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

Author:

Sun Mei1ORCID,Mao Nong-Qi2,Wang Sheng-Long2,Han Xin-Ming2,Yao Gang2,Xue Ping2,Zeng Chong-Yang1,Liu Yu-Ting1,Chen Kai1,Gao Xiao-Qing1,Xiong Jun2

Affiliation:

1. Anhui Key Laboratory of Low Temperature Co-Fired Materials, School of Chemistry and Material Engineering, Huainan Normal University, Huainan 232038, China

2. School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China

Abstract

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.

Funder

Hubei Provincial Natural Science Foundation of China

Science and Technology Plan Project of Huainan City

Doctoral Foundation of Huainan Normal University

Medical Research Project of Hubei University of Science and Technology

Hubei University of Science and Technology Doctoral Research Initiation Project

Innovation and Entrepreneurship training Program for College students of Hubei University of Science and Technology

Publisher

MDPI AG

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