CuSCN-mediated homocoupling of terminal alkynes to 1,3-diynes using 4-nitrobenzenediazonium tetrafluoroborate as oxidant

Article abstract of DOI:10.3184/174751916X14622729380672

Eleven 1,3-diynes have been prepared by a highly efficient base-catalysed homocoupling of terminal alkynes mediated by a novel combination of CuSCN/4-nitrobenzenediazonium tetrafluoroborate.

Full text of DOI:10.3184/174751916X14622729380672

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 JUNE, 335–337
RESEARCH PAPER 335
CuSCN-mediated homocoupling of terminal alkynes to 1,3-diynes using
-nitrobenzenediazonium tetrafluoroborate as oxidant
4
a,c
a
b
b
a,c
Haidong Liu , Bo Chen , Jin Cai , Junqing Chen and Min Ji *
a
School of Biological Science and Medical Engineering, Southeast University, Si Pai Lou 2#, Nanjing city 210096, P.R. China
School of Chemistry and Chemical Engineering, Southeast University Si Pai Lou 2#, Nanjing city 210096, P.R. China
Suzhou Key Laboratory of Biomaterials and Technologies & Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou, 215123, P.R. China
b
c
Eleven 1,3-diynes have been prepared by a highly efficient base-catalysed homocoupling of terminal alkynes mediated by a novel
combination of CuSCN/4-nitrobenzenediazonium tetrafluoroborate.
Keywords: 4-nitrobenzenediazonium tetrafluoroborate, homocoupling reaction, oxidant, terminal alkynes, 1,3-diynes, CuSCN, DBU
1
,3-Diyne derivatives play a very important role in natural
and 1.0 equiv. TMEDA without use of palladium reagent
under argon. However, no desired product was observed in
the presence of Cs CO in DMF at various temperatures.
Interestingly, the homocoupling product of phenylacetylene was
isolated in 87% yield. This encouraging result led us to explore
the homocoupling reaction of phenylacetylene (I; R = Ph) using
arenediazonium salts as oxidant.
In order to optimise the yield, the reaction conditions were
varied by adjusting several parameters, including oxidant,
solvent, base and copper salt loading. The homocoupling
reaction of phenylacetylene 1a was chosen as the model.
As listed in Table 1, the oxidant plays an important role in
the reaction. When the model reaction was performed in the
presence of CuSCN (1.0 equiv.) and TMEDA (1.0 equiv.) in DMF
at room temperature (25–30 °C), 4-nitrobenzenediazonium
tetrafluoroborate exhibited the highest reactivity, and an 87%
yield of the desired oxidative coupling product 3a was isolated
1
2
products, oligomers and polymers, molecular recognition
processes, industrial and pharmaceutical intermediates,
and in electronic and optical materials. Homocoupling of
terminal alkynes to give 1,3-diynes was pioneered by Glaser
in 1869. In recent years, Cu(I) or Cu(II) salt mediated
Glaser coupling and related modified methods are still widely
applied in the synthesis of conjugated diynes. Traditional
homocoupling is catalysed by copper salts in the presence of
a base and a stoichiometric amount of an oxidant such as O
3
4
2
3
5
6
,7
8
9,10
2
11–13
14
15–17
an α-halocarbonyl compound,
and others.
nitrobenzene, iodine,
18–20
However, to the best of our knowledge, the study
of 4-nitrobenzenediazonium tetrafluoroborate (NBDTF) as an
oxidant in Glaser coupling reactions has not been reported.
In this paper, we report a highly efficient preparation of
symmetrical 1,3-diynes from terminal alkynes in the presence
of a strong base and Cu(I)/NBDTF.
(
entry 1). 4-Methylbenzenediazonium tetrafluoroborate 2b
Results and discussion
and benzenediazonium tetrafluoroborate 2c were found to
be inferior, and only 11–34% yields of 3a were obtained
(entries 2–3). Then the effect of solvent on the model reaction
was examined. In MeCN, a 91% yield of 3a was obtained
(entry 4). When the reaction was performed in toluene or
Recently, our research interest has focused on Sonogashira
21,22
cross-coupling reactions.
Our initial study was to attempt the
additionreactionofphenylacetyleneto4-nitrobenzenediazonium
tetrafluoroborate 2a in the presence of 1.0 equiv. CuSCN
Table 1 Effect of variation of solvent, base and catalyst-loading on the yield of 1,4-diphenyldiyne (3a; R = H) formed by the homocoupling of
a
phenylacetylene (1a; R = H) catalysed by CuSCN/DMEDA in the presence of X-benzenediazonium tetrafluoroborate 2a–c (Scheme 1)
b
Entry
1
Oxidant (equiv.)
CuSCN (equiv.)
1.0
Solvent
DMF
Base (equiv.)
Cs CO , 1.0
Yield/(%)
87
2a (1.1)
2
3
2
3
4
5
6
7
8
9
2b (1.1)
2c (1.1)
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.2
1.0
–
DMF
DMF
Cs CO , 1.0
11
34
91
65
38
83
97
37
94
–
2
3
Cs CO , 1.0
2
3
2a (1.1)
MeCN
Toluene
DCM
Cs CO , 1.0
2 3
2a (1.1)
Cs CO , 1.0
2 3
2a (1.1)
Cs CO , 1.0
2 3
2a (1.1)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
K CO , 1.0
2 3
2a (1.1)
DBU, 1.0
DBU, 1.0
DBU, 1.0
DBU, 1.0
DBU, 1.0
DBU, 1.0
2a (1.1)
10
2a (1.1)
11
2a (1.1)
12
–
1.0
1.0
1.0
–
c
13
2a (1.1)
83
14
nitrobenzene (1.1)
DBU, 1.0
–
a
c
b
Reaction conditions: (1a; R = H) (1.0 mmol), 2a–c (1.1 mmol) and CuSCN/DMEDA in solvent (4 mL) within 20 min under an air atmosphere. Isolated yield.
In the absence of TMEDA.
*
Correspondent. E-mail: 101010516@seu.edu.cn

336 JOURNAL OF CHEMICAL RESEARCH 2016
Table 2 Yields of 1,4-aryldiynes 3a–k formed by the homocoupling of
CuSCN
R
X-C H N BF
arylacetylenes 1a–k catalysed by CuSCN/DMEDA in the presence of
6
4
2
4
a
4
-nitrobenzenediazonium tetrafluoroborate 2a
2
1
b
Entry
1
Yield/%
97
94
93
95
a X = NO b X =
c X = H
Me,
2,
1
2
3
4
5
6
7
8
9
Phenylacetylene (1a)
4-Methylphenylacetylene (1b)
4-Ethylphenylacetylene (1c)
1-Ethynyl-4-pentylbenzene (1d)
4-Fluorophenylacetylene (1e)
4-Chlorophenylacetylene (1f)
4-Methoxyphenylacetylene (1g)
1-Hexyne (1h)
Base
DMEDA, solvent, r.t.
R
R
3
89
86
92
Scheme 1
c
85
87
88
76
1-Heptyne (1i)
1-Octyne (1j)
Propargyl alcohol (1k)
dichloromethane, lower yields of 3a was observed (entries
–6). We screened three bases and observed a clear activation
tendency in the following order: K CO < Cs CO < DBU
entries 7, 4 and 8). When the ratio of CuSCN to 1a was
.2:1 and 1:1 (entries 9, 10), 37 and 94% of cross-coupled
1
0
4
11
2
3
2
3
a
Reaction conditions: A mixture of (1a–k) (1.0 mmol), 2a (1.1 mmol), and CuSCN/DMEDA
(
0
in MeCN (4 mL) was treated at r.t. for 20 min under an air atmosphere.
b
Isolated yield.
conjugated 1,3-diyne 3a was obtained. We also performed
three control experiments: (1) in the absence of CuSCN, no
homocoupling product 3a was observed (entry 11); (2) in the
absence of 4-nitrobenzenediazonium tetrafluoroborate 2a, no
desired product 3a was obtained (entry 12); (3) in the absence
of TMEDA, only 83% of the corresponding 1,3-diyne 3a was
obtained (entry 13); and (4) no homocoupling product 3a was
obtained when using nitrobenzene as the oxidant (entry 14).
With the optimised conditions in hand (Table 1, entry 8),
we examined the generality and scope of this method for
the homocoupling of various substituted terminal alkynes.
Gratifyingly, the reaction demonstrated wide scope for the
structure of terminal alkynes and the yields and rates depended
upon the substrates. Terminal aromatic alkynes with various
alkyl substituents successfully underwent the homocoupling to
produce the corresponding products in very good to excellent
yields (Table 2, entries 2–4). For halophenyl alkynes 1e–f, the
corresponding products were obtained in slightly lower yields
due to the sublimation of the corresponding 1,3-diynes (entries
c
The reaction was performed in DMF.
2
2
Based on previous reports, a possible mechanism for the
sp–sp homocoupling reaction of terminal alkynes is depicted
in Scheme 2. The initial reaction of a terminal alkyne with
intermediate A results in the formation of intermediate B.
Next, the intermediate C was formed by its oxidation by
4
-nitrobenzenediazonium tetrafluoroborate 2a with release
of nitrobenzene (which was unambiguously characterised
1
by MS and HNMR). The intermediate C further reacted
with a terminal alkyne to give the intermediate D, reductive
elimination of which afforded the corresponding 1,3-diyne.
Experimental
All reagents including analytical-grade solvents were purchased from
Sigma–Aldrich (USA), Aladdin (P.R. China), or Sinopharm Chemical
Reagent (P.R. China) and used without further purification. Melting
points are uncorrected. NMR spectra were obtained on a Bruker 400
1
13
MHz spectrometer ( H NMR at 400 Hz, C NMR at 100 Hz) in CDCl3
or DMSO-d using TMS as internal standard. Chemical shifts (δ) are
5
–6). In the case of 4-methoxyphenylacetylene, the reaction
6
given in ppm and coupling constants (J) in Hz. Mass spectra (MS)
were obtained from Finnigan (USA) MAT-95 Spectrometry Services.
Silica gel (200–300 µm) for flash chromatography was purchased from
Qingdao Haiyang Chemical (P.R. China).
was sluggish due to the low solubility of the corresponding
copper acetylide, but when the reaction was performed in DMF,
a good yield was obtained (entry 7). For aliphatic alkynes 1h–j
and propargyl alcohol 1k, the corresponding products were
also obtained in moderate to good yields (entries 8–11). All
compounds are known and were characterised by their m.p.,
Synthesis of 1,3-diynes; general procedure
Terminal alkynes (1.0 mmol), CuSCN (1.0 mmol), MeCN (4 mL) and
TMEDA (1.0 mmol) were added to a reaction bottle that was equipped
1
13
23–30
MS, and H and C NMR spectra.
BF4
N2
NO2
N
N
N
N
R
N
N
Cu SCN
Cu
R
R
Cu
R
BF4
Base
2a
B
A
C
R
N
N
Cu
R
R
Base
reductive elimination
R
D
Scheme 2

JOURNAL OF CHEMICAL RESEARCH 2016 337
2
3,27,29
with a stirrer bar under air. DBU (1.0 equiv.) was added to the reaction
mixture dropwise over 10 min. The resulting mixture was stirred at
ambient temperature (25–30 °C) for 10–30 min. A suspension of 2a
Hexadeca-7,9-diyne (3j)
1
Colourless oil, 96 mg (88%); R = 0.9 (hexane); H NMR (CDCl ): δ
ppm) 2.27 (t, J = 6.8 Hz, 4H), 1.27–1.56 (m, 16H), 0.91 (t, J = 6.8 Hz,
f
3
(
(1.1 equiv.) in MeCN (1 mL) was added to the reaction bottle under
13
6
H); C NMR (CDCl ): δ (ppm) 65.3, 31.4, 28.3, 24.7, 22.3, 20.1, 13.8;
MS (EI) for C H [M] calcd 218.2; found: 218.2.
an air atmosphere over 20 min. The mixture was stirred at ambient
temperature for 20 min, and then it was mixed with a small amount of
silica gel and concentrated. It was purified by column chromatography
using hexane to afford the pure products. All products 3a–k are known
and all the melting points are uncorrected.
3
+
16 26
2
3,28,30
Hexa-2,4-diyne-1,6-diol (3k)
White powder, 58 mg (63%), m.p. 112–113 °C (ethyl acetate/hexane)
2
3
1
[
(
lit. m.p. 112–114 °C]; R = 0.9 (ethyl acetate/hexane = 1:2). H NMR
2
3,24,26,29
f
1,4-Diphenylbutadiyne (3a)
-DMSOd ): δ (ppm) 4.83 (t, 1H), 3.50 (m, 2H), 2.39 (t, J = 6.8, 2H);
C NMR (CDCl ): δ (ppm) 66.4, 59.9, 23.5; MS (EI) for C H O [M]
calcd 110.0; found: 110.0.
26
6
White powder, 98 mg (97%), m.p. 86–88 °C (hexane) [lit. m.p.
13
+
1
3
6
6
2
8
7
1
6–87 °C]; R = 0.9 (hexane). H NMR (CDCl ): δ (ppm) 8.27 (m, 4H),
f 3
13
.73 (m, 2H), 7.57 (m, 4H); C NMR (CDCl ): δ (ppm) 132.8, 129.2, 128.7,
3
+
21.9, 81.6, 74.0; MS (EI) for C H [M] calcd 202.1; found: 202.1.
16 10
2
3,25,26,29,31
We are grateful for financial support from the National Basic
Research Program of China (No.2013AA032205).
1
,4-Bis(4-methylphenyl)-1,3-butadiyne (3b)
White powder, 108 mg (94%), m.p. 138–140 °C (hexane); R = 0.9
f
31
1
(
(
(
(
hexane) [lit. m.p. 138–140 °C]; H NMR (CDCl ): δ (ppm) 7.43
3
13
d, J = 8.0 Hz, 4H), 7.15 (d, J = 8.0 Hz, 4H), 2.39 (s, 6H); C NMR
Received 19 February 2016; accepted 1 March 2016
Paper 1603930 doi: 10.3184/174751916X14622729380672
Published online: 17 May 2016
CDCl ): δ (ppm) 139.5, 132.1, 129.2, 118.9, 121.9, 81.6, 73.5, 21.6; MS
EI) for C H [M] calcd 230.1; found: 230.1.
3
+
18
14
2
6,29
1,4-Bis(4-ethylphenyl)-1,3-butadiyne (3c)
2
6
White powder, 139 mg (93%), m.p. 96–97 °C (hexane) [lit. m.p.
References
1
9
6–97 °C]; R = 0.9 (hexanes);. H NMR (CDCl ): δ (ppm) 7.40 (d,
f
3
1
L.K. Annabelle and R.R. Tykwinski, Angew. Chem. Int. Ed., 2006, 45,
034.
J = 8.0 Hz, 4H), 7.18 (d, J = 8.0 Hz, 4H), 2.68 (d, J = 7,6 Hz, 4H), 1.26
1
13
(
8
t, J = 7.6 Hz, 6H); C NMR(CDCl ): δ (ppm) 145.7, 132.5, 128.0, 119.1,
3
+
2
3
R.E. Martin and F. Diederich, Angew. Chem. Int. Ed., 1999, 38, 1350.
J. Breitenbach, J. Boosfeld and F. Vogtle, Comprehensive supramolecular
chemistry, eds V. Vogtle. Pergamon, Oxford, 1996, Vol. 2, chap. 2, pp.
29–67.
1.6, 73.5, 28.9, 15.2; MS (EI) for C H [M] calcd 258.1; found: 258.1.
20 18
2
6,29
1,4-Bis(4-pentylphenyl)-1,3-butadiyne (3d)
2
6
White powder, 163 mg (95%), m.p. 84–85 °C (hexane) [lit. m.p.
4 °C]; R = 0.9 (hexane). H NMR (CDCl ): δ (ppm) 7.45 (d, J = 8.4
f 3
Hz, 4H), 7.16 (d, J = 8.4 Hz, 4H), 2.63 (t, J = 7,6, 8.0 Hz, 4H), 1.63 (t,
J = 7,2, 7,6 Hz, 4H), 1.36 (m, 8H), 0.92 (t, J = 6.8 Hz, 6H); C NMR
CDCl ): δ (ppm) 144.5, 132.4, 128.5, 119.1, 81.6, 73.5, 36.0, 31.4, 22.5,
3.9; MS (EI) for C H [M] calcd 342.2; found: 342.2.
1
4
5
M.M. Haley and R.R. Tykwinski, Carbon-rich compounds: from molecules
to materials. Wiley-VCH, Weinheim, 2006.
8
13
F. Diederich, P.J. Stang and R.R. Tykwinski, Acetylene chemistry:
chemistry, biology and material science. Wiley-VCH, Weinheim, 2005.
C. Glaser, Ber. Dtsch. Chem. Ges., 1869, 2, 422.
(
1
3
+
6
7
8
2
6
30
C. Glaser, Ann. Chem. Pharm., 1870, 154, 137.
2
6,29
1,4-Bis(4-fluorophenyl)-1,3-butadiyne (3e)
K. Kamata, S. Yamaguchi, M. Kotani, K. Yamaguchi and N. Mizuno,
Angew. Chem. Int. Ed., 2008, 47, 2407.
2
6
White powder, 106 mg (89%), m.p. 190–192 °C (hexane) [lit. m.p.
92–193 °C]; R = 0.9 (hexane). H NMR (CDCl ): δ (ppm) 7.54 (m,
H), 7.06 (m, 4H); C NMR (CDCl ): δ (ppm) 164.3, 161.8, 134.6, 117.9,
16.0, 80.4, 73.6; MS (EI) for C H F [M] calcd 238.1; found: 238.1.
1
1
4
1
9
J.-H. Li, Y. Liang and Y.-X. Xie, J. Org. Chem., 2005, 70, 4393.
f
3
13
3
10 A.S. Batsanov, J.C. Collings and J.J. Zhu, Org. Chem., 2005, 70, 703.
11 A. Lei, M. Srivastava and X. Zhang, J. Org. Chem., 2002, 67, 1969.
12 W.A. Chalifoux, M.J. Ferguson and R.R. Tykwinski, Eur. J. Org. Chem.,
+
16
8 2
2
9,30
1,4-Bis(4-chlorophenyl)-1,3-butadiyne (3f)
2
007, 6, 1001.
3
0
White powder, 116 mg (86%), m.p. 256–257 °C (hexane) [lit. m.p.
1
3
R. Rossi, A. Carpita and C. Bigelli, Tetrahedron Lett., 1985, 26, 523.
P. Siemsen, R.C. Livingston and F. Diederich, Angew. Chem. Int. Ed.,
2000, 39, 2632.
1
2
53 °C]; R = 0.9 (hexane). H NMR (CDCl ): δ (ppm) 7.46 (d, J = 8.4
f 3
13
14
Hz, 4H), 7.33 (d, J = 8.8 Hz, 4H); C NMR (CDCl ): δ (ppm) 133.7,
3
+
1
2
28.9, 114.0, 80.4, 74.7; MS (EI) for C H Cl [M] calcd 270.0; found:
16
8
2
15
J. Yan, F. Lin and Z. Yang, Synthesis, 2007, 9, 130.
70.0.
,4-Bis(4-methoxyphenyl)-1,3-butadiyne (3g)
White powder, 121 mg (92%), m.p. 140–142 °C (hexane); R =
16 Q. Liu and D.J. Burton, Tetrahedron Lett., 1997, 38, 4371.
2
3,26,29,30
1
17 D.-f. Li, K. Yin, J. Li and X.-sh. Jia, Tetrahedron Lett., 2008, 49, 5918.
18 J.-H. Li, Y. Liang and X.-D. Zhang, Tetrahedron, 2005, 61, 1903.
19 Y. Liao, R. Fathi and Z. Yang, Org. Lett., 2003, 5, 909.
f
3
0
1
0
(
(
.9 (hexane) [lit. m.p. 142 °C]; H NMR (CDCl ): δ (ppm) 7.49
3
13
d, J = 9.2 Hz, 4H), 6.89 (d, J = 8.8 Hz, 4H), 3.85 (s, 6H); C NMR
20 S.V. Damle, D. Seomoon and P.H. Lee, J. Org. Chem., 2003, 68, 7085.
21 R. Chinchilla and C. Najera, Chem. Rev., 2007, 107, 874.
CDCl ): δ (ppm) 160.3, 134.0, 124.2, 114.2, 81.23, 73.0. 55.3; MS (EI)
3
+
for C H O [M] calcd 262.1; found: 262.1.
22 R. Chinchilla and C. Najera, Chem. Soc. Rev., 2011, 40, 5084.
18
14
2
2
3
T.-M. Wu, Sh.-H. Huang and F.-Y. Tsai, Appl. Organometal. Chem., 2011,
5, 395.
2
9
Dodeca-5,7-diyne (3h)
Colourless oil, 69 mg (85%); R = 0.9 (hexane); H NMR (CDCl ): δ
2
1
f
3
2
2
2
2
4
5
6
7
Q. Liu and D.J. Burton, Tetrahedron Lett., 1997, 38, 4371.
(
ppm) 2.27 (t, J = 6.8 Hz, 4H), 1.51 (m, 8H), 0.91 (t, J = 6.8 Hz, 6H);
C NMR (CDCl ): δ (ppm) 65.3, 30.4, 21.9, 19.7, 13.5; MS (EI) for
C H [M] calcd 162.1; found: 162.1.
J.-H. Li, Y. Liang and X.-D. Zhang, Tetrahedron, 2005, 61, 1903.
Y. Kun, L. Chunju, L. Jian and J. Xueshun, Green Chem., 2011, 13, 591.
S.V. Damle, D. Seomoon and P.H. Lee, J. Org. Chem., 2003, 68, 7085.
13
3
+
12
18
2
6,29
Tetradeca-6,8-diyne (3i)
Colourless oil, 83 mg (87%); R = 0.9 (hexane); H NMR (CDCl ): δ
ppm) 2.26 (t, J = 6.8 Hz, 4H), 1.32–1.57 (m, 12H), 0.91 (t, J = 6.8 Hz,
28 N.A. Milas and O.L. Mageli, J. Am. Chem. Soc., 1953, 75, 5970.
29 D.-f. Li., K. Yin, J. Li and X.-sh. Jia, Tetrahedron Lett., 2008, 49, 5918.
30 E. Merkul, D. Urselmann and T.J.J. Müller, Eur. J. Org. Chem., 2011, 2,
238.
1
f
3
(
6
13
H); C NMR (CDCl ): δ (ppm) 65.3, 31.0, 28.0, 22.1, 19.2, 13.9; MS
3
+
(
EI) for C H [M] calcd 190.2; found: 190.2.
31 J.-H. Li, Y. Liang and X.-D. Zhang, Tetrahedron, 2005, 61, 1903.
14
22