4438
M. Rahman et al. / Tetrahedron Letters 52 (2011) 4437–4439
nano In2O3 (5 mol%)
In summary, an efficient nano In2O3 catalyzed three-component
R1
H + CH2Cl2
NH
N
+
coupling of alkyne, dichloromethane, and amines has been
achieved. To the best of our knowledge, this is the first time report
of a non-transition metal catalyzed synthesis of propargylamines
based on C–H and C–Cl bond activations. This finding should stim-
ulate new applications of nano In2O3 in organic synthesis as an effi-
cient catalyst.
R1
DABCO
DMSO, 65 0
C
Scheme 1. Nano In2O3 catalyzed three-component coupling.
Table 1
Optimization of the reaction conditions
Acknowledgments
Catalyst
Base (2 mmol)
A.H. is pleased to acknowledge the financial support from DST,
Govt. of India (Grant No. SR/S5/GC-05/2010). A.M. acknowledges
financial support from CSIR (Grant No. 01(2251)/08/EMR-II). M.R.
and A.K.B. thank CSIR for the award of fellowships.
Bu2N
Ph
H + CH2Cl2 + n-Bu2NH
Solvent (3 mL)
65 0C, 16 h
Ph
(1 mL)
(2 mmol)
(2.2 mmol)
Entry
Catalyst
Base
Solvent
Yieldsa (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
In2O3 (nano, 5 mol %)
In2O3 (nano, 5 mol %)
In2O3 (nano, 5 mol %)
In2O3 (nano, 5 mol %)
In2O3 (nano, 5 mol %)
In2O3 (nano, 5 mol %)
In2O3 (nano, 5 mol %)
In2O3 (nano, 2 mol %)
In2O3 (nano, 10 mol %)
In2O3 (powder, 5 mol %)
La2O3 (5 mol %)
DABCO
DABCO
DABCO
DABCO
DABCO
DBU
CH3CN
DCE
1,4-Dioxane
DMF
62
60
65
78
84
64
68
65
86
56
20
72
70
38
70
References and notes
1. (a) Dyker, G. Handbook of C–H Transformations; Wiley-VCH: Weinheim, 2005;
(b) Dyker, G. Angew. Chem., Int. Ed. 1999, 38, 1698.
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
2. (a) Zhang, Y.; Li, P.; Wang, M.; Wang, L. J. Org. Chem. 2009, 74, 4364; (b) Yadav, J.
S.; Reddy, B. V. S.; Gopal, A. V.; Patil, K. S. Tetrahedron Lett. 2009, 50, 3493; (c)
Zhang, X.; Corma, A. Angew. Chem., Int. Ed. 2008, 47, 4358; (d) Li, P.; Wang, L.
Tetrahedron 2007, 63, 5455; (e) Wang, M.; Li, P.; Wang, L. Eur. J. Org. Chem.
2008, 2255; (f) Choudary, B. M.; Sridhar, C.; Kantam, M. L.; Sreedhar, B.
Tetrahedron Lett. 2004, 45, 7319; (g) Kantam, M. L.; Prakash, B. V.; Reddy, C. R.
V.; Sreedhar, B. Synlett 2005, 2329; (h) Reddy, K. M.; Babu, N. S.; Prasad, P. S. S.;
Lingaiah, N. Tetrahedron Lett. 2006, 47, 7563; (i) Park, S. B.; Alper, H. Chem.
Commun. 2005, 10, 1315; (j) Gommermann, N.; Koradin, C.; Polborn, K.;
Knochel, P. Angew. Chem., Int. Ed. 2003, 42, 5763; (k) Knopfel, T. F.;
Aschwanden, P. A.; Ichikawa, T.; Watanabe, T.; Carreira, E. M. Angew. Chem.,
Int. Ed. 2004, 43, 5971; (l) Bisai, K. A.; Singh, V. K. Org. Lett. 2006, 8, 2405; (m) Li,
C. J.; Wei, C. Chem. Commun. 2002, 268; (n) Wei, C.; Li, C.-J. J. Am. Chem. Soc.
2003, 125, 9584; (o) Wei, C.; Li, Z.; Li, C.-J. Org. Lett. 2003, 5, 4473; (p) Wei, C.; Li,
C.-J. J. Am. Chem. Soc. 2002, 124, 5638; (q) Wei, C.; Mague, J. T.; Li, C.-J. Proc. Natl.
Acad. Sci. U.S.A. 2004, 101, 5749; (r) Zhang, Q.; Chen, J.-X.; Gao, W.-X.; Ding, J.-
C.; Wu, H.-Y. Appl. Organomet. Chem. 2010, 24, 809; (s) Namitharan, K.;
Pitchumani, K. Eur. J. Org. Chem. 2010, 411.
3. (a) Napta, T.; Takaya, H.; Murahashi, S. I. Chem. Rev. 1998, 98, 2599; (b)
Yamamoto, Y.; Hayashi, H.; Saigoku, T.; Nishiyama, T. H. J. Am. Chem. Soc. 2005,
127, 10804; (c) Jiang, B.; Xu, M. Angew. Chem., Int. Ed. 2004, 43, 2543; (d)
Huffman, M. A.; Yasuda, N.; DeCamp, A. E.; Grabowski, E. J. J. J. Org. Chem. 1995,
60, 1590; (e) Konishi, M.; Ohkuma, H.; Tsuno, T.; Oki, T.; VanDuyne, G. D.;
Clardy, J. J. Am. Chem. Soc. 1990, 112, 3715; (f) Miura, M.; Enna, M.; Okuro, K.;
Nomura, M. J. Org. Chem. 1995, 60, 4999; (g) Jenmalm, A.; Berts, W.; Li, Y. L.;
Luthman, K.; Csoregh, I.; Hacksell, U. J. Org. Chem. 1994, 59, 1139.
K2CO3
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
ZnO (nano, 5 mol %)
CuO (nano, 5 mol %)
NiO (nano, 5 mol %)
FeCl3 (5 mol %)
a
Isolated yields.
Table 2
One-pot synthesis of propargylamines
nano In2O3 (5 mol%)
DABCO (1 equ.)
DMSO, 65 0C
R1
H + CH2Cl2
+
NH
N
R1
Entry
Alkyne R1
Amine
Time (h)
Yieldsa (%)
1
2
3
4
5
6
7
8
Ph
n-Bu2NH
15
15
20
16
20
18
18
16
84
82
72
80
68
84
82
85
4. Aguilar, D.; Contel, M.; Urriolabeitia, E. P. Chem. Eur. J. 2010, 16, 9287.
5. Yu, D.; Zhang, Y. Adv. Synth. Catal. 2011, 353, 163.
Ph
n-Oc2NH
Ph
Ph
Ph
4-MeC6H4
4-MeC6H4
4-MeC6H4
Pyrrolidine
Piperidine
Morpholine
n-Bu2NH
n-Oc2NH
Piperidine
6. (a) Astruc, D.; Lu, F.; Aranzaes, J. R. Angew. Chem., Int. Ed. 2005, 44, 7852; (b)
Astruc, D. Inorg. Chem. 2007, 46, 1884; (c) Durand, J.; Teuma, E.; Gomez, M. Eur.
J. Inorg. Chem. 2008, 3577; (d) Polshettiwar, V.; Baruwati, B.; Varma, R. S. Green
Chem. 2009, 11, 127; (e) Adak, L.; Chattopadhyay, K.; Ranu, B. C. J. Org. Chem.
2009, 74, 3982; (f) Dey, R.; Chattopadhyay, K.; Ranu, B. C. J. Org. Chem. 2008, 73,
9461; (g) Moreno-Manas, M.; Pleixats, R. Acc. Chem. Res. 2003, 36, 638; (h)
Jammi, S.; Sakthivel, S.; Rout, T.; Mandal, S.; Mitra, R.; Saha, P.; Punniyamurthy,
T. J. Org. Chem. 2009, 74, 1971; (i) Zhang, W.; Zhang, X.; Tian, Y.; Yue, Y.; Guo, Y.;
Wang, Z. J. Org. Chem. 2011, 76, 4741.
9
n-Oc2NH
n-Bu2NH
18
20
82
65
S
10
n-C4H9
7. (a) Ghosh, R.; Maiti, S. J. Mol. Catal. A: Chem. 2007, 264, 1; (b) Loh, T. P.; Chua, G.
L. Chem. Commun. 2006, 2739; (c) Chauhan, K. K.; Frost, C. G. J. Chem. Soc., Perkin
Trans. 1 2000, 3015; (d) Cintas, P. Synlett 1995, 1087; (e) Podlech, J.; Maier, T. C.
Synthesis 2003, 633; (f) Nair, V.; Ros, S.; Jayan, C. N.; Pillai, B. S. Tetrahedron
2004, 60, 1959; (g) Ranu, B. C. Eur. J. Org. Chem. 2000, 2347; (h) Auge, J.; Lubin-
Germain, N.; Uziel, J. Synthesis 2007, 1739; (i) Hoppe, H. A. F.; Lloyd-Jones, G. C.;
Murray, M.; Peakman, T. M.; Walsh, K. E. Angew. Chem., Int. Ed. 1998, 37, 1545;
(j) Trost, B. M.; Livingston, R. C. J. Am. Chem. Soc. 2008, 130, 11970; (k)
Nishimoto, Y.; Ueda, H.; Inamoto, Y.; Yasuda, M.; Baba, A. Org. Lett. 2010, 12,
3390; (l) Yasuda, M.; Yamasaki, S.; Onishi, Y.; Baba, A. J. Am. Chem. Soc. 2004,
126, 7186; (m) Koszinowski, K. J. Am. Chem. Soc. 2010, 132, 6032; (n) Yadav, J.
S.; Antony, A.; George, J.; Reddy, B. V. S. Eur. J. Org. Chem. 2010, 591; (o) Jadav, J.
S.; Antony, A.; George, J.; Reddy, B. V. S. Curr. Org. Chem. 2010, 14, 414.
8. (a) Kundu, D.; Samim, M.; Majee, A.; Hajra, A. Chem. Asian J. 2011, 6, 406; (b)
Kundu, D.; Majee, A.; Hajra, A. Tetrahedron Lett. 2009, 50, 2668; (c) Urinda, S.;
Kundu, D.; Majee, A.; Hajra, A. Heteroat. Chem. 2009, 20, 232; (d) Ranu, B. C.;
Dey, S. S.; Hajra, A. Tetrahedron 2002, 58, 2529; (e) Ranu, B. C.; Samanta, S.;
Hajra, A. Synlett 2002, 987; (f) Ranu, B. C.; Hajra, A. J. Chem. Soc., Perkin Trans. 1
2001, 355; (g) Ranu, B. C.; Hajra, A. J. Chem. Soc., Perkin Trans. 1 2001, 2262; (h)
Ranu, B. C.; Hajra, A.; Jana, U. Tetrahedron Lett. 2002, 41, 531; (i) Ranu, B. C.;
Hajra, A.; Jana, U. J. Org. Chem. 2000, 65, 6270; (j) Ranu, B. C.; Hajra, A.; Jana, U.
Org. Lett. 1999, 1, 1141.
a
Isolated yields.
piperidine, pyrrolidine, morpholine, dibutyl amine, and dioctyl
amine reacted well under these conditions. However, the reaction
with N-methylaniline was not successful. In general reactions are
clean, and products were obtained in high yields. The structures
of all the products were determined from their spectral and analyt-
ical data and by direct comparison with the authentic samples.
Regarding the mechanistic path of the present reactions, we as-
sume that it follows the similar route as described for the gold4
and copper5 catalyzed reactions. Accordingly, the plausible reac-
tion path will be the initial formation of alkynylindium species
which reacts with dichloromethane followed by coupling of amine
to afford propargylamines. In2O3 nanoparticles are recyclable with-
out loss of significant catalytic activity. In a typical experiment the
catalyst was reused for three times (recovery amount, 88% and
yield, 76% after 3rd run for entry 1, Table 2).
9. Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org. Lett. 2009, 11, 1697.
10. General procedure:
A mixture of alkyne (2 mmol), amine (2.2 mmol),
dichloromethane (1 mL), DABCO (2 mmol), and nano In2O3 (5 mol %) in