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。     

含氮杂环的N-H和O-H二氟甲基化反应

有机氟化合物具有独特的化学、物理和生物性能,被广泛应用于医药、农药、新型功能材料、生命科学等领域.因此,发展便捷高效的合成方法,将单个的氟原子（-F）、二氟甲基（-CF₂H）或者三氟甲基（-CF₃）引入有机小分子,是有机合成领域的热点.相对于发展相对成熟的三氟甲基化反应,二氟甲基化反应发展相对滞后.利用廉价、易保存的溴二氟乙酸乙酯在Na₂CO₃的条件下产生二氟卡宾,并顺利发生N-H,O-H的二氟甲基化反应,成功的将二氟甲基引入到有机小分子中.该反应的底物适用性很广,官能团的兼容性也很好,卤素、醛基、硝基、腈基等取代的底物均能顺利的发生反应.     

铜促进的三氟甲基化反应研究进展

药物分子中含有三氟甲基可以有效改善其亲脂性、可吸收性以及代谢稳定性.因此,在有机分子中引入三氟甲基引起了人们的广泛关注.近年来,过渡金属催化的三氟甲基化反应得到了快速发展.其中,铜作为一种廉价且活性较高的催化剂能够实现多种三氟甲基化反应.从发生三氟甲基化反应的底物出发,综述了近年来卤代烃、硼试剂、C—H化合物、胺类、羧酸类化合物等的三氟甲基化反应研究进展.     

经由三氟甲基自由基的三氟甲基化反应研究进展

含有三氟甲基的有机分子在功能材料、农业化学品、制药等领域具有广泛应用,发展三氟甲基化的新方法是有机化学中的热点．通过产生三氟甲基自由基形成碳碳键是三氟甲基化的重要策略．本文依据三氟甲基自由基产生的不同方式,分3部分介绍三氟甲基自由基经由的碳碳键形成反应．     

单氟甲基化反应的研究进展

有机氟化物在医药、农业化学等领域发挥着不可缺少的作用,其中,氟甲基官能团具有较强的的亲脂性,可以极大地改善药物分子的药代动力学性质.因此,开发各类氟化反应具有重要的价值,尤其向分子中引入单氟甲基在氟化学领域备受关注.针对不同结构分子的单氟甲基化,按照氟甲基试剂分类总结单氟甲基化反应的研究进展,并对部分反应可能的机理进行讨论.     

5-三氟甲基胡椒醛的合成研究

以香草醛为起始原料,经碘代、脱甲基、亚甲基醚化、三氟甲基化反应以较高收率合成了5-三氟甲基胡椒醛,产物结构经过了1H NMR,13C NMR,19F NMR和HRMS的确证.重点研究了三氟甲基化反应,考察了不同三氟甲基化试剂、溶剂、催化剂用量、反应温度以及反应时间对三氟甲基化反应收率的影响,确定了最佳反应条件.随后,该方法成功运用于3,4位不同取代的5-碘苯甲醛的三氟甲基化反应,制得了三种5-三氟甲基胡椒醛的衍生物.     

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.     

CF3Br参与的三氟甲基化反应研究进展

三氟甲基化反应是向有机物中引入氟原子的重要方法.综述了近年来以CF₃Br为三氟甲基源的三氟甲基化反应研究进展,重点介绍了各类反应涉及到的具体方法、每种方法的特点、适用范围及可能的机理,并对CF₃Br作为三氟甲基源的三氟甲基化反应前景作出展望.     

三氟甲基亚磺酸钠实现的三氟甲基化反应研究进展

三氟甲基能够提高药物的化学和代谢稳定性,改善其亲脂性和生物利用度,增强药物的结合选择性,具有广泛的应用.三氟甲基亚磺酸钠(CF_3SO_2Na)稳定、低价,在有机氟化学领域应用广泛.综述了近三年来CF_3SO_2Na作为三氟甲基源在三氟甲基化反应中的最新研究进展,分别叙述了其在双官能团化、芳烃三氟甲基化、三氟甲硫基化及其他反应中的应用及部分反应机理,希望为今后三氟甲基的引入提供参考.     

可见光促进的光氧化还原催化的三氟甲基化反应

全氟烷基化反应,特别是三氟甲基化反应一直是有机化学领域的研究热点。近几年来,可见光促进的光氧化还原催化的有机化学反应,因其本身所固有的条件温和、绿色和环保等优点而倍受合成化学家的青睐。该方法学也被成功地应用于一系列三氟甲基化反应。本文主要按照三氟甲基源分类,总结了近年来可见光促进的光氧化还原催化的三氟甲基化反应的研究进展,并对其发展趋势进行了展望。     

Synthesis and properties of mercury bis(trifluoromethyl)phosphanides and their phosphane complexes

The thermally unstable compounds Hg(CN)P(CF(3))(2) and Hg[P(CF(3))(2)](2) were obtained by reactions of mercury cyanide and bis(trifluoromethyl)phosphane in solution and characterized by multinuclear NMR spectroscopy. An increase in thermal stability is observed when the products form 18 valence electron complexes. The compounds [Hg(P(CF(3))(2))(2)(dppe)] (dppe = 1,2-bis(diphenylphosphanyl)ethane) and [Hg(P(CF(3))(2))(2)(Me(3)P)(2)] have been isolated in almost quantitative yield by reacting [Hg(CN)(2)(dppe)] or [Hg(CN)(2)(Me(3)P)(2)] with HP(CF(3))(2). [Hg(P(CF(3))(2))(2)(dppe)] crystallizes in the triclinic space group P1. The mercury atom is coordinated in a distorted tetrahedral fashion. The Hg-P(CF(3))(2) bonds, ca. 250 pm, are significantly longer than those of the mercury bis(phosphanides) Hg(PR(2))(2) with R = t-Bu, 245 pm, or SiMe(3), 241 pm. These easily accessible compounds [Hg(P(CF(3))(2))(2)(dppe)] and [Hg(P(CF(3))(2))(2)(Me(3)P)(2)] act as nucleophilic bis(trifluoromethyl)phosphane group transfer reagents.     

Improvements in the detection and analysis of CF3-containing compounds in the background atmosphere by gas chromatography-high-resolution mass spectrometry

An improved method for the gas chromatography/mass spectrometry analysis of CF3-containing compounds in air is described. This method replaces a GS-Q porous layer open tubular (PLOT) column previously used with a 30 m x 0.32 mm GS-GasPro PLOT column. For this exceedingly volatile set of compounds the GS-GasPro column provides improved peak shapes, better signal-to-noise responses and no coelution of compounds. These improvements have allowed eleven CF3-containing compounds to be detected in background air, including CF4 (FC 14), C2F6 (FC 116), CF3Cl (CFC 13), CF3H (HFC 23), CF3Br (Halon 1301), C3F8 (FC 218), CF3CF2Cl (CFC 115), CF3CHF2 (HFC 125), CF3CH3 (HFC 143a), CF3CH2F (HFC 134a), and CF3CFCl2 (CFC 114a). Three of these compounds have not been previously detected in background air, to our knowledge. Quantitative determinations for each of these compounds in the background atmosphere of Montana are also reported.     

Synthesis of trifluoromethylated azines via nucleophilic oxidative substitution of hydrogen by trifluoromethyl carbanions

A novel, three-step method of trifluoromethylation of azines via oxidative nucleophilic substitution of hydrogen in the heteroaromatic ring by a CF3- carbanion is presented. The key reaction of this process is the addition of the CF3- carbanion, generated by treatment of Me3SiCF3 with KF(s) and Ph3SnF catalyst, to N-alkylazinium salts. The resulting dihydroazines containing a trifluoromethyl group are relatively stable compounds and can be isolated in a pure form. Deprotection of the N-p-methoxybenzyl substituent and aromatization of the heterocyclic ring upon treatment with CAN provides azines with a CF3 group in the ring position originally occupied by hydrogen. The whole process can be thus considered as a nucleophilic oxidative displacement of hydrogen by a CF3- carbanion.     

Copper-catalyzed oxidative trifluoromethylation of terminal alkenes using nucleophilic CF3SiMe3: efficient C(sp3)-CF3 bond formation

An efficient C(sp(3))-CF(3) bond-forming reaction via Cu-catalyzed oxidative trifluoromethylation of terminal alkenes has been developed, which proceeds under mild conditions using readily available, less expensive CF(3)SiMe(3) as the source of the CF(3) group. This method allows access to a variety of trifluoromethylated allylic compounds.     

Elimination of R-H from iridium acyl hydrides without loss of CO: evidence for the intervention of metal cation/carbanion pairs

Instead of reductive elimination of aldehyde, or decarbonylation to give a trifluoroalkyl hydride, heating Cp*(PMe3)Ir(H)[C(O)CF3] leads to the quantitative formation of Cp*(PMe3)Ir(CO) and CF3H. Kinetic experiments, isotope-labeling studies, solvent effect studies, and DFT calculations support a mechanism which involves dissociation of trifluoromethyl anion to give the transient ion-pair intermediate [Cp*(PMe3)Ir(H)(CO)]+[CF3]-. Further evidence for the ability of CF3 to act as a leaving group came from investigation of the analogous methyl and chloride derivatives Cp*(PMe3)Ir(Me)[C(O)CF3] and Cp*(PMe3)Ir(Cl)[C(O)CF3]. Both of these compounds undergo a similar loss of trifluoromethyl anion, generating an iridium carbonyl cation and CF3D in CD3OD.     

Synthesis, characterization, and theoretical study of stable isomers of C70(CF3)n (n = 2, 4, 6, 8, 10)

Reaction of C70 with ten equivalents of silver(I) trifluoroacetate at 320-340 degrees C followed by fractional sublimation at 420-540 degrees C and HPLC processing led to the isolation of a single abundant isomer of C70(CF3)n for n = 2, 4, 6, and 10, and two abundant isomers of C70(CF3)8. These six compounds were characterized by using matrix-assisted laser desorption ionization (MALDI) mass spectrometry, 2D-COSY and/or 1D 19F NMR spectroscopy, and quantum-chemical calculations at the density functional theory (DFT) level. Some were also characterized by Raman spectroscopy. The addition patterns for the isolated compounds were unambiguously found to be C1-7,24-C70(CF3)2, C1-7,24,44,47-C70(CF3)4, C2-1,4,11,19,31,41-C70(CF3)6, Cs-1,4,11,19,31,41,51,64-C70(CF3)8, C2-1,4,11,19,31,41,51,60-C70(CF3)8, and C1-1,4,10,19,25,41,49,60,66,69-C70(CF3)10 (IUPAC numbering). Except for the last compound, which is identical to the recently reported, crystallographically characterized C70(CF3)10 derivative prepared by a different synthetic route, these compounds have not previously been shown to have the indicated addition patterns. The largest relative yield under an optimized set of reaction conditions was for the Cs isomer of C70(CF3)8 (ca. 30 mol % of the sublimed mixture of products based on HPLC integration). The results demonstrate that thermally stable C70(CF3)n isomers tend to have their CF3 groups arranged on isolated para-C6(CF3)2 hexagons and/or on a ribbon of edge-sharing meta- and/or para-C6(CF3)2 hexagons. For Cs- and C2-C70(CF3)8 and for C2-C70(CF3)6, the ribbons straddle the C70 equatorial belt; for C1-C70(CF3)4, the para-meta-para ribbon includes three polar hexagons; for C1-7,24-C70(CF3)2, the para-C6(CF3)2 hexagon includes one of the carbon atoms on a C70 polar pentagon. The 10.3-16.2 Hz 7JF,F NMR coupling constants for the end-of-ribbon CF3 groups, which are always para to their nearest-neighbor CF3 group, are consistent with through-space Fermi-contact interactions between the fluorine atoms of proximate, rapidly rotating CF3 groups.     

Synthesis, structure, and 19F NMR spectra of 1,3,7,10,14,17,23,28,31,40-C60(CF3)10

A significant improvement in the selectivity of fullerene trifluoromethylation reactions was achieved. Reaction of trifluoroiodomethane with [60]fullerene at 460 degrees C and [70]fullerene at 470 degrees C in a flow reactor led to isolation of cold-zone-condensed mixtures of C60(CF3)n and C70(CF3)n compounds with narrow composition ranges: 6 < or = n < or = 12 for C(60)(CF3)n and 8 < or = n < or = 14 for C70(CF3)n. The predominant products in the C(60) reaction, an estimated 40+ mol % of the cold-zone condensate, were three isomers of C60(CF3)10. Two of these were purified by two-stage HPLC to 80+% isomeric purity. The third isomer was purified by three-stage HPLC to 95% isomeric purity. Thirteen milligrams of this orange-brown compound was isolated (5% overall yield based on C60, and its C1-symmetric structure was determined to be 1,3,7,10,14,17,23,28,31,40-C60(CF3)10 by X-ray crystallography. The CF3 groups are either meta or para to one another on a p-m-p-p-p-m-p-m-p ribbon of edge-sharing C6(CF3)2 hexagons (each pair of adjacent hexagons shares a common CF3 group). The selectivity of the C70 reaction was even higher. The predominant product was a single C70(CF3)10 isomer representing >40 mol % of the cold-zone condensate. Single-stage HPLC led to the isolation of 12 mg of this brown compound in 95% isomeric purity (27% overall yield based on converted C70. The new compounds were characterized by EI or S(8)-MALDI mass spectrometry and 2D-COSY 19F NMR spectroscopy. The NMR data demonstrate that through-space coupling via direct overlap of fluorine orbitals is the predominant contribution to J(FF) values in these and most other fullerene(CF3)n compounds.     

一类含氟芳基噁二唑化合物的合成及其光物理和电化学性质研究

合成和表征了一类苯环上含F和CF₃基团的1,3,4-噁二唑类化合物, 研究了它们的紫外-可见光谱、荧光光谱和电化学性质. 结果表明, 与不含氟的噁二唑化合物相比, 三氟甲基苯单元可降低化合物的LUMO能级, 而四氟苯单元则对化合物的光学和电化学性质无显著影响.     

Spectroscopic and structural assignment of the absolute stereochemistry in a series of 1,2-difluorovinyl organometalloids. The first crystallographic characterization and structural series of group 14 fluorovinyl compounds

The group 14 trifluorovinyl compounds Ph(3)ECF=CF(2) (E = Ge, Sn, Pb) have been prepared in high yield by the low-temperature reaction of the triphenylelement halide with trifluorovinyllithium, generated from tetrafluoroethane (CF(3)CH(2)F, HFC-134a) and 2 equiv of n-butyllithium. The X-ray crystal structures of these materials have been obtained, so affording the first structural series for such species. Subsequent reaction of Ph(3)GeCF=CF(2) with LiAlH(4) and a range of organolithium reagents has led to preparation of the 1,2-difluorovinylgermanes Ph(3)GeCF=CFR (R = H, Me, n-Bu, t-Bu, Ph). Multinuclear NMR spectroscopic and X-ray crystallographic studies of these compounds have been undertaken and have shown unequivocally the exclusive trans-geometry of the 1,2-difluorovinyl moiety.     

Trifluoromethyl derivatives of insoluble small-HOMO-LUMO-gap hollow higher fullerenes. NMR and DFT structure elucidation of C2-(C74-D3h)(CF3)12, Cs-(C76-Td(2))(CF3)12, C2-(C78-D3h(5))(CF3)12, Cs-(C80-C2v(5))(CF3)12, and C2-(C82-C2(5))(CF3)12

Reaction of a mixture of insoluble higher fullerenes with CF3I at 500 degrees C produced a single abundant isomer of C74(CF3)12, C76(CF3)12, and C80(CF3)12, two abundant isomers of C78(CF3)12 and C82(CF3)12, and an indeterminant number of isomers of C84(CF3)12. Using a combination of 19F NMR spectroscopy, DFT calculations, and the structures and spectra of previously reported fullerene(CF3)n compounds, the most-probable structures of six of the seven isolated compounds were determined to be specific isomers of C2-(C74-D3h)(CF3)12, Cs-(C76-Td(2))(CF3)12), C2-(C78-D3h(5))(CF3)12), Cs-(C80-C2v(5))(CF3)12), C2-(C82-C2(5))(CF3)12), and C2-(C82-C2(3))(CF3)12) containing ribbons and/or loops of edge-sharing para-C6(CF3)2 hexagons. The seventh isolated compound is a C1 isomer of C78(CF3)12 containing two such ribbons. This set of compounds represents only the second reported isolable compound with the hollow C74-D3h cage and the first experimental evidence for the existence of the hollow fullerenes C76-Td(2), C78-D3h(5), C80-C2v(5), and C82-C2(5) in arc-discharge soots.