Ting Wang1, Yu Zhou1,2, Yao Xu1,2, Gui-Juan Cheng3. 1. Warshel Institute for Computational Biology, Shenzhen Key Laboratory of Steroid Drug Development, School of Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), Shenzhen, 518172, China. 2. School of Life Sciences, University of Science and Technology of China, Hefei, 230027, Anhui, China. 3. Warshel Institute for Computational Biology, Shenzhen Key Laboratory of Steroid Drug Development, School of Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), Shenzhen, 518172, China. chengguijuan@cuhk.edu.cn.
Abstract
Selective oxidation is one of the most important and challenging transformations in both academic research and chemical industry. Recently, a highly selective and efficient way to synthesize biologically active γ-hydroxy-α,β-unsaturated molecules from Cu-catalyzed vinylogous aerobic oxidation of α,β- and β,γ-unsaturated compounds has been developed. However, the detailed reaction mechanism remains elusive. Herein, we report a density functional theory study on this Cu-catalyzed vinylogous aerobic oxidation of γ,γ-disubstituted α,β- and β,γ-unsaturated isomers. Our computational study unveils detailed mechanism for each elementary step, i.e. deprotonation, O2 activation, and reduction. Besides, the origin of regioselectivity, divergent reactivities of substrates as well as reducing agents, and the byproduct generation have also been investigated. Notably, the copper catalyst retains the + 2 oxidation state through the whole catalytic cycle and plays essential roles in multiple steps. These findings would provide hints on mechanistic studies and future development of transition metal-catalyzed aerobic oxidation reactions.
Selective oxidation is one of the most important and challenging transformations in both academic research and chemical industry. Recently, a highly selective and efficient way to synthesize biologically active γ-hydroxy-α,β-unsaturated molepan class="Chemical">cules from Cu-catalyzed vinylogous aerobic oxidation of α,β- and β,γ-unsaturated compounds has been developed. However, the detailed reaction mechanism remains elusive. Herein, we report a density functional theory study on this Cu-catalyzed vinylogous aerobic oxidation of γ,γ-disubstituted α,β- and β,γ-unsaturated isomers. Our computational study unveils detailed mechanism for each elementary step, i.e. deprotonation, O2 activation, and reduction. Besides, the origin of regioselectivity, divergent reactivities of substrates as well as reducing agents, and the byproduct generation have also been investigated. Notably, the copper catalyst retains the + 2 oxidation state through the whole catalytic cycle and plays essential roles in multiple steps. These findings would provide hints on mechanistic studies and future development of transition metal-catalyzed aerobic oxidation reactions.