Light-mediated catalytic enantioselective difluoroalkylation of β-ketoesters via phase-transfer catalysis

Callum E. Adams; Craig P. Johnston

doi:10.1039/d4qo00390j

Light-mediated catalytic enantioselective difluoroalkylation of β-ketoesters via phase-transfer catalysis

Callum E. Adams, Craig P. Johnston^*

^*Corresponding author for this work

School of Chemistry

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

Abstract

We report a phase-transfer-catalysed asymmetric α-difluoroalkylation of β-ketoesters through visible light-promoted radical generation. This methodology affords quaternary stereocentres with mild enantioenrichment and isolated yields up to 99%. Through mechanistic investigations, we have determined that the reaction proceeds via difluoroalkyl radical generation arising from an in situ electron donor-acceptor complex capable of absorbing visible light. Extensive optimisation of the reaction parameters was carried in an attempt to overcome a facile racemic background reaction.

Original language	English
Pages (from-to)	3639-3647
Journal	Organic Chemistry Frontiers
Volume	11
Issue number	13
Early online date	9 May 2024
DOIs	https://doi.org/10.1039/d4qo00390j
Publication status	E-pub ahead of print - 9 May 2024

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10.1039/d4qo00390jLicence: CC BY

Adams_2024_OrgChemFront_Light-mediated_CC
This article is licensed under aCreative Commons Attribution 3.0 Unported Licence. http://creativecommons.org/licenses/by/3.0/
Final published version, 1.68 MBLicence: CC BY

RS URF 2018 Craig Johnston: Enantioselective radical reactions facilitated by ion-bindong catalysis
Johnston, C. P. (PI)
1/10/18 → 30/09/23
Project: Fellowship

Light-mediated catalytic enantioselective difluoroalkylation of β-ketoesters via phase-transfer catalysis (dataset)
Johnston, C. P. (Creator) & Adams, C. (Owner), University of St Andrews, 31 Jul 2024
DOI: 10.17630/301fa354-0637-4065-a526-fbc7c3a3f462
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abstract = "We report a phase-transfer-catalysed asymmetric α-difluoroalkylation of β-ketoesters through visible light-promoted radical generation. This methodology affords quaternary stereocentres with mild enantioenrichment and isolated yields up to 99%. Through mechanistic investigations, we have determined that the reaction proceeds via difluoroalkyl radical generation arising from an in situ electron donor-acceptor complex capable of absorbing visible light. Extensive optimisation of the reaction parameters was carried in an attempt to overcome a facile racemic background reaction.",

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note = "The authors acknowledge funding from the Royal Society (University Research Fellowship URF\\R1\\180017 (CPJ)) and the University of St Andrews (CEA). We thank Yitong Wang for his help in the synthesis of starting materials and Reece Hoogesteger for running scale-up experiments. We thank Prof. Andy Smith, Prof. Allan Watson, and their respective research groups for sharing their lab equipment and chemical inventories.",

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AU - Johnston, Craig P.

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Y1 - 2024/5/9

N2 - We report a phase-transfer-catalysed asymmetric α-difluoroalkylation of β-ketoesters through visible light-promoted radical generation. This methodology affords quaternary stereocentres with mild enantioenrichment and isolated yields up to 99%. Through mechanistic investigations, we have determined that the reaction proceeds via difluoroalkyl radical generation arising from an in situ electron donor-acceptor complex capable of absorbing visible light. Extensive optimisation of the reaction parameters was carried in an attempt to overcome a facile racemic background reaction.

AB - We report a phase-transfer-catalysed asymmetric α-difluoroalkylation of β-ketoesters through visible light-promoted radical generation. This methodology affords quaternary stereocentres with mild enantioenrichment and isolated yields up to 99%. Through mechanistic investigations, we have determined that the reaction proceeds via difluoroalkyl radical generation arising from an in situ electron donor-acceptor complex capable of absorbing visible light. Extensive optimisation of the reaction parameters was carried in an attempt to overcome a facile racemic background reaction.

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EP - 3647

JO - Organic Chemistry Frontiers

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Light-mediated catalytic enantioselective difluoroalkylation of β-ketoesters via phase-transfer catalysis

Abstract

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RS URF 2018 Craig Johnston: Enantioselective radical reactions facilitated by ion-bindong catalysis

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Light-mediated catalytic enantioselective difluoroalkylation of β-ketoesters via phase-transfer catalysis (dataset)

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