Citation: Cong-Bin Ji, Ding-Xiong Xie, Mei Chen, Ye-Ying Lan, Bao-Hua Zhang, Ji-Ying Yang, Zheng-Hui Kang, Shu-Jie Chen, Yu-Wei Zhang, Yun-Lin Liu. Green synthesis of 2-trifluoromethylquinoline skeletons via organocatalytic N-[(α-trifluoromethyl)vinyl]isatins CN bond activation[J]. Chinese Chemical Letters, ;2025, 36(7): 110598. doi: 10.1016/j.cclet.2024.110598 shu

Green synthesis of 2-trifluoromethylquinoline skeletons via organocatalytic N-[(α-trifluoromethyl)vinyl]isatins CN bond activation

Cong-Bin Ji ^{a, 1} ,
Ding-Xiong Xie ^{b, 1} ,
Mei Chen ^{b, 1} ,
Ye-Ying Lan ^b ,
Bao-Hua Zhang ^b ,
Ji-Ying Yang ^f ,
Zheng-Hui Kang ^{g, *,} ,
Shu-Jie Chen ^b ,
Yu-Wei Zhang ^{b, c, *,} ,
Yun-Lin Liu ^{b, d, e, *,}

a.
School of Chemistry and Environmental Sciences, Shangrao Normal University, Shangrao 334001, China
b.
School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, China
c.
GDMPA Key Laboratory for Process Control and Quality Evaluation of Chiral Pharmaceuticals, Guangzhou Key Laboratory of Analytical Chemistry for Biomedicine, School of Chemistry, South China Normal University, Guangzhou 510006, China
d.
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
e.
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China
f.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
g.
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China

kangzhenghui@simm.ac.cn

ywzhang@scnu.edu.cn

ylliu@gzhu.edu.cn

Received Date: 29 July 2024
Revised Date: 24 October 2024
Accepted Date: 30 October 2024
Available Online: 3 November 2024

Figures(11)

The Pfitzinger reaction has long served as a notable synthesis pathway for quinoline-4-carboxylic acids. Although recognized for its synthetic potential since its discovery > 138 years ago, a truly catalytic variant has remained elusive until now. Herein, we present a novel 2–tert–butyl–1,1,3,3-tetramethylguanidine (BTMG)-catalyzed Pfitzinger reaction that employs N-[(α-trifluoromethyl)vinyl]isatins with amines and alcohols, providing direct routes to 2-CF₃-quinoline-4-carboxamides and carboxylic esters. This method is not only green and environmentally benign but also accommodates the introduction of other functional groups like CF₂H and CO₂Me at the C2 position of quinoline skeleton. The utility of this methodology was demonstrated by the broad substrate scope, the late-stage modification of commercial drugs, and the diverse derivatization of quinoline framework. More importantly, this work not only opens up a new avenue for the activation of amide CN bonds in catalytic reaction development, but also unlocks the huge potential of some 2-trifluoromethyl quinolines with strong inhibitory activity against PTP1B or optoelectronic application in organic light-emitting diodes.
- N-[(α-Trifluoromethyl)vinyl]isatins,
- Pfitzinger-type reaction,
- 2-CF₃-quinoline-4-carboxamide,
- C-N bond cleavage,
- 2-CF₃-quinoline-4-carboxylic ester
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