Synthesis of Silylbiaryl Triflates by Chemoselective Suzuki Reaction

Article abstract of DOI:10.1055/s-0036-1588332

A modular approach for the synthesis of functionalized silylbiaryl triflates has been developed. Iodinated silylaryl triflates were prepared via a gram-scale diiodination reaction, followed by a one-flask transformation, in 42-52% overall yield. The iodin

Full text of DOI:10.1055/s-0036-1588332

SYNTHESIS
0
0
3
9
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7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–J
paper
A
B. V. Moreira et al.
Paper
Synthesis
Synthesis of Silylbiaryl Triflates by Chemoselective Suzuki
Reaction
Bárbara V. Moreira
R2
B(OH)2
Ana Carolina A. Muraca
R2
gram-scale
reaction
(1.1 equiv)
Cristiano Raminelli*
I
PdCl2(PPh3)2 (5 mol%)
1) I2, H2O2
R1
OTf
R1
OH
R1
OTf
Instituto de Ciências Ambientais, Químicas e Farmacêuticas,
Universidade Federal de São Paulo, Rua Prof. Artur Riedel,
275, Diadema, SP 09972-270, Brazil
K2CO3 (3 equiv)
THF/H2O (1:1)
80 °C, 24 h
2) HMDS
3) n-BuLi
4) Tf2O
TMS
TMS
5 examples
12 examples
raminelli@unifesp.br
47–81% yield
one-flask
transformation
optimized conditions
Received: 16.08.2016
Accepted after revision: 16.09.2016
Published online: 19.10.2016
lylaryl triflates.4,5 However, a critical evaluation reveals that
the approaches for the syntheses of silylaryl triflates have
limitations, which are responsible for the restriction of
structural diversity associated with the silylaryl triflates
eventually produced. Currently, for instance, silylbiaryl tri-
flates 1 have been synthesized exclusively from halogenat-
ed phenylphenols 5.6 This approach restricts the substitu-
tion pattern of the silylbiaryl triflates 1 to a limited number
of commercially available halo(phenyl)phenols 5 (Scheme
1).
DOI: 10.1055/s-0036-1588332; Art ID: ss-2016-m0573-op
Abstract A modular approach for the synthesis of functionalized silyl-
biaryl triflates has been developed. Iodinated silylaryl triflates were pre-
pared via a gram-scale diiodination reaction, followed by a one-flask
transformation, in 42–52% overall yield. The iodinated silylaryl triflates
were subjected to a novel chemoselective Suzuki reaction with arylbo-
ronic acids, using PdCl2(PPh3)2 as catalyst and K2CO3 as base in THF/H2O
(1:1) at 80 °C for 24 hours, which afforded silylbiaryl triflates in 47–81%
yield.
Seeking advances for the synthesis of silylaryl triflates,
we conceived the possibility of achieving silylbiaryl triflates
1 through a modular approach involving the preparation of
iodinated silylaryl triflates 2 from their corresponding phe-
nols 4, employing known transformations,7,8 followed by a
novel chemoselective Suzuki cross-coupling9 between the
iodinated silylaryl triflates 2 and arylboronic acids 3, with
the aim of producing functionalized silylbiaryl triflates 1
(Scheme 1).
Key words iodinated silylaryl triflates, chemoselective cross-coupling,
Suzuki reaction, silylbiaryl triflates, benzyne chemistry
Over the last years, silylaryl triflates have expanded
benzyne chemistry applications in preparative organic
chemistry.1 In this context, arynes generated from silylaryl
triflates have been employed in total syntheses of natural
products2 and preparations of functional materials.3 Pre-
sumably, the dissemination of silylaryl triflates as aryne
precursors in organic preparations1–3 is related to some ad-
vantages, including mild conditions involved in the reac-
tions1,4 and well-established routes for the production of si-
In order to accomplish our goals, we subjected phenols
4 to a gram-scale reaction with I2 and 30% H2O2 in water,
employing mechanical stirring at room temperature or
R2
R2
established
approach
our
approach
I
R2
R1
OH
R1
OTf
TMS
target
R1
OTf
TMS
(HO)2B
+
5
X
2
1
3
X: Br and I
R1
OH
4
Scheme 1 Approaches to produce silylbiaryl triflates 1
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

B
B. V. Moreira et al.
Paper
Synthesis
50 °C for 24 hours, promoting the formation of diiodinated
The sequence of the subsequent one-flask transforma-
tion was optimized employing 2,6-diiodophenol (6a), vary-
ing the amount of n-BuLi (0.9 to 1.1 equiv) and the solvent
(THF and Et2O) for the iodine–lithium exchange reaction,
and the time for the reaction with triflic anhydride (0.5 to
18 h). Thereafter, five iodinated silylaryl triflates 2, contain-
ing an electron-donating or -withdrawing group, or a halo-
gen (Cl and Br) in their structures, were obtained in 59–64%
isolated yield (Scheme 2).8
Next, optimization of the chemoselective Suzuki reac-
tion was carried out employing the iodinated silylaryl tri-
flate 2a and phenylboronic acid (3a), evaluating several pal-
ladium catalysts, bases, and solvents or mixtures, and dif-
ferent temperatures and times, providing the silylbiaryl
triflate 1a (Table 1).
phenols 6 in 71–83% yield (Scheme 2).7
I
I2 (1.5 equiv)
30% aq H2O2 (3 equiv)
R1
OH
R1
OH
H2O, r.t. or 50 °C
24 h
I
4
gram-scale reaction
(10 mmol scale)
6
1) HMDS (1.5 equiv)
80 °C, N2, 2 h
2a: R1 = H (59%)
6a: R1 = H (r.t.; 71%)
2) n-BuLi (0.9 equiv)
6b: R1 = CH3 (50 °C; 77%) 2b: R1 = CH3 (59%)
6c: R1 = CF3 (50 °C; 83%) 2c: R1 = CF3 (63%)
Et2O, –78 °C to r.t., N2, 2 h
3) Tf2O (1.5 equiv)
6d: R1 = Cl (50 °C; 79%)
6e: R1 = Br (50 °C; 75%)
2d: R1 = Cl (64%)
2e: R1 = Br (61%)
–78 °C to r.t., N2, 18 h
I
R1
OTf
Allowing iodinated silylaryl triflate 2a to react with
phenylboronic acid (3a) using Pd(PPh3)4 as catalyst and
K2CO3 as base in toluene/water (1:1) at 80 °C for 24 hours,
we obtained silylbiaryl triflate 1a in 15% isolated yield (Ta-
ble 1, entry 1). In an attempt to improve the yield, we per-
formed the microwave-assisted reaction between com-
pounds 2a and 3a employing Pd(PPh3)4 as catalyst and
TMS
2
one-flask transformation
(5 mmol scale)
Scheme 2 Route for the synthesis of iodinated silylaryl triflates 2
Table 1 Chemoselective Suzuki Cross-Coupling for the Preparation of Silylbiaryl Triflate 1aa
undesired product
I
(HO)2B
palladium catalyst
OTf
TMS
OTf
TMS
+
base
solvent(s)
TMS
2a
1a
3a
7
temperature, time
Entry
Palladium catalyst (% mol)
Base (equiv)
Solvent(s)
Temp (°C)
Time (h)
Isolatedyield
(%) of 1a
1
2
Pd(PPh3)4 (5)
K2CO3 (3)
K2CO3 (3)
K2CO3 (3)
K2CO3 (2.5)
K2CO3 (2.5)
K2CO3 (2.5)
K2CO3 (2)
K2CO3 (2)
K2CO3 (3)
K2CO3 (3)
K2CO3 (3)
KOH (3)
toluene/H2O (1:1)
toluene/H2O (1:1)
toluene/H2O (1:1)
acetone/H2O (1:1)
acetone/H2O (1:1)
acetone/H2O (1:1)
H2O
80
24
3
15
25
25
15c
20c
6c
Pd(PPh3)4 (5)
150 (MO)b
150 (MO)b
reflux
reflux
r.t.
3
Pd(PPh3)4 (10)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
10% Pd/C (5)
3
4
24
2
5
6
2
7
r.t.
24
24
24
3
0d
8
10% Pd/C (5)
MeOH
r.t.
0d
9
PdCl2(PPh3)2 (5)
PdCl2(PPh3)2 (5)
PdCl2(PPh3)2 (10)
PdCl2(PPh3)2 (5)
PdCl2(PPh3)2 (5)
PdCl2(PPh3)2 (5)
PdCl2(PPh3)2 (5)
toluene/H2O (1:1)
toluene/H2O (1:1)
toluene/H2O (1:1)
toluene/H2O (1:1)
toluene/H2O (1:1)
THF/H2O (1:1)
80
60
36
44
52
42
80
56
10
11
12
13
14
15
150 (MO)b
150 (MO)b
80
3
24
24
24
24
t-BuOK (3)
K2CO3 (3)
K2CO3 (3)
80
80
EtOH/H2O (1:1)
80
a Reaction conditions: 2a (1 mmol), 3a (1.1 mmol), palladium catalyst, base, solvent(s) (3 mL), with stirring.
b Reaction performed in a sealed tube under microwave heating.
c Compound 7 was obtained as the major product, according to GC/MS analysis.
d Compound 1a was not obtained and the starting material 2a was partially recovered.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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B. V. Moreira et al.
Paper
Synthesis
K2CO3 as base in toluene/water (1:1) at 150 °C for 3 hours,
which provided compound 1a in 25% yield (Table 1, entry
2). When the same transformation was carried out with a
higher load of Pd(PPh3)4, no improvement in yield was ob-
served (Table 1, entry 3). When the reaction between iodin-
ated aryne precursor 2a and boronic acid 3a was performed
using Pd(OAc)2 as catalyst and K2CO3 as base in acetone/wa-
ter (1:1) under reflux for 24 hours, triflate 1a was obtained
in 15% yield (Table 1, entry 4). For all reactions using
Pd(OAc)2 as catalyst, compound 7 was obtained as the ma-
jor product, according to GC/MS analysis, which could not
be avoided even with reduced reaction time and tempera-
ture (Table 1, entries 4–6). The desired product 1a was not
obtained when 10% Pd/C was employed as catalyst and the
starting material 2a was partially recovered, according to
GC/MS analysis (Table 1, entries 7 and 8). Treatment of 2a
with 3a using PdCl2(PPh3)2 as catalyst and K2CO3 as base in
toluene/water (1:1) at 80 °C for 24 hours gave triflate 1a in
60% yield (Table 1, entry 9). The microwave-assisted reac-
tion between 2a and 3a using PdCl2(PPh3)2 as catalyst and
K2CO3 as base in toluene/water (1:1) at 150 °C for 3 hours
led to 1a in 36% yield (Table 1, entry 10). When the same
reaction was carried out with a higher load of PdCl2(PPh3)2,
the desired product 1a was isolated in 44% yield (Table 1,
entry 11). Allowing compound 2a to react with 3a using
PdCl2(PPh3)2 as catalyst and KOH as base in toluene/water
(1:1) at 80 °C for 24 hours, we obtained 1a in 52% yield
(Table 1, entry 12). When the reaction was performed with
t-BuOK instead of KOH, silylbiaryl triflate 1a was isolated in
42% yield (Table 1, entry 13). The reaction between 2a and
3a using PdCl2(PPh3)2 as catalyst and K2CO3 as base in
THF/water (1:1) at 80 °C for 24 hours gave 1a in 80% yield
(Table 1, entry 14). Finally, when the reaction was carried
out in ethanol/water (1:1), 1a was isolated in 56% yield (Ta-
ble 1, entry 15).
gave silylbiaryl triflates 1g and 1h in 60% and 58% yield, re-
spectively (Table 2, entries 7 and 8).
When the chloro-substituted aryne precursor 2d was
subjected to reactions with phenylboronic acid (3a) and 3-
nitrophenylboronic acid (3e), silylbiaryl triflates 1i and 1j
were obtained in 56% and 64% yield, respectively (Table 2,
entries 9 and 10). Remarkably, even when the bromo-sub-
stituted aryne precursor 2e was treated with phenylboron-
ic acid (3a) and 3-methylphenylboronic acid (3b), we ob-
tained silylbiaryl triflates 1k and 1l in reasonable yields of
55% and 47%, respectively (Table 2, entries 11 and 12).
The reactions that resulted in compounds 1 (Table 2) did
not promote the formation of byproducts corresponding to
compound 7 (Table 1), according to GC/MS analysis. The de-
velopment of this highly selective reaction to produce silyl-
biaryl triflates 1 was only possible based on the prior exten-
sive optimization of the Suzuki cross-coupling conditions
(Table 1).
Silylbiaryl triflates 1 are versatile reagents in organic
synthesis, which can find application, for example, in nuc-
leophilic additions10 and cycloaddition reactions.4,11 Ac-
cordingly, we subjected silylbiaryl triflates 1c and 1e to nu-
cleophilic couplings with benzoic acid (8) and phenol (4a),
respectively, in the presence of cesium fluoride and regio-
selectively obtained the benzoate 9 in 66% yield and the di-
aryl ether 10 in 58% yield (Scheme 3). In addition, when sil-
ylbiaryl triflate 1k was allowed to react with furan (11) and
cesium fluoride, the Diels–Alder adduct 12 was obtained in
a moderate 41% yield.
OMe
OMe
CsF (4 equiv)
OTf
1c TMS
+
HO2C
MeCN
O
r.t., 24 h
8
O
9
Employing the optimal conditions (Table 1, entry 14),
we examined the scope of the transformation using various
iodinated aryne precursors 2 and arylboronic acids 3 (Table
2). When iodinated silylaryl triflate 2a was allowed to react
with arylboronic acids 3b and 3c, which contain an elec-
tron-donating group, silylbiaryl triflates 1b and 1c were ob-
tained in 60% and 61% yield, respectively (Table 2, entries 2
and 3). The reaction between 2a and 4-chlorophenylboron-
ic acid (3d) gave compound 1d in 50% isolated yield (Table
2, entry 4). Treatment of 2a with arylboronic acid 3e, which
contains an electron-withdrawing group, gave 1e in 81%
yield (Table 2, entry 5). The reaction between 2a and 2-hy-
droxyphenylboronic acid (3f) led to compound 1f in 53%
isolated yield (Table 2, entry 6). Treatment of iodinated
silylaryl triflates 2b and 2c, containing an electron-donat-
ing and -withdrawing group, with phenylboronic acid (3a)
66%
(2 equiv)
O2N
O2N
CsF (3 equiv)
OTf
+
HO
MeCN
r.t., 24 h
10
O
1e TMS
(1.5 equiv)
4a
58%
CsF (2 equiv)
Br
OTf
TMS
Br
+
O
MeCN
O
11
(1.6 equiv)
40 °C, 12 h
1k
12
41%
Scheme 3 Reactions employing silylbiaryl triflates 1
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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B. V. Moreira et al.
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Synthesis
Table 2 Silylbiaryl Triflates 1 Prepared by the Chemoselective Suzuki Reactiona
R2
I
(HO)2B
PdCl2(PPh3)2 (5 mol%)
R1
OTf
TMS
R2
R1
OTf
TMS
+
K2CO3 (3 equiv)
THF/H2O (1:1)
80 °C, 24 h
2
3
1
(1.1 equiv)
Entry
1
Iodinated silylaryl triflate 2
Arylboronic acid 3
Silylbiaryl triflate 1
Isolated yield (%)
I
(HO)2B
OTf
80
OTf
1a TMS
Me
3a
2a
TMS
I
Me
OTf
2
3
4
5
60
61
50
81
(HO)2B
OTf
3b
2a TMS
1b TMS
OMe
I
(HO)2B
OMe
OTf
3c
OTf
2a TMS
1c TMS
Cl
I
(HO)2B
Cl
OTf
3d
OTf
1d TMS
O2N
2a TMS
I
NO2
OTf
(HO)2B
OTf
3e
2a TMS
1e TMS
HO
I
HO
OTf
2a TMS
6
7
(HO)2B
53
60
OTf
3f
1f TMS
I
(HO)2B
Me
OTf
2b TMS
Me
OTf
1g TMS
3a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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Synthesis
Table 2 (continued)
Entry
8
Iodinated silylaryl triflate 2
Arylboronic acid 3
Silylbiaryl triflate 1
Isolated yield (%)
I
(HO)2B
F3C
OTf
58
F3C
OTf
1h TMS
3a
2c
TMS
I
(HO)2B
Cl
OTf
9
10
11
12
56
64
55
47
Cl
OTf
3a
2d TMS
1i TMS
O2N
I
NO2
Cl
Br
Br
OTf
(HO)2B
Cl
OTf
1j TMS
3e
2d TMS
I
(HO)2B
OTf
Br
OTf
3a
2e TMS
1k TMS
Me
I
Me
OTf
2e TMS
(HO)2B
Br
OTf
1l TMS
3b
a Reaction conditions: 2 (1 mmol), 3 (1.1 mmol), PdCl2(PPh3)2 (5 mol%), K2CO3 (3 mmol), THF/H2O (1:1) (3 mL), 80 °C, 24 h, with stirring.
1H and 13C NMR spectra were recorded in CDCl3 on a Bruker Ultra-
shield 300 spectrometer operating at 300 MHz and 75 MHz, respec-
tively. The 1H NMR chemical shifts are given in ppm with respect to
TMS used as internal standard, and the 13C NMR chemical shifts are
given in ppm with respect to the deuterated solvent used as reference.
IR spectra were obtained on a Shimadzu IRPrestige-21 spectropho-
tometer using attenuated total reflectance (ATR) or KBr pellets, in the
4000–400 cm–1 region. Mass spectra were recorded employing a Shi-
madzu GC-2010 gas chromatograph connected to a Shimadzu GCMS-
QP2010 Plus mass spectrometer using electron impact ionization at
70 eV. High-resolution mass spectra were obtained using a Bruker
micrOTOF-Q II time-of-flight mass spectrometer. Melting point values
are uncorrected. Column chromatographic separations were carried
out using 70–230 mesh silica gel. Preparative thin-layer chromato-
graphic separations were carried out using a silica gel matrix with in-
organic binder and fluorescent indicator. Commercially obtained re-
agents were employed without further purification. High-purity CsF
(99.99%) was used. THF and Et2O were distilled from sodium/benzo-
phenone under N2 atmosphere before use.12 MeCN was distilled from
CaH2 under anhydrous conditions prior to use.12 n-BuLi was titrated
against s-BuOH using 1,10-phenanthroline as indicator under N2 at-
The structures of compounds 6a–e are supported by
their 1H NMR, 13C NMR, and mass spectra. The structures of
compounds 2a–e, 1a–l, 9, 10, and 12 were assigned accord-
ing to their IR, 1H NMR, 13C NMR, and mass spectra. All new
compounds (2b–e, 1b–l, 9, 10, and 12) provided HRMS data
that are in agreement with the proposed structures.
In summary, a modular approach for the synthesis of
functionalized silylbiaryl triflates was developed. Iodinated
silylaryl triflates were synthesized via a gram-scale diiodin-
ation reaction, followed by a one-flask transformation, in
42–52% overall yield. A novel chemoselective Suzuki reac-
tion involving the iodinated silylaryl triflates and arylbo-
ronic acids then provided functionalized silylbiaryl triflates
in 47–81% yield. The described synthetic route provides an
alternative method for the preparation of silylbiaryl tri-
flates and should find use in the construction of molecules
with interesting biological properties and applications in
materials science.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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B. V. Moreira et al.
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Synthesis
mosphere.13 Solvents were treated, when necessary, according to lit-
erature methods.12
4-Bromo-2,6-diiodophenol (6e)16
Reaction temperature: 50 °C; yield: 3.19 g (75%); off-white solid; mp
128.6–129.8 °C.
Diiodinated Phenols 6a–e; General Procedure
Rf = 0.26 (hexane).
To a suspension of the appropriate phenol 4a–e (10 mmol) and I2
(3.81 g, 15 mmol) in distilled H2O (50 mL) was added 30% (w/v) aque-
ous H2O2 (3.1 mL, 30 mmol). The mixture was maintained under me-
chanical stirring at r.t. or 50 °C for 24 h. Next, a saturated aqueous
solution of sodium thiosulfate (25 mL) was added to the reaction mix-
ture, which was then extracted with EtOAc (3 × 50 mL). The combined
organic phase was dried over MgSO4. After filtration, the solvent was
evaporated under reduced pressure. The residue was purified by col-
umn chromatography on silica gel (hexane), affording the corre-
sponding diiodinated phenol 6a–e.
1H NMR (300 MHz, CDCl3): δ = 7.70 (s, 2 H), 5.66 (s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 153.1, 140.8, 113.5, 82.4.
MS (EI): m/z (%) = 426 (91.6), 424 (100.0), 292 (3.3), 218 (3.2), 170
(20.1), 91 (12.3), 62 (37.0).
Iodinated Silylaryl Triflates 2a–e; General Procedure
To the appropriate diiodinated phenol 6a–e (5 mmol) was added
HMDS (1.6 mL, 1.21 g, 7.5 mmol). The mixture was maintained under
magnetic stirring and N2 atmosphere at 80 °C for 2 h. Then, the vola-
tile residues were removed under reduced pressure for 30 min. In the
same round-bottomed flask, Et2O (50 mL) was added using a syringe
and needle under anhydrous conditions. The solution was cooled to
–78 °C under magnetic stirring and N2 atmosphere. After that, 1.9 M
n-BuLi in hexane (2.4 mL, 4.5 mmol) was added dropwise using a sy-
ringe and needle. The mixture was heated to r.t. and maintained un-
der magnetic stirring and N2 atmosphere for 2 h. Then, the reaction
mixture was cooled to –78 °C and Tf2O (1.3 mL, 2.12 g, 7.5 mmol) was
added. The mixture was heated to r.t. and maintained under magnetic
stirring and N2 atmosphere for 18 h. Next, a 10% (w/v) aqueous solu-
tion of sodium bicarbonate (50 mL) was added to the reaction mix-
ture, which was then extracted with Et2O (3 × 50 mL). The combined
organic phase was dried over MgSO4. After filtration, the solvent was
evaporated under reduced pressure. The residue was purified by col-
umn chromatography on silica gel (hexane) to afford the correspond-
ing iodinated silylaryl triflate 2a–e.
2,6-Diiodophenol (6a)7b
Reaction temperature: r.t.; yield: 2.46 g (71%); off-white solid; mp
67.6–68.2 °C.
Rf = 0.24 (hexane).
1H NMR (300 MHz, CDCl3): δ = 7.69 (d, J = 7.9 Hz, 2 H), 6.41 (t, J = 7.9
Hz, 1 H), 5.78 (s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 153.4, 139.3, 124.1, 82.4.
MS (EI): m/z (%) = 346 (100.0), 152 (0.2), 129 (3.8), 127 (3.3), 92
(43.1), 63 (22.0).
2,6-Diiodo-4-methylphenol (6b)14
Reaction temperature: 50 °C; yield: 2.77 g (77%); off-white solid; mp
60.5–61.0 °C.
Rf = 0.35 (hexane).
1H NMR (300 MHz, CDCl3): δ = 7.40 (s, 2 H), 5.49 (s, 1 H), 2.13 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 151.3, 139.5, 133.8, 81.9, 19.4.
2-Iodo-6-(trimethylsilyl)phenyl Trifluoromethanesulfonate (2a)8a
Yield: 1.25 g (59%); colorless oil.
Rf = 0.44 (hexane).
MS (EI): m/z (%) = 360 (100.0), 233 (28.7), 180 (2.4), 106 (23.9), 74
(3.2), 52 (9.1).
IR (ATR): 3457 (w), 3059 (w), 3005 (w), 2955 (w), 1402 (m), 1383 (m),
1358 (s), 1155 (s), 1072 (s), 868 (m), 569 (s) cm–1
.
2,6-Diiodo-4-(trifluoromethyl)phenol (6c)15
1H NMR (300 MHz, CDCl3): δ = 7.62 (dd, J = 7.7, 1.7 Hz, 1 H), 7.24 (dd,
J = 7.4, 1.7 Hz, 1 H), 6.77 (t, J = 7.6 Hz, 1 H), 0.89 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 151.1, 142.5, 137.4, 136.8, 129.3, 118.5
(q, J = 318.8 Hz), 89.9, 0.2.
Reaction temperature: 50 °C; yield: 3.44 g (83%); off-white solid; mp
104.2–104.5 °C.
Rf = 0.26 (hexane).
1H NMR (300 MHz, CDCl3): δ = 7.85 (s, 2 H), 6.00 (s, 1 H).
MS (EI): m/z (%) = 409 (100.0), 339 (0.61), 291 (14.1), 149 (44.2), 109
13C NMR (75 MHz, CDCl3): δ = 156.4 (q, J = 0.96 Hz), 136.4 (q, J = 3.7
Hz), 126.2 (q, J = 33.5 Hz), 121.9 (q, J = 270.9 Hz), 81.8.
(0.53), 75 (4.3).
2-Iodo-4-methyl-6-(trimethylsilyl)phenyl Trifluoromethanesul-
fonate (2b)
MS (EI): m/z (%) = 414 (100.0), 160 (32.0), 141 (5.6), 132 (19.8), 131
(8.4), 61 (4.5).
Yield: 1.27 g (59%); colorless oil.
4-Chloro-2,6-diiodophenol (6d)7b
Rf = 0.50 (hexane).
Reaction temperature: 50 °C; yield: 3.00 g (79%); off-white solid; mp
103.8–104.9 °C.
IR (ATR): 3231 (w), 3154 (w), 2496 (w), 2313 (w), 2110 (w), 1400 (s),
1379 (m), 1204 (s), 1134 (s), 764 (m), 633 (s) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.56 (d, J = 1.9 Hz, 1 H), 7.12 (d, J = 1.5
Rf = 0.17 (hexane).
1H NMR (300 MHz, CDCl3): δ = 7.58 (s, 2 H), 5.64 (s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 152.7, 138.2, 126.7, 81.7.
Hz, 1 H), 2.15 (s, 3 H), 0.20 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 150.2, 143.9, 140.6, 138.6, 137.8, 119.6
(q, J = 318.7 Hz), 90.7, 21.4, 1.3.
MS (EI): m/z (%) = 382 (31.8), 380 (100.0), 252 (4.6), 199 (0.2), 126
(31.4), 73 (1.8), 62 (13.9).
MS (EI): m/z (%) = 423 (100.0), 290 (73.2), 163 (47.3), 149 (4.7), 73
(15.5), 53 (5.0).
HRMS (ESI): m/z [M – Me]+ calcd for C10H11F3IO3SSi: 422.9189; found:
422.9195.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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B. V. Moreira et al.
Paper
Synthesis
2-Iodo-4-(trifluoromethyl)-6-(trimethylsilyl)phenyl Trifluoro-
methanesulfonate (2c)
duced pressure. The residue was purified by preparative TLC on silica
gel (hexane or hexane/EtOAc, 9:1), affording the corresponding silyl-
biaryl triflate 1a–l.
Yield: 1.55 g (63%); colorless oil.
Rf = 0.55 (hexane).
3-(Trimethylsilyl)-1,1′-biphenyl-2-yl Trifluoromethanesulfonate
IR (ATR): 3292 (w), 3036 (w), 2957 (w), 2872 (w), 2623 (w), 1408 (m),
(1a)6a
1311 (s), 1211 (s), 1128 (s), 766 (m), 717 (s) cm–1
.
Yield: 299 mg (80%); yellowish oil.
1H NMR (300 MHz, CDCl3): δ = 7.93 (d, J = 1.8 Hz, 1 H), 7.55 (d, J = 1.6
Hz, 1 H), 0.20 (s, 9 H).
Rf = 0.36 (hexane).
IR (ATR): 3499 (w), 2955 (w), 2766 (w), 2515 (w), 1400 (s), 1389 (m),
13C NMR (75 MHz, CDCl3): δ = 153.5 (q, J = 1.4 Hz), 139.4 (q, J = 3.6 Hz),
138.9, 133.6 (q, J = 3.6 Hz), 131.3 (q, J = 32.8 Hz), 122.4 (q, J = 271.8
Hz), 118.4 (q, J = 318.9 Hz), 90.2, –0.02.
1202 (s), 1134 (s), 762 (m), 737 (m), 698 (s) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.50–7.45 (m, 1 H), 7.35–7.29 (m, 7 H),
0.37 (s, 9 H).
MS (EI): m/z (%) = 477 (100.0), 344 (76.4), 217 (30.5), 81 (8.4), 73
13C NMR (75 MHz, CDCl3): δ = 149.7, 136.8, 136.2, 135.8, 135.7, 135.5,
129.6, 128.3, 128.0, 127.9, 117.9 (q, J = 318.6 Hz), 0.2.
(14.8), 69 (9.5).
HRMS (ESI): m/z [M – Me]+ calcd for C10H8F6IO3SSi: 476.8907; found:
MS (EI): m/z (%) = 359 (69.5), 225 (49.4), 211 (16.9), 195 (8.8), 141
476.8908.
(100.0), 139 (3.9), 73 (53.4).
4-Chloro-2-iodo-6-(trimethylsilyl)phenyl Trifluoromethanesul-
fonate (2d)
3′-Methyl-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluoromethane-
sulfonate (1b)
Yield: 1.47 g (64%); colorless oil.
Yield: 233 mg (60%); yellowish oil.
Rf = 0.54 (hexane).
Rf = 0.60 (hexane).
IR (ATR): 3456 (w), 3062 (w), 2957 (w), 2907 (w), 1537 (m), 1401 (s),
1362 (m), 1132 (s), 1051 (s), 725 (m), 619 (s) cm–1
.
IR (ATR): 3503 (w), 2955 (w), 2903 (w), 2856 (w), 1400 (s), 1389 (m),
1201 (s), 1136 (s), 800 (m), 773 (m), 704 (s) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.59 (d, J = 2.5 Hz, 1 H), 7.17 (d, J = 2.5
Hz, 1 H), 0.09 (s, 9 H).
1H NMR (300 MHz, CDCl3): δ = 7.47–7.44 (m, 1 H), 7.34–7.10 (m, 6 H),
2.31 (s, 3 H), 0.36 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 149.7, 137.9, 136.7, 136.2, 135.8, 135.6,
13C NMR (75 MHz, CDCl3): δ = 149.7, 141.4, 139.0, 136.3, 134.5, 118.4
(q, J = 318.8 Hz), 90.4, 0.02.
133.6, 130.2, 128.6, 128.3, 128.0, 126.7, 118.0 (q, J = 318.6 Hz), 21.3,
0.2.
MS (EI): m/z (%) = 445 (41.4), 443 (100.0), 312 (33.6), 310 (91.0), 183
(24.4), 147 (5.3), 73 (26.2).
MS (EI): m/z (%) = 373 (59.9), 239 (37.8), 225 (11.2), 165 (21.3), 141
(100.0), 119 (9.2), 73 (74.1).
HRMS (ESI): m/z [M + NH4]+ calcd for C17H23F3NO3SSi: 406.1115;
HRMS (ESI): m/z [M – Me]+ calcd for C9H8ClF3IO3SSi: 442.8643; found:
442.8650.
found: 406.1115.
4-Bromo-2-iodo-6-(trimethylsilyl)phenyl Trifluoromethanesul-
fonate (2e)
4′-Methoxy-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluorometh-
anesulfonate (1c)
Yield: 1.53 g (61%); yellowish oil.
Rf = 0.50 (hexane).
Yield: 246 mg (61%); yellowish solid; mp 59.8–59.9 °C.
Rf = 0.40 (hexane).
IR (ATR): 3219 (w), 3038 (w), 2955 (w), 2901 (w), 2812 (w), 1529 (m),
1404 (s), 1358 (m), 1132 (s), 1049 (s), 723 (m), 656 (s), 609 (s) cm–1
.
IR (KBr): 3518 (w), 3044 (w), 2999 (w), 2902 (w), 1402 (s), 1385 (m),
1H NMR (300 MHz, CDCl3): δ = 7.85 (d, J = 2.4 Hz, 1 H), 7.41 (d, J = 2.4
Hz, 1 H), 0.20 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 150.2, 144.1, 139.6, 139.2, 122.2, 118.4
(q, J = 318.9 Hz), 90.9, 0.03.
1205 (s), 1138 (s), 839 (s), 810 (m), 771 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.30–7.25 (m, 3 H), 6.94–6.84 (m, 4 H),
3.74 (s, 3 H), 0.35 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 149.9, 135.8, 135.7, 135.3, 133.5, 130.8,
128.0, 127.7, 118.0 (q, J = 318.6 Hz), 114.8, 113.8, 55.2, 0.2.
MS (EI): m/z (%) = 489 (100.0), 487 (91.0), 356 (80.6), 226 (9.9), 153
(1.0), 148 (17.7), 73 (48.1).
MS (EI): m/z (%) = 404 (11.9), 398 (2.9), 271 (7.9), 152 (3.0), 141
(15.6), 120 (4.9), 73 (100.0).
HRMS (ESI): m/z [M + NH4]+ calcd for C17H23F3NO4SSi: 422.1064;
HRMS (ESI): m/z [M – Me]+ calcd for C9H8BrF3IO3SSi: 486.8138; found:
486.8145.
found: 422.1064.
Functionalized Silylbiaryl Triflates 1a–l; General Procedure
To a vial were added the appropriate iodinated silylaryl triflate 2a–e
(1 mmol), the appropriate arylboronic acid 3a–f (1.1 mmol),
PdCl2(PPh3)2 (35.1 mg, 0.05 mmol), K2CO3 (415 mg, 3 mmol), and
THF/H2O (1:1) (3 mL). The vial was sealed using a cap, and the mix-
ture was maintained under magnetic stirring at 80 °C for 24 h. Next,
brine (10 mL) was added to the reaction mixture, which was then ex-
tracted with Et2O (3 × 20 mL). The combined organic phase was dried
over MgSO4. After filtration, the solvent was evaporated under re-
4′-Chloro-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluoromethane-
sulfonate (1d)
Yield: 205 mg (50%); yellowish solid; mp 58.0–58.5 °C.
Rf = 0.52 (hexane).
IR (KBr): 3528 (w), 2955 (w), 2924 (w), 2901 (w), 1404 (s), 1381 (m),
1209 (s), 1138 (s), 847 (s), 791 (m), 771 (m) cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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B. V. Moreira et al.
Paper
Synthesis
1H NMR (300 MHz, CDCl3): δ = 7.57 (dd, J = 7.0, 2.2 Hz, 1 H), 7.45–7.34
5-(Trifluoromethyl)-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluo-
(m, 6 H), 0.44 (s, 9 H).
romethanesulfonate (1h)
13C NMR (75 MHz, CDCl3): δ = 149.4, 136.2, 136.1, 135.4, 135.1, 134.2,
133.3, 130.9, 128.6, 128.2, 118.0 (q, J = 318.6 Hz), 0.2.
Yield: 256 mg (58%); yellowish solid; mp 66.3–66.9 °C.
Rf = 0.54 (hexane).
MS (EI): m/z (%) = 408 (4.7), 393 (50.3), 259 (35.6), 165 (23.7), 141
(100.0), 112 (5.3), 73 (62.8).
HRMS (ESI): m/z [M + NH4]+ calcd for C16H20ClF3NO3SSi: 426.0568;
found: 426.0575.
IR (KBr): 3491 (w), 3036 (w), 2957 (w), 2903 (w), 1408 (s), 1284 (m),
1211 (s), 1134 (s), 887 (s), 783 (m), 725 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.69–7.59 (m, 2 H), 7.37–7.32 (m, 5 H),
0.38 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 151.7, 137.8, 137.2, 135.6, 132.4 (q, J =
3.6 Hz), 130.6 (q, J = 3.7 Hz), 129.5, 128.7, 128.6, 127.2, 123.5 (q, J =
272.1 Hz), 117.9 (q, J = 318.8 Hz), 0.01.
3′-Nitro-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluoromethane-
sulfonate (1e)
Yield: 339 mg (81%); yellowish solid; mp 62.8–63.2 °C.
Rf = 0.48 (hexane).
MS (EI): m/z (%) = 442 (2.3), 427 (97.3), 293 (83.4), 279 (32.3), 217
(59.3), 141 (100.0), 73 (50.3).
HRMS (ESI): m/z [M + NH4]+ calcd for C17H20F6NO3SSi: 460.0832;
found: 460.0840.
IR (KBr): 3447 (w), 3074 (w), 2957 (w), 2903 (w), 1398 (m), 1350 (s),
1203 (s), 1136 (s), 839 (s), 810 (m), 771 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 8.32–8.26 (m, 2 H), 7.80–7.44 (m, 5 H),
0.46 (s, 9 H).
5-Chloro-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluoromethane-
sulfonate (1i)
13C NMR (75 MHz, CDCl3): δ = 148.8, 148.1, 138.7, 137.1, 136.6, 135.7,
134.0, 133.2, 129.4, 128.5, 124.5, 122.9, 117.9 (q, J = 318.4 Hz), 0.1.
Yield: 229 mg (56%); yellowish solid; mp 75.5–76.0 °C.
Rf = 0.72 (hexane).
MS (EI): m/z (%) = 404 (94.1), 389 (5.9), 270 (50.6), 225 (54.5), 151
(12.3), 141 (100.0), 73 (52.7).
HRMS (ESI): m/z [M + NH4]+ calcd for C16H20F3N2O5SSi: 437.0809;
IR (KBr): 3491 (w), 2957 (w), 2922 (w), 2851 (w), 1406 (s), 1387 (m),
1207 (s), 1138 (s), 879 (s), 777 (m), 739 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.51–7.50 (m, 1 H), 7.46–7.42 (m, 6 H),
found: 437.0813.
0.48 (s, 9 H).
2′-Hydroxy-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluorometh-
anesulfonate (1f)
13C NMR (75 MHz, CDCl3): δ = 147.9, 138.4, 137.9, 135.7, 135.1, 134.0,
133.1, 129.4, 128.7, 128.5, 117.9 (q, J = 318.8 Hz), 0.4.
Yield: 207 mg (53%); yellowish oil.
MS (EI): m/z (%) = 408 (4.2), 393 (41.5), 263 (2.4), 259 (30.1), 245
Rf = 0.25 (hexane/EtOAc, 9:1).
(13.2), 141 (76.4), 73 (100.0).
HRMS (ESI): m/z [M + NH4]+ calcd for C16H20ClF3NO3SSi: 426.0568;
found: 426.0575.
IR (ATR): 3555 (w), 3493 (w), 2955 (w), 2903 (w), 2855 (w), 1391 (s),
1350 (m), 1202 (s), 1136 (s), 833 (s), 793 (m), 773 (m), 716 (s) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.63–7.59 (m, 1 H), 7.49–7.43 (m, 2 H),
7.32–7.16 (m, 3 H), 7.00–6.98 (m, 1 H), 5.00 (s, 1 H), 0.44 (s, 9 H).
5-Chloro-3′-nitro-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluoro-
methanesulfonate (1j)
13C NMR (75 MHz, CDCl3): δ = 152.9, 150.2, 136.7, 136.1, 134.2, 131.4,
130.1, 128.3, 123.4, 120.7, 118.0 (q, J = 318.6 Hz), 116.6, 115.2, 0.3.
Yield: 291 mg (64%); yellowish solid; mp 127.6–127.9 °C.
Rf = 0.56 (hexane).
MS (EI): m/z (%) = 390 (11.0), 375 (19.8), 241 (8.2), 225 (80.8), 165
(24.3), 141 (25.9), 77 (100.0), 73 (95.3).
HRMS (ESI): m/z [M + NH4]+ calcd for C16H21F3NO4SSi: 408.0907;
IR (KBr): 3372 (w), 2957 (w), 2903 (w), 2853 (w), 1404 (m), 1350 (s),
1215 (s), 1138 (s), 878 (s), 766 (m), 733 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 8.30–8.27 (m, 2 H), 7.78–7.74 (m, 1 H),
found: 408.0919.
7.67–7.62 (m, 1 H), 7.57–7.43 (m, 2 H), 0.46 (s, 9 H).
5-Methyl-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluoromethane-
sulfonate (1g)
13C NMR (75 MHz, CDCl3): δ = 148.2, 146.9, 139.2, 137.4, 136.4, 135.6,
135.5, 134.5, 132.7, 129.6, 124.3, 123.3, 117.9 (q, J = 318.6 Hz), 0.04.
Yield: 233 mg (60%); yellowish solid; mp 77.6–78.0 °C.
Rf = 0.32 (hexane).
MS (EI): m/z (%) = 453 (0.3), 338 (62.1), 304 (41.3), 259 (48.6), 245
(5.4), 141 (100.0), 73 (35.3).
HRMS (ESI): m/z [M + NH4]+ calcd for C16H19ClF3N2O5SSi: 471.0419;
found: 471.0421.
IR (KBr): 3495 (w), 3035 (w), 2955 (w), 2901 (w), 1402 (s), 1251 (m),
1206 (s), 1138 (s), 910 (m), 845 (s), 777 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.19–7.12 (m, 5 H), 7.09–6.98 (m, 2 H),
2.15 (s, 3 H), 0.20 (s, 9 H).
5-Bromo-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluoromethane-
sulfonate (1k)
13C NMR (75 MHz, CDCl3): δ = 147.8, 137.8, 137.0, 136.2, 135.8, 135.4,
134.2, 129.6, 128.3, 127.9, 118.0 (q, J = 318.6 Hz), 20.8, 0.2.
Yield: 249 mg (55%); yellowish solid; mp 99.8–100.2 °C.
Rf = 0.48 (hexane).
MS (EI): m/z (%) = 388 (5.9), 373 (46.1), 239 (29.1), 225 (9.4), 166
(5.4), 141 (74.6), 73 (100.0).
HRMS (ESI): m/z [M + NH4]+ calcd for C17H23F3NO3SSi: 406.1115;
IR (KBr): 3489 (w), 2955 (w), 2936 (w), 2920 (w), 1404 (s), 1387 (m),
1206 (s), 1138 (s), 876 (s), 777 (m), 739 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.36–7.29 (m, 2 H), 7.17–7.12 (m, 5 H),
found: 406.1113.
0.19 (s, 9 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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B. V. Moreira et al.
Paper
Synthesis
13C NMR (75 MHz, CDCl3): δ = 148.5, 138.9, 138.2, 138.0, 136.0, 135.6,
129.4, 128.5, 128.4, 122.3, 117.9 (q, J = 318.8 Hz), 0.04.
Yield: 18.5 mg (58%); colorless oil.
Rf = 0.12 (hexane).
MS (EI): m/z (%) = 454 (1.4), 437 (15.1), 303 (9.3), 246 (1.1), 190 (4.5),
141 (66.9), 73 (100.0).
HRMS (ESI): m/z [M + NH4]+ calcd for C16H20BrF3NO3SSi: 470.0063;
found: 470.0063.
IR (KBr): 3074 (w), 2938 (w), 2851 (w), 1528 (s), 1489 (s), 1350 (s),
1412 (w), 1221 (s), 1163 (m), 737 (m), 684 (m) cm–1
1H NMR (300 MHz, CDCl3): δ = 8.42 (t, J = 2.0 Hz, 1 H), 8.20 (ddd, J =
8.2, 2.2, 0.9 Hz, 1 H), 7.87 (ddd, J = 7.8, 1.5, 1.1 Hz, 1 H), 7.59 (t, J = 8.0
Hz, 1 H), 7.45 (t, J = 7.9 Hz, 1 H), 7.40–7.33 (m, 3 H), 7.28 (t, J = 2.0 Hz,
1 H), 7.17–7.12 (m, 1 H), 7.08–7.03 (m, 3 H).
.
5-Bromo-3′-methyl-3-(trimethylsilyl)-1,1′-biphenyl-2-yl Trifluo-
romethanesulfonate (1l)
13C NMR (75 MHz, CDCl3): δ = 158.1, 156.8, 148.7, 142.2, 140.5, 133.0,
130.5, 129.9, 129.7, 123.7, 122.3, 122.0, 121.9, 119.0, 118.6, 117.5.
Yield: 219 mg (47%); yellowish oil.
Rf = 0.60 (hexane).
MS (EI): m/z (%) = 292 (20.0), 291 (100.0), 263 (8.7), 215 (9.5), 202
(8.7), 152 (43.4), 139 (10.7).
HRMS (ESI): m/z [M + H]+ calcd for C18H14NO3: 292.0968; found:
292.0976.
IR (ATR): 3530 (w), 2955 (w), 2922 (w), 2902 (w), 1402 (s), 1380 (m),
1202 (s), 1130 (s), 872 (s), 787 (s), 760 (m), 741 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.33 (dd, J = 7.3, 2.6 Hz, 2 H), 7.08–6.94
(m, 4 H), 2.14 (s, 3 H), 0.20 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 148.5, 138.8, 138.4, 138.1, 137.9, 136.0,
135.4, 130.0, 129.2, 128.4, 126.5, 122.2, 117.9 (q, J = 318.8 Hz), 21.3,
0.03.
7-Bromo-1,4-dihydro-5-phenyl-1,4-epoxynaphthalene (12)
To vial were added furan (11) (19.0 μL, 17.7 mg, 0.26 mmol), silylbi-
aryl triflate 1k (72.3 mg, 0.16 mmol), MeCN (3 mL), and CsF (48.6 mg,
0.32 mmol). The vial was sealed using a cap, and the mixture was
maintained under magnetic stirring at 40 °C for 12 h. Then, the reac-
tion mixture was cooled to r.t., filtered, and the solvent was evaporat-
ed under reduced pressure. The residue was purified by preparative
TLC on silica gel (hexane) to afford the desired product 12.
MS (EI): m/z (%) = 468 (2.7), 451 (11.9), 318 (6.5), 239 (6.9), 165
(10.2), 141 (53.7), 73 (100.0).
HRMS (ESI): m/z [M + NH4]+ calcd for C17H22BrF3NO3SSi: 484.0220;
found: 484.0217.
Yield: 19.4 mg (41%); brownish oil.
4′-Methoxy-1,1′-biphenyl-3-yl Benzoate (9)
Rf = 0.25 (hexane).
To a vial were added benzoic acid (8) (9.8 mg, 0.08 mmol), silylbiaryl
triflate 1c (64.7 mg, 0.16 mmol), MeCN (3 mL), and CsF (48.6 mg, 0.32
mmol). The vial was sealed using a cap, and the mixture was main-
tained under magnetic stirring at r.t. for 24 h. Next, brine (10 mL) was
added to the reaction mixture, which was then extracted with EtOAc
(3 × 10 mL). The combined organic phase was dried over MgSO4. After
filtration, the solvent was evaporated under reduced pressure. The
residue was purified by preparative TLC on silica gel (hexane/EtOAc,
19:1) to afford the desired product 9.
IR (KBr): 3019 (w), 2922 (w), 2851 (w), 1593 (m), 1425 (m), 1279 (m),
1098 (m), 854 (s), 767 (m), 698 (s) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.50–7.45 (m, 2 H), 7.42–7.37 (m, 2 H),
7.34–7.31 (m, 2 H), 7.24 (d, J = 1.6 Hz, 1 H), 7.16 (dd, J = 5.6, 1.8 Hz, 1
H), 7.09 (dd, J = 5.6, 1.8 Hz, 1 H), 5.79–5.78 (m, 1 H), 5.73–5.72 (m, 1
H).
13C NMR (75 MHz, CDCl3): δ = 151.8, 146.1, 142.9, 142.9, 138.3, 136.2,
128.9, 127.9, 127.6, 122.8, 119.0, 82.1, 81.7.
Yield: 16.1 mg (66%); off-white solid; mp 84.5–87.0 °C.
Rf = 0.28 (hexane/EtOAc, 19:1).
MS (EI): m/z (%) = 298 (8.8), 272 (18.4), 219 (2.7), 191 (100.0), 165
(26.0), 94 (11.2).
HRMS (ESI): m/z [M + H]+ calcd for C16H12BrO: 299.0066; found:
299.0058.
IR (KBr): 3061 (w), 2924 (w), 2851 (w), 1734 (s), 1605 (m), 1521 (m),
1479 (m), 1246 (s), 1177 (m), 787 (m), 698 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 8.24–8.21 (m, 2 H), 7.67–7.62 (m, 1 H),
7.55–7.45 (m, 6 H), 7.40–7.39 (m, 1 H), 7.18–7.14 (m, 1 H), 6.99–6.96
(m, 2 H), 3.85 (s, 3 H).
Acknowledgment
13C NMR (75 MHz, CDCl3): δ = 165.2, 159.4, 151.3, 142.5, 133.6, 132.7,
We are grateful to the São Paulo Research Foundation (FAPESP) for fi-
nancial support (Grant No. 2015/09984-9). B.V.M. and A.C.A.M. also
thank FAPESP for their fellowships.
130.2, 129.7, 129.6, 128.6, 128.2, 124.2, 120.0, 119.8, 114.2, 55.3.
MS (EI): m/z (%) = 304 (28.2), 171 (3.4), 128 (4.4), 106 (8.2), 105
(100.0), 77 (28.7).
HRMS (ESI): m/z [M + H]+ calcd for C20H17O3: 305.1172; found:
Supporting Information
305.1174.
Supporting information for this article is available online at
3-Nitro-3′-phenoxy-1,1′-biphenyl (10)
http://dx.doi.org/10.1055/s-0036-1588332.
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p
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rmoaitn
To a vial were added phenol (4a) (10.0 mg, 0.11 mmol), silylbiaryl tri-
flate 1e (67.0 mg, 0.16 mmol), MeCN (3 mL), and CsF (50.1 mg, 0.33
mmol). The vial was sealed using a cap, and the mixture was main-
tained under magnetic stirring at r.t. for 24 h. Next, brine (10 mL) was
added to the reaction mixture, which was then extracted with EtOAc
(3 × 10 mL). The combined organic phase was dried over MgSO4. After
filtration, the solvent was evaporated under reduced pressure. The
residue was purified by preparative TLC on silica gel (hexane), afford-
ing the desired product 10.
References
(1) For reviews, see: (a) Dubrovskiy, A. V.; Markina, N. A.; Larock, R.
C. Org. Biomol. Chem. 2013, 11, 191. (b) Bhunia, A.; Yetra, S. R.;
Biju, A. T. Chem. Soc. Rev. 2012, 41, 3140. (c) Yoshida, H.; Takaki,
K. Synlett 2012, 23, 1725. (d) Yoshida, H.; Ohshita, J.; Kunai, A.
Bull. Chem. Soc. Jpn. 2010, 83, 199.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

J
B. V. Moreira et al.
Paper
Synthesis
(2) For reviews, see: (a) Tadross, P. M.; Stoltz, B. M. Chem. Rev. 2012,
112, 3550. (b) Gampe, C. M.; Carreira, E. M. Angew. Chem. Int. Ed.
2012, 51, 3766. For selected examples, see: (c) Gouthami, P.;
Chegondi, R.; Chandrasekhar, S. Org. Lett. 2016, 18, 2044.
(d) Rossini, A. F. C.; Muraca, A. C. A.; Casagrande, G. A.;
Raminelli, C. J. Org. Chem. 2015, 80, 10033. (e) Perecim, G. P.;
Rodrigues, A.; Raminelli, C. Tetrahedron Lett. 2015, 56, 6848.
(f) Moschitto, M. J.; Anthony, D. R.; Lewis, C. A. J. Org. Chem.
2015, 80, 3339.
Gebara, K. S.; Muzzi, R. M.; Raminelli, C. J. Braz. Chem. Soc. 2010,
21, 770. (c) Jereb, M.; Zupan, M.; Stavber, S. Chem. Commun.
2004, 2614.
(8) For the preparation of iodinated silylaryl triflates, see:
(a) Medina, J. M.; Mackey, J. L.; Garg, N. K.; Houk, K. N. J. Am.
Chem. Soc. 2014, 136, 15798. (b) Bronner, S. M.; Mackey, J. L.;
Houk, K. N.; Garg, N. K. J. Am. Chem. Soc. 2012, 134, 13966.
(c) Díaz, M.; Cobas, A.; Guitián, E.; Castedo, L. Eur. J. Org. Chem.
2001, 4543.
(3) For a review, see: (a) Wu, D.; Ge, H.; Liu, S. H.; Yin, J. RSC Adv.
2013, 3, 22727. For selected examples, see: (b) Mizukoshi, Y.;
Mikami, K.; Uchiyama, M. J. Am. Chem. Soc. 2015, 137, 74. (c) Li,
J.; Zhao, Y.; Lu, J.; Li, G.; Zhang, J.; Zhao, Y.; Sun, X.; Zhang, Q.
J. Org. Chem. 2015, 80, 109. (d) Shen, Y.-M.; Grampp, G.;
Leesakul, N.; Hu, H.-W.; Xu, J.-H. Eur. J. Org. Chem. 2007, 3718.
(4) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett. 1983,
1211.
(5) (a) Atkinson, D. J.; Sperry, J.; Brimble, M. A. Synthesis 2010, 911.
(b) Bronner, S. M.; Garg, N. K. J. Org. Chem. 2009, 74, 8842.
(c) Peña, D.; Iglesias, B.; Quintana, I.; Pérez, D.; Guitián, E.;
Castedo, L. Pure Appl. Chem. 2006, 78, 451. (d) Peña, D.; Cobas,
A.; Pérez, D.; Guitián, E. Synthesis 2002, 1454.
(6) (a) Lakshmi, B. V.; Wefelscheid, U. K.; Kazmaier, U. Synlett 2011,
345. (b) Yoshida, H.; Ikadai, J.; Shudo, M.; Ohshita, J.; Kunai, A.
J. Am. Chem. Soc. 2003, 125, 6638. (c) Yoshida, H.; Shirakawa, E.;
Honda, Y.; Hiyama, T. Angew. Chem. Int. Ed. 2002, 41, 3247.
(7) For the preparation of diiodinated phenols, see: (a) Gallo, R. D.
C.; Ferreira, I. M.; Casagrande, G. A.; Pizzuti, L.; Oliveira-Silva, D.;
Raminelli, C. Tetrahedron Lett. 2012, 53, 5372. (b) Gallo, R. D. C.;
(9) For reviews, see: (a) Rossi, R.; Bellina, F.; Lessi, M. Adv. Synth.
Catal. 2012, 354, 1181. (b) Rossi, R.; Bellina, F.; Lessi, M. Tetrahe-
dron 2011, 67, 6969.
(10) For selected examples, see: (a) Thangaraj, M.; Bhojgude, S. S.;
Mane, M. V.; Biju, A. T. Chem. Commun. 2016, 52, 1665.
(b) Bhojgude, S. S.; Kaicharla, T.; Biju, A. T. Org. Lett. 2013, 15,
5452. (c) Liu, Z.; Larock, R. C. J. Org. Chem. 2006, 71, 3198.
(d) Liu, Z.; Larock, R. C. Org. Lett. 2004, 6, 99. (e) Liu, Z.; Larock,
R. C. Org. Lett. 2003, 5, 4673.
(11) For selected examples, see: (a) Thangaraj, M.; Bhojgude, S. S.;
Bisht, R. H.; Gonnade, R. G.; Biju, A. T. J. Org. Chem. 2014, 79,
4757. (b) Kaicharla, T.; Bhojgude, S. S.; Biju, A. T. Org. Lett. 2012,
14, 6238. (c) Lu, C.; Dubrovskiy, A. V.; Larock, R. C. J. Org. Chem.
2012, 77, 2279. (d) Dubrovskiy, A. V.; Larock, R. C. Org. Lett.
2010, 12, 1180.
(12) Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory
Chemicals, 4th ed.; Butterworth-Heinemann: Oxford, 1996, 1.
(13) Watson, S. C.; Eastham, J. F. J. Organomet. Chem. 1967, 9, 165.
(14) Kajigaeshi, S.; Kakinami, T.; Yamasaki, H.; Fujisaki, S.; Kondo,
M.; Okamoto, T. Chem. Lett. 1987, 2109.
(15) Kopp, F.; Krasovskiy, A.; Knochel, P. Chem. Commun. 2004, 2288.
(16) Kohn, M.; Sußmann, S. Monatsh. Chem. 1925, 46, 575.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J