Enantioselective Organocatalyzed Oxa-Michael-Aldol Cascade Reactions: Construction of Chiral 4H-Chromenes with a Trifluoromethylated Tetrasubstituted Carbon Stereocenter

• Published in: Advanced synthesis & catalysis Vol. 357; no. 5; pp. 967 - 973
• Main Authors: Zhang, Jing, Ajitha, Manjaly J., He, Lin, Liu, Kai, Dai, Bin, Huang, Kuo-Wei
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 23.03.2015; WILEY‐VCH Verlag; Wiley
• Subjects: 4H-chromenes; Activation; Amines; Asymmetry; Bearing; Carbon; cascade reaction; Cascades; Catalysis; Chemistry; Chemistry, Applied; Chemistry, Organic; iminium-allenamine activation; Maintenance; organocatalysis; Physical Sciences; Science & Technology; Synthesis; trifluoromethylated tetrasubstituted carbon center; ASYMMETRIC-SYNTHESIS; PRIVILEGED STRUCTURES; cascade reaction; ONE-POT SYNTHESIS; COMBINATORIAL LIBRARIES; 4H-chromenes; QUATERNARY STEREOCENTERS; organocatalysis; MEDICINAL CHEMISTRY; KETONES; trifluoromethylated tetrasubstituted carbon center; iminium-allenamine activation; FACILE CONSTRUCTION; DENSELY FUNCTIONALIZED 4H-CHROMENES; FLUORINE
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201400977

The first organocatalytic asymmetric synthesis of 4H‐chromenes bearing a trifluoromethylated tetrasubstituted carbon center is presented. Chiral secondary amines promote the oxa‐Michael–aldol cascade reaction between alkynals and 2‐trifluoroacetylphenols via iminium–allenamine activation to produce pharmaceutically important heterocycles with excellent enantioselectivities. The proposed reaction can be scaled‐up easily with maintenance of the excellent enantioselectivity.