常见三氟甲基源释放三氟甲基自由基能力的理论计算研究

三氟甲基自由基源（·CF₃）是发展自由基三氟甲基化反应的基础.采用密度泛函理论（M06-2X）,系统研究35个常见三氟甲基源释放CF₃自由基的能力（TR^·DA：trifluoromethyl radical donor ability）及可能的途径.计算结果表明,35个三氟甲基源通过化学键均裂释放三氟甲基自由基所需能量跨度为-21.5至95.2 kcal·mol^-1.单电子转移、卤键和硫键给体（halogen/chalcogen-bond donor）可促进CF₃自由基释放.相关研究结果将有助于理解和设计新自由基三氟甲基化试剂和反应.     

自由基三氟甲基化反应进展

近年来,三氟甲基化反应得到了快速的发展和广泛的关注,由于三氟甲基本身的一些特殊化学和物理性质,使得其在医药、农药和材料等领域发挥着越来越重要的作用。 随着有机氟化学的发展,对于自由基三氟甲基化反应也有了新的认识。 本文通过对不同的三氟甲基试剂作为三氟甲基自由基的前体,综述了近年来自由基三氟甲基化反应的研究进展,并予以展望。     

无光敏剂参与的可见光诱导咪唑并[1,2-a]吡啶的三氟甲基化反应(英文)

发展了一个无光敏剂参与的可见光促进的咪唑并[1,2-a]吡啶衍生物的三氟甲基化新反应.该反应利用本课题组此前发展的基于硫叶立德骨架的亲电三氟甲基化试剂作为三氟甲基自由基源,反应条件温和,底物普适性好,同时兼容常见的官能团.机理研究表明该反应可被自由基捕获剂阻断.对两个反应底物及它们的1∶1混合物的紫外-可见光吸收光谱进行了研究,研究表明三氟甲基化试剂与咪唑并[1,2-a]吡啶之间形成了一个Donor-Acceptor加合物.在此基础上提出了一个合理的机理,即该加合物在光照条件下被激发,发生硫-三氟甲基键均裂生成三氟甲基自由基,该自由基与咪唑并[1,2-a]吡啶发生自由基取代反应.同时也成功地将该方法应用于治疗胃溃疡药物佐利米定的三氟甲基化衍生物的合成.     

以三氟乙酸及其衍生物为三氟甲基源的三氟甲基化反应研究进展

含有三氟甲基基团的有机分子中常常表现出独特的物理和化学性质,具有非常广泛的应用.三氟乙酸及其衍生物具有廉价、易得、稳定等优点,并且反应的副产物是二氧化碳,是理想的三氟甲基化试剂,具有广阔的应用前景.综述了以三氟乙酸及其衍生物为三氟甲基源的三氟甲基化反应的最新研究进展,主要包括C—X (X=Br, I)键、C—H键,C=X (X=C, O)的三氟甲基化反应,对反应的相关机理进行了论述.     

可见光促进合成三氟甲基取代的四氢呋喃和四氢吡喃（英文）

利用相对廉价易得、操控简便的三氟甲基磺酰氯为三氟甲基自由基前体,在可见光催化下通过非活化烯烃的自由基1,2-烷氧基-三氟甲基化反应实现了一系列三氟甲基化的四氢呋喃和四氢吡喃化合物的高效合成.     

历经不同高价芳基铜中间体的芳香碳氢键三氟甲基化反应

在温和的铜盐促进反应条件下,四氮杂杯[1]芳烃[3]吡啶化合物发生高效、高选择性芳香碳氢键三氟甲基化反应,高产率地生成了一系列三氟甲基官能化的大环分子.基于结构明确的芳基二价铜和芳基三价铜的三氟甲基化反应的结果,铜促进的芳香碳氢键三氟甲基化反应依据三氟甲基化试剂的性质经历了两条完全不同的途径.当使用亲核性的Ruppert-Prakash试剂时,芳基三价铜与三氟甲基阴离子生成[ArCu(Ⅲ)CF₃]⁺配合物及发生还原消除是反应的关键步,而当使用亲电性的Umemoto试剂时,反应经历了芳基二价铜与三氟甲基自由基的直接偶联过程.     

三氟甲基烯烃的选择性C—F键活化最新进展（英文）

三氟甲基的选择性碳氟键活化是获得偕二氟类化合物的重要途径.鉴于三氟甲基烯烃在合成上的重要性以及反应选择性的多样性,近年来利用这类化合物的选择性碳氟键活化引起了极大的关注.综述了这一领域的研究进展,主要包括亲核加成/脱氟反应(S_N2’类型)、酸促进的脱氟傅克芳基化反应、(形式)原位脱氟官能团化反应以及过渡金属催化的迁移插入/脱氟反应.     

三氟甲基季碳中心的合成进展

三氟甲基是一个重要的含氟基团,常被应用于药物和农药领域.季碳中心是广泛存在于天然产物和合成药物中的结构.近年来,构建含有三氟甲基季碳中心的分子得到了快速发展.从直接三氟甲基化反应、新的合成砌块和新反应的探索几个方面,综述了近十年来合成三氟甲基季碳中心的研究进展.     

2,3-丁二酮介导的CF3SO2Na与烯烃的氧化三氟甲基化反应

以2,3-丁二酮作为光催化剂, 三氟甲基亚磺酸钠作为三氟甲基化试剂, 在可见光诱导下, 采用温和的反应条件高效地实现了烯烃衍生物的氧化三氟甲基化反应, 以52%~78%的收率合成了22个含有三氟甲基酮类结构的化合物(3a~3v). 该反应的特点是用2,3-丁二酮代替昂贵的金属光催化剂, 在可见光范围内从廉价的三氟甲基化试剂中引发出三氟甲基自由基, 并在氧化剂的协同作用下进行烯烃的氧化三氟甲基化反应.     

(二氟甲基)三甲基硅烷试剂参与的二氟甲基化反应

与三氟甲基类似,二氟甲基对于药物开发非常重要,而(二氟甲基)三甲基硅烷试剂(Me₃SiCF₂H,经常被简写为TMSCF₂H)是最常用的二氟甲基化试剂之一. TMSCF₂H试剂参与的二氟甲基化反应曾长时间不受重视直到2011年之后才不断被报道.本文综述了TMSCF₂H试剂的制备方法,并根据不同反应类型的分类(亲核加成、亲核取代、金属参与的交叉偶联反应、C–H键官能团化等),综述了TMSCF2H参与的各类二氟甲基化反应的研究进展.     

Free radical-mediated aryl amination and its use in a convergent [3 + 2] strategy for enantioselective indoline alpha-amino acid synthesis

The scope of aryl radical additions to the nitrogen of azomethines is described. Aryl, trifluoromethyl alkyl, and alpha,beta-unsaturated ketimines engage in regioselective aryl-nitrogen bond formation via 5-exo cyclizations of an aryl radical to azomethine nitrogen. Selectivity for carbon-nitrogen over carbon-carbon bond formation is generally high (>95:5) and competes only with direct aryl radical reduction by stannane (0-10%). Alpha-ketoimines are a promising new class of carbon radical acceptors for which no competitive aryl radical reduction is observed. The reaction conditions are pH-neutral and are therefore among the mildest methods available for amination of an aromatic ring. The ketimines examined did not suffer from competitive reduction by stannane, offering an advantage over the use of diazo and azide functional groups as nitrogen sources for carbon radicals. The free radical-mediated aryl amination was sequenced with the O'Donnell phase transfer-catalyzed enantioselective alkylation strategy of glycinyl imine to provide either enantiomer of indoline alpha-amino acids with high ee. These new constrained phenyl alanine derivatives are now readily available for evaluation across a variety of applications.     

Anodic oxidations and polarity: exploring the chemistry of olefinic radical cations

The cyclization chemistry of radical cations derived from electron-rich olefins has been examined and the relationship between the polarization of the radical cation and the chemoselectivity of the reaction probed. It was found that more polarized radical cations favor carbon-carbon bond formation while less polarized radical cations favor carbon-heteroatom bond formation. A new approach to the synthesis of quaternary carbons was uncovered and the compatibility of ene diol ethers with anodic olefin coupling reactions examined.     

Consecutive carbon-carbon bond formation approach in tandem cyclization reactions

The conventional tandem cyclization reactions involve the formation of alternating carbon-carbon bonds, whereas the newly developed cyclization reactions involve the formation of consecutive carbon-carbon bonds, in which N-aziridinylimines have been utilized as geminal radical acceptor and donor equivalents in a single operation. This unprecedented tandem cyclization approach becomes feasible by the successful generation of 5- and 6-membered ring radicals by radical cyclizations of N-aziridinylimines. The same notion can be applied to the anionic cyclizations of N-aziridinylimines, thereby allowing anionic consecutive carbon-carbon bond formation. This approach has great synthetic potential, particularly for the construction of quaternary carbon centers, and it provides highly efficient routes for the synthesis of natural products.     

Electron transfer initiated heterogenerative cascade cyclizations: polyether synthesis under nonacidic conditions

[reaction: see text] Single-electron oxidation has been employed to initiate heterogenerative cascade cyclization reactions that form polyether compounds under essentially neutral conditions. The reactions proceed through mesolytic benzylic carbon-carbon bond cleavages of homobenzylic ether-derived radical cations followed by intramolecular epoxonium ion formation, leading to further cyclizations. Both oligotetrahydrofuran and tetrahydropyran structures can be prepared by altering substrate topography.     

Electrochemical carboxylation with carbon dioxide

Studies carried out in the past two years on electrochemical fixation of carbon dioxide with carbon-carbon bond formation, so-called electrochemical carboxylation or electrocarboxylation, are reviewed. Among about twenty papers on electrochemical carboxylation published from 2014 to the present, recent advances in electrochemical carboxylation regarding asymmetric carboxylation, sacrificial anode-free carboxylation, and carboxylation following aryl radical cyclization are focused on and discussed.     

A synthetic approach to seven-membered lactones by the microbial transformation of ynones having a trifluoromethyl group

Studies on the microbial transformations of a number of ynones bearing a trifluoromethyl group prepared by the reaction of ethyl trifluoroacetate with a variety of lithium alkynates, have been undertaken. The major products were the corresponding carbinols but microbial carbon-carbon bond degradation and formation occurred also, which proceeded to novel fluorinated seven-membered lactones as significant products.     

Preparation and synthetic application of a novel ketene silyl acetal of methyl trifluoropyruvate

[reaction: see text] A novel trifluoromethyl ketene silyl acetal (4) of methyl trifluoropyruvate (1) was prepared in 82% yield by metal Mg reduction in a (TMS)Cl/THF system. Subsequent carbon-carbon bond formation such as Mukaiyama aldol, Michael addition, and other nucleophilic reactions of 4 at the trifluoromethylated carbon with various electrophiles gave various coupling products in high yields.     

Ring closing enyne metathesis: a powerful tool for the synthesis of heterocycles

The ring closing metathesis (RCM) is a powerful method in organic synthesis for the preparation of cyclic compounds by formation of new carbon-carbon bonds. In the past years a particular subclass of the RCM, the ring closing enyne metathesis (RCEYM), has attracted attention due to its synthetic potential in the generation of ring structures with 1,3-diene moieties, which can subsequently be further functionalised. In this tutorial review mechanistic considerations will be described and the synthetic power of this useful and attractive carbon-carbon bond forming reaction will be illustrated by recent examples of RCEYM applications in the preparation of heterocyclic compounds.     

Practical Enzymatic Production of Carbocycles

The Pd-catalyzed carbon-carbon bond formation pioneered by Heck in 1969 has dominated medicinal chemistry development for the ensuing fifty years. As the demand for more complex three-dimensional active pharmaceuticals continues to increase, preparative enzyme-mediated assembly, by virtue of its exquisite selectivity and sustainable nature, is poised to provide a practical and affordable alternative for accessing such compounds. In this minireview, we summarize recent state-of-the-art developments in practical enzyme-mediated assembly of carbocycles. When appropriate, background information on the enzymatic transformation is provided and challenges and/or limitations are also highlighted.     

A practical diastereoselective synthesis of β-hydroxy-β-trifluoromethyl imines

The asymmetric carbon-carbon bond formation reaction affording chiral β-hydroxy-β-trifluoromethyl imines is reported involving the nucleophilic addition of sulfinimine anions derived from chiral N-(tert-butanesulfinyl) ketimines to trifluoromethyl ketones. The reaction tolerates a wide range of nucleophiles, giving the condensation products in good to excellent total yields with good diastereoselectivities (up to 85:15 dr).