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Article

Synthesis of CF3-Indazoles via Rh(III)-Catalyzed C-H [4+1] Annulation of Azobenzenes with CF3-Imidoyl Sulfoxonium Ylides

by
Yilong Shang
†,
Chen Li
†,
Guiqiu Wang
,
Guiwei Yao
,
Hongliang Wu
,
Xun Chen
* and
Ruirui Zhai
*
Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, International Joint Research Center of Human-Machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan Provincial Key Laboratory of Research and Development on Tropical Herbs, School of Pharmaceutical Sciences, Hainan Medical University, Haikou 571199, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this paper.
Molecules 2025, 30(1), 183; https://doi.org/10.3390/molecules30010183
Submission received: 13 December 2024 / Revised: 1 January 2025 / Accepted: 3 January 2025 / Published: 5 January 2025
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Abstract

:
An efficient Rh(III)-catalyzed C-H activation of azobenzenes and subsequent [4+1] cascade annulation with CF3-imidoyl sulfoxonium ylides was developed, yielding diverse CF3-indazoles. This protocol featured easily available starting materials, excellent functional group tolerance and high efficiency. Moreover, the antitumor activities of selected CF3-indazoles against human cancer cell lines were also studied, and the results indicated that several compounds displayed considerable antiproliferative activities.

1. Introduction

Indazoles have been identified as important skeletons found widely in natural products, drugs and agrochemicals, with a broad spectrum of biological activities, such as anti-cancer activity, viral polymerase inhibition, antiemetic and anti-inflammatory activity [1,2] (Figure 1). Thus, numerous efforts have been made for the construction of such skeletons. Directing group-assisted transition metal-catalyzed C-H bond activation/cyclization is regarded as a powerful approach for the assembly of structurally diverse molecules [3,4,5]. In this regard, azobenzenes have been used as versatile directing substrates and applied in transition metal-catalyzed C-H functionalization with various coupling partners for the synthesis of indazoles. For example, Ellman [6], Wang [7] and Kim [8] independently reported outstanding work on Co(III)-, Re(I)- or Rh(III)-catalyzed C-H bond activation and cascade annulation of azobenzenes with aldehydes to construct indazoles. Xi’s group [9] also described a Rh(III)-catalyzed C-H coupling/annulation between azobenzenes and alkenes employing Cu(OAc)2 as an oxidant, leading to indazoles. Moreover, Cui and co-workers [10] demonstrated an efficient synthesis of indazoles via Rh(III)-catalyzed C-H [4+1] cyclization of azobenzenes with α-Cl ketones. Despite these great achievements, there is great demand for the exploration of other novel and effective coupling partners to synthesize multifarious heterocycles.
CF3-heterocycles serve as privileged frameworks that show promising application in drug development, since introducing the CF3 group into molecular structures could improve their pharmacological activities [11,12,13]. Recent decades have witnessed the flourishing development of the construction of CF3-heterocycles from various CF3-containing building blocks [14,15,16,17,18]. Among them, CF3-imidoyl sulfoxonium ylides (TFISYs), featuring considerable stability and high activity as metal carbene precursors with multifunctional synthons, have been broadly applied in transition metal-catalyzed C-H functionalization of different directing substrates for producing a series of CF3-heterocycles. For example, Wu’s [19] and Chen’s [20] groups employed TFISYs as alkenylating agents to achieve a Rh(III)-catalyzed C-H alkenylation of N-pyrimidylindoles and quinolin-8-carboxaldehydes (Scheme 1a). Moreover, Cheng [21], Wu [22,23,24] and Li [25] reported the synthesis of valuable CF3-heterocycles via transition metal-catalyzed C-H [n+3] annulation by using TFISYs as C3 synthons, in which cascade annulation was triggered by the attack of enamine nitrogen on an electrophilic directing group (Scheme 1b). An alternative application of TFISYs in C-H functionalization focused on the C-H [n+2] annulation induced by the addition of a nucleophilic directing group to the imine moiety of TFISYs. In this respect, Wu [26], Fan [27,28] and our group [29] independently found Rh(III)- or Ru(II)-catalyzed C-H [n+2] annulation with TFISYs assisted by different directing groups, leading to a number of CF3-tethered heterocycles (Scheme 1c). Moreover, Wu and co-workers [30] applied TFISYs as a C1 synthon in a Rh(III)-catalyzed C-H [4+1] annulation reaction, resulting in the formation of CF3-substituted isoindolo [2,1-a]indoles (Scheme 1d). To the best of our knowledge, there is only one successful report on the C-H [n+1] annulation by using TFISYs as C1 synthon. Motivated by the aforementioned groundbreaking works on TFISYs and our ongoing interest in the synthesis of CF3-heterocycles [29,31,32,33,34,35]. Herein, we report an efficient Rh(III)-catalyzed C-H [4+1] annulation reaction of azobenzenes with TFISYs, yielding diverse CF3-indazoles (Scheme 1e).

2. Results and Discussion

We commenced our investigation by using azobenzene (1a) and TFISY (2a) as the model substrates (Table 1). Encouragingly, the desired product 3a was isolated in a 27% yield in the presence of [Cp*RhCl2]2, HOAc and AgOAc in DCE at 80 °C. Subsequently, several solvents such as MeCN, TFE, HFIP, DMF, THF and dioxane were tested (entries 2–7), among which the yield of 3a increased to 50% with HFIP as the reaction solvent. Other commonly used metal catalysts in the C-H activation reactions, such as CoCp*(CO)I2, Pd(OAc)2, [Cp*IrCl2]2 and [Ru(p-cymene)Cl2]2, were proven to be inert or produce a low yield in this transformation (entries 8–11). The product 3a was not obtained when the reaction was performed in the absence of a catalyst (entry 12). Subsequently, the reaction was conducted in the absence of HOAc or by using NaOAc instead of HOAc as the additive (entries 13–14), but these conditions did not improve the reaction yields. Then, we changed AgOAc to other oxidants, including Ag2CO3, Cu(OAc)2·H2O, K2S2O8, PhI(OAc)2 and O2 (entries 15–19), and Cu(OAc)2·H2O was found to give the best result, resulting in a 58% yield of the product 3a. The effect of reaction temperature on this transformation was also investigated. Increasing the reaction temperature to 100 °C could lead to a slightly improved yield of 65%, while lowering the reaction temperature to 60 °C generated a decreased yield of 43% (entries 20–21). Variation of the amount of Cu(OAc)2·H2O revealed that the product 3a could be increased to a 76% yield when 3.0 equiv of Cu(OAc)2·H2O was employed (entry 23). Reducing the loading of [Cp*RhCl2]2 catalyst from 5 mol% to 2 mol% could provide the product 3a with a 71% yield (entry 24).
After the optimized conditions were established, we turned our attention toward examining the scope and limitation of this [4+1] annulation reaction. As shown in Table 2, TFISYs containing electron-donating groups (Me and OMe) as well as electron-withdrawing groups (F, Cl, Br, NO2) at the para-, meta- or ortho-position of benzene ring could smoothly react with 1a to afford the corresponding annulation products 3a–3l at 65–88% yields. Substrate derived from naphthalene also performed well in this catalytic system and delivered the desired product 3m in a 76% yield. Moreover, other fluorinated (C2F5, C3F7) imidoyl sulfoxonium ylides were also allowed for this transformation to assemble the target products 3n and 3o at good to excellent yields. Next, the scope and generality of several azobenzenes were also studied under optimized conditions using 2b as the coupling partner. A series of para-substituted azobenzenes were compatible with this reaction to produce the corresponding products 3p–3t in 56–81% yields. Meta methyl- and chlorine-substituted azobenzenes could provide the single products 3u (86%) and 3v (88%) with excellent regioselectivity. Moreover, azobenzenes bearing fluorine or methyl at the ortho-position were well tolerated to assemble the products 3w and 3x in 71% and 83% yields, respectively, indicating the high steric tolerance in this transformation.
To demonstrate the synthetic utility of this protocol, we performed an annulation reaction of 1a with 2a on a 5 mmol scale, and we found that the product 3a was isolated in a 75% yield (Scheme 2a). Furthermore, we investigated the possible mechanism of this reaction by conducting several control experiments as shown in Scheme 2. Firstly, the five-membered rhodacycle complex I was prepared by the reaction of azobenzene 1a with [Cp*RhCl2]2 and NaOAc in DCE at 130 °C for 24 h (Scheme 2b). Then, we used the prepared complex I to react with 2a under the standard condition without [Cp*RhCl2]2, and the desired product 3a was formed in a 46% yield (Scheme 2c), thus implying the occurrence of C-H activation in this reaction. We also performed the reaction of complex I with 2a without any additive and oxidant, and we found that the desired product 3a was not observed, highlighting the important role of Cu(OAc)2·H2O and HOAc in the success of this reaction (Scheme 2d). Moreover, a deuterium exchange of azobenzene 1a was performed with CD3OD under standard condition, and 26% deuterium incorporation at the ortho-position of 1a was afforded, implying that the C-H bond activation process might be reversible (Scheme 2e). Subsequently, an intermolecular competition experiment was conducted for exploring the electronic preference of this transformation. The result (3t/3p = 1.8:1) suggested that the C-H activation presumably occurs through a concerted metalation-deprotonation (CMD) process (Scheme 2f) [36]. Finally, a kinetic isotopic effect (KIE) experiment was also performed, and a value of 3.0 implied that the C-H bond cleavage was likely to be the rate-determining step of this transformation (Scheme 2g).
Based on our experimental results and the previous literature on C-H functionalization with TFISYs [19,20,21,22,23,24,25,26,27,28,29,30], a plausible catalytic mechanism of this reaction is shown in Scheme 3. Initially, an active [Cp*RhCl2]2 catalyst derived from ligand exchange was coordinated with 1a to produce the five-membered rhodacycle intermediate I via a C-H bond activation process. Then, the coordination of intermediate I with 2a afforded the intermediate II, followed by the α-elimination of DMSO to deliver a Rh-carbene species intermediate III. Subsequently, a six-membered rhodacycle IV was formed through migration insertion, which underwent a protonation process to generate the intermediate V with regeneration of the active [Cp*Rh] catalyst. Finally, the intermediate V proceeded by intramolecular cyclization and oxidation under Cu(OAc)2·H2O to give the desired product 3a.
Finally, the preliminary antitumor activities of selected CF3-containing indazoles against three human cancer cell lines (A549, Hela and HepG2) were studied by Cell Counting Kit-8 assay, with Gefitinib as the reference drug. As shown in Table 3, most of the compounds displayed some degree of growth inhibition against these cancer cells. For example, the inhibitory efficiency (10.2 μM) of compound 3g against Hela cells was superior to that of Gefitinib. Compounds 3a and 3l exhibited equivalent cytotoxicity to that of Gefitinib against A549 cells. In addition, several compounds, such as 3g (2.1 μM), 3m (5.7 μM) and 3t (4.3 μM), were found to display strong growth inhibition against HepG2 cells. These results showed that CF3-containing indazoles may be developed as antitumor lead compounds for drug development.

3. Materials and Methods

3.1. General Information

All reactions were carried out in flame-dried hermetic tubes with magnetic stirring. Unless otherwise noted, materials were purchased from commercial suppliers (Alfa, TCI, Sigma-Aldrich, Shanghai, China), and used without further purification. Purifications of reaction products were carried out by flash chromatography using silica gel (40–63 mm) (Qingdao Haiyang Chemical Corporation Limited, Qingdao, China) 1H NMR, 13C NMR and 19F NMR spectra were measured on a 400 MHz Bruker spectrometer (Bruker, Karlsruhe, Germany). The transform spectrometer was operated at 400 MHz for 1H NMR and 101 MHz for 13C NMR. 1H NMR chemical shifts are reported relative to TMS and were referenced via residual proton resonances of the corresponding deuterated solvent (CDCl3: 7.26 ppm), whereas 13C NMR spectra are reported relative to TMS via the carbon signals of the deuterated solvent (CDCl3: 77.16 ppm). All melting points were determined on XT4B melting point apparatus and uncorrected (Beijing Science Instrument Dianguang Instrument Factory, Beijing, China). High-resolution mass spectra (HRMS) were measured with an ESI source using a time-of-flight (TOF) detector (Agilent, Santa Clara, CA, USA). CF3-imidoyl sulfoxonium ylides were synthesized according to the previously reported procedure [37,38,39,40,41]. Azobenzenes were synthesized according to the previously reported procedure [42].

3.2. The General Procedure

A pressure tube was charged with azobenzenes (0.2 mmol, 1 equiv), CF3-imidoyl sulfoxonium ylides (0.3 mmol, 1.5 equiv), [Cp*RhCl2]2 (5 mol%), Cu(OAc)2·H2O (3 equiv), HOAc (2 equiv) and HFIP (2 mL). Then, the mixture was stirred at 100 °C under an air atmosphere for 24 h. After being cooled to ambient temperature, the mixture was filtered through a pad of Celite and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using ethyl acetate/petroleum ether as an eluent to provide the desired products.

3.3. Characterization Data of Novel Compounds

(Z)-2,2,2-trifluoro-N-phenyl-1-(2-phenyl-2H-indazol-3-yl)ethan-1-imine (3a): brown solid, 55.7 mg, 76% yield, mp 83.9–85.7 °C, 1H NMR (400 MHz, CDCl3) δ: 7.81 (d, J = 9.7 Hz, 2H), 7.44–7.38 (m, 1H), 7.36–7.29 (m, 2H), 7.28–7.23 (m, 2H), 7.02–6.95 (m, 3H), 6.92 (t, J = 7.4 Hz, 2H), 6.15–6.08 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 148.93, 147.56 (q, C-F, 2JC-F = 36.4 Hz), 145.80, 139.14, 129.27, 129.00, 128.86, 127.38, 126.85, 124.87, 124.38, 124.20, 123.22, 120.72, 119.97 (q, C-F, 1JC-F = 279.8 Hz), 119.76 (d, C-F, 3JC-F = 3.0 Hz), 118.68; 19F NMR (376 MHz, CDCl3) δ: −68.87; HRMS (ESI) calcd for C21H15F3N3 (M + H)+: 366.1213, found 366.1211.
(Z)-2,2,2-trifluoro-1-(2-phenyl-2H-indazol-3-yl)-N-(p-tolyl)ethan-1-imine (3b): yellow solid, 66.7 mg, 88% yield, mp 82.2–84.7 °C, 1H NMR (400 MHz, CDCl3) δ: 7.76–7.70 (m, 2H), 7.37–7.31 (m, 1H), 7.29–7.15 (m, 4H), 6.98–6.91 (m, 2H), 6.67 (d, J = 7.8 Hz, 2H), 6.02–5.96 (m, 2H), 2.13 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 148.97, 146.63 (q, C-F, 2JC-F = 36.4 Hz), 143.32, 139.18, 137.16, 129.44, 129.16, 128.98, 127.35, 125.55 (q, C-F, 1JC-F = 279.8 Hz), 124.74, 124.39, 124.06, 123.58, 121.05, 119.82 (d, C-F, 3JC-F = 2.0 Hz), 118.64, 21.08; 19F NMR (376 MHz, CDCl3) δ: −68.68; HRMS (ESI) calcd for C22H17F3N3 (M + H)+: 380.1310, found 380.1369.
(Z)-2,2,2-trifluoro-N-(4-methoxyphenyl)-1-(2-phenyl-2H-indazol-3-yl)ethan-1-imine (3c): brown oil, 51.4 mg, 65% yield, 1H NMR (400 MHz, CDCl3) δ: 7.75 (dt, J = 8.8, 1.0 Hz, 1H), 7.71 (dd, J = 8.6, 1.0 Hz, 1H), 7.34 (ddd, J = 8.7, 6.6, 1.1 Hz, 1H), 7.28–7.17 (m, 4H), 7.01–6.97 (m, 2H), 6.44–6.40 (m, 2H), 6.13–6.09 (m, 2H), 3.62 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 158.72, 148.76, 144.74 (q, C-F, 2JC-F = 36.4 Hz), 138.87, 138.50, 128.84, 128.69, 127.08, 124.39, 124.01, 123.50, 123.48, 123.12, 119.83 (q, C-F, 1JC-F = 279.8 Hz), 119.53 (d, C-F, 3JC-F = 2.0 Hz), 118.31, 113.83, 55.21; 19F NMR (376 MHz, CDCl3) δ: −68.71; HRMS (ESI) calcd for C22H17F3N3O (M + H)+: 396.1319, found 396.1320.
(Z)-N-(4-chlorophenyl)-2,2,2-trifluoro-1-(2-phenyl-2H-indazol-3-yl)ethan-1-imine (3d): brown solid, 52.7 mg, 66% yield, mp 94.7–96.3 °C, 1H NMR (400 MHz, CDCl3) δ: 7.82–7.66 (m, 2H), 7.39–7.33 (m, 1H), 7.32–7.18 (m, 4H), 7.01–6.94 (m, 2H), 6.86–6.80 (m, 2H), 6.00–5.94 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 149.01, 148.29 (q, C-F, 2JC-F = 36.4 Hz), 144.31, 139.07, 132.62, 129.42, 129.32, 129.16, 129.01, 127.54, 126.07, 125.17, 124.31, 124.19, 122.70, 122.08, 119.88 (q, C-F, 1JC-F = 280.8 Hz), 119.65 (d, C-F, 3JC-F = 3.0 Hz), 118.81; 19F NMR (376 MHz, CDCl3) δ: −68.91; HRMS (ESI) calcd for C21H14Cl F3N3 (M + H)+: 400.0823, found 400.0823.
(Z)-N-(4-bromophenyl)-2,2,2-trifluoro-1-(2-phenyl-2H-indazol-3-yl)ethan-1-imine (3e): yellow solid, 69.1 mg, 78% yield, mp 119.7–121.7 °C, 1H NMR (400 MHz, CDCl3) δ: 7.78–7.70 (m, 2H), 7.38–7.33 (m, 1H), 7.32–7.17 (m, 4H), 7.00–6.94 (m, 4H), 5.93–5.87 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 148.99, 148.30 (q, C-F, 2JC-F = 37.4 Hz), 144.77, 139.05, 131.96, 129.41, 129.14, 127.52, 125.17, 124.30, 124.19, 122.64, 122.30, 120.50, 119.88 (q, C-F, 1JC-F = 279.8 Hz), 119.62 (d, C-F, 3JC-F = 3 Hz), 118.80; 19F NMR (376 MHz, CDCl3) δ: −68.81; HRMS (ESI) calcd for C21H14BrF3N3 (M + H)+: 444.0318, found 444.0315.
(Z)-2,2,2-trifluoro-N-(4-fluorophenyl)-1-(2-phenyl-2H-indazol-3-yl)ethan-1-imine (3f): yellow solid, 59.0 mg, 72% yield, mp 147.4–151.3 °C, 1H NMR (400 MHz, CDCl3) δ 7.77–7.65 (m, 4H), 7.38–7.30 (m, 2H), 7.30–7.14 (m, 3H), 6.95 (d, J = 7.8 Hz, 2H), 6.07 (d, J = 9.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 151.21, 150.57 (q, C-F, 2JC-F = 37.4 Hz), 148.95, 145.44, 138.91, 129.69, 129.40, 127.69, 125.69, 124.42, 124.18, 121.77, 120.96, 120.50, 119.57 (q, C-F, 1JC-F = 280.8 Hz), 119.35 (d, C-F, 3JC-F = 3.0 Hz), 118.95, 118.18; 19F NMR (376 MHz, CDCl3) δ −68.70; HRMS (ESI) calcd for C21H14F3N4O2 (M + H)+: 411.1064, found 411.1070.
(Z)-2,2,2-trifluoro-N-(4-fluorophenyl)-1-(2-phenyl-2H-indazol-3-yl)ethan-1-imine (3g): yellow solid, 62.0 mg, 81% yield, mp 79.9–81.6 °C, 1H NMR (400 MHz, CDCl3) δ: 7.00–6.89 (m, 2H), 6.57–6.51 (m, 1H), 6.49–6.36 (m, 4H), 6.20–6.14 (m, 2H), 5.80–5.70 (m, 2H), 5.27–5.17 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 162.91, 160.44, 149.35, 147.93 (q, C-F, 2JC-F = 37.4 Hz), 142.23, 139.40, 129.66, 129.41, 127.81, 125.37, 124.56, 124.41, 123.16, 123.07, 120.27 (q, C-F, 1JC-F = 278.8 Hz), 119.98, 119.08, 116.13, 116.01; 19F NMR (376 MHz, CDCl3) δ: −68.85, −114.35; HRMS (ESI) calcd for C21H14F4N3 (M + H)+: 384.1119, found 384.1118.
(Z)-2,2,2-trifluoro-1-(2-phenyl-2H-indazol-3-yl)-N-(o-tolyl)ethan-1-imine (3h): brown solid, 66.0 mg, 87% yield, mp 91.2–94.6 °C, 1H NMR (400 MHz, CDCl3) δ: 8.12–7.66 (m, 2H), 7.37–7.23 (m, 3H), 7.23–7.14 (m, 2H), 6.89–6.77 (m, 4H), 6.61 (t, J = 6.8 Hz, 1H), 5.72 (d, J = 8.0 Hz, 1H), 1.52 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 148.89, 146.17 (q, C-F, 2JC-F = 37.4 Hz), 144.16, 139.36, 133.59, 130.51, 129.30, 129.21, 127.38, 127.34, 125.95, 124.77, 124.69, 124.27, 123.65, 119.96 (q, C-F, 1JC-F = 279.8 Hz), 119.78 (d, C-F, 3JC-F = 3 Hz), 118.65, 117.63, 17.12; 19F NMR (376 MHz, CDCl3) δ: -68.79; HRMS (ESI) calcd for C22H17F3N3 (M + H)+: 380.1370, found 380.1367.
(Z)-2,2,2-trifluoro-N-(2-methoxyphenyl)-1-(2-phenyl-2H-indazol-3-yl)ethan-1-imine (3i): yellow solid, 61.6 mg, 78% yield, mp 118.1–120.2 °C, 1H NMR (400 MHz, CDCl3) δ: 7.80–7.67 (m, 2H), 7.34–7.26 (m, 2H), 7.26–7.14 (m, 3H), 7.01 (dd, J = 7.6, 2.1 Hz, 2H), 6.90–6.84 (m, 1H), 6.49–6.36 (m, 2H), 5.93 (dd, J = 8.2, 1.7 Hz, 1H), 3.07 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 149.64, 148.84, 148.07 (q, C-F, 2JC-F = 36.4 Hz), 139.31, 134.87, 129.23, 128.73, 127.85, 127.16, 126.02, 124.47, 124.24, 123.45, 121.20, 120.37, 120.10 (d, C-F, 3JC-F = 3 Hz), 119.88 (q, C-F, 1JC-F = 279.8 Hz), 118.39, 110.78, 55.75; 19F NMR (376 MHz, CDCl3) δ: −68.19; HRMS (ESI) calcd for C22H17F3N3O (M + H)+: 396.1319, found 396.1317.
(Z)-N-(2-bromophenyl)-2,2,2-trifluoro-1-(2-phenyl-2H-indazol-3-yl)ethan-1-imine (3j): yellow solid, 62.0 mg, 70% yield, mp 101.8–102.4 °C, 1H NMR (400 MHz, CDCl3) δ: 7.75 (t, J = 7.9 Hz, 2H), 7.35 (ddd, J = 10.7, 7.1, 2.0 Hz, 2H), 7.30–7.16 (m, 4H), 6.96–6.91 (m, 2H), 6.78 (dtd, J = 18.0, 7.5, 1.7 Hz, 2H), 5.81 (d, J = 7.7 Hz, 1H).; 13C NMR (101 MHz, CDCl3) δ: 148.88, 148.40 (q, C-F, 2JC-F = 37.4 Hz), 144.14, 139.08, 133.22, 129.66, 129.59, 128.14, 127.50, 127.42, 125.05, 124.22, 124.16, 122.63, 119.71 (q, C-F, 1JC-F = 280.8 Hz), 119.69 (d, C-F, 3JC-F = 3.0 Hz), 119.34, 119.28, 118.69; 19F NMR (376 MHz, CDCl3) δ: −68.55; HRMS (ESI) calcd for C21H14BrF3N3 (M + H)+: 444.0318, found 444.0315.
(Z)-2,2,2-trifluoro-1-(2-phenyl-2H-indazol-3-yl)-N-(m-tolyl)ethan-1-imine (3k): yellow solid, 66.7 mg, 88% yield, mp 73.9–75.8 °C, 1H NMR (400 MHz, CDCl3) δ: 6.97–6.90 (m, 2H), 6.53 (ddd, J = 8.9, 6.7, 1.0 Hz, 1H), 6.49–6.35 (m, 4H), 6.15–6.09 (m, 2H), 5.94–5.88 (m, 2H), 1.14 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 148.90, 147.49 (q, C-F, 2JC-F = 37.4 Hz), 145.86, 139.13, 138.84, 129.18, 128.81, 128.53, 127.54, 127.34, 124.80, 124.45, 124.22, 123.44, 122.22, 119.98 (q, C-F, 1JC-F = 279.8 Hz), 119.79, 118.64, 116.51, 21.22; 19F NMR (376 MHz, CDCl3) δ: −68.87; HRMS (ESI) calcd for C22H17F3N3 (M + H)+: 380.1370, found 380.1367.
(Z)-N-(3-chlorophenyl)-2,2,2-trifluoro-1-(2-phenyl-2H-indazol-3-yl)ethan-1-imine (3l): yellow solid, 69.4 mg, 87% yield, mp 74.0–77.4 °C, 1H NMR (400 MHz, CDCl3) δ: 7.74 (d, J = 9.4 Hz, 2H), 7.39–7.30 (m, 2H), 7.30–7.13 (m, 3H), 7.00–6.84 (m, 3H), 6.75 (t, J = 8.0 Hz, 1H), 6.02 (t, J = 2.0 Hz, 1H), 5.81 (d, J = 7.4 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ: 149.08 (q, C-F, 2JC-F = 36.4 Hz), 147.03, 138.87, 134.76, 129.71, 129.58, 129.46, 129.23, 127.44, 126.55, 125.16, 124.25, 122.64, 121.74, 119.76 (q, C-F, 1JC-F =280.8 Hz), 119.56, 118.76, 117.12; 19F NMR (376 MHz, CDCl3) δ: −68.86; HRMS (ESI) calcd for C21H14ClF3N3 (M + H)+: 400.0823, found 400.0822.
(Z)-2,2,2-trifluoro-N-(naphthalen-2-yl)-1-(2-phenyl-2H-indazol-3-yl)ethan-1-imine (3m): brown solid, 63.1 mg, 76% yield, mp 84.4–86.3 °C, 1H NMR (400 MHz, CDCl3) δ: 7.83–7.76 (m, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.59 (d, J = 11.0 Hz, 1H), 7.38–7.23 (m, 6H), 7.20–7.14 (m, 1H), 7.01–6.94 (m, 2H), 6.80–6.72 (m, 2H), 6.56 (d, J = 2.1 Hz, 1H), 6.13 (dd, J = 8.7, 2.1 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ: 149.00, 147.80 (q, C-F, 2JC-F = 37.4 Hz), 143.34, 139.18, 133.39, 131.90, 129.17, 129.01, 128.70, 128.37, 127.69, 127.46, 126.63, 126.47, 125.01, 124.30, 124.12, 123.49, 120.21, 120.10 (q, C-F, 1JC-F = 279.8 Hz), 119.84 (d, C-F, 3JC-F = 2.0 Hz), 118.91, 118.74; 19F NMR (376 MHz, CDCl3) δ: −68.65; HRMS (ESI) calcd for C25H17F3N3 (M + H)+: 416.1370, found 416.1368.
(Z)-2,2,3,3,3-pentafluoro-N-phenyl-1-(2-phenyl-2H-indazol-3-yl)propan-1-imine (3n): yellow solid, 67.2 mg, 81% yield, mp 86.5–82.9 °C, 1H NMR (400 MHz, CDCl3) δ: 7.74 (d, J = 8.7 Hz, 1H), 7.70 (d, J = 9.5 Hz, 1H), 7.33 (ddd, J = 8.7, 6.7, 1.1 Hz, 1H), 7.30–7.14 (m, 4H), 6.98–6.85 (m, 5H), 6.16–6.05 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 148.90, 148.36 (q, C-F, J = 36.4 Hz), 145.82, 139.25, 129.22, 129.04, 128.89, 127.39, 127.13, 124.86, 124.39, 124.03, 123.44, 120.92, 119.02 (q, C-F, J = 279.8 Hz), 119.84, 119.79, 118.64; 19F NMR (376 MHz, CDCl3) δ; −79.83, −111.54, −111.66; HRMS (ESI) calcd for C22H15F5N3 (M + H)+: 416.1181, found 416.1177.
(Z)-2,2,3,3,4,4,4-heptafluoro-N-phenyl-1-(2-phenyl-2H-indazol-3-yl)butan-1-imine (3o): yellow solid, 77.6 mg, 81% yield, mp 65.1–66.7 °C, 1H NMR (400 MHz, CDCl3) δ: 7.74 (d, J = 8.8 Hz, 1H), 7.61 (d, J = 8.6 Hz, 1H), 7.37–7.27 (m, 2H), 7.27–7.14 (m, 3H), 7.08–7.00 (m, 2H), 6.99–6.89 (m, 3H), 6.30–6.15 (m, 2H); 13C (101 MHz, CDCl3) δ: 148.59, 145.54, 139.12, 128.96, 128.79, 128.65, 127.06, 126.97, 124.53, 124.09, 123.47, 123.35, 120.69, 119.39, 118.82, 118.33, 109.06, 112.60; 19F NMR (376 MHz, CDCl3) δ: −79.28 (t, J = 10.1 Hz), −108.37, −108.84, −123.23, −123.38; HRMS (ESI) calcd for C23H15F7N3 (M + H)+: 446.1149, found 446.1151.
(Z)-2,2,2-trifluoro-1-(5-methoxy-2-(4-methoxyphenyl)-2H-indazol-3-yl)-N-(p-tolyl)ethan-1-imine (3p): yellow solid, 44.0 mg, 50% yield, mp 157.9–159.5 °C, 1H NMR (400 MHz, CDCl3) δ: 7.61 (d, J = 9.3 Hz, 1H), 7.02 (dd, J = 9.4, 2.3 Hz, 1H), 6.87–6.81 (m, 3H), 6.76–6.66 (m, 4H), 6.10 (d, J = 8.3 Hz, 2H), 3.79 (d, J = 23.4 Hz, 6H), 2.16 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 159.81, 157.09, 146.86 (q, C-F, 2JC-F = 37.4 Hz), 145.49, 143.47, 137.06, 132.48, 129.36, 125.40, 124.23, 122.48, 122.22, 121.15, 120.13 (q, C-F, 1JC-F = 279.8 Hz), 119.80, 114.18, 95.70, 55.68, 55.50, 21.06; 19F NMR (376 MHz, CDCl3) δ: −68.81; HRMS (ESI) calcd for C24H21F3N3O2(M + H)+: 440.1581, found 440.1579.
(Z)-2,2,2-trifluoro-1-(5-methyl-2-(p-tolyl)-2H-indazol-3-yl)-N-(p-tolyl)ethan-1-imine (3q): yellow solid, 66.0 mg, 81% yield, mp 112.7–114.0 °C, 1H NMR (400 MHz, CDCl3) δ: 6.47 (d, J = 9.7 Hz, 1H), 6.29 (s, 1H), 6.06–5.98 (m, 1H), 5.83 (d, J = 8.2 Hz, 2H), 5.65 (d, J = 8.4 Hz, 2H), 5.53 (d, J = 8.2 Hz, 2H), 4.88 (d, J = 8.4 Hz, 2H), 1.27 (s, 3H), 1.14 (s, 3H), 1.00 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 147.82, 146.98 (q, C-F, 2JC-F = 37.4 Hz), 143.44, 138.95, 137.05, 136.86, 134.35, 130.18, 129.61, 129.33, 124.38, 124.11, 122.58, 121.15, 120.06 (q, C-F, 1JC-F = 279.8 Hz), 118.18, 117.79 (d, C-F, 3JC-F = 2.0 Hz), 22.22, 21.24, 21.10; 19F NMR (376 MHz, CDCl3) δ: −68.80; HRMS (ESI) calcd for C24H21F3N3(M + H)+: 408.1683, found 408.1686.
(Z)-1-(5-chloro-2-(4-chlorophenyl)-2H-indazol-3-yl)-2,2,2-trifluoro-N-(p-tolyl)ethan-1-imine (3r): yellow solid, 50.1 mg, 56% yield, mp 125.2–127.9 °C, 1H NMR (400 MHz, CDCl3) δ: 6.94–6.81 (m, 2H), 6.48 (dd, J = 9.2, 1.9 Hz, 1H), 6.39–6.33 (m, 2H), 6.09–6.00 (m, 2H), 5.92 (d, J = 8.2 Hz, 2H), 5.20 (d, J = 6.4 Hz, 2H), 1.36 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 147.40, 145.43 (q, C-F, 2JC-F = 37.4 Hz), 143.00, 137.71, 137.34, 135.38, 130.96, 129.58, 129.36, 129.23, 125.46, 124.38, 123.34, 121.09, 120.17, 119.90 (q, C-F, 1JC-F = 279.8 Hz), 118.60 (d, C-F, 3JC-F = 3.0 Hz), 21.12; 19F NMR (376 MHz, CDCl3) δ: -68.84; HRMS (ESI) calcd for C22H15Cl2F3N3(M + H)+: 448.0590, found 448.0586.
(Z)-1-(5-bromo-2-(4-bromophenyl)-2H-indazol-3-yl)-2,2,2-trifluoro-N-(p-tolyl)ethan-1-imine (3s): yellow solid, 70.9 mg, 66% yield, mp 121.0–123.2 °C, 1H NMR (400 MHz, CDCl3) δ: 7.91 (s, 1H), 7.61 (dd, J = 9.3, 3.7 Hz, 1H), 7.42 (dd, J = 9.2, 2.9 Hz, 1H), 7.36–7.16 (m, 2H), 6.76 (ddd, J = 22.0, 8.5, 3.3 Hz, 4H), 6.01 (dd, J = 8.5, 3.5 Hz, 2H), 2.17 (d, J = 3.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 147.49, 145.46 (q, C-F, 2JC-F = 37.4 Hz), 142.99, 137.79, 137.74, 132.36, 131.53, 129.60, 125.72, 125.10, 123.42, 123.12, 122.00 (d, C-F, 3JC-F = 2.0 Hz), 121.09, 120.33, 119.86 (q, C-F, 1JC-F = 279.8 Hz), 118.95, 21.14; 19F NMR (376 MHz, CDCl3) δ: −68.82; HRMS (ESI) calcd for C22H15Br2F3N3(M + H)+: 537.9559, found 537.9558.
(Z)-2,2,2-trifluoro-1-(5-fluoro-2-(4-fluorophenyl)-2H-indazol-3-yl)-N-(p-tolyl)ethan-1-imine (3t): yellow solid, 64.8 mg, 78% yield, mp 125.4–127.9 °C, 1H NMR (400 MHz, CDCl3) δ: 7.71 (dd, J = 9.4, 4.7 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.18–7.12 (m, 1H), 6.88 (d, J = 6.4 Hz, 4H), 6.73 (d, J = 8.2 Hz, 2H), 6.02 (d, J = 8.4 Hz, 2H), 2.16 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 164.03, 161.44, 158.91, 146.35, 145.73 (q, C-F, 2JC-F = 36.4 Hz), 143.12, 137.58, 135.16, 129.57, 126.11, 123.95, 123.60, 121.11, 120.87, 119.99 (q, C-F, 1JC-F = 279.8 Hz), 119.52, 119.23, 116.18, 102.77, 21.10; 19F NMR (376 MHz, CDCl3) δ: −68.96, −111.28, −114.77; HRMS (ESI) calcd for C22H15F5N3(M + H)+: 416.1181, found 416.1181.
(Z)-2,2,2-trifluoro-1-(6-methyl-2-(m-tolyl)-2H-indazol-3-yl)-N-(p-tolyl)ethan-1-imine (3u): brown solid, 70.0 mg, 86% yield, mp 85.1–87.3 °C, 1H NMR (400 MHz, CDCl3) δ: 7.70 (d, J = 8.7 Hz, 1H), 7.55 (s, 1H), 7.20–7.10 (m, 3H), 6.88 (d, J = 5.8 Hz, 1H), 6.76 (d, J = 6.8 Hz, 2H), 6.63 (s, 1H), 6.05 (d, J = 6.5 Hz, 2H), 2.51 (s, 3H), 2.23 (s, 6H); 13C NMR (101 MHz, CDCl3) δ: 149.53, 147.24 (q, C-F, 2JC-F = 36.4 Hz), 143.44, 139.51, 139.06, 137.36, 136.86, 129.49, 129.35, 128.72, 127.65, 125.26, 123.36, 122.47, 121.20, 121.06, 120.04 (q, C-F, 1JC-F = 279.8 Hz), 119.31, 116.82, 22.26, 21.26, 21.06; 19F NMR (376 MHz, CDCl3) δ: −68.92; HRMS (ESI) calcd for C24H21F3N3 (M + H)+: 408.1683, found 408.1684.
(Z)-1-(6-chloro-2-(3-chlorophenyl)-2H-indazol-3-yl)-2,2,2-trifluoro-N-(p-tolyl)ethan-1-imine (3v): brown solid, 78.7 mg, 88% yield, mp 143.3–147.7 °C, 1H NMR (400 MHz, CDCl3) δ: 7.73–7.67 (m, 2H), 7.25 (dd, J = 8.3, 1.7 Hz, 1H), 7.21–7.15 (m, 2H), 6.93 (d, J = 8.0 Hz, 1H), 6.74 (d, J = 8.4 Hz, 2H), 6.67 (t, J = 1.9 Hz, 1H), 5.95 (d, J = 8.3 Hz, 2H), 2.19 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 149.27, 145.59 (q, C-F, 2JC-F = 36.4 Hz), 142.95, 139.66, 137.93, 135.36, 133.75, 129.95, 129.70, 129.30, 126.69, 125.24, 124.32, 122.46, 122.01, 121.19, 120.86, 119.84 (q, C-F, 1JC-F = 279.8 Hz), 117.59, 20.31; 19F NMR (376 MHz, CDCl3) δ: −68.88; HRMS (ESI) calcd for C22H15Cl2F3N3(M + H)+: 448.0590, found 448.0593.
(Z)-2,2,2-trifluoro-1-(7-fluoro-2-(2-fluorophenyl)-2H-indazol-3-yl)-N-(p-tolyl)ethan-1-imine (3w): brown solid, 58.9 mg, 71% yield, mp 100.4–103.2 °C, 1H NMR (400 MHz, CDCl3) δ: 7.51 (d, J = 7.0 Hz, 1H), 7.26 (dd, J = 13.3, 7.6 Hz, 1H), 7.19–7.11 (m, 1H), 7.07–6.96 (m, 2H), 6.89 (t, J = 7.8 Hz, 1H), 6.74 (dd, J = 14.5, 7.0 Hz, 3H), 6.07 (dd, J = 8.4, 1.9 Hz, 2H), 2.15 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 156.69, 154.32 (d, J = 29.3 Hz), 151.88, 146.07 (q, C-F, 2JC-F = 36.4 Hz), 143.30, 140.68 (d, J = 17.2 Hz), 137.43, 131.10 (d, J = 8.1 Hz), 129.69, 127.79, 127.22 (d, J = 11.1 Hz), 126.41, 126.05, 124.96 (dd, J = 18.2 Hz), 120.81, 119.60 (q, C-F, 2JC-F = 279.8 Hz), 116.62 (d, J = 20.2 Hz), 115.76, 110.48 (d, J = 16.2 Hz), 21.08; 19F NMR (376 MHz, CDCl3) δ: −68.04, −123.04, −127.09; HRMS (ESI) calcd for C22H14F5N3Na (M + Na)+: 438.1001, found 438.1005.
(Z)-2,2,2-trifluoro-1-(7-methyl-2-(o-tolyl)-2H-indazol-3-yl)-N-(p-tolyl)ethan-1-imine (3x): brown solid, 67.6 mg, 83% yield, mp 116.6–118.0 °C, 1H NMR (400 MHz, CDCl3) δ: 7.54 (d, J = 9.2 Hz, 1H), 7.24–7.15 (m, 1H), 7.15–7.03 (m, 4H), 6.77 (d, J = 8.1 Hz, 3H), 6.17 (d, J = 8.2 Hz, 2H), 2.56 (s, 3H), 2.15 (s, 3H), 1.53 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 148.97, 147.52 (q, C-F, 2JC-F = 36.4 Hz), 143.90, 138.25, 137.04, 135.56, 131.67, 131.07, 129.69, 129.56, 128.95, 126.30, 126.24, 126.15, 124.86, 123.72, 121.20, 120.79, 118.86 (q, C-F, 1JC-F = 279.8 Hz), 117.08, 21.05, 17.35, 17.16; 19F NMR (376 MHz, CDCl3) δ: −68.61; HRMS (ESI) calcd for C24H21F3N3 (M + H)+: 408.1683, found 408.1684.

4. Conclusions

In conclusion, we successfully developed a novel and efficient Rh(III)-catalyzed C-H [4+1] annulation of azobenzenes with CF3-imidoyl sulfoxonium ylides via C-H bond activation, synthesizing various CF3-containing indazoles. This transformation was characterized by easily available starting materials, good tolerance of functional groups and excellent regioselectivity. Moreover, in vitro cytotoxicities of selected products were investigated against three kinds of human cancer cells (A549, Hela and HepG2), and several products exhibited excellent antitumor activities.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/molecules30010183/s1: detailed experimental procedures, characterization data of all compounds, cytotoxic activity evaluation, NMR spectra and HRMS spectra for all compounds.

Author Contributions

Conceptualization, Y.S. and C.L.; investigation, Y.S., C.L. and G.W.; in vitro study, G.Y. and H.W.; data curation, Y.S., C.L. and X.C.; writing—original draft preparation, X.C.; writing—review and editing, R.Z.; supervision, R.Z. All authors have read and agreed to the published version of the manuscript.

Funding

This project was supported by the Hainan Provincial Natural Science Foundation of China (222RC683) and the National Natural Science Foundation of China (21901054).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

Conflicts of Interest

The authors declare no conflicts of interest.

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Molecules 30 00183 g001
Figure 1. Selected bioactive molecules containing indazole motifs.
Figure 1. Selected bioactive molecules containing indazole motifs.
Molecules 30 00183 g001
Molecules 30 00183 sch001
Scheme 1. Transition metal-catalyzed C-H functionalization with TFISYs.
Scheme 1. Transition metal-catalyzed C-H functionalization with TFISYs.
Molecules 30 00183 sch001
Molecules 30 00183 sch002
Scheme 2. Preliminary mechanism studies.
Scheme 2. Preliminary mechanism studies.
Molecules 30 00183 sch002
Molecules 30 00183 sch003
Scheme 3. Proposed reaction mechanism.
Scheme 3. Proposed reaction mechanism.
Molecules 30 00183 sch003
Table 1. Optimization of reaction conditions [a].
Table 1. Optimization of reaction conditions [a].
Molecules 30 00183 i001
EntryCatalystAdditiveOxidantSolventYield [b]
1[Cp*RhCl2]2HOAcAgOAcDCE27
2[Cp*RhCl2]2HOAcAgOAcMeCN21
3[Cp*RhCl2]2HOAcAgOAcTFE45
4[Cp*RhCl2]2HOAcAgOAcHFIP50
5[Cp*RhCl2]2HOAcAgOAcDMF0
6[Cp*RhCl2]2HOAcAgOAcTHF0
7[Cp*RhCl2]2HOAcAgOAcDioxane0
8Cp*Co(CO)I2HOAcAgOAcHFIP0
9Pd(OAc)2HOAcAgOAcHFIP0
10[Cp*IrCl2]2HOAcAgOAcHFIP0
11[Ru(p-cymene)Cl2]2HOAcAgOAcHFIP12
12noneHOAcAgOAcHFIP0
13[Cp*RhCl2]2noneAgOAcHFIP42
14[Cp*RhCl2]2NaOAcAgOAcHFIP36
15[Cp*RhCl2]2HOAcAg2CO3HFIP54
16[Cp*RhCl2]2HOAcCu(OAc)2·H2OHFIP58
17[Cp*RhCl2]2HOAcK2S2O8HFIP0
18[Cp*RhCl2]2HOAcPhI(OAc)2HFIP0
19[Cp*RhCl2]2HOAcO2HFIP0
20[Cp*RhCl2]2HOAcCu(OAc)2·H2OHFIP43 [c]
21[Cp*RhCl2]2HOAcCu(OAc)2·H2OHFIP65 [d]
22[Cp*RhCl2]2HOAcCu(OAc)2·H2OHFIP57 [e]
23[Cp*RhCl2]2HOAcCu(OAc)2·H2OHFIP76 [f]
24[Cp*RhCl2]2HOAcCu(OAc)2·H2OHFIP71 [g]
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), catalyst (5 mol%), oxidant (2 equiv), additive (2 equiv), solvent (2 mL), air, 80 °C, 24 h; [b] isolated yield; [c] at 60 °C; [d] at 100 °C; [e] 1 equiv of oxidant; [f] 3 equiv of oxidant; [g] 2 mol% [Cp*RhCl2]2.
Table 2. Substrate scope [a,b].
Table 2. Substrate scope [a,b].
Molecules 30 00183 i002
[a] Reaction conditions: 1 (0.2 mmol), 2 (0.3 mmol), [Cp*RhCl2]2 (5 mol%), HOAc (2 equiv), Cu(OAc)2·H2O (3 equiv), HFIP (2 mL), air, 100 °C, 24 h; [b] isolated yield.
Table 3. Evaluation of antitumor activities of selected compounds.
Table 3. Evaluation of antitumor activities of selected compounds.
CompoundIC50 (μM)
A549HelaHepG2
3a12.826.851.2
3b29.457.337.3
3g25.410.22.1
3i34.042.681.2
3l12.379.811.6
3m20.387.65.7
3o19.940.353.0
3p39.4107.0100.2
3s41.242.689.5
3t63.830.04.3
3v51.2100.525.7
3y55.7164.022.4
Gefitinib12.812.82.3
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MDPI and ACS Style

Shang, Y.; Li, C.; Wang, G.; Yao, G.; Wu, H.; Chen, X.; Zhai, R. Synthesis of CF3-Indazoles via Rh(III)-Catalyzed C-H [4+1] Annulation of Azobenzenes with CF3-Imidoyl Sulfoxonium Ylides. Molecules 2025, 30, 183. https://doi.org/10.3390/molecules30010183

AMA Style

Shang Y, Li C, Wang G, Yao G, Wu H, Chen X, Zhai R. Synthesis of CF3-Indazoles via Rh(III)-Catalyzed C-H [4+1] Annulation of Azobenzenes with CF3-Imidoyl Sulfoxonium Ylides. Molecules. 2025; 30(1):183. https://doi.org/10.3390/molecules30010183

Chicago/Turabian Style

Shang, Yilong, Chen Li, Guiqiu Wang, Guiwei Yao, Hongliang Wu, Xun Chen, and Ruirui Zhai. 2025. "Synthesis of CF3-Indazoles via Rh(III)-Catalyzed C-H [4+1] Annulation of Azobenzenes with CF3-Imidoyl Sulfoxonium Ylides" Molecules 30, no. 1: 183. https://doi.org/10.3390/molecules30010183

APA Style

Shang, Y., Li, C., Wang, G., Yao, G., Wu, H., Chen, X., & Zhai, R. (2025). Synthesis of CF3-Indazoles via Rh(III)-Catalyzed C-H [4+1] Annulation of Azobenzenes with CF3-Imidoyl Sulfoxonium Ylides. Molecules, 30(1), 183. https://doi.org/10.3390/molecules30010183

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