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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
Wootton, Timothy L.
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Porter, Jack A.
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Grewal, Karmjit S.
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Chirila, Paula G.
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Forbes, Sarah
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Coles, Simon J.
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Horton, Peter
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Hamilton, Alex
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Whiteoak, Christopher J.
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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. (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
Restricted to Repository staff only until 31 March 2021.
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Accepted/In Press date: 31 March 2020
Published date: 31 March 2020

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: 23 May 2020 00:27

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