Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines
Herein, we describe a catalytic fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor®, whilst HF serves as both a fluoride source and Brøns...
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doaj-8f44c7183a2d4562a88dc1f4f05c23392021-02-02T04:39:10ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972018-05-011411021102710.3762/bjoc.14.881860-5397-14-88Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolinesFelix Scheidt0Christian Thiehoff1Gülay Yilmaz2Stephanie Meyer3Constantin G. Daniliuc4Gerald Kehr5Ryan Gilmour6Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, GermanyOrganisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, GermanyOrganisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, GermanyOrganisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, GermanyOrganisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, GermanyOrganisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, GermanyOrganisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, GermanyHerein, we describe a catalytic fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor®, whilst HF serves as both a fluoride source and Brønsted acid activator. The C(sp3)–F bond of the mono-fluoromethyl unit and the C(sp3)–O bond of the ring are aligned in a synclinal relationship thereby engaging in stabilising hyperconjugative interactions with vicinal, electron-rich σ-bonds (σC–C→σ*C–F and σC–H→σ*C–O). This manifestation of the stereoelectronic gauche effect was established by X-ray crystallographic analysis of a representative example. Given the importance of fluorine in drug discovery, its ability to modulate conformation, and the prevalence of the 2-oxazoline scaffold in Nature, this strategy provides a rapid entry into an important bioisostere class.https://doi.org/10.3762/bjoc.14.88catalysiscyclisationfluorinationgauche effecthypervalent iodineoxazolines |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Felix Scheidt Christian Thiehoff Gülay Yilmaz Stephanie Meyer Constantin G. Daniliuc Gerald Kehr Ryan Gilmour |
spellingShingle |
Felix Scheidt Christian Thiehoff Gülay Yilmaz Stephanie Meyer Constantin G. Daniliuc Gerald Kehr Ryan Gilmour Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines Beilstein Journal of Organic Chemistry catalysis cyclisation fluorination gauche effect hypervalent iodine oxazolines |
author_facet |
Felix Scheidt Christian Thiehoff Gülay Yilmaz Stephanie Meyer Constantin G. Daniliuc Gerald Kehr Ryan Gilmour |
author_sort |
Felix Scheidt |
title |
Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines |
title_short |
Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines |
title_full |
Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines |
title_fullStr |
Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines |
title_full_unstemmed |
Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines |
title_sort |
fluorocyclisation via i(i)/i(iii) catalysis: a concise route to fluorinated oxazolines |
publisher |
Beilstein-Institut |
series |
Beilstein Journal of Organic Chemistry |
issn |
1860-5397 |
publishDate |
2018-05-01 |
description |
Herein, we describe a catalytic fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor®, whilst HF serves as both a fluoride source and Brønsted acid activator. The C(sp3)–F bond of the mono-fluoromethyl unit and the C(sp3)–O bond of the ring are aligned in a synclinal relationship thereby engaging in stabilising hyperconjugative interactions with vicinal, electron-rich σ-bonds (σC–C→σ*C–F and σC–H→σ*C–O). This manifestation of the stereoelectronic gauche effect was established by X-ray crystallographic analysis of a representative example. Given the importance of fluorine in drug discovery, its ability to modulate conformation, and the prevalence of the 2-oxazoline scaffold in Nature, this strategy provides a rapid entry into an important bioisostere class. |
topic |
catalysis cyclisation fluorination gauche effect hypervalent iodine oxazolines |
url |
https://doi.org/10.3762/bjoc.14.88 |
work_keys_str_mv |
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