注册 English

Trifluoromethoxylation/trifluoromethylthiolation/trifluoro-methylselenolation strategy for the construction of heterocycles

Xin Wang ,  Zhichuan Wang ,  Zhenjian Li ,  Kai Sun

downloadPDF
Citation:  Xin Wang, Zhichuan Wang, Zhenjian Li, Kai Sun. Trifluoromethoxylation/trifluoromethylthiolation/trifluoro-methylselenolation strategy for the construction of heterocycles[J]. Chinese Chemical Letters, 2023, 34(5): 108045. doi: 10.1016/j.cclet.2022.108045 shu

Trifluoromethoxylation/trifluoromethylthiolation/trifluoro-methylselenolation strategy for the construction of heterocycles

    • 作者简介: Xin Wang was born in Heilongjiang, China and received her MS degree from Northeast Normal University in 2012. In July 2013, she joined the College of Chemistry and Chemical Engineering, Anyang Normal University. In 2019, she pursued her Ph.D. degree in Zhengzhou University. Her research program is drug design, structural identification and structural modification of natural products;
    Zhichuan Wang was born in Jiangsu, China in 1997. In 2015, he began his studies at the School of Pharmacy, Jilin Medical University. In 2020, he pursued his MS degree in YanTai University under the direction of associate professor Kai Sun. His current research is focused on radical CH functionalization;
    Zhenjian Li, Doctor, Forestry Research Institute, China Academy of Forestry, Associate researcher, Master's supervisor. He mainly engage in the research on the components and functions of medicinal Dendrobium; Collection and development of ornamental and medicinal Dendrobium germplasm resources;
    Kai Sun was born in Shanxi, China in 1983. He received his Ph.D. degree in organic chemistry from Northeast Normal University in 2013 under the supervision of Prof. Qian Zhang. In July 2020, he joined the College of Chemistry and Chemical Engineering, YanTai University, where he is an professor. His current research is focused on CH functionalization, radical chemistry and organic selenium chemistry;

English

  • 1. Introduction

    Trifluoromethyl compounds play an important role in organic chemistry, the pharmaceutical chemistry, materials science, and many other fields [1-9], prompting organic chemists to connect heteroatoms (such as O, S, Se) with trifluoromethyl compounds to obtain new biological activities. The trifluoromethoxy-, trifluoromethylthio- and trifluoromethylseleno-groups have excellent electron-absorbing capacity (Hammett constants of OCF3: σP = 0.35, σm = 0.38; Hammett constant of SCF3: σP = 0.50 and σm = 0.40; Hammett constant of SeCF3: σP = 0.44 and σm = 0.45), valuable lipophilicity (Hansch-Leo parameter of OCF3: πR = 1.04; Hansch-Leo parameter of SCF3: πR = 1.44; Hansch-Leo parameter of SeCF3: πR = 1.29), bioavailability, and metabolic stability [10-12]. In addition, oxygen, sulfur and selenium, as typical nonmetallic elements in the oxygen group, display little difference in structure and electronic properties, allowing the isostructural substitution of oxygen, sulfur and selenium atoms in drug molecules, and recognition by biological targets. However, the differences are sufficiently large to alter other properties and obtain a variety of biological activities. This has broad prospects in the field of medicinal chemistry and has further stimulated chemists' interest in introducing XCF3 groups.

    Heterocyclic compounds are the key scaffolds in many natural products, organic materials, agrochemicals, and pharmaceuticals [13-18]. Oxygen-containing and nitrogen-containing heterocyclic compounds accounted for 52% of the top 200 brand name drugs by retail sales in 2021 [19]. Therefore, the importance of building heterocyclic compounds is self-evident. By introducing trifluoromethoxy-, trifluoromethylthio-, and trifluoromethylseleno-groups into heterocyclic compounds, the physical and chemical properties of the compounds can be fine-adjusted, including the selectivity, stability, lipophilicity, and membrane permeability. In addition, the novelty of trifluoromethoxylated, trifluoromethylthiolated, and trifluoromethylselenolated heterocyclic compounds has prompted organic chemists to develop multifunctional and practical preparation methods. The rapid development of this field is largely due to the development of trifluoromethoxylation, trifluoromethylthiolation, and trifluoromethylselenolation reagents, including nucleophilic, electrophilic, and radical types [20-23].

    In recent years, although reviews on trifluoromethoxylation, trifluoromethylthiolation, and trifluoromethylselenolation reactions have been published [24-34], systematic reviews exclusively on the synthesis of trifluoromethoxylated, trifluoromethylthiolated, and trifluoromethylselenolated heterocyclic compounds have not been reported. There are two main strategies to synthesize F3CX-containing heterocyclic compounds, one of which is to activate the C–H bond of heterocyclic compounds under the external action of metal or non-metal catalysts and directly introduce the XCF3 group. This method not only avoids the use of prefunctional groups or preactivated reaction substrates, resulting in the waste of resources, but also improves the economic efficiency of atomic use, reduces waste emissions, and adheres to the concept of "green chemistry". The second strategy is through the difunctionalization cyclization strategy of alkenes and alkynes to build F3CX-group heterocyclic compounds, which allows the unstable intermediates involved in the reaction, and plays an important role in the process of building polyheterocycle and heteroatom-rich heterocyclic compounds. This paper reviews the recent progress in the synthesis of trifluoromethoxylated, trifluoromethylthiolated, and trifluoromethylselenolated heterocyclic compounds mainly published in the past 10 years. The direct C–H trifluoromethoxylation, trifluoromethylthiolation, and trifluoromethylselenolation of heterocycles, and the synthesis of trifluoromethoxylated, trifluoromethylthiolated, and trifluoromethylselenolated heterocyclic compounds by the difunctionalization cyclization of alkenes and alkynes are reviewed. In addition, the scope, limitation, and mechanism of the reaction are discussed.

    2. Synthesis of trifluoromethylthiolated heterocycles

    Due to its unique lipophilicity and bioavailability, the trifluoromethylthiol group is widely found in bioactive drugs such as Toltrazuril, Baycox, Zolvix, and has attracted increased attention. The development of trifluoromethylthiolation reagents and new synthetic methods has invigorated the construction of trifluoromethylated heterocycles, which is the fastest growing platform compared with trifluoromethoxylated heterocycles and trifluoromethylselenated heterocycles. Therefore, we will first discuss the construction of trifluoromethylated heterocycle compounds from two aspects.

    2.1 Direct C–H trifluoromethylthiolation of heterocycles

    In 2013, Yang's group [35] reported a copper-catalyzed trifluoromethylthiolation of indoles with trifluoromethanesulfonyl hypervalent iodonium ylide as an SCF3 source (Scheme 1). Trifluoromethanesulfonyl hypervalent iodonium ylide has a low cost and stable performance, and is reduced to active SCF3 species by intramolecular rearrangement.

    Scheme 1

    Scheme 1.  Copper-catalyzed trifluoromethylthiolation of indoles.
    DownLoad: Full-Size Img PowerPoint

    In 2015, Wang's group [36] developed the selective trifluoromethylthiolation of a variety of electron-rich arenes and olefins using N-trifluoromethylthio saccharin as a highly electrophilic trifluoromethylthiolating reagent in the presence of a Lewis acid catalyst such as Fe(Ⅲ) or Au(Ⅲ) (Scheme 2). N-Protected indoles and unprotected indoles all have good yield and functional group tolerance. In the same year, Li's group [37] also reported an Rh(Ⅲ)-catalyzed electrophilic C-2 trifluoromethylthiolation of indoles with N-trifluoromethylthiosaccharin as an electrophilic SCF3 reagent (Scheme 3). It is noteworthy that the reaction occurred exclusively at the 3-position, when 1-phenyl-1H-indole was used as a substrate under standard conditions.

    Scheme 2

    Scheme 2.  Trifluoromethylthiolation of arenes with N-trifluoromethylthiosaccharin.
    DownLoad: Full-Size Img PowerPoint

    Scheme 3

    Scheme 3.  Rh(Ⅲ)-catalyzed electrophilic C-2 trifluoromethylthiolation of indoles.
    DownLoad: Full-Size Img PowerPoint

    In 2015, Huang's group [38] reported a copper-catalyzed trifluoromethylthiolation of pyrroles with trifluoromethanesulfonyl hypervalent iodonium ylide as the SCF3 source (Scheme 4). The reaction features mild reaction conditions, high reaction yields, and excellent functional group compatibility. Of note, 2,2′-dipyrromethane, which is the precursor of porphyrins, can be successfully converted into trifluoromethylthiolated products 11. When 4 equiv. of trifluoromethanesulfonyl hypervalent iodonium ylide is used, the yield of the product can reach 70%. When the ortho- positions of "N" are replaced by methyl, the 3-SCF3 product can be obtained. The possible reaction mechanism was suggested by the results of control experiments and electrospray ionization (ESI)-mass spectral detection of the intermediates. First, trifluoromethanesulfonyl hypervalent iodonium ylide 2 is converted to carbene 15, which is balanced with oxathiirene 16, under the catalysis of copper. Next, oxathiirene 16 rearranges to obtain sulfoxide 17, to give the active intermediate, thioperoxoate 18, by intramolecular nucleophilic collapse. Finally, thioperoxoate 18 reacts with the nucleophile (Nu), and the desired product Nu-SCF3 20 is obtained through the transfer of the trifluoromethylthio group. Thioperoxoate 18 can also give CF3SSCF3 19 in the absence of a nucleophile.

    Scheme 4

    Scheme 4.  Copper-catalyzed trifluoromethylthiolation of pyrroles with trifluoromethanesulfonyl hypervalent iodonium ylide.
    DownLoad: Full-Size Img PowerPoint

    In 2016, Chachignon et al. [39] reported a metal-free C-3 trifluoromethylthiolation of indoles with CF3SO2Cl as the source of electrophilic SCF3 and a phosphine as the reducing agent (Scheme 5). Notably, CF3SO2Cl is readily available compared with sophisticated SCF3 reagents which are difficult to use on a larger scale. The possible reaction mechanism was suggested by nuclear magnetic resonance (NMR) analysis of the reaction mixture. Initially, the S–Cl bond in CF3SO2Cl is broken, which is triggered by the halogen bond between the positive electrostatic potential outside the chlorine atom in CF3SO2Cl 21 and the lone pair of electrons on the phosphorus atom in PMe3 22. The resulting chlorophosphonium sulfinate 25 is converted into CF3SOCl 26 and OPMe3 27. Next, the S–Cl bond in CF3SOCl 26 is broken, which is triggered by the halogen bond between the positive electrostatic potential outside the chlorine atom in CF3SOCl 26 and the lone pair of electrons on the phosphorus atom in PMe3 22. The resulting product 29 is converted into the OPMe3 27, and the active intermediate product CF3SCl 30. Finally, CF3SCl 30 reacts with indole 31 to give the direct trifluoromethylthiolation product 33.

    Scheme 5

    Scheme 5.  Copper-catalyzed trifluoromethylthiolation of pyrroles with trifluoromethanesulfonyl hypervalent iodonium ylide.
    DownLoad: Full-Size Img PowerPoint

    In 2017, Bu et al. [40] reported an electrophilic trifluoromethylthiolation of indoles and pyrroles with CF3SO2Na as the trifluoromethylthiolating reagent at room temperature (Scheme 6). The reaction conditions tolerate a range of functional groups, and indoles carrying electron-donating groups generally obtain higher yields than those with electron-withdrawing groups. However, the C-3 functionalized indole only gave trace C-2 SCF3 product.

    Scheme 6

    Scheme 6.  Trifluoromethylthiolation of indoles and pyrroles with CF3SO2Na.
    DownLoad: Full-Size Img PowerPoint

    In 2018, Liu and coworkers [41] reported the trifluoromethylthiolation-based vicinal bifunctionalization of indoles using sodium trifluoromethanesulfinate as cheap and easily available reagents in the presence of phosphorus oxychloride or phosphorus oxybromide (Scheme 7). In addition, this protocol has been extended to sodium perfluoroalkane sulfinates (RfSO2Na), such as ClCF2CF2SO2Na, n-C4F9SO2Na, and n-C6F13SO2Na, to give the corresponding products in moderate yields.

    Scheme 7

    Scheme 7.  POCl3-promoted trifluoromethylthiolation-based vicinal bifunctionalization of indoles with CF3SO2Na.
    DownLoad: Full-Size Img PowerPoint

    In 2018, Guo et al. [42] reported CuCl-catalyzed C-3 trifluoromethylthiolation of indoles in moderate to good yields with TfNHNHBoc as a SCF3 source in the presence of dimethyl sulfoxide (Scheme 8). The reaction tolerated a variety of functional groups such as alkoxy-, hydroxyl–, fluoro-, chloro–, bromo– and ester-. However, the C-2 SCF3 product was not obtained when the C-3 position of the indole ring was occupied by a substituent. Initially, TfNHNHBoc 37 is decomposed by heat to obtain CF3SSCF3 20, which then reacts with CuCl to form the copper(Ⅲ) species 39. Next, this is attacked by indole 34 to form a copper(Ⅲ) species 40. Finally, the copper(Ⅲ) species 40 is reduced to produce the desired trifluoromethylthiolation product 38 and CuSCF3. Anion exchange between CuSCF3 and HCl releases CF3SH and regenerates CuCl to continue the catalytic cycle. CF3SH is oxidized by dimethyl sulfoxide (DMSO) to give CF3SSCF3.

    Scheme 8

    Scheme 8.  CuCl-catalyzed C-3 trifluoromethylthiolation of indoles.
    DownLoad: Full-Size Img PowerPoint

    In 2018, Jiang and coworkers [43] reported the C–H trifluoromethylthiolation of indoles and thiophenes using CF3SOCl as the trifluoromethylthiolating reagent in the absence of a catalyst and reductant, and the C–H trifluoromethylthiolation of benzothiophenes and benzofurans in the presence of an Ag2CO3 catalyst (Scheme 9). Control experiments and the literature showed that the reaction mechanism is different from the previously reported methods using CF3SO2-based reagents such as CF3SO2Na and CF3SO2Cl. Path 1: CF3SOCl 26 reacts with indole 31 to give the trifluoromethylsulfoxylated compound 45, which is reduced with CF3SOCl to give the desired product 33. Path 2: CF3SOCl 26 is decomposed into CF3SO2Cl 21 and CF3SCl 30. CF3SCl 30 reacts with indole 31 to give the desired product 33.

    Scheme 9

    Scheme 9.  C–H trifluoromethylthiolation of indoles and thiophenes with CF3SOCl.
    DownLoad: Full-Size Img PowerPoint

    2.2 Cyclization of alkenes/alkynes to synthesize F3CS-containing heterocycles

    In 2014, Yin and Wang [44] developed the first silver-mediated radical aryltrifluoromethylthiolation of activated alkenes for the synthesis of trifluoromethylthiole-containing oxindoles (Scheme 10). The reaction features high functional group compatibility, including electron-donating groups (OMe and Me) and electron-withdrawing groups (CF3, F, Cl, Br, I, CO2Et, Ac and NO2).

    Scheme 10

    Scheme 10.  Silver-mediated aryltrifluoromethylthiolation of activated alkenes.
    DownLoad: Full-Size Img PowerPoint

    In 2014, Zhu et al. [45] reported the synthesis of trifluoromethylthiole-containing isoxazolines from unactivated alkenes and AgSCF3 in the presence of the Cu(OAc)2 catalyst (Scheme 11). The notable features of these reactions include moderate to good yields, high functional group compatibility, and the absence of other oxidants. It is noteworthy that the product can be synthesized in one step into a high-function Csp3-SCF3-containing building block in 87% yield, which demonstrates the high potent application of this process.

    Scheme 11

    Scheme 11.  Synthesis of trifluoromethylthiole-containing isoxazolines.
    DownLoad: Full-Size Img PowerPoint

    In 2015, Fuentes and coworkers [46] reported a one-pot synthesis of F3CS-containing indolo[2,1-a]isoquinolin-6(5H)-ones using N-[(2-ethynyl)arylsulfonyl]acrylamides reaction with AgSCF3 (Scheme 12). The presence of electron-withdrawing substituents (fluorine, trifluoromethyl, methylcarboxylate) improves the efficiency of the reaction. This reaction pathway involves radical addition, 1,4-aryl migration, 5-endo-trig cyclization, and rearomatization. Initially, AgSCF3 is oxidized by K2S2O8 and generates the Ag(Ⅱ) cation and SCF3 radical. The SCF3 radical then attacks the alkenyl moiety in the N-acrylamide substrate 55 to give a radical intermediate 56. Next, the intermediate 56 is obtained by ipso-cyclization on Csp2−SO2 atoms. After the rearomatization of intermediate 57, SO2 is removed to obtain the radical intermediate 58 with 1,4-migration of the aryl sulfonyl group. The presence of adjacent alkyne groups in the substrate causes acyl radical cyclization to form a new vinyl radical intermediate 60. Finally, intermediate 61 is obtained by 5-endo-trig cyclization of the vinyl radical intermediate 60, and then rearomatized to give the desired product 62.

    Scheme 12

    Scheme 12.  Synthesis of SCF3-containing indolo[2,1-a]isoquinolin-6(5H)-ones.
    DownLoad: Full-Size Img PowerPoint

    In 2016, Jin's group [47] reported the first synthesis of 3-trifluoromethylthiospiro[4,5]trienones using a series of substituted N-arylpropiolamides in reaction with AgSCF3 (Scheme 13). The reaction features good yield and high functional group compatibility. However, the use of AgSCF3 (1.5 equiv.) is not environmentally acceptable.

    Scheme 13

    Scheme 13.  Synthesis of 3-trifluoromethylthiospiro[4,5]trienones.
    DownLoad: Full-Size Img PowerPoint

    In 2016, Liu and coworkers [48] developed a new chiral bifunctional sulfide catalyst and a new shelf-stable electrophilic SCF3 reagent, which are efficient in the enantioselective trifluoromethylthiolation of alkenes to synthesize trifluoromethylthiolated furan derivatives (Scheme 14). The reaction has moderate to good yields, enantioselectivities, and excellent diastereoselectivities (> 99:1 dr). The authors propose a possible reaction mechanism. First, 67 is converted to salt 69 in the presence of trifluoromethanesulfonic acid (TfOH). Next, the SCF3 reagent reacts with 69 to produce (PhSO2)2NH and species 70. Species 70 reacts with enocarboxylic acid 71 to form the intermediate 72 by creating a trifluoromethylthiazide ion and hydrogen bond. Finally, the oxygen of the carbonyl group attacks the iridium ions to give the trifluoromethylthiolated furans 73 and compound 69.

    Scheme 14

    Scheme 14.  Enantioselective trifluoromethylthiolation of alkenes.
    DownLoad: Full-Size Img PowerPoint

    A new, bifunctional, chiral selenide catalyst was developed by Luo et al. [49] in 2017, which is efficient in the synthesis of F3CS-containing chiral azaheterocycles using an Ns-protected olefinic sulfonamide reaction with (PhSO2)2NSCF3 (Scheme 15). The reaction has good yield and excellent enantiomeric excess (ee) when substrates are (E)-alkenes, except sterically hindered 2-methylphenyl alkene which has poor ee relative to other alkenes. However, when the (Z)-alkene is utilized, there is no reaction because of the reactivity of the alkene or steric hindrance in the alkene.

    Scheme 15

    Scheme 15.  Synthesis of F3CS-containing chiral azaheterocycles.
    DownLoad: Full-Size Img PowerPoint

    In 2017, Pan et al. [50] reported the copper-assisted oxidative trifluoromethylthiolation of 2,3-allenoic acids with AgSCF3 in the presence of (NH4)2S2O8 for the synthesis of trifluoromethylthiolated furan derivatives (Scheme 16). The reaction has moderate to good yields and a wide range of substrates. However, when 2-monosubstituted buta-2,3-dienoic acid (R1 = R2 = H) is utilized, only a trace of the desired products is obtained, which is replaced by a bis-trifluoromethylthiolated product.

    Scheme 16

    Scheme 16.  Copper-assisted oxidative trifluoromethylthiolation of 2,3-allenoic acids with AgSCF3.
    DownLoad: Full-Size Img PowerPoint

    In 2017, Dagousset et al. [51] reported the photocatalytic trifluoromethylthiolation of acrylamides with N-trifluoromethylthiosaccharin for the synthesis of F3CS-containing oxindoles and isoquinolinediones (Scheme 17). Of note, when estrone-derived acrylamide is utilized, the desired product is obtained, showing that this method is applicable to the late-stage functionalization of complex molecules.

    Scheme 17

    Scheme 17.  Photocatalytic trifluoromethylthiolation of acrylamides with N-trifluoromethylthiosaccharin.
    DownLoad: Full-Size Img PowerPoint

    In 2022, Ren et al. [52] reported the synthesis of SCF3-substituted dibenzazepines or dioxodibenzothiazepines through the cascade cyclization of N-benzyl-N-(2-ethynylaryl)amides (or N-(2-ethynylphenyl)-N-alkylbenzenesulfonamides) with AgSCF3 (Scheme 18). This method is applicable to various electron-donating or electron-withdrawing groups substituted on the N-benzyl moiety of the amides, such as methyl, methoxy, trifluoromethyl, cyano, nitro and ester. Notably, the gram-scale production, late-stage modifications of the product further demonstrated the synthetic value of this reaction system. The yield of product decreased significantly after adding a free radical inhibitor such as 2,6-dibutyl-4-methylphenol (BHT) or 1,1-stilbene to the reaction system, which indicated that the reaction involves a free radical pathway. First, AgSCF3 is oxidized by Na2S2O8 to generate an SCF3 radical. Then the addition of the SCF3 radical to the alkynyl bond of 83 leads to the formation of the corresponding vinyl radical 84, which attacks the adjacent aromatic ring and produces intermediate 85. The intermediate 85 is further transformed into an aryl anion radical 86 after deprotonation. Finally, the desired product 87 is obtained through a one-electron oxidation process.

    Scheme 18

    Scheme 18.  Cascade cyclization of aryl acetylenes with AgSCF3.
    DownLoad: Full-Size Img PowerPoint

    In 2022, Chen et al. [53] achieved a new access to F3CS-containing dioxodibenzothiazepines by the Cu-assisted trifluoromethylthiolation and radical cascade cyclization of alkynes with AgSCF3 (Scheme 19). The electron-donating (-Me, -OMe, -tBu) or electron-withdrawing (-COOMe, -CN, -CF3) groups substituted on the arylalkyne ring could react well with AgSCF3 under typical conditions, and a variety of N-protected groups can be used in this transformation, such as -iPr, -Bn, -Bz and -Boc. Notably, substrates with ortho-halogens (-F, -Cl, -Br) substituted on the arylalkyne ring exhibit better reactivity than substrates substituted with meta-halogens.

    Scheme 19

    Scheme 19.  Copper-assisted trifluoromethylthiolation/radical cascade cyclization of alkynes with AgSCF3.
    DownLoad: Full-Size Img PowerPoint

    In 2022, a convenient protocol for the cascade cyclization of N-aryl-3-butenamides with AgSCF3 was developed by Li and coworkers [54], which offers an efficient pathway for the construction of valuable F3CS-substituted 3,4-dihydroquinolin-2-ones and azaspiro[4,5]dienones under different reaction conditions (Scheme 20). In the synthesis of azaspiro[4,5]dienones, various ortho- and meta-substituents such as CH3, F, Cl, and Br are tolerated well in this method, but the yield of substrates with strong electron-withdrawing CF3 substituents is lower. It is worth noting that the substituents are lost and the same product 96 is produced in similar yields under the same conditions when F, Cl, Br, OMe, and NO2 are the para-substituents. In addition, when the substrate has a meta-substituent (-F, -Cl, -Br), the reaction for the synthesis of 3,4-dihydroquinolin-2-ones produces a mixture of two regioisomers (C2 and C6). Neither 90 nor 91 was formed after adding a free radical inhibitor such as 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) or butylated hydroxytoluene (BHT) to the reaction system, which indicates that the reaction system might proceed in a free radical way. First, AgSCF3 is oxidized by K2S2O8 to generate an SCF3 radical. Subsequently, the alkyl radical species 93 is produced via the SCF3 radical attacking the double bond of the substrate 92. Then, the vinyl radical 93 generates a spirocyclic intermediate 94 by ipso-addition 5-exo-type cyclization, or the fused cyclic ring intermediate 97 by ortho-addition 6-endo-type cyclization. In the presence of TBHP, intermediate 94 could be captured by the t-butylperoxy radical formed by the interaction of TBHP with the t-butyl radical, resulting in intermediate 95, which is further transformed into the desired product azaspiro[4,5]dienone 96 through the release of tBuOH. While intermediate 97 could also transformed into the cationic intermediate 98 by Ag2+ oxidation. Finally, the intermediate 98 is deprotonated to give the 3,4-dihydroquinone-2-one product 99.

    Scheme 20

    Scheme 20.  Syntheses of azaspiro[4,5]dienones and 3,4-dihydroquinolin-2-ones.
    DownLoad: Full-Size Img PowerPoint

    3. Synthesis of trifluoromethylthiolated heterocycles

    The trifluoromethoxy group displays strong electron absorption and high lipophilicity, which plays an important role in the fields of medicine and pesticides, such as riluzole, flucarbazone-sodium for example. Due to the development of new trifluoromethoxylation reagents, which can be divided into free radical and nucleophilic types (Fig. 1) [23], more convenient and practical new synthetic strategies have emerged. In particular, the strategy of interacting hydroxyl groups with trifluoromethylating reagents to construct OCF3 bonds eliminates the dependence on trifluoromethylated reagents, as discussed below.

    Figure 1

    Figure 1.  Trifluoromethoxylation reagents.
    DownLoad: Full-Size Img PowerPoint

    3.1 Direct C–H trifluoromethoxylation of heterocycles

    In 2018, Zheng and coworkers [55] reported a radical photocatalytic trifluoromethoxylation of (hetero)arenes (Scheme 21). The protocol uses redox-active cationic reagents, which enables the formation of the OCF3 radical in a controllable and selective manner under visible-light photocatalytic conditions. These reactions have a wide range of substrates include mono-, di-, and tri-substituted (hetero)arenes, and good functional group tolerance, including a variety of electron-donating and electron-withdrawing substituents. It is noteworthy that diacetonefructose and l-menthol derivatives can afford the desired F3CO-containing products in modest yields. Experimental and computational studies suggest this process involves radical mechanisms. Initially, Ru(bpy)32+ produces the triplet-excited state of *Ru(bpy)32+ under blue light-emitting diodes (LEDs). *Ru(bpy)32+ reacts with the redox-active cationic reagent to form Ru(bpy)33+, 104, and the OCF3 radical. Next, the addition of OCF3 radical to arene 105 forms cyclohexadienyl radicals 106. Finally, the cyclohexadienyl radical 106 is oxidized by Ru(bpy)33+ to afford the cyclohexadienyl cation 107, which is deprotonated to give the desired F3CO-containing products 108.

    Scheme 21

    Scheme 21.  Photocatalytic trifluoromethoxylation of (hetero)arenes.
    DownLoad: Full-Size Img PowerPoint

    In 2020, Deng's group [56] reported the silver-mediated C–H trifluoromethoxylation of (hetero)arenes (Scheme 22). It is noteworthy that silver salts afford exclusive ortho-position selective C–H trifluoromethoxylation of pyridines, while the method is also applied to the trifluoromethoxylation of natural products or drugs, such as etoricoxib and rosuvastatin, for example. The notable features of these reactions include their mild reaction conditions and excellent functional group tolerance. In addition, the reaction is applicable to the gram-scale synthesis of trifluoromethoxylated products, which demonstrates the practicality of this reaction.

    Scheme 22

    Scheme 22.  Silver-mediated C–H trifluoromethoxylation of (hetero)arenes.
    DownLoad: Full-Size Img PowerPoint

    3.2 Cyclization of alkenes/alkynes to synthesize F3CO–containing heterocycles

    In 2015, Chen et al. [57] reported the synthesis of 3-OCF3-substituted piperidines in moderate yields using an unactivated alkene reaction with AgOCF3 in the presence of a Pd(CH3CN)2Cl2 catalyst (Scheme 23). Substrates with different sulfonyl protecting groups on nitrogen show a good yield, while substrates with Ns-protecting group have a yield of only 30% and substrates with Bn-protecting group give no yield. In addition, diastereoselectivity is poor when the reaction products are 3,5-cis and 3,5-trans isomers. A study of the mechanism indicates that high-valent palladium plays an important role in this process. The PdⅣ−OCF3 showed better stability, and is more easily eliminated than β-fluorination, and leads to the formation of the C−OCF3 bond.

    Scheme 23

    Scheme 23.  Palladium-catalyzed intramolecular trifluoromethoxylation of alkenes.
    DownLoad: Full-Size Img PowerPoint

    3.3 Synthesis of F3CO–containing heteroarenes through O–CF3 bond formation

    In 2015, Liu's group [58] reported the silver-mediated O-trifluoromethylation of unprotected phenols by O–CF3 bond formation using CF3SiMe3 as a CF3 source in the presence of AgOTf (Tf = trifluoromethanesulfonyl), 2-fluoropyridine, SelectfluorTM, N-fluorobenzenesulfonimide (NFSI), and CsF (Scheme 24). The notable features of the reactions include moderate to good yields, high selectivity, and excellent functional group tolerance, such as nitrile, nitro, sulfone, amide, and ether moieties. However, nitrogen-containing heteroaryl substrates such as pyridine, quinoline, and benzothiazole cannot be tolerated under the reaction conditions, possibly due to the competitive coordination between nitrogen atoms and the silver centers. Excitingly, this protocol has been extended to the O-trifluoromethylation of benzoyl ezetimibe, a plasma cholesterol lowering drug, in 65% yield. According to the results of 19F NMR spectroscopy of the reaction mixture, a possible reaction mechanism is proposed. First, AgⅠOTf reacts with CF3SiMe3 and CsF to generate the AgⅠCF3 species 130. Next, the AgⅠCF3 species 130 undergoes oxidative addition with SelectfluorTM and NFSI to form the [AgⅢ(CF3)(F)] complex 131, which reacts with phenol to provide the key intermediate [AgⅢ(CF3)(OPh)] 131 through the exchange of fluoride and phenoxide. Finally, the reduction elimination of the intermediate 132 forms the desired O–CF3 bonds and provides the desired product 125.

    Scheme 24

    Scheme 24.  Silver-mediated O-trifluoromethylation of unprotected phenols.
    DownLoad: Full-Size Img PowerPoint

    In 2016, Feng's group [59] reported the synthesis of F3CO-containing pyridines and pyrimidines through O–CF3 bond formation (Scheme 25). This strategy uses N-acetyl/methoxycarbonyl-N-pyridinyl/pyrimidinylhydroxylaminein as substrates and Togni reagent as a CF3 source and chloroform (CHCl3) as solvent, and affords the desired product in moderate to good yields at room temperature for 15 h. Under the reaction conditions, many functional groups and heteroaryl substituents can be tolerated. Notably, estrone and Tadalafil-conjugated pyridines can also be trifluoromethoxylated to afford the desired products in good yields, which demonstrates high potent application in a late-stage trifluoromethoxylation. The reaction can be inhibited in the presence of BHT, which indicates a possible involvement of a radical pathway in the reaction process. First, the deprotonation of 138 forms the N–hydroxyl anion 139, which performs a single electron transfer (SET) with Togni reagent I to produce an N-hydroxyl radical 140, trifluoromethyl radical, and alkoxide 141. The N–hydroxyl radical 140 reacts with the trifluoromethyl radical to produce oxytrifluoromethylhydroxylamine 142. Nextly, the N–O bond of the intermediate 142 is thermally induced to break, forming an ion pair 143, which rapidly recombines to produce 144. Finally, the intermediate 144 is converted to the desired product 145 by proton migration.

    Scheme 25

    Scheme 25.  Synthesis of F3CO-containing pyridines and pyrimidines.
    DownLoad: Full-Size Img PowerPoint

    In 2016, Liang et al. [60] reported the synthesis of ortho-N-heteroaromatic trifluoromethoxy derivatives in poor to good yields at 100 ℃ by site-specific O–CF3 bond formation using ortho-hydroxy N-heterocycles as substrates, Togni's reagent as a CF3 source, and CH3NO2 as solvent (Scheme 26). The reaction is affected by the substituent electron effect, and substrates containing electron-withdrawing groups generally have lower yields than substrates containing electron-donating groups. It is noteworthy that 330 g of 2–hydroxy-5-bromopyridine reacted with 200 g Togni's reagent in 6 L of CH3NO2 to give 84 g of the desired product (55% yield) and 152 g of 2–hydroxy-5-bromopyridine was recovered, which demonstrated the practicality of this reaction.

    Scheme 26

    Scheme 26.  Direct O-trifluoromethylation of N-heteroaromatics.
    DownLoad: Full-Size Img PowerPoint

    4. Synthesis of trifluoromethylselenolated heterocycles

    The selenotrifluoride group, which contains the important chemical elements, fluorine and selenium, also has good lipophilicity and potential biological activity. Chemists gradually realized that SeCF3 is also a potential functional group similar to SCF3. With the rapid development of organic fluorine and selenium chemistry [61-63], new trifluoromethylselenolation reagents (Fig. 2) [22,64] and synthetic strategies have emerged.

    Figure 2

    Figure 2.  Trifluoromethylselenolation reagents.
    DownLoad: Full-Size Img PowerPoint

    4.1 Direct C–H trifluoromethylselenolation of heterocycles

    In 2018, Tlili, Billard and coworkers [65] reported the Pd-catalyzed trifluoromethylselenolation of 8-aminoquinoline with F3CSeCl (Scheme 27). It is noteworthy that only C-5 trifluoromethylselenolations have been observed, with no other regioisomers being formed. The reaction has been extended to various amide and sulfonamide derivatives, as well as other fluoroalkyl groups including -CF2CF3, -CF2H and -CF2Br. First, the reaction begins with the formation of a complex 163 of 8-aminoquinoline amide 160 and lead acetate (PdⅡL2). Then, a new PdⅢ-complex 164 and a CF3Se radical are provided by the SET process between the complex 163 and CF3SeCl. Because of the intermolecular electron transfer between the ligand and metal, a PdⅢ-complex 164 forms the new cationic radical complex 165, which react with the CF3Se radical to provide the cationic complex 166. Finally, the cationic complex 166 forms the desired product 162 and PdⅡL2 through a concerted proton transfer-demetallation.

    Scheme 27

    Scheme 27.  Pd-catalyzed trifluoromethylselenolation of 8-aminoquinoline.
    DownLoad: Full-Size Img PowerPoint

    In 2019, Zhao and coworkers [66] reported a practical and environmentally friendly strategy for the synthesis of 3-trifluoromethylthiolation products in moderate to excellent yields by employing TsSeCF3 as a trifluoromethylselenolation reagent and FeCl3 as an efficient activator (Scheme 28). The reaction tolerated indoles with both electron-donating and electron-withdrawing substituents.

    Scheme 28

    Scheme 28.  3-Trifluoromethylthiolation of indoles with TsSeCF3.
    DownLoad: Full-Size Img PowerPoint

    The oxidative trifluoromethylselenolation of electron-rich (hetero)arenes by the nucleophilic [Me4N][SeCF3] reagent was developed by Han and coworkers in 2019 (Scheme 29) [67]. The reaction tolerated (hetero)arenes with both electron-donating and electron-withdrawing substituents, but longer reaction times were required to completely consume (hetero)arenes with electron-withdrawing substituents. This method features a wide range of substrates, good functional group tolerance, mild reaction conditions, and excellent regioselectivity. Based on the results of controlled experiments, the authors propose a possible mechanism. First, [Me4N][SeCF3] 169 is oxidized by an oxidant to provide an SeCF3 radical 170, which can be further oxidized to provide +SeCF3 172 or coupled to produce the CF3SeSeCF3 171 byproduct. Next, indole 93 attacks +SeCF3 172 to produce a cationic intermediate 173. Finally, the cationic intermediate 173 loses a proton to yield the desired product 175.

    Scheme 29

    Scheme 29.  Trifluoromethylselenolation of (hetero)arenes with [Me4N][SeCF3].
    DownLoad: Full-Size Img PowerPoint

    In 2020, Zordo-Banliat et al. [68] developed a new visible-light mediated aerobic C–H trifluoromethylselenolation of heteroarenes using the reagent [Me4N][SeCF3], which has been successfully applied to a wide range of indoles, azaindoles, and pyrroles bearing various functional groups (Scheme 30). This method was fully regioselective in favor of the 3-position, and it is noteworthy that no reaction took place in the case of 3-substituted indoles.

    Scheme 30

    Scheme 30.  Visible-light mediated trifluoromethylselenolation of heteroarenes with [Me4N][SeCF3].
    DownLoad: Full-Size Img PowerPoint

    In 2021, Liu and coworkers [69] realized the TfOH-catalyzed selective trifluoromethylselenolation of benzofurans, as well as the FeCl3-catalyzed intramolecular electrophilic ring-closure trifluoromethylselenolation of 1-methoxy-2-(arylethynyl)benzene derivatives by employing TsSeCF3 as the electrophilic trifluoromethylselenolating reagent (Scheme 31). These methods feature mild reaction conditions as well as a stable and easily prepared trifluoromethylselenolating reagent. Based on relevant literature precedents, an electrophilic pathway was proposed. Regarding the TfOH-catalyzed selective trifluoromethylselenolation of benzofurans, TfOH promotes the nucleophilic attack of benzofuran 178 on TsSeCF3, which is activated by TfOH, to produce the intermediate 180 and 4-methylbenzenesulfinic acid 179. Finally, the deprotonative aromatization of 180 provides the desired product 181. In terms of the FeCl3-catalyzed cyclotrifluoromethylselenylation of 1-methoxy-2-(arylethynyl)benzene derivatives, the decomposition of TsSeCF3 catalyzed by FeCl3 gives an SeCF3 cation, which is attacked by a triple bond moiety of alkyne 182 to form intermediate 183. Then, the intramolecular cyclization of intermediate 183 affords the intermediate 184. Finally, the methyl group of intermediate 184 is removed to give product 181 under the attack of 4-methylbenzene sulfonate or chloride anion.

    Scheme 31

    Scheme 31.  TfOH-catalyzed trifluoromethylselenolation of benzofurans.
    DownLoad: Full-Size Img PowerPoint

    In 2021, Tan and coworkers [70] reported N-acylated and 3-trifluoromethylselanylated indoles in good yields via the treatment of indoles with excess [Me4N][SeCF3] in the presence of acyl peroxides or their derivatives (Scheme 32). The reaction proceeded at room temperature under mild conditions and tolerated a range of functional groups. Both acyl peroxide and peroxycarboxylic acid were effective mediators, behaving not only as oxidants but also as acyl sources in the transformations.

    Scheme 32

    Scheme 32.  Synthesis of N-acylated and 3-trifluoromethylselanylated indoles.
    DownLoad: Full-Size Img PowerPoint

    4.2 Cyclization of alkenes/alkynes to synthesize F3CSe-containing heterocycles

    In 2018, an easy and practical protocol using alkynes and CF3SeCl to access various F3CSe-containing five- and six-membered-ring heterocycles was developed by Glenadel et al. [71] and coworkers, which has also been extended to other fluoroalkylselenyl groups (Scheme 33). It is noteworthy that the newly formed isocoumarins can be further converted into trifluoromethylselenolated isoquinolinones via a multistep pathway, which further proves its potential application prospects, particular in medicinal chemistry.

    Scheme 33

    Scheme 33.  Syntheses of fluoroalkylselenolated five- and six-membered-ring heterocycles.
    DownLoad: Full-Size Img PowerPoint

    In 2022, Wang et al. [72] developed a copper-mediated double trifluoromethylselenolation and cyclization of terminal 2-alkynylanilines using [(bpy)-CuSeCF3]2 as the trifluoromethylselenolating reagent, which provided a useful tool for the synthesis of 2,3-bis(trifluoromethylseleno)indoles (Scheme 34). It is noteworthy that the delicate balance between the electronic and spatial properties of the N-protected groups is crucial for the reaction. The N-Ts and N-Ms groups gave the desired products in moderate to good yields, while the N-Ns groups gave the desired products in poor yields. In addition, Neither N-Me and N-Bz groups, nor N-unprotected groups gave any desired cyclization products. Desulfonylation of N-Ts 2,3-bis(trifluoromethylselenide) compounds, and further N-methylation of the product confirms the utility of this reaction. Based on the control experiments and isolated intermediates, a feasible reaction mechanism is proposed in Scheme 34. First, [(bpy)CuSeCF3]2 195 could undergo a single electron oxidation by 1,2-benzendicarboxylicacid (DMP) to generate CuⅡ species 203. Then electrophilic trifluoromethylselenolation of CuⅡ species 203 with 2-ethylaniline led to intermediate 204. The alkynyl of intermediate 204 coordinates with 203 to form copper complex 205, and then 5-endo cyclization to give 3-copper indoler intermediate 206, which underwent oxidation and deprotonation to generate the intermediate 207. Finally, the reductive elimination of intermediate 207 gave the desired product 208.

    Scheme 34

    Scheme 34.  Synthesis of 2,3-bis(trifluoromethylseleno)indole.
    DownLoad: Full-Size Img PowerPoint

    In 2022, Shi et al. [64] reported the trifluoromethylthiolation/selenolation and lactonization of 2-alkynylbenzoate using a combination of BnS(O)CF3/BnSe(O)CF3 with Tf2O as SCF3/SeCF3 reagents to produce a series of 4-(trifluoromethylseleno/selenolation)isocoumarins (Scheme 35). The reaction is not affected by the electronic properties or steric effects of the substituents. In particular, the desired 3-alkyl-substituted isocoumarins are obtained in moderate to good yields when the alkyne motif (R2) is substituted with an alkyl substituent including n-Bu, t-Bu, or cyclopropyl groups. Based on the results of relevant control experiments and previous literature reports, three possible reaction pathways were described, as shown in Scheme 35. This differs from the previous formation of thiovinyl intermediates, and is an alternative mechanistic pathway involving synergistic trifluoromethyl thiolation/selenation and lactonization processes.

    Scheme 35

    Scheme 35.  BnSe(O)CF3/Tf2O-mediated synthesis of 4-(trifluoromethylseleno)isocoumarins.
    DownLoad: Full-Size Img PowerPoint

    In 2022, Lu et al. [73] developed a convenient protocol for the visible-light-promoted trifluoromethylselenolation of ortho-hydroxyarylenaminones with TsSeCF3, which offers an efficient pathway for the construction of valuable trifluoromethylselenylated chromone derivatives (Scheme 36). The electron-donating (-Me, -OMe) or electron-withdrawing (-F, -Cl, -Br, -CN, -NO2) groups substituted on the phenol react well with TsSeCF3 under typical conditions, and the introduction of substituents at different positions of the benzene ring of enaminone has little effect on the reaction. In addition, the heterocyclic-substituted enaminones, such as thiophene, furan and benzofuran, can also be transformed to the desired products in good yields. The yield of product 228 is poor after adding a free radical inhibitor (TEMPO), which indicates that the reaction proceeds via a free radical pathway. First, the S–Se bond of TsSeCF3 is homogenized under visible-light irradiation to generate CF3Se radicals 170, which attack the alkenyl group of o-hydroxyphenyl enaminone 230 regioselectively to give a radical intermediate 230. Then, the radical intermediate 230 is rapidly oxidized by oxygen to form an imine intermediate 231. Finally, the intermediate 232 undergoes intramolecular cyclization and reductive elimination to yield the desired product 233.

    Scheme 36

    Scheme 36.  Visible-light-promoted trifluoromethylselenolation of ortho-hydroxyarylenaminones.
    DownLoad: Full-Size Img PowerPoint

    In 2022, Wang et al. [74] developed a simple and mild protocol for the trifluoromethylselenolation of N-Ts 2-alkynylaniline with [(bpy)CuSeCF3]2 to synthesize a series of 3-(trifluoromethylseleno)indoles in air at room temperature (Scheme 37). Various N-protecting groups including N-Ts, N-Tf, N-Ns and N-Ms groups were tolerated well in this transformation, but N-Me, N-Bz and N-unprotected groups gave no desired cyclization product. This indicates that a delicate balance between the electronic and spatial properties of the N-protected groups is necessary for this reaction. In addition, the main merits of the method are that the reaction conditions are mild, insensitive to moisture or air, and have broad functional group tolerance.

    Scheme 37

    Scheme 37.  Synthesis of 3-(trifluoromethylseleno)indoles.
    DownLoad: Full-Size Img PowerPoint

    5. Conclusions

    In summary, the synthesis of trifluoromethoxylated, trifluoromethylthiolated, and trifluoromethylselenolated heterocyclic compounds, as well as the scope, limitations and selected mechanisms of the reactions are reviewed. The successful examples described in this review convincingly demonstrate that efficient and practical methods have been developed to incorporate the XCF3 groups (X = O, S, Se) into organic molecules, which has broad prospects in the field of medicinal chemistry. Among these synthesis methods, oxidative trifluoromethoxylation (thiolation/selenolation) activation via heterocyclic C–H bond activation is the most direct, efficient, and economical method that can avoid the use of prefunctional groups or preactivated reaction substrates. Further, the construction of F3CX-containing (X = O, S, Se) heterocyclic compounds by the difunctionalization cyclization strategy of alkenes and alkynes is relatively mild and plays an important role in the construction of polyheterocycle and heteroatom-rich heterocyclic compounds. There are also some synthetic methods for constructing F3CO-containing heterocycles by constructing O–CF3 bonds. Although the substrate requires pretreatment, it is not limited to the need for trifluoromethoxylation reagents, which has important significance for the later derivatization of compounds.

    These studies show that the F3CX-containing (X = O, S, Se) heterocyclic compounds, which have good biological activity, have attracted the attention of chemists, and many synthetic methods have been developed. However, the current synthetic methods also face limitations. On the one hand, the synthesis of F3CX-containing heterocyclic compounds largely depend on the development of trifluoromethoxylation, trifluoromethylthiolation, and trifluoromethylselenolation reagents. Although there are various kinds of trifluoromethoxylated, trifluoromethylthiolated, and trifluoromethylselenolated reagents, most are expensive, complicated to prepare, and have low atomic efficiency. It is very important to develop cheap, nontoxic, and atomically efficient trifluoromethoxylation, trifluoromethylthiolation and trifluoromethylselenolation reagents. On the other hand, the current synthetic method is relatively consistent, with most using metal, acid, or base catalysts to catalyze the generation of trifluoromethoxy-, trifluoromethylthio-, and trifluoromethylseleno-groups. With the development of XCF3 (X = O, S, Se) radical transfer reagents, and some of the electrophilic XCF3 transfer reagents having proven to have the potential to provide XCF3 (X = O, S, Se) radicals, the use of milder, greener photocatalysis and electrocatalysis for the synthesis of F3CX-containing (X = O, S, Se) heterocyclic compounds is an attractive and challenging option.

    Declaration of competing interest

    The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

    Acknowledgment

    This work was supported by the National Natural Science Foundation of China (No. 21801007).


    1. [1]

      K. Müller, C. Faeh, F. Diederich, Science 317 (2007) 1881–1886. doi: 10.1126/science.1131943

    2. [2]

      E.P. Gillis, K.J. Eastman, M.D. Hill, et al., J. Med. Chem. 58 (2015) 8315–8359. doi: 10.1021/acs.jmedchem.5b00258

    3. [3]

      S. Tang, Y.L. Deng, J. Li, et al., J. Org. Chem. 80 (2015) 12599–12605. doi: 10.1021/acs.joc.5b01803

    4. [4]

      S.W. Wang, J. Yu, Q.Y. Zhou, et al., ACS Sustain. Chem. Eng. 7 (2019) 10154–10162. doi: 10.1021/acssuschemeng.9b02178

    5. [5]

      Y. Ogawa, E. Tokunaga, O. Kobayashi, et al., iScience 23 (2020) 101467. doi: 10.1016/j.isci.2020.101467

    6. [6]

      H.B. Mei, A.M. Remete, Y.P. Zou, et al., Chin. Chem. Lett. 31 (2020) 2401–2413. doi: 10.1016/j.cclet.2020.03.050

    7. [7]

      Y.J. Yu, A.Y. Liu, G. Dhawan, et al., Chin. Chem. Lett. 32 (2021) 3342–3354. doi: 10.1016/j.cclet.2021.05.042

    8. [8]

      X. Wang, J. Lei, Y.J. Liu, et al., Org. Chem. Front. 8 (2021) 2079–2109. doi: 10.1039/d0qo01629b

    9. [9]

      N. Chen, J. Lei, Z.C. Wang, et al., Chin. J. Org. Chem. 42 (2022) 1061–1084. doi: 10.6023/cjoc202109033

    10. [10]

      A. Leo, C. Hansch, D. Elkins, Chem. Rev. 71 (1971) 525–616. doi: 10.1021/cr60274a001

    11. [11]

      C. Hansch, A. Leo, R.W. Taft, Chem. Rev. 91 (1991) 165–195. doi: 10.1021/cr00002a004

    12. [12]

      Q. Glenadel, E. Ismalaj, T. Billard, Eur. J. Org. Chem. 2017 (2017) 530–533. doi: 10.1002/ejoc.201601526

    13. [13]

      Y.Y. Xie, Y.C. Wang, H.E. Qu, et al., Adv. Synth. Catal. 356 (2014) 3347–3355. doi: 10.1002/adsc.201400315

    14. [14]

      Y.H. Lv, J.P. Meng, C. Li, et al., Adv. Synth. Catal. 363 (2021) 5235–5265. doi: 10.1002/adsc.202101184

    15. [15]

      X. Wang, Y. Zhang, K. Sun, et al., Chin. J. Org. Chem. 41 (2021) 4588–4609. doi: 10.6023/cjoc202109046

    16. [16]

      H. Sheng, Q. Liu, F. Chen, et al., Chin. Chem. Lett. 33 (2022) 4298–4302. doi: 10.1016/j.cclet.2022.01.028

    17. [17]

      X. Wang, J. Lei, S. Guo, et al., Chem. Commun. 58 (2022) 1526–1529. doi: 10.1039/d1cc06323e

    18. [18]

      M.W. Yu, Z. Zhou, Y.W. Chen, et al., Org. Lett. 24 (2022) 4886–4891. doi: 10.1021/acs.orglett.2c01680

    19. [19]

      J. Njardarson, Top 200 brand name drugs by retail sales in 2021. https://njardarson.lab.arizona.edu/sites/njardarson.lab.arizona.edu/files/Top%20200%20Pharmaceuticals%202021V2.pdf.

    20. [20]

      X.H. Xu, K. Matsuzaki, N. Shibata, Chem. Rev. 115 (2015) 731–764. doi: 10.1021/cr500193b

    21. [21]

      M. Li, J. Guo, X.S. Xue, J.P. Cheng, Org. Lett. 18 (2016) 264–267. doi: 10.1021/acs.orglett.5b03433

    22. [22]

      X.H. Yang, D. Chang, R. Zhao, L. Shi, Asian J. Org. Chem. 10 (2021) 61–73. doi: 10.1002/ajoc.202000575

    23. [23]

      X.H. Jiang, P.P. Tang, Chin. J. Chem. 39 (2021) 255–264. doi: 10.1002/cjoc.202000465

    24. [24]

      K.N. Lee, J.W. Lee, M.Y. Ngai, Tetrahedron 74 (2018) 7127–7135. doi: 10.1016/j.tet.2018.09.020

    25. [25]

      Y. Cao, N.Y. Xu, A. Issakhov, et al., J. Fluor. Chem. 252 (2021) 109901. doi: 10.1016/j.jfluchem.2021.109901

    26. [26]

      Y.M. Li, J.F. Fu, L.Q. He, et al., RSC Adv. 11 (2021) 24474–24486. doi: 10.1039/D1RA02606B

    27. [27]

      B. Sahoo, M.N. Hopkinson, Angew. Chem. Int. Ed. 57 (2018) 7942–7944. doi: 10.1002/anie.201804939

    28. [28]

      J.W. Lee, K.N. Lee, M.Y. Ngai, Angew. Chem. Int. Ed. 58 (2019) 11171–11181. doi: 10.1002/anie.201902243

    29. [29]

      M. Hamzehloo, A. Hosseinian, S. Ebrahimiasl, et al., J. Fluor. Chem. 224 (2019) 52–60. doi: 10.1016/j.jfluchem.2019.05.004

    30. [30]

      M.A. Hardy, H. Chachignon, D. Cahard, Asian J. Org. Chem. 8 (2019) 591–609. doi: 10.1002/ajoc.201900004

    31. [31]

      A.L. Barthelemy, E. Magnier, Guillaume Dagousset, Synthesis (Mass) 50 (2018) 4765–4776. doi: 10.1055/s-0037-1611278

    32. [32]

      A. Hassanpour, M.R.P. Heravi, A. Ebadi, et al., J. Fluor. Chem. 245 (2021) 109762. doi: 10.1016/j.jfluchem.2021.109762

    33. [33]

      H.N. Wang, J.Y. Dong, J. Shi, C.P. Zhang, Tetrahedron 99 (2021) 132476. doi: 10.1016/j.tet.2021.132476

    34. [34]

      D. Louvel, C. Ghiazza, V. Debrauwer, et al., Chem. Rec. 21 (2021) 417–426. doi: 10.1002/tcr.202000184

    35. [35]

      Y.D. Yang, A. Azuma, E. Tokunaga, et al., J. Am. Chem. Soc. 135 (2013) 8782–8785. doi: 10.1021/ja402455f

    36. [36]

      Q. Wang, Z.S. Qi, F. Xie, X.W. Li, Adv. Synth. Catal. 357 (2015) 355–360. doi: 10.1002/adsc.201400717

    37. [37]

      Q. Wang, F. Xie, X.W. Li, J. Org. Chem. 80 (2015) 8361–8366. doi: 10.1021/acs.joc.5b00940

    38. [38]

      Z.Y. Huang, Y.D. Yang, E. Tokunaga, N. Shibata, Org. Lett. 17 (2015) 1094–1097. doi: 10.1021/ol503616y

    39. [39]

      H. Chachignon, M. Maeno, H. Kondo, et al., Org. Lett. 18 (2016) 2467–2470. doi: 10.1021/acs.orglett.6b01026

    40. [40]

      M.J. Bu, G.P. Lua, C. Cai, Org. Chem. Front. 4 (2017) 266–270. doi: 10.1039/C6QO00622A

    41. [41]

      D.W. Sun, X. Jiang, M. Jiang, et al., Eur. J. Org. Chem. 2018 (2018) 2078–2081. doi: 10.1002/ejoc.201800249

    42. [42]

      J.Y. Guo, R.H. Dai, W.C. Xu, et al., Chem. Commun. 54 (2018) 8980–8982. doi: 10.1039/C8CC04600J

    43. [43]

      L.Q. Jiang, Q. Yan, R.K. Wang, et al., Chem. Eur. J. 24 (2018) 18749–18756. doi: 10.1002/chem.201804027

    44. [44]

      F. Yin, X.S. Wang, Org. Lett. 16 (2014) 1128–1131. doi: 10.1021/ol403739w

    45. [45]

      L.P. Zhu, G.Q. Wang, Q.P. Guo, et al., Org. Lett. 16 (2014) 5390–5393. doi: 10.1021/ol502624z

    46. [46]

      N. Fuentes, W.Q. Kong, L. Fernandez-Sanchez, et al., J. Am. Chem. Soc. 137 (2015) 964–973. doi: 10.1021/ja5115858

    47. [47]

      D.P. Jin, P. Gao, D.Q. Chen, et al., Org. Lett. 18 (2016) 3486–3489. doi: 10.1021/acs.orglett.6b01702

    48. [48]

      X. Liu, R. An, X.L. Zhang, et al., Angew. Chem. Int. Ed. 55 (2016) 5846–5850. doi: 10.1002/anie.201601713

    49. [49]

      J. Luo, Y.N. Liu, X.D. Zhao, Org. Lett. 19 (2017) 3434–3437. doi: 10.1021/acs.orglett.7b01392

    50. [50]

      S. Pan, Y.G. Huang, X.H. Xu, F.L. Qing, Org. Lett. 19 (2017) 4624–4627. doi: 10.1021/acs.orglett.7b02249

    51. [51]

      G. Dagousset, C. Simon, E. Anselmi, et al., Chem. Eur. J. 23 (2017) 4282–4286. doi: 10.1002/chem.201700734

    52. [52]

      Y.M. Ren, Q.Q. Yan, Y. Li, et al., J. Org. Chem. 87 (2022) 8773–8781. doi: 10.1021/acs.joc.2c00623

    53. [53]

      X.Y. Chen, C.C. Pei, B. Liu, et al., Chem. Commun. 58 (2022) 8674–8677. doi: 10.1039/d2cc02171d

    54. [54]

      L. Wang, L. Xie, Z.G. Fang, et al., Org. Chem. Front. 9 (2022) 3061–3067. doi: 10.1039/D2QO00207H

    55. [55]

      W. Zheng, J.W. Lee, C.A. Morales-Rivera, et al., Angew. Chem. Int. Ed. 57 (2018) 13795–13799. doi: 10.1002/anie.201808495

    56. [56]

      Z.J. Deng, M.X. Zhao, F. Wang, P.P. Tang, Nat. Commun. 11 (2020) 2569–2577. doi: 10.1038/s41467-020-16451-x

    57. [57]

      C.H. Chen, P.H. Chen, G.S. Liu, J. Am. Chem. Soc. 137 (2015) 15648–15651. doi: 10.1021/jacs.5b10971

    58. [58]

      J.B. Liu, C. Chen, L.L. Chu, et al., Angew. Chem. Int. Ed. 54 (2015) 11839–11842. doi: 10.1002/anie.201506329

    59. [59]

      P.J. Feng, K.N. Lee, J.W. Lee, et al., Chem. Sci. 7 (2016) 424–429. doi: 10.1039/C5SC02983J

    60. [60]

      A.P. Liang, S.J. Han, Z.W. Liu, et al., Chem. Eur. J. 22 (2016) 5102–5106. doi: 10.1002/chem.201505181

    61. [61]

      K. Sun, S.N. Wang, R. R, Feng, et al., Org. Lett. 21 (2019) 2052–2055. doi: 10.1021/acs.orglett.9b00240

    62. [62]

      K. Sun, X. Wang, C. Li, et al., Org. Chem. Front. 7 (2020) 3100–3119. doi: 10.1039/d0qo00849d

    63. [63]

      X. Wang, J.P. Meng, D.Y. Zhao, et al., Chin. Chem. Lett. 34 (2023) 107736. doi: 10.1016/j.cclet.2022.08.016

    64. [64]

      H.F. Shi, X.Z. Wang, X.X. Li, et al., Org. Lett. 24 (2022) 2214–2219. doi: 10.1021/acs.orglett.2c00563

    65. [65]

      C. Ghiazza, M. Ndiaye, A. Hamdi, et al., Tetrahedron Lett. 74 (2018) 6521–6526. doi: 10.1016/j.tet.2018.09.048

    66. [66]

      X. Zhao, X.F. Wei, M.M. Tian, et al., Tetrahedron Lett. 60 (2019) 1796–1799. doi: 10.1016/j.tetlet.2019.06.002

    67. [67]

      Q.Y. Han, C.L. Zhao, T. Dong, et al., Org. Chem. Front. 6 (2019) 2732–2737. doi: 10.1039/c9qo00631a

    68. [68]

      A.D. Zordo-Banliat, L. Barthélémy, F. Bourdreux, et al., Eur. J. Org. Chem. 2020 (2020) 506–509.

    69. [69]

      J.Y. Liu, M.M. Tian, A.K. Li, et al., Tetrahedron Lett. 66 (2021) 152809. doi: 10.1016/j.tetlet.2020.152809

    70. [70]

      K.L. Tan, H.N. Wang, T. Dong, C.P. Zhang, Org. Biomol. Chem. 19 (2021) 5368–5376. doi: 10.1039/d1ob00842k

    71. [71]

      Q. Glenadel, E. Ismalaj, T. Billard, Org. Lett. 20 (2018) 56–59. doi: 10.1021/acs.orglett.7b03338

    72. [72]

      H. Wang, Y.F. Yao, Z.P. Zhang, et al., J. Org. Chem. 87 (2022) 3605–3612. doi: 10.1021/acs.joc.1c03156

    73. [73]

      L.H. Lu, X.J. Zhao, W. Dessie, et al., Org. Biomol. Chem. 20 (2022) 1754–1758. doi: 10.1039/d1ob02402g

    74. [74]

      H. Wang, Y.F. Yao, Y. You, et al., Org. Biomol. Chem. 20 (2022) 2115–2120. doi: 10.1039/d2ob00063f

  • Scheme 1  Copper-catalyzed trifluoromethylthiolation of indoles.

    下载: 全尺寸图片 幻灯片

    Scheme 2  Trifluoromethylthiolation of arenes with N-trifluoromethylthiosaccharin.

    下载: 全尺寸图片 幻灯片

    Scheme 3  Rh(Ⅲ)-catalyzed electrophilic C-2 trifluoromethylthiolation of indoles.

    下载: 全尺寸图片 幻灯片

    Scheme 4  Copper-catalyzed trifluoromethylthiolation of pyrroles with trifluoromethanesulfonyl hypervalent iodonium ylide.

    下载: 全尺寸图片 幻灯片

    Scheme 5  Copper-catalyzed trifluoromethylthiolation of pyrroles with trifluoromethanesulfonyl hypervalent iodonium ylide.

    下载: 全尺寸图片 幻灯片

    Scheme 6  Trifluoromethylthiolation of indoles and pyrroles with CF3SO2Na.

    下载: 全尺寸图片 幻灯片

    Scheme 7  POCl3-promoted trifluoromethylthiolation-based vicinal bifunctionalization of indoles with CF3SO2Na.

    下载: 全尺寸图片 幻灯片

    Scheme 8  CuCl-catalyzed C-3 trifluoromethylthiolation of indoles.

    下载: 全尺寸图片 幻灯片

    Scheme 9  C–H trifluoromethylthiolation of indoles and thiophenes with CF3SOCl.

    下载: 全尺寸图片 幻灯片

    Scheme 10  Silver-mediated aryltrifluoromethylthiolation of activated alkenes.

    下载: 全尺寸图片 幻灯片

    Scheme 11  Synthesis of trifluoromethylthiole-containing isoxazolines.

    下载: 全尺寸图片 幻灯片

    Scheme 12  Synthesis of SCF3-containing indolo[2,1-a]isoquinolin-6(5H)-ones.

    下载: 全尺寸图片 幻灯片

    Scheme 13  Synthesis of 3-trifluoromethylthiospiro[4,5]trienones.

    下载: 全尺寸图片 幻灯片

    Scheme 14  Enantioselective trifluoromethylthiolation of alkenes.

    下载: 全尺寸图片 幻灯片

    Scheme 15  Synthesis of F3CS-containing chiral azaheterocycles.

    下载: 全尺寸图片 幻灯片

    Scheme 16  Copper-assisted oxidative trifluoromethylthiolation of 2,3-allenoic acids with AgSCF3.

    下载: 全尺寸图片 幻灯片

    Scheme 17  Photocatalytic trifluoromethylthiolation of acrylamides with N-trifluoromethylthiosaccharin.

    下载: 全尺寸图片 幻灯片

    Scheme 18  Cascade cyclization of aryl acetylenes with AgSCF3.

    下载: 全尺寸图片 幻灯片

    Scheme 19  Copper-assisted trifluoromethylthiolation/radical cascade cyclization of alkynes with AgSCF3.

    下载: 全尺寸图片 幻灯片

    Scheme 20  Syntheses of azaspiro[4,5]dienones and 3,4-dihydroquinolin-2-ones.

    下载: 全尺寸图片 幻灯片

    Figure 1  Trifluoromethoxylation reagents.

    下载: 全尺寸图片 幻灯片

    Scheme 21  Photocatalytic trifluoromethoxylation of (hetero)arenes.

    下载: 全尺寸图片 幻灯片

    Scheme 22  Silver-mediated C–H trifluoromethoxylation of (hetero)arenes.

    下载: 全尺寸图片 幻灯片

    Scheme 23  Palladium-catalyzed intramolecular trifluoromethoxylation of alkenes.

    下载: 全尺寸图片 幻灯片

    Scheme 24  Silver-mediated O-trifluoromethylation of unprotected phenols.

    下载: 全尺寸图片 幻灯片

    Scheme 25  Synthesis of F3CO-containing pyridines and pyrimidines.

    下载: 全尺寸图片 幻灯片

    Scheme 26  Direct O-trifluoromethylation of N-heteroaromatics.

    下载: 全尺寸图片 幻灯片

    Figure 2  Trifluoromethylselenolation reagents.

    下载: 全尺寸图片 幻灯片

    Scheme 27  Pd-catalyzed trifluoromethylselenolation of 8-aminoquinoline.

    下载: 全尺寸图片 幻灯片

    Scheme 28  3-Trifluoromethylthiolation of indoles with TsSeCF3.

    下载: 全尺寸图片 幻灯片

    Scheme 29  Trifluoromethylselenolation of (hetero)arenes with [Me4N][SeCF3].

    下载: 全尺寸图片 幻灯片

    Scheme 30  Visible-light mediated trifluoromethylselenolation of heteroarenes with [Me4N][SeCF3].

    下载: 全尺寸图片 幻灯片

    Scheme 31  TfOH-catalyzed trifluoromethylselenolation of benzofurans.

    下载: 全尺寸图片 幻灯片

    Scheme 32  Synthesis of N-acylated and 3-trifluoromethylselanylated indoles.

    下载: 全尺寸图片 幻灯片

    Scheme 33  Syntheses of fluoroalkylselenolated five- and six-membered-ring heterocycles.

    下载: 全尺寸图片 幻灯片

    Scheme 34  Synthesis of 2,3-bis(trifluoromethylseleno)indole.

    下载: 全尺寸图片 幻灯片

    Scheme 35  BnSe(O)CF3/Tf2O-mediated synthesis of 4-(trifluoromethylseleno)isocoumarins.

    下载: 全尺寸图片 幻灯片

    Scheme 36  Visible-light-promoted trifluoromethylselenolation of ortho-hydroxyarylenaminones.

    下载: 全尺寸图片 幻灯片

    Scheme 37  Synthesis of 3-(trifluoromethylseleno)indoles.

    下载: 全尺寸图片 幻灯片
  • 加载中
WeChat 扫一扫看文章
计量
  • PDF下载量:  13
  • 文章访问数:  917
  • HTML全文浏览量:  59
文章相关
  • 发布日期:  2023-05-15
  • 收稿日期:  2022-10-31
  • 接受日期:  2022-12-05
  • 修回日期:  2022-12-03
  • 网络出版日期:  2022-12-08
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章

All Rights Reserved by the Chinese Chemical Society   中国化学会 版权所有 京ICP备05002797号

本系统由北京仁和汇智信息技术有限公司开发    技术支持: info@rhhz.net