Unveiling the Lewis Acid Catalyzed Diels-Alder Reactions Through the Molecular Electron Density Theory.

Luis R Domingo,Patricia Pérez,Mar Ríos-Gutiérrez,Mar Ríos-Gutiérrez

doi:10.3390/molecules25112535

Abstract

The effects of metal-based Lewis acid (LA) catalysts on the reaction rate and regioselectivity in polar Diels–Alder (P-DA) reactions has been analyzed within the molecular electron density theory (MEDT). A clear linear correlation between the reduction of the activation energies and the increase of the polar character of the reactions measured by analysis of the global electron density transfer at the corresponding transition state structures (TS) is found, a behavior easily predictable by analysis of the electrophilicity ω and nucleophilicity N indices of the reagents. The presence of a strong electron-releasing group in the diene changes the mechanism of these P-DA reactions from a two-stage one-step to a two-step one via formation of a zwitterionic intermediate. However, this change in the reaction mechanism does not have any chemical relevance. This MEDT study makes it possible to establish that the more favorable nucleophilic/electrophilic interactions taking place at the TSs of LA catalyzed P-DA reactions are responsible for the high acceleration and complete regioselectivity experimentally observed.

Highlights

All TSs correspond to high asynchronous single bond formation processes; iii) an increase of the C1−C6 distance is observed with the increase of the electrophilic character of the Lewis acid (LA) complex; iv) the endo TSs are slightly more advance and more asynchronous than the exo TSs; v) the C1−C6 distances is slightly shorter at the endo TSs than at the exo ones
The role of the metal-based LA catalysts on the Polar DA (P-DA) reactions of a series of substituted Cps of increased nucleophilicity towards acrolein 7 has been analyzed within Molecular Electron Density Theory [10] (MEDT) using DFT calculations at the B3LYP/6-311G(d,p) computational level
Analysis of the electrophilicity ω index of the corresponding LA complexes shows that there is a relationship between the increase of the electrophilic character of the LA complex and the acidic character of the LA salts

Summary

Study of the P-DA Reactions Between Cp 1 and the Series of LA Complexes

In oorrddeerrtotoshsehdedliglihgthotnotnhethroeleroolfethoef LthAecLatAalycastsaloynsttsheonDAthreeaDcAtiornesabcetitownesenbeCtwp e1eanndCpac1roalenidn 7a,crtohleeiPn-D7,AthreaPct-iDoAnsroefacCtipon1saonfdCfipve saenledctfeidveLsAeleccotmedplLexAescoomf ipnlcerxeeasseodf ienleccretraospedhileilcecthraorpahcitleicr wchearreafictresrt wsteurdeifeidrs(tsseteudTiaebdle(s1e)e. All TSs correspond to high asynchronous single bond formation processes; iii) an increase of the C1−C6 distance is observed with the increase of the electrophilic character of the LA complex; iv) the endo TSs are slightly more advance and more asynchronous than the exo TSs; v) the C1−C6 distances is slightly shorter at the endo TSs than at the exo ones This behaviour is a consequence of the most favorable electrostatic interactions appearing in the zwitterionic endo TSs than at the exo ones; and vi) in spite of the high asynchronous character of TSn-AlCl3, intrinsic reaction coordinate (IRC) analysis of this TS indicates that it is associates to a one-step mechanism. The slope of the linear correlation, −46.8 (not shown in Figure 6), can be associated with the extent of activation energy decrease in these P-DA reactions with the increase of the GEDT taking place at the TS

Study of the P-DA Reactions Between Substituted Cps 12–14 and Complex 7-BF3

Thermodynamic Analysis of the P-DA Reactions Between Cp 13 and Complex 7-BF3

Conclusions

Computational Methods