Au-catalyzed synthesis of benzofurans from phenols and alkynes using molecular oxygen

Article abstract of DOI:10.1016/j.catcom.2016.01.009

An efficient Au-catalyzed transformation for the synthesis of benzofurans from phenols and alkynes using molecular oxygen has been developed. The reaction proceeds smoothly with commercially available, eco-friendly oxidant and affords the products in moderate to good yields. This reaction is a facile approach for the formation of C - C and C-O bonds.

Full text of DOI:10.1016/j.catcom.2016.01.009

Catalysis Communications 77 (2016) 22–25
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Au-catalyzed synthesis of benzofurans from phenols and alkynes using
molecular oxygen
⁎
Jinqiang Liao, Pengfeng Guo , Qinlin Chen
School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528458, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient Au-catalyzed transformation for the synthesis of benzofurans from phenols and alkynes using molec-
ular oxygen has been developed. The reaction proceeds smoothly with commercially available, eco-friendly
oxidant and affords the products in moderate to good yields. This reaction is a facile approach for the formation
of C−C and C–O bonds.
Received 15 December 2015
Received in revised form 30 December 2015
Accepted 8 January 2016
Available online 11 January 2016
© 2016 Elsevier B.V. All rights reserved.
Keywords:
Au-catalyzed
Benzofurans
Phenols
Alkynes
Synthesis
1. Introduction
2. Results and discussion
Benzofuran is a core structure (See Scheme 1) that is found in
biocompounds, natural products, and pharmaceuticals and represents
an excellent template in many drug discovery endeavors [1–4]. The de-
velopment of new approaches that synthesize benzofurans [5–8] from
easily available starting materials is an important goal of synthetic
chemistry and also represents a continuing challenge. Recently, transi-
tion metal-catalyzed reactions, such as Pd [9–10], Cu [11], Au [12–14],
and Rh [15] have emerged as powerful tools for the synthesis of furans
and benzofurans in organic chemistry. Although a number of transfor-
mations for the preparation of the furan [16–19] frameworks have
been reported by a number of organic chemists, there is still an intrinsic
need to develop a new strategy for construction of benzofuran
molecules.
During the past few years, Au-catalyzed [20–25] reactions have
attracted much attention for the formation of carbon–carbon and
carbon-hetero bonds in organic chemistry due to their synthetic efficien-
cy. It is extensively used to prepare complex heterocyclic compounds,
such as furans [26–28], indoles [29–31], imidazoles [32–34]. Herein, we
have developed a novel and facile Au-catalyzed transformation from phe-
nols and alkynes utilizing molecular oxygen as the terminal oxidant.
Our initial efforts focused on the reaction of 1,2-diphenylethyne 1a
with phenol 2a for the synthesis of benzofurans and the results are sum-
marized in Table 1. The reaction of 1a with 2a was carried out in the
presence of AuCl3 in benzene only a trace amount of desired product
3a was formed. Other catalysts, such as, AuCl, PPh3Au(I)Cl, Ru(acac)2,
[RuCl2(p-cymene)]2, or Pd(OAc)2 were also employed affording very
poor conversion (Table 1, entries 2–6). To our delight, the reaction
could generate the corresponding product in 43%, 68%, 64% yields
when Au(PPh3)Cl/AgBF4, Au(PPh3)Cl/AgSbF6, or Au(PPh3)Cl/AgOTf
were used as catalyst in the reaction (Table 1, entries 7–9). Then a vari-
ety of oxidants, such as PhI(OAc)2, K2S2O8, and DDQ, were evaluated
(Table 1, entries 10–12), which did not lead to any improvement. The
effects of solvents (DMSO, DMF, dioxane, ClCH2CH2Cl) were also tested
and dioxane gives the best result (Table 1, entries 13–16).
With the establishment of a viable reaction system, the scope of this
transformation was further expanded and the results are described in
Table 2. As shown in Table 2, different substituted phenols were reacted
efficiently with 1,2-diphenylethyne. The results indicated that this pro-
cess is general and applicable for reactions of a wide variety of electron-
rich and -deficient substituted phenols. Various aliphatic substituted
phenols were employed, affording the desired products 3b–3d in good
yields (Table 2, entries 2–4). It is interesting to note that the present ap-
proach was tolerant of many other functional groups including 4-OCH3,
4-SCH3, 4-Cl, 4-Br, 2-Cl, 2-Br, 2-Ph (Table 2, entries 5–11). For further in-
vestigation, commercially available 1, 2-diphenylethyne derivatives
were employed to explore the scope of this process under the opti-
mized reaction conditions. To our delight, the reaction would be
⁎
Corresponding author.
E-mail address: guopengfeng@163.com (P. Guo).
http://dx.doi.org/10.1016/j.catcom.2016.01.009
1566-7367/© 2016 Elsevier B.V. All rights reserved.

J. Liao et al. / Catalysis Communications 77 (2016) 22–25
23
Table 1
Optimization of the reaction conditions.a
Entryb
Catalystc
Oxidant
Solvent
Yield(%)d
1
2
3
4
5
6
7
8
AuCl3
AuCl
Ru(acac)2
[RuCl2(p-cymene)]2
Pd(OAc)2
O2
O2
O2
O2
O2
O2
O2
O2
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DMSO
trace
5
N.P.
11
N.P.
15
43
68
64
32
27
N.P.
45
42
82
51
PPh3Au(I)Cl
Au(PPh3)Cl/AgBF4
Au(PPh3)Cl/AgSbF6
Au(PPh3)Cl/AgOTf
Au(PPh3)Cl/AgSbF6
Au(PPh3)Cl/AgSbF6
Au(PPh3)Cl/AgSbF6
Au(PPh3)Cl/AgSbF6
Au(PPh3)Cl/AgSbF6
Au(PPh3)Cl/AgSbF6
Au(PPh3)Cl/AgSbF6
9
O2
10
11
12
13
14
15
16
PhI(OAc)2
K2S2O8
DDQ
O2
O2
O2
DMF
dioxane
ClCH2CH2Cl
O2
a
Reaction condition:1a (0.5 mmol), 2a (0.7 mmol), catalyst (3 mol%), solvent (3 mL), 100 °C, 12 h.
Carried out in a sealed tube (25 mL).
The catalysts Ph3PAu(I)BF4, Ph3PAu(I)SbF6, and PPh3Au(I)OTf were preformed from PPh3Au(I)Cl and AgBF4, AgSbF6 or AgOTf, respectively.
GC yields.
b
c
d
successfully extended to 1,2-diphenylethyne derivatives and
afforded the desired benzofurans in moderate to good yields
(Table 2, entries 12–15).
On the basis of previous reports [35] and our experimental results, a
proposed reaction mechanism for this Au-catalyzed synthesis of furans
are described in Scheme 2. 1,2-diphenylethyne 1a is activated by gold to
Table 2
Gold-catalyzed synthesis of benzofurans.a
Entry
1
Ar
Ph
R1
H
Product
3a 79%
3b 82%
2
Ph
2-CH3
3
4
Ph
Ph
4-CH3
3c 79%
4-CH(CH3)2
3d 85%
5
6
7
Ph
Ph
Ph
4-OCH3
4-SCH3
4-Cl
3e 86%
3f 74%
(continued on next page)

24
J. Liao et al. / Catalysis Communications 77 (2016) 22–25
Table 2 (continued)
Entry
Ar
R1
Product
3g 87%
8
9
Ph
Ph
4-Br
2-Cl
3 h 76%
3i 82%
10
11
12
Ph
2-Br
2-Ph
Ph
3j 77%
Ph
3k 84%
4-CH3-Ph
3l 83%
13
3-CH3-Ph
Ph
3m 81%
14
15
3-Cl-Ph
4-F-Ph
Ph
Ph
3n 78%
give the complex A. Subsequently, an intermolecular nucleophilic addi-
tion of phenol 2a to complex A generated intermediate B which un-
dergoes an intramolecular dehydrogenation coupling in the presence
of Au and O2 to give the desire product 3a and release the Au catalyst.
3. Conclusion
In conclusion, we have developed a convenient Au-catalyzed
reaction for the synthesis of benzofurans from phenols and alkynes
using molecular oxygen. Our results better in stressing that many
phenols and alkynes are commercially available, which allows a
broad application of the new and beautiful methodology. For
Scheme 1. Important benzofurans.
Scheme 2. Proposed mechanisms.

J. Liao et al. / Catalysis Communications 77 (2016) 22–25
25
[9] Y. Gao, W. Xiong, H. Chen, W. Wu, J. Peng, Y. Gao, H. Jiang, J. Org. Chem. 80 (2015)
7456–7467.
[10] J. Li, Z. Zhu, S. Yang, Z. Zhang, W. Wu, H. Jiang, J. Org. Chem. 80 (2015) 3870–3879.
[11] W. Zeng, W. Wu, H. Jiang, L. Huang, Y. Sun, Z. Chen, X. Li, Chem. Commun. 49 (2013)
6611–6613.
[12] Y. Liu, J. Qian, S. Lou, Z. Xu, J. Org. Chem. 75 (2010) 6300–6303.
[13] A.S.K. Hashmi, T.M. Frost, J.W. Bats, Org. Lett. 3 (2001) 3769–3771.
[14] K. Graf, C.L. Rühl, M. Rudolph, F. Rominger, A.S.K. Hashmi, Angew. Chem. Int. Ed. 52
(2013) 12727–12731.
organic synthesis this is extremely useful, especially since the intermo-
lecular approach will allow the synthesis of whole libraries of benzofu-
rans, which can be extremely useful in pharmaceutical and medicinal
chemistry.
Acknowledgment
[15] Y. Komine, A. Kamisawa, K. Tanaka, Org. Lett. 11 (2009) 2361–2364.
[16] A. Sromek, A. Kel'in, V. Gevorgyan, Angew. Chem. Int. Ed. 43 (2004) 2280–2282.
[17] T. Wang, S. Shi, M.M. Hansmann, E. Rettenmeier, M. Rudolph, A.S.K. Hashmi, Angew.
Chem. Int. Ed. 53 (2014) 3715–3719.
We are grateful to the financial support of the Science and Technology
Program of Guangzhou, China, No.1563000282, the Technological Inno-
vation Special Funds of Guangdong College Students, China, No.
pdjh2015b0276, and the Project of Innovation for Enhancing Guangdong
Pharmaceutical University, Provincial Experimental Teaching Demonstra-
tion Center of Chemistry & Chemical Engineering.
[18] T. Wang, S. Shi, M. Rudolph, A.S.K. Hashmi, Adv. Synth. Catal. 356 (2014)
2337–2342.
[19] H. Cao, H.Y. Zhan, J.H. Cen, J.X. Lin, Y.G. Lin, Q.X. Zhu, M.L. Fu, H.F. Jiang, Org. Lett. 15
(2013) 1080–1083.
[20] W. Debrouwer, T.S.A. Heugebaert, B.I. Roman, C.V. Stevens, Adv. Synth. Catal. 357
(2015) 2975–3006.
[21] A.S.K. Hashmi, G.J. Hutchings, Angew. Chem. Int. Ed. 45 (2006) 7896–7936.
[22] A.S.K. Hashmi, M. Rudolph, Chem. Commun. 47 (2011) 6536–6544.
[23] D.M. Schultz, N.R. Babij, J.P. Wolfe, Adv. Synth. Catal. 354 (2012) 3451–3455.
[24] Y.-W. Sun, X.-Y. Tang, M. Shi, Chem. Commun. 51 (2015).
[25] Y. Zhou, Y. Zhai, X. Ji, G. Liu, E. Feng, D. Ye, L. Zhao, H. Jiang, H. Liu, Adv. Synth. Catal.
352 (2010) 373–378.
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.catcom.2016.01.009.
[26] J. Li, L. Liu, D. Ding, J. Sun, Y. Ji, J. Dong, Org. Lett. 15 (2013) 2884–2887.
[27] X. Zhang, Z. Lu, C. Fu, S. Ma, J. Org. Chem. 75 (2010) 2589–2598.
[28] P. Guo, Catal. Commun. 68 (2015) 58–60.
[29] Y. Wu, L. Zhu, Y. Yu, X. Luo, X. Huang, J. Org. Chem. 80 (2015) 11407–11416.
[30] A.S.K. Hashmi, W. Yang, F. Rominger, Adv. Synth. Catal. 354 (2012) 1273–1279.
[31] S. Undeela, S. Thadkapally, J.B. Nanubolu, K.K. Singarapu, R.S. Menon, Chem.
Commun. 51 (2015) 13748–13751.
[32] S. Li, Z. Li, Y. Yuan, D. Peng, Y. Li, L. Zhang, Y. Wu, Org. Lett. 14 (2012) 1130–1133.
[33] H. Cao, S. Lei, N. Li, L. Chen, J. Liu, H. Cai, S. Qiu, J. Tan, Chem. Commun. 51 (2015)
1823–1825.
References
[1] M.H.A. Aziz, P.S. Sidhu, A. Liang, J.Y. Kim, P.D. Mosier, Q. Zhou, D.H. Farrell, U.R. Desai,
J. Med. Chem. 55 (2012) 6888–6897.
[2] J.J.L. Clair, A.L. Rheingold, M.D. Burkart, J. Nat. Prod. 74 (2011) 2045–2051.
[3] Y. Liu, M. Kubo, Y. Fukuyama, J. Nat. Prod. 75 (2012) 2152–2157.
[4] W. Yuan, S. Ma, Org. Lett. 16 (2014) 193–195.
[5] L. Huang, J. Li, Y. Zhao, X. Ye, Y. Liu, L. Yan, C. Tan, H. Liu, Z. Jiang, J. Org. Chem. 80
(2015) 8933–8941.
[6] M. Takahashi, K. Nakano, K. Nozaki, J. Org. Chem. 80 (2015) 3790–3797.
[7] P. Lan, M.G. Banwell, A.C. Willis, J. Org. Chem. 79 (2014) 2829–2842.
[8] A. Hiremathad, M.R. Patil, C.K.R.K. Chand, M.A. Santos, R.S. Keri, RSC Adv. 5 (2015)
96809–96828.
[34] H. Cao, X.H. Liu, L. Zhao, J.H. Cen, J.X. Lin, Q.X. Zhu, M.L. Fu, Org. Lett. 16 (2014)
146–149.
[35] A.S.K. Hashmi, Angew. Chem. Int. Ed. 49 (2010) 5232–5241.