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Predictable site-selective radical fluorination of tertiary ethers

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  • ReceivedOct 5, 2019
  • AcceptedOct 10, 2019
  • PublishedNov 13, 2019

Abstract


Funded by

the National Natural Science Foundation of China(21702098,21732003,21672099)

and “1000-Youth Talents Plan”. Mr. Xu was supported by the Scientific Research Foundation of Graduate School of Nanjing University(2018CL05)


Acknowledgment

This work was supported by the National Natural Science Foundation of China (21971108, 21702098), the Natural Science Foundation of Jiangsu Province (BK20190006), Fundamental Research Funds for the Central Universities (020514380176), “Jiangsu Six Peak Talent Project”, “1000-Youth Talents Plan’’, and start-up funds from Nanjing University. Mr. Xu was supported by the Scientific Research Foundation of Graduate School of Nanjing University (2018CL05).


Interest statement

The authors declare that they have no conflict of interest.


Supplement

The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


References

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  • Scheme 1

    The prevalence of tertiary alkyl fluorides in bioactive compounds (a) and general radical fluorination strategies (b) (color online).

  • Scheme 2

    Mechanistic hypothesis (radical chain pathway was added: path B) (color online).

  • Scheme 3

    Scope of the ethers in 0.2 mmol scale (yields of isolated products are given) (color online).

  • Scheme 4

    Late-stage modification of complex molecules. See Supporting Information online for details of conditions (color online).

  • Scheme 5

    Consecutive procedures for C–O bond radical fluorination of complex tertiary alcohols (color online).

  • Scheme 6

    The mechanistic investigation. (a) Radical inhibition experiments; (b) radical-clock experiments; (c) luminescence quenching experiments (color online).

  • Table 1   Optimization of the reaction conditions

    Entry

    Variation of standard conditions

    Yield b) (%)

    1

    None

    81 (75)

    2

    2b instead of 2a

    22

    3

    2c instead of 2a

    7

    4

    2d instead of 2a

    19

    5

    DBU c) instead of DBN

    56

    6

    Quinuclidine instead of DBN

    56

    7

    N-phenylmethanesulfonamide instead of DBN

    18

    8

    1 equiv. DBN

    23

    9

    0.1 equiv. DBN

    46

    10

    No DBN

    24

    11

    No photocatalyst

    10

    12

    Dark

    0

    Standard conditions: 1a (0.2 mmol), 2a (2 mol%), DBN (50 mol%), Selectfluor (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), 3 equiv.), MeCN (3 mL), blue LEDs, room temperature, 12 h. b) Measured by GC using acetophenone as internal standard. The isolated yield was given in the parentheses. c) DBU=1,8-diazabicyclo [5.4.0] undec-7-ene.

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