Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 23;60(35):19123-19127.
doi: 10.1002/anie.202104023. Epub 2021 Jul 20.

Chemoselective γ-Oxidation of β,γ-Unsaturated Amides with TEMPO

Sebastian Heindl  1 , Margaux Riomet  1 , Ján Matyasovsky  1 , Miran Lemmerer  1 , Nicolas Malzer  1 , Nuno Maulide  1
Affiliations

Chemoselective γ-Oxidation of β,γ-Unsaturated Amides with TEMPO

Sebastian Heindl et al. Angew Chem Int Ed Engl. .

Abstract

A chemoselective and robust protocol for the γ-oxidation of β,γ-unsaturated amides is reported. In this method, electrophilic amide activation, in a rare application to unsaturated amides, enables a regioselective reaction with TEMPO resulting in the title products. Radical cyclisation reactions and oxidation of the synthesised products highlight the synthetic utility of the products obtained.

Keywords: amides; chemoselectivity; oxidation; radical reactions; regioselectivity.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
a,b) Strategies for γ‐oxidation of β,γ‐unsaturated amides. c) Proposed approach and the challenge of using unsaturated amides in electrophilic activation.
Scheme 2
Scheme 2
Optimised γ‐aminoxylation of unsaturated amides.
Scheme 3
Scheme 3
Scope of the γ‐oxidation of unsaturated amides. [a] The reaction was conducted at 40 °C for 4 hours.
Scheme 4
Scheme 4
a) Oxidation and synthesis of a bioactive compound out of a γ‐OTMP α,β‐unsaturated amide. b) Thermal 5‐exo‐trig radical cyclisations of γ‐OTMP α,β‐unsaturated amides. c) Desaturation of the γ‐OTMP α,β‐unsaturated amide.
Scheme 5
Scheme 5
Proposed mechanism.
See this image and copyright information in PMC

References

    1. Kaiser D., Bauer A., Lemmerer M., Maulide N., Chem. Soc. Rev. 2018, 47, 7899–7925. - PubMed
    1. None
    1. Wallach O., Justus Liebigs Ann. Chem. 1877, 184, 1–127;
    1. Baum J. S., Viehe H. G., J. Org. Chem. 1976, 41, 183–187.
    1. Falmagne J.-B., Escudero J., Taleb-Sahraoui S., Ghosez L., Angew. Chem. Int. Ed. Engl. 1981, 20, 879–880;
    2. Angew. Chem. 1981, 93, 926–931.

LinkOut - more resources