Copper/iron-catalyzed Ullmann coupling of diiodo- and dibromoarenes and diphenols for the synthesis of aryl ether macrocycles

Article abstract of DOI:10.1016/j.tet.2013.12.089

Diiodoarenes (or dibromoarenes) reacted with diphenols, catalyzed by CuI/Fe(acac)₃ in the presence of K₂CO₃ in anhydrous DMSO at 110°C for 7 days under nitrogen atmosphere, to afford macrocyclic aryl ethers effectively. To expand this methodology, a cyclic hepta(p-phenylene oxide) and cyclic deca(p-phenylene oxide) were synthesized in one pot. Some macrocyclic aryl ethers showed strong fluorescence in acetone at 25°C.

Full text of DOI:10.1016/j.tet.2013.12.089

Tetrahedron 70 (2014) 1125e1132
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper/iron-catalyzed Ullmann coupling of diiodo- and
dibromoarenes and diphenols for the synthesis of aryl ether
macrocycles
Qizhong Zhou a
,
b
,
d
,
, Liangjun Su , Tiansheng Jiang , Bin Zhang , Rener Chen ,*,
a
c
a
a
*
a
,
a
a
a
a
*
Huajiang Jiang , Yuyuan Ye , Mengqing Zhu , Deman Han , Jianfen Shen ,
a
b
Guoliang Dai , Zhanting Li
Department of Chemistry, Taizhou University, Taizhou 318000, China
Department of Chemistry, Fudan University, Shanghai 200433, China
College of Natural Sciences and Mathematics, University of Houston, Houston, TX 77204-5008, USA
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, China
a
b
c
d
a r t i c l e i n f o
a b s t r a c t
Article history:
Diiodoarenes (or dibromoarenes) reacted with diphenols, catalyzed by CuI/Fe(acac) in the presence of
3
Received 4 November 2013
Received in revised form 24 December 2013
Accepted 31 December 2013
Available online 8 January 2014
ꢀ
K
2
CO
3
in anhydrous DMSO at 110 C for 7 days under nitrogen atmosphere, to afford macrocyclic aryl
ethers effectively. To expand this methodology, a cyclic hepta(p-phenylene oxide) and cyclic deca(p-
phenylene oxide) were synthesized in one pot. Some macrocyclic aryl ethers showed strong fluorescence
ꢀ
in acetone at 25 C.
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
new efficient method for synthesizing macrocyclic aryl ethers from
diiodoarenes (dibromoarenes) and diphenols catalyzed by copper/
Copper-catalyzed Ullmann-type intermolecular CeO coupling
reactions of aryl halides and phenols have been widely investigated
and found many applications in the preparation of various
iron in one-step because such kind of macrocycles may be used as
new electron-rich receptors for molecular recognition or for as-
sembling new interlocked supramolecular architectures. First, a set
of experiments were performed using 1,4-diiodobenzene (1a) and
diphenol (2a) as model substrates in the presence of different li-
gands (or Fe) or bases at varying temperatures to optimize the re-
1
e14
aryl ether deriviatives,
including natural products myr-
15
icatomentogenin, jugcathanin, galeon, and (þ)-pterocarine, and
16
tricyclic biaryl ether-linked aza-heterocyclic systems. Previously,
we reported the copper-catalyzed highly regioselective 2-
action conditions (Table 1). The preliminary survey, carried out at
17
ꢀ
aryloxylation of 2,x-dihalopyridines. Herein, we describe the
synthesis of macrocyclic aryl ethers through copper/iron-catalyzed
biarylation of diphenols.
140 C with CuI, K
2
CO
3
with various ligands, helped us to evaluate
the most efficient catalytic system for this coupling (entries 1e5).
With CuI as copper source, Me NCH COOH$HCl as ligand and
CO as base, the reaction afforded 3a in 32% isolated yield (entry
). It was found that in DMSO, under the catalysis of CuI and
2
2
K
2
3
5
2
. Results and discussion
Fe(acac)
3
, diphenol was not consumed completely even after 7 d at
ꢀ
140 C, delivering 3a in 33% yield (entry 6). Changing bases from
Staab first reported that symmetric macrocyclic compound 3b1
K
2
CO
NaH, we found that K
placement of CuI with CuBr, CuCl, Cu O, CuO, Cu(OTf) , Cu(OAc) or
3
to KOAc, KHCO
3
, Na
2
CO
3 3 4 2 3 2
, K PO , Cs CO , NaOH, KOH, CaH or
(
4
entry 2, Table 2) could be prepared by the coupling of 1,3-dinitro-
,6-dichlorobenzene and resorcine followed by denitration, but the
2
CO
3
is the best base (entries 6e15). Re-
18
two-step yield was only 0.91%. Wang and co-workers reported
the synthesis of heteroatom-bridged calixarenes
2
2
2
1
9a
CuBr2 showed that CuI is the best copper source (entries 14 and
6e22). Then we screened various iron sources and found that
Fe(acac) was the best (entries 14 and 23e29). Replacement of CuI
and electron-
1
deficient oxacalix[2]arene[2]triazines and their isomeric ana-
19b
logues through nucleophilic reactions.
We planed to develop
3
(
20%)/Fe(acac)
3
(20%) with CuI (5%)/Fe(acac)
3
(5%) or CuI (10%)/
(10%) was the
Fe(acac) (10%) indicated that CuI (10%)/Fe(acac)
3
3
*
Corresponding authors. Tel.: þ86 576 88660177; e-mail addresses: qizhong-
best catalytic system (entries 6 and 30, 31). Screening of the con-
centration of the substrates showed that the best concentration of
chou@yahoo.com, qizhongchou@tzc.edu.cn (Q. Zhou), cre@tzc.edu.cn (R. Chen),
jhj@tzc.edu.cn (H. Jiang).
0
040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.12.089

1126
Q. Zhou et al. / Tetrahedron 70 (2014) 1125e1132
Table 1
a,b
Copper-catalyzed biarylation of diphenol for the synthesis of a macrocyclic aryl ether
ꢀ
Entry
Cu
Ligand or Fe
Base
Solvent
T/ C
Yield%
(
3a)
c
1
2
3
4
5
6
7
8
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuBr (20%)
CuCl (20%)
TMEDA (20%)
3030-47-5 (20%)
L-Proline (20%)
Phen (20%)
K
K
K
K
K
K
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO (AR)
DMF (AR)
1,4-Dioxane (AR)
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
100
110
110
120
130
150
110
110
110
110
Reflux
0
0
0
19
32
33
4
29
27
17
30
0
c
c
c
c
2491-06-7 (20%)
c
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
2
(20%)
20%)
c
KOAc
KHCO
c
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
3
c
9
Na
PO
CO
2
CO
3
c
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
K
3
4
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
d
e
d
d
d
d
d
d
f
Cs
2
3
NaOH
KOH
CaH
NaH
0
2
24
13
17
4
3
0
0
6
8
11
7
CaH
CaH
CaH
CaH
CaH
CaH
CaH
CaH
CaH
CaH
CaH
CaH
CaH
CaH
K
K
K
K
K
K
2
2
2
2
2
2
2
2
2
2
2
2
2
2
Cu
2
O (20%)
CuO (20%)
Cu(OTf)
Cu(OAc)
CuBr
2
(20%)
(20%)
(20%)
2
2
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (5%)
CuI (10%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (10%)
CuI (20%)
CuI (20%)
CuI (20%)
CuI (10%)
CuI (10%)
CuI (10%)
CuI (10%)
CuI (10%)
Fe(OTf)
2
(20%)
dppf (20%)
7
0
0
8
FeCl
FeCl
2
3
(20%)
(20%)
Fe(OTf)
3
(20%)
4
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
3
(5%)
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
3
23
36
44
38
33
44
48
36
29
31
28
15
28
23
0
3
3
3
3
3
(10%)
(20%)
(20%)
(20%)
(20%)
(10%)
(20%)
(20%)
(20%)
(10%)
(10%)
(10%)
(10%)
(10%)
3
3
3
3
3
Fe(acac)
3
2 3
K CO
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
Fe(acac)
3
K
K
K
K
K
K
K
K
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
g
d
d
d
The bold signifies the best reaction condition.
a
Reaction conditions: 1a (1 mmol), 2a (1 mmol), base (4 mmol), DMSO (anhydrous), 7 d.
Isolated yield.
Substrate is 0.02 mol/L.
Substrate is 0.01 mol/L.
Substrate is 0.005 mol/L.
Substrate is 0.05 mol/L.
b
c
d
e
f
g
2 2
Substrate is 0.1 mol/L; 3030-47-5: 1,1,4,7,7-Pentamethyldiethylenetriamine; 2491-06-7: Me NCH COOH$HCl.
substrates was 0.01 mol/L (entries 6, 32, 33, and 40, 41). From re-
With the optimized reaction condition available, the scope of
the reaction of diiodoarenes and diphenols was then investigated
(Table 2). It can be found that the reactions of diiodoarenes (1ae1d)
generally afforded the related macrocyclic products (3ae3h) in
moderate to good yields (36e56%). Reaction of 1,2-diiodobenzene
(1e) and diphenol (2d) gave rise to no product and its reaction
with diphenols (2ee2g) produced the corresponding six-mem-
bered ring (3je3l) in 12e18% yields. Clearly, the new methodology
has the advantages of higher yields, more generality, simpler, and
ꢀ
actions performed at various temperatures, we found that 110
C
was the best temperature (entries 34e39). We examined several
solvents, such as DMSO (anhydrous), DMSO (AR), DMF (AR), and
1
,4-dioxane (AR) (see entries 36 and 42e44), we found that DMSO
anhydrous) is the best solvent. Based on these results, we thus
established the optimized conditions for this reaction: CuI (10%)/
(
Fe(acac)
3
(10%) as the catalysis system, K
2
CO
3
as the base, DMSO
ꢀ
(
anhydrous, 100 mL) as the solvent and at 110 C under nitrogen
18
atmosphere for 7 d.
cheaper catalyst system.

Q. Zhou et al. / Tetrahedron 70 (2014) 1125e1132
1127
Table 2
a,b
Scope of copper/iron-catalyzed biarylation of diphenols using diiodoarenes
Entry
1
1
2
Products
Yield (%)
1a
2a
48
55
3a
2
1b
2b
3
b1
1
6
3
b2
3
1b
2a
56
48
3
c
4
5
1b
1c
2c
2a
3
d
39
3e
(continued on next page)

1128
Q. Zhou et al. / Tetrahedron 70 (2014) 1125e1132
Table 2 (continued )
Entry
1
2
Products
Yield (%)
6
7
1c
2b
2a
36
3f
1d
54
3
g
8
1d
2b
38
3
h
9
1e
1e
2d
2e
0
3
i
10
18
3
j
1
1
1
2
1e
1e
2f
16
12
3
k
2g
3
l
a
ꢀ
3 2 3 2
Reaction condition: 1 (1 mmol), 2 (1 mmol), CuI (10 mol %), Fe(acac) (10 mol %), K CO (4 mmol) in DMSO (anhydrous, 100 mL) at 110 C under N for 7 d.
Isolated yield.
b
By using the above optimized reaction condition, we also in-
oxide) (8). Copper/iron catalyzed coupling reaction is being in-
vestigate the scope of the reaction of dibromoarenes and diphenols
and the results are provided in Table 3. It can be found that all the
studied dibromoarenes (4ae4f) underwent the macrocyclization
and the corresponding macrocyclic products (5ae5i) could be ob-
tained in 5e60% yields.
vestigated and the results will be reported in due course.
4. Experimental section
4.1. General
To expand this methodology, we further performed the reaction
of diiodide (1c) with the longer diphenol (6) (Scheme 1), which
gave rise to cyclic hepta(p-phenylene oxide) (7) and deca(p-phe-
nylene oxide) (8) in 8% and 15% yields, respectively.
Typical procedure for the synthesis of starting material (com-
pound 9): A suspension of 1,3-diiodobenzene (19.8 g, 0.06 mol), 2-
methoxyphenol (37.24 g, 0.3 mol), Fe(acac) (2.12 g, 6 mmol), CuI
3
Interestingly, some macrocyclic aryl ethers showed strong
(1.14 g, 6 mmol), and K CO (33.12 g, 0.24 mol) in DMSO (AR,
2
3
ꢀ
ꢀ
fluorescence in acetone at 25 C (see Fig. 1), which may be used as
200 mL) was stirred at 110 C under nitrogen atmosphere for 6 d.
novel fluorescent probe.
When the reaction mixture was cool, the mixture was filtered. The
2 2
solid was washed with CH Cl (400 mL). The solution was washed
3
. Conclusion
with NaOH (1 mol/L, 400 mLꢁ3). Then organic phase was separated
and distilled off. The residue was subjected to column chroma-
In summary, we have described an effective approach to the
tography (petroleum ether/CH
2 2
Cl , 20:1) to give the desired prod-
synthesis of macrocyclic aryl ethers, which involves the copper/
iron-catalyzed direct biarylation of diphenols. The practicality of
the new method has been demonstrated through the preparation
of cyclic hepta(p-phenylene oxide) (7) and deca(p-phenylene
uct compound 9 (13.42 g, 63%) as a white solid.
4.1.1. Compound 9. White solid; mp 121e122 C; 1H NMR (CDCl
400 MHz): 7.08e7.18 (m, 3H), 6.88e7.01 (m, 6H), 6.57e6.62 (m, 3H),
ꢀ
3
,

Q. Zhou et al. / Tetrahedron 70 (2014) 1125e1132
1129
Table 3
a,b
Scope of copper/iron-catalyzed biarylation of diphenols using dibromoarenes
Entry
4
2
Products
Yield (%)
1
4a
2b
5
5a
2
4b
2a
13
5
b
3
4b
2b
60
5c
4
5
6
7
4b
4c
4d
4e
2c
2a
2a
2a
48
19
16
5
d
5
e
f
5
14
(
continued on next page)
5
g

1130
Q. Zhou et al. / Tetrahedron 70 (2014) 1125e1132
Table 3 (continued )
Entry
4
2
Products
Yield (%)
14
8
4f
2a
5
h
9
4f
2b
5
5
i
a
ꢀ
Reaction condition: 4 (1 mmol), 2 (1 mmol), CuI (10 mol %), Fe(acac) (10 mol %), K CO (4 mmol) in DMSO (anhydrous, 100 mL) at 110 C under N for 7 d.
3 2 3 2
b
Isolated yield.
residue was subjected to column chromatography (CH
0:1 to 10:1) to give the desired product 10 (11.62 g, 95%) as a white
solid.
2 2
Cl /EtOAc,
3
ꢀ
4
4
4
1
(
.1.2. Compound 10. White solid; mp 91e92 C; 1H NMR (CDCl
00 MHz): 7.22e7.27 (m, 1H), 7.03e7.06 (m, 4H), 6.83e6.94 (m,
3
,
13
H), 6.71e6.73 (m, 3H), 5.54 (s, 2H); C NMR (CDCl
58.6, 147.8, 143.0, 131.0, 125.6, 121.1, 119.7, 116.8, 112.7, 107.9; HRMS
EI) calcd for C18 : 294.0894, found: 294.0892.
3
, 100 MHz):
14 4
H O
Procedure for the synthesis of starting material (compound 1d):
1,3-diiodobenzene (1.98 g, 6.0 mmol), 3-iodophenol (0.44 g,
2
2 3
mmol), K CO (0.552 g, 4.0 mmol), CuI (38.0 mg, 10 mol %),
Fe(acac)
3
(70.6 mg, 10 mol %) were dissolved in DMSO (AR, 10 mL).
ꢀ
The solution was stirred at 110 C under nitrogen atmosphere for
Scheme 1. Application of the 1c and 6 to compound 7 and 8.
6
d and then cooled and the solid was filtered off. The filtrate was
dissolved in CH Cl (20 mL). The solution was washed with NaOH
2
2
(
1 mol/L, 20 mLꢁ3) and dried over sodium sulfate. Upon removal of
the solvent with a rotavapor, the resulting residue was subjected to
column chromatography (petroleum ether) to give the desired
product 1d (590.8 mg, 70%) as a colorless oil.
.1.3. Compound 1d.20 Colorless liquid; H NMR (CDCl
1
, 400 MHz):
4
3
7
.46 (d, J¼7.6 Hz, 2H), 7.35 (s, 2H), 7.06 (t, J¼8.4 Hz, 2H), 6.96 (dd,
13
J
1
¼1.2 Hz, J
31.5, 128.3, 118.6, 94.6.
Typical procedure for the biarylation of diphenols using diio-
doarenes or dibromoarenes (3ae3l, 5ae5i): 1,4-diiodobenzene
2
¼1.2 Hz, 2H); C NMR (CDCl
3
, 100 MHz): 157.5, 133.2,
1
(0.330 g, 1.0 mmol), compound 2a (0.294 g, 1 mmol), K
2 3
CO
(
0.552 g, 4.0 mmol), CuI (19.0 mg, 10 mol %), Fe(acac) (35.3 mg,
3
1
0 mol %) were dissolved in DMSO (anhydrous, 100 mL). The so-
ꢀ
lution was stirred at 110 C under nitrogen atmosphere for 7 d.
When the reaction was cool, the mixture was filtered off, and
2 2
washed with CH Cl (200 mL). The solution was washed with NaOH
Fig. 1. Fluorescence of some macrocyclic aryl ethers was excited at 370 nm in acetone
at 25 C (concentration of substrates is 1 mmol/L).
ꢀ
(1 mol/L, 200 mLꢁ3) and dried over sodium sulfate. Upon removal
of the solvent with a rotavapor, the resulting residue was subjected
to column chromatography (petroleum ether/CH
to give the desired product 3a (177.4 mg, 48.2%) as a white solid.
2 2
Cl , 20:1 to 4:1)
3
1
C
.81 (s, 6H); 13C NMR (CDCl
25.3, 121.5, 121.3, 113.0, 111.3, 106.8, 56.2; HRMS (EI) calcd for
: 322.1203, found: 322.1205.
Typical procedure for the synthesis of starting material (com-
pound 10): To a solution of compound 9 (13.4 g, 41.6 mmol) in
anhydrous CHCl (100 mL), BBr (41.6 g, 0.166 mol) was added in
3
, 100 MHz): 159.4, 151.7, 144.9, 130.1,
ꢀ
1
H
20 18
O
4
4.1.4. Compound 3a. White solid; mp >250 C; H NMR (DMSO-d
400 MHz): 7.38 (t, J¼8.4 Hz, 2H), 7.09 (s, 8H), 6.86 (dd, J ¼2.4 Hz,
,100 MHz):
6
,
1
1
3
J
2
¼2.4 Hz, 4H), 5.10 (t, J¼2.4 Hz, 2H); C NMR (DMSO-d
6
3
3
160.8, 151.1, 131.1, 124.3, 109.8, 100.0; HRMS (EI) calcd for C24
16 4
H O :
dropwise. After addition, the mixture was stirred at room tem-
perature for 48 h. Then water (100 mL) was slowly added into the
mixture in an ice bath. The mixture was washed with water
368.1049, found: 368.1048.
4.1.5. Compound 3b1. White solid; mp 234e235 C (lit.18 mp
1
8
ꢀ
ꢀ
1
(
100 mL). Then organic phase was separated and distilled off. The
232e234 C); H NMR (CDCl
3
, 400 MHz): 7.32 (t, J¼8.4 Hz, 4H), 6.86

Q. Zhou et al. / Tetrahedron 70 (2014) 1125e1132
1131
(
(
dd, J
CDCl
1
¼2.0 Hz, J
2
¼2.4 Hz, 8H), 6.31 (t, J¼2.4 Hz, 4H); 13C NMR
J¼2.0 Hz, 2H); 13C NMR (CDCl
3
, 100 MHz): 161.5, 160.5, 155.9, 151.4,
132.1, 130.8, 120.0, 116.5, 112.8, 112.5, 110.9, 101.8; HRMS (EI) calcd
3
, 100 MHz): 158.1, 131.5, 115.2, 107.7.
14 4
for C22H O S: 374.0614, found: 374.0613.
ꢀ
4
(
.1.6. Compound 3b2. White solid; mp 172e173 C; 1H NMR
CDCl
ꢀ
1
3
, 400 MHz): 7.24 (t, J¼8.0 Hz, 8H), 6.74 (dd, J
1
¼2.4 Hz,
4.1.17. Compound 5b. White solid; mp 214e215 C; H NMR (CDCl
3
,
13
J
2
¼2.8 Hz, 16H), 6.61 (t, J¼2.0 Hz, 8H); C NMR (CDCl
3
, 100 MHz):
400 MHz): 8.31 (d, J¼5.6 Hz, 1H), 7.32 (t, J¼8.0 Hz, 2H), 6.99 (s, 4H),
þ
13
1
58.3, 130.9, 114.3, 109.8; MALDI: 736.2 (M ), HRMS (MALDI) calcd
6.72e6.92 (m, 6H), 5.16 (s, 1H), 5.00 (s, 1H); C NMR (CDCl
100 MHz): 166.0, 164.4, 162.1, 162.0, 159.8, 159.7, 152.9, 152.6, 151.7,
31.1, 125.0, 124.7, 116.5, 112.0, 111.9 (d, J¼7.5 Hz), 111.8, 111.4, 103.5,
102.8; HRMS (EI) calcd for C23 : 369.0999, found: 369.1001.
3
,
þ1
for C48H33O8 : 737.2182, found: 737.2170.
1
ꢀ
1
4
.1.7. Compound 3c. White solid; mp 211e212 C; H NMR (CDCl
3
,
H15NO
4
4
00 MHz): 7.25e7.34 (m, 3H), 6.97 (s, 4H), 6.74e6.86 (m, 7H), 5.19
13
ꢀ
1
(
1
(
t, J¼1.6 Hz, 2H); C NMR (CDCl
53.0, 132.0, 130.7, 124.7, 120.2, 118.2, 111.1, 110.0, 102.8; HRMS
MALDI) calcd for C24 : 368.1045, found: 368.1043.
3
, 100 MHz): 162.2, 161.2, 156.5,
4.1.18. Compound 5c. White solid; mp 190e191 C; H NMR (CDCl
400 MHz): 8.21 (d, J¼5.6 Hz, 1H), 7.31e7.39 (m, 3H), 6.79e6.98 (m,
7H), 6.55 (dt, J ¼2.0 Hz, 2H), 6.04 (t, J¼1.6 Hz, 1H), 5.87
¼2.0 Hz, J
, 100 MHz): 167.4, 165.6, 159.4,
3
,
16
H O
4
1
2
13
(
d, J¼2.0 Hz, 1H); C NMR (CDCl
3
.1.8. Compound 3d. White solid; mp 162e163 C; 1H NMR
DMSO-d
J¼7.6 Hz, 4H), 5.33 (s, 2H); C NMR (DMSO-d
ꢀ
158.9, 157.7, 157.3, 155.3, 154.8, 150.6, 132.1, 132.0, 131.6, 118.1, 117.9,
117.3, 116.9, 114.1, 113.9, 111.7, 111.3, 110.4, 105.3, 95.6; HRMS (EI)
4
(
6
, 400 MHz): 7.26 (s, 8H), 7.01 (t, J¼8.0 Hz, 2H), 6.52 (d,
13
6
, 100 MHz): 157.6,
4
calcd for C23H15NO : 369.0997, found: 369.1001.
16 4
145.7,130.4,126.9,125.5,110.0, 102.2; HRMS (EI) calcd for C24H O :
4.1.19. Compound 5d. White solid; mp 157e158 C; 1H NMR
DMSO-d
, 400 MHz): 7.84 (d, J¼2.4 Hz,1H), 7.25e7.34 (m, 8H), 7.04
(t, J¼7.2 Hz, 1H), 6.53e6.59 (m, 3H), 5.31 (s, 1H), 5.06 (s, 1H);
NMR (DMSO-d , 100 MHz): 165.2, 163.7, 157.6, 157.5, 149.1, 145.7,
ꢀ
3
68.1054, found: 368.1049.
(
6
ꢀ
1
13
4
4
2
.1.9. Compound 3e. White solid; mp 227e228 C; H NMR (CDCl
3
,
C
00 MHz): 7.33 (t, J¼8.0 Hz, 2H), 6.93e6.96 (m, 10H), 6.81e6.83 (m,
6
13
H), 6.74 (s, 4H), 6.03 (t, J¼2.4 Hz, 2H); C NMR (CDCl
3
, 100 MHz):
145.3 (d, J¼3.3 Hz), 145.0, 144.3, 130.8, 127.9, 127.4, 127.3, 127.1,
160.5, 158.2, 156.8, 153.5, 151.2, 131.1, 122.5, 122.3, 119.4, 114.3, 113.7,
125.6, 125.5, 125.3, 125.2, 110.5, 107.8, 102.3, 95.6; HRMS (EI) calcd
105.8; HRMS (MALDI) calcd for
C
H
30 20
O
5
:
460.1311, found:
4
for C23H15NO : 369.1004, found: 369.1001.
4
60.1305.
ꢀ
1
4
.1.20. Compound 5e. White solid; mp 238e239 C; H NMR (CDCl
400 MHz): 8.03 (d, J¼2.8 Hz, 1H), 7.41 (dd, J ¼3.2 Hz, J ¼2.8 Hz, 1H),
7.30e7.35 (m, 2H), 6.96e7.02 (m, 5H), 6.84e6.88 (m, 4H), 5.19 (t,
3
,
ꢀ
1
4
4
2
.1.10. Compound 3f. White solid; mp 171e172 C; H NMR (CDCl
3
,
1
2
00 MHz): 7.33 (t, J¼8.0 Hz, 2H), 6.91e7.03 (m, 11H), 6.80e6.83 (m,
H), 6.70 (t, J¼2.0 Hz, 1H), 6.40 (dd, J ¼2.0 Hz, J ¼2.0 Hz, 2H), 6.04
, 100 MHz): 160.1, 158.7, 157.7,
56.6, 151.5, 131.2, 129.6, 122.5, 122.1, 114.0, 113.7, 112.3, 110.7, 105.3;
HRMS (EI) calcd for C30 : 460.1313, found: 460.1311.
13
1
2
J¼2.0 Hz, 1H), 5.07 (t, J¼2.0 Hz, 1H); C NMR (CDCl
3
, 100 MHz):
13
(
1
t, J¼2.4 Hz, 2H); C NMR (CDCl
3
161.7,161.4,160.9,159.5,158.9,152.4,152.2,149.2,143.6,134.4,131.3,
131.2, 124.9, 124.4, 124.3, 124.0, 117.5, 111.5, 111.3, 111.1, 110.7, 102.5,
20
H O
5
101.0; HRMS (EI) calcd for C23
4
H15NO : 369.0999, found: 369.1001.
ꢀ
1
ꢀ
1
4
.1.11. Compound 3g. White solid; mp 175e176 C; H NMR (CDCl
3
,
4.1.21. Compound 5f. White solid; mp 199e201 C; H NMR (CDCl ,
3
4
00 MHz): 7.35 (t, J¼7.6 Hz, 2H), 7.26 (t, J¼8.4 Hz, 2H), 6.72e6.93
400 MHz): 7.86 (d, J¼2.4 Hz, 1H), 7.26e7.34 (m, 3H), 6.98e7.01 (m,
4H), 6.82e6.87 (m, 4H), 5.18 (t, J¼2.4 Hz, 1H), 5.01 (t, J¼2.4 Hz, 1H),
13
(
m, 12H), 6.56 (t, J¼2.4 Hz, 2H), 6.30 (t, J¼2.0 Hz, 2H); C NMR
CDCl , 100 MHz): 158.9, 158.5, 158.2, 158.0, 152.9, 131.2, 130.9,
20.7, 115.6, 115.2, 114.9, 114.6, 109.5, 107.8; HRMS (EI) calcd for
: 460.1316, found: 460.1311.
13
(
1
3
3
2.12 (s, 3H); C NMR (CDCl , 100 MHz): 161.4, 161.2, 160.6, 158.5,
156.6, 152.1, 151.8, 149.1, 140.4, 134.7, 131.0, 127.4, 124.6, 124.2, 123.8,
123.7, 120.8, 111.0, 110.8, 110.6, 110.2, 101.1, 100.7, 15.8; HRMS (EI)
30 20 5
C H O
4
calcd for C24H17NO : 383.1161, found: 383.1158.
ꢀ
4
(
.1.12. Compound 3h. White solid; mp 180e182 C; 1H NMR
CDCl ¼2.8 Hz,
, 400 MHz): 7.29 (t, J¼8.4 Hz, 5H), 6.83 (dd, J
, 100 MHz):
: 460.1313,
4.1.22. Compound 5g. White solid; mp 180e181 C; 1H NMR
(CDCl , 400 MHz): 7.91 (s, 1H), 7.29e7.36 (m, 2H), 6.96e7.03 (m,
4H), 6.83e6.87 (m, 5H), 5.15 (t, J¼2.8 Hz, 1H), 5.06 (t, J¼2.0 Hz, 1H),
ꢀ
3
1
13
J
2
¼2.4 Hz, 10H), 6.41 (t, J¼2.4 Hz, 5H); C NMR (CDCl
3
3
158.4, 131.0, 115.5, 109.3; HRMS (EI) calcd for C30
H
20
O
5
13
found: 460.1311.
2.11 (s, 3H); C NMR (CDCl
58.9, 152.3, 152.2, 147.9, 145.4, 143.2, 131.4, 131.1, 125.0, 124.4,
124.3, 123.8, 118.4, 111.3, 111.1, 111.0, 110.4, 102.3, 99.9, 16.0; HRMS
(EI) calcd for C24 : 383.1153, found: 383.1158.
3
, 100 MHz): 161.7, 161.4, 160.1, 159.6,
1
4
.1.13. Compound 3j.21 White solid; mp 103e104 C; 1H NMR
ꢀ
13
(
(
CDCl
CDCl
3
, 400 MHz): 6.71e6.74 (m, 4H), 6.61e6.64 (m, 4H); C NMR
H17NO
4
3
, 100 MHz): 151.7, 128.5, 117.6.
.1.23. Compound 5h. White solid; mp 241e243 C; 1H NMR
(CDCl
, 400 MHz): 7.77 (t, J¼8.0 Hz, 1H), 7.30 (t, J¼8.0 Hz, 2H), 6.99
(s, 4H), 6.84e6.91 (m, 4H), 6.75 (d, J¼8.0 Hz, 2H), 5.17 (t, J¼2.8 Hz,
ꢀ
4
ꢀ
4
.1.14. Compound 3k.22 White solid; mp 108e109 C; 1H NMR
3
(
CDCl
3
, 400 MHz): 7.59 (dd, J
.83e6.93 (m, 5H), 3.88 (s, 3H); C NMR (CDCl
1
¼1.2 Hz, J
2
¼1.2 Hz, 1H), 7.50 (s, 1H),
1
3
13
6
1
5
3
, 100 MHz): 166.1,
2H); C NMR (CDCl
130.9, 124.9, 114.2, 112.0, 111.7, 103.8; HRMS (EI) calcd for
: 369.1000, found: 369.1001.
3
, 100 MHz): 162.2, 161.9, 159.8, 153.0, 143.9,
46.3, 142.1, 142.0, 141.7, 126.1, 124.7, 124.3, 118.0, 116.8, 116.7, 116.4,
2.4.
23 4
C H15NO
ꢀ
ꢀ
1
4
.1.15. Compound 3l.23 White solid; mp 101e103 C; 1H NMR
, 400 MHz): 7.63 (dd, J
¼2.8 Hz, J ¼2.8 Hz, 2H), 7.23 (s, 2H), 6.93 (s, 4H); C NMR (CDCl
4.1.24. Compound 5i. White solid; mp 174e175 C; H NMR (CDCl
400 MHz): 7.65 (t, J¼7.6 Hz, 1H), 7.18 (q, J¼8.8 Hz, 3H), 6.56e6.81
3
,
(
CDCl
3
1
¼3.2 Hz, J
2
¼3.6 Hz, 2H), 7.32 (dd,
13
13
J
1
2
3
,
(m, 11H); C NMR (CDCl
3
, 100 MHz): 161.9, 158.4,157.7, 155.1, 142.5,
130.6, 130.2, 116.4, 115.2, 113.8, 112.4, 110.3, 105.1; MALDI: 369.6
1
00 MHz): 142.1, 141.9, 131.1, 127.1, 125.5, 124.0, 116.8, 112.4.
þ
þ1
(
M ), HRMS (MALDI) calcd for C23H16NO4 : 370.1071, found:
370.1074.
Typical procedure for the synthesis of compound 7 and 8: A
ꢀ
1
4
4
.1.16. Compound 5a. White solid; mp 182e183 C; H NMR (CDCl
00 MHz): 7.44 (t, J¼8.0 Hz, 1H), 7.25e7.29 (m, 2H), 6.97 (dd,
¼2.8 Hz, J ¼2.0 Hz, 2H), 6.78e6.88 (m, 5H), 6.24 (s, 2H), 6.00 (t,
3
,
0
suspension of 4,4 -diiododiphenylether (422 mg, 1 mmol),
J
1
2

1132
Q. Zhou et al. / Tetrahedron 70 (2014) 1125e1132
compound 6 (294 mg, 1 mmol), Fe(acac)
3
(70.6 mg, 0.2 mmol), CuI
2. (a) Ma, D.; Cai, Q. Org. Lett. 2003, 5, 3799e3802; (b) Ma, D.; Cai, Q.; Xie, X.
Synlett 2005, 1767e1770; (c) Cai, Q.; Zou, B.; Ma, D. Angew. Chem., Int. Ed. 2006,
5, 1276e1279; (d) Cai, Q.; He, G.; Ma, D. J. Org. Chem. 2006, 71, 5268e5273.
(
38 mg, 0.2 mmol) and Cs
2
CO
3
(1.303 g, 4 mmol) in DMSO (anhy-
4
ꢀ
drous, 50 mL) was stirred at 140 C under nitrogen atmosphere for
3
4
5
. Cristau, H.; Cellier, P. P.; Hamada, S.; Spindler, J.; Taillefer, M. Org. Lett. 2004, 6,
913e916.
. D’Angelo, N. D.; Peterson, J. J.; Booker, S. K.; Fellows, I.; Dominguez, C.; Hungate,
R.; Reidera, P. J.; Kim, T. Tetrahedron Lett. 2006, 47, 5045e5048.
. (a) Lv, X.; Bao, W. J. Org. Chem. 2007, 72, 3863e3867; (b) Bao, W.; Liu, Y.; Lv, X.
Synthesis 2008, 1911e1917; (c) Chen, D.; Shen, G.; Bao, W. Org. Biomol. Chem.
7
days. When the reaction was cool, the mixture was filtered, and
washed with CH Cl (100 mL). The filtrate was washed NaOH
1 mol/L, 100ꢁ3 mL). The isolated organic phase was evaporated
and submitted to petroleum ether/CH Cl (3:1), then with CH Cl as
2
2
(
2
2
2
2
2009, 19, 4067e4073; (d) Lv, X.; Bao, W. J. Org. Chem. 2009, 74, 5618e5621.
eluent to afford compound 7 as a white solid in 8% yield and
compound 8 as a white solid in 15% yield.
6. Miao, T.; Wang, L. Tetrahedron Lett. 2007, 48, 95e99.
7. (a) Niu, J.; Zhou, H.; Li, Z.; Xu, J.; Hu, S. J. Org. Chem. 2008, 73, 7814e7817; (b)
Niu, J.; Guo, P.; Kang, J.; Li, Z.; Xu, J.; Hu, S. J. Org. Chem. 2009, 74, 5075e5078.
8. Naidu, A. B.; Jaseer, E. A.; Sekar, G. J. Org. Chem. 2009, 74, 3675e3679.
9. Sreedhar, B.; Arundhathi, R.; Linga Reddy, P.; Lakshmi Kantam, M. J. Org. Chem.
.1.25. Compound 7.24 White solid, mp >250 ꢀC; 1H NMR (CDCl
3
,
4
13
4
00 MHz): 6.95 (s, 28H); C NMR (CDCl
3
, 100 MHz): 153.6, 120.2;
2009, 74, 7951e7954.
HRMS (MALDI) calcd for C42
28
H O
7
: 644.1838, found: 644.1830.
10. Jammi, S.; Sakthivel, S.; Rout, L.; Mukherjee, T.; Mandal, S.; Mitra, R.; Saha, P.;
Punniyamurthy, T. J. Org. Chem. 2009, 74, 1971e1976.
.1.26. Compound 8.24 White solid; mp >250 C; H NMR (DMSO-
ꢀ
1
11. Maiti, D. Chem. Commun. 2011, 8340e8342.
4
d
12. Cheng, A.; Hsieh, J. Tetrahedron Lett. 2012, 53, 71e75.
13
6
, 400 MHz): 7.02 (s, 40H); C NMR (DMSO-d
6
, 100 MHz): 152.6,
13. Qu, X.; Li, T.; Zhu, Y.; Sun, P.; Yang, H.; Mao, J. Org. Biomol. Chem. 2011, 9,
5043e5046.
119.9.
14. (a) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev. 2004, 248, 2337e2364;
(b) Ma, D.; Cai, Q. Acc. Chem. Res. 2008, 41, 1450e1460; (c) Evano, G.; Blanchard,
Acknowledgements
N.; Toumi, M. Chem. Rev. 2008, 108, 3054e3131; (d) Monnier, F.; Taillefer, M.
Angew. Chem., Int. Ed. 2009, 48, 6954e6971.
1
1
5. Salih, M. Q.; Beaudry, C. M. Org. Lett. 2013, 15, 4540e4543.
6. Mestichelli, P.; Scott, M. J.; Galloway, W. R. J. D.; Selwyn, J.; Parker, J. S.; Spring,
D. R. Org. Lett. 2013, 15, 5448e5451.
7. Zhou, Q.; Zhang, B.; Du, T.; Gu, H.; Ye, Y.; Jiang, H.; Chen, R. Tetrahedron 2013, 69,
27e333.
8. Sommer, N.; Staab, H. A. Tetrahedron Lett. 1966, 7, 2837e2841.
9. (a) Wang, M.; Yang, H. J. Am. Chem. Soc. 2004, 126, 15412e15422; (b) Yang, C.;
This work was supported by the Natural Science Foundation of
China (21172166, 21203135 and 21375092), China Postdoctoral
Science Foundation (2013M541456), and Taizhou Science Project
1
3
(
121ZD04).
1
1
Chen, Y.; Wang, D.; Zhao, L.; Wang, M. Org. Lett. 2013, 15, 4414e4417.
0. Tsai, J.; Kottas, G.; Brooks, J.; Yeager, W.; Ansari, N.; Barron, E.; Xia, C. U.S. Pat.
Appl. Publ., 2013; US 20,130,168,656 A1 20130704.
Supplementary data
2
2
2
2
2
1. Lee, H. H.; Denny, W. A. J. Chem. Soc. Perkin 1: Org. Bio-organic Chem.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.12.089.
(1972e1999) 1990, 1071e1074.
2. Hu, S.; Xie, G.; Zhang, D. X.; Davis, C.; Long, W.; Hu, Y.; Wang, F.; Kang, X.; Tan, F.;
Ding, L.; Wang, Y. Bioorg. Med. Chem. Lett. 2012, 22, 6301e6305.
3. Preedasuriyachai, P.; Charoonniyomporn, P.; Karoonnirun, O.; Thongpanchang,
T.; Thebtaranonth, Y. Tetrahedron Lett. 2004, 45, 1343e1346.
4. Takeuchi, D.; Asano, I.; Osakada, K. J. Org. Chem. 2006, 71, 8614e8617.
References and notes
1. Marcoux, J.; Doye, S.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 10539e10540.