Chiral Brønsted Acid‐Mediated Enantioselective Organocatalytic Three‐Component Reaction for the Construction of Trifluoromethyl‐Containing Molecules

Advanced Synthesis and Catalysis - Tập 350 Số 10 - Trang 1457-1463 - 2008
Guangwu Zhang1, Lian Wang1, Jing Nie1, Jun‐An Ma2,3
1Department of Chemsitry, Tianjin University, Tianjin 300072, People's Republic of China, Fax: (+86)‐22‐2740‐3475
2Department of Chemsitry, Tianjin University, Tianjin 300072, People's Republic of China, Fax: (+86)-22-2740-3475
3State Key Laboratory of Elemento‐Organic Chemistry, Nankai University, Tianjin 300071, People's Republic of China

Tóm tắt

AbstractIn combination with the advantages of organocatalysis, we have developed a highly enantioselective Friedel–Crafts aminoalkylation of indoles with imines generated in situ from trifluoroacetaldehyde methyl hemiacetal and aniline. Novel chiral trifluoromethyl‐containing compounds were obtained in high yields with excellent enantioselectivities. This methodology was further extended to difluoroacetaldehyde methyl hemiacetal to demonstrate the broad scope of substrates.

Từ khóa


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A mixture of indole (43.8 mg 0.37 mmol) trifluoroacetaldehyde methyl hemiacetal (48.8 mg 0.37 mmol) Brønsted acid1h(0.025 mmol) and powdered 4 Å molecular sieves (50 mg) in toluene (1.0 mL) was stirred at room temperature for 96 h. No reaction occurred. When the reaction mixture was stirred at 80 °C for 72 h the hydroxyalkylated indole was obtained in 87% yield with a 3%eevalue.

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CCDC 672342 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centreviawww.ccdc.cam.ac.uk/data_request/cif.