Synthesis of Aromatic Sulfonamides through a Copper-Catalyzed

Letter Cite This: Org. Lett. 2018, 20, 1167−1170

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Synthesis of Aromatic Sulfonamides through a Copper-Catalyzed Coupling of Aryldiazonium Tetrafluoroborates, DABCO·(SO2)2, and N‑Chloroamines Feng Zhang,†,∥ Danqing Zheng,‡,∥ Lifang Lai,§ Jiang Cheng,§ Jiangtao Sun,§ and Jie Wu*,‡ †

College of Science, Hunan Agricultural University, Changsha 410128, China Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China § School of Petrochemical Engineering, and Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Changzhou University, Changzhou 213164, China ‡

S Supporting Information *

ABSTRACT: A copper-catalyzed aminosulfonylation of aryldiazonium tetrafluoroborates, DABCO·(SO2)2, and N-chloroamines is described. This coupling reaction provides an efficient and simple approach to a wide range of sulfonamides in moderate to good yields under mild conditions. Mechanistic investigation suggests that a radical process and transition-metal catalysis are merged in this tandem reaction. he medical importance of sulfonamides was first recognized in the 1930s, as the discovery and development of sulfonamide drugs made many bacterial infections curable and saved countless lives.1 Now, sulfonamides have significant applications in a wide range of pharmaceuticals, agrochemicals, and materials.2 Some top-selling drugs such as Sildenafil, Penoxsulam, Probenecid, and Sulfadiazine all feature the sulfonamide group (Figure 1).3 Sulfonamides are generally

T

and co-workers in 2010.8a A range of methods for the generation of sulfonamides and sulfones through transitionmetal catalysis or a radical process have been well developed, considering sulfur dioxide (SO2) is apparently an ideal choice to install a sulfonyl (−SO2−) moiety. However, in the approaches to sulfonamides, the N-nucleophiles were restricted to hydrazines and only N-aminosulfonamides could be obtained.7 Some successful methods for the synthesis of general sulfonamides utilizing the insertion of sulfur dioxide commonly conducted the sulfinate salts as the intermediates, and these methods also suffered from air-sensitive organometallic reagents, multiple steps, or expensive metal catalysts.7,8g,o The direct three-component coupling reaction of arylating reagents, sulfur dioxide, and amines is still rare. In the meantime, some other sulfur-containing starting materials have also been developed to introduce the sulfonyl group into sulfonamides. For instance, Buchwald and coworkers utilized phenyl chlorosulfate as the sulfonyl source and developed a palladium-catalyzed chlorosulfonylation of arylboronic acids for the synthesis of sulfonamides in 2013.4b Recently, Shi and co-workers applied diethylaminosulfur trifluoride (DAST) type reagents for the synthesis of sulfinamides and the corresponding sulfonamides could be achieved through oxidation.10 However, these reagents also required cumbersome procedures for their own preparation and suffered from low atomic economy, and sulfur dioxide still seems to be the best choice. Considering the significant importance of sulfonamides, the core task in this field is still the development of simple and efficient methods to achieve sulfonamides from sulfur dioxide. Herein, we report a copper-catalyzed reductive coupling of

Figure 1. Examples of top-selling drugs.

prepared from the reaction of sulfonyl chlorides with the corresponding amines.4 However, the methods for the synthesis of sulfonyl chlorides (such as electrophilic aromatic substitution with chlorosulfonic acid, oxidative chlorination of organosulfurs) commonly suffer from harsh reaction conditions and scope limitations and usually require hazardous and polluting chlorinating agents or oxidants.5,6 Therefore, the development of simple and efficient methods to construct sulfonamides is still in high demand. Notably, the insertion of sulfur dioxide contributes much to recent advances in the synthesis of sulfonyl-containing compounds7−9 including sulfonamides and sulfones, pioneered by a palladium-catalyzed aminosulfonylation reported by Willis © 2018 American Chemical Society

Received: January 9, 2018 Published: January 26, 2018 1167

DOI: 10.1021/acs.orglett.8b00093 Org. Lett. 2018, 20, 1167−1170

Letter

Organic Letters aryldiazonium tetrafluoroborates, DABCO·(SO2)2, and Nchloroamines for the synthesis of sulfonamides. In our recent reports, we have demonstrated that aryldiazonium salts could directly react with DABCO·(SO2)2 to produce sulfonyl radicals.11 This discovery motivated us to reconsider the three-component reaction of arylating reagents, sulfur dioxide, and amines. Since the formation of sulfonyl radicals was easy, we suspected that the class of amino reagents might be the key issue to success. We envisioned that an electrophilic amine could participate in this transformation through a reductive coupling. It was also known that Nchloroamine was a powerful and easily available electrophilic amine source, and it had higher stability compared to its N−Br or N−I analogues.12 The initial investigation was carried out with the reaction of phenyldiazonium tetrafluoroborate 1a, DABCO·(SO2)2, and Nchloromorpholine 2a in 1,2-dichloroethane (DCE) at room temperature, but only a trace amount of desired product 3a was observed by TLC (Table 1, entry 1). Interestingly, when the

9), probably because DABCO·(SO2)2 acted as not only a sulfonyl source but also a reductant. The utilization of 2.0 equiv of DABCO·(SO2)2 did not improve the efficiency of the reaction (Table 1, entry 10). Solvents were next screened, but no better result was obtained (Table 1, entries 11−14). The yield was decreased to 30% when the reaction was carried out at a lower temperature of 60 °C (Table 1, entry 15). A similar yield of 55% was obtained when the reaction was performed at 100 °C in a sealed tube (Table 1, entry 16). Only a 40% yield of sulfonamide 3a was produced when N-bromomorpholine was used instead of N-chloromorpholine 2a (Table 1, entry 17). As we observed that the reaction system became dark while the reaction went on, we suspected the cycle of the catalyst was not efficient enough. Thus, iPrOH was added to the reaction system as a coreductant. Pleasingly, the yield was improved to 83% when 1.0 equiv of iPrOH was added (Table 1, entry 18). Increasing the amount of iPrOH resulted a similar yield (Table 1, entry 19). With the optimized reaction conditions, we next surveyed the scope of this aminosulfonylation reaction. A number of sulfonamides were obtained in moderate to good yields, as shown in Scheme 1. Generally, electron-rich and electron-

Table 1. Initial Studies for the Reaction of Phenyldiazonium Tetrafluoroborate 1a, DABCO·(SO2)2, and 4Chloromorpholine 2aa

Scheme 1. Scope Investigation for the Reaction of Aryldiazonium Tetrafluoroborates 1, DABCO·(SO2)2, and N-Chloroamines 2 entry

[Cu]

temp (°C)

solvent

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17c 18d 19e

− − CuCl Cu(OAc)2 CuBr2 CuOAc Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2

25 80 80 80 80 80 80 80 80 80 80 80 80 80 60 100 80 80 80

DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE 1,4-dioxane DMF toluene CH3CN DCE DCE DCE DCE DCE

DABSO 1.5 1.5 1.5 1.5 1.5 1.5 1.5 0.7 1.0 2.0 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5

equiv equiv equiv equiv equiv equiv equiv equiv equiv equiv equiv equiv equiv equiv equiv equiv equiv equiv equiv

yield (%)b trace 12 31 37 32 38 53 7 22 47 34 trace 11 24 30 55 40 83 81

a

Reaction conditions: copper catalyst (0.01 mmol), phenyldiazonium tetrafluoroborate 1a (0.2 mmol), DABCO·(SO2)2, N-chloromorpholine 2a (0.24 mmol), solvent (2.0 mL), under N2 protection, 30 min. b Isolated yield based on phenyldiazonium tetrafluoroborate 1a. cNBromomorpholine was used instead of N-chloromorpholine 2a. di PrOH (0.2 mmol) was used as the additive. eiPrOH (0.4 mmol) was used.

deficient aryldiazonium salts were all compatible under the conditions. Common functional groups including alkyl, ether, halo, ester, and even a nitro group were all tolerated in this transformation. The substrates bearing ortho-substitution or polysubstitution could also react well to provide the desired sulfonamides, albeit in a lower yield. Heteroaryl substrates were suitable as well, leading to the corresponding products 3n and 3o in 40% and 31% yields. A range of N-chloroamines 2 prepared from secondary amines was explored subsequently, and the reactions proceeded smoothly to generate the desired products.

reaction was conducted at a higher temperature of 80 °C, the desired sulfonamide 3a could be isolated in 12% yield (Table 1, entry 2). Inspired by the copper-catalyzed amination reactions,12e we next applied a series of copper catalysts to this reaction (Table 1, entries 3−7). To our delight, the yield was increased significantly to 53% when Cu(OTf)2 was used as the catalyst (Table 1, entry 7). Reducing the amount of DABCO·(SO2)2 led to much lower yields (Table 1, entries 8− 1168

DOI: 10.1021/acs.orglett.8b00093 Org. Lett. 2018, 20, 1167−1170

Letter

Organic Letters While N-chloroamines could be easily generated from amines, a more convenient one-pot two-step procedure is operative. The process using morpholine as starting material via the in situ chlorination led to the product 3a in a slightly lower yield of 73% (Scheme 2). Piperidine and N-methyl benzyl-

chloride was used instead of phenyldiazonium tetrafluoroborate 1a and DABCO·(SO2)2 in this reaction, no desired sulfonamide 3a was observed. This result indicated that sufonyl chloride might not be involved as the intermediate. We next performed this reaction by using N-benzyl-N-chloropent-4-en-1-amine as the substrate. It was found that no cyclized product was detected, and only the normal product 10 was obtained in 53% yield. This performance suggested the absence of an aminyl radical species in the amination process. We became interested in the initiation of this reaction, since the single electron transfer (SET) between arydiazonium salt with Cu(I) might give rise to an aryl radical easily (see the wellknown Sandmeyer type reaction13). Initially, experiments between Cu(II) and DABCO·(SO2)2 were performed. We observed that DABCO·(SO2)2 could reduce Cu(II) to Cu(I) very quickly even at room temperature (simply judged by the colors; details are given in the Supporting Information). To address the point further, cyclic voltammetry for DABCO· (SO2)2 was tested (Figure 2) and showed reversible oxidation

Scheme 2. One-Pot Two-Step Synthesis of Sulfonamide

amine could be also applied in the reaction of 4-methylphenyldiazonium tetrafluoroborate 1b and DABCO·(SO2)2. However, only a trace amount of the desired sulfonamide could be observed when a primary amine such as n-butylamine was applied. Subsequently, some experiments were carried out to gain more insights into the mechanism (Scheme 3). The addition of Scheme 3. Investigation of Mechanism Figure 2. Cyclic voltammogram of DABCO·(SO2)2.

at −0.65 V vs SCE, indicating that its reducibility was much stronger than Cu(I). These outcomes suggested the copper catalyst might not be involved in the formation of sulfonyl radicals. Although the exact mechanism for this reaction remains obscure, a possible mechanism is proposed based on the above observations and previous reports (Scheme 4).11 We reasoned that complex A would be formed first through the electrostatic interaction between aryldiazonium cation 1 and DABCO· (SO2)2. The subsequent homolytic cleavage of the N−S bond and a single electron transfer would occur to generate the tertiary amine radical cation B, SO2, and aryl radical C. The aryl Scheme 4. A Plausible Mechanism

2.0 equiv of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) terminated the standard reaction, and the milder radical scavenger of 1,1-diphenylethylene 5 captured two intermediates successfully leading to ethene-1,1,2-triyltribenzene 6 and (2(phenylsulfonyl)ethene-1,1-diyl)dibenzene 7 in 9% and 45% yields. These outcomes suggested a radical process and the existence of an aryl radical and a sulfonyl radical, which were similar as in the previous reports.11 When phenylsulfonyl 1169

DOI: 10.1021/acs.orglett.8b00093 Org. Lett. 2018, 20, 1167−1170

Letter

Organic Letters

N.; Lalezari, N. S.; Niloofari, G.; Golgolab, H. J. Med. Chem. 1969, 12, 696. (4) (a) Hamada, T.; Yonemitsu, O. Synthesis 1986, 1986, 852. (b) DeBergh, J. R.; Niljianskul, N.; Buchwald, S. L. J. Am. Chem. Soc. 2013, 135, 10638. (5) (a) Bahrami, K.; Khodaei, M. M.; Khaledian, D. Tetrahedron Lett. 2012, 53, 354. (b) Prakash, G. K. S.; Mathew, T.; Olah, G. A. J. Org. Chem. 2007, 72, 5847. (c) Wright, S. W.; Hallstrom, K. N. J. Org. Chem. 2006, 71, 1080. (6) (a) Percec, V.; Bera, T. K.; De, B. B.; Sanai, Y.; Smith, J.; Holerca, M. N.; Barboiu, B.; Grubbs, B. B. B.; Fréchet, J. M. J. J. Org. Chem. 2001, 66, 2104. (b) Watson, R. J.; Batty, D.; Baxter, A. D.; Hannah, D. R.; Owen, D. A.; Montana, J. G. Tetrahedron Lett. 2002, 43, 683. (7) For reviews: (a) Liu, G.; Fan, C.; Wu, J. Org. Biomol. Chem. 2015, 13, 1592. (b) Bisseret, P.; Blanchard, N. Org. Biomol. Chem. 2013, 11, 5393. (c) Deeming, A. S.; Emmett, E. J.; Richards-Taylor, C. S.; Willis, M. C. Synthesis 2014, 46, 2701. (d) Emmett, E. J.; Willis, M. C. Asian J. Org. Chem. 2015, 4, 602. (e) Zheng, D.; Wu, J. Sulfur Dioxide Insertion Reactions for Organic Synthesis; Nature Springer: Berlin, 2017. (f) Qiu, G.; Zhou, K.; Gao, L.; Wu, J. Org. Chem. Front. 2018, 5, DOI: 10.1039/C7QO01073G. (8) For selected examples, see: (a) Nguyen, B.; Emmett, E. J.; Willis, M. C. J. Am. Chem. Soc. 2010, 132, 16372. (b) Wang, Y.; Du, B.; Sha, W.; Han, J.; Pan, Y. Org. Chem. Front. 2017, 4, 1313. (c) Liu, N.-W.; Liang, S.; Manolikakes, G. Adv. Synth. Catal. 2017, 359, 1308. (d) Sheng, J.; Li, Y.; Qiu, G. Org. Chem. Front. 2017, 4, 95. (e) Li, W.; Beller, M.; Wu, X.-F. Chem. Commun. 2014, 50, 9513. (f) Wang, X.; Xue, L.; Wang, Z. Org. Lett. 2014, 16, 4056. (g) Deeming, A. S.; Russell, C. J.; Willis, M. C. Angew. Chem., Int. Ed. 2015, 54, 1168. (h) Chen, C. C.; Waser, J. Org. Lett. 2015, 17, 736. (i) Wang, M.; Chen, S.; Jiang, X. Org. Lett. 2017, 19, 4916. (j) Rocke, B. N.; Bahnck, K. B.; Herr, M.; Lavergne, S.; Mascitti, V.; Perreault, C.; Polivkova, J.; Shavnya, A. Org. Lett. 2014, 16, 154. (k) Liu, F.; Wang, J.-Y.; Zhou, P.; Li, G.; Hao, W.-J.; Tu, S.-J.; Jiang, B. Angew. Chem., Int. Ed. 2017, 56, 15570. (l) Wang, H.; Sun, S.; Cheng, J. Org. Lett. 2017, 19, 5844. (m) Johnson, M. W.; Bagley, S. W.; Mankad, N. P.; Bergman, R. G.; Mascitti, V.; Toste, F. D. Angew. Chem., Int. Ed. 2014, 53, 4404. (n) Shavnya, A.; Hesp, K. D.; Mascitti, V.; Smith, A. C. Angew. Chem., Int. Ed. 2015, 54, 13571. (o) Shavnya, A.; Coffey, S. B.; Smith, A. C.; Mascitti, V. Org. Lett. 2013, 15, 6226. (p) Zhang, W.; Luo, M. Chem. Commun. 2016, 52, 2980. (q) von Wolff, N.; Char, J.; Frogneux, X.; Cantat, T. Angew. Chem., Int. Ed. 2017, 56, 5616. (r) Konishi, H.; Tanaka, H.; Manabe, K. Org. Lett. 2017, 19, 1578. (s) Pelzer, G.; Keim, W. J. Mol. Catal. A: Chem. 1999, 139, 235. (9) For selected examples, see: (a) Zheng, D.; An, Y.; Li, Z.; Wu, J. Angew. Chem., Int. Ed. 2014, 53, 2451. (b) Zheng, D.; Mao, R.; Li, Z.; Wu, J. Org. Chem. Front. 2016, 3, 359. (c) Zheng, D.; Chen, M.; Yao, L.; Wu, J. Org. Chem. Front. 2016, 3, 985. (d) Zhou, K.; Xia, H.; Wu, J. Org. Chem. Front. 2017, 4, 1121. (e) Yu, J.; Mao, R.; Wang, Q.; Wu, J. Org. Chem. Front. 2017, 4, 617. (f) Liu, T.; Zheng, D.; Wu, J. Org. Chem. Front. 2017, 4, 1079. (g) Zhang, J.; An, Y.; Wu, J. Chem. - Eur. J. 2017, 23, 9477. (h) Xiang, Y.; Kuang, Y.; Wu, J. Chem. - Eur. J. 2017, 23, 6996. (10) Wang, Q.; Tang, X.-Y.; Shi, M. Angew. Chem., Int. Ed. 2016, 55, 10811. (11) Zheng, D.; Yu, J.; Wu, J. Angew. Chem., Int. Ed. 2016, 55, 11925. (12) (a) Chen, J.-R.; Hu, X.-Q.; Lu, L.-Q.; Xiao, W.-J. Chem. Soc. Rev. 2016, 45, 2044. (b) Kawano, T.; Hirano, K.; Satoh, T.; Miura, M. J. Am. Chem. Soc. 2010, 132, 6900. (c) Miura, T.; Morimoto, M.; Murakami, M. Org. Lett. 2012, 14, 5214. (d) Nishikawa, M.; Inaba, Y.; Furukawa, M. Chem. Pharm. Bull. 1983, 31, 1374. (e) Zhu, H.; Shen, Y.; Deng, Q.; Tu, T. Chem. Commun. 2015, 51, 16573. (13) Meerwein, H.; Dittmar, G.; Göllner, R.; Hafner, K.; Mensch, F.; Steinfort, O. Chem. Ber. 1957, 90, 841.

radical C would react with SO2 leading to the sulfonyl radical D. On the other hand, DABCO·(SO2)2 would reduce Cu(II) to Cu(I) with the assistance of iPrOH. Subsequent oxidative addition gave rise to Cu(III) intermediate E, which would react with the sulfonyl radical to afford a Cu(IV) intemediate F. Finally, reductive elimination of intemediate F would provide the desired product and regenerate the Cu(II) catalyst. In conclusion, we have developed a simple and general approach for the synthesis of sulfonamides via a coppercatalyzed three-component reaction of aryldiazonium tetrafluoroborates, DABCO·(SO2)2, and N-chloroamines. This coupling reaction utilizes N-chloroamines as the amino source in sulfur dioxide insertion reactions, which takes place under mild conditions and shows broad substrate scope. Moreover, amines can be used instead of N-chloroamines via in situ chlorination in a one-pot, two-step process. A possible mechanism involving a radical process and transition-metal catalysis is proposed. This reaction also shows that the merger of metal catalysis and a radical process is a powerful strategy in this field.

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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.8b00093. Experimental procedures, characterization data, copies of 1 H and 13C NMR of products (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Jie Wu: 0000-0002-0967-6360 Author Contributions ∥

F.Z. and D.Z. contributed equally.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support from the National Natural Science Foundation of China (No. 21302051) and “1515” academic leader team program of Hunan Agricultural University is gratefully acknowledged. We sincerely thank Dr. Han Wang and Mr. Xianyin Ma (Fudan University) for their kind help in the cyclic voltammetry testing.

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REFERENCES

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DOI: 10.1021/acs.orglett.8b00093 Org. Lett. 2018, 20, 1167−1170