Synlett 2017; 28(19): 2670-2674
DOI: 10.1055/s-0036-1589079
letter
© Georg Thieme Verlag Stuttgart · New York

Iron-Catalyzed C3-Formylation of Indoles with Formaldehyde and Aqueous Ammonia under Air

Qing-Dong Wang, Bin Zhou, Jin-Ming Yang*, Dong Fang, Jiangmeng Ren, Bu-Bing Zeng*
  • School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. of China   Email: zengbb@ecust.edu.cn
  • School of Pharmacy, Yancheng Teachers University, Yancheng, Jiangsu 224007, P. R. of China   Email: chemyjm@163.com
We thank the National High Technology Research and Development Program of China (2007AA02Z301), the Natural Science Foundation of Jiangsu Province (BK20141257), the Natural Science Foundation of Yancheng Teachers University (09YCKL021, 14YCKL001), and the Fundamental Research Funds for the Central University (WY111307) for their generous financial support
Further Information

Publication History

Received: 22 May 2017

Accepted after revision: 23 June 2017

Publication Date:
14 August 2017 (eFirst)

Abstract

An efficient iron-catalyzed C3-selective formylation of free (N–H) or N-substituted indoles was developed by employing formaldehyde and aqueous ammonia, with air as the oxidant. This new method gave 3-formylindoles in moderate to excellent yields with fairly short reaction times. Moreover, this procedure for catalytic formylation of indoles can be applied to gram-scale syntheses.

Supporting Information

 
  • References and Notes

    • 1a Sravanthi TV. Manju SL. Eur. J. Pharm. Sci. 2016; 91: 1
    • 1b Sugimoto S. Naganuma M. Kanai T. J. Gastroenterol. 2016; 51: 853
    • 1c Zhang M.-Z. Chen Q. Yang G.-F. Eur. J. Med. Chem. 2015; 89: 421
    • 1d Almagro L. Fernández-Pérez F. Angeles Pedreño M. Molecules 2015; 20: 2973
    • 1e França PH. B. Barbosa DP. da Silva DL. Ribeiro ÊA. N. Santana AE. G. Santos BV. O. Barbosa-Filho JM. Quintans JS. S. Barreto RS. S. Quintans-Júnior LJ. de Araújo-Júnior JX. BioMed Res. Int. 2014; 2014: 1
    • 1f Blunt JW. Copp BR. Keyzers RA. Munro MH. G. Prinsep MR. Nat. Prod. Rep. 2014; 31: 160
    • 1g Sakai R. Swanson GT. Nat. Prod. Rep. 2014; 31: 273
    • 1h Xu W. Gavia DJ. Tang Y. Nat. Prod. Rep. 2014; 31: 1474
    • 1i Kaushik NK. Kaushik N. Attri P. Kumar N. Kim CH. Verma AK. Choi EH. Molecules 2013; 18: 6620
    • 1j Blunt JW. Copp BR. Keyzers RA. Munro MH. G. Prinsep MR. Nat. Prod. Rep. 2012; 29: 144
    • 1k Kochanowska-Karamyan AJ. Hamann MT. Chem. Rev. 2010; 110: 4489
    • 2a Netz N. Opatz T. J. Org. Chem. 2016; 81: 1723
    • 2b Yang M.-R. Qin Y.-J. Chen C. Zhang Y.-L. Li B.-Y. Liu T.-B. Gong H.-B. Wang B.-Z. Zhu H.-L. RSC Adv. 2016; 6: 30412
    • 2c Zhang Y.-L. Qin Y.-J. Tang D.-J. Yang M.-R. Li B.-Y. Wang Y.-T. Cai H.-Y. Wang B.-Z. Zhu H.-L. ChemMedChem 2016; 11: 1446
    • 2d Pedada SR. Yarla NS. Tambade PJ. Dhananjaya BL. Bishayee A. Arunasree KM. Philip GH. Dharmapuri G. Aliev G. Putta S. Rangaiah G. Eur. J. Med. Chem. 2016; 112: 289
    • 2e Sundaree S. Vaddula BR. Tantak MP. Khandagale SB. Shi C. Shah K. Kumar D. Med. Chem. Res. 2016; 25: 941
    • 2f Das Mukherjee D. Kumar NM. Tantak MP. Das A. Ganguli A. Datta S. Kumar D. Chakrabarti G. Biochemistry 2016; 55: 3020
    • 2g El-labbad EM. Ismail MA. H. Abou Ei Ella DA. Ahmed M. Wang F. Barakat KH. Abouzid KA. M. Chem. Biol. Drug Des. 2015; 86: 1518
    • 2h Chen C.-H. Genapathy S. Fischer PM. Chan WC. Org. Biomol. Chem. 2014; 12: 9764
    • 2i Jin H. Zhang P. Bijian K. Ren S. Wan S. Alaoui-Jamali MA. Jiang T. Mar. Drugs 2013; 11: 1427
    • 2j Ding S. Jiao N. Angew. Chem. Int. Ed. 2012; 51: 9226
    • 2k Xu H. Yang W. b. Wang Q. Chem. Biol. Drug Des. 2011; 78: 864
    • 3a Bennasar M.-L. Zulaica E. Solé D. Alonso S. Tetrahedron 2007; 63: 861
    • 3b Tohyama S. Choshi T. Matsumoto K. Yamabuki A. Ikegata K. Nobuhiro J. Hibino S. Tetrahedron Lett. 2005; 46: 5263
    • 3c Mayer S. Joseph B. Guillaumet G. Mérour J.-Y. Synthesis 2002; 1871
    • 4a van Niel MB. Collins I. Beer MS. Broughton HB. Cheng SK. F. Goodacre SC. Heald A. Locker KL. MacLeod AM. Morrison D. Moyes CR. O’Connor D. Pike A. Rowley M. Russel N. Sohal BB. Stanton JA. Thomas S. Verrier H. Watt AP. Castro JL. J. Med. Chem. 1999; 42: 2087
    • 4b Chatterjee A. Biswas KM. J. Org. Chem. 1973; 38: 4002
    • 5a Wynberg H. Chem. Rev. 1960; 60: 169
    • 5b Blume RC. Lindwall HG. J. Org. Chem. 1945; 10: 255
  • 6 Wu W. Su W. J. Am. Chem. Soc. 2011; 133: 11924
    • 7a Li L.-T. Huang J. Li H.-Y. Wen L.-J. Wang P. Wang B. Chem. Commun. 2012; 48: 5187
    • 7b Li L.-T. Li H.-Y. Xing L.-J. Wen L.-J. Wang P. Wang B. Org. Biomol. Chem. 2012; 10: 9519
    • 7c Zhang L. Peng C. Zhao D. Wang Y. Fu H.-J. Shen Q. Li J.-X. Chem. Commun. 2012; 48: 5928
    • 7d Chen J. Liu B. Liu D. Liu S. Cheng J. Adv. Synth. Catal. 2012; 354: 2438
    • 7e Zhang B. Liu B. Chen J. Wang J. Liu M. Tetrahedron Lett. 2014; 55: 5618
    • 7f Lu L. Xiong Q. Guo S. He T. Xu F. Gong J. Zhu Z. Cai H. Tetrahedron 2015; 71: 3637
    • 7g Li X. Gu X. Li Y. Li P. ACS Catal. 2014; 4: 1897
    • 7h Tongkhan S. Radchatawedchakoon W. Kruanetr S. Sakee U. Tetrahedron Lett. 2014; 55: 3909
  • 8 Fei H. Yu J. Jiang Y. Guo H. Cheng J. Org. Biomol. Chem. 2013; 11: 7092

    • For select reviews, see:
    • 9a Lv L. Li Z. Top. Curr. Chem. 2016; 374: 38
    • 9b Fürstner A. ACS Cent. Sci. 2016; 2: 778
    • 9c Yang X.-H. Song R.-J. Xie Y.-X. Li J.-H. ChemCatChem 2016; 8: 2429
    • 9d Bauer I. Knölker H.-J. Chem. Rev. 2015; 115: 3170
    • 9e Gopalaiah K. Chem. Rev. 2013; 113: 3248
    • 9f Jana R. Pathak TP. Sigman MS. Chem. Rev. 2011; 111: 1417
    • 9g Czaplik WM. Mayer M. Cvengroš J. Jacobi von Wangelin A. ChemSusChem 2009; 2: 396
    • 10a Kawashita Y. Nakamichi N. Kawabata H. Hayashi M. Org. Lett. 2003; 5: 3713
    • 10b Kawabata H. Hayashi M. Tetrahedron Lett. 2004; 45: 5457
    • 10c Sano Y. Tanaka T. Hayashi M. Chem. Lett. 2007; 36: 1414
    • 10d Hayashi M. Chem. Rec. 2008; 8: 252
    • 10e Kawashita Y. Yanagi J. Fujii T. Hayashi M. Bull. Chem. Soc. Jpn. 2009; 82: 482
    • 10f Kawashita Y. Hayashi M. Molecules 2009; 14: 3073
  • 11 Ratnikov MO. Xu X. Doyle MP. J. Am. Chem. Soc. 2013; 135: 9475
  • 12 Semenov BB. Granik VG. Pharm. Chem. J. 2004; 38: 287
  • 13 Indolecarbaldehydes 2a2aa; General Procedure A 50 mL round-bottomed flask equipped with a magnetic stirring bar was charged with the appropriate indole 1 (0.5 mmol, 1.0 equiv), 37% aq HCHO (0.5 mmol, 0.0406 g, 1.0 equiv), 25% aq NH3 (1.0 mmol, 0.0681 g, 2.0 equiv), FeCl3 (0.01 mmol, 0.0016 g, 2 mol%), and DMF (2 mL). The flask was fitted with a reflux condenser, and the mixture was stirred at 130 °C under open air. When the reaction was complete (TLC), the mixture was cooled to r.t., diluted with sat. aq NaCl (10 mL) and 0.5 M aq HCl (2 mL), and extracted with EtOAc (3 x 7 mL). The organic layers were combined, washed with sat. aq NaHCO3 (10 mL) and sat. aq NaCl (10 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, hexane–EtOAc). 1H-indole-3-carbaldehyde (2a)7f Pale-yellow solid; yield: 0.0676 g (93%); mp 190–192 °C. 1H NMR (400 MHz, CDCl3): δ = 10.07 (s, 1 H), 8.36 – 8.28 (m, 1 H), 7.86 (d, J = 3.0 Hz, 1 H), 7.48 – 7.41 (m, 1 H), 7.36 – 7.31 (m, 2 H). 13C NMR (126 MHz, DMSO-d 6): δ = 185.01, 138.30, 137.05, 124.08, 123.49, 122.15, 120.83, 118.13, 112.38. EI-MS: m/z (%) = 63(30), 90(60), 116(18), 144(100), 145(84) [M+]