Nan Lu*, Chengxia Miao and Xiaozheng Lan

College of Chemistry and Material Science, Shandong Agricultural University, Taian City, P.R. China

*Corresponding Author: Nan Lu, College of Chemistry and Material Science, Shandong Agricultural University, Taian City, P.R. China.

Received: February 26, 2024; Published: March 08, 2024

Abstract

The mechanism is investigated for [3 + 3] annulation of cinnamaldehyde with 5-aminopyrazole catalyzed by N-heterocyclic carbene (NHC) leading to pyrazolo[3,4-b]pyridone. The enal is attacked by NHC generating Breslow intermediate, the oxidation of which gives α,β-unsaturated acyazolium. After donating amino H, the 1,4-addition of 5-aminopyrazole is rate-limiting step. The enantioselectivity is determined by the attack to less hindered face of NHC-enal complex. Once NHC is departed, the intramolecular lactamization readily occurs followed by tautomerization. The product with favored s isomer is cooperatively controlled both by thermodynamics and kinetics with recovered NHC catalyst. Although the 1,4-addition reaction path is reasonable and more easily, the 1,2-addition followed by an intramolecular Claisen rearrangement reaction path is also possible. The positive solvation effect is suggested by decreased absolute and activation energies in THF solution compared with in gas.

Keywords: [3 + 3] Annulation; Enantioselective; N-heterocyclic Carbene; 5-aminopyrazole; Enal

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Citation

Citation: Nan Lu., et al. “Theoretical Investigation on N-heterocyclic Carbene-Catalyzed Enantioselective [3 + 3] Annulation of Enal with 5-aminopyrazole for Construction of Pyrazolo[3,4-b]pyridone".Acta Scientific Pharmaceutical Sciences 8.4 (2024): 43-52.

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Copyright: © 2024 Nan Lu., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.