Chemo-, regio-, and stereoselective tetrafunctionalization of fluoroalkynes enables divergent synthesis of 5-7-membered azacycles
Jiawei Chen, Wenjun Ji, Xueying Huang, Danhua Ge, Zhi‐Liang Shen, Kai Guo, Xue‐Qiang Chu
Abstract
)-1,2-difluorovinyl azacycles. The use of the fluorine atom as a detachable "activator" not only obviates the use of any transition metal catalysts and oxidizing reagents, but also ensures the [3-5 + 2]-annulation and defluorinative functionalization of fluoroalkynes with high chemo-, regio-, and stereoselectivities. This method exhibits a broad substrate scope, good functional group tolerance, and excellent scalability, providing a modular platform for accessing fluorinated skeletons of medicinal and biological interest. The late-stage modification of complex molecules, the multi-component 1,2-diamination of fluoroalkyne, and the synthesis of valuable organofluorides from the obtained products further highlight the real-world utility of this fluoroalkyne annulation technology.