An efficient heterogeneous palladium(0)-catalysed cross-coupling between 1-bromoalkynes and terminal alkynes leading to unsymmetrical 1,3-diynes

Article abstract of DOI:10.3184/174751918X15208574638459

An efficient heterogeneous palladium(0)-catalysed cross-coupling of 1-bromoalkynes with terminal alkynes was achieved in DMF at room temperature in the presence of 5 mol% of MCM-41-immobilised bidentate phosphine palladium(0) complex [MCM-41-2P-Pd(0)] and 2 mol% of CuI with Et₃N as base, yielding a variety of unsymmetrical 1,3-diynes in moderate to good yields. This heterogeneous palladium(0) complex could be easily recovered by a simple filtration of the reaction solution and recycled at least seven times without significant decrease in activity.

Full text of DOI:10.3184/174751918X15208574638459

JOURNAL OF CHEMICAL RESEARCH 2018
VOL. 42 MARCH, 133–137
RESEARCH PAPER 133
An efficient heterogeneous palladium(0)-catalysed cross-coupling between
1-bromoalkynes and terminal alkynes leading to unsymmetrical 1,3-diynes
Zhaotao Xu, Jinting Ai and Mingzhong Cai*
Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Chemistry & Chemical Engineering, Jiangxi Normal University,
Nanchang 330022, P.R. China
An efficient heterogeneous palladium(0)-catalysed cross-coupling of 1-bromoalkynes with terminal alkynes was achieved in DMF at
room temperature in the presence of 5 mol% of MCM-41-immobilised bidentate phosphine palladium(0) complex [MCM-41-2P-Pd(0)]
and 2 mol% of CuI with Et3N as base, yielding a variety of unsymmetrical 1,3-diynes in moderate to good yields. This heterogeneous
palladium(0) complex could be easily recovered by a simple filtration of the reaction solution and recycled at least seven times without
significant decrease in activity.
Keywords: supported palladium catalyst, cross-coupling, 1,3-diyne, 1-bromoalkyne, heterogeneous catalysis, terminal alkynes
Conjugated diynes and polyynes are attractive compounds
since they are frequently found in a variety of biologically
active molecules and natural products.1–3 They have also
shown a wide application in organic synthesis, organometallic
chemistry and advanced organic materials.4–7 Therefore,
the development of efficient methods for the preparation of
conjugated diynes, especially unsymmetrical 1,3-diynes, has
attracted much attention.8,9 The conjugated diyne compounds
are prepared mainly by Glaser–Hay coupling3,10–12 and Cadiot–
Chodkiewicz coupling.13–15 Traditional Glaser–Hay coupling is
usually used for the construction of symmetrical 1,3-diynes.
Cadiot–Chodkiewicz coupling, developed over five decades
ago, utilises a 1-haloalkyne as the electrophile and a terminal
alkyne as the nucleophile to synthesise unsymmetrical
1,3-diynes. However, this methodology usually suffers from
complex reaction conditions16 and poor selectivity, and results in
a considerable amount of homocoupled byproducts, especially
when the electronic nature of the substituents attached to the
1-haloalkynes and the terminal alkynes are similar.1,7,17 To
inhibit homocoupling of 1-haloalkynes, excess of the terminal
alkyne is usually utilised.1 During the past three decades, several
palladium-catalysed 1,3-diyne construction methods have been
developed. Negishi and co-workers reported an efficient tandem
protocol by combining Sonogashira coupling of terminal
alkynes with ICH=CHCl with subsequent base-induced
elimination to furnish 1,3-diynes.18–20 Nye,21 Wityak,22 and
Alami and Ferri23 reported palladium-catalysed C(sp)–C(sp)
cross-coupling reactions for the construction of unsymmetrical
1,3-diynes with improved yields and selectivity in some cases.
Lei and co-workers reported an efficient palladium-catalysed
C(sp)–C(sp) cross-coupling reaction of terminal alkynes with
1-haloalkynes leading to unsymmetrical 1,3-diynes in good to
excellent yields with high selectivity.24 Recently, gold-catalysed
oxidative cross-coupling of terminal alkynes25 and Cadiot–
Chodkiewicz-type cross-coupling of terminal alkynes with
alkynyl hypervalent iodine reagents26 have been reported to be
alternative methods for selective synthesis of unsymmetrical
1,3-diynes.
Although these palladium- or gold-catalysed cross-
coupling reactions are highly efficient for the construction of
unsymmetrical 1,3-diynes, industrial applications of these
homogeneous palladium or gold catalysts remain a challenge
because they are quite expensive and are difficult to separate
from the product mixture. Recycling of homogeneous precious
metal catalysts is a task of great economic and environmental
importance in the chemical and pharmaceutical industries.27
Immobilised metal catalysts have attracted growing attention
because of the advantages of high catalytic efficiency and
easy recycling, which are important for expensive or toxic
heavy metal catalysts and flow chemistry processes.28–30
Recently, mesoporous MCM-41 materials have emerged as
smart and promising supports with great industrial potential
for immobilisation. This is due to their outstanding advantages
such as extremely high surface areas, combined with the large
and defined pore sizes of mesoporous materials, compared with
other solid supports.31–33 In our previous work, we reported the
first synthesis of an MCM-41-immobilised bidentate phosphine
palladium(0) complex [MCM-41-2P-Pd(0)] and found that
it is a highly efficient catalyst for the heterogeneous Suzuki
coupling reaction.34 In continuing our efforts to develop green
synthetic pathways for organic transformations, we report
here the first heterogeneous palladium(0)-catalysed cross-
coupling of 1-bromoalkynes with terminal alkynes leading
to unsymmetrical 1,3-diynes by using the MCM-41-2P-Pd(0)
complex as a recyclable catalyst (Scheme 1).
Results and discussion
The MCM-41-immobilised bidentate phosphine palladium(0)
complex [MCM-41-2P-Pd(0)] was prepared from commercially
readily available reagents according to the procedure34
summarised in Scheme 2. Firstly, the mesoporous material
MCM-41 was treated with 3-aminopropyltriethoxysilane in
toluene at 100 °C for 24 h, followed by silylation with Me3SiCl
in toluene at room temperature for 24 h to afford 3-amino-
propyl-functionalised MCM-41 (MCM-41-NH2). The latter
was subsequently reacted with Ph2PCH2OH, derived from the
Scheme 1
* Correspondent. E-mail: caimzhong@163.com

134 JOURNAL OF CHEMICAL RESEARCH 2018
Scheme 2
Table 1 Optimisation of palladium and copper catalysts loadingsa
reaction of Ph2PH with (CH2O)n, to generate the diphosphino-
functionalised MCM-41 (MCM-41-2P). Finally, the reaction
of MCM-41-2P with PdCl2 in acetone under reflux for 72 h,
followed by reduction with hydrazine hydrate (see SAFETY
CAUTION in Experimental) in ethanol at 30 °C for 5 h, gave
the MCM-41-immobilised bidentate phosphine palladium(0)
complex [MCM-41-2P-Pd(0)] as a grey powder. The palladium
content was determined to be 0.45 mmol g–1 by inductively
coupled plasma-atomic emission spectroscopy (ICP-AES)
analysis.
The MCM-41-immobilised bidentate phosphine palladium(0)
complex [MCM-41-2P-Pd(0)] was then used as a catalyst for
the cross-coupling reaction of 1-bromoalkynes with terminal
alkynes. In our initial screening experiments, the cross-coupling
of bromoethynylbenzene (1a) with 2-methylbut-3-yn-2-ol (2a)
in DMF as solvent with Et3N as base was selected as the model
reaction to optimise the catalyst loadings and the results are
summarised in Table 1. Palladium was essential under the tested
conditions and only 7% of the desired cross-coupling product 3a
was formed after 12 h without the Pd(0) catalyst (Table 1, entry
1). It was found that CuI was also essential in this reaction. In
the absence of CuI, only 25% of 3a was generated and a low
selectivity of 69:31 over the homocoupled product from 1a was
observed (Table 1, entry 2). When the ratio of Pd(0) catalyst to
CuI was 1:1, 72% of 3a was produced and the selectivity was
87:13 (Table 1, entry 3). Increasing the loading of CuI to 5 or
10 mol% resulted in a decreased yield and a lower selectivity
(Table 1, entries 4 and 5). At the same CuI loading (2 mol%),
enhancing the loading of the Pd(0) catalyst was observed to
increase the yield and selectivity (Table 1, entry 6), but further
increasing loading of the Pd(0) catalyst did not improve the
yield and selectivity significantly (Table 1, entry 7). Thus, the
optimal catalyst loadings were 5 mol% MCM-41-2P-Pd(0) and
2 mol% CuI (Table 1, entry 6).
MCM-41-2P-Pd(0)
CuI
+
Br
Et3N, DMF, r.t. 12 h
OH
OH
2a
1a
3a
Entry
Pd(0) (mol%)
CuI (mol%)
Yield (%)b
Selectivityc
1
2
3
4
5
6
7
0
2
2
2
2
5
8
2
0
2
5
10
2
7
25
72
61
49
–
69:31
87:13
82:18
73:27
89:11
90:10
76 (65d)
77
2
aReaction conditions: 1a (1 mmol), 2a (1.5 mmol), Et3N (2 mmol) in 2 mL of DMF at room
temperature under Ar.
bDetermined by gas chromatography with biphenyl as the internal standard.
cMolar ratio of 3a to 1,4-diphenylbutadiyne.
dIsolated yield.
When bromoethynylbenzene (1a) was the electrophile, the
cross-coupling reactions with terminal alkynes bearing either
an alkyl group or an aryl group 2b–f proceeded smoothly to
afford the corresponding unsymmetrical 1,3-diynes 3b–f in
good yields (Table 2, entries 2–6). It was noteworthy that the
protocol exhibited excellent tolerance towards a bromophenyl
group and the reaction of 1a with 1-bromo-4- ethynylbenzene
(2e) gave the desired cross-coupled 1,3-diyne 3e in 72% isolated
yield (Table 2, entry 5). 1-Bromoalkynes bearing either aliphatic
or hydroxyl groups were all suitable coupling partners in the
reactions with various terminal alkynes (Table 2, entries 7–20).
For example, 1-bromooct-1-yne (1b) and 1-bromohept-1-yne
(1c) could undergo the cross-coupling reactions with electron-
neutral, electron-rich and electron-deficient aromatic alkynes
effectively to give the desired unsymmetrical 1,3-diynes 3f–j
in moderate to good yields (Table 2, entries 7–11). The reaction
between 1c and propargyl acetate (2j) afforded the expected
product 3k in 60% yield and the reactive acetate group was
well preserved (Table 2, entry 12). Interestingly, the coupling
reaction of 1c with hex-1-yne (2k) produced the cross-coupled
With this promising result in hand, we started to examine
the scope of this heterogeneous palladium(0)-catalysed cross-
coupling reaction by employing various 1-bromoalkynes and
terminal alkynes and the results are summarised in Table 2.

JOURNAL OF CHEMICAL RESEARCH 2018 135
Table
2 Heterogeneous palladium(0)-catalysed cross-coupling of
1-bromoalkynes with terminal alkynesa
MCM-41-2P-Pd(0) (5 mol%)
CuI (2 mol%)
R1
R2
R1
R2
+
Br
Et3N, DMF, r.t. 12 h
2
3
1
Entry R1
R2
Product
Yield (%)b
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
HOMe C
HOCH2CH
MeOC2H2C2H2
4-MeOC H4
4-BrC6H46
n-C5H11
4-EtOC6H4
4-MeOC H4
4-EtC6H46
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
3f
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
65
64
66
63
72
62
59
52
49
67
58
60
51
57
46
71
52
59
55
48
n-C H13
n-C6H13
n-C6H
9
10
11
12
13
14
15
16
17
18
19
20
n-C6H13
n-C5H11
n-C5H11
4-BrC6H
MeCO C4H2
n-C4H 2
n-C55H11
11
HOMe C
HOMe2C
HOMe2C
HOMe2C
HOCH2CH
HOCH2CH2
HOCH22CH22
4-EtC69H4
3-FC6H
4-EtOC46H4
Me3Si
4-EtC H4
4-EtO6C H4
3-FC6H46
aReaction conditions: 1 (1.0 mmol), 2 (1.5 mmol), Et3N (2 mmol), MCM-41-2P-Pd(0) (5
mol%), CuI (2 mol%) in 2 mL of DMF at room temperature under Ar for 12 h.
bIsolated yield.
Scheme 3
80
70
60
50
40
30
20
10
0
product trideca-5,7-diyne (3l) in moderate yield (Table 2, entry
13). 4-Bromo-2-methylbut-3-yn-2-ol (1d) was coupled with
various terminal aromatic alkynes to give the corresponding
unsymmetrical 1,3-diynes 3m–o in 46–71% yields (Table 2,
entries 14–16). Notably, the reaction of 1d with a trimethysilyl-
functionalised terminal alkyne gave the desired product 3p in
52% yield (Table 2, entry 17). The reactions of 4-bromobut-3-
yn-1-ol (1e) also worked well with different aromatic alkynes
to furnish the corresponding cross-coupled products 3q–s in
moderate yields (Table 2, entries 18–20).
To ensure that the activity of the MCM-41-2P-Pd(0)
complex arises from the palladium sites on the channel walls
and not from the leached palladium species in solution, the
heterogeneity of the MCM-41-2P-Pd(0) complex was tested.
For this, the cross-coupling reaction of 1a with 2a (1.5 equiv.)
was carried out until a conversion of 30% of 1a was reached.
Then the catalyst was removed from the solution by filtration
and the filtrate was allowed to react further under identical
reaction conditions for 8 h. We found that, after removal of the
catalyst, no increase in conversion of 1a was observed. We also
determined the palladium content in the filtrate by ICP-AES
analysis and no palladium was detected in the clear solution.
These results rule out any contribution to the observed catalysis
from the leached palladium species, indicating that the catalyst
was stable during the reaction and the observed catalysis was
intrinsically heterogeneous.
1
2
3
4
5
6
7
8
Run times
Fig. 1 Results from recycling of the MCM-41-2P-Pd(0) catalyst.
elimination of intermediate C affords the desired 1,3-diyne 3
and regenerates the MCM-41-2P-Pd(0) complex to complete the
catalytic cycle.
For the practical application of a supported precious metal
catalyst, its ease of separation, recoverability and reusability
are important factors. This heterogeneous palladium catalyst
can be easily separated and recovered by a simple filtration
of the reaction solution. We next examined the recyclability
of the catalyst by using the cross-coupling of 4-bromo-2-
methylbut-3-yn-2-ol (1d) with 4-ethoxyphenylacetylene (2g).
After completion of the reaction, the catalyst was recovered
by a simple filtration of the reaction solution and washed with
distilled water and ethanol. After being air-dried, it could be
reused directly without further purification. The recovered
palladium catalyst was used in the next run and almost
consistent activity was observed for eight consecutive cycles
(Fig. 1). The satisfactory recyclability of the catalyst is likely
attributable to the chelating action of the bidentate phosphine
ligand on palladium and the mesoporous structure of the
MCM-41 support. The result is important from the standpoint
A plausible mechanism for the heterogeneous palladium(0)-
catalysed cross-coupling reaction of 1-bromoalkynes 1 with
terminal alkynes 2 is illustrated in Scheme 3.24 First, oxidative
addition of 1-bromoalkyne 1 to MCM-41-2P-Pd(0) gives an
MCM-41-bound bidentate phosphine R1C≡C–Pd(II)Br complex
intermediate A. Transmetalation between intermediate A and
alkynylcopper B then forms an MCM-41-bound bidentate
phosphine R1C≡C–Pd(II)–C≡CR2 complex intermediate
C. Alkynylcopper B is generated from the Cu(I) salt and
terminal alkyne 2 with the assistance of Et3N. Finally, reductive

136 JOURNAL OF CHEMICAL RESEARCH 2018
66.1, 58.8, 20.9; HRMS calcd for C13H12O+: [M+]: 184.0888; found:
184.0875.
of green and sustainable chemistry. No copper is retained in
the support.
1-Methoxy-4-(phenylbuta-1,3-diynyl)benzene (3d): White solid;
m.p. 85–87 °C (lit.36 86–89 °C); 1H NMR (400 MHz, CDCl3): δ
7.54–7.50 (m, 2H), 7.48–7.44 (m, 2H), 7.36–7.30 (m, 3H), 6.88–6.84
(m, 2H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.4, 134.1,
132.4, 129.0, 128.4, 122.1, 114.2, 113.8, 81.9, 81.0, 74.2, 72.8, 55.3.
1-Bromo-4-(phenylbuta-1,3-diynyl)benzene (3e): White solid;
In summary, we have developed a novel, efficient and
practical method for the synthesis of unsymmetrical 1,3-diynes
through the cross-coupling of 1-bromoalkynes with terminal
alkynes by using an MCM-41-immobilised bidentate phosphine
palladium(0) complex [MCM-41-2P-Pd(0)] as the catalyst in
the presence of CuI as a cocatalyst. The reactions generated
a variety of unsymmetrical 1,3-diynes in moderate to good
yields under mild conditions and were applicable to various
1-bromoalkynes and terminal alkynes. In addition, this
methodology offers the competitiveness of recyclability of the
palladium catalyst without significant loss of catalytic activity
and the catalyst could be easily recovered and reused at least
seven times, thus making this procedure economically and
environmentally more acceptable.
1
m.p. 142–144 °C (lit.36 143–145 °C); H NMR (300 MHz, CDCl3): δ
7.54–7.50 (m, 2H), 7.48–7.44 (m, 2H), 7.39–7.31 (m, 5H); 13C NMR (75
MHz, CDCl3): δ 134.1, 132.9, 132.1, 129.6, 128.8, 123.8, 121.9, 121.1,
82.6, 80.7, 75.3, 74.1.
Nona-1,3-diynylbenzene (3f):24 Light yellow oil; 1H NMR (300 MHz,
CDCl3): δ 7.48 (d, J = 7.2 Hz, 2H), 7.36–7.31 (m, 3H), 2.36 (t, J = 7.0
Hz, 2H), 1.61–1.57 (m, 2H), 1.43–1.34 (m, 4H), 0.93 (t, J = 7.0 Hz, 3H);
13C NMR (75 MHz, CDCl3): δ 132.8, 129.2, 128.6, 122.5, 85.3, 75.1,
74.7, 65.4, 31.3, 28.3, 22.5, 19.9, 14.2.
1-Hexyl-4-(4-ethoxyphenyl)buta-1,3-diyne (3g): Light yellow oil;
1H NMR (400 MHz, CDCl3): δ 7.39 (d, J = 8.8 Hz, 2H), 6.80 (d, J = 8.8
Hz, 2H), 4.03 (q, J = 6.8 Hz, 2H), 2.34 (t, J = 7.0 Hz, 2H), 1.59–1.26 (m,
11H), 0.90 (t, J = 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 159.4,
134.0, 114.5, 113.9, 84.2, 74.9, 73.1, 65.2, 63.6, 31.3, 28.6, 28.3, 22.5, 19.6,
14.7, 14.1; HRMS calcd for C18H22O+: [M+]: 254.1671; found: 254.1662.
1-Hexyl-4-(4-methoxyphenyl)buta-1,3-diyne (3h): Light yellow
Experimental
All chemicals were obtained from commercial suppliers and used as
received, unless otherwise noted. All products were characterised by
comparison of their spectra and physical data with the literature where
1
possible. H NMR spectra were recorded on a Bruker Avance 400
(400 MHz) spectrometer with TMS as an internal standard in CDCl3
as solvent. 13C NMR spectra were recorded on a Bruker Avance 400
(100 MHz) spectrometer in CDCl3 as solvent. HRMS spectra were
recorded on a quadrupole-time–of-flight Bruker MicroTOF-Q II mass
spectrometer equipped with an ESI and APCI source. The MCM-41-
2P-Pd(0) complex was prepared according to our previous procedure;34
the palladium content was determined to be 0.45 mmol g–1 by ICP-
AES. 1-Bromoalkynes were prepared by the reaction of terminal
alkynes with NBS in the presence of 1,8-diazabicyclo[5.4.0]undec-7-
ene according to a literature method.35
1
oil; H NMR (400 MHz, CDCl3): δ 7.41 (d, J = 7.2 Hz, 2H), 6.82 (d,
J = 7.6 Hz, 2H), 3.81 (s, 3H), 2.35 (t, J = 6.8 Hz, 2H), 1.59–1.52 (m,
2H), 1.44–1.37 (m, 2H), 1.34–1.20 (m, 4H), 0.90 (t, J = 6.2 Hz, 3H);
13C NMR (100 MHz, CDCl3): δ 160.0, 134.1, 114.0, 112.6, 84.3, 74.8,
73.1, 65.2, 55.3, 31.3, 28.6, 28.3, 22.5, 19.6, 14.1; HRMS calcd for
C17H20O+: [M+]: 240.1514; found: 240.1508.
1-Hexyl-4-(4-ethylphenyl)buta-1,3-diyne (3i): Light yellow oil;
1H NMR (400 MHz, CDCl3): δ 7.39 (d, J = 8.0 Hz, 2H), 7.13 (d, J =
8.0 Hz, 2H), 3.81 (s, 3H), 2.64 (q, J = 7.6 Hz, 2H), 2.35 (t, J = 7.0 Hz,
2H), 1.59–1.54 (m, 2H), 1.44–1.39 (m, 2H), 1.36–1.19 (m, 7H), 0.90 (t,
J = 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 145.4, 132.5, 128.0,
119.2, 84.5, 75.0, 73.7, 65.1, 31.3, 28.9, 28.6, 28.3, 22.6, 19.6, 15.3, 14.1;
HRMS calcd for C18H22+: [M+]: 238.1722; found: 238.1734.
1-Bromo-4-(nona-1,3-diynyl)benzene (3j):24 Light yellow oil;
1H NMR (300 MHz, CDCl3): δ 7.35 (d, J = 7.8 Hz, 2H), 7.24 (d, J = 8.0
Hz, 2H), 2.27 (t, J = 7.0 Hz, 2H), 1.51–1.47 (m, 2H), 1.32–1.21 (m, 4H),
0.83 (t, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 134.2, 131.8,
123.4, 121.3, 85.8, 75.9, 73.7, 65.3, 31.3, 28.3, 22.5, 19.9, 14.1.
Deca-2,4-diynyl acetate (3k):24 Light yellow oil; 1H NMR (300
MHz, CDCl3): δ 4.68 (s, 2H), 2.25–2.21 (m, 2H), 2.05 (s, 3H),
1.52–1.47 (m, 2H), 1.35–1.26 (m, 4H), 0.87–0.84 (m, 3H); 13C NMR
(75 MHz, CDCl3): δ 170.2, 82.4, 71.8, 69.4, 64.5, 52.7, 31.2, 28.1, 22.4,
20.9, 19.4, 14.1.
Trideca-5,7-diyne (3l):24 Light yellow oil; 1H NMR (300 MHz,
CDCl3): δ 2.24–2.20 (m, 4H), 1.51–1.44 (m, 4H), 1.37–1.28 (m, 6H),
0.91–0.85 (m, 6H); 13C NMR (75 MHz, CDCl3): δ 77.7, 65.4, 31.3, 30.6,
28.3, 22.5, 22.1, 19.4, 19.1, 14.2, 13.9.
CAUTION: Stringent safety precautions are required in
the preparation of MCM-41-2P-Pd(0) when using hydrazine
hydrate as it is highly toxic and harmful to health.
Heterogeneous Pd(0)-catalysed cross-coupling of 1-bromoalkynes
with terminal alkynes; general procedure
A 25 mL round-bottomed flask equipped with a magnetic stirring
bar was charged with 1-bromoalkyne 1 (1.0 mmol), terminal alkyne
2 (1.5 mmol), Et3N (2 mmol), MCM-41-2P-Pd(0) (0.05 mmol), CuI
(0.02 mmol) and DMF (2 mL) under Ar. The resulting mixture was
stirred at room temperature for 12 h. After completion of the reaction,
the mixture was diluted with ethyl acetate (20 mL) and filtered. The
catalyst was washed with distilled water (5 mL) and EtOH (2 × 5 mL)
and could be reused in the next run. The filtrate was washed with
aqueous 25% NH3, which removed any CuI, and brine. It was then
dried over MgSO4. After removal of the solvent under reduced
pressure, the residue was purified by flash column chromatography on
silica gel using a mixture of petroleum ether (boiling range 60-90 ºC)
and EtOAc as eluent.
2-Methyl-6-phenylhexa-3,5-diyn-2-ol (3a): White solid; m.p. 59–61
°C (lit.24 57–59 °C); 1H NMR (400 MHz, CDCl3): δ 7.51–7.49 (m, 2H),
7.37–7.33 (m, 3H), 2.03 (br, 1H), 1.60 (s, 6H); 13C NMR (100 MHz,
CDCl3): δ 132.6, 129.3, 128.5, 121.5, 86.7, 78.8, 73.2, 67.1, 65.8, 31.1.
6-Phenylhexa-3,5-diyn-1-ol (3b): Colourless oil; 1H NMR
(400 MHz, CDCl3): δ 7.48 (d, J = 6.4 Hz, 2H), 7.38–7.30 (m, 3H), 3.81
(t, J = 6.2 Hz, 2H), 2.65 (t, J = 6.2 Hz, 2H), 1.82 (s, 1H); 13C NMR
(100 MHz, CDCl3): δ 132.6, 129.1, 128.4, 121.7, 81.0, 75.4, 74.0,
66.9, 60.8, 24.0; HRMS calcd for C12H10O+: [M+]: 170.0732; found:
170.0737.
2-Methyl-6-(4-ethylphenyl)hexa-3,5-diyne-2-ol (3m): Light yellow
1
oil; H NMR (400 MHz, CDCl3): δ 7.40 (d, J = 7.2 Hz, 2H), 7.15 (d,
J = 7.0 Hz, 2H), 2.65 (q, J = 7.0 Hz, 2H), 2.11 (br, 1H), 1.58 (s, 6H),
1.22 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 145.9, 132.6,
128.1, 118.6, 86.4, 79.2, 72.5, 67.2, 65.8, 31.2, 28.9, 15.3; HRMS calcd
for C15H16O+: [M+]: 212.1201; found: 212.1192.
2-Methyl-6-(3-fluorophenyl)hexa-3,5-diyne-2-ol (3n): Light yellow
1
oil; H NMR (400 MHz, CDCl3): δ 7.32–7.23 (m, 2H), 7.19–7.14 (m,
1H), 7.10–7.01 (m, 1H), 2.01 (br, 1H), 1.59 (s, 6H); 13C NMR (100
MHz, CDCl3): δ 162.2 (d, 1JC–F = 246.0 Hz), 130.1 (d, 3JC–F = 9.0 Hz),
128.4 (d, 4JC–F = 2.0 Hz), 123.4 (d, 3JC–F = 10.0 Hz), 119.2 (d, 2JC–F = 23.0
Hz), 116.8 (d, 2JC–F = 21.0 Hz), 87.3, 77.3, 74.0, 66.8, 65.8, 31.1; HRMS
calcd for C13H11FO+: [M+]: 202.0794; found 202.0788.
1
(6-Methoxyhexa-1,3-diynyl)benzene (3c): Colourless oil; H NMR
2-Methyl-6-(4-ethoxyphenyl)hexa-3,5-diyne-2-ol (3o): Light yellow
1
(400 MHz, CDCl3): δ 7.48–7.45 (m, 2H), 7.37–7.27 (m, 3H), 3.56 (t,
J = 6.8 Hz, 2H), 3.39 (s, 3H), 2.64 (t, J = 6.8 Hz, 2H); 13C NMR (100
MHz, CDCl3): δ 132.5, 128.9, 128.4, 122.0, 81.1, 75.2, 74.2, 70.2,
oil; H NMR (400 MHz, CDCl3): δ 7.40 (d, J = 7.6 Hz, 2H), 6.82 (d,
J = 7.6 Hz, 2H), 4.02 (q, J = 6.2 Hz, 2H), 2.22 (br, 1H), 1.57 (s, 6H),
1.41 (t, J = 6.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 159.7, 134.1,

JOURNAL OF CHEMICAL RESEARCH 2018 137
3
4
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528–541.
114.6, 113.2, 86.2, 79.1, 72.0, 67.3, 65.7, 63.6, 31.2, 14.7; HRMS calcd
for C15H16O2 : [M+]: 228.1150; found: 228.1153.
+
2-Methyl-6-trimethylsilylhexa-3,5-diyne-2-ol (3p):25 Light yellow
oil; 1H NMR (400 MHz, CDCl3): δ 1.98 (br, 1H), 1.53 (s, 6H), 0.20 (s,
9H); 13C NMR (100 MHz, CDCl3): δ 88.3, 87.6, 82.4, 67.7, 66.0, 31.5,
0.0.
6-(4-Ethylphenyl)hexa-3,5-diyne-1-ol (3q): Light yellow oil;
1H NMR (400 MHz, CDCl3): δ 7.40 (d, J = 8.0 Hz, 2H), 7.14 (d,
J = 8.4 Hz, 2H), 3.80 (t, J = 6.2 Hz, 2H), 2.68–2.60 (m, 4H), 1.83 (br,
1H), 1.22 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 145.7,
132.6, 128.0, 118.8, 80.6, 75.7, 73.3, 67.0, 60.8, 28.9, 24.0, 15.3; HRMS
calcd for C14H14O+: [M+]: 198.1045; found: 198.1033.
6
7
8
9
6-(4-Ethoxylphenyl)hexa-3,5-diyne-1-ol (3r): Light yellow oil;
1H NMR (400 MHz, CDCl3): δ 7.41 (d, J = 8.8 Hz, 2H), 6.81 (d,
J = 8.8 Hz, 2H), 4.02 (q, J = 7.0 Hz, 2H), 3.79 (t, J = 6.2 Hz, 2H), 2.64
(t, J = 6.2 Hz, 2H), 1.85 (br, 1H), 1.42 (t, J = 7.0 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ 159.6, 134.1, 114.6, 113.4, 80.3, 75.7, 72.7, 67.1, 63.6,
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60.9, 24.0, 14.7; HRMS calcd for C14H14O2 : [M+]: 214.0994; found:
+
214.0997.
6-(3-Fluorophenyl)hexa-3,5-diyne-1-ol (3s): Light yellow oil;
1H NMR (400 MHz, CDCl3): δ 7.32–7.23 (m, 2H), 7.19–7.14 (m, 1H),
7.09–7.03 (m, 1H), 3.81 (t, J = 6.2 Hz, 2H), 2.66 (t, J = 6.2 Hz, 2H), 1.84
1
(s, 1H); 13C NMR (100 MHz, CDCl3): δ 162.2 (d, JC–F = 246.0 Hz),
130.1 (d, 3JC–F = 9.0 Hz), 128.5 (d, 4JC–F = 3.0 Hz), 123.6 (d, 3JC–F = 9.0
Hz), 119.3 (d, 2JC–F = 23.0 Hz), 116.6 (d, 2JC–F = 21.0 Hz), 81.8, 74.8, 73.9
(d, 4JC–F = 3.0 Hz), 66.6, 60.7, 24.0; HRMS calcd for C12H9FO+: [M+]:
188.0637; found: 188.0635.
Acknowledgements
We thank the National Natural Science Foundation of China
(No. 21462021) and the Key Laboratory of Functional Small
Organic Molecule, Ministry of Education (No. KLFS-
KF-201704) for financial support.
26 X. Li, X. Xie, N. Sun and Y. Liu, Angew. Chem., Int. Ed., 2017, 56, 6994.
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29 M.J. Climent, A. Corma and S. Iborra, Chem. Rev., 2011, 111, 1072.
30 A. Molnar, Chem. Rev., 2011, 111, 2251.
Received 21 December 2017; accepted 25 February 2018
Paper 1705156
https://doi.org/10.3184/174751918X15208574638459
Published online: 15 March 2018
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