S. Priyadarshini et al. / Tetrahedron Letters 52 (2011) 1615–1618
1617
this coupling reaction (entry 7). When pre-formed dimeric bis(
l
-
the coupled product with slightly longer reaction times (8–12 h)
in comparison to their unhindered counterparts. Thus, the reaction
of 2-iodoaniline with phenylacetylene gave 2-(phenylethynyl)ani-
line as the sole product. Uniquely, the reaction of 2-iodophenol
with phenylacetylene gave 2-phenylbenzofuran instead of the ex-
pected Sonogashira product. The scope of the present protocol was
successfully extended to substituted phenylacetylenes, such as 1-
ethynyl-4-fluorobenzene and 1-ethynyl-4-methoxybenzene. These
substrates also underwent Sonagashira-type coupling and gave
good yields of the desired coupled product (Table 2, entries 18–20).
iodo)bis((ꢀ)-sparteine)dicopper(I) and bis( -chloro)bis((ꢀ)-parte-
l
ine)dicopper(I) complexes were evaluated as catalysts (5 mol %
relative to the substrate) in DMF for the model reaction, excel-
lent yields for the desired coupled product (Table 1, entry 9
and 10) were obtained.
It can be seen that the reaction with pre-formed catalysts gives
much higher yields than that of the in situ system derived from
Cu(I) salts and (ꢀ)-sparteine.
The optimized reaction conditions18 were further extended to
the reactions of a variety of aryl halides with various phenylacetyl-
In conclusion, bis(
l-iodo)bis((ꢀ)-sparteine)dicopper(I) is
enes, using 5 mol % of pre-formed bis(
l
-iodo)bis((ꢀ)-sparte-
shown to be a versatile catalyst for Sonogashira-type cross cou-
pling reactions of various phenylacetylenes with diverse aryl ha-
lides under palladium and phosphine-free reaction conditions.
This protocol is also applicable to activated aryl chloride sub-
strates. Since this catalyst is inexpensive and easily synthesizable,
this catalytic system should find practical usage for the synthesis of
arylacetylenes.
ine)dicopper(I) catalyst, and the results are shown in Table 2. As
it can be seen from Table 2, this protocol is rather general in nature
for the reactions of electron-rich and electron-deficient haloarenes
with phenylacetylenes. The reaction of aryl iodides with phenyl-
acetylene was rather fast, and their coupling reactions gave almost
quantitative yields within 4–7 h (Table 2, entries 1 and 3). Usually,
aryl bromide substrates require slightly longer reaction times as
the reactions of bromobenzene and bromonaphthalene with
phenylacetylene took up to 5 h to afford the coupled products in
almost quantitative yields (entries 4 and 5). As illustrated in Table
2, electron-rich bromoarenes like p-bromoanisole, p-bromotolu-
ene, m-bromoanisole, m-bromotoluene, and p-bromothioanisole
require even longer reaction times (up to 11 h) to afford the
coupled products in >92% yields (entries 6–10). In contrast, reac-
tion of aryl bromide containing an electron-withdrawing group
like p-NO2 proceeded much faster to provide an excellent yield
for the coupled product (entry 11).
Acknowledgments
S.P. thanks the DST, New Delhi for the award of fellowship and
P.J.A.J. thanks the UGC, New Delhi for the award of fellowship. P.S.
thanks the RMIT-IICT joint research centre for the financial
support.
References and notes
1. (a) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed. Engl. 1991, 30, 1387–1416;
(b) Grissom, J. W.; Gunawardena, G. U.; Klingberg, D.; Huang, D. Tetrahedron
1996, 52, 6453–6518; (c) Sonogashira, K. In Synthesis, Handbook of
Organopalladium Chemistry for Organic, Negishi, E., de Meijere, A., Eds.;
Wiley-Interscience: New York, 2002; p 493; (d) Sonogashira, K. In Metal-
Catalyzed Cross-Coupling Reactions; Diedrich, F., de Meijere, A., Eds.; Wiley-VCH:
Weinheim, 2004; Vol. 1, p 319; (e) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D.
Angew. Chem. Int. Ed. Engl. 2005, 44, 4442–4489.
2. (a) Nalwa, H. S.; Miyata, S. Nonlinear Optics of Organic Molecules and Polymers;
CRC Press: Boca Raton, FL, 1997; (b) Matsumi, N.; Naka, K.; Chujo, Y. J. Am.
Chem. Soc. 1998, 120, 5112–5113; (c) Wegner, G.; Müllen, K. Electronic
Materialssthe Oligomer Approach; Wiley-VCH: Weinheim, 1998; (d) Martin, R.
E.; Diederich, F. Angew. Chem., Int. Ed. 1999, 38, 1350–1377; (e) Inouye, M.;
Takahashi, K.; Nakazumi, H. J. Am. Chem. Soc. 1999, 121, 341–345.
3. For reviews on Sonogashira reactions, see: (a) Negishi, E.; Anastasia, L. Chem.
Rev. 2003, 103, 1979–2017; (b) Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107,
874–922; (c) Doucet, H.; Hierso, J.-C. Angew.Chem., Int. Ed. 2007, 46, 834–871;
(d) Plenio, H. Angew.Chem., Int. Ed. 2008, 47, 6954–6956; (e) Heravi, M. M.;
Sadjadi, S. Tetrahedron 2009, 65, 7761–7775.
4. For examples of Pd/Cu/phosphine co-catalyzed Sonogashira reactions, see: (a)
Thorand, S.; Krause, N. J. Org. Chem. 1998, 63, 8551–8553; (b) Hundertmark, T.;
Littke, A. F.; Buchwald, S. L.; Fu, G. C. Org. Lett. 2000, 2, 1729–1731; (c) Batey, R.
A.; Shen, M.; Lough, A. J. Org. Lett. 2002, 4, 1411–1414; (d) Elangovan, A.; Wang,
In the hope of broadening the scope of the Sonogashira protocol,
we decided to check the efficiency of our catalyst system with less
reactive aryl chlorides. As depicted in Table 2, the reactions of
phenylacetylene with various aryl chlorides bearing electron-with-
drawing groups proceeded smoothly, albeit at slightly longer reac-
tion times (8–12 h). Substrates containing p-NO2, p-CN, and p-CF3
and p-COCH3 groups gave excellent yields (81–91%) for the corre-
sponding Sonogashira products (entries 12–16). No side products,
such as hydrolyzed products were obtained for sensitive functional
groups, such as cyano (CN) under our reaction conditions. Notably,
chlorobenzene reacts very slowly with phenylacetylene, and even
after 24 h of reaction, gave only a poor yield (ꢁ10%) of the coupled
product (entry 17). Electron-rich aryl chlorides, such as chlorotol-
uene and chloroanisole, did not react at all under our reaction
conditions. These results are not surprising since most of the
copper based catalysts also fail to activate deactivated substrates,
such as chlorobenzene and electron-rich chloroarenes for coupling
reactions. However, when the reaction of chlorobenzene, chloro-
toluene, and chloroanisole were preformed using high catalyst
loadings (10 and 20 mol %) poor yields were obtained. (Table 2,
entries 17, 21 and 22).
ˇ
Y.-H.; Ho, T.-I. Org. Lett. 2003, 5, 1841–1844; (e) Kollhofer, A.; Plenio, H. Adv.
Synth. Catal. 2005, 347, 1295–1300; (f) Lemay, A. B.; Vulic, K. S.; Ogilvie, W. W. J.
Org. Chem. 2006, 71, 3615–3618.
ˇ
5. For examples of copper free Sonogashira reactions, see: (a) Bohm, V. P. W.;
Herrmann, W. A. Eur. J. Org. Chem. 2000, 3679–3681; (b) Soheili, A.; Albaneze-
Walker, J.; Murry, J. A.; Dormer, P. G.; Hughes, D. L. Org. Lett. 2003, 5, 4191–
4194; (c) Carril, M.; Correa, A.; Bolm, C. Angew. Chem., Int. Ed. 2008, 47, 4862–
4865; (d) de Haro, T.; Nevado, C. J. Am. Chem. Soc. 2010, 132, 1512–1513; (e)
Panda, B.; Sarkar, T. K. Tetrahedron Lett. 2010, 51, 301–305.
6. (a) Okuro, K.; Furuune, M.; Enna, M.; Miura, M.; Nomura, M. J. Org. Chem. 1993,
58, 4716–4721; (b) Guan, J. T.; Yu, G.-A.; Chen, L.; Weng, T. Q.; Yuan, J. J.; Liu, S.
H. Appl. Organomet. Chem. 2009, 23, 75–77; (c) Lin, C.-H.; Wang, Y.-J.; Lee, C.-F.
Eur. J. Org. Chem. 2010, 4368–4371.
The present catalyst system also works efficiently for sterically
hindered aryl halides. For example, o-substituted activated o-nitro-
chlorobenzene (entry 16) and aryl iodides (Scheme 2) reacted
smoothly with phenylacetylene and furnished excellent yields of
[Cu2I2((-)-sparteine)2]
I
7. (a) Gujadhar, R. K.; Bates, C. G.; Venkataraman, D. Org. Lett. 2001, 3, 4315–4317;
(b) Saejueng, P.; Bates, C. G.; Venkataraman, D. Synthesis 2005, 111, 1706; (c)
Wang, Y. F.; Deng, W.; Liu, L.; Guo, Q. X. Chin. Chem. Lett. 2005, 16, 1197–1200.
8. Ma, D.; Liu, F. Chem. Commun. 2004, 111, 1934–1935.
9. Li, J.-H.; Li, J.-L.; Wang, D.-P.; Pi, S.-F.; Xie, Y.-X.; Zhang, M.-B.; Hu, X.-C. J. Org.
Chem. 2007, 72, 2053–2057.
10. Thakur, K. G.; Jaseer, E. A.; Naidu, A. B.; Sekar, G. Tetrahedron Lett. 2009, 50,
2865–2869.
11. Mao, J.; Guo, J.; Ji, S. J. Mol. Catal. A 2008, 284, 85–88.
12. Monnier, F.; Turtaut, F.; Duroure, L.; Taillefer, M. Org. Lett. 2008, 10,
3203–3206.
+
H
DMF, Cs2CO3
120 0C, N2,12 h
O
OH
88 %
[Cu2I2((-)-sparteine)2]
I
H
+
DMF, Cs2CO3
120 0C, N2, 8 h
NH2
NH2
92 %
13. Xie, Y.-X.; Deng, C. L.; Pi, S.-F.; Li, J.-h.; Yin, D.-L. Chin. J. Chem. 2006, 24, 1290–
1294.
Scheme 2. Reactions of 2-iodophenol and 2-iodoaniline with phenylacetylene.