Organocatalytic Enantioselective Construction of Chiral Azepine Skeleton Bearing Multiple-Stereogenic Elements
Shengli Huang
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorHaojun Wen
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorYuhong Tian
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorPengfei Wang
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorWenling Qin
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Dr. Hailong Yan
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorShengli Huang
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorHaojun Wen
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorYuhong Tian
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorPengfei Wang
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorWenling Qin
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Dr. Hailong Yan
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorGraphical Abstract
An organocatalytic enantioselective method for the preparation of polychiral molecules via vinylidene ortho-quinone methide (VQM)-mediated intramolecular electrophilic aromatic substitution was developed. With this methodology, four types of stereogenic elements including chiral nitrogen center, C−N axial chirality, C−C axial chirality and conformational behavior of the seven-membered ring were stereoselectively constructed.
Abstract
Enantioselective construction of molecules bearing multiple stereogenic elements is increasingly related to the synthesis of enantiopure natural products, pharmaceuticals, and functional materials. However, atom-economical and enantioselective approaches to install multiple stereogenic elements in a small molecular template by limited chemical transformation remain challenging. We describe an organocatalytic enantioselective method for the preparation of polychiral molecules bearing four types of stereogenic elements in fused azepines via vinylidene ortho-quinone methide (VQM)-mediated intramolecular electrophilic aromatic substitution. This method was proved robust with a wide range of substrate scope (46–92 % yield), with excellent diastereoselectivity (>20:1 dr) and enantioselectivity achieved (up to 97 % ee). Optical properties and Ru3+-induced fluorescence responses of these compounds suggest their potential applications in optoelectronic materials and heavy metal ion detection.
Conflict of interest
The authors declare no conflict of interest.
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