Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Apr 20;138(15):5000-3.
doi: 10.1021/jacs.6b02391. Epub 2016 Apr 12.

Catalytic, Diastereoselective 1,2-Difluorination of Alkenes

Steven M Banik  1 , Jonathan William Medley  1 , Eric N Jacobsen  1
Affiliations

Catalytic, Diastereoselective 1,2-Difluorination of Alkenes

Steven M Banik et al. J Am Chem Soc. .

Abstract

We describe a direct, catalytic approach to the 1,2-difluorination of alkenes. The method utilizes a nucleophilic fluoride source and an oxidant in conjunction with an aryl iodide catalyst and is applicable to alkenes with all types of substitution patterns. In general, the vicinal difluoride products are produced with high diastereoselectivities. The observed sense of stereoinduction implicates anchimeric assistance pathways in reactions of alkenes bearing neighboring Lewis basic functionality.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Terminal Alkene Substrate Scope
aReactions were conducted on 1.04 mmol scale, with yields of diastereomerically product isolated after chromatographic purification unless noted otherwise. bReactions conducted with 20 mol% catalyst, with slow addition of substrate over 2 hours. cReactions conducted with 10 mol% catalyst and 6 equivalents of pyridine. dReactions conducted with 20 mol% catalyst. eDetermined by 19F NMR of the crude reaction mixture. fIsolated as a mixture of diastereomers.
Figure 2
Figure 2. Internal Alkene Substrate Scope
aReactions were conducted on 0.62–1.94 mmol scale, with yields of diastereomerically pure product isolated after chromatographic purification unless noted otherwise. Diastereomeric ratios (d.r. values) were determined by 19F NMR of crude reaction mixtures. bReactions were conducted with slow addition of substrate over 2 hours and were allowed to progress with stirring for an additional 1 hour. cReaction was conducted at 0 °C with slow addition of substrate over 1 hour and stirring for an additional 1 hour. dReactions were conducted with slow addition of substrate over 2 hours and stirring for an additional 10 hours. eReaction was conducted in neat pyr•9HF for 12 hours. Isolated as a mixture of diastereomers. fReaction was conducted in neat pyr•9HF for 36 hours with a second addition of mCPBA (0.65 equiv) after 24 hours. gReaction was conducted with 20 equiv of HF for 24 hours. Isolated as a mixture of a diastereomers.
Figure 3
Figure 3. Acrylamide Substrate Scope
aReactions were conducted on 0.55–5.71 mmol scale, with yields of diastereomerically pure product isolated after chromatographic purification. Diastereomeric ratios (d.r. values) were determined by 19F NMR of crude reaction mixtures. bReactions were conducted using catalyst 1b. cReaction was conducted on 1 gram scale. dReactions were conducted in neat pyr•9HF using catalyst 1c.
Scheme 1
Scheme 1. 1,2-Difluorination of Alkenes
Scheme 2
Scheme 2. Catalyst Identification
aYields determined by GC with dodecane as an internal standard.
Scheme 3
Scheme 3. Anti Difluorination via Proposed Anchimeric Assistance
Scheme 4
Scheme 4. Highly Enantioselective 1,2-Difluorination
See this image and copyright information in PMC

References

    1. Carey FA, Sundberg RJ. Advanced Organic Chemistry Part B: Re actions and Synthesis. 5. Springer; New York: 2007. pp. 298–305.

    1. For a recent review on catalytic, stereoselective dihalogenation, see Cresswell AJ, Eey STC, Denmark SE. Angew Chem, Int Ed. 2015;54:15642–15682.

    1. For an indirect method method, see Olah GA, Welch JT, Vankar YD, Nojima M, Kerekes I, Olah JA. J Org Chem. 1979;44:3872–3881.

    1. Barton DHR, Lister-James J, Hesse RH, Pechet MM, Rozen S. J Chem Soc, Perkin Trans. 1982;1:1105–1110.
    2. Purrington ST, Kagen BS, Patrick TB. Chem Rev. 1986;86:997–1018.
    3. Sanford G. J Fluorine Chem. 2007;128:90–104.
    1. Tius MA. Tetrahedron. 1995;51:6605–6634.
    2. Tamura M, Takagi T, Quan HD, Sekiya A. J Fluorine Chem. 1999;98:163–166.

Publication types