A DFT Study of the Molecular Mechanisms of the Diels−Alder Reaction between Cyclopentadiene and 3-Phenyl-1-(2-pyridyl)-2-propen-1-one − Role of the Zn2+ Lewis Acid Catalyst and Water Solvent

Abstract

The molecular mechanism of the Diels−Alder reaction between cyclopentadiene (1) and 3-phenyl-1-(2-pyridyl)-2-propen-1-one (2) in the absence and in the presence of a Zn 2+ Lewis acid catalyst has been studied by quantum mechanical calculations at the B3LYP/6-31G* level of theory. A continuum model was selected to represent the effects of the water as solvent. For the uncatalyzed process, two channels, endo and exo, were characterized, and the mechanism corresponded to an asynchronous concerted reaction associated with a [4+2] process. The presence of a Lewis acid catalyst changed the mechanism drastically, the reaction taking place

Synthesis, X-ray crystal structure and theoretical calculations of antileishmanial neolignan analogues

“…Recently, we successfully used three-dimensional MEP surfaces to define the most probable sites of protonation of dipyridamole 66 , aparisthman, 67 cordatin, 8-epicordatin; 68 on the study of the molecular mechanisms the Diels-Alder reaction 69 and to get some clues about the transition state of the catalyzed reaction. 40 The MEP surfaces of compound 1 (active) and compound 14 (inactive) in terms of total electron density show that the lowest electronic potential is in the proximity of oxygen atoms of the carbonyl (O1), and oxygen heteroatom (Figure 8).…”

Synthesis, X-ray crystal structure and theoretical calculations of antileishmanial neolignan analogues

“…Recently, we successfully used three-dimensional MEP surfaces to define the most probable sites of protonation of dipyridamole 66 , aparisthman, 67 cordatin, 8-epicordatin; 68 on the study of the molecular mechanisms the Diels-Alder reaction 69 and to get some clues about the transition state of the catalyzed reaction. 40 The MEP surfaces of compound 1 (active) and compound 14 (inactive) in terms of total electron density show that the lowest electronic potential is in the proximity of oxygen atoms of the carbonyl (O1), and oxygen heteroatom (Figure 8).…”

Lewis Acid Catalyzed Reactions of Chiral Imidazolidinones and Oxazolidinones: Insights on the Role of the Catalyst

“…An interesting result from Cardillo was obtained with ZnCl 2 as LA, a compound that is supposed to easily form neutral chelates . While our theoretical values indeed indicate that this LA should form chelated complexes with compound 3 (Figure ), Cardillo’s results indicate that ZnCl 2 induces no selectivity (Table ).…”

On the method-dependence of transition state asynchronicity in Diels–Alder reactions

“…B3LYP is however not by far the most deviant method compared to CCSD. Bearing in mind that the Diels-Alder reaction mechanism is thought to transit continuously 13,21 from concerted synchronous to a polar asynchronous, and in some cases a stepwise mechanism with increasing activation, 14,22 the results presented here suggest that predictions about such mechanistic distinctions should be made carefully. Perhaps the safest recommendation that can be made from this study is that one should use more than one method for geometry optimizations to obtain a consensus description of the reaction.…”

Synthesis, X-ray crystal structure and theoretical calculations of antileishmanial neolignan analogues

“…Recently, we successfully used three-dimensional MEP surfaces to define the most probable sites of protonation of dipyridamole 66 , aparisthman, 67 cordatin, 8-epicordatin; 68 on the study of the molecular mechanisms the Diels-Alder reaction 69 and to get some clues about the transition state of the catalyzed reaction. 40 The MEP surfaces of compound 1 (active) and compound 14 (inactive) in terms of total electron density show that the lowest electronic potential is in the proximity of oxygen atoms of the carbonyl (O1), and oxygen heteroatom (Figure 8).…”

Lewis Acid Catalyzed Reactions of Chiral Imidazolidinones and Oxazolidinones: Insights on the Role of the Catalyst

“…An interesting result from Cardillo was obtained with ZnCl 2 as LA, a compound that is supposed to easily form neutral chelates . While our theoretical values indeed indicate that this LA should form chelated complexes with compound 3 (Figure ), Cardillo’s results indicate that ZnCl 2 induces no selectivity (Table ).…”

On the method-dependence of transition state asynchronicity in Diels–Alder reactions

“…B3LYP is however not by far the most deviant method compared to CCSD. Bearing in mind that the Diels-Alder reaction mechanism is thought to transit continuously 13,21 from concerted synchronous to a polar asynchronous, and in some cases a stepwise mechanism with increasing activation, 14,22 the results presented here suggest that predictions about such mechanistic distinctions should be made carefully. Perhaps the safest recommendation that can be made from this study is that one should use more than one method for geometry optimizations to obtain a consensus description of the reaction.…”

Synthesis, X-ray crystal structure and theoretical calculations of antileishmanial neolignan analogues

“…Recently, we successfully used three-dimensional MEP surfaces to define the most probable sites of protonation of dipyridamole 66 , aparisthman, 67 cordatin, 8-epicordatin; 68 on the study of the molecular mechanisms the Diels-Alder reaction 69 and to get some clues about the transition state of the catalyzed reaction. 40 The MEP surfaces of compound 1 (active) and compound 14 (inactive) in terms of total electron density show that the lowest electronic potential is in the proximity of oxygen atoms of the carbonyl (O1), and oxygen heteroatom (Figure 8).…”

Lewis Acid Catalyzed Reactions of Chiral Imidazolidinones and Oxazolidinones: Insights on the Role of the Catalyst

“…An interesting result from Cardillo was obtained with ZnCl 2 as LA, a compound that is supposed to easily form neutral chelates . While our theoretical values indeed indicate that this LA should form chelated complexes with compound 3 (Figure ), Cardillo’s results indicate that ZnCl 2 induces no selectivity (Table ).…”

On the method-dependence of transition state asynchronicity in Diels–Alder reactions

“…B3LYP is however not by far the most deviant method compared to CCSD. Bearing in mind that the Diels-Alder reaction mechanism is thought to transit continuously 13,21 from concerted synchronous to a polar asynchronous, and in some cases a stepwise mechanism with increasing activation, 14,22 the results presented here suggest that predictions about such mechanistic distinctions should be made carefully. Perhaps the safest recommendation that can be made from this study is that one should use more than one method for geometry optimizations to obtain a consensus description of the reaction.…”