Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Construction of Unsymmetrical Triphenylenes from Electron-Rich Biphenyls and Diaryliodonium Salts via Copper-Catalyzed Multiple C−H Arylation Yang Wu,† Wen Zhang,† Qiong Peng, Chuan-Kun Ran, Bi-Qin Wang, Ping Hu, Ke-Qing Zhao, Chun Feng,* and Shi-Kai Xiang* College of Chemistry and Materials Science, Sichuan Normal University, Chengdu 610068, China S Supporting Information *
ABSTRACT: An efficient protocol to synthesize unsymmetrical triphenylenes from electron-rich biphenyls and diaryliodonium salts via Cu catalysis was developed. A variety of unsymmetrical triphenylenes with diversified functional groups were synthesized according to this method. This transformation went through multiple direct C−H arylations from easily produced starting materials with high step-economy. The gram-scale synthesis of triphenylenes and their facile transformation into diverse functional organic molecules were illustrated.
M
yls and iodobenzenes via palladium-catalyzed dual C−H activation.10c Recently, Han and Wang presented a new synthetic approach of triphenylenes by combination of bromoarenes and diaryliodonium salts via Pd catalysis.10d In addition, Park and Hong developed another new synthetic approach of substituted triphenylenes with directing strategy from N-pivaloylanilines and cyclic diaryliodonium salts via Pdcatalyzed multiple C−H bond activation.10e All of the abovementioned methods showed their elegance and powerfully promoted the efficiency of syntheses of triphenylenes. However, it is desirable to develop some facile methods for the synthesis of highly substituted triphenylenes from readily available substrates. In particular, the produced polysubstituted triphenylenes can be directly used as functional organic molecules or key synthons for constructing complex and diverse functional organic molecules. The choice to use cheap catalysts to take the place of Pd catalysts in the transformation to reduce the cost of the process was also desirable. In this work, we developed a novel and efficient single-step approach to produce polysubstituted triphenylenes from easily available electron-rich biphenyls and diaryliodonium salts via coppercatalyzed multiple C−H arylation. Many produced triphenylenes can be further transformed into diverse functional organic molecules (Scheme 1). We began to investigate the reaction by using 3,3′,4,4′tetramethoxybiphenyl 1a and 3,4-dibromophenyl(mesityl)iodonium triflate 2a as the model substrates (Table 1). Initially, the reaction of 1a with 3.0 equiv of 2a was carried out using Cu(OTf)2 as a catalyst and DCE as the solvent under N2. To our delight, the target product 3a was isolated in 63% yield
uch attention has been paid to polycyclic aromatic hydrocarbons (PAHs) due to their potential applications in optoelectronic materials such as discotic liquid crystals, organic light-emitting diodes, and organic photovoltaic cells.1 Among various kinds of PAHs, triphenylenes are particularly important compounds.2 Development of efficient methods for synthesis of triphenylenes remains of great significance in the fields of both chemistry and materials, and many chemists have made great achievements in this important field.3 For symmetrically substituted triphenylenes, oxidative trimerization of arenes (mainly catechol derivatives)4 and trimerization of arynes5 are selected preferentially. For the simple unsymmetrically substituted triphenylenes, oxidative cyclization from electron-rich biphenyls (mainly 3,3′,4,4′-tetraalkoxybiphenyls) and electron-rich arenes (mainly catechol derivatives) could be employed; however, the substrate scope was rather limited.4c,d,6 For the complicated unsymmetrically polysubstituted triphenylenes, cyclization of o-terphenyls was considered as a conventional method, while synthesis of the o-terphenyls commonly required a tedious multistep process.7 Therefore, a new synthetic strategy to develop facile access to complicated diversified triphenylenes is highly appealing.8 Direct C−H transformation represents a more environmentally friendly, atom- and step-economic strategy by avoiding circuitous prefunctionalizations of starting materials,9 which has been successfully utilized to the synthesis of triphenylene derivatives.10 In 2013, Nishihara and co-workers reported an efficient synthesis of functionalized triphenylenes by a palladium-catalyzed annulation of o-iodobiphenyls with obromobenzyl alcohols involving C−C and C−H bond cleavages.10a Subsequently, a detailed study concerning this transformation was reported by them in 2015.10b Another beautiful example has been reported by Zhang and co-workers to produce triphenylene and its derivatives from o-iodobiphen© XXXX American Chemical Society
Received: February 21, 2018
A
DOI: 10.1021/acs.orglett.8b00622 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Scheme 2. Substrate Scope of Diaryliodonium Saltsa
Scheme 1. Construction of Unsymmetrical Triphenylenes from Electron-Rich Biphenyls and Diaryliodonium Salts
Table 1. Optimization of Reaction Conditionsa
entry
2a (equiv)
catalyst (mol %)
T (°C)
yield (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15b
3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 2.5 2.0 3.0 3.0 3.0
Cu(OTf)2 (20) CuCl2 (20) CuBr2 (20) CuOTf (20) CuI (20) CuBr (20) CuCl (20) none CuCl (10) CuCl (5) CuCl (20) CuCl (20) CuCl (20) CuCl (20) CuCl (20)
90 90 90 90 90 90 90 90 90 90 90 90 80 70 90
63 50 49 76 65 80 84 0 77 40 64 41 81 60 64
a Reaction conditions: 1a (0.15 mmol), 2a (0.45 mmol), catalyst (0.03 mmol), dried DCE (3.0 mL), 90 °C, 24 h, under N2. The yields of 3 are of isolated products. b4.0 equiv of diaryliodonium salts was used. c The reaction was carried out at 80 °C. dCu(OTf)2 was used as a catalyst. eThe reaction was carried out for 48 h. fAryl(mesityl)iodonium tetrafluoroborates were used.
a
Reaction conditions: 1a (0.15 mmol), 2a (see table), catalyst (see table), dried DCE (3.0 mL), t (see table), 24 h, under N2. The yields of 3a are of isolated products. bDCE (not dried) was used.
(Table 1, entry 1). Screening showed that various copper catalysts effectively gave the product 3a, and CuCl was superior to all other tested copper salts (Table 1, entries 1−7). No desired product 3a was observed in the absence of a copper catalyst (Table 1, entry 8), and the lower loading of catalyst led to a lower yield of 3a (Table 1, entries 9 and 10). The results showed the key role of the Cu catalyst. When the amount of 2a was reduced, the yield significantly decreased (Table 1, entries 11 and 12). An attempt to reduce the temperature to 80 °C resulted in a slightly decreased yield of 3a (Table 1, entry 13). However, while the temperature was lowered to 70 °C, the yield of 3a decreased to 60% (Table 1, entry 14). In addition, the yield decreased to 64%, provided that DCE was not dried (Table 1, entry 15). With the optimized conditions in hand, we next investigated different diaryliodonium salts 2. As shown in Scheme 2, a variety of aryl(mesityl)iodonium salts with both electrondonating groups and electron-withdrawing groups underwent this transformation in moderate to good yields (44−84%). Aryl(mesityl)iodonium salts with two halogen substituents, such as Br, Cl, or F, were workable, and the corresponding products were obtained in good yields of 84%, 62%, and 74%, respectively (3a, 3b, and 3c). Aryl(mesityl)iodonium salts with
one halogen substituent were also good substrates for this transformation (3d, 3e, and 3f). The tolerance of the halogens provided great potential to produce more complex structures through cross coupling. Aryl(mesityl)iodonium salts bearing electron-donating groups, such as methyl and methoxy substituents, were also compatible for obtaining the desired products (3g, 3h, and 3i). Obviously, phenyl(mesityl)iodonium triflate 2j showed credible reactivity, and 2,3,6,7-tetramethoxytriphenylene 3j was afforded in good yield. To our delight, aryl(mesityl)iodonium salt 2k bearing a COOEt group at the para-position gave the product 3k in an acceptible yield. In addition, aryl(mesityl)iodonium salt 2l containing methoxy and COOEt groups at the 3- and 4-positions successfully gave the product 3l. Notably, the COOEt group was hydrolyzed to a COOH group under the reaction conditions. To investigate the substrate scope of biphenyls, (3,4dimethoxyphenyl)(mesityl)iodonium triflate 2m was selected as the partner (Scheme 3). The results indicated that a variety of unsymmetrical biphenyls bearing mixed substituents with alkoxys, alkyls, and/or halogens could undergo this transformation, and the desired unsymmetrical triphenylene B
DOI: 10.1021/acs.orglett.8b00622 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Scheme 3. Substrate Scope of Substituted Biphenylsa
Scheme 4. Gram-Scale Synthesis of the Triphenylene 3a
Scheme 5. Applications to the Synthesis of Functional Molecules
a
Reaction conditions: 1a (0.15 mmol), 2a (0.45 mmol), catalyst (0.03 mmol), dry DCE (3.0 mL), 90 °C, 24 h, under N2. The yields of 3 are of isolated products. b4.0 equiv of diaryliodonium salts was used. cThe reaction was carried out at 100 °C. dThe reaction was carried out for 48 h.
derivatives 3 were isolated in acceptable to good yields (40− 75%). For example, biphenyls containing mixed substituents with alkoxys and alkyls reacted with 2m to obtain the products 3g, 3h, 3m, and 3i, respectively. Biphenyls containing mixed substituents with alkoxys and halogens also successfully gave the corresponding products 3e and 3f in yields of 50% and 58%, respectively. 3,4-Dimethoxy-1,1′-biphenyl provided 3j in 48% yield. To our delight, although 3,3′,4,4′,5-pentamethoxy1,1′-biphenyl could not react, reaction with 2,3,3′,4,4′pentamethoxy-1,1′-biphenyl proceeded smoothly with 2m to produce the same desired product 3n in 40% yield. It is regretful that biphenyl and electron-deficient biphenyls could not undergo this reaction to obtain the corresponding products. Scalable synthesis of compounds is very important in the field of material chemistry. Therefore, scalability of this transformation was also investigated. When 4 mmol of 1a was used to react with 2a, 1.63 g of 3a was obtained in a high yield of 81%, indicating the good scalability of this transformation (Scheme 4). In order to explore the application of this reaction in organic functional materials, the compounds 3a and 3b were employed to transform into functional organic molecules 6, 4b, and 4c (Scheme 5). Compound 3a underwent the demethylation and subsequent etherification to generate the intermediate product 4a in a total yield of 51% for two steps. Then, the intermediate 4a underwent the amination and subsequent hydrolysis to afford intermediate 5 in a total yield of 44%. Intermediate 5 was indeed a key synthon for the synthesis of liquid-crystalline and fluorescent molecule 6.11a Furthermore, compound 3b could
also be converted to liquid-crystalline and semiconducting molecules 4b and 4c11b by the demethylation and subsequent etherification in total yields of 50% and 52% respectively. To date, this is one of the most efficient ways to produce such functional molecules, showing the potential broad applications of this transformation presented in the article. Some control experiments have been carried out to understand the reaction mechanism (see Scheme SI-1). On the basis of the experimental results and previous reports, a possible single-electron-transfer mechanism is illustrated (see Scheme SI-2). In addition, synthesis of unsymmetrical triphenylenes with three differently substituted benzene rings and a more complicated polycyclic aromatic hydrocarbon was also explored (see Schemes SI-3 and SI-4). In summary, we have developed an efficient approach to synthesize polysubstituted unsymmetrical triphenylenes from easily available electron-rich biphenyls and diaryliodonium salts. A variety of unsymmetrical triphenylene derivatives could be synthesized according to this protocol. This approach could be scaled up, and some products could be applied to the synthesis of many functional organic molecules. Preliminary mechanistic studies indicated direct multiple C−H arylation were involved with/without Cu catalysts in this transformation, making the protocol more step-economic. Further studies on efficient synthesis for polycyclic aromatic hydrocarbons by this chemistry are now underway in our laboratory. C
DOI: 10.1021/acs.orglett.8b00622 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b00622. Experimental procedures, spectral and analytical data, and NMR spectra of all compounds (PDF)
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AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. ORCID
Shi-Kai Xiang: 0000-0002-7293-8546 Author Contributions †
Y.W. and W.Z. contributed equally to this work.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We are grateful for the financial support from the National Natural Science Foundation of China (Nos. 21202109 and 21772135) and Sichuan Normal University (Nos. 16ZP10, ZZYQ2017004, DJGX2017004, and DJGX2017005).
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DOI: 10.1021/acs.orglett.8b00622 Org. Lett. XXXX, XXX, XXX−XXX
