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. 2019 Jun;30(10):1178-1182.
doi: 10.1055/s-0037-1611737. Epub 2019 Mar 1.

Electrochemical C(sp3)-H Fluorination

Yusuke Takahira  1 , Miao Chen  1 , Yu Kawamata  1 , Pavel Mykhailiuk  1   2 , Hugh Nakamura  1 , Byron K Peters  1 , Solomon H Reisberg  1 , Chao Li  1 , Longrui Chen  3 , Tamaki Hoshikawa  4 , Tomoyuki Shibuguchi  4 , Phil S Baran  1
Affiliations

Electrochemical C(sp3)-H Fluorination

Yusuke Takahira et al. Synlett. 2019 Jun.

Abstract

A simple and robust method for electrochemical alkyl C-H fluorination is presented. Using a simple nitrate additive, a widely available fluorine source (Selectfluor), and carbon-based electrodes, a wide variety of activated and unactivated C-H bonds were converted to their C-F congeners. The scalability of the reaction was also demonstrated with a 100 gram preparation of fluorovaline.

Keywords: C–H functionalization; electrochemistry; fluorination; organic synthesis; radical.

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Figures

Figure 1.
Figure 1.
A) Electrochemical C(sp3)-H fluorination B) Reaction development.
Figure 2.
Figure 2.
Proposed mechanism.
See this image and copyright information in PMC

References

    1. Organic Electrochemistry, 5th ed., Revised and Expanded (Eds.: Hammerich O, Speiser B), CRC, Boca Raton, FL, 2015. For selected reviews on synthetic electrochemistry, see:
    2. Yan M; Kawamata Y; Baran PS Chem. Rev 2017, 117, 13230 and references therein. - PMC - PubMed
    3. Kärkäs MD Chem. Soc. Rev 2018, 47, 5786. - PubMed
    4. Francke R; Little RD Chem. Soc. Rev 2014, 43, 2492. - PubMed
    5. Sperry JB; Wright DL Chem. Soc. Rev 2006, 35, 605. - PubMed
    6. Moeller KD Tetrahedron, 2000, 56, 9527.
    7. Lantaño B; Postigo A Org. Biomol. Chem 2017, 15, 9954. - PubMed
    1. Horn EJ; Rosen BR; Chen Y; Tang J; Chen K; Eastgate MD; Baran PS Nature 2016, 533, 77. - PMC - PubMed
    1. Kawamata Y; Yan M; Liu Z; Bao DH; Chen J; Starr JT; Baran PS J. Am. Chem. Soc 2017, 139, 7448. - PMC - PubMed

    1. For a general overview of aliphatic C–H fluorination, see:

    2. Bume DD; Harry SA; Lectka T; Pitts CRJ Org. Chem 2018, 83, 8803. For specific examples, see: - PubMed
    3. Kee CW; Chin KF; Wong MW; Tan CH Chem. Commun 2014, 50, 8211. - PubMed
    4. Xia JB; Zhu C; Chen C Chem. Commun 2014, 50, 11701. - PMC - PubMed
    5. Bloom S; Knippel JL; Lectka T Chem. Sci 2014, 5, 1175.
    6. Halperin SD; Fan H; Chang S; Martin RE; Britton R Angew. Chem. Int. Ed 2014, 53, 4690. - PubMed
    7. West JG; Bedell TA; Sorensen EJ Angew. Chem. Int. Ed 2016, 55, 8923. - PMC - PubMed
    8. Egami H; Masuda S; Kawato Y; Hamashima Y Org. Lett 2018, 20, 1367. - PubMed
    1. Liu W; Huang X; Cheng MJ; Nielsen RJ; Goddard WA; Groves JT Science 2012, 337, 1322. - PubMed
    2. Bloom S; Pitts CR; Miller DC; Haselton N; Holl MG; Urheim E; Lectka T. Angew. Chem. Int. Ed 2012, 51, 10580. - PubMed
    3. Amaoka Y; Nagatomo M; Inoue M Org. Lett 2013, 15, 2160. - PubMed
    4. Pitts CR; Ling B; Woltornist R; Liu R; Lectka TJ Org. Chem 2014, 79, 8895. - PubMed
    5. Xia J-B; Ma Y; Chen C Org. Chem. Front 2014, 1, 468. - PMC - PubMed
    6. Zhang X; Guo S; Tang P Org. Chem. Front 2015, 2, 806.