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SCIENCE CHINA Chemistry, Volume 64 , Issue 6 : 999-1003(2021) https://doi.org/10.1007/s11426-021-9965-9

Hypervalent iodine-mediated gem-difluorination of vinyl halides enabled by exclusive 1,2-halo migration

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  • ReceivedJan 19, 2021
  • AcceptedFeb 22, 2021
  • PublishedApr 6, 2021

Abstract


Funded by

the National Natural Science Foundation of China(21961047,21901266,21971261,22022114)


Acknowledgment

This work was supported by the National Natural Science Foundation of China (21961047, 21901266, 21971261, 22022114).


Interest statement

The authors declare no conflict of interest.


References

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  • Scheme 1

    Strategies for the gem-difluorination of olefins. EWG=electron-withdraw group (color online).

  • Figure 1

    Examples of bioactive molecules containing a CF2 moiety (color online).

  • Scheme 2

    Scope with respect to α-alkyl vinyl bromides (color online).

  • Scheme 3

    Scope with respect to β-substituted vinyl bromides (color online).

  • Scheme 4

    1,2-Bromo migratory gem-difluorination of complex small molecules (color online).

  • Scheme 5

    Synthesis of β-difluorinated alkyl chloride 8 (1) and 10 (2) (color online).

  • Scheme 6

    Synthetic utility and product derivatization (color online).

  • Scheme 7

    Proposed mechanism (color online).

  • Table 1   Optimization of the reaction conditionsa)

    Oxidant

    “F” source

    Solvent

    Yield (%)b)

    1

    PhIO

    Py·9HF

    CH2Cl2

    71

    2

    PIDA

    Py·9HF

    CH2Cl2

    84

    3

    PIFA

    Py·9HF

    CH2Cl2

    80

    4

    PIDA

    Py·9HF

    1,4-dioxane

    0

    5

    PIDA

    Py·9HF

    DMF

    0

    6

    PIDA

    Py·9HF

    CH3CN

    0

    7

    PIDA

    Py·9HF

    THF

    0

    8

    PIDA

    Py·9HF

    DCE

    73

    9

    PIDA

    Et3N·3HF

    CH2Cl2

    0

    10

    PIDA

    CsF

    CH2Cl2

    0

    11

    PIDA

    TBAF

    CH2Cl2

    0

    12c)

    PIDA

    Py·9HF

    CH2Cl2

    76

    13d)

    PIDA

    Py·9HF

    CH2Cl2

    74

    14e)

    PIDA

    Py·9HF

    CH2Cl2

    78

    15f)

    Selectfluor

    Py·9HF

    CH2Cl2

    8

    16

    Py·9HF

    CH2Cl2

    0

    Unless otherwise noted, all the reactions were performed by using 1a(0.5 mmol), oxidant (0.75 mmol), and “F” source (25.0 mmol) in solvent (5.0 mL) at room temperature for 4 h. b) Yield of isolated products. c) With 40.0 equiv. of Py·9HF. d) With 0.6 mmol of PIDA. e) With 1.0 mmol of PIDA. f) p-TolI (20 mol%) and Selectfluor (0.75 mmol) were used instead of PIDA.

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