Why Do Five-Membered Heterocyclic Compounds Sometimes Not Participate in Polar Diels–Alder Reactions?

Abstract

The reactions of bicyclic enone (BCE, 1) with cyclopentadiene (Cp, 2) and the five-membered heterocyclic compounds (FHCs) furan 3 and N-methyl pyrrole 4 for the construction of polycyclic heterocyclic compounds have been studied at the B3LYP/6-31G* level. No reaction takes place in the absence of Lewis acid (LA) catalysts as a consequence of the high activation energy associated with these reactions. Electrophilic activation of BCE 1 by formation of a complex with the BF3 LA, 1-BF3, and solvent effects favor the reactions. However, a different reactivity is manifested by Cp 2 and FHCs 3 and 4. Thus, while the reaction of 1-BF3 with Cp 2 yields the expected exo [4 + 2] cycloadduct, the reactions of these FHCs yield Michael adducts. In any case, the reactions are characterized by the nucleophilic/electrophilic interaction between the most nucleophilic centers of these dienes and the most electrophilic center of complex 1-BF3. The greater ability of FHCs 3 and 4 to stabilize positive charges opposed to Cp 2 favors a stepwise mechanism with formation of a zwitterionic intermediate. Although in most stepwise Diels-Alder reactions, the subsequent ring closure has unappreciable barriers, in these FHCs the abstraction of a proton with regeneration of the aromatic ring becomes competitive. Thermodynamic calculations suggest that the exergonic character of the formation of the Michael adducts could be the driving force for the reactions involving FHCs.

Does a fluorinated Lewis acid catalyst change the molecular mechanism of the decomposition process of nitroethyl carboxylates?

“…2]-cycloaddition reactions [29]. The decomposition process of nitroethyl carboxylates is carried out in dichloromethane environment, because it is a good solvent for LAs [26,27,30,31].…”

Understanding the Intramolecular Diels‐Alder Reactions of N‐Substituted N‐Allyl‐Furfurylamines: An MEDT Study

“…The activation enthalpy associated to this intermolecular DA via TSinter is 29.9 kcal mol −1 , the reaction being exothermic by only 0.6 kcal mol −1 . The high activation enthalpy associated to this DA reaction, which is considerably higher than that associated with the non‐polar DA reaction between cyclopentadiene 9 and ethylene 8 , 18.1 kcal mol −1 , is the consequence of the aromatic character of 2‐methylfuran 6 , which is lost along the reaction …”

Understanding the participation of 3-nitropyridine in polar Diels–Alder reactions. A DFT study

“…These reactions are exothermic by À18.8 kcal/mol. Some appealing conclusions can be obtained from these energy results: (i) this P-DA reaction presents a high activation energy, 24.4 kcal/mol, as a consequence of the aromatic character of 3-nitropyridine 1, which is lost along the cycloaddition reaction [23,24]; (ii) this P-DA reaction is para regioselective, TS-2-pn being 2.3 kcal/mol lower in energy than TS-2-mn; and (iii) the reaction is endo stereoselective, TS-2-pn being 1.9 kcal/mol lower in energy than TS-2-px.…”

“…In spite of this high polar character, the lost of aromaticity of the pyridine ring is responsible for the high activation energies found in these P-DA reactions [23,24].…”