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3-Trifluoromethyl Pyrrole Synthesis Based on β-CF3-1,3-Enynamides

Zongxiang Yu, Jintong Li, Yuxuan Cao, Tingwei Dong, Yuanjing Xiao*

*School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, P. R. China, Email: yjxiaochem.ecnu.edu.cn

Z. Yu, J. Li, Y. Cao, T. Dong, Y. Xiao, J. Org. Chem., 2023, 88, 15501-15506.

DOI: 10.1021/acs.joc.3c01790


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Abstract

The electrophilic nature of the double bond of β-CF3-1,3-enynamides enables an efficient, metal-free, and scalable preparation of 3-trifluoromethyl pyrroles using alkyl primary amines as strong nucleophiles. Evidence for a highly regioselective 1,4-hydroamination was observed after the isolation and characterization of an allenamide intermediate.


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Evidence of Activation by the CF3 Group and Confirmation of an Allenamide Intermediate



General procedures for the synthesis of pyrroles

β-CF3-1,3-enynamide (0.2 mmol, 1.0 equiv) and amine (0.4 mmol, 2.0 equiv) are added to a 10.0 mL sealed tube and finally add 2.0 mL of acetonitrile, the reaction was stirred at room temperature for 16-48 h. After β-CF3-1,3-enynamide was completely consumed, which was determined by TLC analysis, the solvent was removed under reduced pressure, and the crude reaction mixture was purified by flash column chromatography on silica gel to give the desired substituted pyrrole.


Key Words

pyrroles, β-CF3-1,3-enynamides


ID: J42-Y2023