Computationally Assisted Mechanistic Investigation into Hypervalent Iodine Catalysis: Cyclization of N-Allylbenzamide

Butt, Smaher; Das, Mirdyul; Sotiropoulos, Jean-Marc; Moran, Wesley

Abstract

Previous experimental work identified 2-iodoanisole as the best precatalyst for the oxidative cyclization of N-alkenylamides into 2-oxazolines. Herein, we describe our investigation into the effect on the reaction rate based on the structure of the iodoarene precatalyst. We also reveal the mechanism of the cyclization based on DFT modeling and obtain a clear correlation between observed reaction rates and computationally derived activation energies for different iodoarenes. In addition, the rate-limiting step is shown to be the cyclization of the substrate that is zero order in the concentration of the iodoarene precatalyst. The rate of cyclization is found to correlate with the ease of oxidation of the iodoarene; however, the most easily oxidized iodoarenes generate iodine(III) species that decompose readily. Finally, loss of iodoarene from the cyclized intermediate can proceed by either ligand-coupling or SN2 displacement (reductive elimination), and this is shown to be substrate-dependent.

Citation

Butt, S., Das, M., Sotiropoulos, J., & Moran, W. (2019). Computationally Assisted Mechanistic Investigation into Hypervalent Iodine Catalysis: Cyclization of N-Allylbenzamide. Journal of Organic Chemistry, 84(23), 15605–15613. https://doi.org/10.1021/acs.joc.9b02623

• Journal Article Type: Article
• Online Publication Date: Nov 1, 2019
• Publication Date: Dec 6, 2019
• Deposit Date: Mar 11, 2024
• Journal: The Journal of Organic Chemistry
• Print ISSN: 0022-3263
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 84
• Issue: 23
• Pages: 15605–15613
• DOI: https://doi.org/10.1021/acs.joc.9b02623
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.joc.9b02623