Synthesis of fused indoline-cyclobutanone derivatives via an intramolecular [2+2] cycloaddition

Rifahath M. Neyyappadath; Mark D. Greenhalgh; David Bradford Cordes; Alexandra M. Z. Slawin; Andrew D. Smith

doi:10.1002/ejoc.201900326

Synthesis of fused indoline-cyclobutanone derivatives via an intramolecular [2+2] cycloaddition

Rifahath M. Neyyappadath, Mark D. Greenhalgh, David Bradford Cordes, Alexandra M. Z. Slawin, Andrew D. Smith

Research output: Contribution to journal › Article › peer-review

Abstract

A serendipitously-discovered process for the synthesis of heterocyclic products containing a novel fused indoline-cyclobutanone ring system is reported. This process is believed to take place through in situ generation of a ketene intermediate, followed by intramolecular [2+2] cycloaddition with a pendant enamide. The formation of a ketene intermediate in this process is significant as the reaction conditions employed are analogous to those commonly used in tertiary amine Lewis base catalysis, where the potential intermediacy of ketenes is an important consideration that is often overlooked.

Original language	English
Journal	European Journal of Organic Chemistry
Volume	Early View
Early online date	12 Apr 2019
DOIs	https://doi.org/10.1002/ejoc.201900326
Publication status	E-pub ahead of print - 12 Apr 2019

Keywords

Lewis base catalysis
Ketene
[2+2]-cycloaddition
N-heterocycles
Indoline-cyclobutanone

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10.1002/ejoc.201900326

Neyyappadath_2019_EJOC_Synthesis_AAM
Copyright © 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1002/ejoc.201900326
Accepted author manuscript, 1.49 MB

Cite this

@article{d3db96fdfb3b443aa8ceb8a5feaee705,

title = "Synthesis of fused indoline-cyclobutanone derivatives via an intramolecular [2+2] cycloaddition",

abstract = "A serendipitously-discovered process for the synthesis of heterocyclic products containing a novel fused indoline-cyclobutanone ring system is reported. This process is believed to take place through in situ generation of a ketene intermediate, followed by intramolecular [2+2] cycloaddition with a pendant enamide. The formation of a ketene intermediate in this process is significant as the reaction conditions employed are analogous to those commonly used in tertiary amine Lewis base catalysis, where the potential intermediacy of ketenes is an important consideration that is often overlooked.",

keywords = "Lewis base catalysis, Ketene, [2+2]-cycloaddition, N-heterocycles, Indoline-cyclobutanone",

author = "Neyyappadath, \{Rifahath M.\} and Greenhalgh, \{Mark D.\} and Cordes, \{David Bradford\} and Slawin, \{Alexandra M. Z.\} and Smith, \{Andrew D.\}",

note = "We thank the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1, R.M.N.) for funding. We thank the European Research Council under the European Union{\textquoteright}s Seventh Framework Programme (FP7/2007–2013) ERC grant agreement no. 279850 (A.D.S.). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. We also thank the EPSRC UK National Mass Spectrometry Service at Swansea. The research data supporting this publication can be accessed at https://doi.org/10.17630/00aff760-0732-438f-a9d1-30c7cf3a87a0",

year = "2019",

month = apr,

day = "12",

doi = "10.1002/ejoc.201900326",

language = "English",

volume = "Early View",

journal = "European Journal of Organic Chemistry",

issn = "1434-193X",

publisher = "Wiley-VCH, Weinheim",

}

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T1 - Synthesis of fused indoline-cyclobutanone derivatives via an intramolecular [2+2] cycloaddition

AU - Neyyappadath, Rifahath M.

AU - Greenhalgh, Mark D.

AU - Cordes, David Bradford

AU - Slawin, Alexandra M. Z.

AU - Smith, Andrew D.

N1 - We thank the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1, R.M.N.) for funding. We thank the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013) ERC grant agreement no. 279850 (A.D.S.). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. We also thank the EPSRC UK National Mass Spectrometry Service at Swansea. The research data supporting this publication can be accessed at https://doi.org/10.17630/00aff760-0732-438f-a9d1-30c7cf3a87a0

PY - 2019/4/12

Y1 - 2019/4/12

N2 - A serendipitously-discovered process for the synthesis of heterocyclic products containing a novel fused indoline-cyclobutanone ring system is reported. This process is believed to take place through in situ generation of a ketene intermediate, followed by intramolecular [2+2] cycloaddition with a pendant enamide. The formation of a ketene intermediate in this process is significant as the reaction conditions employed are analogous to those commonly used in tertiary amine Lewis base catalysis, where the potential intermediacy of ketenes is an important consideration that is often overlooked.

AB - A serendipitously-discovered process for the synthesis of heterocyclic products containing a novel fused indoline-cyclobutanone ring system is reported. This process is believed to take place through in situ generation of a ketene intermediate, followed by intramolecular [2+2] cycloaddition with a pendant enamide. The formation of a ketene intermediate in this process is significant as the reaction conditions employed are analogous to those commonly used in tertiary amine Lewis base catalysis, where the potential intermediacy of ketenes is an important consideration that is often overlooked.

KW - Lewis base catalysis

KW - Ketene

KW - [2+2]-cycloaddition

KW - N-heterocycles

KW - Indoline-cyclobutanone

UR - https://www.scopus.com/pages/publications/85064529012

U2 - 10.1002/ejoc.201900326

DO - 10.1002/ejoc.201900326

M3 - Article

SN - 1434-193X

VL - Early View

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

ER -

Synthesis of fused indoline-cyclobutanone derivatives via an intramolecular [2+2] cycloaddition

Abstract

Keywords

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Fingerprint

RS Wolfson Merit Award: Developing Catalysis Research: New Reaction Discoveries and Practical Applications

CRITICAT CDT: Critical Resource Catalysis - CRITICAT

ERC Starting Grant EnolCat: Emulating nature: Reaction diversity and understanding through asymmetric catalysis

Data underpinning "Synthesis of Fused Indoline-Cyclobutanone Derivatives via an Intramolecular [2+2] Cycloaddition"