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. 2024 Jul 22;63(30):e202404666.
doi: 10.1002/anie.202404666. Epub 2024 Jun 20.

Alkene 1,3-Difluorination via Transient Oxonium Intermediates

Alice C Dean  1 , E Harvey Randle  1 , Andrew J D Lacey  1 , Guilherme A Marczak Giorio  1 , Sayad Doobary  1 , Benjamin D Cons  2 , Alastair J J Lennox  1
Affiliations

Alkene 1,3-Difluorination via Transient Oxonium Intermediates

Alice C Dean et al. Angew Chem Int Ed Engl. .

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.

Keywords: Alkenes; Difunctionalization; Fluorine; Hypervalent iodine; Oxidation.

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