was confirmed. Energy analysis confirms that vdW interactions can be considered as the main part of the solute‐solvent interactions in the cycloaddition reactions. Moreover, cycloaddition reactions of the polar reactants are faster in polar solvents, while nonpolar solvents induce a contrast effect on the rate of these reactions.

Revealing the Origin of Π‐facial and Regioselectivity in the Diels‐Alder Reaction of Unsymmetrical, Cage‐annulated 1,3‐Cyclohexadiene with Ethyl Propiolate Dienophile: a DFT Study

“…[37] NCI analysis is used to predict the attractive and repulsive interactions between the reactant molecules. [31,44,45] These interactions are based on the electron density and the second eigenvalue (λ2) of the Hessian of the electron density. This method provides 2D and 3D NCI plots, which are indicative of the types of interactions for a reaction.…”

“…NCI analysis is used to predict the attractive and repulsive interactions between the reactant molecules [31,44,45] . These interactions are based on the electron density and the second eigenvalue (λ2) of the Hessian of the electron density.…”

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

“…Non-covalent intermolecular interactions (NCIs) between aromatic rings (π•••π) [58,59] and alkyl and aromatic ring (Csp 3 -H)•••π stackings [59][60][61][62] are widely recognized, from both the experimental and theoretical viewpoint, as a major factor governing the conformational equilibrium, supramolecular assembly and stereoselective approaches of substrates and reagents or catalysts in a variety of processes. Examples include the substrate-enzyme recognition (the host-guest interaction) responsible for inducing pharmacological activity, the DNA- intercalation capable of generating biomolecular activity, molecular dynamics [63][64][65][66][67][68][69][70], and pericyclic reactions (Diels-Alder and 1,3-dipolar cycloadditions) [71][72][73][74][75].…”

The Effect of Solvent–Substrate Noncovalent Interactions on the Diastereoselectivity in the Intramolecular Carbonyl-Ene and the Staudinger [2 + 2] Cycloaddition Reactions

“…Furthermore, a solvent is seen to play the most pivotal role in different chemical reactions. , There are several reports investigating the effect of different solvents, − including reports of the explicit role of solvent molecules, on stereoselectivity. In addition to these effects, the role of noncovalent effects such as hydrogen bonding, π–π stacking, and C–H/π and C–H/O interactions has also been investigated, and noncovalent interactions (NCIs) between explicit solvent molecules and the substrate have been seen to be important. ,− It is, however, rare to find reports that show NCIs between solvents and substrates to be the major reason for the observed stereoselectivity. , The reason could be because this is a rare phenomenon, but an interesting hypothesis that we propose and explore here is that this is a widespread occurrence that has not received adequate attention because of a lack of inclusion of explicit solvent effects in computational investigations. In order to give credence to this hypothesis, we have considered two important, highly stereoselective organic reactions: (a) the carbonyl-ene reaction, which is a reaction between the ene and the enophile for selective carbon–carbon bond formation − and (b) the Staudinger [2 + 2] cycloaddition reaction between a ketene and an imine − for the synthesis of β-lactam triflones.…”