Iron- or Copper-Catalyzed Trifluoromethylation of Acrylamide

Dec 9, 2015 - State Key Laboratory of Organometallic Chemistry, Shanghai Institute ... to good yields, respectively, with excellent functional group t...
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Iron or Copper Catalyzed Trifluoromethylation of AcrylamideTethered Alkylidenecyclopropanes: Facile Synthesis of CF3-Containing Polycyclic Benzazepine Derivatives Liu-Zhu Yu, Qin Xu, Xiang-Ying Tang, and Min Shi ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.5b02400 • Publication Date (Web): 09 Dec 2015 Downloaded from http://pubs.acs.org on December 14, 2015

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Iron or Copper Catalyzed Trifluoromethylation of Acrylamide-Tethered Alkylidenecyclopropanes: Facile Synthesis of CF3-Containing Polycyclic Benzazepine Derivatives Liu-Zhu Yu,a Qin Xu,a Xiang-Yiang Tang,b and Min Shi*a,b a

Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry & Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China

ABSTRACT: A novel iron or copper catalyzed trifluoromethylation of acrylamide-tethered alkylidenecyclopropanes with Togni reagent II to construct CF3-containing tetracyclic benzazepine derivatives under mild and convenient conditions has been disclosed. The chemoselective addition of in situ generated trifluoromethyl radical onto the activated alkenes triggers the reaction followed by a ring-opening process of alkylidenecyclopropanes, leading to the formation of two types of CF3-containing tetracyclic benzazepine derivatives in moderate to good yields, respectively with excellent functional group tolerance.

KEYWORDS: Iron or copper catalysis, alkylidenecyclopropanes, tetracyclic benzazepine derivatives, radical addition, activated alkenes, ring-opening difunctionalization of alkenes, especially activated alkenes to synthesize CF3-containing naturally occurring and biologically active carbocyclic or heterocyclic compounds with simultaneous formation of C(sp3)-CF3 and C-O, C-N or C-C bonds has been widely explored.5-7 In the realm of carbo-trifluoromethylation, representative examples are intramolecular aryltrifluoromethylation of alkenes. Since Liu’s group in 2012 first reported a palladium-catalyzed intramolecular oxidative aryltrifluoromethylation of activated alkenes to obtain CF3-substituted oxindoles with a palladium/ytterbium catalytic system,7a the groups of Sodeoka, Zhu and Nevado have independently developed the trifluoromethylation/cyclization cascade reactions of N-phenylacrylamide to yield oxindoles with Togni reagent II as the CF3 source.7e, 7f, 7i Thereafter, other inexpensive CF3 reagents such as sodium triflinate (the Langlois’ reagent) and trimethyl(trifluoromethyl)silane have also been applied to synthesize oxindoles (Scheme 1a).7j-7m Notably, Sodeoka’s group and Liang’s group have independently reported trifluoromethylated five- or

INTRODUCTION Trifluoromethyl groups play a privileged role in modern synthetic chemistry because of its effective improvements on physical and chemical properties of biologically active compounds such as membrane permeability, bioavailability and metabolic stability.1 According to the new drugs published by FDA (Food and Drug Administration), there exist five new approved drugs containing a trifluoromethyl group. For example, enzalutamide and regorafenib have a treatment for metastatic castration-resistant prostate cancer and metastatic colorectal cancer, respectively.2 As a consequence, the developments of versatile and efficacious methodologies to construct the C-CF3 bond have attracted significant attention in the area of organofluorine chemistry as well as homogeneous catalysis.3 Recently, transition-metal-mediated or -catalyzed trifluoromethylation reactions have been developed intensively to synthesize various CF3-containing compounds.4 In particular, the utilization of

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six-membered carbo- and heterocycles using unactivated alkenes and 1,6-enynes.7b, 7g Moreover, Nevado’s group also disclosed the first example of metal-free alkene trifluoromethylation to afford trifluoromethylated isoquinolinediones, oxindoles and spirobicycles (Scheme 1b).7d Meanwhile, we have also developed a tandem trifluoromethylation-annulation reaction to give trifluoromethylated 1,2-benzothiazinane derivatives in good yields.7h However, the fused ring systems are all restricted to five- and six-membered rings in most of these transformations, and the synthesis of functionalized seven-membered ring has never been reported before. Alkylidenecyclopropanes (ACPs), as highly strained but readily accessible molecules, are useful building block in organic synthesis. Thus far, our group and others have focused on the exploration of domino reactions using alkylidenecyclopropanes for rapid generation of molecular complexity for many years.8, 9 Encouraged by recent radical cascade reactions triggered by alkenes to construct useful functionalized carbocyclic or heterocyclic scaffolds,10 we envisaged that acrylamide-tethered alkylidenecyclopropane might undergo a domino ring-opening process to generate a tetracyclic benzazepine derivative. Herein we wish to report a novel iron or copper catalyzed trifluoromethylation of acrylamide-tethered alkylidenecyclopropane coupled with a CF3-containing benzazepine formation (Scheme 1c).

Figure 1. Selected examples of biological polycyclic benzazepines RESULTS AND DISCUSSION At the outset of our studies, we utilized N-(2-(cyclopropylidene(phenyl)methyl)phenyl)-N-methyl methacrylamide 1a as the model substrate to optimize the reaction conditions (Table 1). Initially, the reaction was carried out with Togni reagent II without catalyst in DCE (1,2-dichloroethane) at 80 oC for 12 h. To our delight, the corresponding CF3-containing polycyclic benzazepine derivative 2a was obtained in 48% NMR yield and its structure has been unambiguously identified by X-ray diffraction (Table 1, entry 1).13 Then we further optimized the reaction conditions by screening various catalysts including copper and iron salts. Several selected copper(I) salts could produce 2a in the yields ranging from 56% to 70% and Cu(MeCN)4PF6 was the best one, leading to the highest yield (70%) (Table 1, entries 2-5). Considering that trifluoromethylation reactions catalyzed by iron salts have been also reported by Buchwald’s group and others recently,14 several iron(II) salts were examined as catalysts as well. We found that FeCl2 was the useful catalyst, giving 2a with up to 72% yield than other iron(II) salts such as FeBr2 and Fe(OTf)2 (Table 1, entries 6-7 and entry 9). It should be noted that Fe(OAc)2 and Fe(acac)2 hampered the reaction efficiency and the reactions became sluggish (Table 1, entries 8 and 10). Other type of catalysts such as CoCl2 and RuCl2 were not as efficient as FeCl2 (Table 1, entries 11 and 12). The examination of solvent effects revealed that 1,4-dioxane and methanol had a better reaction outcomes as compared to DCE (Table 1, entries 13 and 17). While in other solvents such as DME (1,2-dimethoxyethane), THF, CHCl3 and CH2Cl2, the desired product 2a was obtained in only 35% to 55% yields (Table 1, entries 14, 16 and 18-19). Changing the solvent to HFIP (1,1,1,3,3,3-hexafluoropropan-2-ol), no reaction occurred (Table 1, entry 15). Gratifyingly, the NMR yield of 2a increased to 80% along with 75% isolated yield when a second portion of FeCl2 and Togni reagent II was added (Table 1, entry 20) (condition A).7h Finally, the temperature and the loading of catalyst were also examined and no better results could be realized (Table 1, entries 21-25).

(a) Aryltrifluoromethylation of activated alkenes for the synthesis of oxindoles (Early reports) R3 CF3 R2 Pd(II), Cu(I), Ru(II), nBu4NI R1 O R1 N 3 X = SO or none 2 N X R R2 O (b) Aryltrifluoromethylation of activated alkenes for the synthesis of isoquinolinediones (Early reports) R3 CF3 R2 O R1 Metal-free 1 N R 3 C R N 2 R O O O (c) Carbo-trifluoromethylation of activated alkenes for the synthesis of benzazepine derivatives (This work) CF3 O O R2 4 R N Fe(II) or Cu(I) R4 N R2

R1

R3

R1

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R3

Scheme 1. Intramolecular aryltrifluoromethylation The benzazepine scaffold containing compounds widely exist in many biologically active molecules such as benazepril, fenoldopam and varenicline.11 Moreover, as shown in Figure 1, the biological activities of some modified benzazepine-containing compounds have been also intensively studied, both in vitro and vivo.12 Encouraged by their significant bioactivities, we decided to further explore this new synthetic protocol to access CF3-containing benzazepine.

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Substrates 1b-1d bearing N-ethyl, benzyl and allyl groups, the reactions proceeded smoothly to furnish the desired products 2b-2d in 60%-76% yields. It has to be mentioned that tosylated substrate 1e failed to give the desired product 2e. Next, we examined the electronic effect of R1 at the para-position of the benzene ring: substrates with electron-withdrawing substituents provided the desired products 2f-2i in 52%-65% yields and substrates with electron-donating ones gave products 2j-2l with better yields up to 85% yield. To be mentioned, when R1 contained more than one benzylic hydrogen atom

Table 1. Optimization of reaction conditionsa

entry

catalyst

solvent

T yield (oC) (%)b 1 DCE 80 48c 2 CuI DCE 80 56 3 CuCl DCE 80 55 4 CuBr DCE 80 54 5 Cu(MeCN)4PF6 DCE 80 70 6 FeCl2 DCE 80 72 7 FeBr2 DCE 80 52 8 Fe(OAc)2 DCE 80 trace 9 Fe(OTf)2 DCE 80 58 10 Fe(acac)2 DCE 80 N Dd 11 CoCl2 DCE 80 37 12 RuCl2 DCE 80 ND 13 FeCl2 1,4-dioxane 80 75 14 FeCl2 DME 80 40 15 FeCl2 HFIP 80 trace 16 FeCl2 THF 80 35 17 FeCl2 MeOH 80 74 18 FeCl2 CHCl3 80 48 19 FeCl2 CH2Cl2 80 55 20e FeCl2 1,4-dioxane 80 80 (75)f 21e FeCl2 1,4-dioxane 60 65 22e FeCl2 1,4-dioxane 50 41 23e FeCl2 1,4-dioxane 40 58 24e FeCl2 1,4-dioxane 30 47 25g, e FeCl2 1,4-dioxane 80 63 a Reaction conditions: catalyst (0.015 mmol, 0.10 eq), Togni reagent II (0.225 mmol, 1.5 eq), 1a (0.15 mmol, 1.0 eq), solvent (1.5 mL), argon atmosphere for 12 h. b Determined by 19F NMR analysis of the reaction mixture using 1-fluoronaphthalene as an internal standard. c The reaction was carried out for 48 h. d No desired product was detected. e A second portion of FeCl2 (0.015 mmol, 0.10 eq), Togni reagent II (0.225 mmol, 1.5 eq) was added after 6 h. f Value in parentheses is the isolated yield. g 5 mol% catalyst was used in every portion.

Table 2. Substrate scope of iron or copper catalyzed cascade trifluoromethylation of 1

With the best reaction conditions in hand, we began to investigate the feasibility of the reaction scope and the results are shown in Table 2. To be noted, the optimized condition should be slightly modified with regard to the substituent groups in substrates 1 to a large extent, indicating that the electronic effect had a prominent impact on the reaction outcomes. The condition B (FeCl2 as a catalyst and MeOH as a solvent) and condition C (Cu(MeCN)4PF6 as a catalyst and MeCN as a solvent) were also adopted on the basis of different functional groups.

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(substrates 1j, 1k, 1n, and 1p) or were strongly electron-donating methoxyl group (substrates 1m, 1o, and 1q), the reactions were carried out with Cu(MeCN)4PF6 as a catalyst and MeCN as the solvent to improve the reaction efficiency and deliver the desired product cleanly. For the ortho-substituted substrates 1m and 1n, the reaction also proceeded efficiently to furnish the corresponding products 2m and 2n in good yields. Moreover, as for meta-substituted substrate 1o, only a single product 2o was obtained in 40% yield. However, the reaction system became very complex when meta-methyl-substituted substrate 1p was utilized for this reaction under above adopted conditions, probably because C-H bond is easily activated at the benzylic position in radical reaction.15 When R3 was substituted by OMe, Cl or NO2, the desired products 2q, 2r and 2s were isolated in 70% to 80% yields. Both phenyl rings substituted substrate 1t was also tolerated, affording 2t in 66% yield. In the case of phenol-linked substrate 1u, the similar seven-membered lactone containing polycyclic product 2u was formed, albeit in 34% yield. Substrates 1v and 1w, replacing methyl group with a phenyl group or a hydrogen atom, could also afford the corresponding products 2v and 2w in 65% and 56% yields, respectively. To further evaluate the generality of this novel cascade trifluoromethylation reaction, we prepared substrates containing cinnamamide or methylenecyclobutane moiety. Unfortunately, the reactions gave complex product mixtures without formation of the desired products (for details, see Scheme S1 in the Supporting Information). Interestingly, when R1 was substituted by a methoxy group at the para-position of the benzene ring, a spirocyclic product 4a was formed via a cyclization and dearomatization process.16 This trifluoromethylated spirocyclic compound contains both benzazepine and benzoquinone moieties. After screening the reaction conditions, we found the reaction proceeded more efficiently if using FeCl2 (15 mol%) as a catalyst in methanol at 50 oC. The exploration of substrate generality indicated that a diverse array of para-methoxy-substituted substrates 3a-3e delivered the corresponding trifluoromethylated spirocyclic benzazepine derivatives 4a-4e in moderated to good yields (Table 3). The electronic effect did not have significant impact on the reaction outcomes and the reactions completed within 1 h. To gain the mechanistic insights of this cascade trifluoromethylation reaction, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), a well-known radical scavenger, was used to react with 1a in the presence of catalytic amount of FeCl2 (20 mol%) in methanol (Scheme 2). The desired product 2a was not detected and the TEMPO-trapping compound 5 was obtained in 26% yield on the basis of 19F NMR spectroscopic analysis, revealing that the trifluoromethyl radical is likely to be the real reactive specie under the current reaction conditions.3i, 6e, 17 The other conventional

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radical scavenger, 2,6-di-tert-butyl-4-methylphenol (BHT), also inhibited the formation of 2a (only 40% isolated yield) (for details, see Scheme S2 in the Supporting Information). Table 3. Substrate scope of iron catalyzed cascade trifluoromethylation of 3a,b

Scheme 2. Radical scavenger experiment of 1a

Scheme 3. Proposed mechanism for the cascade trifluoromethylation reaction for the formation of 2 and 4 On the basis of above control experiments and related precedents on trifluoromethylation of activated alkenes, a plausible mechanism for this reaction is outlined in Scheme

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3. Firstly, CF3 radical is generated via a single-electron transfer (SET) process accompanied by a Fe(III) complex formation. The in situ generated CF3 radical reacts chemoselectively with acrylic moiety of substrate 1 or 3 to give a radical intermediate I. The subsequent addition to the less hindered central carbon of alkylidenecyclopropane produces radical intermediate II, which undergoes a ring-opening process to afford homoallyl radical intermediate III because of high strain of the cyclopropane ring.9f, 18 At this stage, two pathways can take place whether R1 is a para-methoxy-substituent or not. As for path A, a conventional cyclization with benzene ring occurs to give another radical intermediate IV. After oxidation and aromatization, the corresponding trifluoromethylated tetracyclic benzazepine derivative 2 is formed. When R1 is a para-methoxy substituted aromatic ring, an ipso-cyclization with aromatic ring occurs, giving a spirocyclic intermediate V, which is oxidized by Fe(III) to afford oxonium ion VI.16f The oxonium ion can be transformed into 4 in the presence of 2-iodobenzoic acidic anion. In summary, we have developed a novel protocol for synthesis of two types of trifluoromethyl-containing polycyclic benzazepine derivatives by iron or copper catalyzed trifluoromethylation reaction of acrylamide-tethered ACPs with Togni reagent II under mild and convenient conditions. Their reaction conditions and substrate scopes have been well investigated. These reactions proceed via a radical process and are featured by low cost and environmentally benign catalyst, operational simplicity and broad substrate scope. To the best of our knowledge, this is the first accomplishment of trifluoromethylation reactions coupled with seven-membered ring formation. Further investigations on expanding the scope of this reaction towards a variety of novel and potentially useful polycyclic compounds as well as the applications of this protocol to natural product synthesis are in progress.

ethyl acetate = 20 / 1) to afford the product 2 in moderate to good yield. 2a: 42 mg, 75%, A white solid, m.p. 183-185 oC; IR (CH2Cl2): ν 2944, 1652, 1495, 1446, 1359, 1251, 1189, 1108, 1057, 768 cm-1; 1H NMR (400 MHz, CDCl3, TMS): δ 1.69 (s, 3H), 1.91-2.07 (m, 2H), 2.27 (td, 1H, J1 = 16.0 Hz, J2 = 6.0 Hz), 2.73-2.87 (m, 3H), 3.45 (s, 3H), 6.95 (d, 1H, J = 8.4 Hz), 7.08-7.20 (m, 4H), 7.28-7.32 (m, 2H), 7.39-7.43 (m, 1H); 13C NMR (100 MHz, CDCl3, TMS): δ 22.8, 25.6, 28.7, 36.6 (q, JC-F = 27.0 Hz), 38.2, 46.9 (q, JC-F = 1.5 Hz), 121.7, 124.2, 125.7 (q, JC-F = 277.8 Hz), 126.1, 126.8, 127.0, 127.2, 128.7, 130.3, 131.8, 133.2, 136.0, 136.6, 140.6, 141.7, 171.1; 19F NMR (376 MHz, CDCl3, CFCl3): δ -59.8 (t, J = 10.9 Hz); MS (ESI) m/z: 372.2 (M+H+, 100); HRMS (ESI) Calcd. for C22H21F3NO+ requires: 372.1570, Found: 372.1579. General Procedure for 4: 3 (0.15 mmol), Togni reagent II (0.225 mmol), FeCl2 (0.0225 mmol) were added to a Schlenk tube with a magnetic bar. MeOH (1.5 mL) was added and the reaction tube was heated to 50 oC for 1 h. The crude reaction mixture was diluted with EtOAc (5.0 mL) and the organic layer was washed with aqueous NaHCO3 and brine. The mixture was extracted with EtOAc for 3 times. The organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by flash column chromatography on silica gel (eluent: petroleum ether / ethyl acetate = 4 / 1) to afford the product 4 in moderate yield. 4a: 34 mg, 58%, A colorless liquid; IR (CH2Cl2): ν 2923, 2854, 1662, 1625, 1589, 1457, 1376, 1262, 1186, 1115, 1067, 858, 761 cm-1; 1H NMR (400 MHz, DMSO-D6): δ 1.56 (s, 3H), 1.88-1.98 (m, 2H), 2.20-2.38 (m, 2H), 2.73 (dd, 1H, J1 = 17.6 Hz, J2 = 4.8 Hz), 2.95-3.04 (m, 1H), 3.36 (s, 3H), 6.24 (d, 1H, J = 10.4 Hz), 6.36 (d, 1H, J = 10.0 Hz), 6.88 (dd, 1H, J1 = 10.0 Hz, J2 = 2.4 Hz), 7.05 (d, 1H, J = 7.6 Hz), 7.11 (t, 1H, J = 7.2 Hz), 7.36-7.43(m, 3H); 13C NMR (100 MHz, DMSO-D6): δ 21.4, 32.4, 34.6 (q, JC-F = 27.0 Hz), 36.5, 44.0 (q, JC-F = 2.2 Hz), 56.6, 122.7, 124.1, 124.4, 126.1 (q, JC-F = 277.8 Hz), 127.4, 128.1, 128.9, 129.0, 134.8, 141.0, 147.9, 154.6, 154.7, 170.4, 184.8; 19F NMR (376 MHz, DMSO-D6): δ -59.5 (t, J = 10.9 Hz); MS (ESI) m/z: 388.2 (M+H+, 100); HRMS (ESI) Calcd. for C22H21F3NO2+ requires: 388.1519, Found: 388.1516.

EXPERIMENTAL SECTION General Procedure for 2: 1 (0.15 mmol), Togni reagent II (0.225 mmol), FeCl2 (0.015 mmol) were added to a Schlenk tube with a magnetic bar. 1,4-dioxane (1.5 mL) was added and the reaction tube was placed in a pre-heated 80 oC oil bath. After stirring for 6 h, a second portion of Togni reagent II (0.225 mmol) and FeCl2 (0.015 mmol) was added under Ar atmosphere. After stirring at same temperature for additional 6 h, the crude reaction mixture was diluted with EtOAc (5.0 mL) and the organic layer was washed with aqueous NaHCO3 and brine. The mixture was extracted with EtOAc for 3 times. The organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by flash column chromatography on silica gel (eluent: petroleum ether /

ASSOCIATED CONTENT Supporting Information: Experimental procedures, characterization data, and 1H and 13C NMR spectra for new compounds are included. This material is available free of charge via the Internet at http://pubs.acs.org. AUTHOR INFORMATION Corresponding Author *E-mail for M.S.: [email protected].

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Notes The authors declare no competing financial interest. ACKNOWLEDGMENT We are grateful for the financial support from the National Basic Research Program of China (973)-2015CB856603, and the National Natural Science Foundation of China (20472096, 21372241, 21361140350, 20672127, 21421091, 21372250, 21121062, 21302203, 20732008 and 21572052). REFERENCES (1) (a) Shimizu, M.; Hiyama, T. Angew. Chem., Int. Ed. 2005, 44, 214-231. (b) Schlosser, M. Angew. Chem., Int. Ed. 2006, 45, 5432-5446. (c) Müller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881-1886. (2) (a) Mullard, A. Nat. Rev. Drug Discovery. 2013, 12, 87-90. (3) For selected reviews of trifluoromethylation of organic compounds, see: (a) Tomashenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111, 4475-4521. (b) Studer, A. Angew. Chem., Int. Ed. 2012, 51, 8950-8958. (c) Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214-8264. (d) Barata-Vallejo, S.; Postigo, A. Coord. Chem. Rev. 2013, 257, 3051-3069. (e) Liu, H.; Gu, Z.; Jiang, X. Adv. Synth. Catal. 2013, 355, 617-626. (f) Egami, H.; Sodeoka, M. Angew. Chem., Int. Ed. 2014, 53, 8294-8308. (g) Merino, E.; Nevado, C. Chem. Soc. Rev. 2014, 43, 6598-6608. (h) Chu, L.; Qing, F.-L. Acc. Chem. Res. 2014, 47, 1513-1522. (i) Charpentier, J.; Früh, N.; Togni, A. Chem. Rev. 2015, 115, 650-682. (j) Ni, C.; Hu, M.; Hu, J. Chem. Rev. 2015, 115, 765-825. (k) Alonso, C.; de Marigorta, E. M.; Rubiales, G.; Palacios, F. Chem. Rev. 2015, 115, 1847-1935. (4) (a) Zhang, C.-P.; Wang, Z.-L.; Chen, Q.-Y.; Zhang, C.-T.; Gu, Y.-C.; Xiao, J.-C. Angew. Chem., Int. Ed. 2011, 50, 1896-1900. (b) Parsons, A. T.; Buchwald, S. L. Angew. Chem., Int. Ed. 2011, 50, 9120-9123. (c) Xu, J.; Fu, Y.; Luo, D.-F.; Jiang, Y.-Y.; Xiao, B.; Liu, Z.-J.; Gong, T.-J.;. Liu, L. J. Am. Chem. Soc. 2011, 133, 15300-15303. (d) Wang, X.; Ye, Y.; Zhang, S.; Feng, J.; Xu, Y.; Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2011, 133, 16410-16413. (e) Liu, T.; Shao, X.; Wu, Y.; Shen, Q. Angew. Chem., Int. Ed. 2011, 51, 540-543. (f) Xu, J.; Xiao, B.; Xie, C.-Q.; Luo, D.-F.; Liu, L.; Fu, Y. Angew. Chem., Int. Ed. 2012, 51, 12551-12554. (g) Zhang, B.; Mück-Lichtenfeld, C.; Daniliuc, C. G.; Studer, A. Angew. Chem., Int. Ed. 2013, 52, 10792-10795. (h) Dai, J.-J.; Fang, C.; Xiao, B.; Yi, J.; Xu, J.; Liu, Z.-J.; Lu, X.; Liu, L.; Fu, Y. J. Am. Chem. Soc. 2013, 135, 8436-8439. (i) Wang, X.; Xu, Y.; Deng, Y.; Zhou, Y.; Feng, J.; Ji, G.; Zhang, Y.; Wang, J. Chem. - Eur. J. 2014, 20, 961-965. (5) For selected recent examples of oxytrifluoromethylation reactions of C=C bonds, see: (a) Zhang, C.-P.; Wang,

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