Silver-Mediated Perfluoroalkylation of Terminal Alkynes with Perfluoroalkyl Iodides

Article abstract of DOI:10.1021/acs.joc.0c00894

The incorporation of a perfluoroalkyl group (RF) into drug candidates has become an increasingly important strategy in drug molecule design. In this study, the silver-mediated perfluoroalkylation reaction based on the addition-elimination process of terminal alkynes which was initiated by a perfluoroalkyl radical to form a C(sp)-RF bond has been developed. The reaction proceeds under mild conditions using readily available, low-cost perfluoroalkyl iodides as the sources of the RF group. This method allows access to a variety of perfluoroalkylated alkynes.

Full text of DOI:10.1021/acs.joc.0c00894

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Silver-Mediated Perfluoroalkylation of
Terminal Alkynes with Perfluoroalkyl Iodides
Junlan Li, Lihua Liu, Kaiting Zheng, Chenggong Zheng, Hua Xiao, and Shilu Fan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00894 • Publication Date (Web): 08 Jun 2020
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The Journal of Organic Chemistry
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Silver-Mediated Perfluoroalkylation of Terminal
Alkynes with Perfluoroalkyl Iodides
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Junlan Li,† Lihua Liu,§ Kaiting Zheng,† Chenggong Zheng,† Hua Xiao,*, and Shilu Fan*,†,‡
§
†School of Chemistry and Chemical Engineering, Hefei University of Technology, 193 Tunxi Road,
Anhui, 230000, People's Republic of China
‡Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese
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Academy of Sciences, Shanghai 200032, China
§School of Food and Biological Engineering, Hefei University of Technology, 193 Tunxi Road, Anhui,
230009, China
shilu.fan@hfut.edu.cn
TOC
Keywords: silver-mediated, perfluoroalkylation, terminal alkyne, radical, C(sp)-RF bond
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ABSTRACT. The incorporation of perfluoroalkyl group (RF) into drug candidate has become an
increasingly important strategy in the drug molecule design. In this study, the silver-mediated
perfluoroalkylation reaction based on the addition-elimination process of terminal alkynes which was
initiated by perfluoroalkyl radical to form C(sp)-RF bond has been developed. The reaction proceeds under
mild conditions using readily available, low-cost perfluoroalkyl iodides as the sources of the RF group.
This method allows access to a variety of perfluoroalkylated alkynes.
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The perfluoroalkylated compounds are widely used in the fields of agrochemicals, pharmaceuticals and
materials because of their unique characteristics imparted by the perfluoroalkyl group, such as strong
electron-withdrawing effect, lipophilicity and metabolic stability.1,2 Hence, the development of new
methodologies for the installation of perfluoroalkyl group into organic structures has recently been
attracting much attention. As a result, various synthetic methods of perfluoroalkylation have been reported,
including transition-metal-mediated3 or -catalyzed4 perfluoroalkylation using either the nucleophilic or
electrophilic perfluoroalkylating reagents as RF sources. Recent advances in radical-based
perfluoroalkylation protocols5,6 are particularly attractive due to the mild reaction condition, which
encourages us to design our reaction in this way.
In comparison with the advances achieved in perfluoroalkylation of arenes and alkenes, the formation
of C(sp)-RF bonds by perfluoroalkylation of alkynes is still suffering many limitations, despite potentially
high synthetic value of perfluoroalkylated alkynes. The traditional methods for preparation of
perfluoroalkylated alkynes used potassium organotrifluoroborate,7 prefunctionalized alkynyl metals8 or
electrophilic perfluoroalkylating reagents,9 which usually has intrinsic drawbacks in terms of harsh
reaction conditions and uneasy operation of sensitive organometallic reagents. It's still high desirable to
find a fantastic way which direct convert the C(sp)−H bonds of a terminal alkynes into the C(sp)−RF
bonds. To achieve this, Qing and co-workers reported the methods for the copper-mediated/catalyzed
oxidative perfluoroalkylation of terminal alkynes using low-cost nucleophilic perfluoroalkylating reagent
(TMSCF3), and with convenient operations.10 Shortly afterwards, copper-catalyzed/mediated
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perfluoroalkylation of terminal alkynes with electrophilic perfluoroalkylating reagents11 have been
reported by Guo, Xiao, and Weng and Huang, respectively. However, unlike the cheap nucleophilic
perfluoroalkylating reagents, electrophilic perfluoroalkylating reagents are all expensive, which limits the
applications of these protocols in large-scale syntheses. Trifluoromethyl ketones12 and sulfoxides,13 and
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Difluoromethylene Phosphobetaine (Ph3P+CF2CO2 , PDFA)14 are also suitable perfluoroalkylating
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reagent, which were successfully utilized in analogous copper-mediated processes. However, these
methods suffer from several drawbacks such as (1) using explosive perfluoroalkylated reagents and/or (2)
hazardous reaction conditions (3) limitation of the species of perfluoroalkyl group.
Scheme 1. Representative approaches to the formation of C(sp)-RF bonds.
Consequently, developing a new method to install RF structure motif into organic molecules with
readily available, easy to handle and environmentally benign reagents under mild conditions is still
attractive. However, the reactions with cheap perfluoroalkyl iodides (RFI)15 as the ultimate RF source to
achieve perfluoroalkylated alkynes are rare,16 which provides the primary protocol but with obvious
drawbacks. Cho and co-workers accomplished a photoredox catalytic perfluoroalkylation of terminal
alkynes17 and alkynyl bromides,18 in which several perfluoromethylated aromatic alkynes were prepared
in good yields. These photocatalytic reactions have attracted much attentions because of their high
catalytic efficiency. Photocatalysts are, however, an expensive19 and uncommon reagent in a lab, which
limit the application of these methods. We herein describe an efficient method for Ag(I)-mediated
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perfluoroalkylation of terminal alkynes to construct C(sp)-RF bond by using RFI with a wide range of
substrates in moderate to high yields (Scheme 1). This method has notable advantage in mild reaction
conditions, convenient operation, and good RF sources compatibility.
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Table 1. Optimization of the reaction conditionsa
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Entry
1
Silver salt (equiv)
AgOAc (1.2)
AgOAc (1.2)
AgOAc (1.2)
AgOAc (1.2)
AgOAc (1.2)
AgOAc (1.2)
AgOAc (1.2)
AgOAc (1.2)
AgOAc (1.2)
AgNO3 (1.2)
Ag2CO3 (1.2)
Ag2O (1.2)
Base (equiv)
Cs2CO3 (2.0)
Cs2CO3 (2.0)
Cs2CO3 (2.0)
Cs2CO3 (2.0)
Cs2CO3 (2.0)
tBuOLi (2.0)
tBuONa (2.0)
tBuOK (2.0)
K2CO3 (2.0)
tBuOLi (2.0)
tBuOLi (2.0)
tBuOLi (2.0)
tBuOLi (2.0)
tBuOLi (2.0)
…
Solvent
DME
4a/7a (%)b
(20)/(64)
(7)/(86)
(24)/8
(40)/(16)
(54)/(12)
(85)/0
65/0
2
Dioxane
3
DMSO
4
DMF
5
DMAC
6
DMAC (deg.)
DMAC (deg.)
DMAC (deg.)
DMAC (deg.)
DMAC (deg.)
DMAC (deg.)
DMAC (deg.)
DMAC (deg.)
DMAC (deg.)
DMAC (deg.)
DMAC (deg.)
7
8
60/0
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40/0
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16
(75)/0
60/0
65/0
AgOAc (0.5)
AgOAc (0.2)
AgOAc (1.2)
…
43/0
22/0
0/70
tBuOLi (2.0)
0/0
a Reaction conditions (unless otherwise specified): 1a (0.2 mmol, 1.0 equiv), 2b (0.6 mmol, 3.0 equiv),
silver salt (0.24 mmol, 1.2 equiv), base (0.4 mmol, 2.0 equiv), solvent (2.0 mL), 80 °C, 6 h. b NMRyield
determined by 19FNMRusing fluorobenzene as internal standard and number in parentheses is isolated
yield. deg. = degas.
Accordingly, we conducted this reaction by choosing 1-ethynyl-4-propylbenzene 1a and 1-
iodoperfluorobutane 2b as model substrates in the presence of a silver salt. To our delight, after the
solvents had been screened (Table 1, entries 1−5), an 54% isolated yield was obtained when the reaction
was run in degassed DMAC at 80 °C for 6 h using AgOAc as a silver salt and Cs2CO3 as a base (Table 1,
entry 5). We found that the degassed DMAC could reduce the formation of iodoperfluoroalkylated
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product 7a. Further optimization revealed that 85% yield of isolated product 4a was afforded by using
tBuOLi as base (Table 1, entry 6). With the preliminary results in hand, various bases were tested to
increase the efficiency of the reaction (Table 1, entries 7−9). The yield was, however, no longer improved
when tBuONa, tBuOK or K2CO3 were used as a base. Further optimization of the reaction conditions by
testing different silver salts exhibited that all tested metal salts performed well, and the best result was
still obtained from AgOAc (Table 1, entries 10−12). The yields dramatically decreased when the loading
amount of the silver salt was decreased (Table 1, entries 13 and 14). A lower reaction temperature led to
a much lower yield than the reaction run at 80 oC in DMAC (see Table S1 in supporting information). In
addition, silver salt and base are essential for the reaction because the absence of them failed to give any
desired product, which indicates that a silver-mediated process was involved in the reaction (Table 1,
entries 15 and 16).
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With the optimized reaction conditions, a wide range of terminal alkynes was conducted by this method
(Table 2). 4-n-propyl-, 4-n-amyl-, or 4-t-butyl-substituted aryl acetylenes reacted readily with 2b to give
the desired perfluorobutylated products 4a–4c in 85%, 77%, and 80% yields, respectively. The simple
phenylacetylene gave a 56% isolated yield 4d. The electron-rich terminal alkynes reacted smoothly to
give the corresponding products (4e–4g) in 59–74% yields. 4-Ethynyl-1,1'-biphenyl and 2-
ethynylnaphthalene underwent the reaction to furnish 4h and 4i in good yields. Most remarkably, terminal
alkynes bearing a chloride underwent reaction smoothly with yield as high as 71% (4j). Even fluorinated
substrate which contains a high electron withdrawing group was compatible with the present reaction
system, thus providing 4k in good yield. The heterocyclic alkynes were also suitable in this reaction (4l,
4m). Additionally, substrate with alkoxycarbonyl group 1n was also tolerated in this reaction to give a
moderate yield. However, alkynes with nitrile substituent in the benzene ring was not suitable substrate
(4o). Unfortunately, terminal aliphatic alkyne just gave a 12% yield (4p) along with trace amount of
iodoperfluoroalkylated product, but a large amount of raw material 1p was recovered, which suggest that
the radical addition process may be the rate-determining step, but not the dehydrohalogenation process.
We speculate that the radical addition reaction of perfluoroalkyl radical to aliphatic alkynes have a low
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efficiency under the standard condition. In comparison with the aromatic alkynes, the addition rate of
electrophilic radicals (RF) to aliphatic alkynes decreases due to the absence of conjugation effect of
aromatic ring. It is also possible to prepare perfluoroalkylated alkynes on a gram scale without isolated
yield dramatic dropping.
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Table 2. Perfluoroalkylation of terminal alkynes with 2ba
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a Reaction conditions: terminal alkyne 1 (0.2 mmol), C4F9I 2b (0.6 mmol), AgOAc (0.24 mmol), tBuOLi
(0.4 mmol) in DMAC (2.0 mL) at 80 oC for 6 h. The number in parentheses is the NMR yield. b A gram-
scale reaction. deg. = degas.
To expand the scope of the transformation, we next embarked on an exploration of other commercial
available perfluoroalkyl iodides 2a, 2c–2d (Table 3). Generally, moderate to high yields of desired
products (3-6) were afforded under the standard conditions (Table 3). Both electron-neutral and electron-
donation substrates furnished the desired products in good yields. We were glad to find that efficiency of
the reaction does not have a negative influence by increasing the length of fluoroalkyl chain such as
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smooth formation of products 5, even 6a which is otherwise inaccessible. It should be noted that halide
substituent and heteroaromatic substrates still shown a good reactivity (5l, 5m).
Table 3. Perfluoroalkylation of terminal alkynes with 2a–da
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a Reaction conditions: terminal alkyne 1 (0.2 mmol), RFI 2 (0.6 mmol), AgOAc (0.24 mmol), tBuOLi (0.4
mmol) in DMAC (2.0 mL) at 80 oC for 6 h. The number in parentheses is the NMR yield. deg. = degas.
To gain some mechanistic insight into the present reaction, several radical-inhibition experiments were
conducted (Scheme 2, eq 1). Addition of the radical inhibitor TEMPO or hydroquinone to the reaction
mixture of 1a and 2b in the presence of AgOAc (1.2 equiv) and tBuOLi (2.0 equiv) led to a significant
decrease of the reaction efficiency. Thus, these preliminary studies showed that our present
perfluoroalkylation reaction involves radical intermediates. Desired product 3a was also obtained with
high isolated yield (98%) by treating iodoperfluoroalkylated product 7a in the presence of tBuOLi, thus
indicating that an iodoperfluoroalkylated intermediate is involved in the reaction (Scheme 2, eq 2).
Scheme 2. Mechanistic studies.
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Although the exact mechanism of the reaction is still not clear, on the basis of the results reported by
others,17 a plausible mechanism is proposed and shown in Scheme 3. Perfluoroalkyl radical A was
initiated by reaction of AgOAc with perfluoroalkyl iodide 2 via single electron transfer, then combination
of this electron-deficient radical species with a terminal alkyne 1 generates the vinyl radical B. The
iodoperfluoroalkylated intermediate 7 was subsequently formed by iodide abstraction from 2 by B.
Unfortunately, radical chain reaction could not achieve because that radical A may react with byproduct
which was geneated from radical initiation pocess or decompose. As a consequence of
dehydrohalogenation of 7, the desired perfluoroalkylated alkyne 4 was delivered.
Scheme 3. The proposed mechanism.
CONCLUSION
In conclusion, we have described a novel silver-mediated strategy for achieving the perfluoroalkylation
of alkynes with perfluoroalkyl iodides. A series of alkynes and perfluoroalkyl iodides performed well
under standard reaction conditions and provided the corresponding product in good to excellent yields.
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Compared with the reported methods, our strategy does not require preparation of stoichiometric metal
reagents and alkynyl halides. Additionally, the gram-scale reaction was also easily achieved. Further
studies to expand the substrate scope and its applications are now in progress in our laboratory.
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EXPERIMENTAL SECTION
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General information: 1H NMR and 13C NMR spectra were recorded on a Bruker 600 MHz spectrometer
in CDCl3. Data for 1H NMR are reported as follows: chemical shift (parts per million, scale), multiplicity,
coupling constant (hertz), and integration. Data for 13C NMR are reported in terms of chemical shift (parts
per million, scale), multiplicity, and coupling constant (hertz). High-resolution mass spectrometry
(HRMS) analysis was performed by the analytical facility at the University of Science and Technology
of China..
Materials: All reagents were used as received from commercial sources, unless specified otherwise, or
prepared as described in the literature. All reagents were weighed and handled in air, and refilled with an
inert atmosphere of N2 at room temperature. DMF, DMSO, DMPU, NMP, and DCE were distilled under
reduced pressure from CaH2. Toluene, 1,4-Dioxane, THF, Diglyme, and DME were distilled from sodium
and benzophenone immediately before use.
General procedure for silver-mediated perfluoroalkylation of terminal alkynes
To a septum capped 25 mL of sealed tube were added AgOAc (1.2 equiv) and tBuOLi (2.0 equiv) under
N2, followed by DMAC (deg.) (2.0 mL) with stirring. 1 (0.2 mmol, 1.0 equiv) and 2 (0.6 mmol) was then
o
added subsequently. The sealed tube was screw capped and heated to 80 C (oil bath). After stirring for
12 h, the reaction mixture was cooled to room temperature. The reaction mixture was diluted with ethyl
acetate, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified with
silica gel chromatography (Petroleum ether (100%)) to provide pure product.
Procedure for gram-scale reaction
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To a septum capped 100 mL of sealed tube were added AgOAc (1.362g, 8.16 mmol, 1.2 equiv) and
tBuOLi (1.09 g, 13.6 mmol, 2.0 equiv) under N2, followed by DMAC (deg.) (40 mL) with stirring. 1a
(0.98 g, 6.8 mmol, 1.0 equiv) and 2 (7.06 g, 20.4 mmol, 3.0 equiv) was then added subsequently. The
sealed tube was screw capped and heated to 80 oC (oil bath). After stirring for 12 h, the reaction mixture
was cooled to room temperature. The reaction mixture was diluted with ethyl acetate, washed with brine,
dried over Na2SO4, filtered and concentrated. The residue was purified with silica gel chromatography
(Petroleum ether (100%)) to provide pure product 4a (1.97g, 80%) as a pale yellow oil.
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1-(perfluorohex-1-yn-1-yl)-4-propylbenzene (4a). The product (62 mg, 85% yield) as a pale yellow oil
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was purified with silica gel chromatography (Petroleum ether (100%)). H NMR (600 MHz, CDCl3) 
7.47 (d, J = 7.8 Hz, 2H), 7.21 (d, J = 7.8 Hz, 2H), 2.62 (t, J = 7.2 Hz, 2H), 1.65 (m, 2H), 0.94 (t, J = 7.2
Hz, 3H). 13C{1H} NMR (150.8 MHz, CDCl3)  149.1, 135.1 (t, J = 2.4 Hz), 131.5, 121.0 (t, J = 33.5 Hz),
119.1 (q, J = 1.5 Hz), 118.2 (t, J = 2.4 Hz), 111.8 (m), 110.4 (m), 95.5 (t, J = 6.3 Hz), 76.8 (t, J = 36.1
Hz), 40.7, 26.9, 16.3. 19F NMR (564 MHz, CDCl3)  -81.1 (t, J = 9.0 Hz, 3F), -97.1 (s, 2F), -123.8 (t, J =
5.6 Hz, 2F) , -125.5 (q, J = 4.0 Hz, 2F). IR (thin film): max 2248, 1239, 884 cm-1. MS (EI): m/z (%) 362
(M), 333, 164 (100). HRMS (EI) m/z: [M]+ Calculated for C15H11F9 362.0712; Found 362.0714.
1-pentyl-4-(perfluorohex-1-yn-1-yl)benzene (4b). The product (60 mg, 77% yield) as a pale yellow oil
1
was purified with silica gel chromatography (Petroleum ether (100%)). H NMR (600 MHz, CDCl3) 
7.47 (d, J = 7.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 2.64 (t, J = 7.2 Hz, 2H), 1.62 (m, 2H), 1.32 (m, 4H),
0.90 (t, J = 6.6 Hz, 3H). 13C{1H} NMR (150.8 MHz, CDCl3)  149.4, 135.1 (t, J = 2.4 Hz), 131.4, 121.0
(t, J = 32.9 Hz), 119.1 (t, J = 33.3 Hz), 118.2 (t, J = 3.0 Hz) , 111.8 (m), 108.7 (m), 95.5 (t, J = 6.3 Hz),
76.8 (t, J = 36.1 Hz), 38.7, 34.0, 33.4, 25.1, 16.6. 19F NMR (564 MHz, CDCl3)  -81.1 (t, J = 9.6 Hz, 3F),
-97.1 (d, J = 2.3 Hz, 2F), -123.5 (m, 2F), -125.5 (m, 2F). IR (thin film): max 2934, 2248, 1241 cm-1. MS
(EI): m/z (%) 390 (M), 333, 164 (100). HRMS (EI) m/z: [M]+ Calculated for C17H15F9 390.1025; Found
390.1028.
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1-(tert-butyl)-4-(perfluorohex-1-yn-1-yl)benzene (4c). The product This compound is known.18 (61 mg,
80% yield) as a pale yellow oil was purified with silica gel chromatography (Petroleum ether (100%)).
1H NMR (600 MHz, CDCl3)  7.51 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 1.33 (s, 9H). 13C{1H}
NMR (150.8 MHz, CDCl3)  157.5, 134.9 (t, J = 2.4 Hz), 128.4, 121.0 (t, J = 33.3 Hz), 119.1 (t, J = 33.6
Hz), 118.0 (t, J = 3.0 Hz), 112.5 (m), 111.1 (m), 95.4 (t, J = 6.3 Hz), 76.8 (t, J = 36.2 Hz), 37.7, 36.6. 19F
NMR (564 MHz, CDCl3)  -76.9 (t, J = 9.6 Hz, 3F), -92.9 (s, 2F), -119.3 (q, J = 3.4 Hz, 2F), -121.3 (q, J
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= 9.6 Hz, 2F). IR (thin film): max 2972, 2245, 1241 cm-1. MS (EI): m/z (%) 376 (M), 361 (100), 333.
HRMS (EI) m/z: [M]+ Calculated for C16H13F9 376.0868; Found 376.0868.
(perfluorohex-1-yn-1-yl)benzene (4d). This compound is known.18 (36 mg, 56% yield) as a pale yellow
oil was purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz, CDCl3)
 7.57 (d, J = 7.2 Hz, 2H), 7.50 (t, J = 7.8 Hz, 2H), 7.41 (t, J = 7.8 Hz, 2H). 19F NMR (564 MHz, CDCl3)
 -81.7 (s, 3F), -98.0 (s, 2F), -124.1 (s, 2F), -126.1 (s, 2F).
1-methoxy-4-(perfluorohex-1-yn-1-yl)benzene (4e). This compound is known.18 The product (52 mg,
74% yield) as a pale yellow oil was purified with silica gel chromatography (Petroleum ether (100%)).
1H NMR (600 MHz, CDCl3)  7.50 (d, J = 9.0 Hz, 2H), 6.90 (d, J = 9.0 Hz, 2H), 3.84 (s, 3H). 13C{1H}
NMR (150.8 MHz, CDCl3)  164.3, 136.9 (t, J = 2.4 Hz), 121.0 (t, J = 33.3 Hz), 119.1 (t, J = 33.2 Hz),
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117.0, 113.0 (t, J = 3.0 Hz), 112.0 (m), 110.5 (m), 95.6 (t, J = 6.3 Hz), 76.3 (t, J = 36.1 Hz), 58.0. F
NMR (564 MHz, CDCl3)  -81.6 (t, J = 9.6 Hz, 3F), -97.4 (d, J = 5.6 Hz, 2F), -124.0 (s, 2F) , -126.1 (d,
J = 6.8 Hz, 2F). IR (thin film): max 2245, 1514, 1135 cm-1. MS (EI): m/z (%) 350 (M), 212, 181 (100).
HRMS (EI) m/z: [M]+ Calculated for C13H7F9O 350.0348; Found 350.0348.
1-(pentyloxy)-4-(perfluorohex-1-yn-1-yl)benzene (4f). The product (59 mg, 73% yield) as a pale yellow
oil was purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz, CDCl3)
 7.49 (d, J = 9.0 Hz, 2H), 6.89 (d, J = 9.0 Hz, 2H), 3.98 (t, J = 6.0 Hz, 2H), 1.81 (m, 2H), 1.43 (m, 4H),
0.95 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150.8 MHz, CDCl3)  164.0, 136.8, 121.0 (t, J = 33.0 Hz), 119.1
(t, J = 33.5 Hz), 117.4, 112.6 (t, J = 3.0 Hz), 111.9 (m), 110.1 (m), 95.7 (t, J = 6.2 Hz), 76.2 (t, J = 36.1
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Hz), 70.9, 31.4, 30.7, 25.1, 16.5. 19F NMR (564 MHz, CDCl3)  -81.1 (t, J = 9.0 Hz, 3F), -96.8 (q, J = 6.2
Hz, 2F), -123.5 (m, 2F), -125.5 (m, 2F). IR (thin film): max 2938, 2244, 1239 cm-1. MS (EI): m/z (%) 406
(M), 336, 167 (100). HRMS (EI) m/z: [M]+ Calculated for C17H15F9O 406.0974; Found 406.0977.
1,3-dimethoxy-5-(perfluorohex-1-yn-1-yl)benzene (4g). The product (45 mg, 59% yield) as a pale
yellow oil was purified with silica gel chromatography (Petroleum ether / Ethyl ether = 40:1). 1H NMR
(600 MHz, CDCl3)  6.69 (s, 2H), 6.58 (s, 2H), 3.80 (s, 6H). 13C{1H} NMR (150.8 MHz, CDCl3)  163.3,
122.2 (t, J = 2.9 Hz), 121.0 (t, J = 33.3 Hz), 119.5 (t, J = 33.5 Hz), 112.7 (t, J = 2.3 Hz), 111.9 (m), 110.3
(m), 107.0, 94.9 (t, J = 6.3 Hz), 76.5 (t, J = 36.2 Hz), 58.1. 19F NMR (564 MHz, CDCl3)  -81.1 (t, J =
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9.0 Hz, 3F), -97.5 (s, 2F), -123.4 (t, J = 4.5 Hz, 2F), -125.5 (q, J = 4.5 Hz, 2F). IR (thin film): max 2245,
1599, 1234 cm-1. MS (EI): m/z (%) 380 (M), 211 (100), 181. HRMS (APCI-LTQ Orbitrap) m/z: [M+H]+
Calculated for C14H10F9O2 381.0532; Found 381.0535.
4-(perfluorohex-1-yn-1-yl)-1,1'-biphenyl (4h). The product (44 mg, 56% yield) as a white solid was
purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz, CDCl3)  7.64 (s,
J = 9.0 Hz, 4H), 7.61 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.2 Hz, 3H), 7.42(t, J = 7.8 Hz, 1H). 13C{1H} NMR
(150.8 MHz, CDCl3)  146.6, 142.3, 135.6 (t, J = 2.3 Hz), 131.7, 130.9, 130.0, 129.8, 121.2 (m),119.8 (t,
J = 3.0 Hz), 112.0 (m), 110.7 (m), 108.6 (m), 95.0 (t, J = 6.2 Hz), 77.7 (t, J = 36.1 Hz). 19F NMR (564
MHz, CDCl3)  -81.0 (d, J = 7.3 Hz, 3F), -97.3 (s, 2F), -123.4(s, 2F), -125.5 (s, 2F). IR (thin film): max
2251, 1237, 767 cm-1. MS (EI): m/z (%) 396 (M), 377, 227 (100). HRMS (EI) m/z: [M]+ Calculated for
C18H9F9 396.0555; Found 396.0556.
2-(perfluorohex-1-yn-1-yl)naphthalene (4i). The product (49 mg, 66% yield) as a pale yellow oil was
purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz, CDCl3)  8.13 (s,
1H), 7.86 (q, J = 3.6 Hz, 3H), 7.58 (m, 3H). 13C{1H} NMR (150.8 MHz, CDCl3)  136.6, 136.5(t, J = 2.7
Hz), 135.1, 131.2, 130.8, 130.7, 130.6, 130.2, 129.8, 121.0 (m), 119.1 (m), 118.2, 112.0 (m), 108.6 (m),
95.4 (t, J = 6.6 Hz), 77.3 (t, J = 36.2 Hz). 19F NMR (564 MHz, CDCl3)  -81.0 (t, J = 9.6 Hz, 3F), -97.2
(d, J = 2.3 Hz, 2F), -123.3 (m, 2F), -125.4 (m, 2F). IR (thin film): max 2242, 1236, 870 cm-1. MS (EI):
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m/z (%) 370 (M), 232, 201 (100). HRMS (EI) m/z: [M]+ Calculated for C16H7F9 370.0399; Found
370.0398.
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1-chloro-4-(perfluorohex-1-yn-1-yl)benzene (4j). The product (51 mg, 71% yield) as a pale yellow oil
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7.50 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 9.0 Hz, 2H). 13C{1H} NMR (150.8 MHz, CDCl3)  140.3, 136.3 (t,
J = 2.3 Hz), 131.8, 120.9 (t, J = 33.3 Hz), 119.5 (t, J = 2.9 Hz), 119.0 (t, J = 32.9 Hz) , 111.3 (m), 108.6
(m), 93.7 (t, J = 6.3 Hz), 78.1 (t, J = 36.2 Hz). 19F NMR (564 MHz, CDCl3)  -76.8 (t, J = 9.6 Hz, 3F), -
93.5 (s, 2F), -119.2 (s, 2F), -121.3 (s, 2F). IR (thin film): max 2252, 1241, 884 cm-1. MS (EI): m/z (%)
354 (M), 216, 185 (100). HRMS (EI) m/z: [M]+ Calculated for C12H4ClF9 353.9852; Found 353.9853.
1-fluoro-4-(perfluorohex-1-yn-1-yl)benzene (4k). This compound is known.18 The product (43 mg, 63%
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yield) as a pale yellow oil was purified with silica gel chromatography (Petroleum ether (100%)). H
NMR (600 MHz, CDCl3)  7.57 (q, J = 9.0 Hz, 2H), 7.10 (t, J = 8.4 Hz, 2H). 13C{1H} NMR (150.8 MHz,
CDCl3)  166.8, 137.4 (dt, J = 8.9 Hz, 2.4 Hz), 120.9 (t, J = 33.3 Hz), 118.9 (d, J = 22.5 Hz), 117.2 (q, J
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= 3.2 Hz) , 113.1 (m), 110.9 (m), 109.3 (m), 93.9 (t, J = 6.3 Hz), 77.1 (t, J = 35.4 Hz). F NMR (564
MHz, CDCl3)  -81.1 (t, J = 9.6 Hz, 3F), -97.6 (s, 2F), -105.7 (m, 1F), -123.5 (m, 2F), -125.6 (m, 2F). IR
(thin film): max 3445, 1632, 1033 cm-1. MS (EI): m/z (%) 338 (M), 200, 169 (100). HRMS (EI) m/z: [M]+
Calculated for C12H4F10 338.0148; Found 338.0148.
3-(Perfluorohex-1-yn-1-yl)pyridine (4l). The product (42 mg, 65% yield) as a pale yellow oil was
purified with silica gel chromatography (Petroleum ether (100%). 1H NMR (600 MHz, CDCl3)  8.77 (s,
1H), 8.68 (d, J = 4.8Hz, 1H), 7.84 (d, J = 7.8Hz, 1H), 7.33 (m, 1H). 13C{1H} NMR (150.8 MHz, CDCl3)
 152.8 (t, J = 2.4 Hz), 151.2, 139.4, 132.1, 118.4-116.1 (m), 115.8 (t, J = 2.9 Hz), 110.2-105.4 (m), 88.7
(t, J = 6.3 Hz), 77.6 (t, J = 36.3 Hz). 19F NMR (564 MHz, CDCl3)  -85.9 (m, 3F), -103.1 (s, 2F), -128.2
(s, 2F), -130.3(s, 2F). IR (thin film): max 2925, 1237, 1135 cm-1. MS (EI): m/z (%) 321 (M), 99, 152 (100).
HRMS (EI) m/z: [M]+ Calculated for C11H4F9N 321.0200; Found 321.0200.
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3-(Perfluorohex-1-yn-1-yl)thiophene (4m). The product (39 mg, 60% yield) as a pale yellow oil was
purified with silica gel chromatography (Petroleum ether (100%). 1H NMR (600 MHz, CDCl3)  7.73 (d,
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J = 1.8Hz, 1H), 7.34 (m, 1H), 7.20 (d, J = 4.8Hz, 1H). 13C{1H} NMR (150.8 MHz, CDCl3)  133.4 (t, J
= 2.9 Hz), 129.6 (t, J = 1.7 Hz), 126.3, 118.5-118.1 (m), 117.6 (t, J = 3.0 Hz), 116.6-107.3 (m), 87.7 (t, J
= 6.5 Hz), 74.5 (t, J = 36.2 Hz). 19F NMR (564 MHz, CDCl3)  -81.1 (m, 3F), -97.3 (s, 2F), -123.4 (m,
2F), -125.5(m, 2F). IR (thin film): max 2367, 1269, 671 cm-1. MS (EI): m/z (%) 326 (M), 326, 157(100).
HRMS (EI) m/z: [M]+ Calculated for C10H3F9S 325.9812; Found 325.9814.
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Methyl 4-(perfluorohex-1-yn-1-yl)benzoate (4n). The product (24 mg, 32% yield) as a white solid was
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purified with silica gel chromatography (Petroleum ether / Ethyl acetate =20:1). H NMR (600 MHz,
CDCl3)  8.07 (d, J = 8.4Hz, 2H), 7.64 (d, J = 8.4 Hz, 2H), 3.95 (s, 3H). 13C{1H} NMR (150.8 MHz,
CDCl3)  165.9, 132.5 (t, J = 3.3 Hz), 132.4, 129.8, 122.8, 119.2-104.6 (m), 91.0 (t, J = 9.2 Hz), 52.6,
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29.8. F NMR (564 MHz, CDCl3)  -80.0 (s, 3F), -98.0 (s, 2F), -123.4 (s, 2F), -125.5(s, 2F). IR (thin
film): max 2921, 1731, 1028 cm-1. MS (EI): m/z (%) 378 (M), 209, 347 (100). HRMS (EI) m/z: [M]+
Calculated for C14H7F9O2 378.0302; Found 378.0306
1,1,1,2,2,3,3,4,4-Nonafluorohexadec-5-yne (4p). The product (10 mg, 12% yield) as a colorless oil was
purified with silica gel chromatography (Petroleum ether (100%). 1H NMR (600 MHz, CDCl3)  2.35 (dt,
J = 12.6Hz, 6.6Hz, 2H), 1.58 (dt, J = 15.0 Hz, 7.2Hz, 2H), 1.39 (m, 2H), 1.28 (m, 13H), 0.88 (t, J = 6.6Hz,
3H). 13C{1H} NMR (150.8 MHz, CDCl3)  120.4-104.9 (m), 95.4 (t, J = 6.0 Hz), 67.2 (t, J = 35.7 Hz),
31.8, 29.4, 29.3, 29.2, 28.9, 28.5, 27.1 (t, J = 2.0 Hz), 22.6, 18.4 (t, J = 2.4 Hz), 14.0. 19F NMR (564 MHz,
CDCl3)  -81.2 (s, 3F), -96.5(s,2F), -123.6 (s, 2F), -125.5 (s,2F). IR (thin film): max 2921, 1242, 1147 cm-
1. MS (EI): m/z (%) 384 (M), 299, 69 (100). HRMS (EI) m/z: [M]+ Calculated for C16H21F9 384.1500;
Found 384.1505.
1-(perfluoropent-1-yn-1-yl)-4-propylbenzene (3a). The product (43 mg, 69% yield) as a pale yellow oil
was purified with silica gel chromatography (Petroleum ether / Ethyl ether = 40:1). 1H NMR (600 MHz,
CDCl3)  7.48 (d, J = 7.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 2.62 (t, J = 7.8 Hz, 2H), 1.65 (m, 2H), 0.94
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(t, J = 7.8 Hz, 3H). 13C{1H} NMR (150.8 MHz, CDCl3)  149.1, 135.1 (t, J = 2.4 Hz), 131.5, 121.3 (t, J
= 34.1 Hz), 119.4 (t, J = 33.8 Hz), 118.2 (t, J = 3.0 Hz), 109.9 (m), 95.4 (t, J = 6.5 Hz), 76.6 (t, J = 36.1
Hz), 40.7, 26.9, 16.3. 19F NMR (564 MHz, CDCl3)  -80.1 (t, J = 8.5 Hz, 3F), -97.9 (q, J = 6.8 Hz, 2F), -
126.9 (t, J = 6.2 Hz, 2F). IR (thin film): max 2245, 1215, 714 cm-1. MS (EI): m/z (%) 312 (M), 283 (100),
164. HRMS (EI) m/z: [M]+ Calculated for C14H11F7 312.0744; Found 312.0743.
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1-(tert-butyl)-4-(perfluoropent-1-yn-1-yl)benzene (3c). The product (38 mg, 58% yield) as a pale
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yellow oil was purified with silica gel chromatography (Petroleum ether (100%)). H NMR (600 MHz,
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CDCl3)  7.50 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 1.32 (s, 9H). C{1H} NMR (150.8 MHz,
CDCl3)  157.4, 135.0 (t, J = 2.4 Hz), 128.4, 121.5 (m), 119.5 (m), 118.0 (t, J = 2.9 Hz), 110.1 (m), 95.3
(t, J = 6.3 Hz), 76.6 (t, J = 36.2 Hz), 37.7, 33.7. 19F NMR (564 MHz, CDCl3)  -80.1 (t, J = 8.5 Hz, 3F),
-97.9 (q, J = 6.2 Hz, 2F), -126.9 (q, J = 5.6 Hz, 2F). IR (thin film): max 2969, 2241, 1211 cm-1. MS (EI):
m/z (%) 326 (M), 311 (100), 283. HRMS (EI) m/z: [M]+ Calculated for C15H13F7 326.0905; Found
326.0899.
1-(perfluorooct-1-yn-1-yl)-4-propylbenzene (5a). The product (69 mg, 74% yield) as a pale yellow oil
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was purified with silica gel chromatography (Petroleum ether (100%)). H NMR (600 MHz, CDCl3) 
7.47 (d, J = 7.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 2.62 (t, J = 7.8 Hz, 2H), 1.65 (m, 2H), 0.94 (t, J = 7.2
Hz, 3H). 13C{1H} NMR (150.8 MHz, CDCl3)  149.1, 135.1 (t, J = 2.3 Hz), 131.5, 120.8 (t, J = 33.0 Hz),
118.9 (t, J = 33.5 Hz), 118.2 (t, J = 3.0 Hz), 113.1 (m), 110.0 (m), 95.4 (t, J = 6.3 Hz), 76.8 (t, J = 35.9
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Hz), 40.7, 26.9, 16.3. F NMR (564 MHz, CDCl3)  -80.9 (t, J = 9.6 Hz, 3F), -96.8 (s, 2F), -121.4 (s,
2F) , -122.6 (s, 2F), -122.9 (s, 2F),-126.2 (s, 2F),. IR (thin film): max 2245, 1241, 707 cm-1. MS (EI): m/z
(%) 462 (M), 433, 164 (100). HRMS (EI) m/z: [M]+Calculated for C17H11F13 462.0653; Found 462.0648.
1-pentyl-4-(perfluorooct-1-yn-1-yl)benzene (5b). The product (61 mg, 62% yield) as a pale yellow oil
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was purified with silica gel chromatography (Petroleum ether (100%)). H NMR (600 MHz, CDCl3) 
7.47 (d, J = 7.8 Hz, 2H), 7.21 (d, J = 7.8 Hz, 2H), 2.64 (t, J = 7.8 Hz, 2H), 1.61 (m, 2H), 1.32 (m, 4H),
0.90 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150.8 MHz, CDCl3)  149.4, 135.1 (t, J = 2.3 Hz), 131.4, 120.8
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(t, J = 33.0 Hz), 118.9 (t, J = 33.2 Hz), 118.2 (t, J = 2.7 Hz) , 115.3 (m), 113.3 (m), 111.9 (m), 110.0 (m),
95.4 (t, J = 6.3 Hz), 76.8 (t, J = 36.1 Hz), 38.7, 34.0, 33.4, 25.1, 16.6. 19F NMR (564 MHz, CDCl3)  -
80.9 (d, J = 8.5 Hz, 3F), -96.8 (s, 2F), -121.4 (s, 2F), -122.6 (s, 2F), -122.9 (s, 2F), -126.2 (s, 2F). IR (thin
film): max 2927, 2242, 1149 cm-1. MS (EI): m/z (%) 490 (M), 433, 164 (100). HRMS (EI) m/z: [M]+
Calculated for C19H15F13 490.0961; Found 490.0964.
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1-(tert-butyl)-4-(perfluorooct-1-yn-1-yl)benzene (5c). The product (62 mg, 65% yield) as a pale yellow
oil was purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz, CDCl3)
 7.50 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 1.33 (s, 9H). 13C{1H} NMR (150.8 MHz, CDCl3) 
157.4, 134.9 (t, J = 2.3 Hz), 120.8 (t, J = 32.7 Hz), 118.9 (t, J = 33.6 Hz), 118.0 (t, J = 2.7 Hz), 113.5 (m) ,
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112.1 (m), 111.0 (m), 108.0 (m), 95.4 (t, J = 6.2 Hz), 76.8 (t, J = 35.9 Hz), 37.7, 33.6. F NMR (564
MHz, CDCl3)  -80.8 (t, J = 9.6 Hz, 3F), -96.9 (s, 2F), -121.3 (s, 2F), -122.6 (s, 2F), -122.9 (s, 2F), -126.2
(s, 2F). IR (thin film): max 2969, 2245, 1241 cm-1. MS (EI): m/z (%) 476 (M), 461 (100), 433. HRMS
(APCI-LTQ Orbitrap) m/z: [M+H]+ Calculated for C18H14F13 477.0875; Found 477.0872.
(perfluorooct-1-yn-1-yl)benzene (5d). This compound is known. The product (44 mg, 52% yield) as a
colorless oil was purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz,
CDCl3)  7.57 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.8 Hz, 2H), 7.41 (t, J = 7.2 Hz, 2H). 19F NMR (564 MHz,
CDCl3)  -80.9 (t, J = 9.6 Hz, 3F), -97.2 (s, 2F), -121.4 (s, 2F), -122.6 (s, 2F), -122.9 (s, 2F), -126.2 (t, J
= 14.1 Hz, 2F).
1-methoxy-4-(perfluorooct-1-yn-1-yl)benzene (5e). The product (57 mg, 63% yield) as a pale yellow
oil was purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz, CDCl3)
 7.50 (d, J = 9.0 Hz, 2H), 6.90 (d, J = 9.0 Hz, 2H), 3.84 (s, 3H). 13C{1H} NMR (150.8 MHz, CDCl3) 
164.3, 136.9 (t, J = 2.4 Hz), 122.7 (t, J = 33.9 Hz), 120.8 (t, J = 33.2 Hz), 118.9 (t, J = 33.2 Hz), 116.9,
114.5 (m), 112.9 (t, J = 2.6 Hz), 112.0 (m), 110.1 (m), 95.5 (t, J = 6.3 Hz), 76.4 (t, J = 36.1 Hz), 58.0. 19F
NMR (564 MHz, CDCl3)  -81.0 (d, J = 7.9 Hz, 3F), -96.6 (s, 2F), -121.4 (s, 2F), -122.6 (s, 2F), -122.9
(s, 2F), -126.3 (d, J = 7.9 Hz, 2F). IR (thin film): max 3442, 1635, 1244 cm-1. MS (EI): m/z (%) 450 (M),
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212, 181 (100). HRMS (APCI-LTQ Orbitrap) m/z: [M+H]+ Calculated for C15H8F13O 451.0362; Found
451.0363.
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1-(pentyloxy)-4-(perfluorooct-1-yn-1-yl)benzene (5f). The product (57 mg, 57% yield) as a pale yellow
oil was purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz, CDCl3)
 7.48 (d, J = 9.0 Hz, 2H), 6.89 (d, J = 9.0 Hz, 2H), 3.98 (t, J = 6.6 Hz, 2H), 1.80 (m, 2H), 1.41 (m, 4H),
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0.94 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150.8 MHz, CDCl3)  163.9, 136.9, 120.9 (q, J = 33.3 Hz), 118.9
(q, J = 34.2 Hz), 117.4, 113.3 (m), 112.6 (t, J = 2.6 Hz), 111.8 (m), 110.7 (m), 108.6 (m), 95.7 (t, J = 6.0
Hz), 76.3 (t, J = 36.1 Hz), 70.9, 31.4, 30.8, 25.1, 16.6. 19F NMR (564 MHz, CDCl3)  -80.9 (t, J = 10.2
Hz, 3F), -96.5 (s, 2F), -121.4 (s, 2F), -122.5 (s, 2F), -122.9 (s, 2F), -126.2 (q, J = 9.6 Hz, 2F). IR (thin
film): max 2942, 2242, 1242 cm-1. MS (EI): m/z (%) 506 (M), 436, 167 (100). HRMS (APCI-LTQ
Orbitrap) m/z: [M+H]+ Calculated for C19H16F13O 507.0988; Found 507.0981.
1,3-dimethoxy-5-(perfluorooct-1-yn-1-yl)benzene (5g). The product (61 mg, 63% yield) as a pale
yellow oil was purified with silica gel chromatography (Petroleum ether / Ethyl ether = 40:1). 1H NMR
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(600 MHz, CDCl3)  6.69 (d, J = 2.4 Hz, 2H), 6.58 (s, 2H), 3.80 (s, 6H). C{1H} NMR (150.8 MHz,
CDCl3)  163.3, 125.2, 122.2 (t, J = 2.7 Hz), 120.8 (t, J = 33.9 Hz), 118.9 (t, J = 34.4 Hz), 112.7 (t, J =
2.3 Hz), 114.1 (m), 112.7 (t, J = 2.3 Hz), 111.3 (m), 109.2 (m), 107.0, 94.8 (t, J = 6.3 Hz), 76.6 (t, J =
36.1 Hz), 58.2. 19F NMR (564 MHz, CDCl3)  -80.9 (s, 3F), -97.2 (s, 2F), -121.4 (s, 2F), -122.5 (s, 2F), -
122.9 (s, 2F), -126.2 (s, 2F). IR (thin film): max 2245, 1602, 1240 cm-1. MS (EI): m/z (%) 480 (M), 211
(100), 181. HRMS (APCI-LTQ Orbitrap) m/z: [M+H]+ Calculated for C16H10F13O2 481.0468; Found
481.0466.
4-(perfluorooct-1-yn-1-yl)-1,1'-biphenyl (5h). The product (59 mg, 59% yield) as a white solid was
purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz, CDCl3)  7.64 (t,
J = 9.0 Hz, 4H), 7.61 (d, J = 7.8 Hz, 2H), 7.49 (t, J = 7.8 Hz, 3H), 7.42(t, J = 7.2 Hz, 1H). 13C{1H} NMR
(150.8 MHz, CDCl3)  146.6, 142.3, 135.6 (t, J = 2.1 Hz), 131.7, 130.9, 130.9, 130.0, 129.8, 120.8 (t, J =
33.0 Hz), 119.8 (t, J = 2.7 Hz), 118.9 (t, J = 33.0 Hz), 116.8 (m), 115.0 (m), 113.2 (m), 110.3 (m), 94.9
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(t, J = 6.3 Hz), 77.8 (t, J = 36.2 Hz). 19F NMR (564 MHz, CDCl3)  -78.8 (d, J = 7.3 Hz, 3F), -95.0 (s,
2F), -119.3 (s, 2F), -120.4 (s, 2F), -120.8 (s, 2F), -124.1 (s, 2F). IR (thin film): max 2242, 1241, 767 cm-
1. MS (EI): m/z (%) 496 (M), 227 (100), 113. HRMS (EI) m/z: [M]+ Calculated for C20H9F13 496.0491;
Found 496.0491.
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2-(perfluorooct-1-yn-1-yl)naphthalene (5i). The product (58 mg, 62% yield) as a pale yellow oil was
purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz, CDCl3)  8.13 (s,
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1H), 7.86 (t, J = 3.6 Hz, 3H), 7.57 (m, 3H). 13C{1H} NMR (150.8 MHz, CDCl3)  136.6, 136.5(t, J = 2.6
Hz), 135.1, 131.2, 130.8, 130.7, 130.6, 130.2, 129.8, 120.3 (m), 119.1 (m), 118.2 (t, J = 2.7 Hz, 3H), 117.2
19
(m), 115.4(m), 113.3 (m), 111.2 (m), 95.3 (t, J = 6.3 Hz), 77.4 (t, J = 36.1 Hz). F NMR (564 MHz,
CDCl3)  -78.7 (t, J = 9.0 Hz, 3F), -94.8 (s, 2F), -119.2 (s, 2F), -120.3 (s, 2F), -120.7 (s, 2F), -124.1 (s,
2F). IR (thin film): max 2242, 1240, 817 cm-1. MS (EI): m/z (%) 470 (M), 232, 201 (100). HRMS (EI)
m/z: [M]+ Calculated for C18H7F13 470.0335; Found 470.0335.
1-chloro-4-(perfluorooct-1-yn-1-yl)benzene (5j). The product (52 mg, 57% yield) as a pale yellow oil
1
was purified with silica gel chromatography (Petroleum ether (100%)). H NMR (600 MHz, CDCl3) 
7.50 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 9.0 Hz, 2H). 13C{1H} NMR (150.8 MHz, CDCl3)  140.2, 136.3 (t,
J = 2.3 Hz), 131.8, 120.7 (m), 119.5 (t, J = 2.9 Hz), 118.8 (m), 113.7 (m), 112.4 (m), 110.6 (m), 108.5
(m), 93.6 (t, J = 5.9 Hz), 78.2 (t, J = 36.4 Hz). 19F NMR (564 MHz, CDCl3)  -80.9 (t, J = 9.6 Hz, 3F), -
97.5 (s, 2F), -121.4 (s, 2F), -122.5 (s, 2F), -122.9 (s, 2F), -126.2 (d, J = 14.1 Hz, 2F). IR (thin film): max
2252, 1241, 884 cm-1. MS (EI): m/z (%) 454 (M), 216, 185 (100). HRMS (EI) m/z: [M]+ Calculated for
C14H4ClF13 453.9789; Found 453.9791.
1-fluoro-4-(perfluorooct-1-yn-1-yl)benzene (5k). The product (54 mg, 62% yield) as a pale yellow oil
1
was purified with silica gel chromatography (Petroleum ether (100%)). H NMR (600 MHz, CDCl3) 
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7.56 (q, J = 3.6 Hz, 2H), 7.10 (t, J = 2.4 Hz, 2H). C{1H} NMR (150.8 MHz, CDCl3)  166.8 (d, J =
254.0 Hz), 137.4 (dt, J = 8.7 Hz, 2.1 Hz), 120.8 (t, J = 22.5 Hz), 117.2 (q, J = 3.0 Hz), 115.0 (q, J = 31.8
Hz) , 113.5 (m), 110.8 (m), 109.9 (m), 108.6 (m), 93.8 (t, J = 6.3 Hz), 77.2 (t, J = 36.2 Hz). 19F NMR (564
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MHz, CDCl3)  -81.0 (t, J = 10.2 Hz, 3F), -97.4 (s, 2F), -105.8 (m, 1F), -121.5 (s, 2F), -122.6 (s, 2F), -
123.0 (s, 2F), -126.3 (m, 2F). IR (thin film): max 3448, 2928, 1633 cm-1. MS (EI): m/z (%) 438 (M), 250,
169 (100). HRMS (EI) m/z: [M]+ Calculated for C14H4F14 438.0084; Found 438.0085.
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3-(Perfluorohex-1-yn-1-yl)pyridine (5l). The product (51 mg, 60% yield) as a pale yellow oil was
purified with silica gel chromatography (Petroleum ether (100%). 1H NMR (600 MHz, CDCl3)  8.77 (s,
1H), 8.68 (d, J = 4.8Hz, 1H), 7.84 (d, J = 7.8Hz, 1H), 7.33 (m, 1H). 13C{1H} NMR (150.8 MHz, CDCl3)
 152.8 (t, J = 2.4 Hz), 151.2, 139.4, 132.1, 120.2-115.9 [m, -(CF2)CF3], 115.8 (t, J = 2.9 Hz), 114.4-
105.5 [m, -(CF2)CF3], 88.7 (t, J = 6.3 Hz), 77.6 (t, J = 36.3 Hz). 19F NMR (564 MHz, CDCl3)  -85.9 (m,
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3F), -103.1 (s,2F), -128.2 (s, 2F), -130.3(s, 2F). IR (thin film): max 2925, 1239, 1147 cm-1. MS (EI): m/z
(%) 421 (M), 99, 152 (100). HRMS (EI) m/z: [M]+ Calculated for C13H4F13N 421.0136; Found 421.0141.
3-(Perfluorooct-1-yn-1-yl)thiophene (5m). The product (55 mg, 64% yield) as a pale yellow oil was
purified with silica gel chromatography (Petroleum ether (100%). 1H NMR (600 MHz, CDCl3)  7.73 (d,
J = 1.8Hz, 1H), 7.34 (m, 2H), 3.95 (d, J = 4.8Hz, 1H). 13C{1H} NMR (150.8 MHz, CDCl3)  133.4 (t, J
= 4.2 Hz), 129.7, 126.4, 119.0-108.3 (m), 117.6 (t, J = 4.8 Hz), 116.1-104.9 (m) , 87.7 (t, J = 9.8 Hz),
74.6 (t, J = 54.2 Hz). 19F NMR (564 MHz, CDCl3)  -81.1 (t, J = 9.6 Hz, 3F), -97.2 (m,2F), -121.5 (s, 2F),
-122.6(m, 2F), -123.0(m, 2F), -126.4(m, 2F). MS (EI): m/z (%) 362 (M), 333, 164 (100). IR (thin film):

max 2925, 1242, 1145 cm-1. MS (EI): m/z (%) 425 (M), 69, 157 (100). HRMS (EI) m/z: [M]+ Calculated
for C12H3F13S 425.9748; Found 425.9749.
Methyl 4-(perfluorooct-1-yn-1-yl)benzoate (5n). The product (31 mg, 32% yield) as a pale yellow oil
was purified with silica gel chromatography (Petroleum ether / Ethyl ether =15:1). 1H NMR (600 MHz,
CDCl3)  8.06 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 3.93 (s, 3H). 13C{1H} NMR (150.8 MHz,
CDCl3)  165.8, 132.4 (t, J = 1.9 Hz), 132.2, 129.7, 122.7(t, J = 2.9 Hz), 117.9-105.8 (m), 90.8 (t, J = 6.2
Hz), 52.4, 29.6. 19F NMR (564 MHz, CDCl3)  -80.9 (t, J= 8.5Hz, 3F), -97.8 (s, 2F), -121.38 (s, 2F), -
122.5 (s, 2F), -122.9 (s, 2F), -126.2 (s, 2F). IR (thin film): max 2245, 1735, 707 cm-1. MS (EI): m/z (%)
478 (M), 447, 209 (100). HRMS (EI) m/z: [M]+ Calculated for C16H7F13O2 478.0238; Found 478.0238.
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1-(perfluorooct-1-yn-1-yl)-4-propylbenzene (6a). The product (97mg, 72% yield) as a pale yellow oil
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was purified with silica gel chromatography (Petroleum ether (100%)). H NMR (600 MHz, CDCl3) 
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5
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7.47 (d, J = 7.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 2.62 (t, J = 7.2 Hz, 2H), 1.64 (m, 2H), 0.94 (t, J = 7.2
7
8
13
Hz, 3H). C{1H} NMR (150.8 MHz, CDCl3)  149.1, 135.1, 131.5, 120.9 (m), 120.4(m), 120.0(m),
9
119.2(m), 118.8(m), 118.3 (t, J = 2.6 Hz), 114.9 (m), 114.0 (m), 113.5(m), 111.8(m), 110.4(m), 95.4 (t, J
= 6.3 Hz), 76.8 (t, J = 36.1 Hz), 40.7, 26.9, 16.3. 19F NMR (564 MHz, CDCl3)  -80.9 (d, J = 9.0 Hz, 3F),
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-96.8 (s, 2F), -121.1 (s, 2F) , -121.9 (d, J = 9.0 Hz, 8F), -122.5 (s, 2F), -122.8 (s, 2F),. IR (thin film): max
2248, 1210, 901 cm-1. MS (EI): m/z (%) 662 (M), 193, 164 (100). HRMS (APCI-LTQ Orbitrap) m/z:
[M+H]+ Calculated for C21H12F21 663.0604; Found 663.0608.
1-(pentyloxy)-4-(perfluorododec-1-yn-1-yl)benzene (6f). The product (93 mg, 66% yield) as a pale
yellow solid was purified with silica gel chromatography (Petroleum ether (100%)). 1H NMR (600 MHz,
CDCl3)  7.48 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 3.98 (t, J = 6.6 Hz, 2H), 1.80 (m, 2H), 1.42
(m, 4H), 0.94 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150.8 MHz, CDCl3)  163.9, 136.8, 134.4 (m), 131.1
(m), 122.5 (m), 120.6 (m), 118.6 (m), 117.4, 115.1 (m), 113.5 (m), 112.6 (d, J = 2.9 Hz), 111.9 (m), 111.2
(m), 110.5 (m), 95.6 (t, J = 6.2 Hz), 76.3 (t, J = 36.1 Hz), 70.9, 31.4, 30.7, 25.1, 16.6. 19F NMR (564 MHz,
CDCl3)  -81.0 (d, J = 9.6 Hz, 3F), -96.5 (s, 2F), -121.2 (s, 2F), -122.0 (d, J = 86.3 Hz, 8F), -122.5 (s, 2F),
-122.9 (s, 2F), -126.3 (s, 2F). IR (thin film): max 2945, 2241, 1514 cm-1. MS (EI): m/z (%) 706 (M), 417,
187 (100). HRMS (APCI-LTQ Orbitrap) m/z: [M+H]+ Calculated for C23H16F21O 707.0860; Found
707.0865.
ASSOCIATED CONTENT
Supportiong Information. This material is available free of charge via the Internet at http://pubs.acs.org.
Including experimental condition screening and 1H/19F/13C NMR spectra.
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ACKNOWLEDGMENTS. This work was financially supported by the National Natural Science
Foundation of China (grant number: 21602041), the Fundamental Research Funds for the Central
Universities of China, the Anhui Province Key Laboratory of Advanced Catalytic Materials and Reaction
Engineering (grant number: 45000-411104/007), and the Start-up Foundation of Hefei University of
Technology.
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J.; Liu, L. Copper-catalyzed trifluoromethylation of terminal alkenes through allylic C-H bond activation.
J. Am. Chem. Soc. 2011, 133, 15300-15303; b) Liu, T.; Shen, Q. Copper-catalyzed trifluoromethylation
of aryl and vinyl boronic acids with an electrophilic trifluoromethylating reagent. Org. Lett. 2011, 13,
2342-2345; c) Chu, L.; Qing, F.-L. Copper-Catalyzed Oxidative Trifluoromethylation of Terminal
Alkenes Using Nucleophilic CF3SiMe3: Efficient C(sp3)–CF3 Bond Formation. Org. Lett. 2012, 14,
2106-2109; d) Shimizu, R.; Egami, H.; Hamashima, Y.; Sodeoka, M. Copper-catalyzed
trifluoromethylation of allylsilanes. Angew. Chem. Int. Ed. 2012, 51, 4577-4580; e) Kawamura, S.;
Sodeoka, M. Perfluoroalkylation of Unactivated Alkenes with Acid Anhydrides as the Perfluoroalkyl
Source. Angew. Chem. Int. Ed. 2016, 55, 8740-8743; f) Aikawa, K.; Nakamura, Y.; Yokota, Y.; Toya, W.;
Mikami, K. Stable but reactive perfluoroalkylzinc reagents: application in ligand-free copper-catalyzed
perfluoroalkylation of aryl iodides. Chem. Eur. J. 2015, 21, 96-100; g) Kato, H.; Hirano, K.; Kurauchi,
D.; Toriumi, N.; Uchiyama, M. Dialkylzinc-mediated cross-coupling reactions of perfluoroalkyl and
perfluoroaryl halides with aryl halides. Chem. Eur. J. 2015, 21, 3895-3900; h) Bao, X.; Liu, L.; Li, J.;
Fan, S. Copper-Catalyzed Oxidative Perfluoroalkylation of Aryl Boronic Acids Using Perfluoroalkylzinc
Reagents. J. Org. Chem. 2018, 83, 463-468; i) Liu, L.; Bao, X.; Xiao, H.; Li, J.; Ye, F.; Wang, C.; Cai,
Q.; Fan, S. Copper-Catalyzed Perfluoroalkylation of Allyl Phosphates with Stable Perfluoroalkylzinc
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(5) For selected examples for reaction of RFI with alkenes, see: a) Geng, X.; Lin, F.; Wang, X.; Jiao, N.
Azidofluoroalkylation of Alkenes with Simple Fluoroalkyl Iodides Enabled by Photoredox Catalysis. Org.
Lett. 2017, 19, 4738-4741; b) Rosso, C.; Williams, J. D.; Filippini, G.; Prato, M.; Kappe, C. O. Visible-
Light-Mediated Iodoperfluoroalkylation of Alkenes in Flow and Its Application to the Synthesis of a Key
Fulvestrant Intermediate. Org. Lett. 2019, 21, 5341-5345; c) Moon, J.; Moon, Y. K.; Park, D. D.; Choi,
S.; You, Y.; Cho, E. J. Visible-Light-Induced Trifluoromethylation of Unactivated Alkenes with Tri(9-
anthryl)borane as an Organophotocatalyst. J. Org. Chem. 2019, 84, 12925-12932; d) Yajima, T.;
Shigenaga, S. Metal-Free Visible Light Hydroperfluoroalkylation of Unactivated Alkenes Using
Perfluoroalkyl Bromides. Org. Lett. 2019, 21, 138-141; e) Helmecke, L.; Spittler, M.; Baumgarten, K.;
Czekelius, C. Metal-Free Activation of C-I Bonds and Perfluoroalkylation of Alkenes with Visible Light
Using Phosphine Catalysts. Org. Lett. 2019, 21, 7823-7827.
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(6) For selected examples for reaction of RFI with alkynes, see: a) El Soueni, A.; Tedder, J. M.; Walton,
J. C. Free-radical addition to olefins. Part 26.—Kinetics of the addition of trifluoromethyl radicals to
acetylene and substituted acetylenes. Journal of the Chemical Society, Faraday Transactions 1: Physical
Chemistry in Condensed Phases 1981, 77, 89; b) Kitazume, T.; Ishikawa, N. Ultrasound-promoted
selective perfluoroalkylation on the desired position of organic molecules. J. Am. Chem. Soc. 1985, 107,
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53, 4910-4914; e) Choi, S.; Kim, Y. J.; Kim, S. M.; Yang, J. W.; Kim, S. W.; Cho, E. J.
Hydrotrifluoromethylation and iodotrifluoromethylation of alkenes and alkynes using an inorganic
electride as a radical generator. Nat Commun 2014, 5, 4881; f) Li, Z.; García-Domínguez, A.; Nevado, C.
Pd-Catalyzed Stereoselective Carboperfluoroalkylation of Alkynes. J. Am. Chem. Soc. 2015, 137, 11610-
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alkylation of Terminal and Internal Alkynes: A Convenient Route to Tri- and Tetrasubstituted Olefins.
ACS Catalysis 2016, 6, 3452-3456; h) Wang, X.; Studer, A. Regio- and Stereoselective Radical
Perfluoroalkyltriflation of Alkynes Using Phenyl(perfluoroalkyl)iodonium Triflates. Org. Lett. 2017, 19,
2977-2980; i) Domanski, S.; Staszewska-Krajewska, O.; Chaladaj, W. Pd-Catalyzed Carbonylative
Carboperfluoroalkylation of Alkynes. Through-Space (13)C-(19)F Coupling as a Probe for Configuration
Assignment of Fluoroalkyl-Substituted Olefins. J. Org. Chem. 2017, 82, 7998-8007.
(7) a) Presset, M.; Oehlrich, D.; Rombouts, F.; Molander, G. A. Copper-mediated radical
trifluoromethylation of unsaturated potassium organotrifluoroborates. J. Org. Chem. 2013, 78, 12837-
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trifluoromethylation of potassium alkynyltrifluoroborates with Langlois' reagent. Tetrahedron 2014, 70,
2118-2121.
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(8) a) Tresse, C.; Guissart, C.; Schweizer, S.; Bouhoute, Y.; Chany, A.-C.; Goddard, M.-L.; Blanchard,
N.; Evano, G. Practical Methods for the Synthesis of Trifluoromethylated Alkynes: Oxidative
Trifluoromethylation of Copper Acetylides and Alkynes. Adv. Synth. Catal. 2014, 356, 2051-2060; b) He,
L.; Tsui, G. C. Fluoroform-Derived CuCF3 for Trifluoromethylation of Terminal and TMS-Protected
Alkynes. Org. Lett. 2016, 18, 2800-2803.
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(9) Siah, H.-S. M.; Fiksdahl, A. Dual-gold(I)-generated trifluoromethylation of terminal alkynes with
Togni’s reagent. J. Fluorine Chem. 2017, 197, 24-33.
(10) a) Chu, L.; Qing, F. L. Copper-mediated aerobic oxidative trifluoromethylation of terminal alkynes
with Me3SiCF3. J. Am. Chem. Soc. 2010, 132, 7262-7263; b) Zhang, K.; Qiu, X.-L.; Huang, Y.; Qing,
F.-L. An Improved Copper-Mediated Oxidative Trifluoromethylation of Terminal Alkynes. Eur. J. Org.
Chem. 2012, 2012, 58-61; c) Jiang, X.; Chu, L.; Qing, F. L. Copper-catalyzed oxidative
trifluoromethylation of terminal alkynes and aryl boronic acids using (trifluoromethyl)trimethylsilane. J.
Org. Chem. 2012, 77, 1251-1257.
(11) a) Zheng, H.; Huang, Y.; Wang, Z.; Li, H.; Huang, K.-W.; Yuan, Y.; Weng, Z. Synthesis of
trifluoromethylated acetylenes via copper-catalyzed trifluoromethylation of alkynyltrifluoroborates.
Tetrahedron Lett. 2012, 53, 6646-6649; b) Weng, Z.; Li, H.; He, W.; Yao, L.-F.; Tan, J.; Chen, J.; Yuan,
Y.; Huang, K.-W. Mild copper-catalyzed trifluoromethylation of terminal alkynes using an electrophilic
trifluoromethylating reagent. Tetrahedron 2012, 68, 2527-2531; c) Luo, D.-F.; Xu, J.; Fu, Y.; Guo, Q.-X.
Copper-catalyzed trifluoromethylation of terminal alkynes using Umemoto’s reagent. Tetrahedron Lett.
2012, 53, 2769-2772; d) Wang, X.; Lin, J.; Zhang, C.; Xiao, J.; Zheng, X. Copper-Mediated
Trifluoromethylation of Terminal Alkynes byS-(Trifluoromethyl)diarylsulfonium Salt. Chin. J. Chem .
2013, 31, 915-920.
(12) Serizawa, H.; Aikawa, K.; Mikami, K. Direct synthesis of a trifluoromethyl copper reagent from
trifluoromethyl ketones: application to trifluoromethylation. Chem. Eur. J. 2013, 19, 17692-17697.
(13) Li, X.; Zhao, J.; Zhang, L.; Hu, M.; Wang, L.; Hu, J. Copper-mediated trifluoromethylation using
phenyl trifluoromethyl sulfoxide. Org. Lett. 2015, 17, 298-301.
(14) Deng, X.; Lin, J.; Zheng, J.; Xiao, J. Cu-Promoted Oxidative Trifluoromethylation of Terminal
Alkynes with Difluoromethylene Phosphobetaine. Chin. J. Chem . 2014, 32, 689-693.
(15) the price of RF-I (from Shangfluoro Technology Co., Ltd): C3F7I, 100¥/20g; C4F9I, 1500¥/500g;
C6F13I, 150¥/10g; C10F21I, 450¥/50g.
(16) a) Portugues, A.; Lopez-Garcia, I.; Jimenez-Bernad, J.; Bautista, D.; Gil-Rubio, J. Photoinitiated
Reactions of Haloperfluorocarbons with Gold(I) Organometallic Complexes: Perfluoroalkyl Gold(I) and
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Gold(III) Complexes. Chem. Eur. J. 2019, 25, 15535-15547; b) Blancou, H.; Calleja-Rubio, S.; Crette, S.
An Improved Procedure for the Synthesis of Perfluoroalkylacetylenes. Synthesis 2003, 2003, 0361-0364;
c) Konno, T.; Chae, J.; Kanda, M.; Nagai, G.; Tamura, K.; Ishihara, T.; Yamanaka, H. Facile syntheses
of various per- or polyfluoroalkylated internal acetylene derivatives. Tetrahedron 2003, 59, 7571-7580.
(17) Iqbal, N.; Jung, J.; Park, S.; Cho, E. J. Controlled trifluoromethylation reactions of alkynes through
visible-light photoredox catalysis. Angew. Chem. Int. Ed. 2014, 53, 539-542.
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(18) Iqbal, N.; Iqbal, N.; Han, S. S.; Cho, E. J. Synthesis of fluoroalkylated alkynes via visible-light
photocatalysis. Organic & biomolecular chemistry 2019, 17, 1758-1762.
(19) the price of photocatalyst (from Sigma-Aldrich): fac-Ir(ppy)3, 3955.12¥/250mg; Ru(phen)3Cl2,
1728.73¥/1g, the price of AgOAc (from Sigma-Aldrich): 592.52¥/10g.
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