3
Figure 2. ORTEP diagram of 5g
Steinbrucker, C. Angew. Chem. 1960, 72, 267; (c)
Dömling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39,
168; (d) Ugi, I. Pure Appl. Chem. 2001, 73, 187; (e)
3
All products were characterized by NMR, IR and mass
Passerini, M. Gazz. Chim. Ital. 1921, 51, 126; (f)
Van Leusen, D.; Van Leusen, A. M. Org. React.
2003, 57, 419.
spectrometry. The structure of 5g was further confirmed
14
by X-ray crystallography (Figure 2).
2
.
(a) Dömling, A. Chem. Rev. 2006, 106, 17; (b)
Rachel, S.; Eelco, R.; Romano, V. A. O. Top.
Heterocycl. Chem. 2010, 25, 95; (c) Basso, A.;
Banfi, L.; Riva, R. Eur. J. Org. Chem. 2010, 1831;
Mechanistically, the reaction is expected to proceed
through the formation of iminium ion (B) from chloro
aldehyde (1c) and aryl amine (2) via the imine (A).
Attack of the isonitrile (3) onto B generates the nitrilium
ion (C), followed by the cycloaddition of C with azide
(
(
d) Banfi, L.; Riva, R.; Basso, A. Synlett 2010, 23;
e) Zhou, H.; Wang, W.; Khorev, O.; Zhang, Y.;
Miao, Z.; Meng, T.; Shen, J. Eur. J. Org. Chem.
012, 5585; (f) Zhao, T.; Boltjes, A.; Herdtweck, E.;
2
(
4) anion would give the required product 5 as depicted
Dömling, A. Org. Lett. 2013, 15, 639.
(a) Ramon, D. J.; Yus, M. Angew. Chem. Int. Ed.
15
in Scheme 3.
3
.
2
005, 44, 1602; (b) Zhu, J.; Bienayé, H. Multi-
component Reactions, Wiley-VCH, Weinheim,
Germany, 2005; (c) Graff, C.; Ruijter, E.; Orru, R. V.
A. Chem. Soc. Rev. 2012, 41, 3969; (d) Dömling, A.;
Wang, W.; Wang, K. Chem. Rev. 2012, 112, 3083;
(e) Koopmanschap, G.; Ruijter, E.; Orru, R. V. A.
Beilstein J. Org. Chem. 2014, 10, 544; (f) Shinde, A.
H.; Archith, N.; Srilaxmi, M.; Sharada, D. S.
Tetrahedron Lett. 2014, 55, 6821.
4
5
.
.
(a) Soeta, T.; Tamura, K.; Fujinami, S.; Ukaji, Y.
Org. Biomol. Chem. 2013, 11, 2168; (b) Marcos, C.
F.; Marcaccini, S.; Menchi, G.; Pepinob, R.; Torroba,
T. Tetrahedron Lett. 2008, 49, 149;
(a) Gunn, S. J.; Baker, A.; Bertram, R. D.; Warriner,
S. L. Synlett 2007, 2643; (b) Suresh babu, V. V.;
Rao, R. V. R.; Naik, S. A.; Chennakrishnareddy, G.
Tetrahedron Lett. 2007, 48, 7038; (c) Kalinski, C.;
Umkehrer, M.; Gonnard, S.; Jager, N.; Ross, G.;
Hiller, W. Tetrahedron Lett. 2006, 47, 2041; (d)
Nixey, T.; Kelly, M.; Semin, D.; Hulme, C.
Tetrahedron Lett. 2002, 43, 3681; (e) May, B. C. H.;
Abell, A. D. Tetrahedron Lett. 2001, 42, 5641; (f)
Thomas, N.; Michael, K.; Hulme, C. Tetrahedron
Lett. 2000, 41, 8729; (g) Satoh, Y.; Moliterni, J.
Synlett 1998, 528; (h) Yoo, S. E.; Gong, Y. D.
Heterocycles 1997, 45, 1251; (i) Duncia, J. V.;
Pierce, M. E.; Santella, J. B., III, J. Org. Chem.
Scheme 3. A plausible reaction path way
In conclusion, we have developed a novel Ugi-azide
coupling strategy for the synthesis of 1-tetrazolyl
tetrahydro--carboline derivatives. This method works
with a diverse range of substrates through a five-
centered four component coupling reaction. This method
is operationally simple and more convenient to produce
biologically more relevant scaffolds, which may find
application in drug discovery.
1
991, 56, 2395; (j) Zhao, T.; Boltjes, A.; Herdtweck,
Acknowledgements
E.; Dömling, A. Org. Lett. 2013, 15, 639; (k) Kaim,
L. E.; Grimaud, L. Tetrahedron 2009, 65, 2153.
K.K. thanks UGC, New Delhi for the award of a fellowship.
Supplementary data
6. (a) Wu, R.; Gao, S.; Chen, X.; Yang, G.; Pan, L.; Hu,
1
13
G.; Jia, P.; Zhong, W.; Yu, C. Eur. J. Org. Chem.
2
M. P. Molecules 2014, 19, 1544.
Wei, C.-X.; Bian, M.; Gong, G.-H. Molecules 2015,
Experimental details, characterization data, copies of H and
C
014, 3379; (b) Laine, A. E.; Lood, C.; Koskinen, A.
NMR spectrum of products can be found, in the online version, at
7
8
9
.
.
.
2
0, 5528.
References and Notes
Muszalska, I.; Sobczak, A.; Dołhań, A.; Jelińska, A.
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(a) Zabrocki, J.; Smith, G. D.; Dunbar, J. B., Jr.;
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1
.
(a) Ugi, I.; Meyer, R.; Fetzer, U.; Steinbrücker, C.
Angew. Chem. 1959, 71, 386; (b) Ugi, I.;