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

Abstract

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.