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

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

Research output: Contribution to journalArticle

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 S N2 displacement (reductive elimination), and this is shown to be substrate-dependent.

Original languageEnglish
Pages (from-to)15605-15613
Number of pages9
JournalJournal of Organic Chemistry
Volume84
Issue number23
Early online date1 Nov 2019
DOIs
Publication statusPublished - 6 Dec 2019

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Cyclization
Iodine
Catalysis
Reaction rates
Substrates
Discrete Fourier transforms
Activation energy
Ligands
Oxidation

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title = "Computationally Assisted Mechanistic Investigation into Hypervalent Iodine Catalysis: Cyclization of N-Allylbenzamide",
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 S N2 displacement (reductive elimination), and this is shown to be substrate-dependent.",
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Computationally Assisted Mechanistic Investigation into Hypervalent Iodine Catalysis : Cyclization of N-Allylbenzamide. / Butt, Smaher; Das, Mirdyul; Sotiropoulos, Jean-Marc; Moran, Wesley.

In: Journal of Organic Chemistry, Vol. 84, No. 23, 06.12.2019, p. 15605-15613.

Research output: Contribution to journalArticle

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T2 - Cyclization of N-Allylbenzamide

AU - Butt, Smaher

AU - Das, Mirdyul

AU - Sotiropoulos, Jean-Marc

AU - Moran, Wesley

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