Phosphinothio(seleno)ation of alkynes/olefins and application on the late-stage functionalization of natural products

Chang-Wei Shao; Pei-Feng Wan; Quan Xu; Ze-Nan Yang; Mei-Yu Geng; Yu Zhang; Xing-Hua Zhang; Xu-Wen Li

doi:10.1038/s42004-024-01326-9

Phosphinothio(seleno)ation of alkynes/olefins and application on the late-stage functionalization of natural products

Commun Chem. 2024 Dec 5;7(1):290. doi: 10.1038/s42004-024-01326-9.

Authors

Chang-Wei Shao^#^{1

2

3}, Pei-Feng Wan^#³, Quan Xu^#^{2

3}, Ze-Nan Yang^{2

3}, Mei-Yu Geng^{2

3}, Yu Zhang^{4

5}, Xing-Hua Zhang⁶, Xu-Wen Li^{7

8}

Affiliations

¹ School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, China.
² State Key Laboratory of Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhangjiang Hi-Tech Park, Shanghai, China.
³ Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, China.
⁴ State Key Laboratory of Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhangjiang Hi-Tech Park, Shanghai, China. [email protected].
⁵ Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, China. [email protected].
⁶ School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, China. [email protected].
⁷ State Key Laboratory of Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhangjiang Hi-Tech Park, Shanghai, China. [email protected].
⁸ Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, China. [email protected].

^# Contributed equally.

Abstract

Non-metallic catalysis has been known as a remarkable development strategy for hydrofunctionalization of unsaturated hydrocarbons. Herein, we report a unique chemically active method of BF₃·OEt₂ promoted multi-component, highly regioselective, and chemoselective hydrothio(seleo)phosphonylation of unsaturated hydrocarbons, which exhibits high yield and good substrate universality. The reaction mechanism was further elucidated to be Markovnikov addition by controlling experiments, ³¹P and ¹⁹F NMR spectra tracking experiments, X-ray diffraction analysis, and DFT calculations. Furthermore, the gram-scale attempt and the application of the reaction on the derivatization of natural products have been successfully conducted, leading to the discovery of 3as with potential anti-Parkinson's disease (PD) activities at 1 μM. This streamlined and efficient methodology has established a new platform for non-metallic Lewis acids-promoted hydrofunctionalization of unsaturated hydrocarbons and its application on new drug research.