Photoinduced Radical Relay Way Toward α-CF ₃ Ketones with Low-Cost Trifluoromethylation Reagents

Abstract

Open AccessCCS ChemistryRESEARCH ARTICLE1 Jun 2021Photoinduced Radical Relay Way Toward α-CF3 Ketones with Low-Cost Trifluoromethylation Reagents Huamin Wang, Wenyan Shi, Yongli Li, Mingming Yu, Yuan Gao and Aiwen Lei Huamin Wang , Wenyan Shi , Yongli Li , Mingming Yu , Yuan Gao and Aiwen Lei *Corresponding author: E-mail Address: [email protected] https://doi.org/10.31635/ccschem.020.202000386 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesTrack Citations ShareFacebookTwitterLinked InEmail The utilization of economic and practical trifluoromethyl reagents to introduce trifluoromethyl (CF3) groups into organic molecules is an important research focus due to their role as vital structural motifs in the pharmaceutical and agricultural industries. Herein, we disclose a cost-efficient and practical approach of photoinduction of a radical relay process for the synthesis of α-CF3 ketones. We showed that trifluoromethylation reagents such as TES-OTf, Tf2O, TMS-OTf, TBS-OTf, H-OTf, and others, could be used successfully as inexpensive CF3 precursors under metal-free and redox-neutral conditions. The potential application of this protocol was highlighted further by late-state modification of drug segments and gram-scale synthesis. Our mechanistic studies revealed that this transformation might involve a radical process, and acetic acid (CH3COOH) not only promoted the formation of enol triflates, but also accelerated the in situ conversion from enol triflates to α-CF3 ketones. Download figure Download PowerPoint Introduction The incorporation of trifluoromethyl (CF3) group into an organic molecule is a momentous issue.1–11 This is because the CF3 moiety possesses unique physical and chemical advantages, which has been used widely in both pharmaceutical and synthetic research.12,13 Hence, the methods for the introduction of CF3 into compounds containing pharmacological relevance have attracted much attention. Over the past decades, the strategies for the synthesis of α-CF3 ketones have relied on various radical,14–16 electronic,17,18 and nucleophilic trifluoromethyl reagents.19 Despite the significant progress made in this field, many of the reported examples generally required large excess of the expensive trifluoromethylation reagents, resulting in limited application of these methods in industrial chemistry. To date, direct utilization of low-cost trifluoromethylation reagents such as TES-OTf, TMS-OTf, H-OTf, and Tf2O for the synthesis of α-CF3 ketones, has been scarcely developed. To avert employing expensive trifluoromethylation reagents, Su et al.20 developed a novel method for the formation of α-CF3 ketones by using enol triflates as starting materials via persulphate-mediated oxidative radical desulfur-fragmentation process, in which extra steps for the preparation and isolation of enol triflates were necessary. Thus, a straightforward and cost-efficient approach to accessing α-CF3 ketones was attractive yet challenging. Recently, photoredox catalysis has emerged as a powerful tool for the synthesis of triflate derivatives,21–31 and a significant breakthrough in photocatalyzed radical trifluoromethylation reactions was made.32–38 In this regard, alkenes and carbonyl compounds were always employed as radical acceptors. Additionally, CF3I, CF3SO2Cl, CF3SO2Na, and others have been utilized successfully as CF3 radical sources (Figure 1), which still has room for further improvement in the utility of low-cost trifluoromethylation reagents. In 2018, Ouyang et al.39 developed a cost-efficient route to trifluoromethylation of (hetero)arenes using the low-cost Tf2O as a source of trifluoromethyl radical in the presence of pyridine. Nonetheless, accessing α-CF3 ketones by using inexpensive trifluoromethylation reagents such as H-OTf, TES-OTf, TMS-OTf, or Tf2O as starting materials in a redox-neutral manner without external redox reagents or photocatalysts, although highly significant, remains unexplored. Figure 1 | Previous methods for the synthesis of α-CF3 ketones scaffolds and the research scheme of this work. Download figure Download PowerPoint In view of the electrophilic character of trifluoromethanesulfonic acid, silicon-based trifluoromethane sulfonate, and trifluoromethanesulfonic anhydride (H-OTf, TES-OTf, TMS-OTf, Tf2O, etc.),40,41 intermediate A could be formed quickly using alkynes as reaction partners through the addition reaction with these trifluoromethylation reagents (Figure 2). Then an intermediate A might undergo homolytic cleavage under light irradiation to form CF3 radical, owing to the weakness of the S–O bond of Tf2O. In principle, an addition of CF3 radical to A afforded the carbon center radical intermediate B, which generated the α-CF3 ketones along with the production of radical C. Subsequently, radical C decomposed to CF3 radical with the evolution of SO2. This newly formed CF3 radical, added to the radical acceptor A reinitiated the radical chain process. Hence, we hypothesized that a photoinduced radical relay method could enable rapid access to the α-CF3 ketone scaffolds using low-cost trifluoromethylation reagents. Figure 2 | The radical relay approach enables access to α-CF3 ketones scaffolds using cheap raw materials as trifluoromethylation reagents. Download figure Download PowerPoint Herein, we describe an unprecedented, cost-efficient, and operationally simple method for the synthesis of α-CF3 ketones. In this transformation, TES-OTf, Tf2O, TMS-OTf, TBS-OTf, H-OTf, and others were used as low-cost CF3 precursors under metal-free and redox-neutral conditions. Mechanistically, CH3COOH facilitated the formation of enol triflates and also enhanced their transformation in target molecules. Experimental Methods General procedure for the synthesis of α-CF3 ketones using Tf2O as trifluoromethylation reagent A mixture of alkynes (0.3 mmol), trifluoromethanesulfonic anhydride ( 2a, 0.3 mmol), and CH3COOH (0.3 equiv) in degassed dry CHCl3 (2.0 mL) was stirred under a nitrogen atmosphere and irradiated for 24 h using a commercially available blue light-emitting diode (LED). Then the reaction system was concentrated under reduced pressure, followed by the residue separation on a silica gel column with petroleum ether (30–60 °C) and elution with ethyl acetate to afford the desired product, α-CF3 ketone. General procedure for the synthesis of α-CF3 ketones using TES-OTf as trifluoromethylation reagent A mixture of alkynes (0.3 mmol), triethylsilyl trifluoromethanesulfonate ( 5a, 0.3 mmol), and CH3COOH (0.2 equiv), in degassed dry CHCl3 (2.0 mL), was stirred under a nitrogen atmosphere and irradiated for 48 h using a commercially available blue LED. Then the reaction system was concentrated under reduced pressure. Subsequently, the residue was separated on a silica gel column with petroleum ether (30–60°C) and eluted with ethyl acetate to afford the desired product, α-CF3 ketone. More experimental details and characterization are available in the Supporting Information. Results and Discussion Optimization of the reaction conditions Initially, trifluoromethanesulfonic anhydride ( 2a), a low-cost and commercially available CF3 reagent, was used as a coupling partner to react with phenylacetylene ( 1a). After various screening of the reaction parameters, we found that the treatment of 1a and 2a with CH3COOH as a mediator in chloroform (CHCl3) under blue LEDs irradiation provided 1 in 72% yield ( Supporting Information Table S1, entry 1). In this transformation, CH3COOH not only played an essential role in supporting the formation of enol triflates, but also accelerated the in situ conversion from enol triflates to α-CF3 ketones (Figures 3c and 3d and Supporting Information Table S1, entries 1–4). Besides, increasing the amount of CH3COOH did not improve the yield of 1 ( Supporting Information Table S1, entry 2). Subsequently, changing the amount of CHCl3 rendered the reaction unfavorable ( Supporting Information Table S1, entries 5 and 6). Further experiments suggested that the type of solvent and the amount used in the reaction played an essential role in this transformation ( Supporting Information Table S1, entries 7–9). In comparison with green LEDs and white LEDs, blue LEDs provided an optimal light source for this transformation ( Supporting Information Table S1, entries 10 and 11). Decreasing the amount of 2a led to a decrease in yield ( Supporting Information Table S1, entry 12). Notably, 1 was observable in the absence of irradiation of visible light ( Supporting Information Table S1, entry 13). Figure 3 | (a–e) Mechanistic studies in reference to the synthesis of α-CF3 ketones from trifluoromethylation reagents. Download figure Download PowerPoint Substrate scope With the optimal conditions in hand, the substrate scope was evaluated with trifluoromethanesulfonic anhydride (Tf2O) as the reaction partner (Figure 4). Halogen groups, such as F, Cl, and Br, afforded the desired products with good efficiency, and enabled further transformation to other useful molecules via activation of C–X (X = F, Cl, and Br) bonds ( 2–4). It is worth noting that CF3O and cyan groups were amenable to this protocol, affording 6 and 7 in 58% and 67% yields, respectively. Not only aryl ester groups ( 8 and 9), but also long-chain alkyl ester group, ( 10) were well tolerated. With regard to meta-substituted phenylacetylenes, methyl and F group were well tolerated in this transformation ( 11 and 12). Ortho-substituted aryl alkynes, having steric hindrance, reacted smoothly with Tf2O to afford the corresponding product ( 13). When diethynylbenzene was used as the reaction partner, 14 was obtained in a 51% yield. A heterocyclic substrate was also evaluated. Remarkably, 3-ethynylthiophene was found to be suitable for this transformation ( 15). In addition, various cycloalkyl compounds were compatible with this photoinduced protocol, affording the corresponding products in moderate to good yields ( 17– 20). Furthermore, sulfonyl groups were also well tolerated ( 22 and 23). Gratifyingly, oxygen heterocycles were found to be suitable for this transformation ( 24– 26), which include tetrahydropyran ( 24), tetrahydrofuran ( 25), and 1,3-dioxolane ( 26). Alkyl chloride ( 21) and aryl iodide ( 27) were also good reaction partners. More importantly, this protocol was compatible with compounds that contained drug molecule fragments. Compound 28 was successfully generated when using cyclobutanone derivative as a reaction partner. Ibuprofen and flurbiprofen derivatives that always served as efficient drugs for relieving pain were compatible with this protocol ( 29 and 30). Probenecid alkyne reacted smoothly with Tf2O to afford 31 with good efficiency. These results highlighted good functional group tolerance of this protocol. On the contrary, alkyl alkynes, such as 1-heptyne and 4-phenyl-1-butyne, were not suitable for this transformation. Figure 4 | Substrates scope for the synthesis of α-CF3 ketones using Tf2O as trifluoromethylation reagent. Unless otherwise noted the standard conditions were as follows: alkynes (0.3 mmol), 2a (0.3 mmol), CH3COOH (0.3 equiv), CHCl3 (2.0 mL), N2, 3 W blue LEDs, 24 h. b36 h, isolated yield. c30 h, isolated yield. The yields in parentheses were determined by 19F NMR using benzotrifluoride as a standard; the values of the isolated yields are those presented without parentheses. Download figure Download PowerPoint Mechanistic studies We sought to understand the mechanism of this protocol by performing radical trapping experiments (Figure 3). We found no apparent conversion when the radical scavengers, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), and 2,4-di-tert-butyl-4-methylphenol (BHT) were added to this reaction system suggesting that a radical pathway was involved in this transformation (Figure 3a). We confirmed the radical process by using allyl ether ( 3a), a coupling partner, and observed that the reaction was strongly inhibited, with the detection of 4a by gas chromatography–mass spectrometry (GC–MS) (Figure 3b). Subsequently, we conducted intermediate experiments in which 7′ was transformed successfully to 7 under the standard experimental conditions, which revealed that 7′ might be an intermediate in this transformation (Figure 3c). On the contrary, only a trace amount of 7 was detected in the absence of CH3COOH, suggesting that CH3COOH not only promoted the generation of 7′ but also accelerates the transformation from 7′ to 7 (Figure 3d). Further, 19F NMR experiments were carried out to monitor the reaction with 4-F-phenylacetylene as a coupling partner. As shown in Figure 3e, compound 2′ was produced during this transformation. The consumption of 2 ′ resulted in the formation of the desired product 2, further confirming that 2′ was the intermediate in this protocol. Extension to the use of other low-cost trifluoromethylation reagents and gram-scale synthesis Based on the understanding of the mechanism, triethylsilyl trifluoromethanesulfonate ( 5a) was used as the CF3 source, as shown in Figure 5. Halogen groups, such as Cl ( 3) and Br ( 4), were well tolerated, delivering the corresponding products in 58% and 61% yields, respectively. Moreover, phenyl ( 32), amyl ( 5), and cyan ( 7) groups were found to be suitable in this reaction. To our delight, various functional groups, such as alkyl fluorine ( 34), chloride ( 21), sulfonyl ( 22 and 23), and oxygen heterocycles ( 24 and 25), were compatible as well. Significantly, a series of pharmaceutical molecule structures were amenable to this protocol. Ibuprofen ( 29), probenecid ( 31), loxoprofen ( 35), and ciprofibrate ( 36) derivatives were compatible with this visible-light-induced trifluoromethylation. The late-stage modification of such drugs demonstrated the prospective utility of this protocol. Additionally, H-OTf, TMS-OTf, TIPS-OTf, and TBS-OTf were used as trifluoromethylation reagents to react with phenylacetylene, as shown in Figure 6a. Favorably, a desired product 1 could be generated facilely under the redox-neutral condition, suggesting the versatility of this protocol. Most importantly, this method could be carried out on a larger scale, as shown in Figure 6b. Good yields were obtained when we used Tf2O, TMS-OTf, and TES-OTf as coupling partners to react with phenylacetylene ( 1a), demonstrating the potential application of this protocol in pharmaceutical and synthetic industries (see Supporting Information). Figure 5 | Substrates scope using TES-OTf as trifluoromethylation reagent. Unless otherwise noted the standard conditions were as follows: alkynes (0.3 mmol), 5a (0.3 mmol), CH3COOH (0.2 equiv), CHCl3 (2.0 mL), N2, 3 W blue LEDs, 48 h. b60 h, isolated yield. c36 h, isolated yield. The yields in parentheses were determined by 19F NMR using benzotrifluoride as standard; the values of the isolated yields are those presented without parentheses. Download figure Download PowerPoint Conclusion We have disclosed an unprecedented photoinduced radical relay method for the synthesis of α-CF3 ketones using alkynes and low-cost trifluoromethylation reagents as the starting materials, such as Tf2O, TES-OTf, TMS-OTf, TBS-OTf, H-OTf, and so forth. A series of α-CF3 ketones could be facilely obtained under metal-free and redox-neutral conditions. Notably, the late-state modification of drug segments and the gram-scale synthesis capabilities of the reaction demonstrated further, the utility of this protocol. Our mechanistic studies revealed the reliability of the process utilizing this procedure; also, CH3COOH not only promoted the formation of enol triflates but also accelerated the transformation of enol triflates to target molecules. Ongoing investigations, including further mechanism and scopes of this novel reaction paths are currently underway. Figure 6 | (a) Various trifluoromethylated derivatives (R-OTf) used as trifluoromethylation reagents. Different R-OTf using as trifluoromethylation reagents. aPhenylacetylene (1a, 0.3 mmol), H-OTf (0.3 mmol), CHCl3 (4.0 mL), N2, 3 W blue LEDs, 48 h. bPhenylacetylene (1a, 0.3 mmol), R-OTf (0.3 mmol), CH3COOH (0.2 equiv), CHCl3 (2.0 mL), N2, 3 W blue LEDs, 48 h. (b) Gram-scale reactions. Download figure Download PowerPoint Footnote a For a cost comparison of various trifluoromethylation reagents from Fluorochem, see the Supporting Information. Supporting Information Supporting Information is available. Conflict of Interest The authors declare no competing interest. Acknowledgments This work was supported by the National Natural Science Foundation of China (nos. 21390402 and 21520102003) and the Hubei Province Natural Science Foundation of China (no. 2017CFA010). The Program of Introducing Talents of Discipline to Universities of China (111 Program) is also appreciated. References 1. Cho E. J.; Senecal T. D.; Kinzel T.; Zhang Y.; Watson D. A.; Buchwald S. L.The Palladium-Catalyzed Trifluoromethylation of Aryl Chlorides.Science2010, 328, 1679–1681. Google Scholar 2. Mukherjee S.; Maji B.; Tlahuext-Aca A.; Glorius F.Visible-Light-Promoted Activation of Unactivated C(sp3)–H Bonds and Their Selective Trifluoromethylthiolation.J. Am. Chem. Soc.2016, 138, 16200–16203. Google Scholar 3. Neumann C. N.; Hooker J. M.; Ritter T.Concerted Nucleophilic Aromatic Substitution with 19F– and 18F–.Nature2016, 534, 369–373. Google Scholar 4. Wang F.; Wang D. H.; Zhou Y.; Liang L.; Lu R. H.; Chen P. H.; Lin Z. Y.; Liu G. S.Divergent Synthesis of CF3-Substituted Allenyl Nitriles by Ligand-Controlled Radical 1,2- and 1,4-Addition to 1,3-Enynes.Angew. Chem. Int. Ed.2018, 57, 7140–7145. Google Scholar 5. Xie Q.; Li L.; Zhu Z.; Zhang R.; Ni C.; Hu J.From C1 to C2: TMSCF3 as a Precursor for Pentafluoroethylation.Angew. Chem. Int. Ed.2018, 57, 13211–13215. Google Scholar 6. Zhu S. Q.; Liu Y. L.; Li H.; Xu X. H.; Qing F. L.Direct and Regioselective C–H Oxidative Difluoromethylation of Heteroarenes.J. Am. Chem. Soc.2018, 140, 11613–11617. Google Scholar 7. Li X.-T.; Gu Q.-S.; Dong X.-Y.; Meng X.; Liu X.-Y.A Copper Catalyst with a Cinchona-Alkaloid-Based Sulfonamide Ligand for Asymmetric Radical Oxytrifluoromethylation of Alkenyl Oximes.Angew. Chem. Int. Ed.2018, 57, 7668–7672. Google Scholar 8. Lin J. S.; Wang F.-L.; Dong X.-Y.; He W.-W.; Yuan Y.; Chen S.; Liu X.-Y.Catalytic Asymmetric Radical Aminoperfluoroalkylation and Aminodifluoromethylation of Alkenes to Versatile Enantioenriched-Fluoroalkyl Amines.Nat. Commun.2017, 8, 14841–14852. Google Scholar 9. Lin J.-S.; Dong X.-Y.; Li T.-T.; Jiang N.-C.; Tan B.; Liu X.-Y.A Dual-Catalytic Strategy to Direct Asymmetric Radical Aminotrifluoromethylation of Alkenes.J. Am. Chem. Soc.2016, 138, 9357–9360. Google Scholar 10. Fu L.; Zhou S.; Wan X. L.; Chen P. H.; Liu G. S.Enantioselective Trifluoromethylalkynylation of Alkenes via Copper-Catalyzed Radical Relay.J. Am. Chem. Soc.2018, 140, 10965–10969. Google Scholar 11. Wu L. Q.; Wang F.; Wan X. L.; Wang D. H.; Chen P. H.; Liu G. S.Asymmetric Cu-Catalyzed Intermolecular Trifluoromethylarylation of Styrenes: Enantioselective Arylation of Benzylic Radicals.J. Am. Chem. Soc.2017, 139, 2904–2907. Google Scholar 12. Cametti M.; Crousse B.; Metrangolo P.; Milani R.; Resnati G.The Fluorous Effect in Biomolecular Applications.Chem. Soc. Rev.2012, 41, 31–42. Google Scholar 13. Muller K.; Faeh C.; Diederich F.Fluorine in Pharmaceuticals: Looking Beyond Intuition.Science2007, 317, 1881–1886. Google Scholar 14. Allen A. E.; Macmillan D. W.The Productive Merger of Iodonium Salts and Organocatalysis: A Non-Photolytic Approach to the Enantioselective Alpha-Trifluoromethylation of Aldehydes.J. Am. Chem. Soc.2010, 132, 4986–4987. Google Scholar 15. Deb A.; Manna S.; Modak A.; Patra T.; Maity S.; Maiti D.Oxidative Trifluoromethylation of Unactivated Olefins: An Efficient and Practical Synthesis of Alpha-Trifluoromethyl-Substituted Ketones.Angew. Chem. Int. Ed.2013, 52, 9747–9750. Google Scholar 16. Cantillo D.; Frutos O. D.; Rincoón J. A.; Mateos C.; Kappe C. O.Continuous Flow α-Trifluoromethylation of Ketones by Metal-Free Visible Light Photoredox Catalysis.Org. Lett.2014, 16, 896–899. Google Scholar 17. Umemoto T.; Ishihara S.Power-Variable Electrophilic Trifluoromethylating Agents. S-, Se-, and Te-(trifluoromethyl)dibenzothio-, -seleno-, and -tellurophenium Salt System.J. Am. Chem. Soc.1993, 115, 2156–2164. Google Scholar 18. He Z. B.; Zhang R.; Hu M. Y.; Li L. C.; Ni C. F.; Hu J. B.Copper-Mediated Trifluoromethylation of Propiolic Acids: Facile Synthesis of α-Trifluoromethyl Ketones.Chem. Sci.2013, 4, 3478–3483. Google Scholar 19. Novak P.; Lishchynskyi A.; Grushin V. V.Trifluoromethylation of Alpha-Haloketones.J. Am. Chem. Soc.2012, 134, 16167–16170. Google Scholar 20. Su X.; Huang H.; Yuan Y.; Li Y.Radical Desulfur-Fragmentation and Reconstruction of Enol Triflates: Facile Access to Alpha-Trifluoromethyl Ketones.Angew. Chem. Int. Ed.2017, 56, 1338–1341. Google Scholar 21. Chen B.; Wu L. Z.; Tung C. H.Photocatalytic Activation of Less Reactive Bonds and Their Functionalization via Hydrogen-Evolution Cross-Couplings.Acc. Chem. Res.2018, 51, 2512–2523. Google Scholar 22. Chen J.-R.; Hu X.-Q.; Lu L.-Q.; Xiao W.-J.Visible Light Photoredox-Controlled Reactions of N-Radicals and Radical Ions.Chem. Soc. Rev.2016, 45, 2044–2056. Google Scholar 23. Chen J. R.; Hu X. Q.; Lu L. Q.; Xiao W. J.Exploration of Visible-Light Photocatalysis in Heterocycle Synthesis and Functionalization: Reaction Design and Beyond.Acc. Chem. Res.2016, 49, 1911–1923. Google Scholar 24. Fabry D. C.; Rueping M.Merging Visible Light Photoredox Catalysis with Metal Catalyzed C–H Activations: On the Role of Oxygen and Superoxide Ions as Oxidants.Acc. Chem. Res.2016, 49, 1969–1979. Google Scholar 25. Nicewicz D. A.; Nguyen T. M.Recent Applications of Organic Dyes as Photoredox Catalysts in Organic Synthesis.ACS. Catal.2013, 4, 355–360. Google Scholar 26. Prier C. K.; Rankic D. A.; MacMillan D. W.Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis.Chem. Rev.2013, 113, 5322–5363. Google Scholar 27. Strieth-Kalthoff F.; James M. J.; Teders M.; Pitzer L.; Glorius F.Energy Transfer Catalysis Mediated by Visible Light: Principles, Applications, Directions.Chem. Soc. Rev.2018, 47, 7190–7202. Google Scholar 28. Wang H.; Gao X.; Lv Z.; Abdelilah T.; Lei in Oxidative with via Google Scholar Yu J.; Wu Z.; Zhu Strategy for Selective Radical Difluoromethylation of Chem. Int. Ed.2018, 57, Google Scholar Hu X. Q.; X. T.; Chen J. R.; Q.; Y.; Xiao Reaction of by Oxidative Transfer and Google Scholar Liu Li L.; Li C. a and Alkyl with Light in Google Scholar D. A.; MacMillan D. of and by of Photoredox Google Scholar Li L.; X.; Liu Wang Y.; Z.; Li C. and Aromatic Trifluoromethylation Am. Chem. Soc.2016, 138, Google Scholar Lin J.; Li Z.; J.; Huang S. J.; Su W. P.; Li Y. Trifluoromethylation of (hetero)arenes with Commun.2017, 8, Google Scholar Xu Wang Liu T.; Xie J.; Zhu of Benzylic C–H Google Scholar B.; Yu D.; Xu Qing Photoredox of for C–H Trifluoromethylation of 8, Google Scholar Liu S.; J.; Yu J.; Light Access to Ketones from Enol Google Scholar Q.; Chen J.; Hu X.; X.; Lu B.; Xiao Radical Synthesis of and Google Scholar Ouyang Y.; Xu X. H.; Qing F. as a Low-Cost and Versatile Trifluoromethylation Chem. Int. Ed.2018, 57, Google Scholar X.; X.; J. L.; Zhu Y. C.; X. J.; S.; An for Chem. Int. Google Scholar Li X. Lin F. G. R.; Huang M.; J. L.; Li X. Y.; Wang X. Y.; X. Y.; and of Chem. Int. Ed.2017, 56, Google Scholar Previous Information trifluoromethylation work was supported by the National Natural Science Foundation of China (nos. 21390402 and 21520102003) and the Hubei Province Natural Science Foundation of China (no. 2017CFA010). The Program of Introducing Talents of Discipline to Universities of China (111 Program) is also appreciated.

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