NHC-Catalyzed [2 + 4] Annulation of Alkynyl Ester with Chalcone
Fangfang Lu, Yangxu Chen, Xue Song, Chenxia Yu, Tuanjie Li*, Kai Zhang* and Changsheng Yao*
*School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P. R. China,
Email: ltj2008
jsnu.edu.cn, zhangkaijsnu.edu.cn,
csyaojsnu.edu.cn
F. Lu, Y. Chen, X. Song, C. Yu, T. Li, K. Zhang, C. Yao, J. Org. Chem., 2022, 87, 6902-6909.
DOI: 10.1021/acs.joc.2c00022
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Abstract
An NHC-catalyzed [2 + 4] cyclization of alkynyl ester with α,β-unsaturated ketone provides highly substituted 4H-pyran derivatives in gooy yields. This strategy offers cheap and easily available starting materials, mild reaction conditions, and high atom economy.
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proposed mechanism
Details
The document discusses the development of an NHC-catalyzed [2 + 4] cyclization of alkynyl ester with α,β-unsaturated ketone to form a pyran scaffold. This method uses inexpensive and readily available starting materials, operates under mild conditions, and achieves moderate to excellent yields with high atom economy, making it an attractive strategy for synthesizing highly substituted 4H-pyran derivatives. The study explores various NHC catalysts and reaction conditions, identifying tert-butyl-substituted imidazolium salt N4 and cesium carbonate in acetonitrile as optimal for achieving high yields. The substrate scope includes various chalcones and alkynyl esters, demonstrating broad applicability and good yields, although some substrates with strong electron-withdrawing groups or without γ-H did not react. The proposed mechanism involves NHC attacking the β-carbon of the alkynyl ester, followed by 1,4-addition with chalcone, isomerization, and subsequent addition and elimination to release the final product and regenerate the NHC catalyst. This work significantly expands the field of NHC catalysis and the chemistry of alkynyl esters, providing a new method for synthesizing 4H-pyran derivatives.
Key Words
ID: J42-Y2022
