Understanding the Intramolecular Diels‐Alder Reactions of N‐Substituted N‐Allyl‐Furfurylamines: An MEDT Study

Abstract

The intramolecular Diels‐Alder (IMDA) reactions of N‐allyl‐furfurylamine (1a) and N‐trityl‐allyl‐furfurylamine (1b), were studied within the molecular electron density theory (MEDT) using density functional theory method [B3LYP/6‐31G(d)]. In spite of the high activation enthalpies, the low unfavourable activation entropies associated to these intramolecular processes permit these IMDA reactions to take place. The IMDA reaction of 1a is thermodynamically unfavourable. The presence of the bulky −CPh3 group in the amine nitrogen atom that destabilises the extended conformation of 1b turns the process into an exergonic one. This behaviour does not only affect the thermochemistry of the reaction, but also the kinetic parameters, thus accelerating the reaction. Electron localisation function topological analysis of the C−C single bond formation along the IMDA reaction of 1a shows a bonding pattern similar to non‐polar intermolecular Diels‐Alder reactions. The present MEDT study explains the experimental results; although the steric buttress is able to change the direction of these reversible IMDA reactions, this change is only possible due to the aromatic nature of the furanyl diene system.

Investing in entropy: the strategy of cucurbit[n]urils to accelerate the intramolecular Diels–Alder cycloaddition reaction of tertiary furfuryl amines

“…An effective strategy to accelerate these disfavored IMDA reactions in the bulk relied on installing steric buttresses on the N atom. [32][33][34] The idea at work has to do with restricting the conformational freedom of the molecules and their reactive groups. Nevertheless, this strategy requires the synthesis of elaborated substrates, and the subsequent removal -when possible-of the bulky protecting groups.…”

Understanding the regio-and diastereoselective synthesis of a potent antinociceptive isoxazolidine from C-(pyridin-3-yl)-N-phenylnitrone in the light of molecular electron density theory

“…Molecular electron density theory 3 (MEDT) proposed by Domingo in 2016 states that change in electron density is responsible for molecular reactivity in organic reactions. This theory has been widely illustrated for 32CA reactions [4][5][6] as well as for other processes, for which one-step "pericyclic mechanism" has been earlier postulated such as Diels-Alder reactions, 7,8 thermal elimination reaction, 9,10 [3,3] sigmatropic shifts, 11 etc. Initially, topological analysis of the electron localisation function 12 (ELF) and detailed analysis of conceptual density function theory (CDFT) indices 13 at the ground state of the reagents is performed within MEDT.…”

Exploring the Mechanism of the Intramolecular Diels–Alder Reaction of (2E,4Z,6Z)-2(allyloxy)cycloocta-2,4,6-trien-1-one Using Bonding Evolution Theory

“…In view of the scope of the IMDA reaction, computational studies on its mechanism are important in the areas of theoretical and synthetic organic chemistry. However, few computational/theoretical studies applying BET to the corresponding mechanisms have been published to date [28,29]. Herein, we report on a theoretical study, based on BET, to disclose the nature of the reaction mechanisms for the three possible reactive channels for the transformation of 1 (Scheme 1).…”