Citation: Xiangwei Chen, Yunyun Liu, Jie-Ping Wan. Disclosing α-trichloromethyl ketone—secondary amine combination as peptide coupling reagent based on the three-component access to β-acyloxyl alkenyl amides[J]. Chinese Chemical Letters, ;2026, 37(12): 112469. doi: 10.1016/j.cclet.2026.112469 shu

Disclosing α-trichloromethyl ketone—secondary amine combination as peptide coupling reagent based on the three-component access to β-acyloxyl alkenyl amides

Xiangwei Chen ^a ,
Yunyun Liu ^{a, *,} ,
Jie-Ping Wan ^{a, b, *,}

a.
Jiangxi Province Key Laboratory of Natural and Biomimetic Drugs Research, College of Chemistry and Materials, Jiangxi Normal University, Nanchang 330022, China
b.
International Innovation Center for Forest Chemicals and Materials, Nanjing Forestry University, Nanjing 210037, China

chemliuyunyun@jxnu.edu.cn

wanjieping@jxnu.edu.cn

Received Date: 11 November 2025
Revised Date: 16 January 2026
Accepted Date: 27 January 2026
Available Online: 28 January 2026

Figures(5)

The direct three-component reactions of carboxylic/amino acids, secondary amines and α-trichloromethyl ketone for the direct synthesis of β-acyloxyl alkenyl amides (AAAs) has been realized simply with the promotion of Cs₂CO₃ under mild conditions. As activated form of carboxylic and amino acids, the AAAs have been verified with excellent performance in the synthesis of di- to tetra peptides under mild and catalyst-/promoter-free conditions without confronting evident racemization or epimerization. The three-component protocol breaks the previous method relying on multi-step linear synthesis involving highly sensitive intermediate, showing amazingly high step efficiency by offering one-step access to these activated acid esters in fashion of target-oriented synthesis, delivering the discovery of simple α-trichloromethyl ketone—secondary amine combination as new coupling reagent for peptide synthesis
- Three-component reaction,
- α-Trichloromethyl ketone,
- Secondary amine,
- β-Acyloxyl alkenyl amides,
- Peptide,
- Coupling reagent
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