A facile synthetic route to new fluorinated building-blocks of 1-fluoroalkynes and 1-fluorodiynes

Article abstract of DOI:10.1002/cjoc.201100445

A facile and direct fluorination process of alkynes and diynes was developed. In the presence of n-butyllithium, the reaction of a series of terminal alkynes and diynes with the electrophilic fluorinating reagent (NFSI) proceeded to afford various 1-fluoroalkynes and 1-fluoro-1,3-diynes in moderate to high yields. Copyright

Full text of DOI:10.1002/cjoc.201100445

FULL PAPER
DOI: 10.1002/cjoc.201100445
A Facile Synthetic Route to New Fluorinated Building-Blocks of
1-Fluoroalkynes and 1-Fluorodiynes†
Liu, Cuibo(刘翠波)
Ma, Hai(马海)
Nie, Jing*(聂晶)
Ma, Junan*(马军安)
Department of Chemistry, Tianjin University, Tianjin 300072, China
A facile and direct fluorination process of alkynes and diynes was developed. In the presence of n-butyllithium,
the reaction of a series of terminal alkynes and diynes with the electrophilic fluorinating reagent (NFSI) proceeded
to afford various 1-fluoroalkynes and 1-fluoro-1,3-diynes in moderate to high yields.
Keywords electrophilic fluorination, terminal alkyne, terminal 1,3-diyne, 1-fluoroacetylene
Introduction
Results and Discussion
The application of organofluorine compounds has
received extensive attention in the area of pharmaceuti-
cal industry, agrochemical and material science due to
their unique chemical, physical and biological proper-
ties.[1] Construction of new fluorinated building-blocks
applicable to the synthesis of organofluorine compounds
is of considerable importance and still in great de-
mand.[2] Fluorinated alkynes are potentially intriguing
building blocks due to the unique behavior of acetylene,
especially in transition metal-catalyzed processes.[3]
Among all the useful methods for synthesis of 1-fluoro-
acetylenes,[4] curiously, the direct fluorination process
remains underdeveloped. While there are many effec-
tive reaction systems for the efficient synthesis of
1-haloacetylenes,[5] no known protocols exist for which
the analogous transformation can be performed with
alkynes.
Since the emergence of electrophilic fluorinating
agents, there are an increasing number of reports on
their applications in the construction of various fluori-
nated molecules, including fluoroalkanes, fluoroalkenes,
fluoroarenes, α-fluorocarbonyl compounds and ana-
logues.[6] However, electrophilic fluorination transfor-
mation of alkynes has been ignored. Development of
new organic transformations for the construction of
fluorinated building-blocks has been our interest and
research objective.[7] As part of our ongoing studies,
herein we present a facile and direct fluorination reac-
tion of alkynes with electrophilic fluorinating reagents
in the presence of n-butyllithium. This rapid approach
would provide a wide range of fluorinated alkynes and
dikynes.
We envisioned that acidic alkynes could be trans-
formed into the corresponding acetylide anion in the
treatment with suitable base, subsequently tripped by
electrophilic fluorinating reagents to furnish the fluoro-
alkynes. To test this hypothesis, we conducted a fluori-
nation reaction of phenylacetylene 1a in the presence of
sodium hydroxide and N-fluorobenzenesulfonimide
(NFSI) as electrophilic fluorinating reagent in tetrahy-
drofuran (THF) at room temperature (Table 1, Entry 1).
The 19F NMR analysis of the crude reaction mixture
revealed that only a trace amount of fluorinated product
2a was detected. The use of sodium hydride and di-
ethylzinc gave the similar results (Entries 2 and 3).
When n-butyllithium was used as base, the fluorinated
product 2a was obtained in 21% yield (Entry 4). Further
examination on the temperature in the same test reaction
revealed that the yield can be significantly improved
from 38% (Entry 5) to 63% (Entry 6). Other electro-
philic fluorinating reagents such as Selectfluor and
N-fluoropyridinium triflate (NFPY-OTf) displayed
lower reactivity in this transformation reaction (Entries
7 and 8). A substantial change of the solvent to toluene
and ether led to a marginal lower yield (Entries 9 and
10). It was noteworthy that the fluorinated product 2a is
stable at room temperature for three months, and no
change was detected by the 19F NMR spectrum.
To determine the scope of this protocol, a series of
aromatic-substituted acetylenes were employed as sub-
strates under the optimized reaction conditions. Not
only electron-donating but also electron-withdrawing
substituents on the aromatic ring of acetylenes were
*
E-mail: njtjuchem@gmail.com, majun_an68@tju.edu.cn; Tel.: 86-22-2740 2903; Fax: 86-22-2740 3475
Received October 1, 2011; accepted November 29, 2011.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201100445 or from the author.
† Dedicated to Professor Weiyuan Huang on the occasion of his 90th birthday.
Chin. J. Chem. 2012, 30, 47—52
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
47

Liu et al.
FULL PAPER
Table 1 Screening of base and fluorinating reagents in the syn-
thesis of fluorinated phenylacetylene
Table 2 Synthesis of 1-fluoroalkynesa
n-BuLi
Ar
F
Ar
H
NFSI
THF, -78 oC to r.t.
Base
H
+ F-reagent
F
2
solvent, temp
1
1a
2a
Entry
Alkyne 1
Product 2
Yieldb/%
Entrya Base
Fluorinating reagent
Temp./℃ Yieldb/%
F
F
F
H
1
2
3
4
5
6
7
8
9c
NaOH
NaH
NFSI
NFSI
25
—
—
—
21
38
63
10
8
1
2
63
25
2a
Et2Zn
NFSI
25
H
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
NFSI
25
48
58
48
57
65
73
76
68
53
80
NFSI
－40 to 25
－78 to 25
－78 to 25
－78 to 25
－78 to 25
－78 to 25
Me
Me
2b
2c
2d
NFSI
H
Selectfluor
NFPY-OTf
NFSI
3
MeO
MeO
MeO
MeO
52
60
10d n-BuLi
NFSI
F
F
H
a
The reaction employed a molar ratio of 1a∶base∶fluorinating
reagent＝1∶1.1∶1.2 (equiv.).
c Toluene was used. d Ether was used.
4
b
Yield of isolated product.
H
tolerated to this reaction, giving the fluorinated products
in 48%—80% yield (Table 2). It appears that the posi-
tions of the substituents on the aromatic ring of alkynes
have a very limited effect on the reactivity. For example,
2-, 3- and 4-methoxyl-substituted 1-aromaticacetylenes
gave the corresponding products in the yields of 57%,
48% and 58%, respectively (Table 2, Entries 3—5).
Additionally, 1-ethynylnaphthalene is also a viable sub-
strate, affording the desired product in 80% yield. Inter-
estingly, when 1-fluorophenylacetylene was treated with
(1-diazo-2,2,2-trifluoroethyl)benzene, the novel fluori-
nated cyclopropene 3 was obtained in 95% yield
(Scheme 1).[8]
5
OMe
OMe
2e
F
H
PhO
PhO
6
2f
2g
2h
F
F
H
7
F
F
H
H
8
Cl
Cl
Br
Scheme 1 Synthetic transformation of 1-fluoroacetylene
F
F3C Ph
N2
9
AgOTf
Ph
F
Br
CH2Cl2
F
Ph
2i
2j
CF3
Ph
F
H
3, 95% yield
2a
10
11
Br
In spite of the structural similarities between an al-
kyne and 1,3-diyne, the unique juxtaposition of two
acetylene units in a 1,3-diyne could beget unusual prop-
erties, both from a chemical as well as biological point
of view.[3c,9] However, such substrates are unexplored in
the electrophilic fluorination reactions. In order to ex-
tend our novel protocol to the synthesis of fluorinated
diynes, a series of terminal 1,3-diynes 4 were tested
(Table 3). The reaction of terminal 1,3-diynes 4 with
NFSI proceeded smoothly in presence of n-BuLi to af-
ford the 1-fluoro-1,3-diynes 5 in good to high yields
(63%—90%) (Entries 1—8). Notably, when a cyclo-
hexenyl-substituted diyne was employed, the fluorinated
product 5i was also obtained in 85% yield (Entry 9).
Br
F
H
2k
a
The reaction employed a molar ratio of 1∶base∶fluorinating
reagent＝1∶1.1∶1.2 (equiv.). b Yield of isolated product.
Conclusions
In conclusion, we have developed a convenient and
rapid procedure for the synthesis of fluorinated alkynes
by using NFSI as electrophilic fluorinating reagent. This
protocol is compatible with a large variety of
48
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 47—52

Synthetic Route to New Fluorinated Building-Blocks of 1-Fluoroalkynes and 1-Fluorodiynes
Table 3 Synthesis of 1-fluoro-1,3-diynesa
n-BuLi
R
F
R
H
NFSI
THF, -78 oC to r.t.
4
5
Entrya
Alkyne 1
Product 2
Yieldb/%
65
H
F
1
4a
5a
H
F
2
3
4
5
6
7
8
9
63
88
78
57
73
82
90
85
Me
MeO
F
Me
MeO
F
4b
5b
H
F
4c
5c
H
F
4d
5d
H
F
Cl
Cl
4e
4f
5e
5f
H
F
Br
Br
H
F
OMe
OMe
4g
5g
H
F
4h
5h
H
F
4i
5i
a The reaction employed a molar ratio of 4: base: fluorinating reagent＝1∶1.1∶1.2 (equiv.). b Yield of isolated product.
terminal alkynes, furnishing the fluorinated alkynes in
48%—80% yields. In the following transformation of
fluorinated alkyne synthesized, a highly functionalized
fluorocyclopropene has been successfully prepared in
excellent yield (95%). Furthermore, by extending this
protocol to terminal 1,3-diynes, the direct fluorination
reactions proceeded well to afford the novel fluorinated
diynes in good to high yields. Further synthetic applica-
Chin. J. Chem. 2012, 30, 47—52
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
49

Liu et al.
FULL PAPER
tion of these fluorinated alkynes and diynes are ongoing
in our laboratory and will be reported in due course.
1-Fluoro-2-(4-methoxyphenyl)acetylene
(2c)
1
Yellow solid; H NMR (400 MHz, CDCl3) δ: 7.48 (d,
J＝8.8 Hz, 2H), 6.87 (d, J＝8.7 Hz, 2H), 3.84 (s, 3H);
19F NMR (376 MHz, CDCl3) δ: －134.34 (s); 13C NMR
(100 MHz, CDCl3) δ: 134.04, 130.72, 129.27, 114.19,
81.25, 72.99, 55.32; IR (KBr) ν: 2931, 2843, 2137, 1599,
Experimental
Tetrahydrofuran (THF), toluene, and ether were dis-
tilled from sodium/benzophenone prior to use. All pur-
chased reagents were used without further purification.
Analytical thin layer chromatography was performed on
0.20 mm Qingdao Haiyang silica gel plates. Silica gel
(200—300 mesh) (from Qingdao Haiyang Chem. Com-
pany, Ltd.) was used for flash chromatography.
n-Butyllithium (2.4 mol/L solution in toluene) was pur-
chased from ACROS Organics. Standard reagents and
solvents were purified according to known procedures.
1H, 13C and 19F NMR were recorded on Bruker AV
400 MHz at 400 MHz (1H), 100 MHz (13C), as well as
376 MHz (19F). Chemical shifts were reported relative
to the solvent resonance as the internal standard (CDCl3
and CFCl3). MS spectra were recorded on a VG-7070E
or HP 5988A spectrometer using the ESI method.
－
1
1505, 1248, 1165, 1021, 915, 832, 687, 596, 531 cm ;
MS (70 eV) m/z (%): 101.7 (100), 189.5 ([M＋K]＋, 5).
1-Fluoro-2-(3-methoxyphenyl)acetylene
(2d)
Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.94 (d, J＝
7.2 Hz, 2H), 7.54—7.65 (m, 2H), 4.06 (s, 3H); 19F
NMR (376 MHz, CDCl3) δ: －103.50 (s); 13C NMR
(100 MHz, CDCl3) δ: 129.40, 124.65, 124.37, 117.03,
116.73, 115.31, 84.30, 83.58, 55.22; IR (film) ν: 2921,
2853, 2348, 1729, 1432, 1297, 1189, 1081, 995, 813,
－
1
688, 656, 528 cm ; MS (70 eV) m/z (%): 101.7 (100),
189.5 ([M＋K]＋, 10).
1-Fluoro-2-(2-methoxyphenyl)acetylene
(2e)
1
Yellow oil; H NMR (400 MHz, CDCl3) δ: 7.24—7.26
(m, 1H), 7.06 (d, J＝1.2 Hz, 1H), 7.02 (d, J＝1.2 Hz,
1H), 6.88—6.95 (m, 1H), 3.84 (s, 3H); 19F NMR (376
MHz, CDCl3) δ: －103.42 (s); 13C NMR (100 MHz,
CDCl3) δ: 134.14, 130.32, 128.79, 120.44, 11.32,
110.72, 81.38, 80.24, 55.66; IR (film) ν: 2919, 2855,
2196, 1726, 1589, 1489, 1462, 1245, 1162, 1025, 940,
General procedure for the synthesis of 1-fluoroace-
tylene 2
A solution of phenylacetylene (0.20 mmol, 20.4 mg)
in THF (5.0 mL) was added dropwise with n-BuLi (2.40
mol/L, 92 μL, 0.22 mmol, 1.1 equiv.) over 5 min at
－78 ℃ under Ar atmosphere. The resulting suspen-
sion was stirred at this temperature for 30 min, and a
solution of NFSI (98%, 0.24 mmol, 77.1 mg, 1.2 equiv.)
in THF (3.0 mL) was added. After stirring at this tem-
perature for 1 h, the cooling bath was removed and the
reaction was allowed to slowly warm to room tempera-
ture and stirred for 18 h. The reaction was quenched
with saturated ammonium chloride solution and the or-
ganic layers were separated. The aqueous layer was
washed twice with diethyl ether and the combined or-
ganic layer was washed with brine, dried over MgSO4,
filtered, then concentrated in vacuo. The residue was
purified on silica using hexane as solvent system to af-
ford the fluorinated product 2a (15.1 mg, 63% yield).
－
1
786, 752, 591 cm ; MS (70 eV) m/z (%): 101.7 (100),
189.3 ([M＋K]＋, 7).
1-Fluoro-2-(3-phenoxyphenyl)acetylene
(2f)
1
Yellow oil; H NMR (400 MHz, CDCl3) δ: 7.40—7.34
(m, 2H), 7.32—7.25 (m, 2H), 7.20—7.11 (m, 2H), 7.10
—6.99 (m, 3H); 19F NMR (376 MHz, CDCl3) δ:
－103.48 (s); 13C NMR (100 MHz, CDCl3) δ: 129.91,
129.75, 126.98, 123.94, 123.75, 123.57, 122.01, 119.54,
119.42, 119.26, 83.05, 77.68; IR (film) ν: 2919, 2850,
2196, 1585, 1392, 1265, 1154, 969, 797, 771, 637, 605,
－
1
564 cm ; MS (70 eV) m/z (%): 101.9 (15), 110.9 (100),
156.8 (52), 212.0 ([M]＋, 5).
1-Fluoro-2-(4-fluorophenyl)acetylene (2g) Yel-
1
low oil; H NMR (400 MHz, CDCl3) δ: 7.15—7.09 (m,
2H), 7.02—6.98 (m, 2H); 19F NMR (376 MHz, CDCl3)
δ: －101.17 (s), －108.46 (s); 13C NMR (100 MHz,
CDCl3) δ: 134.59, 134.50, 116.03, 115.81, 80.43, 73.54;
IR (film) ν: 2924, 2853, 2195, 1679, 1593, 1488, 1220,
1-Fluoro-2-phenylacetylene (2a)
White solid;
1
m.p. 75—77 ℃; H NMR (400 MHz, CDCl3) δ: 7.56
(dd, J＝7.8, 1.6 Hz, 2H), 7.43—7.33 (m, 3H); 19F NMR
(376 MHz, CDCl3) δ: －100.81 (s); 13C NMR (100
MHz, CDCl3) δ: 132.53, 129.24, 128.47, 121.84, 81.61,
73.99; IR (KBr) ν: 2924, 2850, 2150, 1592, 1485, 1439,
－
1
1091, 1016, 824, 755, 620, 513 cm ; MS (70 eV) m/z
(%): 109.2 (16), 110.7 (100), 138.3 ([M]＋, 6).
1-Fluoro-2-(2-chlorophenyl)acetylene (2h) Yel-
low oil; 1H NMR (400 MHz, CDCl3) δ: 7.60 (d, J＝7.6
Hz, 1H), 7.44 (d, J＝8.0 Hz, 1H), 7.33 (t, J＝7.1 Hz,
1H), 7.28—7.24 (t, J＝7.2, 1H); 19F NMR (376 MHz,
CDCl3) δ: －107.42 (s); 13C NMR (100 MHz, CDCl3) δ:
136.99, 134.39, 130.29, 129.47, 126.57, 121.83, 79.42,
78.39; IR (film) ν: 2926, 2856, 2197, 1696, 1489, 1377,
－
1
1264, 1024, 915, 755, 686, 525 cm ; MS (70 eV) m/z
(%): 79.0 (100), 101.1 ([M－F]＋, 62).
1-Fluoro-2-(4-methylphenyl)acetylene (2b) Yel-
1
low oil; H NMR (400 MHz, CDCl3) δ: 7.44 (d, J＝8.1
Hz, 2H), 7.17 (d, J＝7.9 Hz, 2H), 2.39 (s, 3H); 19F
NMR (376 MHz, CDCl3) δ: －101.80 (s); 13C NMR
(100 MHz, CDCl3) δ: 139.50, 132.41, 129.23, 118.81,
81.56, 73.47, 21.55; IR (KBr) ν: 2921, 2853, 2348, 1729,
1432, 1297, 1189, 1081, 995, 813, 737, 688, 656, 528
－
1
1093, 962, 836, 730, 520 cm ; MS (70 eV) m/z (%):
102.1 (73), 113.0 (100), 155.0 ([M＋H]＋, 10).
1-Fluoro-2-(2-bromophenyl)acetylene (2i) Yel-
1
low oil; H NMR (400 MHz, CDCl3) δ: 7.50—7.40 (m,
－
cm ; MS (70 eV) m/z (%): 87 (100), 102.1 (82), 134.0
2H), 7.38―7.28 (m, 2H); 19F NMR (376 MHz, CDCl3)
δ: －120.10 (s); 13C NMR (100 MHz, CDCl3) δ: 129.02,
1
([M]＋, 20).
50
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 47—52

Synthetic Route to New Fluorinated Building-Blocks of 1-Fluoroalkynes and 1-Fluorodiynes
128.84, 128.55, 127.74, 126.03, 125.80, 82.00, 74.40;
at －78 ℃ under Ar atmosphere. The resulting sus-
IR (film) ν: 2926, 2856, 2196, 1600, 1493, 1377, 1248,
pension was stirred at this temperature for 30 min, and a
solution of NFSI (98%, 0.24 mmol, 77.1 mg, 1.2 equiv.)
in THF (3.0 mL) was added. After stirring at this tem-
perature for 1 h, the cooling bath was removed and the
reaction was allowed to slowly warm to room tempera-
ture and stirred for 18 h. The reaction was quenched
with saturated ammonium chloride solution and the lay-
ers were separated. The aqueous layer was washed
twice with diethyl ether and the combined organic layer
was washed with brine, dried over MgSO4, filtered then
concentrated in vacuo. The residue was purified on sil-
ica using hexane as solvent system to afford the fluori-
nated product 5a (18.7 mg, 65% yield).
－
1
1086, 1031, 834, 755, 699, 516 cm ; MS (70 eV) m/z
(%): 113.0 (16), 296.1 (2[M－H]－, 100).
1-Fluoro-2-(4-bromophenyl)acetylene (2j) Yel-
low oil; 1H NMR (400 MHz, CDCl3) δ: 7.37 (dd, J＝7.5
Hz, 3.6 Hz, 2H), 7.06 (t, J＝8.0 Hz, 2H); 19F NMR (376
MHz, CDCl3) δ: －108.49 (s); 13C NMR (100 MHz,
CDCl3) δ: 132.51, 128.46, 116.02, 115.80, 80.43, 73.74;
IR (film) ν: 2920, 2851, 1967, 1668, 1638, 1459, 1400,
－
1
1235, 969, 752, 524 cm ; MS (70 eV) m/z (%): 113.0
(20), 296.1 (2[M－H]－, 100).
1-Fluoro-2-(1-naphthyl)acetylene (2k)
Yellow
1
solid; m.p. 175—177 ℃; H NMR (400 MHz, CDCl3)
δ: 8.46 (d, J＝8.3 Hz, 1H), 7.94 (d, J＝8.0 Hz, 1H),
7.86 (d, J＝7.6 Hz, 1H), 7.81 (d, J＝7.1 Hz, 1H), 7.68
—7.51 (m, 2H), 7.50—7.46 (m, 1H); 19F NMR (376
MHz, CDCl3) δ: －103.37 (s); 13C NMR (100 MHz,
CDCl3) δ: 133.61, 132.18, 131.32, 129.36, 128.39,
127.04, 126.57, 126.14, 125.17, 119.88, 81.17, 78.92;
IR (KBr) ν: 2919, 2850, 2197, 1585, 1456, 1392, 1154,
1-(4-Fluorobuta-1,3-diynyl)benzene (5a) White
1
solid; m.p. 110—112 ℃; H NMR (400 MHz, CDCl3)
δ: 7.60—7.51 (m, 2H), 7.45—7.32 (m, 3H); 19F NMR
(376 MHz, CDCl3) δ: －62.75 (s); 13C NMR (100 MHz,
CDCl3) δ: 133.31, 130.12, 128.65, 120.54, 77.96, 74.63,
67.42, 63.92; IR (KBr) ν: 2917, 2849, 2199, 1600, 1486,
－
1
1442, 1280, 1177, 998, 906, 747, 678, 523 cm ; MS
(70 eV) m/z (%): 84.6 (46), 101.8 (100), 144.0 ([M]＋,
9).
－
1
1012, 969, 797, 757, 637, 576 cm ; MS (70 eV) m/z
(%): 112.7 (100), 156.8 (50), 170.2 ([M]＋, 8).
1-(4-Fluorobuta-1,3-diynyl)-4-methylbenzene (5b)
White solid; m.p. 143―145 ℃; H NMR (400 MHz,
Procedure for Ag(I)-catalyzed cyclopropenation of
1-fluoro-2-phenyl alkyne with (1-diazo-2,2,2-
trifluoroethyl)benzene
1
CDCl3) δ: 7.45 (d, J＝8.0 Hz, 2H), 7.16 (d, J＝7.9 Hz,
2H), 2.39 (s, 3H); 19F NMR (376 MHz, CDCl3) δ:
－128.79 (s); 13C NMR (100 MHz, CDCl3) δ: 140.59,
133.15, 129.36, 117.43, 78.02, 73.99, 67.06, 63.75,
21.71; IR (KBr) ν: 2919, 2851, 2195, 1679, 1599, 1359,
A mixture of 1-fluoro-2-phenylacetylene (0.4 mmol,
48.0 mg, 2.0 equiv.) and AgOTf catalyst (98%, 0.02
mmol, 1.0 mg, 0.1 equiv.) was weighed in a 25-mL
one-necked round bottom flask covered with aluminum
foil to exclude light. The mixture was dissolved in di-
chloromethane (2 mL) and stirred at room temperature
under an atmosphere of argon. (1-Diazo-2,2,2-trifluoro-
ethyl)benzene (0.2 mmol, 37.3 mg, 1.0 equiv.) in di-
chloromethane (8.0 mL) was then added to the former
solution via syringe pump for 1 h. Then, the mixture
was stirred for additional 1 h and concentrated in vacuo.
The residue was purified on silica using hexane as sol-
vent system to afford the desired product 3 as yellow oil
(52.9 mg, 95% yield).
－
1
1182, 937, 883, 755, 689, 590, 522 cm ; MS (70 eV)
m/z (%): 112.9 (38), 157.1 (100), 158.8 ([M]＋, 11).
1-(4-Fluorobuta-1,3-diynyl)-4-methoxybenzene
1
(5c) Yellow solid; m.p. 187—189 ℃; H NMR (400
MHz, CDCl3) δ: 7.50 (d, J＝8.8 Hz, 2H), 6.87 (d, J＝
8.7 Hz, 2H), 3.85 (s, 3H); 19F NMR (376 MHz, CDCl3)
δ: －103.49; 13C NMR (100 MHz, CDCl3) δ: 134.95,
134.29, 114.40, 112.45, 77.99, 73.60, 67.06, 63.89,
29.68; IR (KBr) ν: 2918, 2849, 2199, 1664, 1507, 1463,
－
1
1252, 1174, 1026, 822, 730, 527 cm ; MS (70 eV) m/z
(%): 84.9 (32), 102.0 (100), 174.0 ([M]＋, 5).
1,3-Diphenyl-2-fluoro-3-trifluoromethylcycoprop-
1-(4-Fluorobuta-1,3-diynyl)-4-fluorobenzene (5d)
1
ene (3) Yellow oil; H NMR (400 MHz, CDCl3) δ:
1
Yellow oil; H NMR (400 MHz, CDCl3) δ: 7.55 (dd,
7.79—7.73 (m, 1H), 7.66—7.55 (m, 2H), 7.54—7.45
(m, 3H), 7.44—7.41 (m, 1H), 7.41—7.30 (m, 3H); 19F
NMR (376 MHz, CDCl3) δ: －64.11 (s), －67.15 (s);
13C NMR (100 MHz, CDCl3) δ: 132.091, 130.56,
J＝8.0, 4.0 Hz, 2H), 7.06 (dd, J＝8.0, 4.0 Hz, 2H); 19F
NMR (376 MHz, CDCl3) δ: －74.68 (s), －106.65 (s);
13C NMR (100 MHz, CDCl3) δ: 135.42, 135.33, 116.24,
116.01, 75.25, 74.23, 67.14, 63.54; IR (film) ν: 2923,
2851, 2195, 1679, 1489, 1260, 1091, 1014, 801, 755,
1
130.07, 129.56, 129.09, 128.65 (q, JF-C ＝249 Hz),
2
128.51, 128.02, 127.67, 122.01, 103.34, 76.89 (q, JF-C
－
1
704, 524 cm ; MS (70 eV) m/z (%): 110.7 (100), 160.7
＝32.5 Hz); IR (film) ν: 2921, 2851, 2202, 1490, 1445,
([M－H]－, 9).
1298, 1253, 1164, 1132, 1028, 924, 757, 689, 591, 525
－
1
1-(4-Fluorobuta-1,3-diynyl)-4-chlorobenzene (5e)
cm ; MS (70 eV) m/z (%): 227.9 (100), 233.9 (80),
1
318.3 ([M＋K＋H]＋, 45).
Yellow oil; H NMR (400 MHz, CDCl3) δ: 7.55 (dd,
J＝8.1, 4.0 Hz, 2H), 7.06 (dd, J＝8.0, 4.0 Hz, 2H); 19F
NMR (376 MHz, CDCl3) δ: －106.63 (s); 13C NMR
(100 MHz, DMSO) δ: 134.11, 131.82, 124.11, 119.97,
74.61, 74.20, 71.93, 67.93; IR (film) ν: 2921, 2851,
2202, 1669, 1588, 1488, 1398, 1261, 1089, 1013, 823,
General procedure for the synthesis of 1-fluoro-
1,3-diynes 5
To a solution of 1, 3-diyne (0.20 mmol, 20.4 mg, 1.0
equiv.) in THF (5.0 mL) was added dropwise n-BuLi
(2.40 mol/L, 92 μL, 0.22 mmol, 1.1 equiv.) over 5 min
－
1
760, 521 cm ; MS (70 eV) m/z (%): 110.6 (100), 178.0
Chin. J. Chem. 2012, 30, 47—52
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
51

Liu et al.
FULL PAPER
([M]＋, 5).
Weinheim, 2004; (b) Thayer, A. M. Chem. Eng. News 2006, 84, 15.
[2] (a) Uneyama, K. Organofluorine Chemistry, Blackwell Publishing,
Oxford, 2006; (b) Prabhakaran, J.; Underwood, M. D.; Parsey, R. V.;
Arango, V.; Majo, V. J.; Simpson, N. R.; Heertum, R. V.; Mann, J.
J.; Kumar, J. S. D. Bioorg. Med. Chem. 2007, 15, 1802.
1-(4-Fluorobuta-1,3-diynyl)-4-bromobenzene (5f)
1
Yellow oil; H NMR (400 MHz, CDCl3) δ: 7.55 (dd,
J＝8.0, 3.6 Hz, 2H), 7.40—7.36 (m, 2H); 19F NMR
(376 MHz, CDCl3) δ: －108.65 (s); 13C NMR (100
MHz, CDCl3) δ: 134.90, 134.82, 116.03, 115.81, 74.28,
73.31, 71.33, 67.99; IR (film) ν: 2919, 2851, 2198, 1598,
1505, 1376, 1261, 1029, 996, 813, 748, 723, 521 cm–1;
MS (70 eV) m/z (%): 110.7 (100), 222.2 ( [M]＋, 7).
1-(4-Fluorobuta-1,3-diynyl)-2-methoxybenzene
(5g) Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.7—
7.50 (m, 2H), 7.42 (d, J＝7.2 Hz, 1H), 7.28 (t, J＝7.3
Hz, 1H), 3.88 (s, 3H); 19F NMR (376 MHz, CDCl3) δ:
－103.57 (s); 13C NMR (100 MHz, CDCl3) δ: 135.04,
133.69, 129.23, 127.79, 120.64, 110.80, 78.12, 74.71,
67.94, 64.18, 30.77; IR (film) ν: 2962, 2925, 2198, 1726,
1592, 1450, 1358, 1271, 1183, 1021, 938, 883, 737, 687,
[3] (a) Stang, P. J.; Diederich, F. Modern Acetylene Chemistry,
Wiley-VCH, Weinheim, Germany, 1995; (b) Siemsen, P.;
Livingston, R. C.; Diederich, F. Angew. Chem., Int. Ed. 2000, 39,
2632; (c) Minto, R. E.; Blacklock, B. J. Prog. Lipid Res. 2008, 47,
233.
[4] (a) Middleton, W. J.; Sharkey, W. H. J. Am. Chem. Soc. 1959, 81,
803; (b) Viehe, H. G.; Merényi, R.; Oth, J. F. M.; Sender, J. R.;
Valange, P. Angew. Chem., Int. Ed. 1964, 76, 955; (c) Sauvetre, R.;
Normant, J. F. Tetrahedron Lett. 1982, 23, 4325; (d) Markin, S.;
Sauvetre, R. Tetrahedron Lett. 1982, 23, 4329; (e) Runge, A.;
Sander, W. W. Tetrahedron Lett. 1990, 31, 5453; (f) Hanamoto, T.;
Koga, Y.; kawanami, T.; Furuno, H.; Inanaga, J. Angew. Chem., Int.
Ed. 2004, 43, 3582.
－
[5] (a) Tajbakhsh, M.; Habibzadeh, S. Letters in Organic Chemistry
2007, 4, 512; (b) Hein, J. E.; Tripp, J. C.; Krasnova, L. T.; Sharpless,
B.; Fokin, V. V. Angew. Chem., Int. Ed. 2009, 48, 8018; (c) Li, L.-S.;
Wu, Y.-L. Tetrahedron Lett. 2002, 43, 2427; (d) Reddy, K. R.;
Venkateshwar, W.; Maheswari, C. U.; Kumar, P. S. Tetrahedron
Lett. 2010, 51, 2170; (e) Luithle, J. E. A.; Pietruzka, J. Eur. J. Org.
Chem. 2000, 2557; (f) Manickam, M. C. D.; Annalakshmi, S.;
Pitchumani, K.; Srinivasan, C. Org. Biomol. Chem. 2005, 3, 1008;
(g) Chen, Z.; Jiang, H.; Li, Y.; Qi, C. Chem. Commun. 2010, 46,
8049; (h) Abele, E.; Rubina, K.; Abele, R.; Gaukhman, A.; Lukevics,
E. J. Chem. Res. (S) 1998, 618; (i) Martins, M. A. P.; Emmerich, D.
J.; Pereira, C. M. P.; Cunico, W.; Rossato, M.; Zanatta, N.; Bona-
corso, H. G. Tetrahedron Lett. 2004, 45, 4935; (j) Tajbakhsh, M.;
Khazaei, A.; Mahalli, M. S.; Vaghi, R. G. Phosphorus, Sulfur, Sili-
con 2004, 179, 1159; (k) Usanov, D.; Yamamoto, H. J. Am. Chem.
Soc. 2011, 133, 1286; (l) Liu, Y.; Zhong, Z.; Nakajima, K.; Takaha-
shi, T. J. Org. Chem. 2002, 67, 7451; (m) Yao, M.-L.; Reddy, M. S.;
Yong, L.; Walfish, I.; Blevins, D. W.; Kabalka, G. W. Org. Lett.
2010, 12, 700.
1
591 cm ; MS (70 eV) m/z (%): 84.6 (30), 102.1 (100),
174.2 ([M]＋, 8).
1-(4-Fluorobuta-1,3-diynyl)naphthalene
(5h)
1
Yellow solid; m.p. 175—177 ℃; H NMR (400 MHz,
CDCl3) δ: 8.34 (d, J＝8.0 Hz, 1H), 7.90 (dd, J＝8.2, 4.0
Hz, 2H), 7.84 (d, J＝7.1 Hz, 1H), 7.65 (dd, J＝8.2, 3.9
Hz, 1H), 7.58 (t, J＝7.4 Hz, 1H), 7.46 (t, J＝7.7 Hz,
1H); 19F NMR (376 MHz, CDCl3) δ: －101.87 (s); 13C
NMR (100 MHz, CDCl3) δ: 134.30, 133.32, 133.06,
130.63, 128.67, 127.61, 126.92, 125.92, 125.21, 118.20,
79.05, 76.57, 68.44, 64.40; IR (KBr) ν: 2924, 2850,
2196, 1600, 1457, 1397, 1264, 1031, 824, 755, 699, 514
－
1
cm ; MS (70 eV) m/z (%): 84.9 (77), 101.9 (100),
130.0 (54), 194.0 ([M]＋, 10).
1-(4-Fluorobuta-1,3-diynyl)cyclohex-1-ene
(5i)
Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 6.41 (d, J＝
1.6 Hz, 1H), 2.15—2.05 (m, 4H), 1.69—1.58 (m, 2H),
1.41—1.28 (m, 2H); 19F NMR (376 MHz, CDCl3) δ:
－82.00 (s); 13C NMR (100 MHz, CDCl3) δ: 141.68,
118.78, 79.59, 72.20, 66.53, 63.55, 28.29, 26.11, 21.96,
21.14; IR (film) ν: 2925, 2853, 2191, 1615, 1457, 1264,
[6] Lal, G. S.; Pez, G. P.; Syvret, R. G. Chem. Rev. 1996, 96, 1737.
[7] (a) Ma, J.-A.; Cahard, D. Tetrahedron: Asymmetry 2004, 15, 1007;
(b) Ma, J.-A.; Cahard, D. J. Fluorine Chem. 2004, 125, 1357; (c)
Cui, H.-F.; Dong, K.-Y.; Zhang, G.-W.; Wang, L.; Ma, J.-A. Chem.
Commun. 2007, 22, 2284; (d) Nie, J.; Zhu, H.-W.; Cui, H.-F.; Hua,
M.-Q.; Ma, J.-A. Org. Lett. 2007, 9, 3053; (e) Wang, L.; Meng, W.;
Zhu, C.-L.; Zheng, Y.; Nie, J.; Ma, J.-A. Angew. Chem., Int. Ed.
2011, 50, 9442.
－
1
918, 741, 706, 518 cm ; MS (70 eV) m/z (%): 85.0
(29), 101.9 (100), 130.0 (30), 166.9 ([M＋NH4]＋, 24).
Acknowledgement
[8] Briones, J. F.; Davies, H. M. Org. Lett. 2011, 13, 3984.
[9] (a) Reber, S.; Knöpfel, T. F.; Carreira, E. M. Tetrahedron 2003, 59,
6813; (b) Trost, B. M.; Chan, V. S.; Yamamoto, D. J. Am. Chem.
Soc. 2010, 132, 5186; (c) Aikawa, K.; Hioki, Y.; Mikami, K. Org.
Lett. 2010, 12, 5716; (d) Turlington, M.; Du, Y.; Ostrum, S. G.;
Santosh, V.; Wren, K.; Lin, T.; Sabat, M.; Pu, L. J. Am. Chem. Soc.
2011, 133, 11780; (e) Graham, E. R.; Tykwinski, R. R. J. Org.
Chem. 2011, 76, 6574.
This work was supported financially by the National
Natural Science Foundation of China (Nos. 20972110
and 21002068).
References
[1] (a) Kirsch, P. Modern Fluoroorganic Chemistry, Wiley-VCH,
(Zhao, X.)
52
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 47—52