The gold catalyst system was then applied to various
terminal alkynes and arynes, and the results are summarized
in Table 2. A range of alkyl-substituted alkynes afforded the
desired biphenyl derivatives in good yields (Table 2, entries
1–2, 8–9). Aryl substituents were well tolerated with electron-
donating and fluoride-substituted aryl alkynes (Table 2,
entries 3–7). The coupling reaction also demonstrated a toler-
ance toward a variety of arynes (Table 2, entries 8–14).
Notably, the conjugated enyne smoothly underwent the selec-
tive reaction and afforded the biphenyl compounds containing
1,4-enyne (Table 2, entries 15–16). The 2-ethynylpyridine was
also found to be a viable substrate for the gold-catalyzed aryne
reaction (Table 2, entry 17). Moreover, terminal alkyne bear-
ing activated hydrogen like prop-2-yn-1-ol has been found to
be a reliable reaction parterner and a moderate yield can be
obtained (Table 2, entry 18). The reaction of 4-methylbenzyne
and 4-fluorobenzyne gave a mixture of regioisomers.
In conclusion, the gold catalysts have been proven to be
unique catalysts for the tandem assembly of terminal alkynes
and arynes, which leads to a facile and efficient method for the
preparation of useful alkynylated biphenyl derivatives under
mild conditions. Further studies for elucidating the reaction
mechanism and extending the substrates are ongoing.
This work was supported by Natural Science Foundation of
P.R. China (No. 205710631).
Notes and references
1 A. Stephen and K. Hashmi, Chem. Rev., 2007, 107, 3180–3211; A.
Furstner and P. W. Davies, Angew. Chem., Int. Ed., 2007, 46,
¨
3410–3449; D. J. Gorin and F. D. Toste, Nature, 2007, 446, 395–403.
2 M. Haruta, Nature, 2005, 437, 1098–1099; E. Mizushima, K. Sato, T.
Hayashi and M. Tanaka, Angew. Chem., Int. Ed., 2002, 41, 4563–4565.
3 T. Schwier, A. W. Sromek, D. M. L. Yap, D. Chernyak and V.
Gevorgyan, J. Am. Chem. Soc., 2007, 129, 9868–9878; M. Schelwies,
A. L. Dempwolff, F. Rominger and G. Helmchen, Angew. Chem.,
Int. Ed., 2007, 46, 5598–5601; C.-Y. Zhou and C.-M. Che, J. Am.
Chem. Soc., 2007, 129, 5828–5829; J. Zhao, C. O. Hughes and F. D.
Toste, J. Am. Chem. Soc., 2006, 128, 7436–7437.
4 C. Nieto-Oberhuber, P. Perez-Galan, E. Herrero-Gomez, T.
Lauterbach, C. Rodriguez, S. Lopez, C. Bour, A. Rosellon, D. J.
Cardenas and A. M. Echavarren, J. Am. Chem. Soc., 2008, 130,
269–279; N. Marion and S. P. Nolan, Angew. Chem., Int. Ed.,
2007, 46, 2750–2752; D. J. Gorin, P. Dube and F. D. Toste, J. Am.
Chem. Soc., 2006, 128, 14480–14481; I. V. Seregin and
V. Gevorgyan, J. Am. Chem. Soc., 2006, 128, 12050–12051.
5 S. L. Buchwald and R. D. Broene, in Comprehensive Organome-
tallic Chemistry II, ed. E. W. Able, F. G. A. Stone and G.
Willkinson, Pergamon, Oxford, 1995, vol. 12, pp. 771–784; M.
A. Bennett and E. Wenger, Chem. Ber., 1997, 130, 1029–1042.
6 Y. Himeshima, T. Sonoda and H. Kobayashi, Chem. Lett., 1983,
1211–1214.
7 K. R. Buszek, D. Luo, M. Kondrashov, N. Brown and D.
VanderVelde, Org. Lett., 2007, 9, 4135–4137; H. Yoshida, T.
Morishita, H. Fukushima, J. Ohshita and A. Kunai, Org. Lett.,
2007, 9, 3367–3370; J. Pawlas and M. Begtrup, Org. Lett., 2002, 4,
2687–2690; Z. Liu, F. Shi, P. D. G. Martinez, C. Raminelli and R.
C. Larock, J. Org. Chem., 2008, 73, 219–226.
8 T. T. Jayanth and C.-H. Cheng, Angew. Chem., Int. Ed., 2007, 46,
5921–5924; N. Chatani, A. Kamitani, M. Oshita, Y. Fukumoto
and S. Murai, J. Am. Chem. Soc., 2001, 123, 12686–12687.
In order to study the role of gold, we performed the reaction in
the absence of gold catalyst (Table 1, entries 7–9). Given the
presence of triphenylphosphine, 1,2-diphenylethyne was isolated
in moderate to good yields with CuI, CuCl, or CuCl2 as the
catalyst, showing the crucial effect of the gold catalyst on the
reaction. Based on these results, a plausible mechanism was
proposed as shown in Scheme 2. First, the gold catalyst interacts
with benzyne to form the intermediate 1. Subsequent nucleophilic
addition of organocopper intermediate 2 generated in situ from
benzyne and copper acetylide forms the organogold intermediate
3, which liberates the addition product biphenyl derivative and
the gold catalyst by protodemetallation. In the absence of gold
catalyst, the organocopper intermediate 2 undergoes protonolysis
and provides internal alkynes. It has to be noted that the
protonolysis of the organocopper intermediate 2 was fully sup-
pressed in the presence of gold catalyst, presumably due to the
rapid ensuing transformations. The products formed were not
found when the reaction temperature was increased to 90 1C.
The intramolecular hydroarylation of as-prepared alkynylated
biphenyl derivatives was tested, which is particularly useful in the
synthesis of polycyclic aromatic systems.18 One example is the
cyclization of a catalyzed by 10 mol% AuCl(PPh3) and
10 mol% AgSbF6 to form 9-phenylphenanthrene in a moderate
yield of 63% (Scheme 3). Reactions of this type have been used in
the synthesis of several natural products.19
9 D. Pena, S. Escudero, D. Perez, E. Guitian and L. Castedo, Angew.
´ ´ ´
Chem., Int. Ed., 1998, 37, 2659–2660.
10 D. Pena, D. Perez, E. Guitian and L. Castedo, J. Am. Chem. Soc.,
1999, 121, 5827–5828; E. Yoshikawa, K. V. Radhakrishnan and Y.
Yamamoto, J. Am. Chem. Soc., 2000, 122, 7280–7286.
11 T. T. Jayanth, M. Jeganmohan and C.-H. Cheng, Org. Lett., 2005,
7, 2921–2924; E. Yoshikawa and Y. Yamamoto, Angew. Chem.,
Int. Ed., 2000, 39, 173–175.
12 Z. Liu and R. C. Larock, J. Org. Chem., 2007, 72, 223–232; T. T.
Jayanth and C.-H. Cheng, Chem. Commun., 2006, 894–896.
13 J. L. Henderson, A. S. Edwards and M. F. Greaney, J. Am. Chem.
Soc., 2006, 128, 7426–7427.
14 B. Iglesias, A. Cobas, D. Perez, E. Guitian and K. P. C. Vollhardt,
Org. Lett., 2004, 6, 3557–3560; T. T. Jayanth, M. Jeganmohan and
C.-H. Cheng, J. Org. Chem., 2004, 69, 8445–8450; Y. Sato, T.
Tamura and M. Mori, Angew. Chem., Int. Ed., 2004, 43, 2436–2440.
15 N. Asao and K. Sato, Org. Lett., 2006, 8, 5361–5363.
16 C. Xie, Y. Zhang, Z. Huang and P. Xu, J. Org. Chem., 2007, 72,
5431–5434; C. Xie and Y. Zhang, Org. Lett., 2007, 9, 781–784.
17 C. Jia, W. Lu, J. Oyamada, T. Kitamura, K. Matsuda, M. Irie and
Y. Fujiwara, J. Am. Chem. Soc., 2000, 122, 7252–7263.
Scheme 2 The possible mechanism.
18 V. Mamane, P. Hannen and A. Furstner, Chem.–Eur. J., 2004, 10,
¨
¨
4556–575; A. Furstner and V. Mamane, J. Org. Chem., 2002, 67,
6264–6267; H. Inoue, N. Chatani and S. Murai, J. Org. Chem., 2002,
67, 1414–1417.
19 A. Furstner and J. W. J. Kennedy, Chem.–Eur. J., 2006, 12,
¨
7398–7410.
Scheme 3
ꢀc
This journal is The Royal Society of Chemistry 2008
4812 | Chem. Commun., 2008, 4810–4812