Origin of the endo Selectivity in the Diels–Alder Reaction between Cyclopentadiene and Maleic Anhydride

Abstract

The Diels–Alder reactions of cyclopentadiene with maleic anhydride and with some other dienophile models in which the C=O bonds were replaced by less polarizable C=NH bonds and by C=CH2 bonds were studied theoretically. Comparison of interactions in these systems disclosed a key to understanding the high reactivity of maleic anhydride and the endo selectivity in the reaction. It is not orbital interactions that favor the endo addition, but the electrostatic attractions introduced by the presence of highly polarized C=O bonds. The bonds also play important roles in depressing the unfavorable growth of overlap repulsion by storing a large amount of π‐type electron populations outside the region of interactions and in strengthening electron delocalization by providing a positive charge field to the reaction sites of the dienophile.

Effect of an α‐Methyl Substituent on the Dienophile on Diels‐Alder endo:exo Selectivity

“…[11] In the case of methyl methacrylate (7 b) as dienophile, the ASDs show a higher stabilization of the exo-interaction curve due to the presence of the α-methyl substituent, similar to methacrylonitrile (6 b) case. However, our EDA calculations show that this higher stabilization is consequence of small differences in the electrostatic interactions [15] (Figure 4 D). Here, this higher interaction is capable to overcome the strain-penalty of the exo approach, thus prompting exo-cycloadduct formation.…”

“…Thus, dismounting the orbital interaction-based explanation for the endo rule. This same reaction was analyzed by Sakata et al [15] more recently. In this case, the authors propose that the electrostatic attractions derived from the presence of highly polarized CÀ O bonds are the responsible of the endopreference, and not the orbital interactions.…”

“…Thus, dismounting the orbital interaction‐based explanation for the endo rule. This same reaction was analyzed by Sakata et al . more recently.…”

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

“…The latter rule has been traditionally attributed to secondary orbital interactions (SOI) [78][79][80], although a controversy exists due to the lack of solid evidence for this hypothesis [81]. Consequently, a lot of research has been carried out to provide additional insights into the factors controlling the endo outcome [53,[82][83][84][85], documenting in some cases a key role of NCIs in the preferential stereocontrol [86].…”

Force constant decomposition for penta‐coordinated XH3Cl2‐(X = C, Si, Ge) structures

“…For E INT , many decomposition schemes have been proposed . Here, we simply decompose the INT term to the electrostatic attraction ( E ES ), the exchange (or overlap) repulsion ( E EX ), and the delocalization–polarization ( E D–P ) terms within the restricted Hartree‐Fock formalism: …”