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钯催化的苯甲酸邻位碳氢键氟化反应研究

汪成 张志鹏

汪成, 张志鹏. 钯催化的苯甲酸邻位碳氢键氟化反应研究[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20210823001
引用本文: 汪成, 张志鹏. 钯催化的苯甲酸邻位碳氢键氟化反应研究[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20210823001
WANG Cheng, ZHANG Zhipeng. Palladium-Catalyzed ortho-C(sp2)-H Fluorination of Benzoic Acid[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20210823001
Citation: WANG Cheng, ZHANG Zhipeng. Palladium-Catalyzed ortho-C(sp2)-H Fluorination of Benzoic Acid[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20210823001

钯催化的苯甲酸邻位碳氢键氟化反应研究

doi: 10.14135/j.cnki.1006-3080.20210823001
基金项目: 国家自然科学基金(21702059);上海市浦江人才计划(18PJ1402200)和中央高校基本科研业务费专项资金(222201814014)
详细信息
    作者简介:

    汪成:汪 成(1995—),男,安徽人,硕士生,主要研究方向为碳氢键活化研究。 E-mail:chengw0116@163.com

    通讯作者:

    张志鹏,E-mail:zhipengzhang@ecust.edu.cn

  • 中图分类号: O621.3

Palladium-Catalyzed ortho-C(sp2)-H Fluorination of Benzoic Acid

  • 摘要: 含氟有机分子通常具有一些独特的物理、化学以及生物学性质,因而在材料科学和药物化学中有着重要的应用价值。通过惰性碳氢键的活化来实现有机分子的官能团化近年来受到了极其广泛的关注,因此通过碳氢键的氟化反应来合成含氟有机分子也是有机合成中非常重要且具有挑战性的研究方向。以苯甲酸作为反应底物、以羧基作为导向基,通过对反应的添加剂、溶剂、氟化试剂和配体等的系统筛选,实现了其邻位碳氢键的氟化反应,以最高13%的分离收率得到了相应的单氟化产物。

     

  • 图  1  钯催化的苯甲酸邻位C(sp2)−H键氟化反应

    Figure  1.  Palladium-catalyzed ortho-C(sp2)−H fluorination of benzoic acid

    表  1  无机盐添加剂对苯甲酸邻位C−H键氟化反应的影响

    Table  1.   Influence of additive I (inorganic salt) on ortho-C(sp2)−H fluorination of benzoic acid

    EntryAdditive I2
    1NaCln.d.
    2NaBrn.d.
    3NaOAcn.d.
    4Na2CO3n.d.
    5NaIn.d.
    6NaFdetected
    7Li2CO3n.d.
    8LiCln.d.
    9KFn.d.
    10KCln.d.
    11KIn.d.
    12CsFn.d.
    13CsCltrace
    14Cs2CO3n.d.
    15CsOAcn.d.
    Reaction conditions: 1 (0.1 mmol), x(Pd(OAc)2)= 10%, NFSI (0.2 mmol), DCE (1.0 mL), 100 °C, under air, 24 h; n.d.−Not detected
    下载: 导出CSV

    表  2  其他添加剂对苯甲酸邻位C−H键氟化反应的影响

    Table  2.   Influence of other additive on ortho-C(sp2)−H fluorination of benzoic acid

    EntryAdditive IIYield/%
    1Ac2O1.0
    2TFAAn.d.
    31,4-Benzoquinone0.8
    4Cu(OAc)2n.d.
    5K2S2O80.6
    6H2O20.9
    7N-Hydroxyphthalimiden.d.
    8AgNO33.5
    9NaNO21.4
    10NaNO33.1
    11KNO31.0
    12Cu(NO3)2n.d.
    13AgCl0.8
    14AgOAc0.5
    15Ag2CO31.0
    16AgOTf1.2
    Reaction conditions: 1 (0.1 mmol), x(Pd(OAc)2) = 10%, NaF (0.1 mmol), NFSI (0.2 mmol), DCE (1.0 mL), 100 °C, under air, 24 h; Yields were determined by GC using 1,3,5-trimethoxybenzene as the internal standard; n.d.−Not detected
    下载: 导出CSV

    表  3  溶剂对苯甲酸邻位C−H键氟化反应的影响

    Table  3.   Solvent effect on ortho-C(sp2)−H fluorination of benzoic acid

    EntrySolvent (1.0 mL)yield/%
    1DCE3.4
    2n-pentane7.2
    3n-hexane9.8
    4n-heptane4.0
    5cyclo-pentanen.d.
    6cyclo-hexanetrace
    7CF3Ph6.2
    8Toluene4.8
    9Octafluorotoluene7.0
    10t-amyl-OHn.d.
    11Dioxane3.4
    12DCM2.1
    13CHCl39.6
    14CCl46.4
    15DME4.2
    16EA3.8
    Reaction conditions: 1 (0.1 mmol), x (L1)=20%, x(Pd(OAc)2)=10%, NaF (0.1 mmol), NFSI (0.2 mmol), AgNO3 (0.2 mmol), 100 °C, under air, 24 h; Yields were determined by GC using 1,3,5-trimethoxybenzene as the internal standard; n.d.−Not detected, DME-lycol dimethyl ether
    下载: 导出CSV

    表  4  吡啶类配体对苯甲酸邻位C−H键氟化反应的影响

    Table  4.   Ligand effect on ortho-C(sp2)−H fluorination of benzoic acid

    No.LigandsYield/%
    L24.6%
    L32.8%
    L41.2%
    L59.2%
    L61.2%
    L7trace
    L82.8%
    L93.2%
    L103.2%
    Reaction conditions: 1 (0.1 mmol), x (Pd(OAc)2) =10%, NaF (0.1 mmol), NFSI (0.2 mmol), AgNO3 (0.2 mmol), n-hexane (1 mL), 100 °C, under air, 24 h; Yields were determined by GC using 1,3,5-trimethoxybenzene as the internal standard; n.d.−not detected
    下载: 导出CSV

    表  5  吡啶酮类配体对苯甲酸邻位C−H键氟化反应的影响a,b

    Table  5.   Ligand effect on ortho-C(sp2)−H fluorination of benzoic acida,b

    No.LigandsYield/%
    L19.8%
    L116.0%
    L12n.d.
    L134.8%
    L14trace
    L156.0%
    L161.4%
    L175.8%
    L182.0%
    L192.0%
    L20trace
    L218.0%
    L2210.0%
    L2310.4%
    L245.0%
    L252.8%
    Reaction conditions: 1 (0.1 mmol), x (Pd(OAc)2) =10%, NaF (0.1 mmol), NFSI (0.2 mmol), AgNO3 (0.2 mmol), n-hexane (1 mL), 100 °C, under air, 24 h; Yields were determined by GC using 1,3,5-trimethoxybenzene as the internal standard
    下载: 导出CSV

    表  6  其他配体对苯甲酸邻位C−H键氟化反应的影响

    Table  6.   Ligand effect on ortho-C(sp2)−H fluorination of benzoic acid

    No.LigandsYield/%
    L263.4%
    L272.6%
    L283.6%
    Reaction conditions: 1 (0.1 mmol), x (Pd(OAc)2) =10%, NaF (0.1 mmol), NFSI (0.2 mmol), AgNO3 (0.2 mmol), n-hexane (1 mL), 100 °C, under air, 24 h; Yields were determined by GC using 1,3,5-trimethoxybenzene as the internal standard
    下载: 导出CSV

    表  7  氟化试剂和温度对苯甲酸邻位C−H键氟化反应的影响a

    Table  7.   Influence of fluorination reagent and temperature on ortho-C(sp2)−H fluorination of benzoic acida

    Entry[F+] sourceT/℃yield/%
    1NFSI10010.5
    2Selectfluor1008.0
    3[NFP-][BF4+]1006.4
    4NFSI13013.5/13*
    5NFSI15012.3
    Reaction conditions: 1 (0.1 mmol), L23 (x=20 %), Pd(OAc)2 (x=10 %), NaF (0.1 mmol), AgNO3 (0.2 mmol), n-hexane (1 mL), under air, 24 h; Yields were determined by GC using 1,3,5-trimethoxybenzene as the internal standard; *- Not detected; [NFP][BF4+]:1-fluoropyridinium tetrafluoroborate
    下载: 导出CSV
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出版历程
  • 收稿日期:  2021-08-23
  • 网络出版日期:  2022-04-12

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