Copper-Catalyzed Oxidative Perfluoroalkylation of Aryl Boronic Acids Using Perfluoroalkylzinc Reagents

Article abstract of DOI:10.1021/acs.joc.7b02557

An efficient and synthetically convenient method for copper-catalyzed cross-coupling of aryl boronic acids with perfluoroalkyl zinc reagents has been described. The reaction proceeds under mild reaction conditions with a high efficiency and broad substrate scope and provides a general access to perfluoroalkylated arenes, which are of interest in life and materials science.

Full text of DOI:10.1021/acs.joc.7b02557

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Note
Copper-Catalyzed Oxidative Perfluoroalkylation of
Aryl Boronic Acids Using Perfluoroalkylzinc Reagents
Xifei Bao, Lihua Liu, Junlan Li, and Shilu Fan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02557 • Publication Date (Web): 01 Dec 2017
Downloaded from http://pubs.acs.org on December 1, 2017
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The Journal of Organic Chemistry
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Copper-Catalyzed Oxidative Perfluoroalkylation of Aryl
Boronic Acids Using Perfluoroalkylzinc Reagents
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†
Xifei Bao,† Lihua Liu, ‡ Junlan Li,† and Shilu Fan*,
†School of Chemistry and Chemical Engineering, Hefei University of Technology, 193 Tunxi
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Road, Anhui, 230000, People's Republic of China.
‡School of Biological and Medical Engineering, Hefei University of Technology, 193 Tunxi
Road, Anhui, 230000, People's Republic of China.
shilu.fan@hfut.edu.cn
TOC
Keywords: Copper, Cross-coupling, Perfluoroalkylation, Boronic acid
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ABSTRACT. An efficient and synthetically convenient method for copper-catalyzed cross-coupling of
aryl boronic acids with perfluoroalkylznic reagents has been described. The reaction proceeds under
mild reaction conditions with high efficiency and broad subatrate scope, and provides a general access
to perfluoroalkylated arenes which are of interest in life and material sciences.
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The introduction of perfluoroalkyl (Rf) groups into organic molecules can substantially alter their
chemical and metabolic stability, lipophilicity, and binding selectivity due to the strong electron
withdrawing effect and large hydrophobic domain of perfluoroalkyl groups.1,2 Accordingly, it has been
of great synthetic interest to develop efficient methods for incorporation of various perfluoroalkyl
groups into aromatic compounds.3 A variety of Cu4, Pd5 and Pt6-based protocols have been developed
for the perfluoroalkylation of aryl halides, arylboronic acids, and aromatic carbon—hydrogen bonds
using perfluoroalkyl halides, allowing efficient access to a diverse array of perfluoroalkylated analogues.
The generation of aryl-Rf bonds, however, remains synthetically challenging, particularly via transition
metal catalysis.4a,4d-h,7 Recent advances in photoredox-catalyzed C—H perfluoroalkylation protocols are
particularly attractive because of obviating the need for prefunctionalization of the substrates,8 but poor
regioselectivity is often encountered in this kind of reaction.6,8b,9
In 2010, Qing and co-workers reported a method for the copper-mediated oxidative
trifluoromethylation of alkynes.10 Soon afterward, Qing,7h,11 Buchwald,12 Gooβen,13 and Grushin14
independently applied this oxidative trifluoromethylation protocol to aryl boronic acids, allowing access
to a variety of trifluoromethylated arenes. Analogous to this transformation, we postulated that a copper-
catalyzed oxidative coupling could be used to access perfluoroalkyl arenes. In the above cases,
nucleophilic/electrophilic perfluoroalkylating reagents have been employed. However, only CF3SiR3,
C2F5SiR3, C3F7SiR3, Togni, andUmemoto reagents are commercial available. In 2011, Daugulis and co-
workers synthesized Rf2Zn from 1H-perfluoroalkane by deprotonative metalation with TMP2Zn and
used it in copper-catalyzed perfluoroalkylation of aromatic iodides.15 The intrinsic limitation of this
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method is that TMP2Zn is extremely water- and air-sensitive. The groups of Mikami16 and Uchiyama17
stabilized these sensitive znic reagents with DMPU (1,3-dimethyltetrahydropyrimidin-2(1H)-one) to
form stable perfluoroalkylznic reagents which were utilized in copper-catalyzed cross-coupling
reactions with aryl iodides. However, coupling of perfluoroalkylating reagents (L2ZnRf2) with
nucleophilic arylboronic acids has not been reported to date. Herein, we report a copper-catalyzed
oxidative perfluoroalkylation of aryl boronic acids with stable perfluoroalkylznic reagents (Scheme 1).
Scheme 1. Copper-cataylzed perfluoroalkylation reactions.
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We began our studies of perfluoroalyklation of [1,1'-biphenyl]-4-ylboronic acid 1a by choosing
perfluoroalkylzinc reagents 2c as substrate because it is easily prepared16 and thermally stable under the
following conditions: 1a (0.2 mmol), 2c (0.2 mmol), CuI (10 mol%), 1,10-Phenanthroline (10 mol%),
KOAc (2.0 equiv.), and AgOAc (1.2 equiv.) in DMSO (2.0 mL) at 80 oC for 12h (Table 1, entry 1). The
desired cross-coupling product 3ac was isolated in 59% yield. We were pleased to observe the
formation of 3ac in 81% isolated yield when oxygen was chosen as co-oxidant (Table 1, entry 2). With
the preliminary result in hand, different bases were examined and K3PO4 was found to be the optimum
base, providing 3ac in 90% isolated yield (Table 1, entry 3). Other bases, such as KOAc, CsOAc,
Na2CO3, and K2CO3 proved to be less effective (Table 1, entries 4-7). Besides Cu(acac)2, many copper
catalysts, such as Cu(OAc)2, CuCN, CuSCN were shown the good yields (Table 1, entries 8-11). The
reaction was found to be sensitive to the nature of solvents (Table 1, entries 12-15). The reaction
preferred to be run in polar solvents (such as DMPU, DMF). Futher optimization showed that a good
yield of isolated product (86%) was afforded by decreasing the CuI loading to 5 mol% with use of phen.
(5 mol%; Table 1, entry 16). In addition, CuI is essential for the reacion, because the absence of it failed
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to give any desired product, and therefore indicated the copper intermediate involving in this catalytic
cycle (Table 1, entry 17). Interestingly, 64% isolated yield was obtained in a ligand free condition
(Table 1, entry 18). Oxygen showed less activity (Table 1, entry 19).
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Table 1. Representative results for optimization of copper-catalyzed perfluoroalkylation of aromatic
boronic acid 1a a
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Entry
1 c
2 d
3
CuX
CuI
Base
KOAc
KOAc
K3PO4
KOAc
CsOAc
Na2CO3
K2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
Solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMPU
Toluene
DMF
Yield(%)b
(59)
(81)
(90)
(78)
(89)
(86)
(74)
(70)
(69)
(81)
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CuI
CuI
4
CuI
5
CuI
6
CuI
7
CuI
8
Cu(OAc)2
CuCN
CuSCN
Cu(acac)2
CuI
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18e
19 f
(63)
31
CuI
CuI
41
CuI
Dioxane
DMSO
DMSO
DMSO
DMSO
19
CuI
(86)
0
…
CuI
(64)
25
CuI
a Conditions: 1a (0.2 mmol), 2c (0.2 mmol), CuX (10 mol%), phen (10 mol%), Base (2.0 equiv),
AgOAc (0.6 equiv), O2 (1 atm), in solvent (2.0 mL), 80 C, 12h. b NMR yield determined by 19F NMR
o
c
using fluorobenzene as internal standard and number in parentheses is isolated yield. 1.2 equiv. of
AgOAc and without oxygen balloon. d 1.2 equiv. of AgOAc. e Reaction run without phen. f Reaction run
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without AgOAc. phen = 1,10-Phenanthroline.
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With the optimum reaction conditions (Table 1, entry 2) in hand, the substrate scope of the
perfluoroalkylation of aryl boronic acids 1 was tested and the representative results were illustrated in
Scheme 2. It was found that a variety of aromatic boronic acids can be successfully perfluoroalkylated
to the desired product in modest to good yields. Phenyl substituted aryl boronic acids were found to
undergo the desired transformation, providing the corresponding perfluoroalkylated compounds in good
to excellent yields (3ac-3dc). Sterically hindered aromatic boronic acid 1e was also suitable substrates,
providing compound 3ec in synthetically useful yield. To our delight, aryl diboronic acid 1f run with 2c
smoothly and 61% yield was obtained (3fc). A series of aryl boronic acids with electron-rich and
electron-deficient substitutes on the aromatic ring afforded satisfying results (3gc-3nc). Unfortunately,
the simple phenylboronic acid was just gave 21% NMR yield (3mc). Reactions with halogen-
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substituded aryl boronic acids also gave the desired products 3pc and 3qc, in 29% and 45% F NMR
yields, respectively. Additionally, heteroaromatic boronic acid was also tolerated in this reaction to give
the desired product in moderate yield (3rc). It is noteworthy that many versatile functional groups, such
as aryl, ether, ester, ketone, sulfone, halogen, and heterocycle, were compatible with the reaction
conditions.
Scheme 2. Copper-catalyzed perfluoroalkylation of aromatic boronic acids 1.a
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a Conditions: 1 (0.2 mmol), 2c (0.2 mmol), CuI (10 mol%), 1,10-Phenanthroline (10 mol%), K3PO4 (2.0
o
equiv), AgOAc (0.6 equiv), O2 (1 atm), in DMSO (2.0 mL), 80 C, 12h. b Conditions: 1 (0.2 mmol), 2c
(0.2 mmol), CuI (10 mol%), 4,4'-Dimethyl-2,2'-dipyridyl (10 mol%), K3PO4 (2.0 equiv), AgOAc (0.6
o
equiv), O2 (1 atm), in DMSO (2.0 mL), 80 C, 12h. c NMR yield determined by 19F NMR using
fluorobenzene as internal standard.
To further probe the applicability of this methodology, couplings of various perfluoroalkylznic
reagents 2 with aryl boronic acids 1 were also tested (Scheme 3). Generally, moderate to high yields of
desired products 3 were afforded under the standard conditions. Phenyl substituted aromatic boronic
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acid 1a still shows a higher reactivity (3aa-3ad). Both electron-rich 3h and electron-deficient 3k aryl
boronic acids furnished the desired products in moderate yields. It should be pointed out that (4-
(methylsulfonyl)phenyl)boronic acid 1n was also a suitable substrate, and 3na-3nd were provided in
moderate to high yields under the present reaction conditions.
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Scheme 3. Copper-catalyzed perfluoroalkylation of aryl boronic acids 1 with various perfluoroalkylznic
reagents 2.a
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a
Conditions: 1 (0.2 mmol), 2 (0.2 mmol), CuI (10 mol%), 1,10-Phenanthroline (10 mol%), K3PO4 (2.0
equiv), AgOAc (0.6 equiv), O2 (1 atm), in DMSO (2.0 mL), 80 C, 12h. b Conditions: 1 (0.2 mmol), 2
o
(0.2 mmol), CuI (10 mol%), 4,4'-Dimethyl-2,2'-dipyridyl (10 mol%), K3PO4 (2.0 equiv), AgOAc (0.6
equiv), O2 (1 atm), in DMSO (2.0 mL), 80 oC, 12h.
To gain some mechanistic insight into the present reaction, radical inhibition experiment was
performed (Scheme 4). When a reaction run under standard condition was treated with the radical
inhibitor TEMOP, the yield of 3ac was decreased to 62%. This preliminary study suggests against a
purely free radical pathway, and implicate the formation of organometallic intermediates (CuI/CuIII
species).
Schemem 4. Radical inhibition experiment
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Although the exact mechanism of the reaction is still not clear, on the basis of the results reported by
others4c,15-17, there are several potential mechanisms for these reactions. One plausible mechanism is
proposed and shown in Scheme 5. First, a Cu(I) species transmetalation with perfluoroalkylznic reagent
2 would afford the RfCuILn species I as the key intermediate. Subsequent reaction with aryl boronic
acid to form (aryl)CuIRfLn species II which could be oxidized to the corresponding (aryl)CuIIIRfLn
intermediate III. As the final step of the catalytic cycle, reductive elimination of III produces
perfluoroalkylated arenes 3 upon the regeneration of Cu(I) species. An alternative mechanistic
possibility would involve Cu/base-promoted generation of free perfluoroalkyl radical that could react
with the aromatic boronic acids under copper-catalyzed conditions.4c
Scheme 5. Proposed reaction mechanism
CONCLUSION
In summary, we have disclosed an efficient and synthetically convenient method for the synthesis of
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perfluoroalkyl arenes from perfluoroalkylznic reagents and broadly available aryl boronic acids through
a copper-catalyzed process. The reactions are an improvement over current perfluoroalkylation reactions
of aryl iodides because arylboronic acids are significantly less expensive and more stable than aryl
iodides. Ongoing studies will focus on probing the mechanism and expanding the scope of this
transformation.
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EXPERIMENTAL SECTION
1
General information: H NMR and 13C NMR spectra were recorded on a Bruker 600 MHz
1
spectrometer in CDCl3 and (CD3)2SO. Data for H NMR are reported as follows: chemical shift (ppm,
scale), multiplicity, coupling constant (Hz), and integration. Data for 13C NMR are reported in terms of
chemical shift (ppm, scale), multiplicity, and coupling constant (Hz). High-resolution mass spectra were
obtained by ESI on a TOF mass analyzer.
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.
Preparation of bis(pentafluoroethyl)zinc reagent Zn(C2F5)2(DMPU)2.
To an oven-dried 100-mL two-neck round-bottomed flask equipped with a magnetic stir bar were
added Toluene (15 mL) and DMPU (2.4 mL, 20 mmol) under argon atmosphere. Pentafluoroethyl
iodide (3.0 mL, 25 mmol) was added to the solution. Diethyl zinc solution (1.0 M in hexanes, 10 mL, 10
mmol) was then added dropwise at -35 °C. After the reaction mixture was stirred at -5 °C for 24 h, the
precipitate was obtained. After removing the solution, the precipitate obtained was washed with hexane
(50 mL) three times and dried under vacuum to give Zn(C2F5)2(DMPU)2 as a white powder (5.4 g, 95%
yield). This compound is known.16
Preparation of bis(heptafluoropropyl)zinc reagent Zn(C3F7)2(DMPU)2
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To an oven-dried 100-mL two-neck round-bottomed flask equipped with a magnetic stir bar were
added Toluene (15 mL) and DMPU (2.4 mL, 20 mmol) under argon atmosphere. Heptafluoropropyl
iodide (3.6 mL, 25 mmol) was added to the solution. Diethyl zinc solution (1.0 M in hexanes, 10 mL, 10
mmol) was then added dropwise at -35 °C. After the reaction mixture was stirred at -5 °C for 24 h, the
precipitate was obtained. After removing the solution, the precipitate obtained was washed with hexane
(50 mL) three times and dried under vacuum to give Zn(C3F7)2(DMPU)2 as a white powder (6.1 g, 93%
yield). This compound is known.16
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Preparation of bis(Perfluorobutyl)zinc reagent Zn(C4F9)2(DMPU)2.
To an oven-dried 100-mL two-neck round-bottomed flask equipped with a magnetic stir bar were
added Toluene (15 mL) and DMPU (2.4 mL, 20 mmol) under argon atmosphere. Perfluorobutyl iodide
(4.3 mL, 25 mmol) was added to the solution. Diethyl zinc solution (1.0 M in hexanes, 10 mL, 10 mmol)
was then added dropwise at -35 °C. After the reaction mixture was stirred at -5 °C for 24 h, the
precipitate was obtained. After removing the solution, the precipitate obtained was washed with hexane
(50 mL) three times and dried under vacuum to give Zn(C4F9)2(DMPU)2 as a white powder (6.9 g, 89%
yield). This compound is known.16
Preparation of bis(tridecafluorohexyl)zinc reagent Zn(C6F13)2(DMPU)2
To an oven-dried 100-mL two-neck round-bottomed flask equipped with a magnetic stir bar were
added Toluene (15 mL) and DMPU (2.4 mL, 20 mmol) under argon atmosphere. Tridecafluorohexyl
iodide (5.4 mL, 25 mmol) was added to the solution. Diethyl zinc solution (1.0 M in hexanes, 10 mL, 10
mmol) was then added dropwise at -35 °C. After the reaction mixture was stirred at -5 °C for 24 h, the
precipitate was obtained. After removing the solution, the precipitate obtained was washed with hexane
(50 mL) three times and dried under vacuum to give Zn(C6F13)2(DMPU)2 as a white powder (8.4 g, 88%
yield). This compound is known.16
Representative General Procedure for Copper-Catalyzed Perfluoroalklation of Boronic Acids.: To
a septum capped 25 mL of sealed tube equipped with a magnetic stir bar were added 4-Biphenylboronic
acid(40 mg, 0.2 mmol), Zn(C4F9)2(DMPU)2 (151 mg, 0.2 mmol), AgOAc (20 mg, 0.12 mmol), K3PO4
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(85 mg, 0.4 mmol), CuI (3.8 mg, 0.02 mmol) and phen (3.6 mg, 0.02 mmol) under O2 atmosphere, then
an O2 balloon was attached to the Schlenk tube, followed by DMSO (2.0 mL) with stirring. The sealed
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tube was screw capped and heated to 80 C (oil bath). After stirring for 12 h, the reaction mixture was
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cooled to room temperature, and diluted with ethyl acetate, washed with brine, dried over Na2SO4,
filtered and concentrated. The residue was purified with silica gel chromatography to provide pure
product.
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4-(Perfluorobutyl)-1,1'-biphenyl (3ac) The product (66 mg, 90% yield) was purified with silica gel
1
chromatography (Petroleum ether (100%)) as a white solid. H NMR (600 MHz, CDCl3) δ 7.73 (d, J
=7.8 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 7.2 Hz, 2 H), 7.49 (t, J = 7.8 Hz, 2 H), 7.42 (t, J =
7.2 Hz, 1 H). 19F NMR (564 MHz, CDCl3) δ -81.1 (m, 3F), -110.9 (t, J = 13.0 Hz, 2F), -122.8 (m, 2F), -
125.6 (m, 2F). This compound is known.7q
3-(Perfluorobutyl)-1,1'-biphenyl (3bc) The product (50 mg, 67% yield) was purified with silica gel
1
chromatography (Petroleum ether (100%)) as a colorless oil. H NMR (600 MHz, CDCl3) δ 7.80 (m, 2
13
H), 7.60 (m, 4 H), 7.49 (m, 2 H), 7.41 (m, 1 H). C NMR (150.8 MHz, CDCl3) δ 144.6, 142.4, 133.3,
132.1 (t, J = 22.6 Hz), 131.8, 131.7, 130.7, 129.9, 128.2 (m), 121.1, 120.2, 119.2, 118.5. 19F NMR
(564MHz, CDCl3) δ -81.63 (tt, J = 9.6, 2.8 Hz, 3F), -110.98 (t, J = 12.4 Hz, 2F), -122.68 (m, 2F), -
125.62 (m, 2F). IR (neat) v: 1241, 1134, 742 cm-1. MS (EI): m/z (%), 372 (M), 203 (100), 353. HRMS:
Calculated for C16H9F9: 372.0561; Found: 372.0551.
2-(Perfluorobutyl)-1,1'-biphenyl (3cc) The product (24 mg, 32%) was purified with silica gel
chromatography (Petroleum ether (100%)) as a colorless oil. 1H NMR (600 MHz, CDCl3) δ 7.67 (d, J =
7.8 Hz, 1 H), 7.57 (d, J = 7.2 Hz, 1 H), 7.51 (d, J = 7.8 Hz, 1 H), 7.37 (m, 3H), 7.30 (d, J = 7.8 Hz, 1 H),
7.26 (m, 1 H). 19F NMR (564MHz, CDCl3) δ -81.1 (m, 3 F), -103.1 (m, 2 F), -120.7 (m, 2 F), -125.9 (m,
2F). This compound is known.17
2-(Perfluorobutyl)naphthalene (3dc) The product (50 mg, 73% yield) was purified with silica gel
chromatography (Petroleum ether (100%)) as a pale yellow oil. 1H NMR (600 MHz, CDCl3) δ 8.15(s, 1
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H), 7.96 (m, 2 H), 7.92 (d, J = 7.8 Hz, 2 H), 7.62 (m, 3 H). 19F NMR (564 MHz, CDCl3) δ -81.0 (tt, J =
9.6Hz, 2.8 Hz, 3F), -110.4 (t, J = 13.0 Hz, 2F), -122.54 (m, 2F), -125.61 (m, 2F). This compound is
known.7q
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9-(Perfluorobutyl)phenanthrene (3ec) The product (52 mg, 65% yield) was purified with silica gel
chromatography (Petroleum ether (100%)) as a white solid. m.p 79.5-81 oC. 1H NMR (600 MHz, CDCl3)
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δ 8.77 (d, J = 8.4Hz, 1 H), 8.70 (d, J = 8.4Hz, 1 H), 8.31 (d, J = 8.4 Hz, 1 H), 8.17 (s, 1 H), 7.97 (d, J =
8.4 Hz, 1 H), 7.80 (t, J = 7.8Hz, 1 H), 7.74-7.76 (m,3H). 13C NMR (150.8 MHz, CDCl3) δ 134.6, 133.7,
133.3(t, J = 10.4 Hz), 132.6, 132.1, 131.9, 130.6, 129.9, 129.8, 128.4, 125.9 (t, J = 21.4 Hz), 125.8,
125.3, 122.1, 121.2, 120.4, 119.3. 19F NMR (564 MHz, CDCl3) δ -80.88 (m, 3F), -104.55 (t, J = 14.0 Hz,
2F), -120.70 (m, 2F), -125.63 (m, 2F). IR (neat) v: 1244, 1129, 718 cm-1. MS (EI): m/z (%), 308 (M),
227 (100), 372. HRMS: Calculated for C18H9F9: 396.0561; Found: 396.0551.
4,4'-Bis(perfluorobutyl)-1,1'-biphenyl (3fc) The product (72 mg, 61% yield) was purified with silica
gel chromatography (Petroleum ether (100%)) as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.74 (d, J
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= 8.4 Hz, 4 H), 7.70 (d, J = 8.4 Hz, 4 H). F NMR (564 MHz, CDCl3) δ -81.5 (m, 3F), -111.0 (t, J =
13.0 Hz, 2F), -122.7 (m, 2F) , -125.6 (m, 2F). This compound is known.7q
1-Methoxy-4-(perfluorobutyl)benzene (3gc) The product (26 mg, 41% yield) was purified with silica
gel chromatography (Petroleum ether / Ethyl ether = 20:1) as a colorless oil. 1H NMR (600 MHz, CDCl3)
δ 7.38 (d, J = 9.0 Hz, 2 H), 6.80 (d, J = 9.0 Hz, 2 H), 3.78 (s, 3 H). 19F NMR (564 MHz, CDCl3) δ -81.1
(m, 3F), -110.9 (t, J = 18.6 Hz, 2F), -122.8 (m, 2F) , -125.6 (m, 2F). This compound is known.7p
1-Methoxy-3-(perfluorobutyl)benzene (3hc) The product (32 mg, 49% yield) was purified with silica
gel chromatography (Petroleum ether / Ethyl ether = 20:1) as a yellow oil. 1H NMR (600MHz, CDCl3) δ
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7.36 (t, J = 8.4 Hz, 4 H), 7.19 (m, 1 H), 7.13 (t, J = 1.8, 1 H), 6.91 (m , 2 H), 3.87 (s , 3 H). F NMR
(564 MHz, CDCl3) δ -81.0 (t, J = 9.6 Hz, 3F), -110.9 (t, J = 13.0 Hz, 2F), -122.8 (m, 2F), -125.7 (m, 2F).
This compound is known.7p
1-(Perfluorobutyl)-4-phenoxybenzene (3ic) The product (49 mg, 63% yield) was purified with silica
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gel chromatography (Petroleum ether (100%)) as a pale yellow oil. 1H NMR (600 MHz, CDCl3) δ 7.81
(d, J = 7.8 Hz, 2H), 7.61 (d, J = 7.2 Hz, 2H), 7.59 (m, 4.8 Hz, 2 H), 7.49 (t, J = 7.8 Hz, 2 H), 7.42 (t, J =
7.2 Hz, 1 H). 13C NMR (150.8 MHz, CDCl3) δ 144.6, 142.4, 133.3 (m), 132.1.8 (t, J = 24.3 Hz), 131.7,
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131.6, 130.7, 129.9, 128.2 (m), 121.1, 120.2, 119.2, 118.7. 19F NMR (564 MHz, CDCl3) δ -81.0 (m, 3F),
-110.0 (t, J = 13.0Hz, 2F), -122.7 (m, 2F), -125.6 (m, 2F). IR (neat) v: 1235, 1138, 718 cm-1. MS (EI):
m/z (%) 203 (100). HRMS: Calculated for C16H9F9O: 388.0510; Found: 388.0502.
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Ethyl 4-(perfluorobutyl)benzoate (3jc) The product (37 mg, 50% yield) was purified with silica gel
chromatography (Petroleum ether / Ethyl ether = 20:1) as a pale yellow oil. 1H NMR (600 MHz, CDCl3)
δ 8.17 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 4.11 (q, J = 7.2 Hz, 2 H), 4.22 (t, J = 7.2 Hz, 3 H).
13C NMR (150.8 MHz, CDCl3) δ 167.9, 136.6, 135.4 (t, J = 24.3 Hz), 132.3, 129.5 (t, J = 6.0 Hz), 121.0,
119.8, 119.1, 118.1, 64.3, 16.7. 19F NMR (564 MHz, CDCl3) δ -81.0 (tt, J = 9.6 Hz, 1.8 Hz, 3F), -111.5
(t, J = 13.0 Hz, 2F), -122.7 (m, 2F), -125.6 (m, 2F). IR (neat) v: 1730, 1236, 715 cm-1. MS (EI): m/z (%)
368 (M), 323 (100), 171. HRMS: Calculated for C13H9F9O2: 368.0459; Found: 368.0461.
Methyl 4-(perfluorobutyl)benzoate (3kc) The product (35mg, 50% yield) was purified with silica gel
chromatography (Petroleum ether / Ethyl ether = 20:1) as a colorless oil. 1H NMR (600 MHz, CDCl3) δ
8.17 (d, J = 8.4 Hz, 1 H), 7.68 (t, J = 7.8 Hz, 1 H), 3.96 (s, 3 H). 19F NMR (564MHz, CDCl3) δ -81.0 (m,
3 F), -111.5 (d, J = 14.7 Hz, 2 F), -122.7 (d, J = 9.6 Hz, 2 F), -125.6 (m, 2F). This compound is known.7p
Ethyl 3-(perfluorobutyl)benzoate (3lc) The product (23 mg, 31% yield) was purified with silica gel
chromatography (Petroleum ether / Ethyl ether = 20:1) as a pale yellow oil. 1H NMR (600 MHz, CDCl3)
δ 8.24 (d, J = 9.0 Hz, 2 H), 7.76 (d, J = 7.8 Hz, 1 H), 7.59 (t, J = 7.8 Hz, 1 H), 4.43 (q, J = 7.2 Hz, 2 H),
1.41 (t, J = 7.2 Hz, 3 H), 3.77 (s, 3 H). 13C NMR (150.8 MHz, CDCl3) δ 167.8, 135.6, 134.0, 133.5 (t, J
= 6.0 Hz), 132.0 (t, J = 24 Hz), 131.5, 130.6 (t, J = 6.0 Hz), 121.2, 119.9, 118.1, 116.4 64.19, 16.82. 19F
NMR (564 MHz, CDCl3) δ -81.2 (t, J = 7.9 Hz, 3F), -111.2 (t, J = 13.0 Hz, 2F), -122.7 (m, 2F), -125.7 (t,
J = 12.4 Hz, 2F). IR (neat) v: 1728, 1241 cm-1. MS (EI): m/z (%) 368 (M), 323 (100), 171. HRMS:
Calculated for C13H9F9O2: 368.0459; Found: 368.0454.
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1-(3-(Perfluorobutyl)phenyl)ethan-1-one (3mc) The product (29 mg, 43% yield) was purified with
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silica gel chromatography (Petroleum ether / Ethyl ether = 20:1) as a colorless oil. 1H NMR (600 MHz,
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CDCl3) δ 8.16 (d, J = 6.6 Hz, 2 H), 7.78 (d, J = 7.8 Hz, 1 H), 7.63 (t, J = 8.4 Hz, 1 H). F NMR (564
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MHz, CDCl3) δ -81.1 (t, J = 9.6 Hz, 3F), -111.2 (t, J = 13.5 Hz, 2F), -122.7 (m, 2F), -125.6 (m, 2F).
This compound is known.7q
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1-(Methylsulfonyl)-4-(perfluoropentyl)benzene (3nc) The product (59 mg, 79% yield) was purified
with silica gel chromatography (Petroleum ether / Ethyl ether = 3:1) as a white solid. m.p 89.5-91 oC 1H
NMR (600 MHz, CDCl3) δ 8.11 (d, J = 8.4 Hz, 2H), 7.82 (m, J = 8.4 Hz, 2H), 3.11 (s, 3 H). 13C NMR
(150.8 MHz, CDCl3) δ 146.9, 16.7 (t, J = 24.6 Hz), 130.8 (t, J = 6.5 Hz), 130.5, 122.8, 120.9, 119.0,
117.7, 46.9. 19F NMR (564 MHz, CDCl3) δ -81.0 (t, J = 9.6 Hz, 3F), -111.6 (t, J = 13.5 Hz, 2F), -122.6
(m, 2F), -125.6 (m, 2F). IR (neat) v: 1129, 752 cm-1. MS (EI): m/z (%) 374 (M), 143 (100), 205. HRMS:
Calculated for C11H7F9O2S: 374.0023; Found: 374.0026.
4-(Perfluoroethyl)-1,1'-biphenyl (3aa) The product (50 mg, 92%) was purified with silica gel
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chromatography (Petroleum ether (100%)) as a white solid. H NMR (600 MHz, CDCl3) δ 7.72 (d, J =
7.2 Hz, 2 H), 7.68 (d, J = 7.2 Hz, 2 H), 7.62 (d, J = 6.6 Hz, 2 H), 7.49 (d, J = 6.6 Hz, 2 H), 7.43 (d, J =
6.6 Hz, 1 H). 19F NMR (564 MHz, CDCl3) δ -84.7 (s, 3F), -114.8 (s, 2F). This compound is known.7q
4-(Perfluoropropyl)-1,1'-biphenyl (3ab) The product (42 mg, 65%) was purified with silica gel
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chromatography (Petroleum ether (100%)) as a white solid. H NMR (600 MHz, CDCl3) δ 7.22 (d, J =
7.8 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.8 Hz, 2 H), 7.42 (m, 1 H).
19F NMR (564 MHz, CDCl3) δ -80.0 (m, 3 F), -111.6 (m, 2 F), -126.4 (s, 2 F). This compound is
known.7q
4-(Perfluorohexyl)-1,1'-biphenyl (3ad) The product (53 mg, 56%) was purified with silica gel
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chromatography (Petroleum ether (100%)) as a white solid. H NMR (600 MHz, CDCl3) δ 7.72 (d, J =
7.8 Hz, 2 H), 7.67 (d, J = 7.8 Hz, 2 H), 7.62 (d, J = 7.8 Hz, 2 H), 7.49 (t, J = 7.2 Hz, 2 H), 7.42 (t, J = 7.2
Hz, H). 19F NMR (564 MHz, CDCl3) δ -80.9 (t, J = 10.2 Hz, 3F), -110.7 (t, J = 14.7 Hz, 2F), -121.6 (s,
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2F), -121.9 (s, 2F), -122.9 (m, 2F), -126.3 (m, 2F). This compound is known.18
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1-Methoxy-3-(perfluoroethyl)benzene (3ha) The product (19mg, 41% yield) was purified with silica
gel chromatography (Petroleum ether / Ethyl ether = 20:1) as a colorless oil. 1H NMR (600 MHz, CDCl3)
δ 7.36 (t, J = 7.8 Hz, H), 7.18 (d, J = 7.8 Hz, H), 7.12 (m, 1H), 6.91 (m, H), 3.84 (s, 3 H). 19F NMR (564
9
MHz, CDCl3) δ -84.7 (s, 3F), -114.8 (s, 2F). This compound is known.7q
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Methyl 4-(perfluorohexyl)benzoate (3hd) The product (31mg, 36% yield) was purified with silica gel
chromatography (Petroleum ether / Ethyl ether = 20:1) as a colorless oil. 1H NMR (600 MHz, CDCl3) δ
7.36 (t, J = 7.8 Hz, H), 7.18 (d, J = 7.8 Hz, H), 7.12 (m, H), 6.90 (m, 1H), 3.84 (s, 3 H). 19F NMR (564
MHz, CDCl3) δ -81.0 (m, 3F), -111.3 (m, 2F), -121.5 (s, 2F), -121.9 (m, 2F), -122.9 (s, 2F), -126.3 (m,
2F). This compound is known.7q
Methyl 4-(perfluoroethyl)benzoate (3ka) The product (25mg, 49% yield) was purified with silica gel
chromatography (Petroleum ether / Ethyl ether = 20:1) as a colorless oil. 1H NMR (600 MHz, CDCl3) δ
8.16 (d, J = 8.4 Hz, 2 H), 7.68 (d, J = 8.4 Hz, 2 H), 3.96 (s, 3 H). 19F NMR (564 MHz, CDCl3) δ -84.5 (t,
3F), -115.5 (t, 2F). This compound is known.7q
Methyl 4-(perfluorohexyl)benzoate (3kd) The product (39mg, 43% yield) was purified with silica gel
chromatography (Petroleum ether / Ethyl ether = 20:1) as a colorless oil. 1H NMR (600 MHz, CDCl3) δ
8.17(d, J = 8.4 Hz, 2 H), 7.68 (d, J = 8.4 Hz, 2 H), 3.96 (s, 3 H). 19F NMR (564 MHz, CDCl3) δ -80.9 (t,
J = 9.56 Hz, 3F), -111.3 (t, J = 14.7 Hz, 2F), -121.5 (s, 2F), -121.9 (m, 2F), -122.9 (m, 2F), -126.2 (m,
2F). This compound is known.7q
1-(Methylsulfonyl)-4-(perfluoroethyl)benzene (3na) The product (45 mg, 82%) was purified with
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silica gel chromatography (Petroleum ether / Ethyl ether = 3:1) as a white solid. m.p 85-87.5oC. H
NMR (600 MHz, CDCl3) δ 8.11 (d, J = 7.8 Hz, 2 H), 7.83 (d, J = 7.8 Hz, 2 H), 3.10 (s, 3 H). 13C NMR
(150.4MHz, CDCl3) δ 146.8, 136.6 (t, J = 24.1 Hz), 130.6, 130.5 (t, J = 6.0 Hz), 122.3, 120.4, 46.9. 19F
NMR (564 MHz, CDCl3) δ -89.3 (s, 3F), -120.2 (s, 2F). IR (neat) v: 1212, 769 cm-1. MS (EI): m/z (%)
274(M), 145 (100), 195. HRMS: Calculated for C9H7F5O2S: 274.0087; Found: 274.0081.
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1-(Methylsulfonyl)-4-(perfluoropropyl)benzene (3nb) The product (47 mg, 73%) was purified with
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silica gel chromatography (Petroleum ether / Ethyl ether = 3:1) as a white solid. m.p 92-93.5 C. H
NMR (600 MHz, CDCl3) δ 8.11 (d, J = 7.8 Hz, 2 H), 7.82 (d, J = 8.4 Hz, 2 H), 3.11 (s, 3 H). 13C NMR
(150.8 MHz, CDCl3) δ 146.9, 136.8 (t, J = 24.1 Hz), 130.8 (t, J = 6.0 Hz), 130.5, 120.7, 118.8, 117.8,
9
46.9. 19F NMR (564 MHz, CDCl3) δ -79.9 (t, J = 10.2 Hz, 3F), -122.5 (m, 2F), -126.2 (m, 2F). IR (neat)
v: 1156, 730 cm-1. MS (EI): m/z (%) 325 (M+ + H+), 324 (M), 143 (100). HRMS: Calculated for
C10H7F7O2S: 324.0055; Found: 324.0056.
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1-(Methylsulfonyl)-4-(perfluorohexyl)benzene (3nd) The product (60 mg, 63%) was purified with
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silica gel chromatography (Petroleum ether / Ethyl ether = 3:1) as a white solid. m.p 92.5-94 C. H
NMR (600 MHz, CDCl3) δ 8.12 (d, J = 7.8 Hz, 2 H), 7.83 (d, J = 7.8 Hz, 2 H), 8.11 (s, 3 H). 13C NMR
(150.8 MHz, CDCl3) δ 146.9, 136.6 (t, J = 24.1 Hz), 130.7 (t, J = 6.3 Hz), 130.5, 121.4, 119.5, 117.2,
19
115.5, 111.3, 111.0, 46.9. F NMR (564 MHz, CDCl3) δ -80.80 (m, 3F), -111.4 (t, J = 13.5 Hz, 3F), -
121.5 (s, 2F), -121.7 (s, 2F), -122.9 (s, 2F), -126.2 (s, 2F). IR (neat) v: 1117, 789 cm-1. MS (EI): m/z (%)
475 (M+ + H+), 474 (M+), 205 (100). HRMS: Calculated for C13H7F13O2S: 473.9959; Found: 473.9950.
ASSOCIATED CONTENT
Supportiong Information. 1H NMR, 19F NMR, and 13C NMR Spectra for Compounds.
This material is available free of charge via the Internet at http://pubs.acs.org
ACKNOWLEDGMENTS. This work was financially supported by the National Natural Science
Foundation of China (grant number: 21602041), the Natural Science Foundation of Anhui Province
(grant number: 1708085QB38), and Start-up Foundation of Hefei University of Technology.
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