Alkene 1,3-Difluorination via Transient Oxonium Intermediates

Alastair J J Lennox; Alice C Dean; E. Harvey Randle; Andrew J D Lacey; Gui Marczak Giorio; Sayad Doobary; Benjamin D. Cons

doi:10.1002/anie.202404666

Alkene 1,3-Difluorination via Transient Oxonium Intermediates

Alastair J J Lennox^*, Alice C Dean, E. Harvey Randle, Andrew J D Lacey, Gui Marczak Giorio, Sayad Doobary, Benjamin D. Cons

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

2 Citations (Scopus)

Abstract

The 1,3-difunctionalization of unactivated alkenes is an under-explored transformation that leads to moieties that are otherwise challenging to prepare. Herein, we report a hypervalent iodine-mediated 1,3-difluorination of homoallylic (aryl) ethers to give unreported 1,3-difluoro-4-oxy groups with moderate to excellent diastereoselectivity. The transformation proceeds through a different mode of reactivity for 1,3-difunctionalization, in which a regioselective addition of fluoride opens a transiently formed oxonium intermediate to rearrange an alkyl chain. The optimized protocol is scalable and shown to proceed well with a variety of functional groups and substitution on the alkenyl chain, hence providing ready access to this fluorinated, conformationally controlled moiety.

Original language	English
Article number	e202404666
Number of pages	8
Journal	Angewandte Chemie International Edition
Volume	63
Issue number	30
Early online date	2 May 2024
DOIs	https://doi.org/10.1002/anie.202404666
Publication status	Published - 22 Jul 2024

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© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

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title = "Alkene 1,3-Difluorination via Transient Oxonium Intermediates",

abstract = "The 1,3-difunctionalization of unactivated alkenes is an under-explored transformation that leads to moieties that are otherwise challenging to prepare. Herein, we report a hypervalent iodine-mediated 1,3-difluorination of homoallylic (aryl) ethers to give unreported 1,3-difluoro-4-oxy groups with moderate to excellent diastereoselectivity. The transformation proceeds through a different mode of reactivity for 1,3-difunctionalization, in which a regioselective addition of fluoride opens a transiently formed oxonium intermediate to rearrange an alkyl chain. The optimized protocol is scalable and shown to proceed well with a variety of functional groups and substitution on the alkenyl chain, hence providing ready access to this fluorinated, conformationally controlled moiety.",

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T1 - Alkene 1,3-Difluorination via Transient Oxonium Intermediates

AU - Lennox, Alastair J J

AU - Dean, Alice C

AU - Randle, E. Harvey

AU - Lacey, Andrew J D

AU - Marczak Giorio, Gui

AU - Doobary, Sayad

AU - Cons, Benjamin D.

PY - 2024/7/22

Y1 - 2024/7/22

N2 - The 1,3-difunctionalization of unactivated alkenes is an under-explored transformation that leads to moieties that are otherwise challenging to prepare. Herein, we report a hypervalent iodine-mediated 1,3-difluorination of homoallylic (aryl) ethers to give unreported 1,3-difluoro-4-oxy groups with moderate to excellent diastereoselectivity. The transformation proceeds through a different mode of reactivity for 1,3-difunctionalization, in which a regioselective addition of fluoride opens a transiently formed oxonium intermediate to rearrange an alkyl chain. The optimized protocol is scalable and shown to proceed well with a variety of functional groups and substitution on the alkenyl chain, hence providing ready access to this fluorinated, conformationally controlled moiety.

AB - The 1,3-difunctionalization of unactivated alkenes is an under-explored transformation that leads to moieties that are otherwise challenging to prepare. Herein, we report a hypervalent iodine-mediated 1,3-difluorination of homoallylic (aryl) ethers to give unreported 1,3-difluoro-4-oxy groups with moderate to excellent diastereoselectivity. The transformation proceeds through a different mode of reactivity for 1,3-difunctionalization, in which a regioselective addition of fluoride opens a transiently formed oxonium intermediate to rearrange an alkyl chain. The optimized protocol is scalable and shown to proceed well with a variety of functional groups and substitution on the alkenyl chain, hence providing ready access to this fluorinated, conformationally controlled moiety.

U2 - 10.1002/anie.202404666

DO - 10.1002/anie.202404666

M3 - Article (Academic Journal)

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JF - Angewandte Chemie International Edition

IS - 30

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ER -

Alkene 1,3-Difluorination via Transient Oxonium Intermediates

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