842
X. Zhang et al. / Catalysis Communications 12 (2011) 839–843
Table 3
stoichiometric organic [15] or inorganic base [16] was provided to get
reasonable yields.
Studies on the reuse of CuI/[bmim]OAc in [bmim]PF6.a,b
To better understand the roles played by [bmim]OAc in this
tandem reaction, 10 mol% of CuI together with 1 equiv of NaOAc in
[bmim]PF6 were used. It turned out that no 4a but 5a was obtained
after the mixture being stirred for 6 h (Table 1, entry 21). Then, 1
equiv of Cu(OAc)2 in [bmim]PF6 were tried as both catalyst and base
for the same reaction, but 4a was not obtained either(Table 1, entry
22). Further investigations are still underway to explore the reasons
behind the superiority of CuI/[bmim]OAc over CuI/NaOAc and Cu
(OAc)2 in promoting this tandem reaction.
Round
Time (h)
Temp. (°C)
Yield (%)c
1
2
3
4
5
6
6
6
6
6
6
6
80
80
80
80
80
80
89
88
85
85
82
81
a1a, 1 mmol; 2a, 1.5 mmol; 3a, 1.2 mmol for each run.
bCuI, 0.1 mmol; [bmim]OAc, 0.2 mmol; [bmim]PF6, 1.5 g for the first run.
cIsolated yield.
3.2. Plausible pathway of the catalytic reaction
the reaction mixture was extracted with diethyl ether to remove
the product and possible by-products. The residual containing CuI/
[bmim]OAc/[bmim]PF6 was concentrated and dried under reduced
pressure at 80 °C overnight. The recovered CuI/[bmim]OAc/[bmim]PF6
system was successively reused for 5 times and no obvious loss in
its efficiency was observed (Table 3). In these reactions, [bmim]PF6
not only acted as solvent, but also as an immobilizing agent to
facilitate the catalysts recycling. It is worth to be noted herein that
with literature protocols toward 2,3-disubstituted benzo[b]furan, the
precious cuprous catalyst and the volatile and toxic organic solvents
were not recycled, which is, in our opinion, neither economically
nor environmentally sustainable.
Based on the above observations, a plausible pathway for the
formation of 2,3-disubstituted benzo[b]furan is proposed in Scheme 1.
Firstly, the condensation between 2-hydroxybenzaldehyde (1) with
amine (3) gives an active iminium intermediate A. At the same time,
CuI reacts with terminal alkyne (2) to form a Cu–alkynyl complex.
The resulting cuprous acetylide intermediate reacts with A to form
propargylamine 5. At this stage, the OAc anion of [bmim]OAc plays
its role as a base to promote the polarization of the O―H bond in 5
and thus increase the nucleophilicity of oxygen and facilitate the
intramolecular hydroaryloxylation of the C―C triple bond coordinated
with Cu(I) to give 2,3-disubstituted benzo[b]furan (4) as the final
product. It is noted that along with the formation of 4, both Cu(I) and
OAc anion are released from the intermediates and ready for the
next catalytic cycle. In this procedure, the activation effect of [bmim]
PF6 or [bmim]OAc on the condensation of 1 and 3 via hydrogen bond
formation between H on the 2-position of imidazolium cation in
[bmim]PF6 or [bmim]OAc and O of the carbonyl of aldehyde cannot be
excluded.
4. Conclusion
In summary, a highly practical and efficient synthesis of 2,3-
disubstituted benzo[b]furans via CuI/[bmim]OAc catalyzed tandem
reactions in [bmim]PF6 was developed. Compared with literature
methods, notable advantages of this procedure include: 1) low loading
of catalyst and base; 2) convenient recovery and efficient reuse of the
catalytic system; 3) avoidance of volatile organic solvents, and 4) no
aqueous work-up thereby avoiding the generation of toxic wastes.
Further studies in searching more applications of this novel catalysis
protocol are currently underway and the results will be reported in
due course.
3.3. Preparation of various benzofuran derivatives
With the optimized reaction conditions (Table 1, entry 18),
the scope and generality of this protocol was evaluated with various
2-hydroxybenzaldehydes, alkynes and amines (Table 2). It was demon-
strated that the reaction accommodated various 2-hydroxybenzaldehyde
derivatives and generated the corresponding products in good
yields. With aliphatic secondary amines including morpholine,
dibenzylamine and piperidine, the corresponding benzofuran
derivatives were produced in high efficiency. On the other hand,
no benzo[b]furan product was formed when aromatic secondary
amines, such as N-benzylaniline or N-methylaniline, were used
(Table 2, entries 19 and 20). This result was reasonably attributed to
the reduced nucleophilicity of the ―NH― moiety conjugated to an
aromatic ring. Aromatic primary amine such as aniline was also
tried, and no benzo[b]furan product was obtained (Table 2, entry
21). It was revealed that for the alkyne substrates, aromatic alkynes
were more reactive than aliphatic alkyne for this reaction (Table 2,
entry 18).
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (Nos. 20772025 and 20972042), Innovation Scientists and
Technicians Troop Construction Projects of Henan Province (No.
104100510019) and the Natural Science Foundation of Henan
Province (No. 092300410237).
Appendix A. Supplementary data
Supplementary data to this article can be found online at
doi:10.1016/j.catcom.2011.01.024.
All products were substantially purified by flash chromatography
and characterized by m.p., 1H NMR, 13C NMR and MS analysis. Spectra
data of 4a are listed as follows:
References
[1] J. Boukouvalas, M. Pouliot, J. Robichaud, S. MacNeil, V. Snieckus, Org. Lett. 8 (2006)
3597–3599.
[2] A.M. Venkatesan, O.D. Santos, J. Ellingboe, D.A. Evrard, B.L. Harrison, D.L. Smith, R.
Scerni, G.A. Hornby, L.E. Schechter, T.H. Andree, Bioorg. Med. Chem. Lett. 20
(2010) 824–827.
[3] J.R. Wang, K. Manabe, J. Org. Chem. 75 (2010) 5340–5342.
[4] M.M. Heravi, S. Sadjadi, Tetrahedron 65 (2009) 7761–7775.
[5] K. Kobayashi, Y. Shirai, S. Fukamachi, H. Konishi, Synthesis (2010) 666–670.
[6] Z. Shen, V.M. Dong, Angew. Chem. Int. Ed. 48 (2009) 784–786.
[7] C. Martínez, R. Álvarez, J.M. Aurrecoechea, Org. Lett. 11 (2009) 1083–1086.
[8] T.L. Boehm, H.D.H. Showalter, J. Org. Chem. 61 (1996) 6498–6499.
[9] N. Takeda, O. Miyata, T. Naito, Eur. J. Org. Chem. (2007) 1491–1509.
[10] M. Nakamura, L. Ilies, S. Otsubo, E. Nakamura, Org. Lett. 8 (2006) 2803–2805.
[11] R. Bernini, S. Cacchi, I. De Salve, G. Fabrizi, Synthesis (2007) 873–882.
[12] L. De Luca, G. Giacomelli, G. Nieddu, J. Org. Chem. 72 (2007) 3955–3957.
[13] M. Carril, R. SanMartin, L. Tellitu, E. Dominguez, Org. Lett. 8 (2006) 1467–1470.
4-(2-Benzyl-benzofuran-3-yl)-morpholine (4a): m.p. 107–108 °C
16
(lit.
105–108 °C);1H NMR (CDCl3, 400 MHz) δ: 3.17 (t, J=4.8 Hz,
4 H), 3.84 (t, J=4.8 Hz, 4 H), 4.16 (s, 2 H), 7.15–7.38 (m, 8 H), 7.65–
7.67 (m, 1 H); 13C NMR (CDCl3, 100 MHz) δ: 32.26, 52.57, 67.68,
111.67, 119.87, 122.06, 123.44, 126.06, 126.44, 128.48, 128.52, 128.72,
138.15, 150.21, 153.46. MS: m/z 294 [M+H].
3.4. Studies on the recovery and reuse of CuI/[bmim]OAc/[bmim]PF6
The recovery and reuse of CuI/[bmim]OAc in [bmim]PF6 were
studied by using 1a, 2a and 3a as model substrates. Upon completion,