4-(1,1,2,2-tetrafluoroethyl)-1,1'-biphenyl

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(1,1,2,2-tetrafluoroethyl)-1,1'-biphenyl
• 英文别名: 4-(1,1,2,2-tetrafluoroethyl)biphenyl；1-phenyl-4-(1,1,2,2-tetrafluoroethyl)benzene
• 化学式: C₁₄H₁₀F₄
• 分子量: 254.227
• InChiKey: FONVUBYIDBOPOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-联苯基乙二醛 在 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以78%的产率得到4-(1,1,2,2-tetrafluoroethyl)-1,1'-biphenyl
  参考文献：
  名称：

  Concentration-Dependent Reactions of Deoxofluor with Arylglyoxal Hydrates:  A New Route to Polyfluoro Ethers

  摘要：

  [GRAPHICS]In concentrated solutions (CH2Cl2) at 25 degreesC, arylglyoxal hydrates, ArCOCHO .H2O (Ar = 3,4-OCH2O-C6H3-, 4-MeO-C6H4-, 4-Me-C6H4-, 4-F-C6H4-, Ph-, S-CH=CH-CH=C-) (2a-f) with Deoxofluor gave fluorinated ethers, ArCF2CHFOCHFCF2Ar, (3a-f) in > 90% yields as meso/racemic mixtures (similar to1:1). Under very dilute conditions, mixtures of ArCF2CHO (major) (4a-f) and ArCF2CF2H (6a-f) (minor) were obtained. The structures of 3b (racemic) and 4a (meso) have been confirmed by single-crystal X-ray analysis.

  DOI：

  10.1021/ol016319l

文献信息

• Access to Difluoromethylated Arenes by Pd-Catalyzed Reaction of Arylboronic Acids with Bromodifluoroacetate
  作者：Zhang Feng、Qiao-Qiao Min、Xingang Zhang

  DOI：10.1021/acs.orglett.5b03206

  日期：2016.1.4

  of aryl boronic acids with bromodifluoroacetate is described. The reaction proceeds under mild reaction conditions with hydroquinone and Fe(acac)3 as additives. Preliminary mechanistic studies reveal that a difluorocarbene pathway is involved in the reaction, which is unusual compared to the most traditional approaches. This reaction has advantages of high efficiency and excellent functional group compatibility

  描述了用溴代二氟乙酸酯进行钯催化的芳基硼酸二氟甲基化的前所未有的例子。反应在温和的反应条件下以对苯二酚和Fe（acac）3为添加剂进行。初步的机理研究表明，该反应涉及二氟卡宾途径，与大多数传统方法相比，这是不寻常的。该反应具有高效和优异的官能团相容性（甚至对溴化物和羟基而言）的优点，因此为药物发现和开发提供了有用的方案。
• Chlorodifluoromethane-triggered formation of difluoromethylated arenes catalysed by palladium
  作者：Zhang Feng、Qiao-Qiao Min、Xia-Ping Fu、Lun An、Xingang Zhang

  DOI：10.1038/nchem.2746

  日期：2017.9

  represents the ideal and most straightforward difluoromethylating reagent, but introduction of the difluoromethyl group (CF2H) from ClCF2H into aromatics has not been reported. Here, we describe a direct palladium-catalysed difluoromethylation method for coupling ClCF2H with arylboronic acids and esters to generate difluoromethylated arenes with high efficiency. The reaction exhibits a remarkably broad substrate

  二氟甲基化的芳族化合物在制药，农用化学品和材料中的重要性日益增加。氯二氟甲烷（ClCF 2 H）是一种廉价，丰富且广泛使用的工业原料，是理想且最直接的二氟甲基化试剂，但尚未见到将ClCF 2 H中的二氟甲基（CF 2 H）引入芳族化合物的报道。在这里，我们描述了偶联ClCF 2的直接钯催化的二氟甲基化方法H与芳基硼酸和酯生成高效二氟甲基化的芳烃。该反应表现出非常广泛的底物范围，包括杂芳基硼酸，并且被用于一系列药物和生物活性化合物的二氟甲基化。初步的机理研究表明，该反应涉及钯二氟卡宾中间体。尽管已经制备了许多金属-二氟卡宾配合物，但涉及金属-二氟卡宾配合物的二氟甲基化或二氟甲基化化合物的催化合成并未受到太大关注。因此，这一新反应也为理解金属-二氟卡宾络合物催化的反应打开了大门。
• Controllable catalytic difluorocarbene transfer enables access to diversified fluoroalkylated arenes
  作者：Xia-Ping Fu、Xiao-Song Xue、Xue-Ying Zhang、Yu-Lan Xiao、Shu Zhang、Yin-Long Guo、Xuebing Leng、Kendall N. Houk、Xingang Zhang

  DOI：10.1038/s41557-019-0331-9

  日期：2019.10

  Difluorocarbene has important applications in pharmaceuticals, agrochemicals and materials, but all these applications proceed using just a few types of reaction by taking advantage of its intrinsic electrophilicity. Here, we report a palladium-catalysed strategy that confers the formed palladium difluorocarbene (Pd=CF2) species with both nucleophilicity and electrophilicity by switching the valence state of the palladium centre (Pd(0) and Pd(ii), respectively). Controllable catalytic difluorocarbene transfer occurs between readily available arylboronic acids and the difluorocarbene precursor diethyl bromodifluoromethylphosphonate (BrCF2PO(OEt)2). From just this simple fluorine source, difluorocarbene transfer enables access to four types of product: difluoromethylated and tetrafluoroethylated arenes and their corresponding fluoroalkylated ketones. The transfer can also be applied to the modification of pharmaceuticals and agrochemicals as well as the one-pot diversified synthesis of fluorinated compounds. Mechanistic and computational studies consistently reveal that competition between nucleophilic and electrophilic palladium difluorocarbene ([Pd]=CF2) is the key factor controlling the catalytic difluorocarbene transfer. Difluorocarbene transfer is mostly limited to reactions that utilize its intrinsic electrophilicity. Now, a controllable palladium-catalysed difluorocarbene transfer reaction is reported that involves nucleophilic and electrophilic palladium difluorocarbene species. The selective reactions between arylboronic acids and the difluorocarbene precursor BrCF2PO(OEt)2 give four different products—difluoromethylated and tetrafluoroethylated arenes and their corresponding fluoroalkylated ketones.

  二氟羰基在医药、农用化学品和材料领域有着重要的应用，但所有这些应用都只是利用其固有的亲电性，通过少数几种反应进行的。在此，我们报告了一种钯催化策略，通过切换钯中心的价态（分别为 Pd(0) 和 Pd(ii)），使形成的钯二氟碳（Pd=CF2）物种同时具有亲核性和亲电性。在容易获得的芳基硼酸和二氟羰基前体溴二氟甲基膦酸二乙酯（BrCF2PO(OEt)2）之间会发生可控的二氟羰基催化转移。仅从这个简单的氟源，二氟碳转移就能获得四种类型的产物：二氟甲基化和四氟乙基化的炔类化合物及其相应的氟烷基化酮类化合物。这种转移还可应用于药品和农用化学品的改性，以及含氟化合物的一锅多元合成。机理和计算研究一致表明，亲核和亲电性钯二氟碳（[Pd]=CF2）之间的竞争是控制催化二氟碳转移的关键因素。二氟碳的转移大多局限于利用其固有亲电性的反应。现在，报告了一种可控的钯催化二氟碳转移反应，该反应涉及亲核和亲电的钯二氟碳物种。芳基硼酸与二氟碳前体 BrCF2PO(OEt)2 的选择性反应产生了四种不同的产物：二氟甲基化和四氟乙基化的炔类化合物及其相应的氟烷基化酮类化合物。
• Controllable Single and Double Difluoromethylene Insertions into C–Cu Bonds: Copper-Mediated Tetrafluoroethylation and Hexafluoropropylation of Aryl Iodides with TMSCF₂H and TMSCF₂Br
  作者：Xiu Wang、Shitao Pan、Qinyu Luo、Qian Wang、Chuanfa Ni、Jinbo Hu

  DOI：10.1021/jacs.2c03104

  日期：2022.7.13

  The selective difluoromethylene insertion into a C–Cu bond is a challenging task and is currently limited to either a single CF2 insertion into CuCF3 or double CF2 insertions into CuC6F5 (or (Z)-CF3CF = CFCu). Achieving both selective single and double CF2 insertions into the same C–Cu bond is even more difficult. Herein, highly controllable single and double CF2 insertions into CuCF2H species with

  选择性地将二氟亚甲基插入 C-Cu 键是一项具有挑战性的任务，目前仅限于单 CF 2插入 CuCF 3或双 CF 2插入 CuC 6 F 5（或 ( Z )-CF 3 CF = CFCu） . 在相同的 C-Cu 键中实现选择性单和双 CF 2插入甚至更加困难。在此，已经描述了使用 TMSCF 2 Br 试剂将高度可控的单和双 CF 2插入到 CuCF 2 H 物质中，提供了两种以前未知的氟烷基铜物质“Cu(CF 2 ) nCF 2 H” ( n = 1 和 2) 在不同反应条件下独立。这项工作代表了单和双 CF 2以高选择性方式插入同一 C-Cu 键的第一个例子。所获得的“Cu(CF 2 ) n CF 2 H” ( n = 1 和 2) 物质的合成价值通过它们与芳基碘、卤化剂和肉桂酰氯的反应来证明，这使得 HCF 2 CF的直接转移成为可能2和HCF 2 CF 2 CF 2部分变成有机分子。碳氟化合物链可控伸长率的关键1到
• Tetrafluoroethylation of Electron‐Rich Alkenyl Iodides Enabled by <i>in situ</i> Generation of Solvent‐Stabilized “Ligandless” CuCF2CF2H
  作者：Cristina Maria Segovia、Luana L. T. N. Porto、Paula Casasús、Isabel Bascuas、Amena Ahmad、Jordi Mestre、Miguel Bernús Pérez、Sergio Castillon、R. Tom Baker、Omar Boutureira

  DOI：10.1002/adsc.202301409

  日期：——

  for potential biological testing, an additional step was employed to eliminate these impurities. This step involves treating the reaction mixture with N-iodosuccinimide (NIS) and H2O, resulting in formation of the corresponding 2-deoxy-2-iodolactol (only from the D-glycal).21 This product can be easily separated from the reaction mixture, allowing for the isolation of the desired pure 2-(1,1,2,2-tet

  1,1,2,2-四氟乙基 (CF 2 CF 2 H) 基序属于多氟烷基家族 (R F =CF 3 、CF 2 H、CF 2 CF 3 ），它们在制药、农化和电子行业中引起了极大的兴趣。 1 由于其优异的生物物理特性和广泛的应用，该片段常见于杀菌剂、杀虫剂、除草剂和液晶成分中。它有助于增强药物效力、生物利用度、代谢稳定性和靶点选择性，这主要是由于 CF 2 H 末端形成氢键的能力（方案 1A）。 2 在掺入 1,1,2,2-四氟乙基部分的方法中， 3 金属介导的交叉偶联方法导致 C(sp 2 )−R F 键特别有吸引力，因为金属配合物与其芳基/烯基卤化物伙伴之间的特定相互作用所实现的位点选择性。现有的金属介导方法目前依赖于 Co 2 (CO) 8 、 4 M(C 2 的原位生成F 4 H)L n (M=Cu, Pd), 5, 6 以及预先形成的配合物 Cu(CF 2 CF 2 H)(PPh 2