Highly Carbon-Selective Monofluoromethylation of β-Ketoesters with Fluoromethyl Iodide

Ding, Tianqi; Jiang, Lvqi; Yang, Jie; Xu, Yimin; Wang, Guixiang; Yi, Wen‐Bin

doi:10.1021/acs.orglett.9b02175

“…Eine der wichtigsten Anwendungen von CH 2 FBr ist seine Verwendung im letzten Schritt der Synthese von Fluticasone, welche die Fluormethylierung eines Thiocarboxylat‐Vorläufers am Schwefelatom umfasst (Schema ). Fluoriodmethan und die monosubstituierten Derivate CHRFI und CHRFBr wurden in mehreren Fällen zur Einführung der CH 2 F‐ oder CHRF‐Gruppe verwendet. Die ersten systematischen Studien über die Fluormethylierung von Phenolen, Thiophenolen, Imidazolen und Indolen mit CH 2 FCl (Schema ) wurden 2007 von Hu und Mitarbeitern berichtet …”

Section: Reagenzien Für Die Direkte Monofluormethylierungunclassified

Reagenzien für die selektive Fluormethylierung: Herausforderungen der Organofluorchemie

Reichel

¹

,

Karaghiosoff

²

2020

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Die Einführung einer CH2F‐Gruppe in organische Moleküle ist in den letzten Jahren zweifellos zu einem sehr wichtigen Forschungsgebiet geworden. Aufgrund der vorteilhaften Eigenschaften von Organofluorverbindungen – wie ihre metabolische Stabilität – ist der Einbau der CH2F‐Gruppe als bioisosterer Ersatz für verschiedene funktionelle Gruppen eine attraktive Strategie, um z. B. neue Medikamente zu entwickeln. Darüber hinaus findet die Monofluormethyleinheit auch in der Agrochemie, in der pharmazeutischen Chemie und in der Feinchemie einen breiten Einsatz. Aufgrund des menschengemachten Klimawandels und des wachsenden Bedarfs an umweltfreundlichen industriellen Prozessen sind Alternativen zu den häufig verwendeten Fluormethylierungsmitteln auf FCKW‐ und HFBKW‐Basis (CH2FCl und CH2FBr) dringend erforderlich und im Montrealer Protokoll auch gefordert. Dies hat in letzter Zeit viele Forscher dazu veranlasst, die Entwicklung umweltfreundlicher Fluormethylierungsmittel zu entwickeln. Dieser Kurzaufsatz umfasst sowohl die klassischen als auch die neue Generation von Fluormethylierungsmitteln. Es werden Reagenzien und deren Vorläuferverbindungen diskutiert, die sowohl direkt als auch indirekt über elektrophile und nukleophile als auch radikalische Wege reagieren.

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“…9B). [192][193][194][195] For example, β-ketoesters can react with fluoroiodomethane and lithium tert-butoxide to produce α-monofluoromethyl adducts. 193 Commonly, competitive Omonofluoromethylation is a complicating factor and in a few cases it is a predominant reaction pathway 196 that is proposed to occur via a radical process.…”

Section: [H2] Monofluoromethylationmentioning

confidence: 99%

Contemporary synthetic strategies in organofluorine chemistry

Britton

¹

,

Gouverneur

²

,

Lin

³

et al. 2021

Nat Rev Methods Primers

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At this stage, I've edited the manuscript for brevity and clarity. Queries are meant to draw your attention to edits, inconsistencies or issues that are unclear. If we just ask you to confirm edits are correct, a simple yes/ok between the brackets will do [Au:OK? Is this what you meant? Edits OK? yes]. If questions are asked, please rephrase/update the manuscript text when addressing queries, so that the message is conveyed to the reader (please do not just type your answer to our query unless it is unclear).As the reviewers noted, the manuscript is in very good shape and most comments and edits are fairly minor. However, there is an outstanding issue that must be addressed before we go forward. Figures 7 and 8 are currently referred to in the text in an alternating fashion (e.g. Figure 7A, 8A, 7B, 8B). This is against our style and might make that part of the manuscript difficult to follow for the reader owing to the need to refer to multiple figures at a time while reading the text. To clarify this issue, I recommend restructuring these figures. To do this, can you provide new chemdraw/PDFs with amended figures, including the following amendments: a. Merge Figures 7A and 8A to create a new 'Figure 7' that shows the methods of introducing CF2H at sp3-carbons. b. Merge figures 7B and 8B to make a new figure 8 that shows the main protocols of introducing CF2H at heteroaromatic carbons. 7C could be shown in it's own small figure (Figure 9) or could be added as panel B in the new figure 8. c. Amend the figure legends accordingly Apologies for another figure change but this is essential to keep the figure callouts in style and I think it will make the figures much easier for the reader to follow. I've asked the art editor to delay redrawing these particular figures until we receive these updated chemdraws/PDFs. If there are any issues with this change, please do let me know as soon as possible and we can discuss further.

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“…[192][193][194][195] For example, β-ketoesters can react with fluoroiodomethane and lithium tert-butoxide to produce α-monofluoromethyl adducts. 193 Commonly, competitive Omonofluoromethylation is a complicating factor and in a few cases it is a predominant reaction pathway 196 that is proposed to occur via a radical process. 197,198 In this example, competitive O-monofluoromethylation, which is proposed to occur via a radical process 197,198 , is a complicating factor and in a few cases the [Au:OK?…”

Section: [H2] Monofluoromethylationmentioning

confidence: 99%

Contemporary synthetic strategies in organofluorine chemistry

2021

Nat Rev Methods Primers

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At this stage, I've edited the manuscript for brevity and clarity. Queries are meant to draw your attention to edits, inconsistencies or issues that are unclear. If we just ask you to confirm edits are correct, a simple yes/ok between the brackets will do [Au:OK? Is this what you meant? Edits OK? yes]. If questions are asked, please rephrase/update the manuscript text when addressing queries, so that the message is conveyed to the reader (please do not just type your answer to our query unless it is unclear).As the reviewers noted, the manuscript is in very good shape and most comments and edits are fairly minor. However, there is an outstanding issue that must be addressed before we go forward. Figures 7 and 8 are currently referred to in the text in an alternating fashion (e.g. Figure 7A, 8A, 7B, 8B). This is against our style and might make that part of the manuscript difficult to follow for the reader owing to the need to refer to multiple figures at a time while reading the text. To clarify this issue, I recommend restructuring these figures. To do this, can you provide new chemdraw/PDFs with amended figures, including the following amendments: a. Merge Figures 7A and 8A to create a new 'Figure 7' that shows the methods of introducing CF2H at sp3-carbons. b. Merge figures 7B and 8B to make a new figure 8 that shows the main protocols of introducing CF2H at heteroaromatic carbons. 7C could be shown in it's own small figure (Figure 9) or could be added as panel B in the new figure 8. c. Amend the figure legends accordingly Apologies for another figure change but this is essential to keep the figure callouts in style and I think it will make the figures much easier for the reader to follow. I've asked the art editor to delay redrawing these particular figures until we receive these updated chemdraws/PDFs. If there are any issues with this change, please do let me know as soon as possible and we can discuss further.

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Highly Carbon-Selective Monofluoromethylation of β-Ketoesters with Fluoromethyl Iodide

Cited by 29 publications

References 57 publications

Reagenzien für die selektive Fluormethylierung: Herausforderungen der Organofluorchemie

Reagenzien für die selektive Fluormethylierung: Herausforderungen der Organofluorchemie

Contemporary synthetic strategies in organofluorine chemistry

Contemporary synthetic strategies in organofluorine chemistry

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