One-Step Construction of 1,3,4-Oxadiazoles with Anticancer Activity from Tertiary Amines via a Sequential Copper(I)-Catalyzed Oxidative Ugi/aza-Wittig Reaction
Mei Sun,
Nong-Qi Mao,
Sheng-Long Wang,
Xin-Ming Han,
Gang Yao,
Ping Xue,
Chong-Yang Zeng,
Yu-Ting Liu,
Kai Chen,
Xiao-Qing Gao,
Jun Xiong
Affiliations
Mei Sun
Anhui Key Laboratory of Low Temperature Co-Fired Materials, School of Chemistry and Material Engineering, Huainan Normal University, Huainan 232038, China
Nong-Qi Mao
School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Sheng-Long Wang
School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Xin-Ming Han
School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Gang Yao
School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Ping Xue
School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Chong-Yang Zeng
Anhui Key Laboratory of Low Temperature Co-Fired Materials, School of Chemistry and Material Engineering, Huainan Normal University, Huainan 232038, China
Yu-Ting Liu
Anhui Key Laboratory of Low Temperature Co-Fired Materials, School of Chemistry and Material Engineering, Huainan Normal University, Huainan 232038, China
Kai Chen
Anhui Key Laboratory of Low Temperature Co-Fired Materials, School of Chemistry and Material Engineering, Huainan Normal University, Huainan 232038, China
Xiao-Qing Gao
Anhui Key Laboratory of Low Temperature Co-Fired Materials, School of Chemistry and Material Engineering, Huainan Normal University, Huainan 232038, China
Jun Xiong
School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
An unparalleled copper(I)-catalyzed synthesis of 1,3,4-oxadiazoles from tertiary amines in one step has been described. The one-pot reactions involving (N-isocyanimine)triphenylphosphorane, tertiary amines, and carboxylic acids resulted in the formation of 1,3,4-oxadiazoles in moderate to good yields through a consecutive oxidative Ugi/aza-Wittig reaction, enabling the direct functionalization of sp3 C-H bonds adjacent to the nitrogen atom. This method offered several notable advantages, including ligands-free, exceptional productivity and a high functional group tolerance. The preliminary biological evaluation demonstrated that compound 4f inhibited hepatoma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.
