Fusion of Aromatic Ring to Azoarenes: One-Pot Access to 5, 6

Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

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Fusion of Aromatic Ring to Azoarenes: One-Pot Access to 5,6Phenanthroliniums for Mitochondria-Targeted Far-Red/NIR Fluorescent Probes Zheng Liu, Yonghua Xian, Jingbo Lan,* Yuanyuan Luo, Weixin Ma, and Jingsong You* Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China

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ABSTRACT: Disclosed herein is a highly efficient strategy to fuse an aromatic ring to azoarenes for one-pot access to 5,6phenanthrolinium skeletons via tandem ortho-C−H arylation and aryl quaternization. This protocol enables ortho-hindered azobenzenes to solely form 5-aryl-5,6-phenanthroliniums and ortho-unhindered azobenzenes to exclusively generate 5,7-diaryl5,6-phenanthroliniums. The diarylated products (5k−5r) exhibit far-red to NIR emissions (678−742 nm) with large Stokes shifts, can specifically light up mitochondria in living cells, and, moreover, possess excellent photostability and low cytotoxicity.

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Scheme 1. Design and Synthesis of 5,6-Phenanthroliniums

henanthridinium derivatives, such as ethidium bromide, have been widely used as the fluorescent staining agents of cells and biotissues.1 Despite extensive literature on this subject, there remain considerable limitations for practical use, such as cytotoxicity and relatively short absorption and emission wavelengths.1,2 Far-red and near-infrared (NIR) fluorescent probes have many advantages, including minimum photodamage, low autofluorescence interference, and deep tissue penetration.3,4 The development of novel far-red/NIR organelle-targeted imaging agents is an appealing yet significantly challenging task. Aryl azo compounds constitute the largest and most diverse class of coloring agents, accounting for nearly 60% of currently available dyes.5 They have vivid colors, mainly red, orange, and yellow, and are extensively used as dyes and pigments. However, as we all know, azoarenes are nonfluorescent or only weakly fluorescent in most cases due to the energy loss from the excited state through the photoisomerization of the NN bond.5,6 We conceive that the fusion of an aromatic ring to azoarenes to construct 5-aryl-5,6-phenanthroliniums can not only address the issue of the photoisomerization but also endow the resultant product with a red-shifted emission due to increased π-conjugation (Scheme 1). 5,6-Phenanthrolinium is very similar to phenanthridinium in molecular structure (Scheme 1). Its N(sp2) at the 6-position provides an additional hydrogen-bonding site and, moreover, endows the 5,6-phenanthrolinium core with a stronger electron-withdrawing property than phenanthridinium, which is in favor of the red shift of the emission wavelength due to the intramolecular charge transfer (ICT) effect. To date, there is no sufficiently effective strategy to access 5aryl-5,6-phenanthroliniums. The only synthetic method that © XXXX American Chemical Society

can be retrieved is accomplished by the photocyclization of 1,1,2-triphenyldiazenium,7 but in a low yield (50%), and moreover, the diazenium substrate is not readily accessible (Scheme 1, route B).8 The 5-aryl-5,6-phenanthroliniums can also be disconnected retrosynthetically at the other two Received: December 20, 2018

A

DOI: 10.1021/acs.orglett.8b04072 Org. Lett. XXXX, XXX, XXX−XXX

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of 2e. Finally, 2e was obtained in 77% yield by [Cp*IrCl2]2/ AgSbF6 with Ag2CO3 as an oxidant and HOAc as an additive in TFE at 120 °C for 24 h under an air atmosphere. The tandem C−H arylation/aryl quaternization succeeded with a variety of para- and meta-substituted phenyliodonium trifluoromethanesulfonate salts (Scheme 3, 2f−2n). Phenyl-

positions, which correspond to two kinds of aryl quaternizations (Scheme 1, routes A and C), respectively. Apparently, routes A and B are not generally applicable methods because it is difficult to control the regioselectivity of reactions while employing unsymmetrical substrates, which inevitably leads to an intractable mixture of regioisomers. We initially tried to investigate the intramolecular aryl quaternization (route C). Considering that the oxidation of electron-rich arenes can form a radical cation, which may be attacked by the pyridine nitrogen atom to generate a Narylpyridinium cation,9 the intramolecular aryl quaternization of 2-phenyl azobenzene (1a) was conducted in the presence of various oxidants (Table S1). Delightedly, 2a was obtained in 82% yield while employing Ag2CO3 as an oxidant (Scheme 2,

Scheme 3. Monoarylation/Aryl Quaternization of Azoarenesa,b

Scheme 2. Intramolecular Aryl Quaternization of 2-Phenyl Azobenzenesa,b

Isolated yields. bEmission maxima in CH2Cl2 (1.0 × 10−5 M) are recorded in brackets. cTFE = 2,2,2-trifluoroethanol.

a

Isolated yields. bEmission maxima in CH2Cl2 (1.0 × 10−5 M) are recorded in brackets. cPh2IOTf was used. d150 °C. ePh2IBF4 was used.

a

2a). Other azobenzenes also gave the corresponding products (2b−d) in good to excellent yields. To our knowledge, this is the first example of aryl quaternization of azobenzenes via a direct C−H functionalization. 2-Aryl substituted azobenzenes (1) are usually synthesized from nitrosobenzene and 2-amino biphenyl,10 and the latter typically comes from the Suzuki coupling of 2-haloanilines with arylboronic acids.11 Recently, the chelation-assisted ortho-C− H arylation has emerged as a powerful approach to unsymmetrical biaryls.12 The direct C−H arylation strategy is apparently a more ideal synthetic approach to 2-aryl azobenzenes.13 Moreover, if the C−H arylation and intramolecular N-arylation (aryl quaternization) are accomplished in one pot, it would doubtless provide a more concise and stepeconomical route to 5,6-phenanthroliniums from readily available azo substrates. However, accomplishing the twostep conversions in one pot remains challenging because Cand N-arylation conditions are usually incompatible to one another.14 To achieve the tandem ortho-C−H arylation and aryl quaternization of azoarenes in one pot, the optimal reaction conditions were explored by employing 3,3′-bis(tert-butyl)azobenzene (3a) and diphenyliodonium trifluoromethanesulfonate (4a) as substrates and silver salts as oxidants (Tables S2−S6). To our delight, both Pd(II) and Ir(III) could effectively promote the one-pot transformation, and [Cp*IrCl2]2 was a much better choice. Further optimization of solvents showed that 2,2,2-trifluoroethanol (TFE) could give the best yield of 5,6-phenanthrolinium 2e. After additives were screened, it was found that the addition of base could restrain this reaction, and HOAc could promote the formation

iodoniums with electron-deficient fluoro, chloro, and bromide substituents were compatible, but in slightly lower yields (Scheme 3, 2l−2n). The reactions of unsymmetrical azoarenes exhibited good selectivity and took place at the side of the more electron-rich aromatic ring (Scheme 3, 2p, 2q, and 5a). Diphenyliodonium tetrafluoroborate salt 4k could also react with 2-phenyl-3′,5′-bis(trifluoromethyl)azobenzene (3e) under this condition, affording 5,7-diaryl-5,6-phenanthrolinium 5a in 62% yield. With a library of 5-aryl-5,6-phenanthroliniums (2) in hand, their photophysical properties were measured (Scheme 3, Table S9, and Figure S1). These compounds present tunable emission colors from green to orange in CH2Cl2 (500−600 nm) with fluorescence quantum yields from 0.01 to 0.25 (Table S9). It is worth noting that 5,7-diaryl-5,6-phenanthrolinium 5a exhibits a much more red-shifted emission than 5-aryl-5,6-phenanthroliniums (2), clearly demonstrating that the introduction of an aryl group at the 7-position may uniquely contribute to a large red-shifted emission. However, as mentioned above, the synthesis of 2-aryl azobenzene for preparing 5a requires a multistep process.10,11 Apparently, it is a shortcut to access 5,7-diaryl-5,6-phenanthroliniums by the tandem diarylation/aryl quaternization, starting from the readily available azobenzenes. It is known that diarylated products are readily obtained from the ortho-C−H arylation of unhindered substrates.15 When employing ortho-unhindered azobenzenes as substrates, the diarylation/aryl quaternization smoothly took place as expected, affording the corresponding 5,7-diaryl-5,6-phenanthroliniums (5b−5r) in up to almost quantitative yields B

DOI: 10.1021/acs.orglett.8b04072 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters (Scheme 4). The products of monoarylation/aryl quaternization were not observed. 5b and 5k were also prepared in 96%

Scheme 5. Plausible Mechanistic Pathway

Scheme 4. Diarylation/Aryl Quaternization of Azoarenesa,b

and subsequent ortho-C−H activation form cyclometalated complex IM1. IM1 is oxidized by 4a to generate the Ir(V) species IM2, which undergoes reductive elimination to provide IM3.16 Subsequently, the second ortho-C−H activation takes place, delivering IM4. IM4 is further oxidized by 4a to generate IM5, and then reductive elimination gives 7a, followed by a single electron transfer (SET) pathway from 7a to Ag(I), forming the radical cationic intermediate IM6.9 IM6 undergoes an intramolecular nucleophilic attack by the azo nitrogen atom to generate radical IM7. IM7 is oxidized by Ag(I) via a SET process to give cationic IM8, which then undergoes a deprotonation process, forming the product 5b. After a variety of 5,7-diaryl-5,6-phenanthroliniums (5) were obtained, their absorptions, emissions, and quantum yields were measured (Scheme 4, Table S10, and Figure S2). The UV−vis absorption spectra of 5 in CH2Cl2 (1 × 10−5 M) generally exhibit two or three absorption bands. The shortwavelength absorptions are assigned to the localized π−π* and/or n−π* transitions of the chromophores. The longwavelength absorptions are due to the charge-transfer (CT) transition. As expected, 5,7-diaryl-5,6-phenanthroliniums (5) generally show higher molar absorption coefficients in CT transitions than 5-aryl-5,6-phenanthroliniums (2) in solution due to the extended conjugation (Tables S9−S10 and Figures S1−S2). Moreover, the diaryl substituted products 5 exhibit more red-shifted emissions (572−742 nm) with higher fluorescence quantum yields up to 0.41, when compared with the corresponding monoaryl substituted 2 (Tables S9 and S10). 5,7-Diaryl-5,6-phenanthroliniums (5k−5r) with electron-donating substituents, such as methoxy and phenoxy groups, at the 3-position of the phenanthrolinium skeleton and para-position of 7-phenyl exhibit much more red-shifted emissions compared with 5a−5j (Scheme 4, Table S10, and Figure S2). These results demonstrate that the introduction of the phenyl ring (Ar3) with the electron-donating methoxy and phenoxy groups to the electron-deficient phenanthrolinium core is conducive to a red-shifted emission due to the ICT effect, and therefore, 5k−5r exhibit far-red to NIR fluorescence emissions (678−742 nm) with large Stokes shifts (3764−4562 cm−1). However, alkoxy groups at the 9-position of the phenanthrolinium core lead to a blue-shifted emission (5a: λem = 649 nm vs 5j: λem = 581 nm; 5b: λem = 605 nm vs 5e: λem = 572 nm; 5p: λem = 742 nm vs 5o: λem = 680 nm), indicating

Isolated yields. bEmission maxima in CH2Cl2 (1.0 × 10−5 M) are recorded in brackets. cPh2IOTf was used. dGram-scale reactions.

a

and 94% yields on gram scales (1.11 and 1.22 g), respectively (Scheme S1). The structure of 5b was further confirmed by single crystal X-ray diffraction (CCDC 1884013; Scheme 4). To clarify the mechanism of the tandem reaction, Ir(III) cyclometalated complex (6) was synthesized (Scheme S2). Using 6 as a catalyst, 5b was obtained in 103% yield while calculated by the amount of azobenzene (3f), indicating that the catalyst itself was also transformed into 5b (eq 1).

Subsequently, the kinetic isotope effect (KIE) experiments were performed for both 3f and 4a. A larger KIE value of 2.30 was observed at the parallel reactions between 3f and [D10]-3f with 4a, and a KIE value of 1.17 was observed for the parallel reactions between 4a and [D10]-4a with 3f (Scheme S3). These results suggested that the C−H bond cleavage of 4a might not be in a rate-determining step, while the ortho-C−H activation of 3f might be involved in the rate-determining step. In addition, the addition of radical inhibitors, such as 2,2,6,6tetramethylpiperidine oxide (TEMPO), 2,6-bis(tert-butyl)-4methylphenol (BHT), and ascorbic acid, could effectively suppress both the intramolecular aryl quaternization and the tandem diarylation/aryl quaternization, indicating a possible radical process of the quaternization reaction (Tables S7−S8). Accordingly, a plausible pathway is proposed (Scheme 5). [Cp*IrCl2]2 is first transformed into a cationic Ir(III) species in the presence of AgSbF6. The coordination of 3f to Ir(III) C

DOI: 10.1021/acs.orglett.8b04072 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters that introducing electron-donating alkoxys on the aromatic ring (Ar1) of azo substrates is not favorable for a red-shifted emission. Next, the solvent polarity-dependent emission behavior of 5k was studied (Figure S3a). Its emission spectra present a remarkable blue shift with the increase of the solvent polarity: from 711 nm in low-polar CH2Cl2 to 661 nm in highpolar methanol, indicating typical ICT character in the excited state.17 The effect of solvent polarity on the photophysical property of 2e was also investigated (Figure S3b). The emission spectra of 2e show a slight change within the scope of 12 nm as the solvent polarity increases, indicating negligible ICT effect. Subsequently, the confocal fluorescence imaging experiments were performed in live cells. To our delight, the diarylated products (5b−5r) all successfully penetrated the cell membranes of HepG2 cells and were localized in mitochondria as verified by colocalization studies with MitoTracker Green (MTG) (Table S11 and Figures S4−S20). Although the farred/NIR-emitting 5k−5r show low fluorescence quantum yields (∼0.01), all of them exhibit a bright fluorescent image in live cells (Figure 1 and Figures S13−S20). We speculated that

Figure 2. (a) Signal loss (%) of fluorescent emissions of 5n, 5p, 5q, and 5r in PBS containing 1% DMSO, MTG and MTR in living HepG2 cells with increasing number of scans using confocal microscope (irradiation time: 0.97 s/scan). (b) Cell viability values (%) estimated by CCK-8 assays using HepG2 cells, cultured in the presence of 0.625−10.0 μM of 5n, 5p, 5q, and 5r for 24 h at 37 °C.

In summary, we have developed a highly efficient one-pot synthetic protocol to 5,6-phenanthrolinium skeletons via tandem ortho-C−H arylation and aryl quaternization of azoarenes. The current Ir/Ag catalyst system exhibits good compatibility to C−H and N-arylations that are usually orthogonal to one another. ortho-Hindered azobenzenes solely deliver the products of monoarylation/aryl quaternization, while ortho-unhindered azobenzenes exclusively generate the products of diarylation/aryl quaternization. 5,7-Diaryl-5,6phenanthroliniums (5) exhibit more red-shifted emissions (572−742 nm) with higher fluorescence quantum yields up to 0.41, when compared with the 5-aryl-5,6-phenanthroliniums (2). Moreover, these diarylated products (5) show significantly enhanced emissions with increasing solution viscosities and AIE properties, which can successfully penetrate the cell membranes of HepG2 cells and be localized in mitochondria. Phenanthroliniums 5k−5r exhibit far-red to NIR emissions (678−742 nm) with large Stokes shifts (3764−4562 cm−1) and possess excellent photostability and low cytotoxicity, which would be potential mitochondria-targeted reagents.

Figure 1. Fluorescent images of HepG2 cells cultured with 5n (a), 5p (d), 5q (g), and 5r (j) (λex = 488 nm, λem = 650−750 nm); with MTG (b, e, h, and k) (λex = 488 nm, λem = 500−540 nm); merged images (c, f, i, and l).

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ASSOCIATED CONTENT

* Supporting Information

the increasing intracellular viscosity or aggregation induced emission (AIE) might result in enhanced emission. Thus, the viscochromism and AIE properties were investigated. The fluorescence intensities of 5k−5r increase significantly by 13− 29 times in methanol/glycerol mixtures with the increasing ratio of glycerol to methanol, perhaps because the increasing viscosity of the environment restricts intramolecular rotation and nonradiative relaxation (Figures S23−S30).18 In addition, 5r exhibits faint emission in DMSO. Upon addition of water from 0 to 80 vol% into its DMSO solution, the emission has little changes. While the water fraction changes from 80 to 99 vol%, the emission remarkably increases up to 13-fold, demonstrating the AIE property (Figure S35).19 Furthermore, 5b, 5c, 5d, and 5g also show the AIE property (Figures S31− 34). The emission of 5g is dramatically enhanced up to 60-fold with the increase in the water fraction (Figure S34). Photostability experiments were conducted in living HepG2 cells using a confocal microscope with increasing number of scans. Phenanthroliniums 5k−5r exhibit better photostabilities than commercially available mitochondria-targeted trackers, MTG and MitoTracker Red FM (MTR) (Figure 2a and Figure S21). Moreover, the photostabilities of 5n, 5p, 5q, and 5r are more excellent. After 50 scans, their fluorescence intensities remain more than 60%. Finally, the cytotoxicities of 5k−5r were assessed (Figure 2b and Figure S22). 5l, 5n, 5o, 5p, 5q, and 5r do not exhibit distinct toxicity to cultured HepG2 cells in the concentration range 0.625−5.0 μM.

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b04072. Detailed experimental procedures, characterization data, copies of 1H and 13C NMR spectra of products, and Xray crystal structure of 5b (PDF) Accession Codes

CCDC 1884013 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Jingbo Lan: 0000-0001-5937-0987 Jingsong You: 0000-0002-0493-2388 Notes

The authors declare no competing financial interest. D

DOI: 10.1021/acs.orglett.8b04072 Org. Lett. XXXX, XXX, XXX−XXX

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(18) (a) Haidekker, M. A.; Theodorakis, E. A. Org. Biomol. Chem. 2007, 5, 1669. (b) Kuimova, M. K.; Yahioglu, G.; Levitt, J. A.; Suhling, K. J. Am. Chem. Soc. 2008, 130, 6672. (19) Liang, L.; Tang, B. Z.; Liu, B. Chem. Soc. Rev. 2015, 44, 2798.

ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (Nos. 21871193, 21672154, and 21432005) for financial support. We also thank the Comprehensive Training Platform Specialized Laboratory, College of Chemistry, Sichuan University.

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REFERENCES

(1) (a) Olmsted, J.; Kearns, D. R. Biochemistry 1977, 16, 3647. (b) Zimmermann, H. Z. Angew. Chem., Int. Ed. Engl. 1986, 25, 115. (2) (a) Waring, M. J. J. Mol. Biol. 1965, 13, 269. (b) Vacquier, V. D.; Brachet, J. Nature 1969, 222, 193. (c) van der Wiel, I. M.; Cheng, J.; Koukiekolo, R.; Lyn, R. K.; Stevens, N.; O’Connor, N.; Turro, N. J.; Pezacki, J. P. J. Am. Chem. Soc. 2009, 131, 9872. (d) Prunkl, C.; Pichlmaier, M.; Winter, R.; Kharlanov, V.; Rettig, W.; Wagenknecht, H.-A. Chem. - Eur. J. 2010, 16, 3392. (3) Weissleder, R. Nat. Biotechnol. 2001, 19, 316. (4) (a) Yuan, L.; Lin, W.; Zheng, K.; He, L.; Huang, W. Chem. Soc. Rev. 2013, 42, 622. (b) Guo, Z.; Park, S.; Yoon, J.; Shin, I. Chem. Soc. Rev. 2014, 43, 16. (5) (a) Bock, H.; Rudolph, G.; Baltin, E.; Kroner, J. Angew. Chem., Int. Ed. Engl. 1965, 4, 457. (b) Lee, H. Y.; Song, X.; Park, H.; Baik, M.-H.; Lee, D. J. Am. Chem. Soc. 2010, 132, 12133. (c) Merino, E. Chem. Soc. Rev. 2011, 40, 3835. (6) (a) Hartley, G. S. Nature 1937, 140, 281. (b) Rau, H.; Lüddecke, E. J. Am. Chem. Soc. 1982, 104, 1616. (c) Bandara, H. M. D.; Burdette, S. C. Chem. Soc. Rev. 2012, 41, 1809. (7) Cauquis, G.; Reverdy, G. Tetrahedron Lett. 1977, 18, 3267. (8) Zelenin, K. N.; Verbov, V. N. Khim. Geterotsikl. Soedin. 1979, 11, 1547. (9) (a) Ristagno, C. V.; Shine, H. J. J. Org. Chem. 1971, 36, 4050. (b) Schlesener, C. J.; Kochi, J. K. J. Org. Chem. 1984, 49, 3142. (c) Morofuji, T.; Shimizu, A.; Yoshida, J. J. Am. Chem. Soc. 2013, 135, 5000. (10) Wang, Z.; Yin, Z.; Zhu, F.; Li, Y.; Wu, X.-F. ChemCatChem 2017, 9, 3637. (11) Cho, S. H.; Yoon, J.; Chang, S. J. Am. Chem. Soc. 2011, 133, 5996. (12) (a) McGlacken, G. P.; Bateman, L. M. Chem. Soc. Rev. 2009, 38, 2447. (b) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792. (c) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215. (d) Li, B.-J.; Shi, Z.-J. Chem. Soc. Rev. 2012, 41, 5588. (e) Kuhl, N.; Hopkinson, M. N.; Wencel-Delord, J.; Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 10236. (f) Zhang, M.; Zhang, Y.; Jie, X.; Zhao, H.; Li, G.; Su, W. Org. Chem. Front. 2014, 1, 843. (g) Liu, C.; Yuan, J.; Gao, M.; Tang, S.; Li, W.; Shi, R.; Lei, A. Chem. Rev. 2015, 115, 12138. (h) Yang, Y.; Lan, J.; You, J. Chem. Rev. 2017, 117, 8787. (13) (a) Miyamura, S.; Tsurugi, H.; Satoh, T.; Miura, M. J. Organomet. Chem. 2008, 693, 2438. (b) Qian, C.; Lin, D.; Deng, Y.; Zhang, X.-Q.; Jiang, H.; Miao, G.; Tang, X.; Zeng, W. Org. Biomol. Chem. 2014, 12, 5866. (c) Hubrich, J.; Himmler, T.; Rodefeld, L.; Ackermann, L. ACS Catal. 2015, 5, 4089. (d) Li, M.; Ye, Y. ChemCatChem 2015, 7, 4137. (e) Deng, H.; Li, H.; Wang, L. Org. Lett. 2016, 18, 3110. (14) Modha, S. G.; Greaney, M. F. J. Am. Chem. Soc. 2015, 137, 1416. (15) (a) Zhao, X.; Yeung, C. S.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 5837. (b) Arockiam, P. B.; Fischmeister, C.; Bruneau, C.; Dixneuf, P. H. Angew. Chem., Int. Ed. 2010, 49, 6629. (c) Kitahara, M.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. J. Am. Chem. Soc. 2011, 133, 2160. (16) (a) Shin, K.; Park, S.-W.; Chang, S. J. Am. Chem. Soc. 2015, 137, 8584. (b) Gao, P.; Guo, W.; Xue, J.; Zhao, Y.; Yuan, Y.; Xia, Y.; Shi, Z. J. Am. Chem. Soc. 2015, 137, 12231. (c) Tan, G.; You, Q.; You, J. ACS Catal. 2018, 8, 8709. (17) (a) Buncel, E.; Rajagopal, S. Acc. Chem. Res. 1990, 23, 226. (b) Reichardt, C. Chem. Rev. 1994, 94, 2319. E

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