DFT study on the reaction mechanism and regioselectivity for the [1, 2]-anionic rearrangement of 2-benzyloxypyridine derivatives. Issue 33 (16th August 2019)

• Record Type: Journal Article
• Authors: Yang, Jingyue; Guo, Yingjie; Wang, Juhui; Dudley, Gregory B.; Sun, Keju
• Is Part Of: Tetrahedron. Volume 75:Issue 33(2019)
• Page Start: 4451
• Page End: 4457
• Publication Date: 2019-08-16
• Subjects: Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2019.06.018
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The reaction mechanism of the [1, 2]-anionic rearrangement of 2-benzyloxypyridines has been investigated using DFT calculations. Calculated results indicate that: the deprotonation step is relatively fast and the rearrangement step is the rate-determining step; electron-donating group on the benzene ring decreases the activation energy of the rearrangement, which correlates with an increase in reaction yield, while electron-withdrawing groups show the opposite effect. The rearrangement is calculated to proceed by way of an oxirane-like transition state that had previously been postulated as a transient intermediate. Furthermore, the mechanism for the rearrangement of 2-(benzyloxy)nicotinonitrile was discussed. The quick formation of the five membered ring intermediate leads to the predominant formation of 2-phenylfuro[2, 3- b ]pyridin-3-amine. The calculation results indicate the possibilities of derivatizing the starting pyridyl ether as well as facilitating the rearrangement reaction by adding an appropriate electron-donating group on the benzene ring or electron-withdrawing group on the pyridine ring for future studies. Graphical abstract: Image 1