7334
M. L. Kantam et al. / Tetrahedron Letters 48 (2007) 7332–7334
aldehyde (Table 2, entries 4–7) or aliphatic aldehydes
Table 2, entries 12 and 13) and phenylacetylene. Diben-
zylamine and diallylamine (Table 2, entries 6 and 7)
show little difference in the yield compared to other
aliphatic amines.
69, 1–44; (e) Normant, H. Adv. Org. Chem. 1960, 2, 1; (f)
Ioffe, S. T.; Nesmeyanov, A. N. The Organic Compounds
of Magnesium, Beryllium, Calcium, Strontium and Barium;
North-Holland: Amsterdam, 1976.
. (a) Ringdahl, B. In The Muscarinic Receptors; Brown, J.
H., Ed.; Humana Press: Clifton, NJ, 1989; (b) Miura, M.;
Enna, M.; Okuro, K.; Nomura, M. J. Org. Chem. 1995,
(
2
The order of reactivity for these amines in terms of
yields and the reaction time was piperidine > pyr-
rolidine > morpholine > dibenzylamine > dially amine.
Amongst the various aldehydes tested (aliphatic, aro-
matic and heteroaromatic aldehydes), aryl aldehydes
possessing an electron-withdrawing group such as 4-
cyanobenzaldehyde afforded better yields (Table 2,
entry 8) than those with an electron-donating group
such as 4-methoxybenzaldehyde (Table 2, entry 9).
Heteroaromatic aldehydes such as furfuraldehyde and
6
0, 4999; (c) Jenmalm, A.; Berts, W.; Li, Y. L.; Luthman,
K.; Csoregh, I.; Hacksell, U. J. Org. Chem. 1994, 59, 1139;
(d) Dyker, G. Angew. Chem. 1999, 38, 1698; (e) Naota, I.;
Takaya, H.; Murahashi, S. I. Chem. Rev. 1998, 98, 2599.
3. (a) Kopka, I. E.; Fataftah, Z. A.; Rathke, M. W. J. Org.
Chem. 1980, 45, 4612–4616; (b) Imada, Y.; Yuassa, M.;
Nakamura, I.; Murahashi, S. I. J. Org. Chem. 1994, 59,
2
282–2284; (c) Czerneck, S.; Valery, J. M. J. Carbohydr.
Chem. 1990, 9, 767.
. (a) Fischer, C.; Carreira, E. M. Org. Lett. 2001, 3, 4319–
4
4
(
5
321; (b) Li, C. J.; Wei, C. Chem. Commun. 2002, 268–269;
c) Wei, C.; Li, C. J. J. Am. Chem. Soc. 2002, 124, 5638–
639; (d) Koradin, C.; Polborn, K.; Knochel, P. Angew.
Chem., Int. Ed. 2002, 41, 2535–2538.
2
-thiophenecarboxaldehyde reacted with piperidine
and phenylacetylene to afford the corresponding propar-
gylamines in good yields. The reactivity of aliphatic
aldehydes such as cyclohexanecarboxaldehyde, valeral-
dehyde and isovaleraldehyde was low compared to aro-
matic aldehydes (Table 2, entries 12–14). There was not
much difference in the yield when the aryl group of the
phenyl acetylene was substituted with a 4-methoxy or
5. (a) Yan, W.; Wang, R.; Xu, Z.; Xu, J.; Lin, L.; Shen, Z.;
Zhou, Y. J. Mol. Catal. A: Chem. 2006, 255, 81; (b)
Zhang, Y.; Santos, A. M.; Herdtweck, E.; Mink, J.; Kuhn,
F. E. New J. Chem. 2005, 29, 366; (c) Wei, C.; Li, Z.; Li, C.
J. Org. Lett. 2003, 5, 4473; (d) Li, Z.; Wei, C.; Chen, L.;
Varma, R. S.; Li, C. J. Tetrahedron Lett. 2004, 45, 2443–
4
-methyl group (Table 2, entries 15–18).
2
446.
6
. (a) Wei, C.; Li, Z.; Li, C. J. Synlett 2004, 1472; (b) Wei, C.;
Li, C. J. J. Am. Chem. Soc. 2003, 125, 9584.
. Lo, V. K. Y.; Liu, Y.; Wong, M. K.; Che, C. M. Org. Lett.
2006, 8, 1529.
It is assumed that zinc forms a zinc acetylide intermedi-
15
ate by the C–H bond activation of the alkyne. The zinc
acetylide intermediate thus generated will react with the
iminium ion prepared in situ from the aldehyde and the
amine and form the corresponding propargylamine,
water and metallic zinc. Thus the regenerated zinc par-
ticipates further in the reaction and completes the cata-
lytic cycle.
7
8. (a) Shi, L.; Tu, Y. Q.; Wang, M.; Zhang, F. M.; Fan, C. A.
Org. Lett. 2004, 6, 1001; (b) Syeda, H. Z. S.; Halder, R.;
Karla, S. S.; Das, J.; Iqbal, J. Tetrahedron Lett. 2002, 43,
6
485; (c) Kabalka, G. W.; Wang, L.; Pagni, R. M. Synlett
001, 676.
2
9
. Fischer, C.; Carreira, E. M. Org. Lett. 2001, 3, 4319.
1
1
0. Hua, L. P.; Lei, W. Chin. J. Chem. 2005, 23, 1076.
1. Choudary, B. M.; Sridhar, C.; Kantam, M. L.; Sreedhar,
B. Tetrahedron Lett. 2004, 45, 7319.
In conclusion, we have developed a simple and efficient
method for the three-component coupling of aldehydes,
amines and alkynes in acetonitrile at reflux to yield
propargylamines in moderate to very good yields using
Zn dust. Zinc dust can be readily recovered and reused
thus making this procedure more environmentally
acceptable. We believe that this methodology will find
widespread use in organic synthesis for the preparation
of propargylamines.
1
2. Kantam, M. L.; Prakash, B. V.; Reddy, C. R. V.;
Sreedhar, B. Synlett 2005, 2329.
13. (a) Kidwai, M.; Bansal, V.; Kumar, A.; Mozumdar, S.
Green Chem. 2007, 9, 742; (b) Kidwai, M.; Bansal, V.;
Mishra, N. K.; Kumar, A.; Mozumdar, S. Synlett 2007,
1
581.
1
4. (a) Bazin, S.; Feray, L.; Vanthuyne, N.; Siri, D.; Bertrand,
M. P. Tetrahedron 2007, 63, 77; (b) Fan, R.; Pu, D.; Qin,
L.; Wen, F.; Yao, G.; Wu, J. J.Org. Chem. 2007, 72, 3149.
5. Fischer, C.; Carreira, E. M. Org. Lett. 2004, 6, 1497.
1
Acknowledgement
16. Typical procedure for the 3CC reaction: Zn dust (10 mg or
5 mol %) was added to a mixture of 4-chlorobenzalde-
hyde (1 mmol), piperidine (1.1 mmol) and phenylacetylene
1.2 mmol) in acetonitrile (3 mL) at reflux, and the mixture
1
V.B., K.B.S.K. and G.T.V. thank the CSIR and UGC,
India, for their fellowships.
(
was stirred for 8 h. The progress of the reaction was
monitored by TLC and on completion, the reaction
mixture was centrifuged and the centrifugate was concen-
trated under reduced pressure to afford the crude product,
which after chromatography on silica gel (100–200 mesh)
using hexane/ethyl acetate, 90/10, gave the corresponding
References and notes
1
. For representative monographs and reviews, see: (a)
Wakefield, B. J. Organomagnesium Methods in Organic
Chemistry; Academic Press, 1995; (b) Blomberg, C. The
Barbier Reaction and Related One-Step Processes;
Springer, 1993; (c) Lai, Y. H. Synthesis 1981, 585–604;
propargylamine, N-[1-(4-chlorophenyl)-3-phenyl-2-propy-
1
nyl]piperidine. H NMR (200 MHz, CDCl
3
) d 7.57–7.54
(m, 2H), 7.49–7.45 (m, 2H), 7.31–7.28 (m, 5H), 4.72 (s,
1H), 2.54–2.5 (m, 4H), 1.62–1.54 (m, 4H), 1.5–1.45 (m,
+
(
d) Courtois, G.; Miginiac, L. J. Organomet. Chem. 1974,
2H), ESI MS (m/z): 310 (M+H) .