Revisiting the stability of endo/exo Diels-Alder adducts between cyclopentadiene and 1,4-benzoquinone

Abstract

Neste trabalho é apresentada uma análise teórica detalhada da estabilidade relativa dos adutos endo/exo formados entre o ciclopentadieno (1) e a 1,4-benzoquinona (2). As coordenadas intrínsecas de reação (IRC) indicaram a presença de apenas um estado de transição para a reação, mostrando que se trata de um mecanismo concertado para ambos os adutos, endo 3 e exo 4. As energias dos adutos foram calculadas com um alto nível de teoria (CBS-Q) confirmando que o aduto endo é mais estável que o exo, o que está em desacordo com o que é observado para reações que usualmente seguem a regra de Alder. Uma análise estrutural eletrônica foi realizada através da metodologia NBO, a qual indicou que interações atrativas predominam sobre as interações estéricas repulsivas no aduto endo. Em resumo, para a reação de cicloadição estudada o aduto endo é o produto termodinâmico e cinético, o que pode ser confirmado também pelos dados experimentais mencionados neste trabalho.In this work it is presented a detailed theoretical analysis of the relative stability of endo/exo Diels-Alder adducts formed by the reaction between cyclopentadiene (1) and 1,4-benzoquinone (2). The intrinsic reaction coordinate (IRC) showed the existence of only one transition state for the reaction studied, for both endo 3 and exo 4 adducts. The energies of both adducts were obtained at high level of theory (CBS-Q) confirming that the endo adduct is more stable than exo, which is in the opposite way to the observed in reactions that usually follow Alder's rule. An electronic structure analysis was performed through NBO methodology, indicating that the attractive delocalization interaction predominates over the steric repulsive interaction in the endo adducts. In summary, for the studied cycloaddition reaction the endo adduct is the thermodynamic and kinetic product, which can be also confirmed by experimental data mentioned in this work.Keywords: Diels-Alder reaction, endo/exo stability, theoretical calculation, NBO analysis IntroductionThe Diels-Alder reaction is one of the most interesting and useful reactions found in organic chemistry in 20 th century. [1][2][3][4][5][6][7][8] This cycloaddition is widely used to construct, in a regio-and stereo-controlled way, a six-membered ring with up to four stereogenic centers. 1-8 Historically, in 1906 Albrecht 9 published the reaction between the cyclopentadiene (1) and 1,4-benzoquinone (2) as a 1:1 adduct. However, Albrecht's considerations about the structure of the obtained adduct were inconsistent. After several studies, in 1928 Otto Diels and Kurt Alder, 10 established a correct structure for the mono-and bis-adducts formed by the reaction between these compounds through a [4+2] cycloaddition, in opposition to the reactional course suggested by Albrecht: an 1,4-addition of cyclopentadiene (1) into 1,4-benzoquinone (2). Since then, the Diels-Alder reaction has appeared in more than 32,000 papers involving synthetic and theoretical approaches. 11In general, Diels-Alder reactions are excellent reactional models ...

Recent advances in 1,4-benzoquinone chemistry

“…Tormena et al 229 carried out a detailed theoretical analysis of the relative stability of endo/exo Diels-Alder adducts formed by the reaction between cyclopentadiene and 1,4-benzoquinone. The energies of both endo and exo adducts were obtained at CBS-Q level of theory, which showed that endo adduct is more stable than exo.…”

“…Trauner and colleges 317 demonstrated the viability of vinyl quinones in Diels-Alder reactions. They utilized this strategy to synthesize medicinally significant (-)-halenaquinone (229 Kang et al 320 studied a specific Diels-Alder reaction of 1,4-benzoquinone (1) with a thiophene dioxide derivative (213) catalyzed by a self assembled molecular capsule (Scheme 62).…”

Chlorin Photosensitizers Sterically Designed To Prevent Self-Aggregation

“…In this work, the Diels–Alder reaction between protoporphyrin IX dimethyl ester and substituted maleimides is described. Maleimide dienophiles have been utilized in order to induce endo addition by secondary orbital stabilization. Compared to the other antiaggregation strategies we have proposed, these new photosensitizers have a bulkier substituent and a smaller photosensitizer core, allowing the synthesis of new chlorin molecules that have a nonplanar and rigid “L”-type shape, which completely prevents aggregation, even at high concentrations (10 –2 mol L –1 ).…”

Origins of stereoselectivity in uncatalyzed and ZnBr2-catalyzed Diels–Alder reactions of a chiral sulfinylquinone

“…They do not contribute significantly to the reaction. Previous calculations by de Oliveira et al 19 on the Diels-Alder reaction of cyclopentadiene with the parent 1,4-benzoquinone showed a kinetic endo selectivity amounting to ca. 2 kcal/mol.…”