Copper-Catalyzed Diaryl Ether Formation from (Hetero)aryl Halides at Low Catalytic Loadings

Article abstract of DOI:10.1021/acs.joc.7b00493

Diaryl formation is achieved by coupling phenols and (hetero)aryl halides under the catalysis of CuI/N,N′-bis(2-phenylphenyl) oxalamide (BPPO) or CuI/N-(2-phenylphenyl)-N′-benzyl oxalamide (PPBO) at 90 °C using DMF or MeCN as the solvent. Only 0.2-2 mol % CuI and ligand are required for complete conversion, which represents the lowest catalytic loadings for a general Cu/ligand-catalyzed diaryl ether formation.

Full text of DOI:10.1021/acs.joc.7b00493

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Note
Copper-Catalyzed Diaryl Ether Formation from
(Hetero)aryl Halides at Low Catalytic Loadings
Yuntong Zhai, Xiaofei Chen, Wei Zhou, Mengyang Fan, Yisheng Lai, and Dawei Ma
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 21 Apr 2017
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The Journal of Organic Chemistry
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Copper-Catalyzed Diaryl Ether Formation from (Hetero)aryl
Halides at Low Catalytic Loadings
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Yuntong Zhai,a Xiaofei Chen,b Wei Zhou,b Mengyang Fan,b Yisheng Laia and Dawei
Mab*
aState Key Laboratory of Natural Medicines, Center of Drug Discovery, China
Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China
bState Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu,
Shanghai 200032, China
madw@sioc.ac.cn
Abstract
0.2-2 mol % CuI
0.2-2 mol % ligand
ArX + Ar'OH
Ar OAr'
K3PO4, DMF or MeCN
90 oC, 24 h
Ph
H
O
N
H
N
N
Bn
H
O
Ph
O
2
BPPO (for aryl bromides)
PPBO (for aryl iodides)
Diaryl formation is achieved by coupling phenols and (hetero)aryl halides under the
catalysis of CuI/N,N’ꢀbis(2ꢀphenylphenyl) oxalamide (BPPO) or CuI/
o
Nꢀ(2ꢀphenylphenyl)ꢀN’ꢀbenzyl oxalamide (PPBO) at 90 C using DMF or MeCN as
the solvent. Only 0.2ꢀ2 mol % CuI and ligand are required for complete conversion,
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which represents the lowest catalytic loadings for a general Cu/ligandꢀcatalyzed diaryl
ether formation.
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During the past two decades great attention has been directed to the
development of ligandꢀpromoted copperꢀcatalyzed coupling reactions between
phenols and aryl halides.1 To date more than dozens of N,Oꢀ,2 N,Nꢀ3 or O,Oꢀbidentate
ligands4 have been discovered to have such promoting ability. These newly developed
catalytic systems make diaryl ether formation proceed under relatively mind
conditions, and have been intensively applied in the synthesis of bioactive compounds
and material molecules with scale from miligrams1,5 to hundreds of kilograms.6
Although the progress in this area is significant, further improvements are still
desirable. For examples, in most cases, catalytic loadings are still considerably high
(5ꢀ20 mol % copper salts and ligands),7 which is unfavorable from economical and
environmental viewpoint.2ꢀ4 Recently, we found that some N,N’ꢀdisubstituted
oxalamides are powerful ligands for Cuꢀcatalyzed coupling reactions of aryl chlorides
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o
with phenols, leading to the formation of diaryl ethers at 120 C.8 Further
investigations demonstrated that when more reactive aryl bromides and iodides were
used as the coupling partners, our new catalytic systems worked well at much lower
catalytic loadings in comparison with the previous Cu/ligand catalytic systems.
Herein, we wish to disclose our results.
As indicated in Table 1, using CuIꢀcatalyzed coupling of 4ꢀmethylbromoꢀ
benzene and phenol as a model reaction, we screened a series of ligands at 0.5 mol %
o
loading. It was found that at 90 C after 24 h, almost complete conversion was
achieved by using Nꢀ(2ꢀphenylꢀ4ꢀmethylphenyl)ꢀN’ꢀbenzyl oxalamide (PMPBO, L1)
as a ligand (entry 1).8 Similar results were seen when other N,N’ꢀdisubstituted
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oxalamides were employed (entries 2ꢀ7).9 Under the same conditions, other known
ligands like diketone L8, glyoxal bis(phenylhydrazone) L9, N,Nꢀdimethylglycine L10,
picolinic acid L11 and 8ꢀhydroxyquinline L12 gave poor to moderate conversions.
These results illustrated that N,N’ꢀdisubstituted oxalamides are superior to the
previous ligands for CuIꢀcatalyzed coupling of aryl bromides and phenols. Considered
the availability, we chose N,N’ꢀbis(2ꢀphenylphenyl) oxalamide (BPPO, L6) for further
studies. CuI/BPPO catalyzed reaction could also proceed smoothly in DMA and
MeCN, although reaction yields were slightly decreased (entries 13 and 14). However,
a poor conversion was observed when dioxane was used as the solvent (entry 15).
Using K3PO4 as the base is essential for the reaction, as evident from that KOH and
K2CO3 gave only 14ꢀ18% conversions. To achieve complete conversion, we increased
the catalytic loading for both CuI and BPPO to 1 mol %, and were pleased that 3a was
obtained in 92% yield.
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Table 1. CuIꢀcatalyzed Coupling of 4ꢀMethylbromobenzene with Phenol under the
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Assistance of Different Ligandsa
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entry
ligand
L1
yield (%)b
entry
10
ligand
L10
L11
L12
L6
yield (%)b
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2
3
4
5
6
7
8
9
88
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87
86
89
89
85
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38
71
72
36
18
14
92
11
L2
12
L3
13c
14d
15e
16f
17g
18h
L4
L5
L6
L6
L6
L7
L6
L8
L6
L9
L6
aGeneral conditions: 1a (5 mmol), phenol (7.5 mmol), CuI (0.025 mmol), ligand
b
1
(0.025 mmol), K3PO4 (10 mmol), DMF (2.0 mL). The yield was determined by H
c
NMR analysis of crude products using CH2Br2 as the internal standard. DMA as the
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solvent. dMeCN as the solvent. Dioxane as the solvent. fKOH as the base. K2CO3 as
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the base. h1 mol % CuI and L6 were used.
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The established optimized conditions were examined by varying (hetero)aryl
bromides and phenols and the results are summarized in Table 2. A series of aryl
bromides bearing either electronꢀdonating or electronꢀwithdrawing groups at the
paraꢀposition worked well, giving diaryl ethers 3bꢀ3j in 88ꢀ96% yields. Coupling of
three metaꢀsubstituted and one orthoꢀsubstituted aryl bromides with different phenols
proceeded smoothly to afford 3kꢀ3n in 82ꢀ93% yields. For phenols, electronꢀrich ones
gave the better results (3oꢀ3q), while less reactive electronꢀpoor ones required
increasing catalytic loadings to 2 mol % to obtain the corresponding in reasonable
yields (3rꢀ3t). Additionally, a number of heteroaryl bromides are also compatible with
these conditions, leading to formation of heterocycleꢀembodied diaryl ethers 3uꢀ3ac
with excellent yields.
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Table 2. CuI/BPPO Catalyzed Coupling of (Hetero)aryl Bromides with Phenolsa
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O
O
OPh
F3C
Cl
OMe
OMe
Y
3i
3j
(96%)
(92%)
3b
3c
3d
3e
t
: Y = Bu- , 88%
: Y = TMS, 90%
O
Me
b
: Y = Ph, 95% (96% )
PhO
: Y = OBu- , 93%
t
b
3f
: Y = SMe, 90% (92% )
NH2
Me
(84%)
OMe
OMe
b
3g
3h
3l
: Y = COMe, 96% (92% )
: Y = CO2Me, 94%
(82%)
O
3k
MeO
O
O
3o
(92%)
CN
3n
Me
3m
(93%)
OH
MeO
MeO
(92%)
O
O
NH2
O
MeO
Cl
3q
3r (72%c)
(84%)
O
3p
(92%)
N
SMe
O
c
3t
(68% )
MeO
N
O
MeO
CO2Me
c
3u
(95%)
3s
(52% )
O
OPh
N
N
OMe
N
H2N
Me
N
O
b
b
3w
3x
(95%)
3v
(92%, 94% )
(96%, 93% )
O
O
N
OMe
N
OMe
3z
3y
(96%)
PhO
(94%)
N
N
O
Me
MeO
O
S
N
3ac
(90%)
3aa
(94%)
3ab
(95%)
Bn
a1 (5 mmol), 2 (7.5 mmol), CuI (0.5 mmol), BBPO (0.5 mmol), K3PO4 (10 mmol),
DMF (2.0 mL). bReaction was carried out in MeCN. cReaction was carried out with 2
mol % CuI and BBPO.
For coupling with more reactive aryl iodides, we quickly screened some
N,N’ꢀdisubstituted oxalamide ligands and found that two NꢀarylꢀN’ꢀalkyl substituted
oxalamides L1 and L2 gave the best results when coupling reaction of
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4ꢀmethyliodobenzene with phenol was conducted in MeCN at 90 C (Table 3, entries
1ꢀ5). Thus, we chose relatively simple Nꢀ(2ꢀphenylphenyl)ꢀN’ꢀbenzyl oxalamide
(PPBO, L2) for further reaction condition optimization. Among the solvents examined,
DMF and DMA gave similar results with MeCN (entries 6 and 7), NMP led to a
decreased yield (entry 8), while a poor yield was seen in dioxane (entry 9).
Accordingly, we decided to use PPBO as the ligand and MeCN as the solvent to
explore the reaction scope. Under these conditions the loading for both catalyst and
ligand could be reduced to 0.2 mol % without affecting the reaction yield (entry 10).
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Table 3. CuIꢀCatalyzed Coupling of 4ꢀMethyliodobenzene with Phenol under the
Assistance of Different Ligandsa
entry
ligand
L1
yield (%)b
entry
6c
ligand
L2
yield (%)b
1
2
3
4
5
93
92
80
84
82
91
88
76
34
90
L2
7d
L2
8e
L4
L2
9f
L5
L2
10g
L6
L2
aGeneral conditions: 4a (10 mmol), phenol (15 mmol), CuI (0.1 mmol), ligand (0.1
b
1
mmol), K3PO4 (20 mmol), MeCN (4.0 mL). The yield was determined by H NMR
analysis of crude products using CH2Br2 as the internal standard. cDMF as the solvent.
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dDMA as the solvent. NMP as the solvent. Dioxane as the solvent. 0.2 mol % CuI
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and L2 were used.
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The reaction scope and limitations were explored with a range of (hetero)aryl
iodides and phenols (Table 4). Generally, they all gave the corresponding diaryl ethers
with excellent yields. When sterically hindered 2ꢀmethyliodobenzene was used,
coupling reaction still proceeded smoothly under these conditions to give 3af,
although a decreased yield was observed.
Another notable feature for present coupling reactions is that a wide range of
functional groups such as ester, ketone, alcohol, amino, cyanide and chloro moieties,
are tolerated under these conditions. Additionally, a series of heterocycles that include
thiophene, pyridine, pyrimidine, quinoline, isoquinoline, quinoxaline, benzothiaphene,
indole and benzofuran could be introduced into the coupling products by choosing
suitable heteroaryl halides or hydroxylated heteroarenes as the starting materials.
These advantages allow diverse synthesis of functionalized diaryl ethers.
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Table 4. CuI/PPBO Catalyzed Coupling of (Hetero)aryl Iodides with Phenolsa
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aGeneral conditions: 4 (10 mmol), 2 (15 mmol), CuI (0.02 mmol), ligand (0.02 mmol),
K3PO4 (20 mmol), MeCN (4.0 mL).
In conclusion, we have identified that two easily available N,N’ꢀdisubstituted
oxalamides are efficient ligands for Cuꢀcatalyzed coupling of phenols with
(hetero)aryl bromides and iodides. The reactions worked well even with 0.2ꢀ2 mol %
catalyst loadings to give a broad range of diaryl ethers in good to excellent yields. The
present results represent the lowest catalytic loadings for
a
general
Cu/ligandꢀcatalyzed diaryl ether formation, and further demonstrated the power of
N,N’ꢀdisubstituted oxalamide ligands to promote Cuꢀcatalyzed arylation of
nucleophiles.
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Experimental
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General procedure for coupling of (hetero)aryl bromides with phenols. A Schlenk
tube was charged with CuI (9.5 mg, 0.05 mmol), BPPO (19.6 mg, 0.05 mmol),
(hetero)aryl bromide (if solid, 5.0 mmol), phenol (if solid, 7.5 mmol) and K3PO4 (2.12
g, 10 mmol). The tube was evacuated and backfilled with argon before anhydrous
DMF (2.0 mL) or MeCN (2.0 mL) was added via syringe (NOTE: for liquid
substrates, they were added into the tube via syringe after the tube was backfilled with
argon). The mixture was sealed and stirred at 90 °C for 24 h before diluted with about
50 mL of EtOAc and filtrated. The filtrate was concentrated in vacuo. The residue was
purified by flash chromatography on silica gel to afford the corresponding diaryl
ethers.
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General procedure for coupling of (hetero)aryl iodides with phenols. A Schlenk
tube was charged with CuI (3.8 mg, 0.02 mmol), PPBO (6.6 mg, 0.02 mmol),
(hetero)aryl iodide (if solid, 10.0 mmol), phenol (if solid, 15.0 mmol) and K3PO4
(4.24 g, 20 mmol). The tube was evacuated and backfilled with argon before
anhydrous MeCN (4.0 mL) was added via syringe (Note: for liquid substrates, they
were added into the tube via syringe after the tube was backfilled with argon). The
mixture was sealed and stirred at 90 °C for 24 h before diluted with EtOAc and
filtrated. The filtrate was concentrated in vacuo. The residue was purified by flash
chromatography on silica gel to afford the corresponding diaryl ethers.
1-Methyl-4-phenoxybenzene (3a). 3a was prepared from 4ꢀbromotoluene and phenol
or from 4ꢀiodotoluene and phenol, and purified by flash chromatography (petroleum
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ether, Rf = 0.6) as colorless liquid (846 mg, 92% from 4ꢀbromotoluene; 1.66 g, 90%
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1
from 4ꢀiodotoluene). H NMR (500 MHz, CDCl3) δ 7.35ꢀ7.29 (m, 2H), 7.14 (d, J =
8
9
8.0 Hz, 2H), 7.07 (td, J = 7.5, 1.0 Hz, 1H), 6.98 (d, J = 7.5 Hz, 2H), 6.92 (dd, J = 8.0,
1.0 Hz, 2H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.9, 154.8, 133.0, 130.3,
129.8, 122.9, 119.2, 118.5, 20.8; HRMS (EIꢀTOF) m/z calcd for C13H12O (M+)
184.0888, found 184.0881.
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1-(tert-Butyl)-4-phenoxybenzene (3b). 3b was prepared from 1ꢀbromoꢀ4ꢀ(tertꢀbutyl)ꢀ
benzene and phenol, and purified by flash chromatography (eluting with petroleum
1
ether, Rf = 0.5) as colorless liquid (994 mg, 88%). H NMR (500 MHz, CDCl3) δ
7.37ꢀ7.31 (m, 4H), 7.11ꢀ7.07 (m, 1H), 7.03ꢀ7.01 (m, 2H), 6.95 (td, J = 8.5, 2.0 Hz,
13
2H), 1.34 (s, 9H); C NMR (100 MHz, CDCl3) δ 157.7, 154.8, 146.1, 129.7, 126.6,
123.0, 118.7, 118.6, 34.4, 31.6; HRMS (EIꢀTOF) m/z calcd for C16H18O (M+)
226.1358, found 226.1366.
1-Trimethylsilyl-4-phenoxybenzene (3c). 3c was prepared from (4ꢀbromophenyl)ꢀ
trimethylsilane and phenol, and purified by flash chromatography (eluting with
1
petroleum ether, Rf = 0.5) as colorless liquid (1.09 g, 90%). H NMR (500 MHz,
CDCl3) δ 7.49 (dd, J = 8.5, 1.5 Hz, 2H), 7.36 (t, J = 7.5 Hz, 2H), 7.13 (td, J = 7.5, 1.0
Hz, 1H), 7.05 (dd, J = 7.5, 1.0 Hz, 2H), 7.01 (dd, J = 8.5, 1.0 Hz, 2H), 0.28 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 158.2, 157.0, 135.0, 134.6, 129.9, 123.5, 119.3, 118.1,
ꢀ0.8; HRMS (EIꢀTOF) m/z calcd for C15H18OSi (M+) 242.1127, found 242.1124.
4-Phenoxy-1,1'-biphenyl (3d). 3d was prepared from 4ꢀbromobiphenyl and phenol or
from 4ꢀiodobiphenyl and phenol, and purified by flash chromatography (eluting with
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petroleum ether, Rf = 0.4) as white solid (from 4ꢀbromobiphenyl, 1.17 g, 95% in DMF;
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7
o
1
1.18 g, 96% in MeCN; from 4ꢀiodobiphenyl, 2.36 g, 96%); mp 62ꢀ64 C; H NMR
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(400 MHz, CDCl3) δ 7.58ꢀ7.55 (m, 4H), 7.44 (t, J = 7.6 Hz, 2H), 7.38ꢀ7.32 (m, 3H),
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7.13 (t, J = 7.2 Hz, 1H), 7.09ꢀ7.06 (m, 4H); C NMR (100 MHz, CDCl3) δ 157.3,
157.0, 140.7, 136.4, 129.9, 128.9, 128.6, 127.2, 127.0, 123.5, 119.2, 119.2; HRMS
(EIꢀTOF) m/z calcd for C18H14O (M+) 246.1045, found 246.1039.
1-(tert-Butoxy)-4-phenoxybenzene (3e). 3e was prepared from 1ꢀ(tertꢀbutoxy)ꢀ
4ꢀbromobenzene and phenol, and purified by flash chromatography (eluting with
1
petroleum ether, Rf = 0.6) as colorless liquid (1.13 g, 93%). H NMR (500 MHz,
CDCl3) δ 7.35ꢀ7.32 (m, 2H), 7.09 (t, J = 7.5 Hz, 1H), 7.03ꢀ6.95 (m, 6H), 1.38 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 157.8, 152.7, 151.0, 129.6, 125.4, 122.8, 119.4, 118.2,
78.1, 28.7; HRMS (EIꢀTOF) m/z calcd for C16H18O2 (M+) 242.1307, found 242.1303.
Methyl(4-phenoxyphenyl)sulfane (3f). 3f was prepared from 4ꢀbromothioanisole and
phenol or from 4ꢀiodothioanisole and phenol, and purified by flash chromatography
(eluting with 1:100 EtOAc/petroleum ether, Rf = 0.5) as colorless liquid (from
4ꢀbromothioanisole, 972 mg, 90% in DMF; 994 mg, 92% in MeCN; from
1
4ꢀiodothioanisole, 1.94 g, 90%). H NMR (500 MHz, CDCl3) δ 7.35ꢀ7.31 (m, 2H),
7.27 (dt, J = 8.5, 2.5 Hz, 2H), 7.10 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 8.5 Hz, 2H), 6.96
13
(dt, J = 9.0, 2.5 Hz, 2H), 2.48 (s, 3H); C NMR (100 MHz, CDCl3) δ 157.4, 155.4,
132.4, 129.9, 129.3, 123.4, 119.7, 118.8, 17.3; HRMS (EIꢀTOF) m/z calcd for
C13H12OS (M+) 216.0609, found 216.0605.
1-(4-Phenoxyphenyl)ethanone (3g). 3g was prepared from 4ꢀbromoacetophenone and
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phenol or from 4ꢀiodoacetophenone and phenol, and purified by flash
chromatography (eluting with petroleum ether, Rf = 0.4) as yellow solid (from
4ꢀbromoacetophenone, 1.02 g, 96% in DMF; 975 mg, 92% in MeCN; from
4ꢀiodoacetophenone, 2.04 g, 96%). mp 45ꢀ47 oC; 1H NMR (400 MHz, CDCl3) δ 7.94
(d, J = 8.8 Hz, 2H), 7.40 (t, J = 8.0 Hz, 2H), 7.20 (t, J = 7.6 Hz, 1H), 7.07 (d, J = 8.0
Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 2.57 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 196.2,
161.6, 155.2, 131.6, 130.3, 129.8, 124.3, 119.8, 116.9, 26.1; HRMS (ESIꢀTOF) m/z
calcd for C14H13O2 (M + H)+ 213.0910, found 213.0912.
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Methyl 4-phenoxybenzoate (3h). 3h was prepared from methyl 4ꢀbromobenzoate and
phenol or from methyl 4ꢀiodobenzoate and phenol, and purified by flash
chromatography (eluting with petroleum ether, Rf = 0.5) as white solid (from
o
4ꢀbromobenzoate, 1.07 g, 94%; from 4ꢀiodobenzoate, 2.05 g, 90%), mp 57ꢀ59 C; 1H
NMR (500 MHz, CDCl3) δ 8.03ꢀ8.00 (m, 2H), 7.40 (t, J = 8.0 Hz, 2H), 7.20 (t, J = 7.5
13
Hz, 1H), 7.08 (d, J = 8.5 Hz, 2H), 7.03ꢀ6.98 (m, 2H), 3.91 (s, 3H); C NMR (100
MHz, CDCl3) δ 166.7, 161.9, 155.7, 131.8, 130.1, 124.6, 124.5, 120.2, 117.3, 52.1;
HRMS (ESIꢀTOF) m/z calcd for C14H13O3 (M + H)+ 229.0859, found 229.0859.
2-(4-(Trifluoromethyl)phenoxy)naphthalene (3i). 3i was prepared from 1ꢀbromoꢀ4ꢀ
(trifluoromethyl)benzene and 2ꢀnaphthol, and purified by flash chromatography
(eluting with petroleum ether, Rf = 0.5) as white solid (1.32 g, 92%), mp 66ꢀ68 oC; 1H
NMR (500 MHz, CDCl3) δ 7.90 (t, J = 9.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 1H), 7.63 (d,
J = 8.5 Hz, 2H), 7.55ꢀ7.46 (m, 3H), 7.29 (dt, J = 8.5, 2.5 Hz, 1H), 7.13 (d, J = 8.5 Hz,
13
2H); C {19F}NMR (100 MHz, CDCl3) δ 160.5 (q, J = 1.3 Hz), 153.5, 134.3, 130.8,
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130.3, 127.9, 127.3, 127.2 (q, J = 3.8 Hz), 126.8, 125.4, 125.1 (q, J = 32.6 Hz), 124.3
(q, J = 270.1 Hz), 120.2, 118.1, 115.9; HRMS (EIꢀTOF) m/z calcd for C17H11OF3 (M+)
288.0762, found 288.0764.
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1-Chloro-4-(4-methoxyphenoxy)benzene (3j). 3j was prepared from 1ꢀchloroꢀ4ꢀ
bromobenzene and 4ꢀmethoxyphenol, and purified by flash chromatography (eluting
with 1:100 EtOAc/petroleum ether, Rf = 0.3) as white solid (1.12 g, 96%), mp 49ꢀ51
oC; 1H NMR (400 MHz, CDCl3) δ 7.24 (d, J = 9.2 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H),
13
6.90ꢀ6.86 (m, 4H), 3.81 (s, 3H); C NMR (100 MHz, CDCl3) δ 157.3, 156.3, 149.9,
129.7, 127.5, 121.0, 118.9, 115.1, 55.8; HRMS (EIꢀTOF) m/z calcd for C13H11O2Cl
(M+) 234.0448, found 234.0442.
3-(3,5-Dimethylphenoxy)aniline (3k). 3k was prepared from 3ꢀbromoaniline and
3,5ꢀdimethylphenol or from 3ꢀiodoaniline and 3,5ꢀdimethylphenol, and purified by
flash chromatography (eluting with 1:5 EtOAc/petroleum ether, Rf = 0.4) as white
solid (from 3ꢀbromoaniline, 895 mg, 84%; from 3ꢀiodoaniline, 1.83 g, 86%), mp
77ꢀ78 oC; 1H NMR (400 MHz, CDCl3) δ 7.09 (t, J = 8.0 Hz, 1H), 6.74 (s, 1H), 6.65 (s,
13
2H), 6.40 (t, J = 7.6 Hz, 2H), 6.32 (s, 1H), 3.67 (s, 2H), 2.29 (s, 6H); C NMR (100
MHz, CDCl3) δ 158.7, 157.1, 148.0, 139.6, 130.4, 125.1, 116.9, 110.0, 109.1, 105.6,
21.4; HRMS (ESIꢀTOF) calcd for C14H16NO (M + H)+ 214.1226, found 214.1226.
1,3-Dimethoxy-5-phenoxybenzene (3l). 3l was prepared from 5ꢀbromoꢀ1,3ꢀdimethoxyꢀ
benzene and phenol, and purified by flash chromatography (eluting with petroleum
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ether, Rf = 0.4) as colorless liquid (943 mg, 82%). H NMR (500 MHz, CDCl3) δ
7.36ꢀ7.32 (m, 2H), 7.11 (td, J = 7.5, 1.0 Hz, 1H), 7.05 (dt, J = 7.5, 1.0 Hz, 2H), 6.22 (t,
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J = 2.0 Hz, 1H), 6.18 (d, J = 2.0 Hz, 2H), 3.75 (s, 6H); 13C NMR (100 MHz, CDCl3) δ
161.7, 159.4, 156.8, 129.9, 123.6, 119.4, 97.4, 95.6, 55.5; HRMS (EIꢀTOF) m/z calcd
for C14H14O3 (M+) 230.0943, found 230.0937.
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2-(3-Methoxyphenoxy)naphthalene (3m). 3m was prepared from 3ꢀbromoanisole (or
3ꢀiodoanisole) and 2ꢀnaphthol, and purified by flash chromatography (eluting with
1:100 EtOAc/petroleum ether, Rf = 0.4) as white solid (from 3ꢀbromoanisole, 1.16 g,
o
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93%; from 3ꢀiodoanisole, 2.30 g, 92%), mp 50ꢀ52 C. H NMR (400 MHz, CDCl3) δ
7.85ꢀ7.82 (m, 2H), 7.72 (d, J = 8.0, 1H), 7.48ꢀ7.34 (m, 2H), 7.35 (d, J = 2.0 Hz, 1H),
7.28ꢀ7.23 (m, 2H), 6.71ꢀ6.68 (m, 1H), 6.66ꢀ6.64 (m, 2H), 3.79 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 161.1, 158.5, 154.9, 134.4, 130.3 (2C), 130.0, 127.9, 127.3, 126.6,
124.9, 120.2, 114.5, 111.3, 109.3, 105.1, 55.5; HRMS (ESIꢀTOF) calcd for C17H15O2
(M + H)+ 251.1067, found 251.1066.
2-(p-Tolyloxy)benzonitrile (3n). 3n was prepared from 2ꢀbromobenzonitrile (or
2ꢀiodobenzonitrile) and pꢀcresol, and purified by flash chromatography (eluting with
1:50 EtOAc/petroleum ether, Rf = 0.3) as white solid (from 2ꢀbromobenzonitrile, 961
o
mg, 92%; from 2ꢀiodobenzonitrile , 1.92 g, 92%), mp 55ꢀ56 C. 1H NMR (500 MHz,
CDCl3) δ 7.62 (dd, J = 7.5, 1.5 Hz, 1H), 7.44 (ddd, J = 8.5, 7.5, 1.5 Hz, 1H), 7.19 (d,
J = 8.5 Hz, 2H), 7.10 (t, J = 7.5 Hz, 1H), 6.98ꢀ6.95 (m, 2H), 6.82 (d, J = 8.5 Hz, 1H),
2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.2, 152.6, 134.8, 134.2, 133.8, 130.6,
122.5, 120.0, 116.4, 116.1, 103.2, 20.8; HRMS (ESIꢀTOF) m/z calcd for C14H12NO
(M + H)+ 210.0913, found 210.0913.
2-(2-Methoxyphenoxy)naphthalene (3o). 3o was prepared from 2ꢀbromonaphthalene
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and guaiacol, and purified by flash chromatography (eluting with 1:100
EtOAc/petroleum ether, Rf = 0.3) as white solid (1.15 g, 92%), mp 79ꢀ81 oC. 1H NMR
(400 MHz, CDCl3) δ 7.82ꢀ7.79 (m, 2H), 7.66 (d, J = 8.0 Hz, 1H), 7.44ꢀ7.34 (m, 2H),
7.30ꢀ7.26 (m, 1H), 7.20ꢀ7.16 (m, 2H), 7.06ꢀ7.04 (m, 2H), 6.96 (td, J = 7.6, 1.2 Hz,
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1H), 3.84 (s, 3H); C NMR (100 MHz, CDCl3) δ 156.0, 151.6, 145.0, 134.4, 129.9,
129.7, 127.8, 127.1, 126.5, 125.1, 124.4, 121.5, 121.3, 119.1, 113.0, 111.9, 56.1;
HRMS (ESIꢀTOF) m/z calcd for C17H15O2 (M + H)+ 251.1067, found 251.1067.
(3-Phenoxyphenyl)methanol (3p). 3p was prepared from bromobenzene and
3ꢀhydroxybenzyl alcohol, and purified by flash chromatography (eluting with 1:5
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EtOAc/petroleum ether, Rf = 0.3) as colorless liquid (920 mg, 92%). H NMR (400
MHz, CDCl3) δ 7.36ꢀ7.30 (m, 3H), 7.13ꢀ7.09 (m, 2H), 7.03ꢀ7.00 (m, 3H), 6.94 (d, J =
8.0 Hz, 1H), 4.68 (d, J = 5.6 Hz, 2H), 1.66 (t, J = 5.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 157.7, 157.2, 143.1, 130.0, 129.9, 123.5, 121.7, 119.2, 118.1, 117.2, 65.1;
HRMS (ESIꢀTOF) m/z calcd for C13H13O2 (M + H)+ 201.0910, found 201.0911.
3-(4-Methoxyphenoxy)aniline (3q). 3q was prepared from 4ꢀbromoanisole and
3ꢀaminophenol, and purified by flash chromatography (eluting with 1:5
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EtOAc/petroleum ether, Rf = 0.3) as yellow liquid (903 mg, 84%). H NMR (500
MHz, CDCl3) δ 7.06 (t, J = 8.0 Hz, 1H), 6.98 (dt, J = 9.0, 3.0 Hz, 2H), 6.87 (dt, J =
9.0, 3.0 Hz, 2H), 6.36 (dd, J = 7.5, 2.5 Hz, 1H), 6.33 (dd, J = 7.5, 2.5 Hz, 1H), 6.26 (t,
13
J = 2.5 Hz, 1H), 3.80 (s, 3H), 3.66 (br s, 2H); C NMR (100 MHz, CDCl3) δ 159.9,
156.0, 150.1, 148.0, 130.4, 121.2, 114.9, 109.5, 107.9, 104.4, 55.8; HRMS (ESIꢀTOF)
m/z calcd for C13H14NO2 (M + H)+ 216.1019, found 216.1019.
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1-Chloro-4-(4-methoxyphenoxy)benzene (3r). 3r was prepared from 4ꢀmethoxyꢀ
bromobenzene and 4ꢀchlorophenol, and purified by flash chromatography (eluting
with 1:100 EtOAc/petroleum ether, Rf = 0.3) as white solid (842 mg, 72%), mp 49ꢀ51
oC. 1H NMR (400 MHz, CDCl3) δ 7.24 (d, J = 9.2 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H),
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6.90ꢀ6.86 (m, 4H), 3.81 (s, 3H); C NMR (100 MHz, CDCl3) δ 157.3, 156.3, 149.9,
129.7, 127.5, 121.0, 118.9, 115.1, 55.8; HRMS (EIꢀTOF) m/z calcd for C13H11O2Cl
(M+) 234.0448, found 234.0442.
Methyl 4-(4-Methoxyphenoxy)benzoate (3s). 3s was prepared from 1ꢀbromoꢀ4ꢀ
methoxybenzene and methyl 4ꢀhydroxybenzoate, and purified by flash
chromatography (eluting with 1:20 EtOAc/petroleum ether, Rf = 0.4) as light yellow
solid (671 mg, 52%), mp 93ꢀ95 oC. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.8 Hz,
2H), 7.02 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 4H), 3.89 (s, 3H), 3.83 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 166.8, 162.9, 156.8, 148.8, 131.8, 124.0, 121.8, 116.5,
115.2, 55.8, 52.1; HRMS (ESIꢀTOF) m/z calcd for C15H15O4 (M + H)+ 259.0965,
found 259.0967.
3-(4-Methoxyphenoxy)pyridine (3t). 3t was prepared from 3ꢀhydroxypyridine and
1ꢀbromoꢀ4ꢀmethoxybenzene or from 3ꢀiodopyridine and 4ꢀmethoxyphenol, and
purified by flash chromatography (eluting with 1:5 EtOAc/petroleum ether, Rf = 0.3)
as white solid (from 1ꢀbromoꢀ4ꢀmethoxybenzene, 683 mg, 68%; from 3ꢀiodopyridine,
1.89 g, 94% yield), mp 36ꢀ37 oC. 1H NMR (400 MHz, CDCl3) δ 8.36 (s, 1H), 8.31 (m,
1H), 7.23ꢀ7.20 (m, 2H), 7.00 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 3.82 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 156.6, 155.2, 149.3, 143.8, 140.6, 124.2, 124.1,
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121.0, 115.2, 55.8; HRMS (ESIꢀTOF) m/z calcd for C12H12NO2 (M + H)+ 202.0863,
found 202.0863.
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2-Methoxy-6-(4-methylthiophenoxy)pyridine (3u). 3u was prepared from 2ꢀbromoꢀ6ꢀ
methoxypyridine (or 2ꢀiodoꢀ6ꢀmethoxypyridine) and 4ꢀmethylthiophenol, and
purified by flash chromatography (eluting with 1:50 EtOAc/petroleum ether 1:50, Rf =
0.3) as light yellow liquid (from 2ꢀbromoꢀ6ꢀmethoxypyridine, 1.17 g, 95%; from
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2ꢀiodoꢀ6ꢀmethoxypyridine, 2.27 g, 92%). H NMR (400 MHz, CDCl3) δ 7.51 (t, J =
8.0 Hz, 1H), 7.30ꢀ7.26 (m, 2H), 7.10ꢀ7.08 (m, 2H), 6.44 (d, J = 8.4 Hz, 1H), 6.30 (d, J
= 8.0 Hz, 1H), 3.81 (s, 3H), 2.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.3, 162.3,
152.0, 141.4, 133.8, 128.3, 121.7, 104.2, 101.3, 53.5, 16.7; HRMS (ESIꢀTOF) m/z
calcd for C13H14NO2S (M + H)+ 248.0740, found 248.0740.
6-(Naphthalen-2-yloxy)pyridin-2-amine (3v). 3v was prepared from 2ꢀbromoꢀ6ꢀ
aminopyridine and 2ꢀnaphthol, and purified by flash chromatography (eluting with
1:3 EtOAc/petroleum ether, Rf = 0.4) as light yellow solid (1.13 g, 96% in DMF; 1.10
o
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g, 93% in MeCN), mp 92ꢀ94 C. H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.8, 2.0
Hz, 2H), 7.77 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 2.0 Hz, 1H), 7.49ꢀ7.39 (m, 3H), 7.30
(dd, J = 9.2, 2.4 Hz, 1H), 6.21 (d, J = 7.6 Hz, 1H), 6.14 (d, J = 7.6 Hz, 1H), 4.39 (br s,
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2H); C NMR (100 MHz, CDCl3) δ 163.2, 157.9, 152.4, 141.0, 134.3, 130.8, 129.6,
127.9, 127.5, 126.5, 125.2, 121.4, 117.1, 102.6, 99.6; HRMS (ESIꢀTOF) m/z calcd for
C15H13N2O (M + H)+ 237.1022, found 237.1021.
5-(4-Methoxyphenoxy)pyrimidine (3w). 3w was prepared from 5ꢀbromopyrimidine
and 4ꢀmethoxyphenol, and purified by flash chromatography (eluting with 1:3
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94% in MeCN), mp 54ꢀ56 C. H NMR (400 MHz, CDCl3) δ 8.91 (s, 1H), 8.41 (s,
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2H), 7.02 (dt, J = 9.2, 2.8 Hz, 2H), 6.93 (dt, J = 9.2, 2.8 Hz, 2H), 3.82 (s, 3H); C
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NMR (100 MHz, CDCl3) δ 157.1, 153.4, 152.7, 148.2, 146.0, 121.0, 115.5, 55.8;
HRMS (ESIꢀTOF) m/z calcd for C11H11N2O2 (M + H)+ 203.0815, found 203.0815.
6-Phenoxyquinoline (3x). 3x was prepared from 6ꢀbromoquinoline and phenol, and
purified by flash chromatography (eluting with 1:3 EtOAc/petroleum ether, Rf = 0.4)
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as yellow liquid (1.05 g, 95%). H NMR (400 MHz, CDCl3) δ 8.84 (d, J = 3.2 Hz,
1H), 8.10 (d, J = 9.2 Hz, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.50 (dd, J = 9.2, 2.8 Hz, 1H),
7.42ꢀ7.35 (m, 3H), 7.26ꢀ7.17 (m, 2H), 7.10 (d, J = 8.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 156.6, 155.7, 149.1, 145.2, 135.2, 131.4, 130.0, 129.2, 124.1, 123.3, 121.5,
119.6, 112.9; HRMS (ESIꢀTOF) m/z calcd for C15H12NO (M + H)+ 222.0913, found
222.0913.
6-(4-Methoxyphenoxy)-2-methylquinoline (3y). 3y was prepared from 6ꢀbromoꢀ
2ꢀmethylquinoline and 4ꢀmethoxyphenol, and purified by flash chromatography
(eluting with 1:10 EtOAc/petroleum ether, Rf = 0.4) as yellow liquid (1.06 g, 94%). 1H
NMR (500 MHz, CDCl3) δ 7.97 (d, J = 9.0 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.43 (dd,
J = 9.0, 2.5 Hz, 1H), 7.23 (d, J = 8.5 Hz, 1H), 7.08 (d, J = 2.5 Hz, 1H), 7.05 (dt, J =
13
9.0, 3.0 Hz, 2H), 6.93 (dt, J = 9.0, 3.0 Hz, 2H), 3.83 (s, 3H), 2.71 (s, 3H); C NMR
(100 MHz, CDCl3) δ 157.4, 156.4, 156.3, 149.8, 144.5, 135.4, 130.5, 127.3, 122.5,
122.5, 121.3, 115.1, 111.5, 55.8, 25.3; HRMS (ESIꢀTOF) m/z calcd for C17H16NO2 (M
+ H)+ 266.1176, found 266.1178.
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6-(4-Methoxyphenoxy)isoquinoline (3z). 3z was prepared from 6ꢀbromoiosquinoline
(or 6ꢀiodoiosquinoline) and 4ꢀmethoxyphenol, and purified by flash chromatography
(eluting with 1:1 EtOAc/petroleum ether, Rf = 0.4) as light yellow solid (from
6ꢀbromoiosquinoline, 1.20 g, 96%; from 6ꢀiodoiosquinoline, 2.41 g, 96%), mp 76ꢀ79
oC. 1H NMR (400 MHz, CDCl3) δ 9.15 (s, 1H), 8.42 (d, J = 6.0 Hz, 1H), 7.92 (d, J =
8.8 Hz, 1H), 7.44 (d, J = 5.6 Hz, 1H), 7.35 (dd, J = 9.2, 2.4 Hz, 1H), 7.10ꢀ7.06 (m,
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2H), 7.01 (d, J = 2.4 Hz, 1H), 6.98ꢀ6.94 (m, 2H), 3.85 (s, 3H); C NMR (100 MHz,
CDCl3) δ 160.4, 156.7, 151.7, 148.5, 143.4, 137.3, 129.8, 125.0, 121.7, 120.3, 119.8,
115.1, 109.1, 55.6; HRMS (ESIꢀTOF) m/z calcd for C16H14NO2 (M + H)+ 252.1019,
found 252.1019.
6-(m-Tolyloxy)quinoxaline (3aa). 3aa was prepared from 6ꢀbromoꢀquinoxaline (or
6ꢀiodoꢀquinoxaline) and 3ꢀmethylphenol, and purified by flash chromatography
(eluting with 1:5 EtOAc/petroleum ether, Rf = 0.3) as light yellow solid (from
6ꢀbromoꢀquinoxaline, 1.11 g, 94%; from 6ꢀiodoꢀquinoxaline, 2.27 g, 96%), mp 44ꢀ46
oC. 1H NMR (500 MHz, CDCl3) δ 8.74 (d, J = 9.0 Hz, 2H), 8.07 (d, J = 9.5 Hz, 1H),
7.57 (dd, J = 9.5, 2.5 Hz, 1H), 7.41 (d, J = 2.5 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 7.05
13
(d, J = 7.5 Hz, 1H), 6.98ꢀ6.94 (m, 2H), 2.37 (s, 3H); C NMR (100 MHz, CDCl3) δ
159.6, 155.4, 145.3, 144.3, 143.3, 140.6, 139.8, 131.0, 130.0, 125.8, 123.8, 121.2,
117.5, 113.0, 21.5; HRMS (ESIꢀTOF) m/z calcd for C15H13N2O (M + H)+ 237.1022,
found 237.1024.
1-Benzyl-5-(4-methoxyphenoxy)-1H-indole (3ab). 3ab was prepared from 1ꢀbenzylꢀ5ꢀ
bromoꢀindole (or 1ꢀbenzylꢀ5ꢀiodoꢀindole) and 4ꢀmethoxyphenol, and purified by flash
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chromatography (eluting with 1:50 EtOAc/petroleum ether, Rf = 0.3) as yellow liquid
(from 1ꢀbenzylꢀ5ꢀbromoꢀindole, 1.57 g, 95%; from 1ꢀbenzylꢀ5ꢀiodoꢀindole, 3.17 g,
96%). 1H NMR (400 MHz, CDCl3) δ 7.33ꢀ7.26 (m, 3H), 7.22ꢀ7.20 (m, 2H), 7.14ꢀ7.12
(m, 3H), 6.95 (d, J = 8.8 Hz, 2H), 6.90 (dd, J = 8.8, 2.0 Hz, 1H), 6.85 (d, J = 9.2 Hz,
2H), 6.46 (d, J = 2.4 Hz, 1H), 5.31 (s, 2H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 155.1, 152.5, 151.6, 137.5, 133.0, 129.4, 129.3, 128.9, 127.8, 126.9, 119.5, 114.8,
114.7, 110.6, 110.0, 101.6, 55.8, 50.4. HRMS (ESIꢀTOF) m/z calcd for C22H20NO2 (M
+ H)+ 330.1489, found 330.1489.
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5-Phenoxybenzo[b]thiophene (3ac). 3ac was prepared from 5ꢀbromobenzo[b]ꢀ
thiophene and phenol, and purified by flash chromatography (eluting with 1:100
EtOAc/petroleum ether, Rf = 0.5) as white solid (1.02 g, 90%), mp 49ꢀ51 oC. 1H NMR
(500 MHz, CDCl3) δ 7.83 (d, J = 8.5 Hz, 1H), 7.48 (d, J = 5.5 Hz, 1H), 7.43 (d, J =
2.5 Hz, 1H), 7.35 (t, J = 8.0 Hz, 2H), 7.25 (d, J = 5.5 Hz, 1H), 7.11 (td, J = 8.0, 1.5
Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 158.0, 154.6, 140.9,
134.9, 129.9, 128.1, 123.8, 123.6, 123.1, 118.6, 117.6, 113.2; HRMS (EIꢀTOF) m/z
calcd for C14H10OS (M+) 226.0452, found 226.0451.
1-Methoxy-4-phenoxybenzene (3ad). 3ad was prepared from 1ꢀmethoxyꢀ4ꢀ
iodobenzene and phenol, and purified by flash chromatography (eluting with
1
petroleum ether, Rf = 0.4) as colorless liquid (1.52 g, 76%). H NMR (500 MHz,
CDCl3) δ 7.32ꢀ7.28 (m, 2H), 7.04 (td, J = 7.5, 1.0 Hz, 1H), 7.00ꢀ6.97 (m, 2H), 6.96ꢀ
13
6.93 (m, 2H), 6.91ꢀ6.87 (m, 2H), 3.81 (s, 3H); C NMR (100 MHz, CDCl3) δ 158.7,
156.0, 150.3, 129.7, 122.6, 121.0, 117.7, 115.0, 55.8; HRMS (EIꢀTOF) m/z calcd for
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C13H12O2 (M+) 200.0837, found 200.0841.
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(4-Phenoxyphenyl)methanol (3ae). 3ae was prepared from 4ꢀiodobenzyl alcohol and
phenol, and purified by flash chromatography (eluting with 1:3 EtOAc/petroleum
ether, Rf = 0.4) as light yellow solid (1.80 g, 90%), mp 48ꢀ50 oC. 1H NMR (500 MHz,
CDCl3) δ 7.35ꢀ7.32 (m, 4H), 7.12ꢀ7.09 (m, 1H), 7.02ꢀ6.99 (m, 4H), 4.66 (d, J = 5.5
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Hz, 2H), 1.77 (br s, 1H); C NMR (100 MHz, CDCl3) δ 157.3, 156.9, 135.8, 129.9,
128.8, 123.4, 119.1, 119.0, 65.0; HRMS (EIꢀTOF) m/z calcd for C13H12O2 (M+)
200.0837, found 200.0840.
1-Methyl-2-(p-tolyloxy)benzene (3af). 3af was prepared from 2ꢀiodotoluene and
pꢀcresol, and purified by flash chromatography (eluting with petroleum ether, Rf = 0.6)
1
as colorless liquid (1.43 g, 72%). H NMR (500 MHz, CDCl3) δ 7.24 (d, J = 7.5 Hz,
1H), 7.14 (t, J = 7.5 Hz, 1H), 7.10 (d, J = 8.5 Hz, 2H), 7.04 (t, J = 7.5 Hz, 1H), 6.87
13
(d, J = 8.0 Hz, 1H), 6.82 (d, J = 8.5 Hz, 2H), 2.32 (s, 3H), 2.26 (s, 3H); C NMR
(100 MHz, CDCl3) δ 155.6, 155.1, 132.0, 131.5, 130.2, 129.8, 127.2, 123.7, 119.3,
117.6, 20.8, 16.4; HRMS (ESIꢀTOF) m/z calcd for C14H15O (M + H)+ 199.1117, found
199.1117.
4-Methoxy-2-(4-methylthiophenoxy)pyrimidine (3ag). 3ag was prepared from
2ꢀiodoꢀ4ꢀmethoxypyrimidine and 4ꢀmethylthiophenol, and purified by flash
chromatography (eluting with 1:5 EtOAc/petroleum ether, Rf = 0.4) as white solid
o
1
(2.33 g, 94%), mp 106ꢀ108 C. H NMR (500 MHz, CDCl3) δ 8.18 (d, J = 6.0 Hz,
1H), 7.31 (dt, J = 9.0, 2.5 Hz, 2H), 7.14 (dt, J = 9.0, 2.5 Hz, 2H), 6.45 (d, J = 5.5 Hz,
13
1H), 3.95 (s, 3H), 2.50 (s, 3H); C NMR (100 MHz, CDCl3) δ 171.9, 165.1, 158.6,
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150.6, 135.1, 128.2, 122.4, 103.5, 54.2, 16.6; HRMS (ESIꢀTOF) m/z calcd for
C12H13O2N2S (M + H)+ 249.0692, found 249.0694.
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3-(4-Fluorophenoxy)thiophene (3ah). 3ah was prepared from 3ꢀiodothiophene and
4ꢀfluorophenol, and purified by flash chromatography (eluting with petroleum ether,
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Rf = 0.5) as yellow liquid (1.86 g, 96%). H NMR (500 MHz, CDCl3) δ 7.25 (dd, J =
5.0, 3.0 Hz, 1H), 7.02 (d, J = 6.0 Hz, 4H), 6.83 (dd, J = 5.0, 1.5 Hz, 1H), 6.53 (dd, J =
3.5, 1.5 Hz, 1H); 13C {19F}NMR (100 MHz, CDCl3) δ 158.9 (d, J = 240.3 Hz), 155.0,
153.9 (d, J = 2.4 Hz), 125.5, 120.5, 119.7 (d, J = 8.3 Hz), 116.3 (d, J = 23.2 Hz),
106.1; HRMS (ESIꢀTOF) m/z calcd for C10H8OFS (M + H)+ 195.0274, found
195.0275.
5-(4-Methoxyphenoxy)benzofuran (3ai). 3ai was prepared from 5ꢀiodobenzofuran and
4ꢀmethoxyphenol, and purified by flash chromatography (eluting with 1:100
EtOAc/petroleum ether, Rf = 0.4) as light yellow solid (2.28 g, 95%), mp 39ꢀ41 oC. 1H
NMR (400 MHz, CDCl3) δ 7.62 (d, J = 2.0 Hz, 1H), 7.43 (d, J = 8.8 Hz, 1H), 7.13 (d,
J = 2.0 Hz, 1H), 7.00ꢀ6.94 (m, 3H), 6.89ꢀ6.86 (m, 2H), 6.69 (m, 1H), 3.80 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 155.6, 154.1, 151.7, 151.2, 146.2, 128.3, 120.0, 116.1,
114.9, 112.1, 110.0, 106.9, 55.7; HRMS (EIꢀTOF) m/z calcd for C15H12O3 (M+)
240.0786, found 240.0783.
5-(4-Methoxyphenoxy)benzo[b]thiophene
(3aj). 3aj was prepared from
5ꢀiodobenzo[b]thiophene and 4ꢀmethoxyphenol, and purified by flash
chromatography (eluting with 1:100 EtOAc/petroleum ether, Rf = 0.4) as light yellow
solid (2.41 g, 94%), mp 69ꢀ71 oC. 1H NMR (500 MHz, CDCl3) δ 7.79 (d, J = 9.0 Hz,
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1H), 7.46 (d, J = 5.5 Hz, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.22 (d, J = 5.5 Hz, 1H), 7.08
(dd, J = 9.0, 2.5 Hz, 1H), 7.03ꢀ6.99 (m, 2H), 6.92ꢀ6.88 (m, 2H), 3.82 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 156.1, 155.9, 150.9, 140.8, 134.1, 128.0, 123.8, 123.5,
120.6, 116.7, 115.0, 111.6, 55.8; HRMS (EIꢀTOF) m/z calcd for C15H12O2S (M+)
256.0558, found 256.0556.
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3-(4-Methoxyphenoxy)benzo[b]thiophene (3ak). 3ak was prepared from
3ꢀiodobenzo[b]thiophene and 4ꢀmethoxyphenol, and purified by flash
chromatography (eluting with 1:100 EtOAc/petroleum ether, Rf = 0.5) as light yellow
solid (2.25 g, 88%), mp 93ꢀ95 oC. 1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 9.2, 5.6
Hz, 2H), 7.39ꢀ7.37 (m, 2H), 7.10 (d, J = 9.2 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 6.44 (s,
13
1H), 3.82 (s, 3H); C NMR (100 MHz, CDCl3) δ 156.2, 150.9, 149.7, 138.1, 132.2,
125.3, 124.2, 123.2, 121.2, 120.1, 114.9, 104.3, 55.8; HRMS (EIꢀTOF) m/z calcd for
C15H12O2S (M+) 256.0558, found 256.0555.
Acknowledgements: The authors are grateful to the National Natural Science
Foundation of China (grant 21132008) and Chinese Academy of Sciences (supported
by the Strategic Priority Research Program, grant XDB20020200
QYZDJꢀSSWꢀSLH029) for their financial support.
&
Supporting Information: The copies of 1H and 13C NMR spectrum of products. This
material is available free of charge via the Internet at http://pubs.acs.org
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B.; Shingare, M. S. Tetrahedron Lett. 2009, 50, 4019ꢀ4021. (h) Monnier, F.;
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Li, Z.; Xu, J.; Hu, S. J. Org. Chem. 2008, 73, 7814ꢀ7817. (j) Navarro, L.; Pujol,
M. D. Tetrahedron Lett. 2015, 56, 1812ꢀ1815. (k) Rovira, M.; Soler, M.; Güell, I.;
Wang, M.ꢀZ.; Gómez, L.; Ribas, X. J. Org. Chem. 2016, 81, 7315ꢀ7325.
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5691ꢀ5693. (g) Song, G.ꢀL.; Zhang, Z.; Da, Y.ꢀX.; Wang, X.ꢀC. Tetrahedron 2015,
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Chem. 2016, 81, 10392ꢀ10403. (c) Tan, G.; Chen, S.; Siu, C.; Langlois, A.; Qiu,
Y.; Fan, H.; Ho, C.; Harvey, P. D.; Lo, Y.; Liu, L. J. Mat. Chem. C, 2016, 4,
6016ꢀ6026. (d) Lee, M.; Ikejiri, M.; Klimpel, D.; Toth, M.; Espahbodi, M.; Hesek,
D.; Forbes, C.; Kumarasiri, M.; Noll, B. C.; Chang, M. ACS Med. Chem. Lett.
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6. Enache, L. A.; Kennedy, I.; Sullins, D. W.; Chen, W.; Ristic, D.; Stahl, G. L.;
Dzekhtser, S.; Erickson, R. A.; Yan, C. R.; Muellner, F. W. Org. Proc. Res. Dev.
2009, 17, 1173ꢀ1184.
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7. Taillefer and Bolm groups have described Cuꢀcatalyzed diaryl formation at low
catalytic loadings, see references 3b, 3c, 3h, 4e and 4f. However in their studies
only one example was demonstrated, implying that the generality of their
methods is questionable.
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