Fluorine substituent effect on the stereochemistry of catalyzed and non-catalyzed Diels–Alder reactions. The case of R-butenone with cyclopentadiene: a computational assessment of the mechanism

Abstract

The present work studies theoretically the mechanisms involved in the fluorine substituent effect on the stereochemistry of Diels-Alder reactions. The case of R-butenone with cyclopentadiene is used for the purpose of modelling more general α-fluoro-α,β-unsaturated carbonyl compounds, in catalyzed and uncatalyzed cases. A thorough analysis of the mechanism is performed using energy decomposition analysis (EDA) and conceptual DFT tools. It is shown that the endo conformation is privileged in all the studied cases with the exception of the α-fluorinated ketone. It is found that the endo selectivity of the non-fluorinated reactions is only due to the decrease of dispersion energy. On the other hand, the presence of a fluorine atom in the dienophile moieties increases remarkably the magnitude not only of the interaction energy between the reactants but that of the strain energy as well. Moreover, it is the strong destabilization strain energy occurring at the transition state of the endo pathway of the reaction cyclopentadiene/3-fluorobutenone that is mainly responsible for the exo selectivity. The effect of a Lewis acid catalyst on these reactions is also studied. The Lewis acid catalyst affects the activation energy of the studied Diels-Alder reactions but not their stereoselectivity. Furthermore, the dual descriptor results shed light onto the mechanism. Besides, natural bond orbital analysis (NBO) and determination of the condensed values of the state-specific dual descriptors (SSDD) are carried out to evaluate the donor-acceptor properties in these reactions. For the first time, a semiquantitative prediction of stereoselectivity due to substitutions of dienophile is obtained, thus complementing the previous interpretations (R. Hoffmann and R. B. Woodward, J. Am. Chem. Soc., 1965, 87, 4388; I. Fernández and F. M. Bickelhaupt, Chem. Soc. Rev., 2014, 43, 4953). Finally, since the role of dispersion forces is evidenced in some cases, a comparison between some popular exchange-correlation functionals is presented, assessing the performance of some standard functionals besides functionals with explicit dispersion corrections.

A computational investigation of the selectivity and mechanism of the Lewis acid catalyzed oxa‐Diels–Alder cycloaddition of substituted diene with benzaldehyde

“…In a previous study, 56 it was determined that the dispersion energy plays an important role in Diels–Alder reactions selectivity. Thus, the dispersion energy incidence on these reactions kinetics is evaluated by comparing the relative energies of the four TS optimized with the ωB97XD functional (which explicitly includes some dispersion) with the ones optimized with MPWB1K.…”

“…To uncover the effect of solvent‐solute interactions along the reaction process, further calculations have also been performed considering tetrachloromethane as solvent. Indeed, several previous studies devoted to polar [4 + 2] reactions have indicated that the inclusion of solvent effects on geometry optimization produces only minor changes in comparison with that of gas‐phase 55,56 . The total energies of the first step in tetrachloromethaneare given in Table S9, whereas relative ones are given in red in Scheme 5.…”

“…Indeed, several previous studies devoted to polar [4 + 2] reactions have indicated that the inclusion of solvent effects on geometry optimization produces only minor changes in comparison with that of gas-phase. 55,56 The total energies of the first step in tetrachloromethaneare given in Table S9, whereas relative ones are given in red in Scheme 5.…”

Does the gradient‐regulated connection improve the description of correlated metal bond properties?

“…It fast delivers energies computed from densities self‐consistently optimized with the PBE exchange‐correlation potential. As previously discussed by some of us, this alternative protocol may induce a performance deterioration more or less important depending on the number of empirical parameters. Energies reported here may thus differ somewhat from results reported in literature.…”

Understanding the intermolecular Diels–Alder cycloaddition promotion: Activation strain model/energy decomposition analysis model and conceptual density functional theory viewpoints

“…The ASM 31 of reactivity is a powerful method contributing to the current understanding of chemical transformations. A wide range of S C H E M E 1 The Diels-Alder reaction between 2-bromocyclobutenone and 1,3-R-butadiene (Dn-1 to Dn-10) reactions and processes such as endo/exo stereoselectivity, 32 transition metal-mediated reactions, cycloaddition reactions and biological processes were studied. 13,[33][34][35][36][37][38][39][40][41][42][43] The ASM, 44 also called distortion/interaction model has been introduced by Houk et al 11,[44][45][46] This is a systematic extension of fragment approach from equilibrium structures to transition states including the nonstationary points lying along a reaction path.…”