Copper-catalyzed oxidative trifluoroethoxylation of aryl boronic acids with CF3CH2OH

Article abstract of DOI:10.1016/j.jfluchem.2016.07.008

A mild and efficient copper-catalyzed oxidative trifluoroethoxylation of aryl and heteroaryl boronic acids with CF₃CH₂OH has been developed. This protocol tolerates a range of functional groups, allowing access to a variety of aryl and heteroaryl trifluoroethyl ethers.

Full text of DOI:10.1016/j.jfluchem.2016.07.008

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FLUOR 8814 No. of Pages 8
Journal of Fluorine Chemistry xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Copper-catalyzed oxidative trifluoroethoxylation of aryl boronic acids
with CF3CH2OH
Ke Zhanga, Xiu-Hua Xub, Feng-Ling Qinga,b,
*
a
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North Renmin Lu, Shanghai 201620, China
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling Lu, Shanghai 200032, China
b
A R T I C L E I N F O
A B S T R A C T
Article history:
A mild and efficient copper-catalyzed oxidative trifluoroethoxylation of aryl and heteroaryl boronic acids
with CF3CH2OH has been developed. This protocol tolerates a range of functional groups, allowing access
to a variety of aryl and heteroaryl trifluoroethyl ethers.
Received 14 May 2016
Received in revised form 12 July 2016
Accepted 17 July 2016
Available online xxx
ã 2016 Elsevier B.V. All rights reserved.
Keywords:
Copper
Trifluoroethoxylation
Oxidative coupling
Aryl boronic acids
Aryl trifluoroethyl ethers
1. Introduction
with trifluoroethanol provided alternative and potentially valuable
routes to trifluoroethyl aryl ethers (Scheme 1c) [7]. But a large
Due to the specific and useful properties of fluorine and
fluorine-containing groups, fluorinated compounds play an
increasingly important role in pharmaceuticals, agrochemicals
and material sciences [1]. Consequently, a large number of novel
methods, especially transition-metal mediated/catalyzed fluori-
nation and fluoroalkylation reactions, have been developed for the
preparation of fluorinated compounds [2]. Among them, trifluor-
oethyl aryl ethers (ArOCH2CF3) have received increasing attention
because of the unique properties of the trifluoroethoxy group
(OCH2CF3), such as high metabolic stability and significant
lipophilicity [3]. These compounds have been widely used in the
development of new drugs and materials [4].
Trifluoroethyl aryl ethers were usually synthesized by trifluor-
oethylation of phenols via SN2 reactions (Scheme 1a) [5]. But these
reactions required the elevated temperatures. Very recently, Ritter
and co-workers reported a novel synthesis of aryl trifluoroethyl
ethers from the reaction of phenols with 2,2,2-trifluoroethanol in
the presence of PhenoFluor at 23 ꢀC (Scheme 1b) [6]. In addition,
transition-metal catalyzed cross-coupling reactions of aryl halides
excess of 2,2,2-trifluoroethanol was necessary for copper-cata-
lyzed trifluoroethoxylation [7a], and the palladium-catalyzed
cross-coupling reaction was restricted to activated aryl halides
[7b,c]. Very recently, MacMillan reported a photoredox/nickel dual
catalyzed cross-coupling reaction between 4-bromoacetophenone
and 2,2,2-trifluoroethanol [7d]. Furthermore, Weng and co-work-
ers disclosed the reactions of aryl and heteroaryl bromides with
copper(I) trifluoroethoxide complexes [7e]. Despite the substantial
progress of the transition-metal mediated/catalyzed cross-cou-
pling of aryl halides with 2,2,2-trifluoroethanol has been made, the
development of the cross-coupling of an alternative partner with
2,2,2-trifluoroethanol for the synthesis of trifluoroethyl aryl ethers
still remains an attractive goal.
In 1998, Chan, Evans and Lam simultaneously developed the
Cu-mediated oxidative cross-coupling of aryl boronic acids with
amines or phenols [8]. Recent modification of this oxidative cross-
coupling reaction have extended to unactivated alcohols [9a] and
serines [9b]. In 2003 Qauch and Batey reported the copper-
catalyzed reaction of potassium organotrifluoroborate salts and
aliphatic alcohols including 2,2,2-trifluoroethanol [9a], but this
reaction was not effective for the electron-deficient aryl trifluor-
oborates. Recently, we have developed the oxidative trifluorome-
thylation and trifluoromethylthiolation of arylboronic acids [10].
Inspired by these results, we envisioned that the oxidative
* Corresponding author at: College of Chemistry, Chemical Engineering and
Biotechnology, Donghua University, 2999 North Renmin Lu, Shanghai 201620,
China.
E-mail address: flq@mail.sioc.ac.cn (F.-L. Qing).
http://dx.doi.org/10.1016/j.jfluchem.2016.07.008
0022-1139/ã 2016 Elsevier B.V. All rights reserved.
Please cite this article in press as: K. Zhang, et al., Copper-catalyzed oxidative trifluoroethoxylation of aryl boronic acids with CF3CH2OH, J.
Fluorine Chem. (2016), http://dx.doi.org/10.1016/j.jfluchem.2016.07.008

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FLUOR 8814 No. of Pages 8
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Scheme 1. Different approaches to aryl trifluoroethyl ethers.
coupling of aryl boronic acids with 2,2,2-trifluoroethanol should be
feasible. Herein we describe the oxidative trifluoroethoxylation of
arylboronic acids with 2,2,2-trifluoroethanol for preparation of
aryl trifluoroethyl ethers (Scheme 1d). Although Zou and Wu have
disclosed a similar reaction for the synthesis of aryl trifluoroethyl
ethers recently [11], their reaction required an excess of 2,2,2-
trifluoroethanol, oxygen atmosphere, and high temperature for
some substrates. Our protocol employs only two equivalents of
2,2,2-trifluoroethanol and the reaction is carried out under milder
reaction conditions (ambient atmosphere and room temperature),
thus providing a practical means to prepare aryl trifluoroethyl
ethers.
2. Results and discussion
Initially, 4-biphenylboronic acid (1a) was chosen as the model
substrate to optimize the reaction conditions for oxidative
trifluoroethoxylation (Table 1). The reaction of 1a with 2,2,2-
trifluoroethanol was investigated in the presence of Cu(OAc)2 and
NEt3 or pyridine (Py) under an oxygen atmosphere (entries 1 and
2). Pyridine was superior to NEt3 to give the desired product 2a in
54% yield. Then, several ligands including 4-dimethylaminopyr-
idine (DMAP), 2-fluoropyridine (2-F-Py), 4-methylpyridine (4-Me-
Py), and 1,10-phenanthroline (phen) were screened (entries 3–6).
However, none of them gave better results. In consideration of the
Table 1
Optimization of reaction conditionsa.
Entry
Cu salt
Ligand
Additive
Solvent
Atmosphere
Yield (%)b
1
2
3
4
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OCOCF3)2
CuBr2
NEt3
Py
ꢁꢁ
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
THF
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
Air
Air
N2
37
54
42
12
39
37
53
44
66
Trace
7
Trace
36
16
55
39
73
45
20
72
0
ꢁꢁ
DMAP
2-F-Py
4-Me-Py
Phen
Py
Py
Py
Py
Py
Py
Py
Py
Py
Py
Py
Py
Py
ꢁꢁ
ꢁꢁ
5
ꢁꢁ
6
ꢁꢁ
7c
ꢁꢁ
8
9
NaOAc
Na2CO3
K3PO4
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
10
11
12
13
14
15
16
17d
18d,e
19d,f
20d
21
22d
CuTC
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
ꢁꢁ
CH2Cl2
Toluene
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
Py
Py
Py
Cu(OAc)2
0
a
Reaction conditions: 1a (0.2 mmol), CF3CH2OH (0.4 mmol), Cu salt (0.2 mmol), ligand (0.2 mmol), additive (0.4 mmol), 4 Å MS (100 mg), solvent (2.0 mL), rt, 14 h.
b
c
d
e
f
Yields were determined by 19F NMR spectroscopy using trifluoromethoxylbenzene as an internal standard.
Py (0.4 mmol).
Cu(OAc)2 (10 mol%).
Py (20 mol%).
Py (10 mol%). CuTC Copper thiophene-2-carboxylate.
¼
Please cite this article in press as: K. Zhang, et al., Copper-catalyzed oxidative trifluoroethoxylation of aryl boronic acids with CF3CH2OH, J.
Fluorine Chem. (2016), http://dx.doi.org/10.1016/j.jfluchem.2016.07.008

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FLUOR 8814 No. of Pages 8
K. Zhang et al. / Journal of Fluorine Chemistry xxx (2016) xxx–xxx
3
acidity of trifluoroethanol (pKa = 12.4) [12], we thought it might be
necessary to add more base to promote this reaction. However, the
yield of compound 2a was not improved when the amount of
pyridine was increased (entry 7). Then several inorganic bases
were screened. Na2CO3 was the optimal choice and led to a higher
yield of 2a (entries 8–10). To improve the reaction yield further,
different Cu salts and solvents were investigated (entries 11–16).
Unfortunately, no higher yield was obtained. Interestingly, a
catalytic amount of Cu(OAc)2 (10 mol%) slightly improved the yield
of 2a to 73% (entry 17). In contrast, the yield decreased sharply in
the presence of catalytic amount of pyridine (entries 18 and 19).
These results indicated that pyridine might play a dual role as a
base and a ligand. Furthermore, switching the oxygen atmosphere
to ambient atmosphere resulted in a similar yield of 2a (entry 20),
which made this reaction easy handling and safe to run. It was
noteworthy that no 2a was obtained in the absence of Cu(OAc)2 or
under nitrogen atmosphere (entries 21 and 22). From these results,
it was concluded that both of the Cu salt and the oxidant (O2) were
crucial to this reaction.
1q) and cyano (1r). Aryl boronic acids bearing chloro (1i), bromo
(1j) and even iodo (1k) groups were suitable substrates, providing
the corresponding trifluoroethyl aryl ethers in good yields. The
reserved halo groups could be further transformed into other
functional groups. Furthermore, aryl boronic acids bearing ketones
(1n) and aldehydes (1o) were well tolerated in this oxidative
trifluoroethyoxylation. Heteroaryl boronic acids can also be
trifluoroethoxylated. Quinolin-3-ylboronic acid (1u) was a com-
petent substrate, whereas dibenzo[b,d]thiophen-4-ylboronic acid
(1w) gave low yield due to the steric effect. Subsequently, the
oxidative trifluoroethoxylation of 1a on a 5.0 mmol scale was also
tested to demonstrate the practicability of this reaction. The
reaction proceeded smoothly and led to the isolated product 2a in
63% yield that was almost same as that of the reaction on 0.5 mmol
scale.
To investigate the utility of this oxidative trifluoroethoxylation
in late-stage functionalization, we attempted to synthesize a
Cinacalcet analogue [13] from the corresponding aryl boronic acid
(Scheme 2). The desired trifluoroethoxylated product (2x) was
isolated in 67% yield from the copper-catalyzed cross-coupling
reaction of aryl boronic acid (1x) with 2,2,2-trifluoroethanol. This
result showed the feasibility for the development of new
pharmaceutical molecules in late-stage trifluoroethoxylation
using this method.
With the optimal reaction conditions (Table 1, entry 20) in
hand, we then investigated the substrate scope of this copper-
catalyzed trifluoroethoxylation of aryl boronic acids. Both elec-
tron-rich and ꢁdeficient aryl boronic acids can be trifluoroethoxy-
lated in moderate to good yields (Table 2). The mild conditions
allowed the tolerance of many functional groups, such as ether
(1c), thioether (1d), amide (1f), ester (1l, 1m), vinyl (1h), nitro (1p,
Finally, the reactivity of different aryl boronic acids and alcohols
was also compared (Scheme 3). We found that electron-rich aryl
Table 2
Scope of substratesa.
aReaction conditions: 1 (0.5 mmol), Cu(OAc)2 (0.05 mmol), CF3CH2OH (1.0 mmol), pyridine (0.5 mmol), Na2CO3 (1.0 mmol), 4 Å MS (250 mg), DCE (5.0 mL), rt, under air, 14 h,
isolated yields.
b1a (5.0 mmol).
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FLUOR 8814 No. of Pages 8
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Scheme 2. Late-stage trifluoroethoxylation of a Cinacalcet analogue.
Scheme 3. Comparing the reactivities of different aryl boronic acids and alcohols.
boronic acid 1c reacted faster than electron-poor aryl boronic acid
1p (Scheme 3a), which was consistent with the common oxidative
cross-coupling reactions with aryl boronic acids. Surprisingly,
2,2,2-trifluoroethanol showed higher reactivity than ethanol
despite its diminished nucleophilicity (Scheme 3b).
CF3CH2OH (100.0 mg,1.0 mmol, 2.0 equiv) were added respectively
via syringe. The mixture was stirred vigorously under a balloon of
air at room temperature for 14 h. Then the reaction solution was
vacuum-filtered over a sintered-glass funnel with a tightly packed
pad of Celite (1 cm thick), and the filter cake was rinsed with DCM
(20 mL). The combined filtrates were concentrated. The residue
was purified with silica gel column chromatography to provide the
desired product.
3. Conclusion
In conclusion, we have developed a Cu-catalyzed oxidative
trifluoroethoxylation of aryl- and heteroaryl boronic acids at room
temperature. The mild reaction conditions afforded a high level
functional group tolerance, making this protocol very practical in
organic synthesis. Furthermore, the use of low-cost reagents, such
as CF3CH2OH, pyridine, and Na2CO3, especially the use of air as the
oxidant, made this process more attractive than other trifluor-
oethoxylation methods.
4.2.1. 4-(2,2,2-Trifluoroethoxy)-1,10-biphenyl (2a)
Compound 2a was prepared according to the general procedure
from 4-biphenyl boronic acid (99.0 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane as the eluent, compound 2a was obtained as a white
solid (82.2 mg, 65%). mp 99–100 ꢀC. 1H NMR (400 MHz, CDCl3)
d
ppm 7.56 (d, J = 7.2 Hz, 4H), 7.43 (t, J = 7.6 Hz, 2H), 7.34 (t, J = 7.2 Hz,
1H), 7.07 (d, J = 8.4 Hz, 2H), 4.40 (q, J = 8.2 Hz, 2H). 13C NMR
4. Experimental section
(100 MHz, CDCl3)
d ppm 157.0, 140.4, 135.8, 128.9, 128.4, 127.1,
126.9, 123.5 (q, J = 278.0 Hz), 115.3, 66.0 (q, J = 35.4 Hz). 19F NMR
4.1. General information
(376 MHz, CDCl3)
d
ppm ꢁ73.98 (t, J = 8.1 Hz, 3F). MS (EI): m/z 252
[M]+. HRMS (EI-TOF) m/z: [M]+ Calcd for C14H11F3O: 252.0762;
1H NMR (TMS as the internal standard), 19F NMR spectra (CFCl3
Found: 252.0757.
as the outside standard and low field is positive), and 13C NMR
were recorded on a 400 MHz spectrometer. Chemical shifts (
d
) are
4.2.2. 2-(2,2,2-Trifluoroethoxy)-1,10-biphenyl (2b)
reported in ppm, and coupling constants (J) are in Hertz (Hz). The
following abbreviations were used to explain the multiplicities:
s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. HRMS
using EI were obtained on a GC-TOF mass spectrometer. DCE was
distilled under reduced pressure from CaH2 and stored over 4 Å
molecular sieves. 4 Å molecular sieves were activated at 400 ꢀC for
10 h and stored in a nitrogen-filled glove box. Substrates 1a–1w
were used as received from commercial sources. Compound 1 x
was prepared according to the literature [10c].
Compound 2b was prepared according to the general procedure
from 2-biphenyl boronic acid (99.0 mg, 0.5 mmol, 1.0 equiv). After
purification by silica gel column chromatography using n-hexane
as the eluent, compound 2b was obtained as a colorless oil
(44.2 mg, 35%). 1H NMR (400 MHz, CDCl3)
d
ppm 7.52 (d, J = 7.5 Hz,
2H), 7.43–7.29 (m, 5H), 7.14 (t, J = 7.5 Hz, 1H), 6.98 (d, J = 8.2 Hz, 1H),
4.23 (q, J = 8.2 Hz, 2H). 13C NMR (100 MHz, CDCl3)
ppm 154.5,
137.5, 132.0, 131.4, 129.4, 128.7, 128.1, 127.3, 123.4 (q, J = 279.4 Hz),
123.3, 114.5, 66.8 (q, J = 35.4 Hz). 19F NMR (376 MHz, CDCl3)
ppm
d
d
ꢁ73.93 (t, J = 8.2 Hz, 3F). IR (KBr) ymax 3063, 2941, 1482, 1287, 1168,
976, 862, 752, 668 cmꢁ1. MS (EI): m/z 252 [M]+. HRMS (EI-TOF) m/z:
[M]+ Calcd for C14H11F3O: 252.0762; Found: 252.0765.
4.2. General procedure for trifluoroethoxylation of aryl boronic acids
In a nitrogen-filled glove box, a 25 mL Schlenk tube equipped
with a magnetic stir bar was charged with Cu(OAc)2 (9.3 mg,
0.05 mmol, 0.1 equiv), aryl boronic acid 1 (0.5 mmol, 1.0 equiv),
Na2CO3 (106.0 mg, 1.0 mmol, 2.0 equiv) and 4 Å MS (250.0 mg). The
vessel was sealed with a septum before removing from the glove
box. The tube was evacuated and backfilled with air for 3 times.
Then DCE (5.0 mL), pyridine (39.6 mg, 0.5 mmol, 1.0 equiv) and
4.2.3. 1-Phenoxy-4-(2,2,2-trifluoroethoxy)benzene (2c)
Compound 2c was prepared according to the general procedure
from 4-phenoxyphenyl boronic acid (107.0 mg, 0.5 mmol, 1.0
equiv). After purification by silica gel column chromatography
using n-hexane as the eluent, compound 2c was obtained as a
white solid (93.5 mg, 70%). mp 119–121 ꢀC. 1H NMR (400 MHz,
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5
CDCl3)
(m, 3H), 6.93 (t, J = 7.6 Hz, 3H), 4.33 (q, J = 8.2 Hz, 2H). 13C NMR
(100 MHz, CDCl3) ppm 157.9, 153.6, 152.0, 129.8, 123.3 (q,
J = 287.2 Hz), 123.0, 120.6, 118.1, 116.4, 66.7 (q, J = 35.5 Hz). 19F NMR
(376 MHz, CDCl3)
d
ppm 7.32 (t, J = 7.6 Hz, 2H), 7.08 (t, J = 7.4 Hz, 1H), 7.01–6.97
4.2.8. 1-(2,2,2-Trifluoroethoxy)-4-vinylbenzene (2h)
Compound 2h was prepared according to the general procedure
from 4-vinylphenyl boronic acid (74.0 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane as the eluent, compound 2h was obtained as colorless oil
d
d
ppm ꢁ74.06 (t, J = 8.2 Hz, 3F). IR (KBr) ymax
3042, 2943, 1590, 1490, 1285, 1221, 1168, 1103, 975, 842, 750,
(75.5 mg, 75%). 1H NMR (400 MHz, CDCl3)
d ppm 7.36 (d, J = 8.8 Hz,
692 cmꢁ1. MS (EI): m/z 268 [M]+. HRMS (EI-TOF) m/z: [M]+ Calcd for
2H), 6.89 (d, J = 8.8 Hz, 2H), 6.65 (dd, J = 17.6, 10.9 Hz, 1H), 5.64 (dd,
J = 17.6, 0.9 Hz, 1H), 5.17 (dd, J = 10.9, 0.9 Hz, 1H), 4.33 (q, J = 8.1 Hz,
C14H11F3O2: 268.0711; Found: 268.0712.
2H). 13C NMR (100 MHz, CDCl3)
d
ppm 157.1, 135.8, 132.3, 127.6,
4.2.4. Methyl(4-(2,2,2-trifluoroethoxy)phenyl)sulfane (2d)
123.3 (q, J = 278.0 Hz), 115.0, 112.8, 65.9 (q, J = 35.6 Hz). 19F NMR
Compound 2d was prepared according to the general procedure
from 4-(methylthio)phenyl boronic acid (84.0 mg, 0.5 mmol, 1.0
equiv). After purification by silica gel column chromatography
using n-hexane as the eluent, compound 2d was obtained as a
white solid (87.6 mg, 79%). mp 29–30 ꢀC. 1H NMR (400 MHz, CDCl3)
(376 MHz, CDCl3)
d
ppm ꢁ74.02 (t, J = 8.2 Hz, 3F). IR (KBr) ymax
2940, 1607, 1510, 1320, 1239, 1163, 1080, 975, 834, 659 cmꢁ1. MS
(EI): m/z 202 [M]+. HRMS (EI-TOF) m/z: [M]+ Calcd for C10H9F3O:
202.0605; Found: 202.0602.
d
ppm 7.25 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 4.31 (q,
J = 8.2 Hz, 3H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3)
ppm 155.8,
131.5, 129.5, 123.3 (q, J = 278.1 Hz), 115.7, 66.1 (q, J = 35.5 Hz), 17.3.
19F NMR (376 MHz, CDCl3)
ppm ꢁ74.02 (t, J = 8.2 Hz, 3F). IR (KBr)
4.2.9. 2-Chloro-1-methyl-4-(2,2,2-trifluoroethoxy)benzene (2i)
Compound 2i was prepared according to the general procedure
from 3-chloro-4-methylphenyl boronic acid (85.2 mg, 0.5 mmol,
1.0 equiv). After purification by silica gel column chromatography
using n-hexane as the eluent, compound 2i was obtained as
d
d
ymax 2923, 1595, 1492, 1288, 1236, 1169, 1074, 973, 821, 691 cmꢁ1
.
MS (EI): m/z (%) 222 [M]+. HRMS (EI-TOF) m/z: [M]+ Calcd for
colorless oil (90.6 mg, 81%). 1H NMR (400 MHz, CDCl3)
d
ppm 7.14
(d, J = 8.4, 1H), 6.95 (d, J = 2.7 Hz, 1H), 6.75 (dd, J = 8.4, 2.7 Hz, 1H),
4.29 (q, J = 8.1 Hz, 2H), 2.30 (s, 3H). 13C NMR (100 MHz, CDCl3)
ppm 156.0, 134.9, 131.5, 130.1, 123.2 (q, J = 278.3 Hz), 115.9, 113.5,
66.2 (q, J = 35.7 Hz), 19.1. 19F NMR (376 MHz, CDCl3)
C9H9F3OS: 222.0326; Found: 222.0329.
d
4.2.5. 1-(Tert-butyl)-4-(2,2,2-trifluoroethoxy)benzene (2e)
Compound 2e was prepared according to the general procedure
from 4-(tert-butyl)phenyl boronic acid (89.1 mg, 0.5 mmol, 1.0
equiv). After purification by silica gel column chromatography
using n-hexane as the eluent, compound 2e was obtained as a
d
ppm ꢁ74.05
(t, J = 8.1 Hz, 3F). IR (KBr) ymax 2928, 1609, 1496, 1288, 1165, 1085,
976, 909, 836, 812, 660 cmꢁ1. MS (EI): m/z 224 [M]+. HRMS (EI-TOF)
m/z: [M]+ Calcd for C9H8ClF3O: 224.0216; Found: 224.0220.
colorless oil (83.5 mg, 72%). 1H NMR (400 MHz, CDCl3)
d
ppm 7.33
(d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 4.32 (q, J = 8.2 Hz, 2H), 1.30
(s, 9H). 13C NMR (100 MHz, CDCl3)
ppm 155.3, 145.4, 126.5, 123.5
(q, J = 278.2 Hz), 114.5, 66.1 (q, J = 35.4 Hz), 34.2, 31.4. 19F NMR
4.2.10. 1-Bromo-4-(2,2,2-trifluoroethoxy)benzene (2j)
d
Compound 2j was prepared according to the general procedure
from 4-bromophenyl boronic acid (100.4 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane as the eluent, compound 2j was obtained as a white solid
(376 MHz, CDCl3)
d
ppm ꢁ74.09 (t, J = 8.2 Hz, 3F). IR (KBr) ymax
2964, 1513, 1286, 1239, 1165, 1078, 975, 829 cmꢁ1. MS (EI): m/z 232
[M]+. HRMS (EI-TOF) m/z: [M]+ Calcd for C12H15F3O: 232.1075;
Found: 232.1081.
(91.5 mg, 72%). mp 38–40 ꢀC. 1H NMR (400 MHz, CDCl3)
d
ppm 7.41
(d, J = 9.1 Hz, 2H), 6.81 (d, J = 9.1 Hz, 2H), 4.30 (q, J = 8.1 Hz, 2H). 13
NMR (100 MHz, CDCl3) ppm 156.5, 132.6, 123.2 (q, J = 278.1 Hz),
116.8, 115.0, 66.1 (q, J = 35.8 Hz). 19F NMR (376 MHz, CDCl3)
ppm
C
d
4.2.6. N-(3-(2,2,2-trifluoroethoxy)phenyl)acetamide (2f)
d
Compound 2f was prepared according to the general procedure
from 3-acetamidophenyl boronic acid (89.5 mg, 0.5 mmol, 1.0
equiv). After purification by silica gel column chromatography
using n-hexane/ethyl acetate (3/1) as the eluent, compound 2f
was obtained as a white solid (60.3 mg, 52%). mp 108–109 ꢀC. 1H
ꢁ73.99 (t, J = 8.1 Hz, 3F). IR (KBr) ymax 3050, 2937, 1597, 1513, 1452,
1156, 1076, 974, 830, 670 cmꢁ1. MS (EI): m/z 254 [M]+. HRMS (EI-
TOF) m/z: [M]+ Calcd for C8H6BrF3O: 253.9554; Found: 253.9560.
4.2.11. 1-Iodo-4-(2,2,2-trifluoroethoxy)benzene (2k)
NMR (400 MHz, CDCl3)
d
ppm 7.41 (d, J = 2.3 Hz, 1H), 7.32 (bs, 1H),
Compound 2k was prepared according to the general procedure
from 4-iodophenyl boronic acid (123.9 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane as the eluent, compound 2k was obtained as a colorless oil
7.26–7.17 (m, 2H), 6.96 (d, J = 8.1 Hz, 1H), 6.68 (dd, J = 8.2, 2.5 Hz,
1H), 4.33 (q, J = 8.1 Hz, 2H), 2.16 (s, 3H). 13C NMR (100 MHz, CDCl3)
d
ppm 169.0, 157.8, 139.5, 129.9, 123.3 (q, J = 277.8 Hz), 113.7, 110.7,
106.8, 65.8 (q, J = 35.6 Hz), 24.5. 19F NMR (376 MHz, CDCl3)
d
ppm
(102.5 mg, 68%). 1H NMR (400 MHz, CDCl3)
d
ppm 7.59 (d, J = 8.2 Hz,
2H), 6.70 (d, J = 8.2 Hz, 2H), 4.30 (q, J = 8.1 Hz, 2H). 13C NMR
(100 MHz, CDCl3) ppm 157.3, 138.6, 123.2 (q, J = 278.2 Hz), 117.3,
85.1, 65.9 (q, J = 35.9 Hz). 19F NMR (376 MHz, CDCl3)
ꢁ74.00 (t, J = 8.1 Hz, 3F). IR (KBr) ymax 3306, 1670, 1602, 1447,
1278, 1161, 974, 869, 770, 684 cmꢁ1. MS (EI): m/z 233 [M]+. HRMS
(EI-TOF) m/z: [M]+ Calcd for C10H10F3NO2: 233.0664; Found:
233.0659.
d
d
ppm ꢁ73.95
(t, J = 8.1 Hz, 3F). IR (KBr) ymax 2940, 1586, 1485, 1289, 1236, 1164,
1057, 1004, 975, 819, 681 cmꢁ1. MS (EI): m/z 302 [M]+. HRMS (EI-
TOF) m/z: [M]+ Calcd for C8H6IF3O: 301.9415; Found: 301.9420.
4.2.7. 5-(2,2,2-Trifluoroethoxy)benzo[d][1,3]dioxole (2 g)
Compound 2 g was prepared according to the general procedure
from benzo[d][1,3]dioxol-5-ylboronic acid (83.5 mg, 0.5 mmol, 1.0
equiv). After purification by silica gel column chromatography
using n-hexane as the eluent, compound 2 g was obtained as a
white solid (76.5 mg, 69%). mp 56–57 ꢀC. 1H NMR (400 MHz, CDCl3)
4.2.12. Ethyl 4-(2,2,2-trifluoroethoxy)benzoate (2l)
Compound 2l was prepared according to the general procedure
from 4-(ethoxycarbonyl)phenyl boronic acid (97.0 mg, 0.5 mmol,
1.0 equiv). After purification by silica gel column chromatography
using n-hexane/ethyl acetate (10/1) as the eluent, compound 2l
was obtained as a white solid (93.1 mg, 75%). mp 58–60 ꢀC. 1H NMR
d
ppm 6.70 (d, J = 8.4 Hz,1H), 6.53 (d, J = 2.6 Hz, 1H), 6.35 (dd, J = 8.4,
2.6 Hz, 1H), 5.92 (s, 2H), 4.25 (q, J = 8.2 Hz, 2H). 13C NMR (100 MHz,
CDCl3) ppm 152.9,148.5, 143.1,123.3 (q, J = 278.1 Hz),108.0,106.6,
101.5, 99.0, 67.2 (q, J = 35.3 Hz). 19F NMR (376 MHz, CDCl3)
ppm
d
(400 MHz, CDCl3)
2H), 4.39 (q, J = 8.1 Hz, 2H), 4.34 (q, J = 7.2 Hz, 2H), 1.37 (t, J = 7.1 Hz,
4H). 13C NMR (100 MHz, CDCl3)
ppm 166.0, 160.7, 131.7, 124.8,
123.1 (q, J = 277.9 Hz), 114.3, 65.5 (q, J = 36.3 Hz), 60.9, 14.3. 19F NMR
(376 MHz, CDCl3)
ppm ꢁ73.90 (t, J = 8.1 Hz, 3F). IR (KBr) ymax
d ppm 8.02 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz,
d
ꢁ74.16 (t, J = 8.2 Hz, 3F). IR (KBr) ymax 2898, 1488, 1288, 1170, 1039,
973, 941, 857, 816 cmꢁ1. MS (EI): m/z 220 [M]+. HRMS (EI-TOF) m/z:
[M]+ Calcd for C9H7F3O3: 220.0347; Found: 220.0344.
d
d
Please cite this article in press as: K. Zhang, et al., Copper-catalyzed oxidative trifluoroethoxylation of aryl boronic acids with CF3CH2OH, J.
Fluorine Chem. (2016), http://dx.doi.org/10.1016/j.jfluchem.2016.07.008

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FLUOR 8814 No. of Pages 8
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2988, 1701, 1608, 1511, 1282, 1168, 1106, 974, 847, 769, 741,
695 cmꢁ1. MS (EI): m/z 248 [M]+. HRMS (EI-TOF) m/z: [M]+ Calcd
for: C11H11F3O3: 248.0660; Found: 248.0659.
7.52 (t, J = 8.2 Hz, 1H), 7.34–7.30 (m, 1H), 4.46 (q, J = 7.9 Hz, 2H). 13
NMR (100 MHz, CDCl3) ppm 157.7, 149.2, 130.5, 122.9 (q,
J = 277.9 Hz) 121.9, 117.6, 109.3, 66.1 (q, J = 36.2 Hz). 19F NMR
(376 MHz, CDCl3)
3103, 1585, 1533, 1483, 1353, 1321, 1163, 1066, 973, 859, 801, 738,
658 cmꢁ1. MS (EI): m/z 221 [M]+. HRMS (EI-TOF) m/z: [M]+ Calcd for
C8H6F3NO3: 221.0300; Found: 221.0307.
C
d
d
ppm ꢁ73.83 (t, J = 7.9 Hz, 3F). IR (KBr) ymax
4.2.13. Benzyl 4-(2,2,2-trifluoroethoxy)benzoate (2m)
Compound 2m was prepared according to the general proce-
dure from 4-((benzyloxy)carbonyl)phenyl boronic acid (128.0 mg,
0.5 mmol, 1.0 equiv). After purification by silica gel column
chromatography using n-hexane/ethyl acetate (10/1) as the eluent,
compound 2m was obtained as a white solid (121.0 mg, 78%). mp
4.2.18. 4-(2,2,2-Trifluoroethoxy)benzonitrile (2r)
Compound 2r was prepared according to the general procedure
from 4-cyanophenyl boronic acid (73.5 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane/ethyl acetate (20/1) as the eluent, compound 2r was
obtained as a white solid (58.1 mg, 58%). 1H NMR (400 MHz, CDCl3)
67–68 ꢀC. 1H NMR (400 MHz, CDCl3)
d
ppm 8.05 (d, J = 9.0 Hz, 2H),
7.47–7.28 (m, 5H), 6.95 (d, J = 9.0 Hz, 2H), 5.33 (s, 2H), 4.39 (q,
J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3)
ppm 165.8, 160.8, 136.1,
132.0, 128.6, 128.3, 128.2, 124.4, 123.5 (q, J = 278.7 Hz), 114.4, 66.7,
65.5 (q, J = 36.0 Hz). 19F NMR (376 MHz, CDCl3)
d
d
ppm ꢁ73.87 (t,
d
ppm 7.65 (d, J = 8.9 Hz, 2H), 7.04 (d, J = 8.9 Hz, 2H), 4.44 (q,
J = 7.9 Hz, 2H). 13C NMR (100 MHz, CDCl3)
ppm 160.3, 134.2, 122.9
(q, J = 277.9 Hz), 118.6, 115.5, 106.1, 65.6 (q, J = 36.3 Hz). 19F NMR
J = 8.0 Hz, 3F). IR (KBr) ymax 2949, 1718, 1607, 1509, 1456, 1288, 1101,
975, 865, 752, 696 cmꢁ1. MS (EI): m/z 310 [M]+. HRMS (EI-TOF) m/z:
[M]+ Calcd for C16H13F3O3: 310.0817; Found: 310.0815.
d
(376 MHz, CDCl3)
d
ppm ꢁ73.83 (t, J = 7.9 Hz, 3F). MS (EI): m/z 201
[M]+. HRMS (EI-TOF) m/z: [M]+ Calcd for C9H6F3NO: 201.0401;
Found: 201.0399. These assignment matched with that previously
reported [7b].
4.2.14. 1-(4-(2,2,2-Trifluoroethoxy)phenyl)ethan-1-one (2n)
Compound 2n was prepared according to the general procedure
from 4-acetylphenyl boronic acid (82.0 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane/ethyl acetate (10/1) as the eluent, compound 2n was
obtained as a white solid (73.0 mg, 67%). mp 72–73 ꢀC. 1H NMR
4.2.19. 9,9-Dimethyl-2-(2,2,2-trifluoroethoxy)-9H-fluorene (2s)
Compound 2s was prepared according to the general procedure
from 9,9-dimethyl-9H-fluoren-2-yl boronic acid (119.0 mg,
0.5 mmol, 1.0 equiv). After purification by silica gel column
chromatography using n-hexane as the eluent, compound 2s
was obtained as a colorless oil (87.2 mg, 60%). 1H NMR (400 MHz,
(400 MHz, CDCl3)
2H), 4.42 (q, J = 8.0 Hz, 2H), 2.58 (s, 3H). 13C NMR (100 MHz, CDCl3)
ppm 196.6,160.8,131.9,130.7,123.1 (q, J = 277.8 Hz),114.5, 65.5 (q,
d ppm 7.97 (d, J = 8.9 Hz, 2H), 6.99 (d, J = 8.9 Hz,
d
J = 36.2 Hz), 26.4. 19F NMR (376 MHz, CDCl3)
d
ppm ꢁ73.87 (t,
CDCl3)
7.38–7.26 (m, 2H), 7.04 (d, J = 2.4 Hz, 1H), 6.90 (dd, J = 8.3, 2.4 Hz,
1H), 4.41 (q, J = 8.1 Hz, 2H),1.48 (s, 6H). 13C NMR (100 MHz, CDCl3)
d ppm 7.65 (dd, J = 8.0, 4.3 Hz, 2H), 7.42 (d, J = 8.0 Hz, 1H),
J = 8.0 Hz, 3F). MS (EI): m/z 218 [M]+. HRMS (EI-TOF) m/z: [M]+ Calcd
for C10H9F3O2: 218.0555; Found: 218.0559.
d
ppm 157.3, 155.8, 153.3, 138.7, 134.0, 127.1, 126.7, 123.5 (q,
4.2.15. 4-(2,2,2-Trifluoroethoxy)benzaldehyde (2o)
J = 278.0 Hz), 122.6, 120.9, 119.5, 113.4, 110.0, 66.3 (q, J = 35.3 Hz),
Compound 2o was prepared according to the general procedure
from 4-formylphenyl boronic acid (75.0 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane/ethyl acetate (10/1) as the eluent, compound 2o was
obtained as a colorless oil (62.3 mg, 61%). 1H NMR (400 MHz,
47.0, 27.2.19F NMR (376 MHz, CDCl3)
d
ppm ꢁ73.95 (t, J = 8.1 Hz, 3F).
IR (KBr) ymax 2961,1611, 1488,1426,1260,1165,1088, 974, 775, 758,
735, 665 cmꢁ1. MS (EI): m/z 292 [M]+. HRMS (EI-TOF) m/z: [M]+
Calcd for C17H15F3O: 292.1075; Found: 292.1070.
CDCl3)
2H), 4.45 (q, J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3)
161.8, 132.0, 131.4, 123.0 (q, J = 277.9 Hz), 115.1, 65.6 (q, J = 36.3 Hz).
19F NMR (376 MHz, CDCl3)
ymax 2833, 1700, 1601, 1509, 1289, 1245, 1162, 1072, 975, 896, 831,
678 cmꢁ1. MS (EI): m/z 204 [M]+. HRMS (EI-TOF) m/z: [M]+ Calcd for
C9H7F3O2: 204.0398; Found: 204.0397.
d
ppm 9.94 (s, 1H), 7.89 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz,
4.2.20. 2-Methoxy-6-(2,2,2-trifluoroethoxy)naphthalene (2t)
Compound 2t was prepared according to the general procedure
from 6-methoxynaphthalen-2-yl boronic acid (101.0 mg, 0.5 mmol,
1.0 equiv). After purification by silica gel column chromatography
using n-hexane as the eluent, compound 2t was obtained as a
white solid (89.3 mg, 70%). mp 91–92 ꢀC. 1H NMR (400 MHz, CDCl3)
d
ppm 190.6,
d
ppm ꢁ73.83 (t, J = 8.0 Hz, 3F). IR (KBr)
d
ppm 7.67 (d, J = 8.9 Hz, 1H), 7.63 (d, J = 8.9 Hz, 1H), 7.19–7.12 (m,
2H), 7.11 (d, J = 2.8 Hz, 2H), 4.43 (q, J = 8.0 Hz, 2H), 3.89 (s, 3H). 13
NMR (100 MHz, CDCl3) ppm 156.8, 153.8, 130.7, 129.3, 128.7,
128.3, 123.4 (d, J = 278.0 Hz), 119.4, 118.6, 108.2, 106.1, 66.1 (q,
J = 35.8 Hz), 55.3. 19F NMR (376 MHz, CDCl3)
C
4.2.16. 1-Nitro-4-(2,2,2-trifluoroethoxy)benzene (2p)
d
Compound 2p was prepared according to the general procedure
from 4-nitrophenyl boronic acid (83.5 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane/ethyl acetate (20/1) as the eluent, compound 2p was
obtained as a white solid (60.2 mg, 55%). 1H NMR (400 MHz, CDCl3)
8.24 (d, J = 9.2 Hz, 2H), 7.06 (d, J = 9.2 Hz, 2H), 4.49 (q, J = 7.9 Hz, 2H).
d
ppm ꢁ73.89 (t,
J = 8.0 Hz, 3F). IR (KBr) ymax 2966, 1606, 1395, 1283, 1164, 1029, 975,
853, 663 cmꢁ1. MS (EI): m/z 256 [M]+. HRMS (EI-TOF) m/z: [M]+
Calcd for C13H11F3O2: 256.0711; Found: 256.0709.
13C NMR (100 MHz, CDCl3)
d
ppm 161.8, 142.8, 126.0, 122.8 (q,
4.2.21. 3-(2,2,2-Trifluoroethoxy)quinoline (2u)
J = 278.0 Hz),114.9, 65.8 (q, J = 36.2 Hz). 19F NMR (376 MHz, CDCl3)
d
Compound 2u was prepared according to the general procedure
from quinolin-3-yl boronic acid (86.5 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane/ethyl acetate (5/1) as the eluent, compound 2u was
obtained as a white solid (73.5 mg, 65%). mp 62–64 ꢀC. 1H NMR
ppm ꢁ73.85 (t, J = 7.9 Hz, 3F). MS (EI): m/z 221 [M]+. HRMS (EI-TOF)
m/z: [M]+ Calcd for C8H6F3NO3: 221.0300; Found: 221.0298. These
assignment matched with that previously reported [7b]
4.2.17. 1-Nitro-3-(2,2,2-trifluoroethoxy)benzene (2q)
(400 MHz, CDCl3) d ppm 8.71 (d, J = 2.8 Hz, 1H), 8.05 (d, J = 8.3 Hz,
Compound 2q was prepared according to the general procedure
from 3-nitrophenyl boronic acid (83.5 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane/ethyl acetate (20/1) as the eluent, compound 2q was
obtained as a white solid (78.5 mg, 71%). mp 58–59 ꢀC. 1H NMR
1H), 7.70 (d, J = 8.1 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.51 (t, J = 7.5 Hz,
1H), 7.39 (d, J = 2.8 Hz, 1H), 4.46 (q, J = 8.0 Hz, 2H). 13C NMR
(100 MHz, CDCl3)
127.6, 126.9, 123.1 (q, J = 278.1 Hz), 114.5, 65.9 (q, J = 36.0 Hz). 19F
NMR (376 MHz, CDCl3)
ppm ꢁ73.67 (t, J = 8.0 Hz, 3F). IR (KBr) ymax
3028, 1608, 1443, 1283, 1161, 978, 855, 749, 653 cmꢁ1. MS (EI): m/z
d ppm 150.7, 144.2, 143.8, 129.2, 128.2, 127.8,
d
(400 MHz, CDCl3)
d ppm 7.96–7.92 (m, 1H), 7.79 (t, J = 2.3 Hz, 1H),
Please cite this article in press as: K. Zhang, et al., Copper-catalyzed oxidative trifluoroethoxylation of aryl boronic acids with CF3CH2OH, J.
Fluorine Chem. (2016), http://dx.doi.org/10.1016/j.jfluchem.2016.07.008

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FLUOR 8814 No. of Pages 8
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227 [M]+. HRMS (EI-TOF) m/z: [M]+ Calcd for C11H8F3NO: 227.0558;
Found: 227.0560.
respectively via syringe. The mixture was stirred vigorously under
a balloon of air at room temperature for 14 h. Then the reaction
solution was vacuum-filtered over a sintered-glass funnel with a
tightly packed pad of Celite (1 cm thick), and the filter cake was
rinsed with DCM (10 mL). The combined filtrates were concentrat-
ed. The residue was purified with silica gel column chromatogra-
phy using n-hexane/ethyl acetate (20/1) as the eluent to provide 2c
(21.8 mg, 41%) and 2p (3.0 mg, 6%).
4.2.22. 9-(4-(2,2,2-Trifluoroethoxy)phenyl)-9H-carbazole (2v)
Compound 2v was prepared according to the general procedure
from 4-(9H-carbazol-9-yl)phenyl boronic acid (143.6 mg,
0.5 mmol, 1.0 equiv). After purification by silica gel column
chromatography using n-hexane/ethyl acetate (5/1) as the eluent,
compound 2v was obtained as a white solid (139.5 mg, 82%). mp
In a nitrogen-filled glove box, a 25 mL Schlenk tube equipped
with a magnetic stir bar was charged with Cu(OAc)2 (3.7 mg,
0.02 mmol, 0.1 equiv), 4-biphenyl boronic acid 1a (39.6 mg,
0.2 mmol, 1.0 equiv), Na2CO3 (42.4 mg, 1.0 mmol, 2.0 eq.) and 4 Å
MS (100.0 mg). The tube was evacuated and backfilled with air for 3
times. Then DCE (2.0 mL), pyridine (17.5 mg, 0.2 mmol, 1.0 equiv),
CF3CH2OH (40.0 mg, 0.4 mmol, 2.0 equiv) and CH3CH2OH (18.5 mg,
0.4 mmol, 2.0 equiv) were added respectively via syringe. The
mixture was stirred vigorously under a balloon of air at room
temperature for 14 h. Then the reaction solution was vacuum-
filtered over a sintered-glass funnel with a tightly packed pad of
Celite (1 cm thick), and the filter cake was rinsed with DCM
(10 mL). The combined filtrates were concentrated. The residue
was purified with silica gel column chromatography using n-
hexane as the eluent to provide 2a (32.7 mg, 65%) and 2a' (4.5 mg,
117–118 ꢀC. 1H NMR (400 MHz, CDCl3)
7.53–7.46 (m, 2H), 7.45–7.40 (m, 2H), 7.36–7.27 (m, 4H), 7.19–7.11
(m, 2H), 4.44 (q, J = 8.1 Hz, 2H). 13C NMR (100 MHz, CDCl3)
ppm
156.5, 141.2, 132.2, 128.8, 126.0, 123.3 (q, J = 278.0 Hz), 123.3, 120.4,
120.0, 116.3, 109.6, 66.2 (q, J = 35.9 Hz). 19F NMR (376 MHz, CDCl3)
d ppm 8.16 (d, J = 7.8 Hz, 2H),
d
d
ppm ꢁ73.83 (t, J = 8.1 Hz, 3F). IR (KBr) ymax 2943, 1580, 1453, 1236,
1165, 966, 753, 727 cmꢁ1. MS (EI): m/z 341 [M]+. HRMS (EI-TOF)
m/z: [M]+ Calcd for C20H14F3NO: 341.1027; Found: 341.1020.
4.2.23. 4-(2,2,2-Trifluoroethoxy)-1,10-biphenyl (2w)
Compound 2w was prepared according to the general proce-
dure from dibenzo[b,d]thiophen-4-yl boronic acid (114.1 mg,
0.5 mmol, 1.0 equiv). After purification by silica gel column
chromatography using n-hexane as the eluent, compound 2w
was obtained as a white solid (49.3 mg, 35%). mp 50–51 ꢀC. 1H NMR
11%). Compound 2a': 1H NMR (400 MHz, CDCl3)
d ppm 7.56–7.50
(400 MHz, CDCl3)
7.43 (m, 2H), 7.41 (t, J = 7.9 Hz, 1H), 6.91 (d, J = 7.9 Hz, 1H), 4.56 (q,
J = 8.1 Hz, 2H). 13C NMR (100 MHz, CDCl3)
ppm 152.4, 139.8, 138.0,
135.6, 128.8, 123.3 (d, J = 278.1 Hz), 127.1, 125.6, 124.5, 123.0, 122.0,
116.0, 108.8, 66.4 (q, J = 36.1 Hz). 19F NMR (376 MHz, CDCl3)
ppm
d
ppm 8.17–8.08 (m,1H), 7.89–7.84 (m, 2H), 7.51–
(m, 4H), 7.41 (t, J = 8.0 Hz, 2H), 7.31–7.28 (m, 1H), 6.96 (d, J = 8.8 Hz,
2H), 4.07 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H); MS (EI): m/z 198
[M]+. These assignment matched with that previously reported
[14].
d
d
ꢁ73.84 (t, J = 8.1 Hz, 3F). IR (KBr) ymax 2968, 1568, 1443, 1287, 1248,
1166, 1075, 973, 748 cmꢁ1. MS (EI): m/z 282 [M]+. HRMS (EI-TOF)
m/z: [M]+ Calcd for C14H9F3OS: 282.0326; Found: 282.0321.
Acknowledgements
We thank the National Natural Science Foundation of China
(21421002, 21332010, 21272036), the National Basic Research
Program of China (2012CB21600), and the Fundamental Research
Funds for the Central Universities for funding this work.
4.2.24. (R)-tert-butyl-(1-(naphthalen-1-yl)ethyl)(3-(3-(2,2,2
trifluoroethoxy)phenyl)propyl)carbamate (2x)
Compound 2x was prepared according to the general procedure
from
(S)-3-(3-((tert-butoxycarbonyl)(1-(naphthalen-1-yl)ethyl)
Appendix A. Supplementary data
amino)propyl)phenyl boronic acid (216.7 mg, 0.5 mmol, 1.0 equiv).
After purification by silica gel column chromatography using n-
hexane/ethyl acetate (5/1) as the eluent, compound 2x was
obtained as a viscous light yellow liquid (163.5 mg, 67%). 1H NMR
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.
jfluchem.2016.07.008.
(400 MHz, CDCl3)
d ppm 8.17 (d, J = 8.2 Hz, 1H), 7.85 (d, J = 7.7, 1H),
7.79 (dd, J = 6.7, 2.7 Hz, 1H), 7.59–7.44 (m, 2H), 7.43–7.38 (m, 2H),
7.07 (t, J = 7.9 Hz, 1H), 6.65 (dd, J = 8.2, 2.6 Hz, 1H), 6.42 (d, J = 7.7 Hz,
1H), 6.22–6.20 (m, 2H), 4.22 (q, J = 8.2 Hz, 2H), 2.96 (brs, 1H), 2.75
(brs,1H), 2.10 (brs, 2H),1.59 (d, J = 6.8 Hz, 3H),1.51 (s, 9H),1.34–1.20
References
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4.3. Comparing the reactivities of different aryl boronic acids and
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In a nitrogen-filled glove box, a 25 mL Schlenk tube equipped
with a magnetic stir bar was charged with Cu(OAc)2 (3.7 mg,
0.02 mmol, 0.1 equiv), 4-phenoxyphenyl boronic acid 1c (42.8 mg,
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Fluorine Chem. (2016), http://dx.doi.org/10.1016/j.jfluchem.2016.07.008