Abstract
Heterocyclic compounds having a nitrogen atom in the ring exhibit very interesting biological activities. Indole is the core structure of many bioactive compounds owing to its high affinity to bind with most biological targets. Indole is an electron-rich compound and generally prefers electrophilic rather than nucleophilic substitution. Hence, many important indole derivatives are difficult to synthesize through the conventional reactivity of indole. This limitation can be avoided by using the umpolung, from the German word meaning polarity inversion. In umpolung, the indole molecule, especially the C2 and C3 positions, behave as an electrophile. As C2-functionalized indoles have substantial importance in synthetic and pharmaceutical chemistry, this review focuses on the C2 umpolung of indoles via the indirect approach which is less explored. Unlike direct approaches of indole umpolung, indirect methods have several advantages and therefore a number of research articles have been published in this field. But no review is available up till now. This is the first review on this topic and we believe that it will surely motivate the readers to work in this area further.
Similar content being viewed by others
Abbreviations
- Ac:
-
Acyl
- AcOH:
-
Acetic acid
- Ar:
-
Aryl
- BHT:
-
Butylated hydroxytoluene
- Bn:
-
Benzyl
- Boc:
-
tert-Butyloxycarbonyl
- CAN:
-
Ceric ammonium nitrate
- DCE:
-
Dichloroethane
- DCM:
-
Dichloromethane
- DIB:
-
(Diacetoxyiodo)benzene
- DMDO:
-
Dimethyldioxirane
- DMF:
-
Dimethylformamide
- DMSO:
-
Dimethyl sulfoxide
- DTBP:
-
Di-tert-butyl peroxide
- EDG:
-
Electron-donating group
- EWG:
-
Electron-withdrawing group
- Eq.:
-
Equivalent
- LG:
-
Leaving group
- NCS:
-
N-Chlorosuccinimide
- NIS:
-
N-Iodosuccinimide
- Nu:
-
Nucleophile
- PPTS:
-
Pyridinium p-toluenesulfonate
- rt:
-
Room temperature
- TBHP:
-
tert-Butyl hydrogen peroxide
- TBAI:
-
Tetrabutyl ammonium iodide
- TEMPO:
-
2,2,6,6-Tetramethylpiperidin-1-oxyl
- TFA:
-
Trifluoroacetic acid
- pTSA:
-
p-Toluenesulfonic acid
References
Nikoofar K, Kadivar D, Shirzadnia S (2014) Iran Chem Commun 2:300–315
Ford J, Capon RJ (2000) Nat J Prod 63:1527–1528
Whitehead CW, Whitesitt CA (1974) J Med Chem 17:1298–1304
Cutignano A, Bifulco G, Bruno I, Casapullo A, Gomez-Paloma L, Riccio R (2000) Tetrahedron 56:3743–3748
Sidhu JS, Singla R, Mayank, Jaitak V (2015) Anticancer Agents Med Chem 16:160–173
Nicolaou KC, Chen JS (2009) Chem Soc Rev 38:2993–3009
Touré BB, Hall DG (2009) Chem Rev 109:4439–4486
Yadav DK, Patel R, Srivastava VP, Watal G, Yadav LDS (2010) Tetrahedron Lett 51:5701–5703
Contractor R, Samudio IJ, Estrov Z, Harris D, McCubrey JA, Safe SH, Andreeff M, Konopleva M (2005) Cancer Res 65:2890–2898
Deng J, Sanchez T, Neamati N, Briggs JM (2006) J Med Chem 49:1684–1692
Reddy BVS, Reddy MR, Madan C, Kumar KP, Rao MS (2010) Bioorg Med Chem Lett 20:7507–7511
de Sá Alves FR, Barreiro EJ, Fraga CAM (2009) Mini-Rev Med Chem 9:782–793
Welsch ME, Snyder SA, Stockwell BR (2010) Curr Opin Chem Biol 14:347–361
Abe T, Kukita A, Akiyama K, Naito T, Uemura D (2012) Chem Lett 41:728–729
Cimanga K, De Bruyne T, Pieters L, Vlietinck AJ (1997) J Nat Prod 60:688–691
Higuchi K, Sato Y, Tsuchimochi M, Sugiura K, Hatori M, Kawasaki T (2009) Org Lett 11:197–199
Liu Y, McWhorter WW (2003) J Am Chem Soc 125:4240–4252
Kawasaki T, Terashima R, Sakaguchi K, Sekiguchi H, Sakamoto M (1996) Tetrahedron Lett 37:7525–7528
Fukuda Y, Itoh Y, Nakatani K, Shiro T (1994) Tetrahedron 50:2793–2808
Kawasaki T, Nonaka Y, Akahane M, Maeda N, Sakamoto M (1993) J Chem Soc 1:1777–1781
Buzas A, Merour JY (1989) Synthesis 1989:458–461
Liu JF, Jiang ZY, Wang RR, Zheng YT, Chen JJ, Zhang XM, Ma YB (2007) Org Lett 9:4127–4129
Wolfard J, Xu J, Zhang H, Chung CK (2018) Org Lett 20:5431–5434
Deb ML, Bhuyan PJ (2007) Tetrahedron Lett 48:2159–2163
Zhang L, Zhu Y, Yin G, Lu P, Wang Y (2012) J Org Chem 77:9510–9520
Deb ML, Das C, Deka B, Saikiab PJ, Baruah PK (2016) Synlett 27:2788–2794
Deb ML, Borpatra PJ, Saikia PJ, Baruah PK (2017) Synthesis 49:1401–1409
Deb ML, Deka B, Saikia PJ, Baruah PK (2017) Tetrahedron Lett 58:1999–2003
Deb ML, Borpatra PJ, Saikia PJ, Baruah PK (2017) Org Biomol Chem 15:1435–1443
Deka B, Thakuria R, Deb ML, Baruah PK (2018) Monatsh Chem 149:2245–2252
Bandini M (2013) Org Biomol Chem 11:5206–5212
Yang P, Wang L, Xie X (2012) Future Med Chem 4:187–204
Tong L, Shankar BB, Chen L, Rizvi R, Kelly J, Gilbert E, Huang C, Yang D, Kozlowski JA, Shih NY, Gonsiorek W, Hipkin RW, Malikzay A, Lunn CA, Lundell DJ (2010) Bioorg Med Chem Lett 20:6785–6789
Barden TC (2010) Top Heterocycl Chem 26:31–46
Kim JS, Shin-ya K, Furihata K, Hayakawa Y, Seto H (1997) Tetrahedron Lett 38:3431–3434
Flynn BL, Hamel E, Jung MK (2002) J Med Chem 45:2670–2673
Li Y, Ji K, Wang H, Ali S, Liang Y (2011) J Org Chem 76:744–747
Wu WB, Huang JM (2012) Org Lett 14:5832–5835
Ghosh SK, Nagarajan R (2014) RSC Adv 4:20136–20144
Beukeaw D, Udomsasporn K, Yotphan S (2015) J Org Chem 80:3447–3454
Katrun P, Mueangkaew C, Pohmakotr M, Reutrakul V, Jaipetch T, Soorukram D, Kuhakarn C (2014) J Org Chem 79:1778–1785
Hostier T, Ferey V, Ricci G, Pardoa DG, Cossy J (2015) Chem Commun 51:13898–13901
Ferrer C, Amijs CHM, Echavarren AM (2007) Chem Eur J 13:1358–1373
Tokimizu Y, Oishi S, Fujii N, Ohno H (2014) Org Lett 16:3138–3141
Pathak TP, Gligorich KM, Welm BE, Sigman MS (2010) J Am Chem Soc 132:7870–7871
Deb ML, Pegu CD, Deka B, Dutta P, Kotmale AS, Baruah PK (2016) Eur J Org Chem 20:3441–3448
Badigenchala S, Rajeshkumar V, Sekar G (2016) Org Biomol Chem 14:2297–2305
Badigenchala S, Sekar G (2017) J Org Chem 82:7657–7665
Deka B, Baruah PK, Deb ML (2018) Org Biomol Chem 16:7806–7810
Bailly C, Laine W, Baldeyrou B, De Pauw-Gillet MC, Colson P, Houssier C, Cimanga K, Miert SV, Vlietinck AJ, Pieters L (2000) Anti-Cancer Drug Des 15:191–201
Jonckers THM, Miert SV, Cimanga K, Bailly C, Colson P, De Pauw-Gillet MC, Heuvel H, Claeys M, Lemiere F, Esmans EL, Rozenski J, Quirijnen L, Maes L, Dommisse R, Lemiere GLF, Vlietinck A, Pieters L (2002) J Med Chem 45:3497–3508
Lavrado J, Moreira R, Paulo A (2010) Curr Med Chem 17:2348–2370
Vecchione MK, Sun AX, Seidel D (2011) Chem Sci 2:2178–2181
Marcos IS, Moro RF, Costales I, Basabe P, Diez D (2013) Nat Prod Rep 30:1509–1526
Rongved P, Kirsch G, Bouaziz Z, Jose J, Le BM (2013) Eur J Med Chem 69:465–479
Ramirez A, Garcia-Rubio S (2003) Curr Med Chem 10:1891–1915
Ruiz-Sanchis P, Savina SA, Albericio F, Alvarez M (2011) Chem Eur J 17:1388–1408
Aygun A, Pindur U (2003) Curr Med Chem 10:1113–1127
Roche SP, Tendoung JY, Tréguier B (2015) Tetrahedron 71:3549–3591
Keane JM, Harman WD (2005) Organometallics 24:1786–1798
Smith PL, Chordia MD, Harman WD (2001) Tetrahedron 57:8203–8225
Magdziak D, Meek SJ, Pettus TRR (2004) Chem Rev 104:1383–1430
Ghosh AK, Chen Z (2014) Org Biomol Chem 12:3567–3571
Tayu M, Higuchi K, Ishizaki T, Kawasaki T (2014) Org Lett 16:3613–3615
Nowrouzi F, Batey RA (2013) Angew Chem Int Ed 52:892–895
Morimoto N, Morioku K, Suzuki H, Takeuchi Y, Nishina Y (2016) Org Lett 18:2020–2023
Nandi RK, Ratsch F, Beaud R, Guillot R, Kouklovsky C, Vincent G (2016) Chem Commun 52:5328–5331
Deka B, Deb ML, Thakuria R, Baruah PK (2018) Catal Commun 106:68–72
Kong L, Wang M, Zhang F, Xu M, Li Y (2016) Org Lett 18:6124–6127
Acknowledgements
MLD is thankful to the Science and Engineering Research Board (SERB), India [Grant no. SB/FT/CS-073/2014] for the financial support under the “Fast Track” Scheme. BD acknowledges MHRD, Govt of India for research fellowship under the TEQIP-III Project.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no competing financial interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Deka, B., Deb, M.L. & Baruah, P.K. Recent Advances on the C2-Functionalization of Indole via Umpolung. Top Curr Chem (Z) 378, 22 (2020). https://doi.org/10.1007/s41061-020-0287-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s41061-020-0287-7