Issue 39, 2018

The mechanism of the triple aryne–tetrazine reaction cascade: theory and experiment

Abstract

This article describes an experimental and computational investigation on the possible aryne reactivity modes in the course of the reaction of two highly energetic molecules, an aryne and a 1,2,4,5-tetrazine. Beyond the triple aryne–tetrazine (TAT) reaction, it was observed that combinations of several reactivity modes afford several heterocyclic compounds. Density Functional Theory (DFT) calculations of competition between a second Diels–Alder reaction and the nucleophilic addition pathways indicates the latter to be more favorable. Crossover experiments and computational study of the proton transfer step reveal that the reaction proceeds intermolecularly with the assistance of a water molecule, rather than intramolecularly. The resulting enamine intermediate was found to undergo either a stepwise formal [2 + 2] or [4 + 2] cycloaddition, and their energetic profiles were compared against each other. Isolation of an ene-product and a rearranged product shows the potential competition with oxidation/desaturation. These studies show how multiple arynes react with a highly reactive starting material and provide guidance for future applications of aryne-based multicomponent cascade reactions.

Graphical abstract: The mechanism of the triple aryne–tetrazine reaction cascade: theory and experiment

Supplementary files

Article information

Article type
Edge Article
Submitted
19 Apr 2018
Accepted
10 Aug 2018
First published
23 Aug 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2018,9, 7688-7693

The mechanism of the triple aryne–tetrazine reaction cascade: theory and experiment

S. Suh, S. Chen, K. N. Houk and D. M. Chenoweth, Chem. Sci., 2018, 9, 7688 DOI: 10.1039/C8SC01796D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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