Environmental Chemistry Letters

, Volume 16, Issue 2, pp 677–682 | Cite as

Efficient microwave-assisted diastereoselective synthesis of indole-based 4,5-dihydrofurans via a one-pot, three-component reaction in water

  • Robabeh Baharfar
  • Razieh Azimi
  • Zeinab Asdollahpour
Original Paper


The combination of two or more different heterocyclic moieties in a single molecule would enhance biological activity significantly. The indole and furan scaffolds are promising candidates in drug design, and they have been widely found in natural products and therapeutic agents. Owing to their pharmaceutical importance, there is an urgent need to design rapid, efficient and environmentally benign protocols for the synthesis of indole–dihydrofuran biheterocycles. Herein, we have developed a novel ecofriendly approach for the diastereoselective synthesis of indole-based 4,5-dihydrofurans through a three-component reaction of 3-cyanoacetyl indoles with various aldehydes and N-phenacylpyridinium bromides in the presence of potassium carbonate as an inexpensive and non-toxic base in water under low power microwave irradiation. The findings show that aromatic and heteroaromatic aldehydes tolerated well in this reaction. The products were obtained in 85–98% yields in 4–20 min. The advantages of this method consist of the environmental friendly reaction conditions, use of green solvent and safe base, availability of raw materials, wide range of usable substrates, short reaction times, excellent yields and absence of any tedious workup or purification.


Dihydrofuran Microwave Green synthesis Stereoselective Three-component reaction 



We are thankful to the Research Council of Mazandaran University for the financial support of this work.


  1. Azimi R, Baharfar R (2014) DABCO-functionalized mesoporous SBA-15: an efficient and recyclable catalyst for the synthesis of spiro-pyranoxindoles as antioxidant agents. Can J Chem 92:1163–1168. CrossRefGoogle Scholar
  2. Baharfar R, Asghari S, Zaheri F, Shariati N (2017) Three-component synthesis of novel spirooxindole–furan derivatives using pyridinium salts. C R Chim 20:359–364. CrossRefGoogle Scholar
  3. Bialonska D, Zjawiony JK (2009) Aplysinopsins-marine indole alkaloids: chemistry, bioactivity and ecological significance. Mar Drugs 7:166–183. CrossRefGoogle Scholar
  4. Chuang CP, Chen KP (2012) N-Phenacylpyridinium bromides in the one-pot synthesis of 2,3-dihydrofurans. Tetrahedron 68:1401–1406. CrossRefGoogle Scholar
  5. Govender T, Maguire GEM, Kruger HG, Shiri M (2013) A review of cyanoacetyl indoles (CAIs): versatile starting materials in organic synthesis. Curr Org Synth 10:737–750. CrossRefGoogle Scholar
  6. Gunasekaran P, Balamurugan K, Sivakumar S, Perumal S, Menéndez JC, Almansourc AI (2012) Domino reactions in water: diastereoselective synthesis of densely functionalized indolyldihydrofuran derivatives. Green Chem 14:750–757. CrossRefGoogle Scholar
  7. Hailes HC (2007) Reaction solvent selection: the potential of water as a solvent for organic transformations. Org Process Res Dev 11:114–120. CrossRefGoogle Scholar
  8. Kobayashi J, Ohizumi Y, Nakamura H (1986) Hippospongin a novel furanosesterterpene possessing antispasmodic activity from the okinawan marine sponge hippospongia sp. Tetrahedron Lett 27:2113–2116. CrossRefGoogle Scholar
  9. Kupchan SM, Eakin MA, Thomas AM (1971) Tumor inhibitors. 69. Structure-cytotoxicity relations among the sesquiterpene lactones. J Med Chem 14:1147–1152. CrossRefGoogle Scholar
  10. Lakshmi NV, Thirumurugan P, Noorulla KM, Perumal PT (2010) InCl3 mediated one-pot multicomponent synthesis, anti-microbial, antioxidant and anticancer evaluation of 3-pyranyl indole derivatives. Bioorg Med Chem Lett 20:5054–5061. CrossRefGoogle Scholar
  11. Majumder S, Sharma M, Bhuyan PJ (2013) Microwave promoted diastereoselective synthesis of dihydroindeno[1,2-b]furans via one-pot three-component reaction in solvent-free conditions. Tetrahedron Lett 54:6868–6870. CrossRefGoogle Scholar
  12. Murugavel G, Punniyamurthy T (2015) Microwave-assisted copper-catalyzed four-component tandem synthesis of 3-N-sulfonylamidine coumarins. J Org Chem 80:6291–6299. CrossRefGoogle Scholar
  13. Rathi AK, Gawande MB, Zboril R, Varma RS (2015) Microwave-assisted synthesis–catalytic applications in aqueous media. Coord Chem Rev 291:68–94. CrossRefGoogle Scholar
  14. Schreiber SL (2000) Target-oriented and diversity-oriented organic synthesis in drug discovery. Science 287:1964–1969. CrossRefGoogle Scholar
  15. Sugimoto K, Tamura K, Tohda C, Toyooka N, Nemoto H, Matsuya Y (2013) Structure–activity-relationship studies on dihydrofuran-fused perhydrophenanthrenes as an anti-Alzheimer’s disease agent. Bioorg Med Chem 21:4459–4471. CrossRefGoogle Scholar
  16. Sun C, Ji SJ, Liu Y (2007) Facile synthesis of 3-(2-furanyl)indoles via a multicomponent reaction. Tetrahedron Lett 48:8987–8989. CrossRefGoogle Scholar
  17. Sundberg RJ (1996) The chemistry of indoles. Academic Press, New YorkGoogle Scholar
  18. Wagare DS, Netankar PD, Shaikh M, Farooqui M, Durrani A (2017) Highly efficient microwave-assisted one-pot synthesis of 4-aryl-2-aminothiazoles in aqueous medium. Environ Chem Lett. CrossRefGoogle Scholar
  19. Xia L, Idhayadhulla A, Lee YR, Wee YJ, Kim SH (2014) Anti-tyrosinase, antioxidant, and antibacterial activities of novel 5-hydroxy-4-acetyl-2,3-dihydronaphtho[1,2-b]furans. Eur J Med Chem 86:605–612. CrossRefGoogle Scholar
  20. Zhang Y, Zhong H, Wang T, Geng D, Zhang M, Li K (2012) Synthesis of novel 2, 5-dihydrofuran derivatives and evaluation of their anticancer activity. Eur J Med Chem 48:69–80. CrossRefGoogle Scholar
  21. Zhang MZ, Chen Q, Yang GF (2015) A review on recent developments of indole-containing antiviral agents. Eur J Med Chem 89:421–441. CrossRefGoogle Scholar
  22. Zhang D, Zhang Y, Zhao T, Li J, Hou Y, Gu Q (2016) A rapid and efficient solvent-free microwave-assisted synthesis of pyrazolone derivatives containing substituted isoxazole ring. Tetrahedron 72:2979–2987. CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Faculty of ChemistryUniversity of MazandaranBabolsarIran
  2. 2.Research Institute of Forests and RangelandsAgricultural Research, Education and Extension Organization (AREEO)TehranIran

Personalised recommendations