有机化合物氟化反应的研究进展

有机氟化物具有独特的物理、化学性质及生理活性，在医学、农业化学、材料科学等领域引起了广泛关注。本文综述了氟气直接氟化、Balz-Schiemann反应、亲核氟化、亲电氟化和自由基氟化等氟化反应的优缺点，旨在为相关有机氟化物的化学合成提供新思路。     

亲电氟化反应的新进展

介绍了自八十年代以来亲电氟化反应的最新进展, 其中包括众多的N-F类电氟化试剂的制备, 它们和各种底物的反应以及此类亲电氟化反应可能的机理。     

对映选择性亲电氟化反应研究进展

含氟有机化合物, 特别是手性氟化物在医药、农药及功能性材料等相关领域的作用备受注目. 尽管在分子中有立体选择性地引入一个氟原子一直是有机化学家面临的一个挑战性问题, 近年来在化学家们的不断努力下, 对映选择性氟化反应研究取得重要进展. 高光学活性的手性氟化物可通过手性亲电氟化试剂诱导的立体选择性氟化反应, 基于底物的手性氟化反应以及手性催化剂诱导的不对称催化氟化反应等来制备. 特别是, 手性金属配合物和有机催化剂诱导的不对称催化氟化反应被广泛应用于各类手性氟化物的合成, 已成为不对称氟化反应研究的热点. 全面介绍对映选择性亲电氟化反应研究概况和最新进展, 讨论各种不对称氟化反应的特点及应用范围.     

离子液体在氟化反应中的应用进展

离子液体作为一类新型绿色溶剂,具有制备简单、稳定性好、溶解能力强、挥发性小、安全性强等优点,因此在有机单元反应包括酯化、氧化、还原、重排反应等中的应用相当广泛,有着十分诱人的应用前景.虽然其在氟化反应中的应用研究开始得较晚,但发展很快,目前在重氮化氟化、亲核氟化、亲电氟化以及电化学氟化等方面都取得了较大的进展.本文综述了近年来离子液体在氟化反应中应用的最新进展情况,并对其未来发展方向和应用前景进行了展望.     

高价碘试剂介导的8-氨基喹啉C(5)位碳-氢键亲核氟化反应

8-氨基喹啉的C(5)位碳-氢键氟化反应近年来受到广泛关注,但大多需要使用过渡金属催化剂和亲电氟化试剂来实现.在高价碘试剂的介导下实现了无过渡金属催化条件下的8-氨基喹啉C(5)位碳-氢键亲核氟化反应.使用廉价易得且安全稳定的氟化银作为亲核氟化试剂,反应无需惰性气体保护,条件简单,操作方便,区域选择性好,底物范围较广,为喹啉类化合物的氟化提供了一种有潜在应用价值的新方法.     

三乙胺三(氟化氢)在有机合成中的应用

氟化反应在有机合成中有着广泛的应用, 三乙胺三(氟化氢)作为氟化试剂有着其它氟化试剂所无法比拟的优越性. 对近年来三乙胺三(氟化氢)在有机合成中的应用进行了总结和概述, 重点介绍了亲核取代、环氧开环反应、亲电加成反应和脱硅保护基等反应.     

微波辅助离子液体合成法在亲核氟化中的应用

采用微波辅助合成法快捷、高效地制备了系列咪唑类和吡啶类离子液体,并对其在亲核氟化中的应用进行了研究.结果表明,N-苄基吡啶四氟硼酸盐([bepy]BF4)是一种稳定性高、使用效果好的离子液体.在微波作用下,以N-苄基吡啶四氟硼酸盐和乙腈为共溶剂,以氟化铯为氟化试剂,高效合成了系列含氟化合物.在优化反应条件下,其收率为54.1%～76.3%,反应时间较常规油浴加热最好时可缩短50%以上.     

亲核性氟源在碳碳不饱和键选择性氟化官能化反应中的应用

含氟化合物表现出的特殊理化和生物活性使得其在药物、农用化学品和材料科学等领域有着广泛而重要的应用,因此,含氟化合物的高效制备不仅成为了合成化学的研究热点之一,而且极大地推动了相关领域的蓬勃发展.其中,在有机分子内直接引入氟原子的方法主要有亲电氟化和亲核氟化.相较于亲电氟化,亲核氟化反应所用的氟化试剂通常廉价易得,所需的反应条件也比较温和.作者课题组借助过渡金属催化、可见光氧化还原催化和可见光促进策略,拓展了亲核性氟源在碳碳不饱和键选择性氟化官能化反应中的应用,合成了一系列结构新颖的含氟化合物.在该研究评论中将对此做出小结,并对该领域值得关注的研究方向进行简要的展望.     

PhI(OAc)_2参与的β-酮酸酯及β-酮酰胺亲核氟化反应

报道了一种构建含氟的β-酮酸酯及β-酮酰胺的亲核氟化反应.该反应采用Ph I(OAc)_2为氧化剂、3HF·Et3N为氟化试剂,在室温下反应30min高效构建一系列含有季碳中心的含氟化合物.与传统的亲电氟化反应相比,该方法具有无金属参与、反应时间短、反应条件简单、反应收率高等优点.     

不同氨基保护下的α-羟基-γ-氨基磷酸酯的氟化反应

比较了不同氨基保护基对α-羟基-γ-氨基磷酸酯亲核氟化反应的影响,以 Boc, Ts和Bz保护氨基时未得到预期的氟化产物;以Phth, Fmo和CH3OCO-保护氨基时可得到氟化产物,其中Phth保护氨基的效果最好,氟化产物的收率42%     

Highly selective electrochemical fluorination of organic compounds in ionic liquids

Recent studies on electrochemical partial fluorination in ionic liquid fluoride salts are reviewed. At first, historical background and some problems of electrochemical fluorination in organic solvents are briefly mentioned. Solvent-free electrochemical fluorinations in ionic liquids are explained as follows. Ultrasonication was found to improve both the yield and current efficiency for electrochemical fluorination of α-phenylthioacetate, which is mainly attributable to marked mass transport promotion of the substrate and the suppression of anode passivation. Highly regioselective and efficient fluorination of cyclic ethers, lactones, and cyclic carbonate was achieved in Et₄NF·4HF and Et₃N·5HF. Selective fluorination of hardly oxidizable phthalide was realized using a combination of imidazolium and fluoride ionic liquids. The unique effect of imidazolium ionic liquids on electrochemical fluorodesulfurization of 3-phenylthiophthalide was explained. Reuse of ionic liquids for electrochemical fluorination is also possible.     

Copper-Mediated Fluorination of Aryl Trisiloxanes with Nucleophilic Fluoride

A method for the nucleophilic fluorination of heptamethyl aryl trisiloxanes to form fluoroarenes is reported. The reaction proceeds in the presence of Cu(OTf)₂ and KHF₂ as the fluoride source under mild conditions for a broad range of heptamethyltrisiloxyarenes with high functional group tolerance. The combination of this method with the silylation of aryl C−H bonds enables the regioselective fluorination of non-activated arenes controlled by steric effects following a two-step protocol.     

电化学氟化最新进展

本文从全氟化和部分氟化角度系统地叙述了电化学氟化在国内外的最新进展情况,并简要介绍了含氟有机物在医药上的应用.     

Rapid Synthesis of Aryl Fluorides in Continuous Flow through the Balz–Schiemann Reaction

The Balz–Schiemann reaction remains a highly utilized means for preparing aryl fluorides from anilines. However, the limitations associated with handling aryl diazonium salts often hinder both the substrate scope and scalability of this reaction. To address this, a new continuous flow protocol was developed that eliminates the need to isolate the aryl diazonium salts. The new process has enabled the fluorination of an array of aryl and heteroaryl amines.     

New synthesis methods for fluorinated carbon nanofibres and applications

Several new synthesis methods of fluorinated carbon nanofibres, such as controlled fluorination using fluorinating agent (TbF₄ or XeF₂), or assisted fluorination under UV and gamma irradiation, are reviewed and compared with the direct fluorination using undiluted fluorine gas. The results highlight the different fluorination mechanisms for the direct fluorination and the new methods. The other advantage of those alternative fluorination routes is the possibility to provide fine tuning of the fluorination level, i.e. from F/C atomic ratio close to zero, as a functionalization, to the unity (CF₁) according to the required application, electrochemical or tribological. Two applications are described in this paper as a function of the fluorine content: protection against ozonation and use as solid lubricants.     

Novel methods for the facile construction of 3,3-disubstituted and 3, 3-spiro-2H,4H-benzo[e]1,2-thiazine-1,1-diones: synthesis of (11S,12R, 14R)-2-fluoro-14-methyl-11-(methylethyl)spiro[4H-benzo[e]- 1, 2-thiazine-3,2'-cyclohexane]-1,1-dione, an agent for the electrophilic asymmetric fluorination of aryl ketone enolates

Novel methods for the facile construction of 3,3-disubstituted and 3, 3-spiro 2H,4H-benzo[e][1,2]thiazine-1,1-diones 8a-h are described. o-Methyl lithiation of N-Boc-o-toluenesulfonamide 6 followed by reaction with a variety of ketones gave the corresponding carbinol sulfonamides 7a-g, which underwent cyclization under acidic (methanesulfonic acid) or neutral (NaI/TMSCl/MeCN) conditions to afford the sultams 8a-h in high yields. The chiral spiro sultams 8g, h were subjected to FClO(3) fluorination to give the N-fluorosultams 11a,b, respectively, which were tested for electrophilic asymmetric fluorination of aryl ketone enolates. As a result, the N-fluorosultam 11a exhibited modest asymmetric inducing abilities with the highest ee, reaching 70% for enantioselective fluorination of the lithium enolate of 2-methyl-1-tetralone.     

CF Activation in Perfluorinated Arenes with Isonitriles under UV‐Light Irradiation

Due to the great value of fluorinated arenes in agrochemistry, medicinal chemistry and materials science, development of methods for preparation of fluorinated arenes is of high importance. They can be either accessed by arene fluorination or by partial arene defluorination. However, the carbon?fluorine bond belongs to the strongest σ‐bonds, which renders C?F activation highly challenging. Here it is shown that aryl and alkyl isonitriles efficiently activate the strong C?F bond in perfluoroarenes by simple UV irradiation under mild conditions. Reactions proceed by formal direct insertion of the isonitrile into the C?F bond without any transition metal. Activation occurs at arene C?F bonds whereas aliphatic C?F bonds remain unreacted. For selected perfluoroarenes C?F activation occurs with high regioselectivity and resulting imidoyl fluorides are transformed into other valuable compounds. Theoretical studies give insights into the reaction mechanism.     

甲基磺酰氟Simons电化学氟化过程特性和机理研究

选择CH₃SO₂F电化氟化制备CF₃SO₂F过程为研究系统,研究了电化氟化过程操作电压和反应时间的关系、操作条件对氟化产物组成的影响规律以及Ni电极在电化氟化过程的变化情况. 实验结果表明,Simons电化学氟化过程主要由三个步骤组成：F-在阳极发生电化学氧化反应生成F,该步骤是Simons电化学氟化过程的控制步骤;在Ni电极上生成的F与Ni或NiF₂反应生成高价NiF_n (n≥3),NiFn为Simons电化学氟化过程的氟化剂;NiF_n可以在电极/电解液界面与有机物发生氟化反应生成氟化产物,也可以发生分解反应生成游离F²,NiF_n与有机物发生氟化反应的机理与用CoF₃等为氟化剂氟化有机物的机理相同. 但NiF_n的反应活性比CoF₃高,且在实验条件下极不稳定.     

Silver-mediated fluorination of aryl silanes

A regiospecific silver-mediated fluorination of aryl silanes is reported. The reaction is operationally simple, and employs Ag₂O as readily available, inexpensive silver source, which can be recovered.     

Electrochemical fluorination of the n-methylmorpholine

The results of some researches as regards the possibility to carry out selective electrochemical fluorinations of organic compounds by use of organic solvents are reported.Various organic solvents (acetonitrile, 1,4-dioxane, N,N-dimethylformamide) have been employed in the electrochemical fluorination of the N-methylmorpholine (NMM), but the results have not been those expected. Because of strong interactions taken place within certain ratios solvent/HF, many difficulties have been got into as regards the conductivity.Better results were obtained working without the solvent and with a great concentration (40 %) of the NMM in hydrogen fluoride. In the experiments carried out, the electrochemical fluorination of the NMM appeared highly selective: at first it took place on the positions beside the oxygen atom, then on those beside the nitrogen atom and at last on the methylic group. A mechanism of the reaction is proposed.