Issue 6, 2023

Coupling of α-bromoamides and unactivated alkenes to form γ-lactams through EDA and photocatalysis

Abstract

γ-Lactams are prevalent in small-molecule pharmaceuticals and provide useful precursors to highly substituted pyrrolidines. Despite numerous methods for the synthesis of this valuable motif, previous redox approaches to γ-lactam synthesis from α-haloamides and olefins require additional electron withdrawing functionality as well as N-aryl substitution to promote electrophilicity of the intermediate radical and prevent competitive O-nucleophilicity about the amide. Using α-bromo imides and α-olefins, our strategy enables the synthesis of monosubstituted protected γ-lactams in a formal [3 + 2] fashion. These species are poised for further derivatization into more complex heterocyclic scaffolds, complementing existing methods. C–Br bond scission occurs through two complementary approaches, the formation of an electron donor–acceptor complex between the bromoimide and a nitrogenous base which undergoes photoinduced electron transfer, or triplet sensitization with photocatalyst, to furnish an electrophilic carbon-centered radical. The addition of Lewis acids allows for further increased electrophilicity of the intermediate carbon-centered radical, enabling tertiary substituted α-Br-imides to be used as coupling partners as well as internal olefins.

Graphical abstract: Coupling of α-bromoamides and unactivated alkenes to form γ-lactams through EDA and photocatalysis

Supplementary files

Article information

Article type
Edge Article
Submitted
28 Oct 2022
Accepted
15 Jan 2023
First published
20 Jan 2023
This article is Open Access

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

Chem. Sci., 2023,14, 1569-1574

Coupling of α-bromoamides and unactivated alkenes to form γ-lactams through EDA and photocatalysis

S. M. Treacy, D. R. Vaz, S. Noman, C. Tard and T. Rovis, Chem. Sci., 2023, 14, 1569 DOI: 10.1039/D2SC05973H

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements