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 2015; 26(17): 2467-2471
DOI: 10.1055/s-0035-1560210
DOI: 10.1055/s-0035-1560210
letter
A New Method for the Synthesis of 3-Substituted Indoles
Further Information
Publication History
Received: 25 June 2015
Accepted after revision: 09 August 2015
Publication Date:
07 September 2015 (online)
Abstract
Starting from readily accessible nitrones and electron-deficient acetylenes, a highly efficient and versatile synthetic protocol for 3-substituted indoles has been developed.
Key words
indoles - nitrones - electron-deficient acetylenes - nucleophilic addition - 1,3-dipolar additionsSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560210.
- Supporting Information
-
References and Notes
- 1a Sundberg RJ. The Chemistry of Indoles . Academic Press; New York: 1970
- 1b Sugden JK, Yoloye TO. Pharm. Acta Helv. 1978; 53: 65
- 1c Sundberg RJ. Indoles . Academic Press; London: 1996
- 1d Rahman A, Basha A. Indole Alkaloids . Harwood Academic; Amsterdam: 1998: 141
- 1e Gupta RR. Heterocyclic Chemistry . Vol. 2. Springer; New York: 1999: 193
- 1f Horton DA, Bourne GT, Smythe ML. Chem. Rev. 2003; 103: 893
- 1g Somei M, Yamada F. Nat. Prod. Rep. 2004; 21: 278
- 1h Somei M, Yamada F. Nat. Prod. Rep. 2005; 22: 73
- 1i Kawasaki T, Higuchi K. Nat. Prod. Rep. 2007; 24: 843
- 1j Kochanowska-Karamyan AJ, Hamann MT. Chem. Rev. 2010; 110: 4489
- 1k Maes BU. W. Heterocyclic Scaffolds II: Reactions and Applications of Indoles. In Topics in Heterocyclic Chemistry. Vol. 26. Gribble GW. Springer; Berlin: 2010
- 1l Barden TC. Heterocyclic Scaffolds II: Reactions and Applications of Indoles. In Topics in Heterocyclic Chemistry. Vol. 26. Gribble GW. Springer; Berlin: 2010: 31
- 1m Biswal S, Sahoo U, Sethy S, Kumar HK. S, Banerjee M. Asian J. Pharm. Clin. Res. 2012; 5: 1
- 2 Fischer E, Jourdan F. Ber. Dtsch. Chem. Ges. 1883; 16: 2241
- 3a Robinson B. Chem. Rev. 1969; 69: 227
- 3b Gribble GW. J. Chem. Soc., Perkin Trans. 1 2000; 1045
- 3c Gribble GW. Pure Appl. Chem. 2003; 75: 1417
- 3d Cacchi S, Fabrizi G. Chem. Rev. 2005; 105: 2873
- 3e Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
- 3f Kruger K, Tillack A, Beller M. Adv. Synth. Catal. 2008; 350: 2153
- 3g Patil SA, Patil R, Miller DD. Curr. Med. Chem. 2009; 16: 2531
- 3h Russel JS, Pelkey ET. Prog. Heterocycl. Chem. 2009; 20: 122
- 3i Barluenga J, Rodriguez F, Fananas FJ. Chem. Asian J. 2009; 4: 1036
- 3j Candeias NR, Branco LC, Gois PM. P, Afonso CA. M, Trindade AF. Chem. Rev. 2009; 109: 2703
- 3k Palmisano G, Penoni A, Sisti M, Tibiletti F, Tollari S, Nicholas KM. Curr. Org. Chem. 2010; 14: 2409
- 3l Song JJ, Reeves JT, Fandrick DR, Tan Z, Yee NK, Senanayake CH. ARKIVOC 2010; (i): 390
- 3m Cacchi S, Fabrizi G, Goggiamani A. Org. Biomol. Chem. 2011; 9: 641
- 3n Vicente R. Org. Biomol. Chem. 2011; 9: 6469
- 3o Patil SA, Patil R, Miller DD. Curr. Med. Chem. 2011; 18: 615
- 3p Taber DF, Tirunaharai PV. Tetrahedron 2011; 67: 7195
- 3q Platon M, Amardeil R, Djakovitch L, Hierso JC. Chem. Soc. Rev. 2012; 41: 3929
- 3r Dalpozzo R, Bartoli G, Bencivenni G. Chem. Soc. Rev. 2012; 41: 7247
- 3s Shiri M. Chem. Rev. 2012; 112: 3508
- 3t Gataullin RR. Russ. J. Org. Chem. 2013; 49: 151
- 3u Inman M, Moody CJ. Chem. Sci. 2013; 4: 29
- 3v Melander RJ, Minvielle MJ, Melander C. Tetrahedron 2014; 70: 6363
- 4a Newman SG, Lautens M. J. Am. Chem. Soc. 2010; 132: 11416
- 4b Cacchi S, Fabrizi G, Goggiamani A, Perboni A, Sferrazza A, Stabile P. Org. Lett. 2010; 12: 3279
-
4c Levesque P, Forunier P.-A. J. Org. Chem. 2010; 75: 7033
- 4d He Z, Li H, Li Z. J. Org. Chem. 2010; 75: 4296
- 4e McAusland D, Seo S, Pintori DG, Finlayson J, Greaney MF. Org. Lett. 2011; 13: 3667
- 4f Kothandaraman P, Mothe SR, Toh SS. M, Chan PW. H. J. Org. Chem. 2011; 76: 7633
- 4g Bonnamour J, Bolm C. Org. Lett. 2011; 13: 2012
- 4h Kim JH, Lee S.-G. Org. Lett. 2011; 13: 1350
- 4i Yan Q, Luo J, Zhang-Negrerie D, Li H, Qi X, Zhao K. J. Org. Chem. 2011; 76: 8690
- 4j Zhao Y, Li D, Zhao L, Zhang J. Synthesis 2011; 873
- 4k Ali MA, Punniyamurthy T. Synlett 2011; 623
- 4l Yoshida K, Hayashi K, Yanagisawa A. Org. Lett. 2011; 13: 4762
- 4m Zhang Z.-G, Haag BA, Li J.-S, Knochel P. Synthesis 2011; 23
- 4n Varela-Fernández A, Varela JA, Saá C. Synthesis 2012; 44: 3285
- 4o Wei Y, Deb I, Yoshikai N. J. Am. Chem. Soc. 2012; 134: 9098
- 4p Gore S, Baskaran S, König B. Org. Lett. 2012; 14: 4568
- 4q Porcheddu A, Mura MG, De Luca L, Pizzetti M, Taddei M. Org. Lett. 2012; 14: 6112
- 4r Jadhav J, Gaikwad V, Kurane R, Salunkhe R, Rashinkar G. Synlett 2012; 23: 2511
- 4s Selander N, Worrell BT, Chuprakov S, Velaparthi S, Fokin VV. J. Am. Chem. Soc. 2012; 134: 14670
- 4t Nanjo T, Tsukano C, Takemoto Y. Org. Lett. 2012; 14: 4270
- 4u Lu BZ, Wei H.-X, Zhang Y, Zhao W, Dufour M, Li G, Farina V, Senanayake CH. J. Org. Chem. 2013; 78: 4558
- 4v Reddy BV. S, Reddy MR, Rao YG, Yadav JS, Srighar B. Org. Lett. 2013; 15: 464
- 4w Gogoi A, Guin S, Rout SK, Patel BK. Org. Lett. 2013; 15: 1802
- 4x Lin A, Yang J, Hashim M. Org. Lett. 2013; 15: 1950
- 4y Ji X, Huang H, Wu W, Jiang H. J. Org. Chem. 2013; 78: 11155
- 5a Radhamani S, Natarajan R, Unnikrishnan PA, Prathapan S, Rappai JP. New J. Chem. 2015; 39: 5580
- 5b John PR. PhD Thesis . Cochin University of Science and Technology; Cochin, India: 2010
- 5c Sandhya R. PhD Thesis . Cochin University of Science and Technology; Cochin, India: 2014
- 6 For a similar cyclization reaction, see: Pecak WH, Son J, Burnstine AJ, Anderson LL. Org. Lett. 2014; 16: 3440
- 7a Reaction of N-arylnitrone and ketenimine: Tsuge O, Watanabe H, Masuda K, Yousif MM. J. Org. Chem. 1979; 44: 4543
- 7b Reaction of nitrones with (phenylsulfonyl)alkynes: Parpani P, Zecchi G. J. Org. Chem. 1987; 52: 1417
- 7c Reaction of α,β-unsaturated N-arylnitrones with acetylenes: Huehls CB, Hood TS, Yang J. Angew. Chem. Int. Ed. 2012; 51: 5110
- 8 General Procedure A 1:1 mixture (1 mmol each) of nitrone and acetylene in MeCN (10 mL) was stirred under reflux for 4 h. After complete consumption of starting materials, solvent was evaporated off, and the residue was redissolved in CH2Cl2 (10 mL) in the same flask. Oxalic acid (1 mmol) adsorbed on silica gel (1 g) was added to the same pot, and the mixture was stirred at r.t. for 1 h. After completion of the reaction, the solvent was removed, and the products were isolated by column chromatography over silica gel using mixtures of hexane and EtOAc as eluents. In all reactions, fluorenone was formed as a byproduct in yields comparable to those cited for the indoles. Nitrones were prepared by recycling the fluorenone.
- 9a Nanjo T, Yamamoto S, Tsukano C, Takemoto Y. Org. Lett. 2013; 15: 3754
- 9b Black DS, Debdas RB, Kumar N. Aust. J. Chem. 1992; 45: 611
- 9c Coffman KC, Palazzo TA, Hartely TP, Fettinger JC, Tantillo DJ, Kurth MJ. Org. Lett. 2013; 15: 2062
- 9d Hopkins CR, Czekaj M, Kaye SS, Gao Z, Pribish J, Pauls H, Liang G, Sides K, Cramer D, Cairns J, Luo Y, Lim H.-K, Vaz R, Rebello S, Maignan S, Dupuy A, Mathieue M, Levella J. Bioorg. Med. Chem. Lett. 2005; 15: 2734
- 9e Yamazaki K, Nakamura Y, Kondo Y. J. Org. Chem. 2003; 68: 6011
- 9f Ji X, Huang H, Wu W, Li X, Jiang H. J. Org. Chem. 2013; 78: 11155
- 9g Hirano S, Akai R, Shinoda Y, Nakatsuka S. Heterocycles 1995; 41: 255
- 9h Mongel A, Palopl J, Ramirez C, Font M, Fernandez AE. Eur. J. Med. Chem. 1991; 26: 179
- 9i Mitchell G, Rees CW. J. Chem. Soc., Chem. Commun. 1986; 399
- 9j Mitchell G, Rees CW. J. Chem. Soc., Perkin Trans. 1 1987; 413
- 10 Characterization Data for 5b and 5c (E)-1-{2′,5′-Diphenyl-2′H-spiro[fluorene-9,3′-isoxazole]-4′-yl}-3-phenylprop-2-en-1-one (5b) Yellow solid, yield 16%; mp 105 °C. IR (KBr): νmax = 3058 (=CH stretch), 1649 (C=O stretch) cm–1. 1HNMR (400 MHz, CDCl3): δ = 7.89–7.86 (m, 2 H), 7.67 (d, J = 7.6 Hz, 2 H), 7.64–7.60 (m, 1 H), 7.57–7.53 (m, 4 H), 7.36–7.32 (m, 2 H), 7.27–7.16 (m, 6 H), 6.99–6.91 (m, 4 H), 6.81–6.76 (m, 1 H), 6.61–6.58 (m, 2 H), 6.36 (d, J = 15.6 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 183.9, 163.1, 145.9, 144.9, 140.8, 140.7, 134.9,131.7, 130.2, 129.8, 129.4, 128.8, 128.6, 128.1, 128.0, 127.9, 127.0, 125.4, 124.7, 123.6, 120.1, 118.3, 117.0, 84.9. MS: m/z = 503 [M+]. Anal. Calcd for C36H25NO2: C, 85.86; H, 5.00, N, 2.78. Found: C, 85.82; H, 4.98; N, 2.75. 1-{2′,5′-Diphenyl-2′H-spiro[fluorene-9,3′-isoxazole]-4′-yl}ethanone (5c) Yellow solid, yield 18%, mp 124 °C. IR (KBr): νmax = 3058 (=CH stretch), 1649 (C=O stretch) cm–1. 1HNMR (400 MHz, CDCl3): δ = 7.84–7.81 (m, 2 H), 7.65–7.52 (m, 6 H), 7.37–7.33 (m, 2 H), 7.26–7.22 (m, 3 H), 6.93–6.89 (m, 2 H), 6.79–6.75 (m, 1 H), 6.56–6.53 (m, 2 H), 2.28 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 192.4, 163.4, 145.9, 144.9, 140.6, 131.4, 129.7, 129.4, 128.6, 128.3, 128.0, 127.9, 125.5, 123.6, 120.2, 117.3, 117.1, 84.5, 28.7. MS: m/z = 415 [M+]. Anal. Calcd for C29H21NO2: C, 83.83; H, 5.09; N, 3.37. Found: C, 83.78; H, 5.05; N, 3.35
- 11a Boger DL, Desharnais J, Capps K. Angew. Chem. Int. Ed. 2003; 42: 4138
- 11b Tietze LF, Schuster HJ, Schmuck K, Schuberth I, Alves F. Bioorg. Med. Chem. 2008; 16: 6312
- 11c Helsley GC, Effland RC, Davies L. US 3997557, 1976 ; Chem. Abstr. 1977, 86, 139850
- 11d Chen J, Burghart A, Derecskei-Kovacs A, Burgess K. J. Org. Chem. 2000; 65: 2900
- 12a Johnson AW. J. Org. Chem. 1963; 28: 252
- 12b Mugnier Y, Gard J.-C, Huang Y, Couture Y, Lasia A, Lessarc J. J. Org. Chem. 1993; 58: 5329
- 12c Abou-Gharbia M, Joullie MM. Synthesis 1977; 5: 318
- 12d Magid A, Abou-Gharbia MA, Joulli MM. J. Org. Chem. 1979; 44: 2961
- 12e Breuer E, Aurich HG, Nielsen A In Nitrones and Nitronic Acid Derivatives: An Update in Nitrones, Nitronates and Nitroxides . John Wiley and Sons; Chichester: 1989
- 12f Feuer H In Nitrile Oxides, Nitrones and Nitronates in Organic Synthesis: Novel Strategies in Synthesis. 2nd ed. John Wiley and Sons; Chichester: 2008
For reviews on indole synthesis, see:
For some recent reports on indole synthesis, see:
For earlier reports on nitrone to indole conversions, see:
For additional references on 3-substituted indoles, see:
For nitrone syntheses, see: