S. Shaaban, A. Roller, N. Maulide
SHORT COMMUNICATION
H+ generated during the first nucleophilic attack (DǞE)
triggers a ring-opening process to (at least reversibly) afford
stabilized carbenium F.[21] Attack by a second equivalent of
nucleophile finally gives title compound G.
(ESI+): calcd. for C27H25N3O [M
430.1886.
+
Na]+ 430.1895; found
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, characterization data, and copies of the
1H NMR and 13C NMR spectra for all key intermediates and final
products.
Acknowledgments
Generous financial support of this research by the Deutsche For-
schungsgemeinschaft (DFG) (grant numbers MA 4861/1-2 and
MA 4861/4-2) and the University of Vienna is acknowledged.
N. M. is recipient of the EurJOC Young Researcher Award 2015.
[1] a) R. J. Sundberg, Indoles, Academic, London, UK, 1996; b) J.
Saxton, Nat. Prod. Rep. 1997, 14, 559–590; c) E. Fattorusso,
O. Taglialatela-Scafati, Modern Alkaloids. Structure, Isolation,
Synthesis and Biology, Wiley-VCH, Weinheim, Germany, 2008;
d) M. Bandini, A. Eichholzer, Angew. Chem. Int. Ed. 2009,
48, 9608–9644; Angew. Chem. 2009, 121, 9786–9824; e) A. J.
Kochanowska-Karamyan, M. Hamann, Chem. Rev. 2010, 110,
4489–4497.
[2] a) M. Makosza, K. Wojciechowski, Chem. Rev. 2004, 104,
2633–2666; b) S. Lakhdar, M. Westermaier, F. Terrier, R. Gou-
mont, T. Boubaker, A. Ofial, H. Mayr, J. Org. Chem. 2006, 71,
9088–9095; c) C. T. Walsh, ACS Chem. Biol. 2014, 9, 2718–
2728.
[3] a) R. Veluri, I. Oka, I. Wagner-Döbler, H. Laatsch, J. Nat.
Prod. 2003, 66, 1520–1523; b) M. Bhuiyan, Y. Li, S. Banerjee,
F. Ahmed, Z. Wang, S. Ali, F. Sarkar, Cancer Res. 2006, 66,
10064–10072; c) S. Bharate, S. Sawant, P. Singh, R. Vishwak-
arma, Chem. Rev. 2013, 113, 6761–6815.
[4] a) D. Vassylyev, S. Sekine, O. Laptenko, J. Lee, M. Vassylyeva,
S. Borukhov, S. Yokoyama, Nature 2002, 417, 712–719; b) E.
Johnston, P. Lewis, R. Griffith, Protein Sci. 2009, 18, 2287–
2297; c) N. Bhatnagar, X. Li, Y. Chen, X. Zhou, S. Garrett, B.
Guo, Cancer Prev. Res. 2009, 2, 581–589; d) A. Kamal, Y. V.
Srikanth, M. Khan, T. Shaik, M. Ashraf, Bioorg. Med. Chem.
Lett. 2010, 20, 5229–5231.
Scheme 6. Proposed mechanism for this transformation.
Conclusions
In conclusion, we developed a new synthesis of bis(ind-
olyl)alkane derivatives. This method hinges on the visible-
light mediated, metal-free catalytic transformation of diazo-
nium salts through facile 1,5-hydrogen migration of an aryl
radical intermediate. The use of a diol as a bis-nucleophile
generates a cyclic acetal, which showcases the versatility of
the process.
[5] a) B. Bandgar, K. Shaikh, Tetrahedron Lett. 2003, 44, 1959–
1961; b) X. Feng, C. Guan, C. Zhao, Synth. Commun. 2004,
34, 487–492; c) B.-S. Liao, J.-T. Chen, S.-T. Liu, Synthesis 2007,
3125–3128; d) H. Veisi, R. Gholbedaghi, J. Malakootikhah, A.
Sedrpoushan, B. Maleki, D. Kordestani, J. Heterocycl. Chem.
2010, 47, 1398–1405; e) S. Mendes, S. Thurow, M. Fortes, F.
Penteado, E. Lenardao, D. Alves, G. Perin, R. Jacob, Tetrahe-
dron Lett. 2012, 53, 5402–5406.
[6] a) V. K. Rao, M. S. Rao, N. Jain, J. Panwar, A. Kumar, Org.
Med. Chem. Lett. 2011, 1, 1–7; b) M. Munoz, M. de la Torre,
M. Sierra, Chem. Eur. J. 2012, 18, 4499–4504; c) N. Groome,
E. Elboray, M. Inman, H. Dondas, R. Phillips, C. Kilner, R.
Grigg, Chem. Eur. J. 2013, 19, 2180–2184.
[7] a) H. Xu, Y. Zi, X. Xu, S. Wang, S. Ji, Tetrahedron 2013, 69,
1600–1605; b) M. Mari, A. Tassoni, S. Lucarini, M. Fanelli,
G. Piersanti, G. Spadoni, Eur. J. Org. Chem. 2014, 3822–3830;
c) M. Mielczarek, R. Devakaram, C. Ma, X. Yang, H. Kande-
mir, B. Purwono, D. Black, R. Griffith, P. Lewis, N. Kumar,
Org. Biomol. Chem. 2014, 12, 2882–2894.
[8] a) H. Cano-Yelo, A. Deronzier, J. Chem. Soc. Perkin Trans. 2
1984, 1093–1098; b) D. Nagib, M. Scott, D. W. C. MacMillan,
J. Am. Chem. Soc. 2009, 131, 10875–10877; c) J. Du, T. Yoon,
J. Am. Chem. Soc. 2009, 131, 14604–14605; d) J. Nguyen, E.
D’Amato, J. R. Narayanam, C. Stephenson, Nat. Chem. 2012,
4, 854–859; e) X. Shu, M. Zhang, Y. He, H. Frei, F. Toste, J.
Am. Chem. Soc. 2014, 136, 5844–5847; f) D. P. Hari, T. Hering,
B. König, Angew. Chem. Int. Ed. 2014, 53, 725–728; Angew.
Chem. 2014, 126, 743–747.
Experimental Section
N-[4,4-Di(1H-indol-3-yl)butyl]benzamide (4a). Typical Procedure: In
a tube equipped with a magnetic stirring bar, Eosin Y (0.02 equiv.),
aryl diazonium tetrafluoroborate 2a (0.2 mmol, 1 equiv.), and ind-
ole 3a (2.5 equiv.) were dissolved in dry DMSO (0.2 m). The tube
was irradiated through the tube’s bottom side by using green light-
emitting diodes (110 W). After 2 h of irradiation, the mixture was
transferred to a separatory funnel and diluted with ethyl acetate.
The mixture was then sequentially washed with water and extracted
with ethyl acetate. The combined organic layer was dried with
Na2SO4, filtered, and concentrated in vacuo. Purification of the
crude product by flash column chromatography (hexane/ethyl acet-
ate, 5:1 to 1:1) gave 4a as a purple oil in 71% yield. 1H NMR
(400 MHz, CDCl3): δ = 7.91–7.85 (s, 2 H), 7.58–7.53 (d, J = 7.8 Hz,
2 H), 7.51–7.48 (d, J = 8.0 Hz, 2 H), 7.40–7.34 (t, J = 7.2, 7.4 Hz,
1 H), 7.32–7.26 (t, J = 7.9, 7.7 Hz, 2 H), 7.24–7.19 (d, J = 8.5 Hz,
2 H), 7.08–7.03 (t, J = 7.8, 7.7 Hz, 2 H), 6.96–6.90 (t, J = 7.5,
7.3 Hz, 2 H), 6.87–6.84 (d, J = 2.4 Hz, 2 H), 5.94–5.86 (s, 1 H),
4.44–4.38 (t, J = 7.5, 7.4 Hz, 1 H), 3.40–3.34 (q, 2 H), 2.25–2.17
(q, 2 H), 1.66–1.57 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 167.6, 136.7, 134.2, 131.4, 128.5, 127.0, 128.5 (2 C), 126.9, 126.7
(2 C), 121.8 (2 C), 121.6 (2 C), 119.8 (2 C), 119.5 (2 C), 119.1 (2
C), 111.2 (2 C), 40.1, 33.9, 32.9, 28.3 ppm. IR (neat): ν = 3412,
˜
3053, 3938, 1640, 1527, 1455, 1264, 1095, 1010, 791 cm–1. HRMS
7646
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 7643–7647