Computational Study of Electronic Influence of Guanidine Substitution on Diels-Alder Reactions of Heterocyclic Dienes

Abstract

Quantum-chemical calculations of cycloaddition properties of cyclic heterodienes substituted with guanidine functionality were carried out. Molecular and electronic structures of series of dienes (pyrrole, furan, thiophene, isoindole and 1,3-butadiene) were calculated and reactivity order established on the basis of FMO theory. Transition state calculations of model [4+2] cycloaddition reaction with acetylene indicate that guanidine substitution influences reaction barriers in moderate extent (up to ~4 kcal mol–1). The substitution position plays an important role on the sign and magnitude of the effect and protonation of nitrogen possessing substituents increases reactivity of dienes.

Mechanistic DFT Study of 1,3-Dipolar Cycloadditions of Azides with Guanidine

“…The B3LYP/6-311+G(2d,p) method [18,19] was used to study the mechanism of azide addition to guanidine. Structures of reactants, transition states, and products were optimized without any symmetry constraints in the gas phase.…”

“…Different synthetic strategies are employed for the synthesis of tetrazoles [16]; however, the direct addition of azide to guanidine was not utilized. Realizing that this type of reaction has not been not theoretically studied to date, and in continuation of our interest in cycloaddition reactions [17,18] and study of the effects of the substitution of dienes with guanidines [19], we conducted this computational study to address several scientific questions: What is the reactivity of guanidine in 1,3-dipolar cycloadditions, and what is the regioselectivity of this reaction? This study aims to establish the cycloaddition (dipolarophilic) properties of imine bond in guanidine and the regioselectivity of the formation of tetrazoles.…”

N,N′-Di-Boc-2H-Isoindole-2-carboxamidine—First Guanidine-Substituted Isoindole

“…The objective of this work is to prepare isoindole-2-carboxamidine 2, the first representative of an isoindole guanidine cycloaddition delivery reagent, and assess its cycloaddition properties experimentally and computationally. Our preliminary DFT computational study revealed that this approach is feasible and both pyrrole and isoindole dienes are predicted to have sufficient reactivity [14].…”

Cycloaddition of Thiourea- and Guanidine-Substituted Furans to Dienophiles: A Comparison of the Environmentally-Friendly Methods

“…Indeed, diamines have often been used in synthesis of novel basic organocatalysts [8][9][10] or fluorophores [11]. Triggered by these results, we became interested in using guanidine substituted dienes in cycloaddition reactions [12].…”