Copper-catalyzed cross-coupling reactions of bromoalkynols with terminal alkynes in supercritical carbon dioxide

Article abstract of DOI:10.1055/s-2007-966058

Copper-catalyzed cross-coupling reactions of bromoalkynols and terminal alkynes were carried out in supercritical carbon dioxide (scCO₂) to afford the corresponding unsymmetrical diynes with good yields. The reaction is sensitive to temperature and the pressure of CO₂. Methanol, as a cosolvent of scCO₂, could promote dissolution of the inorganic salt and thus facilitated the reaction. This new heterocoupling reaction system is more environmentally friendly than more traditional methods, since it uses scCO₂ as solvent and sodium acetate as base instead of amines. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-966058

PAPER
1649
Copper-Catalyzed Cross-Coupling Reactions of Bromoalkynols with Terminal
Alkynes in Supercritical Carbon Dioxide
C
ross-Coupling of
u
Bromoalkyn
a
ols
w
ith Te
n
r
minal Alky
-nes Feng Jiang,* A-Zhong Wang
College of Chemistry, South China University of Technology, Guangzhou 510640, P. R. of China
Fax +86(20)87112906; E-mail: jianghf@scut.edu.cn
Received 12 March 2007; revised 9 April 2007
Chodkiewicz coupling might be also carried out under the
Abstract: Copper-catalyzed cross-coupling reactions of bromo-
alkynols and terminal alkynes were carried out in supercritical car-
bon dioxide (scCO2) to afford the corresponding unsymmetrical
diynes with good yields. The reaction is sensitive to temperature
same conditions. We herein wish to report a mild protocol
for the Cadiot–Chodkiewicz coupling of bromoalkynols
with terminal acetylenes in scCO2 using sodium acetate as
and the pressure of CO2. Methanol, as a cosolvent of scCO2, could base.
promote dissolution of the inorganic salt and thus facilitated the re-
The Cadiot–Chodkiewicz coupling reaction of 4-bromo-
action. This new heterocoupling reaction system is more environ-
mentally friendly than more traditional methods, since it uses scCO2
as solvent and sodium acetate as base instead of amines.
2-methylbut-3-yn-2-ol (1a) with phenylacetylene (2a) in
scCO2 was conducted as a model in order to optimize the
reaction conditions; the results are summarized in
Table 1. Initially, the dosage of sodium acetate was tested
under 14 MPa of CO2 using methanol (1 mL) as cosolvent
at 40 °C. It was found that the heterocoupling reaction
strongly depended on the amount of base used. When 4
mmol of sodium acetate was used, the reaction afforded
only a small amount of the heterocoupling product (entry
1). A clear yield enhancement was observed with decreas-
ing amounts of base (entries 1–4), with an optimum yield
of 78% (GC) being observed when 1.5 mmol sodium ace-
tate was used (entry 4). Further reduction of the amount of
sodium acetate reduced the yield (entry 5). The effect of
temperature and the pressure of CO2 on the reaction was
also investigated. As can be seen in Table 1, both factors
had significant effects on the heterocoupling (entries 4–
11). Decreasing the reaction pressure greatly accelerated
the reaction, giving the desired product 3 in 93% GC yield
at a pressure of 9 MPa (entry 8). For the temperatures
evaluated, 40 °C was found to give the best result (entries
8–11). Other copper catalysts were also evaluated and it
was found that CuCl was superior to other Cu(I) catalysts
such as CuBr and CuI (entries 12 and 13). When the reac-
tion was conducted in either pure methanol or scCO2
alone, lower yields were obtained (entries 14 and 15), thus
showing that both methanol and scCO2 were important to
the reaction. Suitable amounts of methanol presumably
makes the sodium acetate partially dissolve in the scCO2,
which leads to the observed large acceleration in the reac-
tion rate.12
Key words: unsymmetrical diynes, heterocoupling reaction,
alkynes, supercritical carbon dioxide
Unsymmetrical diynes play an important structural role in
many natural products1 and possess a wide range of poten-
tial applications in material science.2 A general method for
the synthesis of unsymmetrically substituted 1,3-diynes
uses the Cadiot–Chodkiewicz cross-coupling reaction of
terminal alkynes with 1-bromoacetylenes in the presence
of a copper(I) salt and a suitable amine.3 Besides the orig-
inal Cadiot–Chodkiewicz coupling, several complemen-
tary variations have been reported.4–9 For example, the
copper iodide catalyzed cross-coupling reaction between
1-haloalkynes and terminal alkynes, in which pyrrolidine
was used as the amine solvent, gave superior yields and
reduced the reaction time.5 Kurth and co-workers6 devel-
oped a polymer-supported technique which inhibited the
mutual interaction between haloalkynes and thus reduced
the self-coupling efficiently. Unsymmetrical diynes could
be prepared by a palladium-catalyzed heterocoupling re-
action of 1-iodoalkynes and terminal alkynes in a mixture
of acetonitrile and water.8 However, amine bases have al-
ways been required in both copper- and palladium-cata-
lyzed systems. Therefore, the need to develop the use of
environmentally benign bases and solvents for the cross-
coupling reaction is still significant. Supercritical carbon
dioxide (scCO2), as an environmentally benign reaction
medium, has the advantages of greater selectivity and the
ease with which the reaction rate can be controlled. As a
result, much progress has been made on using scCO2 as a
‘green’ solvent for organic reactions.10 Previously, we re-
ported a Cu(II)-promoted method for the homocoupling
of alkynes in scCO2 using sodium acetate as base.11 En-
couraged by these results, we envisioned that Cadiot–
To assess the efficiency and scope of the method, the
cross-coupling reactions of bromoalkynols with several
other terminal acetylenes were carried out; the results are
shown in Table 2. It can be seen that the heterocouplings
generally performed well in the scCO2 system, with the
yields and rates dependent upon the substrates. As shown
in Table 2, coupling of 1a with a range of alkynes pro-
ceeds smoothly to give the corresponding products in
good to excellent yields (entries 1–3). Other bro-
moalkynols derived from prop-2-yn-1-ol (entries 4 and 5),
SYNTHESIS 2007, No. 11, pp 1649–1654
x
x.
x
x
.
2
0
0
7
Advanced online publication: 11.05.2007
DOI: 10.1055/s-2007-966058; Art ID: F05107SS
© Georg Thieme Verlag Stuttgart · New York

1650
H.-F. Jiang, A-Z. Wang
PAPER
a
Table 1 Reaction Conditions for Heterocoupling of 4-Bromo-2-methylbut-3-yn-2-ol (1a) with Phenylacetylene (2a) in scCO2
OH
OH
CuCl, NaOAc
scCO2
Br
1a
2a
3
Entry
1
NaOAc (mmol)
CO2 pressure (MPa)
Temp (°C)
Yieldb (%)
4
14
14
14
14
14
12
10
9
40
40
40
40
40
40
40
40
r.t
6
2
3
19
3
2
55
4
1.5
1
78
5
71
6
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
86
7
91
8
93 (91)c
47
9
9
10
11
12d
13e
14f
15g
9
50
60
40
40
40
40
85
9
81
9
86
9
83
0
26
9
17
a Reaction conditions: phenylacetylene (1.2 mmol), 4-bromo-2-methylbut-3-yn-2-ol (1 mmol), CuCl (0.05 mmol), MeOH (1 mL), 4 h.
b Determined by GC.
c Isolated yield.
d CuBr as the catalyst.
e CuI as the catalyst.
f MeOH (10 mL) as solvent.
g Without MeOH.
but-3-yn-1-ol (entries 6–8), pent-4-yn-1-ol (entries 9 and no desired heterocoupled product was observed (entries
10), hex-5-yn-1-ol (entries 11 and 12) and 1-ethynylcy- 22 and 23).
clohexanol (entries 13–15) undergo heterocoupling with
In summary, the copper-catalyzed Cadiot–Chodkiewicz
aromatic alkynes in moderate to good yields. However,
cross-coupling of bromoalkynols with terminal alkynes in
only 69% yield of the desired coupled product 14 was ob-
scCO2 was found to be a high-yielding process. This pro-
tocol uses sodium acetate as base and avoids the use of en-
tained in the coupling of 6-bromohex-5-yn-1-ol with 2a
after six hours under the same conditions (entry 11). For
vironmentally problematic amine salts. We also found
fluoro-substituted phenylacetylenes, the strong electron-
that high reaction temperature and pressure disfavored the
withdrawing effect and enhanced solubility in scCO2
heterocoupling. The yields and rates of the heterocoupling
caused by the fluorine atom may account for the higher re-
reaction depended upon the substrates. It is noteworthy
activities (entries 3, 5, 7, 12 and 15).13,14 The coupling re-
that this new Cadiot–Chodkiewicz coupling reaction pro-
tocol is more environmentally friendly than the more tra-
action of 1a with ethyl propiolate afforded the
corresponding diyne in high yields (entry 16). Octyne
ditional methods.
showed somewhat lower reactivity as compared to aro-
matic alkynes: the cross-coupling with 1a, 1b, 1c, 1d and
1e for six hours, afforded the corresponding products 20–
24 in 81%, 83%, 78%, 71% and 42% yields, respectively
(entries 17–21). Thus, for bromoalkynols, increasing the
carbon chain length resulted in a clear decrease in the
yield. Unfortunately, when bromoalkynes with no hy-
droxyl group were used in the cross-coupling reactions,
1H NMR spectra were recorded on Bruker DRX-400 and Varian
NMR System 400 spectrometers using CDCl3 as solvent and TMS
as an internal standard. Mass spectra were recorded on a Shimadzu
GCMS-QP5050A spectrometer. Elemental analyses were per-
formed on a Vario EL Elemental Analyzer. TLC was performed us-
ing commercially prepared silica gel plates (GF254). Bromoalkynes
were prepared according to the literature.6 All other reagents were
obtained commercially.
Synthesis 2007, No. 11, 1649–1654 © Thieme Stuttgart · New York

PAPER
Cross-Coupling of Bromoalkynols with Terminal Alkynes
1651
a
Table 2 Copper-Catalyzed Heterocoupling of Bromoalkynols and Acetylenes in scCO2
CuCl, NaOAc
R'
R
Br
R
R'
MeOH, scCO2
1
2
4–24
Entry
1
Bromoalkyne
Alkyne
Product
Time (h)
4
Yieldb (%)
87
OH
Br
4
(2b)
(2c)
(1a)
OH
OMe
Br
Br
2
3
5
6
4
4
86
93
(1a)
F
OH
(1a)
(2d)
(2a)
(2e)
(2a)
Br
4
5
6
7
8
9
4
4
4
89
89
88
HO
(1b)
Br
F
HO
(1b)
HO
Br
Br
Br
(1c)
F
HO
7
10
4
89
(1c)
(2d)
(2c)
(2a)
(2b)
(2a)
(2f)
HO
OMe
8
9
11
12
13
14
15
5
5
5
6
5
86
84
82
69
76
(1c)
HO
Br
Br
(1d)
10
11
12
HO
(1d)
Br
Br
HO
(1e)
F
HO
(1e)
OH
OH
13
14
16
17
4
5
87
85
Br
Br
(2a)
(2b)
(1f)
(1f)
Synthesis 2007, No. 11, 1649–1654 © Thieme Stuttgart · New York

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H.-F. Jiang, A-Z. Wang
PAPER
Table 2 Copper-Catalyzed Heterocoupling of Bromoalkynols and Acetylenes in scCO2a (continued)
CuCl, NaOAc
R'
R
Br
R
R'
MeOH, scCO2
1
2
4–24
Entry
15
Bromoalkyne
Alkyne
Product
Time (h)
4
Yieldb (%)
OH
F
18
88
85
Br
(2f)
(1f)
OH
COOEt
Br
16
19
6
(2g)
(1a)
OH
n-Hex
n-Hex
Br
17
18
20
21
6
6
81
83
(2h)
(2h)
(1a)
Br
HO
(1b)
HO
n-Hex
n-Hex
19
20
21
22
22
23
24
–
6
6
6
8
78
71
42
0
Br
(2h)
(2h)
(2h)
(1c)
HO
Br
(1d)
Br
n-Hex
HO
(1e)
OH
n-Hex
Br
(1g)
(2i)
Br
23
–
4
0
(1h)
(2b)
a Reaction conditions: bromoalkyne (1 mmol), alkyne (1.2 mmol), NaOAc (1.5 mmol), Pco2 = 9 MPa, 40 °C, MeOH (1 mL).
b Isolated yield.
Copper-Catalyzed Cadiot–Chodkiewicz Coupling Reaction in
scCO2: General Procedure
2-Methyl-6-p-tolylhexa-3,5-diyn-2-ol (4)15
1H NMR (CDCl3, 400 MHz): d = 1.56 (s, 6 H), 2.34 (s, 3 H), 7.10
(d, J = 8 Hz, 2 H), 7.35 (d, J = 8 Hz, 2 H).
The reaction was carried out in a HF-15 autoclave. CuCl (4.95 mg,
0.05 mmol), AcONa (1.5 mmol), MeOH (1 mL), bromoalkyne (1
mmol) and alkyne (1.2 mmol) were added to a 15 mL autoclave ves-
sel in sequence. Liquid CO2 was pumped into the autoclave by a
cooling pump until the desired pressure was reached then the auto-
clave was heated in an oil bath under magnetic stirring for the de-
sired reaction time. After the reaction finished, the autoclave was
allowed to cool to 0 °C and CO2 was vented and the residue was ex-
tracted with Et2O (1 × 20 mL). The extract was filtered and concen-
trated under reduced pressure to give a residue that was purified by
chromatography on a silica gel column using light PE–EtOAc as
eluent.
13C NMR (CDCl3, 100 MHz): d = 21.8, 31.3, 66.0, 67.4, 72.7, 79.3,
86.5, 118.6, 129.4, 132.6, 139.8.
MS (EI, 70 eV): m/z (%) = 198 (55) [M+], 183 (71), 155 (46), 139
(34), 115 (20), 43 (100).
6-(4-Methoxyphenyl)-2-methylhexa-3,5-diyn-2-ol (5)15
1H NMR (CDCl3, 400 MHz): d = 1.55 (s, 6 H), 3.78 (s, 3 H), 6.80,
(t, J = 5.6 Hz, 2 H), 7.38 (t, J = 5.6 Hz, 3 H).
13C NMR (CDCl3, 100 MHz): d = 31.3, 55.5, 65.9, 67.4, 72.1, 79.2,
86.3, 113.6, 114.3, 134.3, 160.5.
MS (EI, 70 eV): m/z (%) = 214 (71) [M+], 199 (75), 171 (36), 128
(23), 43 (100).
2-Methyl-6-phenylhexa-3,5-diyn-2-ol (3)15
1H NMR (CDCl3, 400 MHz): d = 1.56 (s, 6 H), 7.28–7.35 (m, 3 H),
7.45–7.48 (m, 2 H).
13C NMR (CDCl3, 100 MHz): d = 31.3, 65.9, 67.2, 73.3, 78.9, 86.9,
121.7, 128.6, 129.4, 132.7.
MS (EI, 70 eV): m/z (%) = 184 (51) [M+], 169 (100), 141 (58), 126
(32), 115 (40).
6-(3-Fluorophenyl)-2-methylhexa-3,5-diyn-2-ol (6)
1H NMR (CDCl3, 400 MHz): d = 1.56 (s, 6 H), 7.05–7.14 (m, 1 H),
7.15–7.16 (m, 1 H), 7.23–7.27 (m, 2 H).
13C NMR (CDCl3, 100 MHz): d = 31.0, 65.7, 66.7, 74.0, 87.3, 116.7,
119.2, 123.3, 128.4, 130.0, 160.9, 163.4.
Synthesis 2007, No. 11, 1649–1654 © Thieme Stuttgart · New York

PAPER
Cross-Coupling of Bromoalkynols with Terminal Alkynes
1653
MS (EI, 70 eV): m/z (%) = 202 (46) [M+], 187 (72), 159 (39), 133
(32), 43 (100).
13C NMR (CDCl3, 100 MHz): d = 16.1, 30.9, 61.3, 65.5, 74.1, 74.9,
83.7, 121.9, 128.3, 128.9, 132.5.
Anal. Calcd for C13H11FO: C, 77.22; H, 5.45. Found: C, 77.31; H,
5.46.
MS (EI, 70 eV): m/z (%) = 184 (64) [M+], 165 (79), 139 (100), 115
(43).
Anal. Calcd for C13H12O: C, 84.78; H, 65.22. Found: C, 84.68; H,
65.41.
5-Phenylpenta-2,4-diyn-1-ol (7)9
1H NMR (CDCl3, 400 MHz): d = 4.40 (s, 2 H), 7.28–7.35 (m, 3 H),
7.46–7.49 (m, 2 H).
7-p-Tolylhepta-4,6-diyn-1-ol (13)
13C NMR (CDCl3, 100 MHz): d = 51.8, 70.6, 73.3, 78.7, 80.6, 121.5,
128.6, 129.5, 132.8.
MS (EI, 70 eV): m/z (%) = 156 (73) [M+], 139 (21), 128 (88), 102
(100).
1H NMR (CDCl3, 400 MHz): d = 1.78–1.84 (m, 2 H), 2.33 (s, 3 H),
2.48 (t, J = 6.8 Hz, 2 H), 3.77 (t, J = 6.0 Hz, 2 H), 7.09 (d, J = 8.0
Hz, 2 H), 7.34 (d, J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 100 MHz): d = 16.1, 21.6, 30.9, 61.4, 65.6, 73.5,
75.2, 83.3, 118.8, 129.1, 132.4, 139.2.
5-(4-Fluorophenyl)penta-2,4-diyn-1-ol (8)
1H NMR (CDCl3, 400 MHz): d = 4.40 (s, 2 H), 6.97–7.03 (m, 2 H),
7.44–7.48 (m, 2 H).
13C NMR (CDCl3, 100 MHz): d = 51.9, 70.5, 73.1, 77.7, 80.6, 116.0,
117.8, 134.9, 164.5.
MS (EI, 70 eV): m/z (%) = 198 (79) [M+], 165 (74), 153 (100), 139
(51), 115 (43).
Anal. Calcd for C14H14O: C, 84.85; H, 7.07. Found: C, 84.72; H,
7.26.
MS (EI, 70 eV): m/z (%) = 174 (63) [M+], 157 (28), 146 (83), 126
(37), 120 (100).
8-Phenylocta-5,7-diyn-1-ol (14)
1H NMR (CDCl3, 400 MHz): d = 1.56–1.68 (m, 4 H), 2.34 (t,
J = 6.8 Hz, 2 H), 3.61 (t, J = 6.0 Hz, 2 H), 7.19–7.28 (m, 3 H), 7.38–
7.41 (m, 2 H).
Anal. Calcd for C11H7FO: C, 75.86; H, 4.02. Found: C, 75.97; H,
3.96.
13C NMR (CDCl3, 100 MHz): d = 19.6, 24.7, 31.9, 62.4, 65.6, 74.4,
75.1, 84.5, 122.2, 128.5, 129.0, 132.7.
MS (EI, 70 eV): m/z (%) = 198 (13) [M+], 170 (71), 139 (100), 115
(46).
6-Phenylhexa-3,5-diyn-1-ol (9)
1H NMR (CDCl3, 400 MHz): d = 2.62 (t, J = 6.0 Hz, 2 H), 3.78 (t,
J = 6.0 Hz, 2 H), 7.27–7.33 (m, 3 H), 7.44–7.47 (m, 2 H).
13C NMR (CDCl3, 100 MHz): d = 23.9, 60.7, 66.8, 73.9, 75.3, 81.0,
121.7, 128.3, 129.0, 132.5.
MS (EI, 70 eV): m/z (%) = 170 (46) [M+], 139 (100), 113 (10), 89
Anal. Calcd for C14H14O: C, 84.85; H, 7.07. Found: C, 84.68; H,
7.23.
(8).
8-(4-Fluorophenyl)octa-5,7-diyn-1-ol (15)
1H NMR (CDCl3, 400 MHz): d = 1.63–1.72 (m, 4 H), 2.40 (t,
J = 6.8 Hz, 2 H), 3.68 (t, J = 6.0 Hz, 2 H), 6.95–7.00 (m, 2 H), 7.41–
7.45 (m, 2 H).
Anal. Calcd for C12H10O: C, 84.71; H, 5.88. Found: C, 84.58; H,
5.94.
6-(3-Fluorophenyl)hexa-3,5-diyn-1-ol (10)
13C NMR (CDCl3, 100 MHz): d = 19.3, 24.5, 31.7, 62.2, 65.3, 73.8,
1H NMR (CDCl3, 400 MHz): d = 2.63 (t, J = 6.0 Hz, 2 H), 3.79 (t,
J = 6.0 Hz, 2 H), 7.02–7.06 (m, 1 H), 7.12–7.16 (m, 1 H), 7.22–7.24
(m, 1 H), 7.24–7.27 (m, 1 H).
74.0, 84.2, 115.7, 118.1, 134.4, 164.0.
MS (EI, 70 eV): m/z (%) = 216 (20) [M+], 198 (32), 188 (68), 170
(43), 157 (100), 144(37).
13C NMR (CDCl3, 100 MHz): d = 23.9, 60.7, 66.5, 73.9, 74.8, 81.8,
116.5, 119.2, 123.5, 128.4, 130.0, 163.4.
MS (EI, 70 eV): m/z (%) = 190 (61) [M+], 173 (36), 157 (100), 120
Anal. Calcd for C14H13FO: C, 77.78; H, 6.02. Found: C, 77.78; H,
5.97.
(58).
1-(4-Phenylbuta-1,3-diynyl)cyclohexanol (16)
1H NMR (CDCl3, 400 MHz): d = 1.52–1.73 (m, 8 H), 1.91–1.97 (m,
2 H), 7.28–7.34 (m, 3 H), 7.46–7.48 (m, 2 H).
Anal. Calcd for C12H9FO: C, 75.79; H, 4.74. Found: C, 75.59; H,
4.95.
13C NMR (CDCl3, 100 MHz): d = 23.4, 25.2, 39.9, 69.1, 69.6, 73.6,
78.7, 86.3, 121.8, 128.6, 129.4, 132.7.
MS (EI, 70 eV): m/z (%) = 224 (100) [M+], 195 (29), 181 (87), 167
(78), 153 (90).
6-(4-Methoxyphenyl)hexa-3,5-diyn-1-ol (11)
1H NMR (CDCl3, 400 MHz): d = 2.62 (t, J = 6.0 Hz, 2 H), 3.77 (t,
J = 6.0 Hz, 2 H), 3.77 (s, 3 H), 6.81 (q, J = 4.0 Hz, 2 H), 7.40 (m,
1 H), 7.12–7.16 (m, 1 H), 7.22–7.24 (m, 1 H), 7.24–7.27 (m, 1 H).
Anal. Calcd for C16H16O: C, 85.71; H, 7.14. Found: C, 85.63; H,
7.19.
13C NMR (CDCl3, 100 MHz): d = 23.9, 55.3, 60.7, 66.9, 72.7, 75.5,
80.3, 113.6, 114.0, 134.1, 160.1.
MS (EI, 70 eV): m/z (%) = 200 (73) [M+], 182 (4), 169 (100), 154
(27), 126 (30).
1-(4-p-Tolylbuta-1,3-diynyl)cyclohexanol (17)
1H NMR (CDCl3, 400 MHz): d = 1.52–1.71 (m, 8 H), 1.93–2.00 (m,
2 H), 2.33 (s, 3 H), 7. 10 (d, J = 8.0 Hz, 2 H), 7.36 (d, J = 8.0 Hz,
2 H).
13C NMR (CDCl3, 100 MHz): d = 21.8, 23.4, 25.2, 39.9, 69.2, 69.6,
72.9, 79.0, 85.9, 118.6, 129.4, 132.6, 139.8.
Anal. Calcd for C13H12O2: C, 78.00; H, 6.00. Found: C, 78.13; H,
5.96.
7-Phenylhepta-4,6-diyn-1-ol (12)
1H NMR (CDCl3, 400 MHz): d = 1.78–1.85 (m, 2 H), 2.49 (t,
J = 6.8 Hz, 2 H), 3.77 (t, J = 6.0 Hz, 2 H), 7.26–7.32 (m, 3 H), 7.44–
7.46 (m, 2 H).
MS (EI, 70 eV): m/z (%) = 238 (100) [M+], 209 (31), 195 (85), 167
(92), 139 (73).
Anal. Calcd for C17H18O: C, 85.71; H, 7.56. Found: C, 86.79; H,
7.48.
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1654
H.-F. Jiang, A-Z. Wang
PAPER
1-[4-(4-Fluorophenyl)buta-1,3-diynyl]cyclohexanol (18)
1H NMR (CDCl3, 400 MHz): d = 1.51–1.72 (m, 8 H), 1.93–1.97 (m,
2 H), 6.98–7.02 (m, 2 H), 7.44–7.47 (m, 2 H).
13C NMR (CDCl3, 100 MHz): d = 23.4, 25.2, 39.9, 69.0, 69.6, 73.4,
77.6, 86.3, 116.0, 117.9, 134.8, 164.4.
13C NMR (CDCl3, 100 MHz): d = 14.0, 18.9, 19.1, 22.5, 24.6, 28.2,
28.5, 31.2, 31.7, 62.2, 65.1, 65.6, 76.7, 77.7.
MS (EI, 70 eV): m/z (%) = 205 (1) [M+], 159 (13), 145 (16), 135
(35), 117 (52), 91 (100).
MS (EI, 70 eV): m/z (%) = 242 (91) [M+], 214 (36), 199 (100), 186
(72), 144 (74).
Acknowledgment
We thank the National Natural Science Foundation of China (Nos.
20625205, 20572027 and 20332030) for financial support.
Anal. Calcd for C16H15FO: C, 79.34; H, 6.20. Found: C, 79.15; H,
6.17.
Ethyl 6-Hydroxy-6-methylhepta-2,4-diynoate (19)
1H NMR (CDCl3, 400 MHz): d = 1.29 (t, J = 7.2 Hz, 3 H), 1.53 (s,
6 H), 4.23 (q, J = 7.2 Hz, 2 H), 1.50 (s, 6 H), 2.25 (t, J = 6.8 Hz,
2 H).
13C NMR (CDCl3, 100 MHz): d = 14.1, 30.9, 62.8, 65.5, 65.8, 69.3,
70.3, 89.1, 152.9.
References
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MS (EI, 70 eV): m/z (%) = 180 (1) [M+], 165 (29), 137 (100), 109
(44), 93 (57).
Anal. Calcd for C10H12O3: C, 66.67; H, 6.67. Found: C, 66.58; H,
6.62.
2-Methyldodeca-3,5-diyn-2-ol (20)16
1H NMR (CDCl3, 400 MHz): d = 0.87 (t, J = 6.8 Hz, 3 H), 1.23–
1.30 (m, 6 H), 1.34–1.38 (m, 2 H), 1.50 (s, 6 H), 2.25 (t, J = 6.8 Hz,
2 H).
13C NMR (CDCl3, 100 MHz): d = 14.0, 19.3, 22.5, 28.1, 28.5, 31.2,
31.3, 64.2, 65.6, 67.4, 79.8, 82.0.
MS (EI, 70 eV): m/z (%) = 192 (2) [M+], 177 (37), 135 (24), 91 (18),
43 (100).
Undeca-2,4-diyn-1-ol (21)6
1H NMR (CDCl3, 400 MHz): d = 0.86 (t, J = 6.8 Hz, 3 H), 1.24–
1.36 (m, 6 H), 1.49–1.52 (m, 2 H), 2.25 (t, J = 6.8 Hz, 2 H), 4.29 (s,
2 H).
(3) (a) Cadiot, P.; Chodkiewicz, W. In Chemistry of Acetylenes;
Viehe, H. G., Ed.; Dekker: New York, 1969, Chap. 9, 597–
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13C NMR (CDCl3, 100 MHz): d = 14.0, 19.2, 22.5, 28.1, 28.5, 31.2,
51.5, 64.3, 70.9, 73.5, 81.9.
MS (EI, 70 eV): m/z (%) = 163 (1) [M+], 135 (36), 107 (28), 91 (78),
79 (100).
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6829.
Dodeca-3,5-diyn-1-ol (22)6
1H NMR (CDCl3, 400 MHz): d = 0.86 (t, J = 6.8 Hz, 3 H), 1.23–
1.29 (m, 4 H), 1.35–1.51 (m, 2 H), 2.22 (t, J = 6.8 Hz, 2 H), 2.51 (t,
J = 6.0 Hz, 2 H), 3.71 (t, J = 6.0 Hz, 2 H).
(9) Wityak, J.; Chan, J. B. Synth. Commun. 1991, 21, 977.
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13C NMR (CDCl3, 100 MHz): d = 14.0, 19.1, 22.5, 23.6, 28.2, 28.5,
31.3, 60.8, 64.9, 67.2, 73.6, 78.4.
MS (EI, 70 eV): m/z (%) = 178 (1) [M+], 149 (53), 131 (18), 105
(61), 91 (100), 79 (75).
Trideca-4,6-diyn-1-ol (23)6
1H NMR (CDCl3, 400 MHz): d = 0.86 (t, J = 6.8 Hz, 3 H), 1.23–
1.28 (m, 4 H), 1.33–1.37 (m, 2 H), 1.45–1.51 (m, 2 H), 1.74–7.77
(m, 2 H), 2.22 (t, J = 6.8 Hz, 2 H), 2.37 (t, J = 6.0 Hz, 2 H), 3.74 (t,
J = 6.8 Hz, 2 H).
13C NMR (CDCl3, 100 MHz): d = 14.0, 15.7, 19.2, 22.5, 28.3, 28.5,
31.0, 31.3, 61.4, 65.0, 65.8, 76.4, 77.9.
MS (EI, 70 eV): m/z (%) = 192 (1) [M+], 164 (12), 145 (18), 105
(43), 91 (100), 79 (76).
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T. R.; Hurtado, G. R. Tetrahedron 2001, 57, 4271.
Tetradeca-5,7-diyn-1-ol (24)6
1H NMR (CDCl3, 400 MHz): d = 0.86 (t, J = 6.8 Hz, 3 H), 1.24–
1.27 (m, 6 H), 1.47–1.50 (m, 2 H), 1.59–1.66 (m, 4 H), 2.22 (t,
J = 6.8 Hz, 2 H), 2.28 (t, J = 6.8 Hz, 2 H), 3.64 (t, J = 6.0 Hz, 2 H).
Synthesis 2007, No. 11, 1649–1654 © Thieme Stuttgart · New York