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Synthesis 2025; 57(04): 812-819
DOI: 10.1055/a-2495-3296
paper

Inverse Electron-Demand Diels–Alder Reaction of Pyrazines with 2,5-Norbornadiene as Acetylene Precursor

Alexey P. Krinochkin
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
b   I. Ya. Postovskiy Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, 22 S. Kovalevskoy, 620219 Ekaterinburg, Russian Federation
,
Maria I. Valieva
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
b   I. Ya. Postovskiy Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, 22 S. Kovalevskoy, 620219 Ekaterinburg, Russian Federation
,
Ekaterina A. Kudryashova
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
,
Svetlana S. Potapova
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
b   I. Ya. Postovskiy Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, 22 S. Kovalevskoy, 620219 Ekaterinburg, Russian Federation
,
Anastasia P. Potapova
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
,
Ramil F. Fatykhov 
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
,
Igor A. Khalymbadzha  ∗
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
,
Ainur D. Sharapov
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
,
Dmitry S. Kopchuk
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
b   I. Ya. Postovskiy Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, 22 S. Kovalevskoy, 620219 Ekaterinburg, Russian Federation
,
Igor S. Kovalev
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
,
Victoria E. Petrova
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
,
Nikolai V. Krivoshchapov
c   N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prospect, 119991 Moscow, Russian Federation
,
Grigory V. Zyryanov
a   Ural Federal University, Mira 19, 620002 Ekaterinburg, Russian Federation
› Author AffiliationsThis work was supported by the Russian Science Foundation (grant no. 23-73-10050, synthesis of compounds 1g–k, 3g–k, and 4g–j) and the Ministry of Education and Science of the Russian Federation within the state assignment (State Reg. No. 124020200072-0, synthesis of compounds 3a–d, 5, 6, 7, 1l–r, 3l,o,p).
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Abstract

The reaction of pyrazines with 2,5-norbornadiene, an acetylene precursor, as a cascade of Diels–Alder reactions is reported yielding substituted pyridines. In contrast to the known examples of intermolecular Diels–Alder type reaction of pyrazines with acetylene, which usually leads to a mixture of products, in our case the formation of a single isomer was observed. The proposed approach allows the conversion of pyrazines with different types of substitution, except those containing methyl and amino donor groups, to pyridines. In addition, highly functionalized aminonicotic esters were obtained, which can be used for the synthesis of bioactive compounds. An unusual course of the Diels–Alder reaction was found in the case of tetrasubstituted pyrazines, which cleave organic nitriles instead of HCN. Quantum-chemical modeling of possible transition states showed that this Diels–Alder reaction proceeds via cycloaddition of 2,5-norbornadiene to pyrazine with sequential elimination of HCN and cyclopentadiene; the reaction pathway including initial formation of acetylene from norbornadiene and subsequent Diels–Alder reaction with the acetylene was rejected as kinetically unfavorable.

Key words

pyrazine - pyridine - inverse-electron-demand Diels–Alder reaction - 2,5-norbornadiene

Supporting Information



Publication History

Received: 23 September 2024

Accepted after revision: 03 December 2024

Accepted Manuscript online:
03 December 2024

Article published online:
14 January 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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