Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2016; 27(06): 868-875
DOI: 10.1055/s-0035-1561335
DOI: 10.1055/s-0035-1561335
letter
Copper-Catalyzed Regioselective C–H Iodination of Aromatic Carboxamides
Further Information
Publication History
Received: 08 October 2015
Accepted after revision: 29 December 2015
Publication Date:
26 January 2016 (online)
![](https://www.thieme-connect.de/media/synlett/201606/lookinside/thumbnails/st-2015-w0803-l_10-1055_s-0035-1561335-1.jpg)
Abstract
A concise and efficient copper-catalyzed C–H iodination of 8-aminoquinoline-based aromatic carboxamides was reported. The reaction has the broad substrate scope and shows moderate to high yields, also offers other attractive advantages including simplicity of operation, compatibility with heteroarenes, and the use of low-cost copper catalyst. The new approach was further applied to cyanation of N-(quinolin-8-yl)benzamide, offering a potentially attractive alternative to the synthesis of aromatic nitriles.
Key words
aryl halide - aromatic carboxamides - C–H halogenation - copper catalyst - heteroarenes - regioselective iodinationSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561335.
- Supporting Information
-
References and Notes
- 1a Bergman RG. Nature (London, U.K.) 2007; 446: 391
- 1b Wencel-Delord J, Glorius F. Nat. Chem. 2013; 5: 369
- 1c Ackermann L. Chem. Rev. 2011; 111: 1315
-
1d Engle KM, Mei T.-S, Wasa M, Yu J.-Q. Acc. Chem. Res. 2012; 45: 788
- 1e Li B.-J, Shi Z.-J. Chem. Soc. Rev. 2012; 41: 5588
- 2a Hartwig JF. Nature (London, U.K.) 2008; 455: 314
- 2b Daugulis O, Do H.-Q, Shabashov D. Acc. Chem. Res. 2009; 42: 1074
- 2c Chen X, Engle KM, Wang D.-H, Yu J.-Q. Angew. Chem. Int. Ed. 2009; 48: 5094
- 2d Yoo EJ, Ma S, Mei T.-S, Chan KS. L, Yu J.-Q. J. Am. Chem. Soc. 2011; 133: 7652
- 2e Mu X, Wu T, Wang H, Guo Y, Liu G. J. Am. Chem. Soc. 2012; 134: 878
- 2f Shi Z, Suri M, Glorius F. Angew. Chem. Int. Ed. 2013; 52: 4892
- 2g Yan J.-X, Li H, Liu X.-W, Shi J.-L, Wang X, Shi Z.-J. Angew. Chem. Int. Ed. 2014; 53: 4945
- 3a Dick AR, Hull KL, Sanford MS. J. Am. Chem. Soc. 2004; 126: 2300
- 3b Wan XB, Ma ZX, Li BJ, Zhang KY, Cao SK, Zhang SW, Shi ZJ. J. Am. Chem. Soc. 2006; 128: 7416
- 3c Zhao XD, Dimitrijević E, Dong VM. J. Am. Chem. Soc. 2009; 131: 3466
-
3d Wang X.-C, Hu Y, Bonacorsi S, Hong Y, Burrell R, Yu J.-Q. J. Am. Chem. Soc. 2013; 135: 10326
- 3e Chu L, Wang X.-C, Moore CE, Rheingold AL, Yu J.-Q. J. Am. Chem. Soc. 2013; 135: 16344
- 3f Moyano A, Rosol M, Moreno RM, Lopez C, Maestro MA. Angew. Chem. Int. Ed. 2005; 44: 1865
- 3g Mei T.-S, Giri R, Maugel N, Yu J.-Q. Angew. Chem. Int. Ed. 2008; 47: 5215
- 3h Sun X, Sun Y, Zhang C, Rao Y. Chem. Commun. 2014; 50: 1262
- 3i Du B, Jiang X, Sun P. J. Org. Chem. 2013; 78: 2786
- 3j Kalyani D, Dick AR, Anani WQ, Sanford MS. Org. Lett. 2006; 8: 2523
- 3k Song B, Zheng X, Mo J, Xu B. Adv. Synth. Catal. 2010; 352: 329
- 4a Silverman GS, Rakita PE. Handbook of Grignard Reagents. Marcel Dekker; New York: 1996
- 4b Nicolaou KC, Bulger PG, Sarlah D. Angew. Chem. Int. Ed. 2005; 44: 4442
- 4c Hassan J, Vignon M, Gozzi C, Schulz E, Lemaire M. Chem. Rev. 2002; 102: 1359
- 5a Beak P, Snieckus V. Acc. Chem. Res. 1982; 15: 306
-
5b Snieckus V. Chem. Rev. 1990; 90: 879
- 5c Gilman H, Dietrich JJ. J. Am. Chem. Soc. 1957; 79: 1439
- 5d Merkushev EB. Synthesis 1988; 923
- 6 Chen X, Hao X.-S, Goodhue CE, Yu J.-Q. J. Am. Chem. Soc. 2006; 128: 6790
- 7 Yang L, Lu Z, Stahl SS. Chem. Commun. 2009; 42: 6460
- 8 Yao B, Wang ZL, Zhang H, Wang DX, Zhao LM, Wang X. J. Org. Chem. 2012; 77: 3336
- 9 Truong T, Klimovica K, Daugulis O. J. Am. Chem. Soc. 2013; 135: 9342
- 10a Tran LD, Popov I, Daugulis O. J. Am. Chem. Soc. 2012; 134: 18237
- 10b Suess AM, Ertem MZ, Cramer CJ, Stahl SS. J. Am. Chem. Soc. 2013; 135: 9797
- 10c Shang M, Sun S.-Z, Dai H.-X, Yu J.-Q. J. Am. Chem. Soc. 2014; 136: 3354
- 10d Zhang Q, Chen K, Rao W.-H, Zhang Y.-J, Chen F.-J, Shi B.-F. Angew. Chem. Int. Ed. 2013; 52: 13588
- 10e Wang Z, Ni J.-Z, Kuninobu Y, Kanai M. Angew. Chem. Int. Ed. 2014; 53: 3496
- 10f Wu X, Zhao Y, Zhang G, Ge H. Angew. Chem. Int. Ed. 2014; 53: 3706
- 10g Li X, Liu Y.-H, Gu W.-J, Li B, Chen F.-J, Shi B.-F. Org. Lett. 2014; 16: 3904
- 10h Li Q, Zhang S.-Y, He G, Ai Z, Nack WA, Chen G. Org. Lett. 2014; 16: 1764
- 10i Urones B, Martínez AM, Rodríguez N, Arrayás RG, Carretero JC. Chem. Commun. 2013; 49: 11044
- 11a Ding ST, Jiao N. J. Am. Chem. Soc. 2011; 133: 12374
- 11b Kim J, Choi J, Shin K, Chang S. J. Am. Chem. Soc. 2012; 134: 2528
- 11c Gong T.-J, Xiao B, Cheng W.-M, Su W, Xu J, Liu Z.-J, Liu L, Fu Y. J. Am. Chem. Soc. 2013; 135: 10630
- 11d Sundermeier M, Zapf A, Beller M. Angew. Chem. Int. Ed. 2003; 42: 1661
- 11e Wen Q, Jin J, Mei Y, Lu P, Wang Y. Eur. J. Org. Chem. 2013; 4032
- 11f Okamoto K, Watanabe M, Murai M, Hatano R, Ohe K. Chem. Commun. 2012; 48: 3127
- 12a Amantini D, Beleggia R, Fringuelli F, Pizzo F, Vaccaro L. J. Org. Chem. 2004; 69: 2896
- 12b Jia X, Yang D, Zhang S, Cheng J. Org. Lett. 2009; 11: 4716
- 12c Hong X, Wang H, Qian G, Tan Q, Xu B. J. Org. Chem. 2014; 79: 3228
-
13a Yeung CS, Dong VM. Chem. Rev. 2011; 111: 1215
- 13b Cho SH, Kim JY, Kwak J, Chang S. Chem. Soc. Rev. 2011; 40: 5068
- 13c Hull KL, Sanford MS. J. Am. Chem. Soc. 2007; 129: 11904
- 13d Li B.-J, Tian S.-L, Fang Z, Shi Z.-J. Angew. Chem. Int. Ed. 2008; 47: 1115
- 13e Wei Y, Su W. J. Am. Chem. Soc. 2010; 132: 16377
- 14a Hewgley JB, Stahl SS, Kozlowski MC. J. Am. Chem. Soc. 2008; 130: 12232
- 14b Do H.-Q, Daugulis O. J. Am. Chem. Soc. 2009; 131: 17052
- 14c Roithová J, Schröder D. Chem. Eur. J. 2008; 14: 2180
- 14d Monguchi D, Yamamura A, Fujiwara T, Somete T, Mori A. Tetrahedron Lett. 2010; 51: 850
- 14e Wendlandt AE, Suess AM, Stahl SS. Angew. Chem. Int. Ed. 2011; 50: 11062
-
15a Rouquet G, Chatani N. Angew. Chem. Int. Ed. 2013; 52: 11726
- 15b John A, Nicholas KM. J. Org. Chem. 2011; 76: 4158
- 15c Takamatsu K, Hirano K, Satoh T, Miura M. Org. Lett. 2014; 16: 2892
- 15d Chen X, Dobereiner G, Hao X.-S, Giri R, Mauel N, Yu J.-Q. Tetrahedron 2009; 65: 3085
- 16a Casitas A, Canta M, Solá M, Costas M, Ribas X. J. Am. Chem. Soc. 2011; 133: 19386
- 16b Nishino M, Hirano K, Satoh T, Miura M. Angew. Chem. Int. Ed. 2013; 52: 1
- 17a Tran LD, Roane J, Daugulis O. Angew. Chem. Int. Ed. 2013; 52: 6043
- 17b Dong J, Wang F, You J. Org. Lett. 2014; 16: 2884
- 18a Ribas X, Jackson DA, Donnadieu B, Mahía J, Parella T, Xifra R, Hedman B, Hodgson KO, Llobet A, Stack TD. P. Angew. Chem. Int. Ed. 2002; 41: 2991
- 18b King AE, Huffman LM, Casitas A, Costas M, Ribas X, Stahl SS. J. Am. Chem. Soc. 2010; 132: 12068
- 18c Wang Z.-L, Zhao L, Wang M.-X. Org. Lett. 2011; 13: 6560
- 19a Maeda H, Ishikawa Y, Matsuda T, Osuka A, Furuta H. J. Am. Chem. Soc. 2003; 125: 11822
- 19b Ribas X, Xifra R, Parella T, Poater A, Solà M, Llobet A. Angew. Chem. Int. Ed. 2006; 45: 2941
- 19c Chmielewski PJ, Latos-Grażyński L, Schmidt I. Inorg. Chem. 2000; 39: 5475
- 19d Yao B, Wang D.-X, Huang Z.-T, Wang M.-X. Chem. Commun. 2009; 2899
- 19e Zhang H, Zhao L, Wang D-X, Wang M.-X. Org. Lett. 2013; 15: 3836
- 20 The Preparation of Aromatic Carboxamide – General Procedure To a 50 mL three-necked flask, isonicotinic acid (2.5 g, 20 mmol), DMF (5 drops), and anhydrous CH2Cl2 (30 mL) were added under a N2 atmosphere. Oxalyl chloride (2.1 mL, 24 mmol, 1.2 equiv) was added dropwise at 0 °C resulting in vigorous bubbling. The mixture was stirred for 5 h at room temperature, and the solvent was then removed in vacuo. The resulting acid chloride was used immediately without further purification. To a 100 mL three-necked flask, 8-aminoquinoline (3.8 g, 26 mmol, 1.3 equiv), Et3N (5.7 mL, 40 mmol, 2 equiv), and anhydrous CH2Cl2 (30 mL) were added. A solution of the acid chloride in anhydrous CH2Cl2 (10 mL) was added dropwise to the solution at 0 °C, and the solution was then warmed to room temperature. After stirring overnight, the reaction system was quenched with NaHCO3 (30 mL of sat. aq solution) and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (2 × 15 mL). The combined organic layers were washed with aq HCl (30 mL, 1 M) and brine (30 mL), dried over MgSO4, filtered, and evaporated in vacuo. The obtained crude amide was purified by column chromatography on silica gel (eluant: CH2Cl2–PE = 5:1) to afford the desired amide. Copper-Catalyzed C–H Iodination of Aromatic Carboxamides; General Procedure A mixture of 1 (74.5 mg, 0.3 mmol), I2 (76.2 mg, 0.3 mmol), PhI(OAc)2 (193.2 mg, 0.6 mmol), and Cu(OAc)2 (10.9 mg, 0.06 mmol) in NMP (2 mL) was stirred at 100 °C under O2 (1 atm) for 20 h. The reaction mixture was cooled to room temperature and diluted with CH2Cl2 (2 mL). The suspension was filtered through a pad of Celite, and the residue was washed three times with CH2Cl2 (3 × 5 mL). The filtrate was concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography to afford the desired product. Analytical Data of Some Typical Compounds 4-Methyl-N-(quinolin-8-yl)benzamide (2) Brown solid (yield, 62%). 1H NMR (300 MHz, CDCl3): δ = 10.72 (s, 1 H), 8.92 (d, 1 H), 8.85 (d, 1 H), 8.21 (d, 1 H), 8.0 (d, 2 H) 7.62–7.47 (m, 3 H), 7.34 (d, 3 H), 2.45 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 165.18, 148.48, 142.14, 140.33, 139.10, 138.16, 135.50, 131.95, 131.01, 129.30, 127.12, 122.96, 117.67, 89.01, 21.50. ESI-HRMS: m/z calcd for C17H14N2O [M + H]+: 263.1179; found: 263.1227. 4-Methyl-N-(5-iodoquinolin-8-yl)benzamide (2a) White solid (yield, 93%). 1H NMR (300 MHz, CDCl3): δ = 10.73 (s, 1 H), 8.86–8.82 (m, 1 H), 8.75–8.69 (d, 2 H), 8.44–8.37 (m, 1 H), 8.16 (d, 1 H), 8.00–7.92 (d, 2 H), 7.60–7.54 (m, 1 H), 7.39–7.32 (d, 2 H), 2.45 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 165.16, 148.58, 140.53, 138.16, 131.92, 131.95, 129.30, 129.47, 127.12, 122.95, 117.67, 89.91, 21.35. ESI-HRMS: m/z calcd for C17H13IN2O [M + H]+: 389.0145; found: 389.0160. N-(5-Iodoquinolin-8-yl)isonicotinamide (9a) White solid (yield, 75%). 1H NMR (300 MHz, CDCl3): δ = 10.82 (s, 1 H), 8.87–8.84 (m, 3 H), 8.69 (d, 1 H), 8.43 (d, 1 H), 8.16 (d, 1 H), 7.91 (d, 2 H), 7.62–7.59 (m, 1 H). 13C NMR (75 MHz, CDCl3): δ = 163.18, 150.66, 149.14, 142.06, 140.98, 139.18, 138.27, 134.70, 129.77, 123.49, 121.20, 118.25, 90.64. ESI-HRMS: m/z calcd for C15H10N3O [M + H]+: 375.9941; found: 375.9970. 3-Iodo-N-(5-iodoquinolin-8-yl)isonicotinamide (9b) Brown solid (yield, 17%). 1H NMR (300 MHz, CDCl3): δ = 10.23 (s, 1 H), 9.10 (d, 1 H), 8.76 (s, 1 H), 8.70 (d, 1 H), 8.66 (d, 1 H), 8.40 (d, 1 H), 8.16 (d, 1 H), 7.57–7.54 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 164.95, 158.74, 149.40, 149.14, 148.31, 140.89, 138.99, 138.18, 134.57, 129.77, 123.47, 122.74, 118.43, 91.50, 90.97. ESI-HRMS: m/z calcd for C15H9N3O [M + H]+: 501.8908; found: 501.8941.