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 reaction rate based on the structure of the iodoarene precatalyst. We also reveal the mechanism of the cyclisation based on DFT modelling 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 which is zero order in the concentration of the iodoarene precatalyst. The rate of the 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.
Original languageEnglish
JournalJournal of Organic Chemistry
Early online date1 Nov 2019
DOIs
Publication statusE-pub ahead of print - 1 Nov 2019

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

Cite this

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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 reaction rate based on the structure of the iodoarene precatalyst. We also reveal the mechanism of the cyclisation based on DFT modelling 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 which is zero order in the concentration of the iodoarene precatalyst. The rate of the 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.",
author = "Smaher Butt and Mirdyul Das and Jean-Marc Sotiropoulos and Wesley Moran",
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month = "11",
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journal = "Journal of Organic Chemistry",
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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, 01.11.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Computationally Assisted Mechanistic Investigation into Hypervalent Iodine Catalysis

T2 - Cyclization of N-Allylbenzamide

AU - Butt, Smaher

AU - Das, Mirdyul

AU - Sotiropoulos, Jean-Marc

AU - Moran, Wesley

PY - 2019/11/1

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AB - 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 reaction rate based on the structure of the iodoarene precatalyst. We also reveal the mechanism of the cyclisation based on DFT modelling 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 which is zero order in the concentration of the iodoarene precatalyst. The rate of the 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.

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