The University of Southampton
University of Southampton Institutional Repository

Merging Cu-catalysed C-H functionalisation and intramolecular annulations: computational and experimental studies on an expedient construction of complex fused heterocycles

Merging Cu-catalysed C-H functionalisation and intramolecular annulations: computational and experimental studies on an expedient construction of complex fused heterocycles
Merging Cu-catalysed C-H functionalisation and intramolecular annulations: computational and experimental studies on an expedient construction of complex fused heterocycles
Intramolecular annulation reactions provide a powerful opportunity to access complex heterocyclic compounds with higher complexity than intermolecular conversions. This report details how, previously unknown fused dihydrobenzofuran-isoquinolone compounds, exhibiting an unusually strained shared aromatic unit, can be readily obtained from simply prepared benzamide derivatives bearing a tethered alkyne moiety, using copper C–H bond functionalisation catalysis. The mechanism has been proposed based on detailed DFT and topological analysis studies, and shows that the two key heterocycles are formed during distinct mechanistic steps; the dihydrobenzofuran arises from a migratory insertion and the isoquinolone from the following reductive elimination, resulting in an efficient Double Annulation Reaction (DAR). Actually, the results present an unprecedented migratory insertion of alkynes with benzamides when using copper as catalyst with the 8-aminoquinoline directing group and also study why the intermolecular variant is not operative.
2052-4129
1235-1242
Wootton, Timothy L.
d8707ac5-68b1-4c8b-976a-0800ce43046a
Porter, Jack A.
14471533-51e8-484b-b614-24e54e6b02ba
Grewal, Karmjit S.
4c4c9741-6828-4475-9702-531a7b7ff34a
Chirila, Paula G.
e2b3d337-815c-4f1d-b9c3-488bfc2fdcab
Forbes, Sarah
2f54ddf4-46bf-4257-8243-9546978969e7
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Horton, Peter
154c8930-bfc3-495b-ad4a-8a278d5da3a5
Hamilton, Alex
9e0da4d2-3894-4bb9-993f-786ea4c45aa8
Whiteoak, Christopher J.
59ad4b4f-4e4a-42e2-b82c-0fd0cd3e9d55
Wootton, Timothy L.
d8707ac5-68b1-4c8b-976a-0800ce43046a
Porter, Jack A.
14471533-51e8-484b-b614-24e54e6b02ba
Grewal, Karmjit S.
4c4c9741-6828-4475-9702-531a7b7ff34a
Chirila, Paula G.
e2b3d337-815c-4f1d-b9c3-488bfc2fdcab
Forbes, Sarah
2f54ddf4-46bf-4257-8243-9546978969e7
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Horton, Peter
154c8930-bfc3-495b-ad4a-8a278d5da3a5
Hamilton, Alex
9e0da4d2-3894-4bb9-993f-786ea4c45aa8
Whiteoak, Christopher J.
59ad4b4f-4e4a-42e2-b82c-0fd0cd3e9d55

Wootton, Timothy L., Porter, Jack A., Grewal, Karmjit S., Chirila, Paula G., Forbes, Sarah, Coles, Simon J., Horton, Peter, Hamilton, Alex and Whiteoak, Christopher J. (2020) Merging Cu-catalysed C-H functionalisation and intramolecular annulations: computational and experimental studies on an expedient construction of complex fused heterocycles. Organic Chemistry Frontiers, 7 (10), 1235-1242. (doi:10.1039/D0QO00283F).

Record type: Article

Abstract

Intramolecular annulation reactions provide a powerful opportunity to access complex heterocyclic compounds with higher complexity than intermolecular conversions. This report details how, previously unknown fused dihydrobenzofuran-isoquinolone compounds, exhibiting an unusually strained shared aromatic unit, can be readily obtained from simply prepared benzamide derivatives bearing a tethered alkyne moiety, using copper C–H bond functionalisation catalysis. The mechanism has been proposed based on detailed DFT and topological analysis studies, and shows that the two key heterocycles are formed during distinct mechanistic steps; the dihydrobenzofuran arises from a migratory insertion and the isoquinolone from the following reductive elimination, resulting in an efficient Double Annulation Reaction (DAR). Actually, the results present an unprecedented migratory insertion of alkynes with benzamides when using copper as catalyst with the 8-aminoquinoline directing group and also study why the intermolecular variant is not operative.

Text
Revised Manuscript_Hamilton and Whiteoak (002) - Accepted Manuscript
Download (852kB)

More information

Accepted/In Press date: 31 March 2020
Published date: 31 March 2020
Additional Information: Funding Information: Financial support for this work was provided by the Sheffield Hallam University “Creating Knowledge Implementation Plan (CKIP)”. P. G. C. would like to thank the Biomolecular Sciences Research Centre (BMRC) at Sheffield Hallam University for funding of a PhD studentship. P. G. C. and C. J. W. would also like to acknowledge COST Action – CA15106: C–H Activation in Organic Synthesis (CHAOS) for support. We thank the Engineering and Physical Sciences Research Council National Crystallography Service at the University of Southampton.26 Publisher Copyright: © 2020 the Partner Organisations.

Identifiers

Local EPrints ID: 440693
URI: http://eprints.soton.ac.uk/id/eprint/440693
ISSN: 2052-4129
PURE UUID: 4c96fbfc-9a8b-4998-992d-ce3738583431
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272
ORCID for Peter Horton: ORCID iD orcid.org/0000-0001-8886-2016

Catalogue record

Date deposited: 13 May 2020 16:36
Last modified: 17 Mar 2024 05:32

Export record

Altmetrics

Contributors

Author: Timothy L. Wootton
Author: Jack A. Porter
Author: Karmjit S. Grewal
Author: Paula G. Chirila
Author: Sarah Forbes
Author: Simon J. Coles ORCID iD
Author: Peter Horton ORCID iD
Author: Alex Hamilton
Author: Christopher J. Whiteoak

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×