Jump to main content
Jump to site search
SCHEDULED MAINTENANCE Close the message box

Maintenance work is planned for Monday 16 August 2021 from 07:00 to 23:59 (BST).

Website performance may be temporarily affected and you may not be able to access some PDFs or images. If this does happen, refreshing your web browser should resolve the issue. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 3, 2016

Discovery and mechanistic study of a photocatalytic indoline dehydrogenation for the synthesis of elbasvir

Author affiliations

Abstract

Elbasvir is a potent NS5A antagonist for the treatment of chronic hepatitis C. A seemingly trivial indoline oxidation en route to the target compound was complicated by epimerization of a stereogenic hemiaminal center under most standard oxidation conditions. To address this issue, a novel visible light photoredox process for indoline oxidation was developed involving an iridium photosensitizer and environmentally-benign perester oxidant. The reaction was discovered through a high-throughput experimentation campaign and the optimized process was demonstrated on 100 g scale in flow to afford a key intermediate towards the target compound. A battery of kinetic, electrochemical, and spectroscopic studies of this process indicates a radical chain mechanism of dehydrogenation involving selective HAT from the substrate by an alkoxy radicals. Notably, isotope effects were used to validate the chain mechanism when quantum yield data proved ambiguous.

Graphical abstract: Discovery and mechanistic study of a photocatalytic indoline dehydrogenation for the synthesis of elbasvir

Supplementary files

Article information


Submitted
05 Sep 2015
Accepted
27 Nov 2015
First published
07 Dec 2015

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2016,7, 2066-2073
Article type
Edge Article
Author version available

Discovery and mechanistic study of a photocatalytic indoline dehydrogenation for the synthesis of elbasvir

H. G. Yayla, F. Peng, I. K. Mangion, M. McLaughlin, L. Campeau, I. W. Davies, D. A. DiRocco and R. R. Knowles, Chem. Sci., 2016, 7, 2066 DOI: 10.1039/C5SC03350K

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

Search articles by author

Spotlight

Advertisements