Letter pubs.acs.org/OrgLett
Organic Dye-Catalyzed Atom Transfer Radical Addition−Elimination (ATRE) Reaction for the Synthesis of Perfluoroalkylated Alkenes Deo Prakash Tiwari, Saumya Dabral, Jian Wen, Jan Wiesenthal, Steven Terhorst, and Carsten Bolm* Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany S Supporting Information *
ABSTRACT: An atom transfer radical addition elimination (ATRE) reaction of terminal alkenes with perfluoroalkyl halides under visible light is described. The photoredox catalysis with Eosin Y provides perfluoroalkenes in good yields. The reaction has been utilized for the late stage perfluoroalkenylation of an estrone-derived alkene. ntroduction of fluorine into organic compounds has been one of the major areas of research in recent years.1 Owing to their tendency to alter the lipophilicity, metabolic stability, and electronic properties, fluorinated organic compounds have been widely used in medicinal chemistry,2 crop science,3 and several other industrial functions.4 Perfluoroalkylation5−11 is one of the most popular methods to incorporate fluorine into organic compounds. Since the first report by Kharasch and coworkers5a,b in 1945, atom transfer radical addition (ATRA)5 has extensively been utilized for perfluoroalkylation of organic compounds.6 ATRA-based approaches often require peroxide,7a Na2S2O4,7b,d Et3B,7c metal catalysts,7e,j,m or UV light8 as the radical initiators. Recently, photoredox catalysis9 has emerged as an alternative to the traditional initiator-promoted radical reactions. The past decade witnessed exponential progress in visible-light-promoted perfluoroalkylation reactions.10,11 Even after undergoing a significant renaissance in recent years, photoredox-catalyzed perfluoroalkylation encounters several issues to be addressed such as (1) employment of very costly Ru/Ir polypyridyl metal complexes as photoredox catalysts; (2) use of the several additives, which could promote side reactions; and (3) a narrow photocatalyst scope for different kinds of reactions and perfluoroalkylating reagents. The high price and tedium involved in the synthesis of traditional Ru/Ir-photocatalysts prompted researchers to uncover several alternative photocatalysts such as TiO2,8f Cu(dap)2Cl,10h,i EDA-complexes,10e photosensitizers,10j and organic dyes.11 We were interested in developing a one-step route for the synthesis of perfluoroalkenes12 directly from alkenes through an atom transfer radical addition elimination (ATRE)13 reaction utilizing organic dye-promoted photoredox catalysis (Scheme 1). ATRA of perfluoroalkyl halides to alkenes and alkynes leads to the generation of halo perfluoroalkanes A (-enes, C) (Scheme 1, eqs 1 and 2). If a proton source is present, perfluorolalkanes (-enes) are the observed products. Often the solvent and additives determine which product will be generated. We hypothesized that a suitable combination of base and solvent could generate perfluoroalkenes14 through ATRE directly from terminal alkenes (Scheme 1, eq 3).
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© XXXX American Chemical Society
Scheme 1. Perfluoroalkylation of Compounds with Carbon− Carbon Multiple Bonds
For our initial studies, we performed the reaction of 4-phenyl but-1-ene (1a) and C4F9I (2a, 3.0 equiv) employing Eosin Y (5 mol %) as the photocatalyst under visible light from a 16 W white fluorescent lamp under argon. The results are summarized in Table 1. In THF and water, using Cs2CO3 as the base, only addition occurred, and iodoperfluoroalkane 4 was obtained as the sole product in 66% and 63% yield, respectively (Table 1, entries 1 and 2). In MeCN, however, the desired 1-perfluoroalkene 3a (45%) was indeed generated, albeit still in combination with 4 (13%) (Table 1, entry 3). The desired 3a was formed in 72% yield as the sole product when the reaction was performed in DMF (Table 1, entry 4). Switching to dimethylacetamide (DMAc) as the solvent significantly improved the yield of 3a (95%), and also in this case 4 remained undetected (Table 1, entry 5). Reduction in the amount of the perfluoroalkyl iodide from the standard 3 equiv to 1 equiv of 2a lowered the yield of 3a to 75% (Table 1, entry 6). In general, the transformation was highly dependent on additives, and weaker bases such as Received: June 26, 2017
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DOI: 10.1021/acs.orglett.7b01952 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters Table 1. Optimization Studiesa
Scheme 2. Substrate Scopea
entry
base
photocatalyst
solvent
1 2 3 4 5 6d 7e 8 9 10 11f,g 12f,g 13 14 15h
Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 K2HPO4 DIPEA TBD DBU Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3
Eosin Y Eosin Y Eosin Y Eosin Y Eosin Y Eosin Y Eosin Y Eosin Y Eosin Y Eosin Y Rose Bengal Rhodamine B Bn2NH − Eosin Y
THF water CH3CN DMF DMAc DMAc DMAc DMAc DMAc DMAc DMAc DMAc DMAc DMAc DMAc
3ab (%) (E/Z) − − 45 72 95 75 41 34 71 72 55 75 50 49 22
(3.4:1) (4.5:1) (5:1) (5:1) (3.2:1) (−) (3.7:1) (4.3:1) (3.4:1) (3.1:1) (−) (4.4:1) (−)
4c (%) 66 63 13 − − − 30 75 29 − − − − − −
a Reaction conditions: 1a (0.38 mmol), C4F9I (1.14 mmol, 3.0 equiv), Eosin Y (5 mol %), Cs2CO3 (2.0 equiv), and DMAc (3.8 mL) at rt for 48 h in visible light under argon. bIn parentheses, E/Z ratios as determined by 1H NMR spectroscopy. cRatio of 3a and 4 as determined by 1H NMR using 1,3,5-trimethoxybenzene (TMB) as the internal standard. dUse of 1.0 equiv of C4F9I. e16% of 1a remain unreacted. f1H NMR yield using TMB as the internal standard. gYields based on unreacted 1a. hWithout light source; 10% of 1a remained unreacted, and the yield of 3a was determined by 1H NMR using 1,3,5-trimethoxybenzene (TMB) as the internal standard.
a
In parentheses, E/Z ratios as determined by 1H NMR spectroscopy. On a 1.5 mmol scale: 88% of 3a (E:Z = 4:1). cFormation of the E isomer exclusively. dN.D. = not determined (due to its volatility).
K2HPO4 and DIPEA promoted formation of mixtures of both 3a and 4 (Table 1, entries 7 and 8). Unlike other photoredox-catalyzed perfluoroalkylation reactions, DBU10b and TBD were less effective although complete conversion of the alkene 1a was observed (Table 1, entries 9 and 10). Other organic dyes (Rose Bengal and Rhodamine B) were inferior in terms of yield when compared to Eosin Y (Table 1, entries 11 and 12). The recently reported dibenzyl amine-catalyzed perfluoroalkyation10k was less efficient, producing 3a in 50% yield only (Table 1, entry 13). When the reaction was performed without a photocatalyst, the yield of 3a was only 49% (Table 1, entry 14).15 In the absence of the light source, 3a was obtained in 22% yield and 10% of 1a remained unreacted (Table 1, entry 15). Next, the scope of the photocatalysis was examined. The results are shown in Scheme 2. Reacting the corresponding alkenes with perfluoroalkyl iodides C3F7I, i-C3F7I C4F9I, C6F13I, and C8F17I under the aforementioned optimized conditions afforded perfluoroalkenes 3a−x in good yields. Functional groups had only a minor effect on the reaction outcome. On a 1.5 mmol scale, the reaction of 4-phenyl but-1-ene (1a) with C4F9I (2a) provided 3a in 88% yield (E/Z = 4:1).
b
Several observations are noteworthy: The first one relates to the formation of iodo-substituted perfluoroalkene 3l. Starting from sulfonate 1l it was formed by a multistep pathway involving an initial ATRE reaction followed by a subsequent SN2 substitution with in situ generated iodide. Second, whereas internal olefins produced complex mixtures of regioisomers and E/Z-isomers (not shown), 2,2-disubstituted alkenes coupled well as illustrated by the formation of 3o in 76% yield. Reacting styrene, representing an aryl-substituted alkene, with C4F9I afforded perfluoroalkene 3x in 52% yield. Compared to the other transformations, this yield was only moderate, presumably due to the high volatility of perfluorinated 3x. Finally, the analogous reaction with estrone-derived alkene 1y led to product 3y in 95% yield, confirming the pronounced functional group tolerance of the process, which might prove useful for late-stage functionalizations of complex natural products of drug-like molecules.16 B
DOI: 10.1021/acs.orglett.7b01952 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters
perfluoroalkyl halides. It utilizes visible light and inexpensive organic dyes as photocatalysts. Various functional groups on the alkene are tolerated, and the process is applicable for latestage perfluoroalkenylations of complex and diversely substituted molecules.
Next, we examined if the same conditions could also be applied for difluoroalkylations of alkenes. Upon reaction of the corresponding alkenes 1 with CF2Br2 (5a),10d bromodifluoroalkenes 6a−c were generated in yields ranging from 65% to 80% (Scheme 3). Similarly, ICF2CO2Et (5b)10b reacted with
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Scheme 3. Organic Dye-Catalyzed Synthesis of Difluoroalkenesa
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b01952. General experimental procedure and characterization details (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Carsten Bolm: 0000-0001-9415-9917 Notes a b
The authors declare no competing financial interest.
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In parentheses, E/Z ratios as determined by 19F NMR spectroscopy. Instead of Eosin Y, Rhodamine B was used as photocatalyst.
ACKNOWLEDGMENTS D.P.T. acknowledges the Alexander von Humboldt Foundation for a postdoctoral fellowship. S.D. thanks the European Union for support (Marie Curie ITN “SuBiCat” PITN-GA-2013607044), and J.W. is grateful to the China Scholarship Council for a predoctoral stipend.
alkenes to give 6d and 6e in 68% and 73% yield, respectively. For the reactions involving 5b as a perfluoroalkyl halide, Rhodamine B was found to be superior over Eosin Y as a photocatalyst.11g Scheme 4 shows a plausible mechanism for the visible light promoted ATRE reaction. First, photoexcited Eosin Y (EY) is
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REFERENCES
(1) (a) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications, 2nd ed.; Wiley-VCH: Weinheim, 2013. (b) Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214. (2) (a) Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Aceña, J. L.; Soloshonok, V. A.; Izawa, K.; Liu, H. Chem. Rev. 2016, 116, 422. (b) Müller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881. (c) Kirk, K. L. J. Fluorine Chem. 2006, 127, 1013. (d) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320. (e) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. J. Med. Chem. 2015, 58, 8315. (f) Schweizer, E.; Hoffmann-Röder, A.; Scharer, K.; Olsen, J. A.; Fäh, C.; Seiler, P.; ObstSander, U.; Wagner, B.; Kansy, M.; Diederich, F. A. ChemMedChem 2006, 1, 611. (g) Prchalová, E.; Štěpánek, O.; Smrček, S.; Kotora, M. Future Med. Chem. 2014, 6, 1201. (h) Swallow, S. Prog. Med. Chem. 2015, 54, 65. (i) García-Moreno, I. M.; de la Mata, M.; SánchezFernández, E. M.; Benito, J. M.; Díaz-Quintana, A.; Fustero, S.; Nanba, E.; Higaki, K.; Sánchez-Alcázar, J. A.; Fernández, J. M. G.; Mellet, C. O. J. Med. Chem. 2017, 60, 1829. (3) (a) Jeschke, P. ChemBioChem 2004, 5, 570. (b) Jeschke, P. Pest Manage. Sci. 2010, 66, 10. (c) Fujiwara, T.; O’Hagan, D. J. Fluorine Chem. 2014, 167, 16. (4) (a) Berger, R.; Resnati, G.; Metrangolo, P.; Weber, E.; Hulliger, J. Chem. Soc. Rev. 2011, 40, 3496. (b) Stuart, A. C.; Tumbleston, J. R.; Zhou, H.; Li, W.; Liu, S.; Ade, H.; You, W. J. Am. Chem. Soc. 2013, 135, 1806. (c) Brooks, A. F.; Topczewski, J. J.; Ichiishi, N.; Sanford, M. S.; Scott, P. J. H. Chem. Sci. 2014, 5, 4545. (d) Preshlock, S.; Tredwell, M.; Gouverneur, V. Chem. Rev. 2016, 116, 719. (5) (a) Kharasch, M. S.; Jensen, E. V.; Urry, W. H. Science 1945, 102, 128. (b) Kharasch, M. S.; Skell, P. S.; Fisher, P. J. Am. Chem. Soc. 1948, 70, 1055. (c) For reviews on ATRA, see: Kamigaito, M.; Ando, T.; Sawamoto, M. Chem. Rev. 2001, 101, 3689. (d) Pintauer, T.; Matyjaszewski, K. Chem. Soc. Rev. 2008, 37, 1087.
Scheme 4. Plausible Reaction Pathways
oxidatively quenched by the perfluoroalkyl halide (RfX) leading to a perfluoroalkyl radical and a halide anion. Addition of the perfluoroalkyl radical (Rf•) to the alkene generates radical A. From here, two reaction pathways are possible. On the first one, A is oxidized to give carbocationic intermediate B, which either directly or via organohalide C affords olefinic products 3 and 6 by deprotonation with base. Also the second pathway involves intermediate C, but it distinguished itself by formation of this product by a radical chain propagation process. The fact that C could indeed be a relevant intermediate was independently confirmed by treatment of preformed 4 (prepared by addition of 2a to 1a in water; see Table 1, entry 2) with Cs2CO3 (2 equiv) in DMAc (0.1 M), which gave 3a in 78% yield (E/Z = 5.8:1)17 after 48 h at room temperature. In summary, we developed a direct ATRE protocol for the synthesis substituted perfluoroalkenes from terminal olefins and C
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Kawashima, A.; Takemoto, Y.; Miyabe, H. J. Org. Chem. 2016, 81, 7217. (h) Yajima, T.; Ikegami, M. Eur. J. Org. Chem. 2017, 2017, 2126. (12) For synthetic utilization of perfluorolalkenes, see: (a) Dmowski, W. J. Fluorine Chem. 1985, 29, 287. (b) Ramachandran, P. V.; Jennings, M. P.; Brown, H. C. Org. Lett. 1999, 1, 1399. (c) Ramachandran, P. V.; Jennings, M. P. Org. Lett. 2001, 3, 3789. (d) Boydell, A. J.; Vinader, V.; Linclau, B. Angew. Chem., Int. Ed. 2004, 43, 5677. (e) Kang, J.-P.; Lu, J.-Y.; Li, Y.; Wang, Z.-X.; Mao, W.; Lu, J. RSC Adv. 2016, 6, 39387. (f) Billard, T. Chem. - Eur. J. 2006, 12, 974. (13) Meyer, D.; Vin, E.; Wyler, B.; Lapointe, G.; Renaud, P. Synlett 2016, 27, 745. (14) For alternative syntheses of perfluoroalkenes, see: (a) He, Z.; Luo, T.; Hu, M.; Cao, Y.; Hu, J. Angew. Chem., Int. Ed. 2012, 51, 3944. (b) Patra, T.; Deb, A.; Manna, S.; Sharma, U.; Maiti, D. Eur. J. Org. Chem. 2013, 2013, 5247. (c) Li, G.; Wang, T.; Fei, F.; Su, Y.-M.; Li, Y.; Lan, Q.; Wang, X.-S. Angew. Chem., Int. Ed. 2016, 55, 3491. (d) Lai, Y.L.; Lin, D.-Z.; Huang, J.-M. J. Org. Chem. 2017, 82, 597. (15) As kindly pointed out by a reviewer, the fluorescent lamp has a broad emission spectrum including UV A, which could initiate direct photochemistry leading to the observed formation of 3a. (16) Cernak, T.; Dykstra, K. D.; Tyagarajan, S.; Vachal, P.; Krska, S. W. Chem. Soc. Rev. 2016, 45, 546. (17) Under photocatalytic conditions, the E/Z ratio of 3a generated from 4 was found to be 4.2:1.
(6) For some selected examples of ATRA in perfluoroalkykations, see: (a) Wallentin, C.-J.; Nguyen, J. D.; Finkbeiner, P.; Stephenson, C. R. J. J. Am. Chem. Soc. 2012, 134, 8875. (b) Ni, C.; Hu, M.; Hu, J. Chem. Rev. 2015, 115, 765. (c) Tang, X.-J.; Dolbier, W. R., Jr. Angew. Chem., Int. Ed. 2015, 54, 4246. (d) Leifert, D.; Studer, A. Angew. Chem., Int. Ed. 2016, 55, 11660. (e) Ma, J.-J.; Yi, W.-B. Org. Biomol. Chem. 2017, 15, 4295 and references therein. (7) For perfluoroalkylations, see: (a) Bravo, A.; Bjorsvik, H.-R.; Fontana, F.; Liguori, L.; Mele, A.; Minisci, F. J. Org. Chem. 1997, 62, 7128. (b) Bazhin, D. N.; Gorbunova, T. I.; Zapevalov, A. Y.; Saloutin, V. I. Russ. J. Org. Chem. 2009, 45, 491. (c) Erdbrink, H.; Peuser, I.; Gerling, U. I. M.; Lentz, D.; Koksch, B.; Czekelius, C. Org. Biomol. Chem. 2012, 10, 8583. (d) Zhang, C.-P.; Chen, Q.-Y.; Guo, Y.; Xiao, J.C.; Gu, Y.-C. Chem. Soc. Rev. 2012, 41, 4536. (e) Xu, T.; Cheung, C. W.; Hu, X. Angew. Chem., Int. Ed. 2014, 53, 4910. (f) Zhong, S.; Hafner, A.; Hussal, C.; Nieger, M.; Bräse, S. RSC Adv. 2015, 5, 6255. (g) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97, 757. (h) Matsnev, A.; Noritake, S.; Nomura, Y.; Tokunaga, E.; Nakamura, S.; Shibata, N. Angew. Chem., Int. Ed. 2010, 49, 572. (i) Barata-Vallejo, S.; Postigo, A. J. Org. Chem. 2010, 75, 6141. (j) Takagi, T.; Kanamori, T. J. Fluorine Chem. 2011, 132, 427. (k) Postigo, A. Can. J. Chem. 2012, 90, 493. (l) Macé, Y.; Magnier, E. Eur. J. Org. Chem. 2012, 2012, 2479. (m) Egami, H.; Shimizu, R.; Kawamura, S.; Sodeoka, M. Angew. Chem., Int. Ed. 2013, 52, 4000. (n) Vázquez, A. J.; Nudelman, N. S. ARKIVOC 2015, No. v, 190. (8) For UV light promoted perfluoroalkylation, see: (a) Yoshida, M.; Kamigata, N.; Sawada, H.; Nakayama, M. J. Fluorine Chem. 1990, 49, 1. (b) Chen, Q.-Y.; Li, Z.-T. J. Chem. Soc., Perkin Trans. 1 1992, 1443. (c) Habib, M. H.; Mallouk, T. M. J. Fluorine Chem. 1991, 53, 53. (d) Qiu, Z.-M.; Burton, D. J. J. Org. Chem. 1995, 60, 3465. (e) Tsuchii, K.; Imura, M.; Kamada, N.; Hirao, T.; Ogawa, A. J. Org. Chem. 2004, 69, 6658. (f) Iizuka, M.; Yoshida, M. J. Fluorine Chem. 2009, 130, 926. (9) For some selected examples of photoredox catalysis, see: (a) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322. (b) Skubi, K. L.; Yoon, T. P. Nature 2014, 515, 45. (c) Xie, J.; Shi, S.; Zhang, T.; Mehrkens, N.; Rudolph, M.; Hashmi, A. S. K. Angew. Chem., Int. Ed. 2015, 54, 6046. (d) Ravelli, D.; Protti, S.; Fagnoni, M. Chem. Rev. 2016, 116, 9850. (e) Chen, J.-R.; Hu, X.-Q.; Lu, L.-Q.; Xiao, W.-J. Acc. Chem. Res. 2016, 49, 1911. (f) Nicholls, T. P.; Leonori, D.; Bissember, A. C. Nat. Prod. Rep. 2016, 33, 1248. (g) Douglas, J. J.; Sevrin, M. J.; Stephenson, C. R. J. Org. Process Res. Dev. 2016, 20, 1134. (h) Shaw, M. H.; Twilton, J.; MacMillan, D. W. C. J. Org. Chem. 2016, 81, 6898. (i) Mukherjee, S.; Maji, B.; TlahuextAca, A.; Glorius, F. J. Am. Chem. Soc. 2016, 138, 16200. (10) For examples of visible light promoted perfluoroalkylations, see: (a) Mizuta, S.; Verhoog, S.; Engle, K. M.; Khotavivattana, T.; O’Duill, M. O.; Wheelhouse, K.; Rassias, G.; Medebielle, M.; Gouverneur, V. J. Am. Chem. Soc. 2013, 135, 2505. (b) Yu, C.; Iqbal, N.; Park, S.; Cho, E. J. Chem. Commun. 2014, 50, 12884. (c) Iqbal, N.; Jung, J.; Park, S.; Cho, E. J. Angew. Chem., Int. Ed. 2014, 53, 539. (d) Lin, Q.-Y.; Xu, X.H.; Qing, F.-L. Org. Biomol. Chem. 2015, 13, 8740. (e) Wozniak, Ł.; Murphy, J. J.; Melchiorre, P. J. Am. Chem. Soc. 2015, 137, 5678. (f) Lin, Q.-Y.; Ran, Y.; Xu, X.-H.; Qing, F.-L. Org. Lett. 2016, 18, 2419. (g) Straathof, N. J. W.; Cramer, S. E.; Hessel, V.; Noël, T. Angew. Chem., Int. Ed. 2016, 55, 15549. (h) Rawner, T.; Knorn, M.; Lutsker, E.; Hossain, A.; Reiser, O. J. Org. Chem. 2016, 81, 7139. (i) Reiser, O. Acc. Chem. Res. 2016, 49, 1990. (j) Beniazza, R.; Atkinson, R.; Absalon, C.; Castet, F.; Denisov, S. A.; McClenaghan, N. D.; Lastécouères, D.; Vincent, J.-M. Adv. Synth. Catal. 2016, 358, 2949. (k) Sun, X.; Wang, W.; Li, Y.; Ma, J.; Yu, S. Org. Lett. 2016, 18, 4638. (l) Wang, Y.; Wang, J.; Li, G.-X.; He, G.; Chen, G. Org. Lett. 2017, 19, 1442. (11) For organic dyes in photoredox catalysis, see: (a) Neumann, M.; Füldner, S.; König, B.; Zeitler, K. Angew. Chem., Int. Ed. 2011, 50, 951. (b) Hari, D. P.; Kö nig, B. Chem. Commun. 2014, 50, 6688. (c) Fukuzumi, S.; Ohkubo, K. Org. Biomol. Chem. 2014, 12, 6059. (d) Nicewicz, D. A.; Nguyen, T. M. ACS Catal. 2014, 4, 355. (e) Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016, 116, 10075. (f) Pitre, S. P.; McTiernan, C. D.; Scaiano, J. C. ACS Omega 2016, 1, 66. (g) Yoshioka, E.; Kohtani, S.; Jichu, T.; Fukazawa, T.; Nagai, T.; D
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