A modified Cu(0)-Cu(I)-mediated Caryl-CarylUllmann coupling for the synthesis of biaryls

Article abstract of DOI:10.1016/j.tet.2016.07.063

A novel Cu(0)-Cu(I)-mediated C_aryl-C_arylUllmann coupling has been successfully developed. The use of Cu(I) salts allowed the reactions to proceed under relatively mild conditions (65?°C in DMSO for 15–72?h). The developed method was compatible with a relatively wide range of functional groups simultaneously present on the aromatic ring of different electronic nature. The aryl halides with an electron-withdrawing group ortho to the halide or an electron-donating group meta or para to the halide furnished the corresponding products in good to excellent yields (up to 98%).

Full text of DOI:10.1016/j.tet.2016.07.063

Tetrahedron 72 (2016) 5994e6000
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A modified Cu(0)-Cu(I)-mediated Caryl-Caryl Ullmann coupling for
the synthesis of biaryls
,
,b,c,d
Kittisak Yasamut a b, Jira Jongcharoenkamol c, Somsak Ruchirawat a
,
Poonsakdi Ploypradith a
,b,c,d,
*
a Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand
b Institute of Molecular Science, Mahidol University, Salaya Campus, Nakhon Pathom 73170, Thailand
c Program in Chemical Biology, Chulabhorn Graduate Institute, 54 Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand
d Center of Excellence on Environmental Health and Toxicology, Commission on Higher Education, Ministry of Education, Bangkok, Thailand
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 May 2016
Received in revised form 11 July 2016
Accepted 25 July 2016
Available online 27 July 2016
A novel Cu(0)-Cu(I)-mediated Caryl-Caryl Ullmann coupling has been successfully developed. The use of
Cu(I) salts allowed the reactions to proceed under relatively mild conditions (65 ꢀC in DMSO for
15e72 h). The developed method was compatible with a relatively wide range of functional groups si-
multaneously present on the aromatic ring of different electronic nature. The aryl halides with an
electron-withdrawing group ortho to the halide or an electron-donating group meta or para to the halide
furnished the corresponding products in good to excellent yields (up to 98%).
Keywords:
Ullmann coupling
Biaryls
Ó 2016 Elsevier Ltd. All rights reserved.
Aryl halides
Copper powder
Copper-2-thiophenecarboxylate (CuTC)
1. Introduction
of excess amount (2e3 equiv) of Cu(I) salts, especially copper-2-
thiophene carboxylate (CuTC), could lower the temperature and
Copper and its copper (I) as well as copper (II) salts have been
recognized as useful and relatively inexpensive reagents for
a number of organic transformations.1e5 Based on the type of bond
formation, the Ullmann reactions could be classified into Caryl-Caryl
and Caryl-heteroatom (N, O, or S) subtypes.6e8 Since their discovery,
the Cu(0)/Cu(I)-mediated Ullmann reactions have been employed
in various syntheses of natural products, functional materials,
among others.9,10 While the Caryl-O/Caryl-N Ullmann-type coupling
reactions have attracted much attention and their new de-
velopments have been reported from research groups worldwide,11
those of the Caryl-Caryl Ullmann bond formation have received rel-
atively less attention.12 This is partly due to the recent de-
velopments of other metal-mediated/catalyzed reactions,
especially those involving Pd- or Ni-catalysis.8,13
shorten the reaction time.14 More recently, a modification to the
Ullmann reaction conditions by adding catalytic amount of palla-
dium(0) has been made,15 leading to some moderate to excellent
improvement of yields of the desired biaryl products. However,
developing a general Caryl-Caryl Ullmann reaction condition for
a wide substrate scope remains a challenge. Herein, we wish to
report our investigation and modification of the Ullmann condi-
tions to expand the substrate scope to include aromatic rings with
different types, positions, and numbers of functional groups of
various electronic natures.
2. Results and discussion
Our interest in the synthesis of some specific phenanthrenes 1
containing different number of methoxy groups at different posi-
tions (Scheme 1) has prompted us to consider using the Caryl-Caryl
Ullmann coupling reactions to generate the requisite homobiaryl
systems 2. Subsequent conversions of the homobiaryl systems
bearing the ortho-formyl groups could lead to the desired phen-
anthrene skeleton via dialdehyde/diene coupling to form the ole-
fin.16 Then, Lewis/Brønsted acid-mediated benzylation could
furnish the desired arylmethylenated phenanthrenes 1.17 It is
Typical conditions for the classical Ullmann reactions may re-
quire excess copper metal (up to 10 equiv), high temperature
(normally 180e220 ꢀC), or long reaction times (up to 72 h).8,15 Thus,
some modifications were made to circumvent such problems. Use
* Corresponding author. Fax: þ662 553 8527; e-mail address: poonsakdi@cri.or.th
(P. Ploypradith).
http://dx.doi.org/10.1016/j.tet.2016.07.063
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

K. Yasamut et al. / Tetrahedron 72 (2016) 5994e6000
5995
anticipated that the Caryl-Caryl Ullmann coupling reactions could
provide the homobiaryls more directly than other metal-mediated/
catalyzed reactions for which other reagents such as boronic acid or
organotin derivatives may be necessary.
experimentation with adding CuI as a Cu(I) source, it was found
that 2 equiv of CuI, 10 equiv of Cu(0) in DMSO at 65 ꢀC for 72 h gave
the desired product 4 in 62% yield (entries 4e10). The presence/
absence of Pd(0) did not greatly affect the reaction (58% and 62%
yields in the presence and absence of Pd(0), respectively). Changing
the equivalents of Cu(0) and CuI (entries 10e14) did not show any
significant improvement of yields. In addition, microwave heating
did not show any improvement over conventional heating. In fact,
microwave heating, under otherwise identical conditions, gave
only trace amount of the product (entry 7). Different sources of
Cu(I) were also explored; the best result of 79% yield was obtained
from the reaction employing CuTC (entries 10 and 15e17). It should
be noted that changing the amount and ratio of Cu(0) and CuTC
decreased the yield of the product (entries 17 vs 20, 18 vs 21, and 19
vs 22). Increasing temperature to 110 or 170 ꢀC (entries 17 vs 18e19
and 20 vs 21e22) gave 4 in lower yields. Moreover, when Cu(I) salts
were employed alone, without Cu(0), no desired product could be
obtained (entry 23). Only starting material 3 was virtually fully
recovered. Similarly, no biaryl product 4 was formed upon changing
solvent to NMP at 25 or 65 ꢀC (entries 24 and 25). Thus, for the
bromobenzaldehyde 3, 10 equiv of Cu(0) powder, 2 equiv of CuTC in
DMSO at 65 ꢀC for 72 h was the optimized Ullmann condition.
Scheme 1. A general structure of the phenanthrene of interest (1) and its retrosyn-
thesis via the corresponding homobiaryl dialdehyde 2.
2.1. Optimization of the modified Ullmann reaction
As
summarized
in
Table
1,
using
2-bromo-4-
methoxybenzaldehyde 3 as a model, we explored the use of Cu(0)
and/or Cu(I) salts, in N,N,-dimethylformamide (DMF), dime-
thylsulfoxide (DMSO), and N-methylpyrrolidinone (NMP) as sol-
vent under various reaction conditions including those developed
by Liebeskind.14 Only trace amount of the homobiaryl product 4
was obtained when catalytic amount of Cu(0) (20 mol %) was used
regardless of the reaction conditions (entry 1). Adding catalytic
amount of Pd(0) (5 mol %) did not improve the yield. Increasing the
amount of Cu(0) to 10 equiv under various conditions (entries 2e3)
slightly improved the yield up to 25%; adding catalytic amount of
Pd(0) to this condition provided 4 in 35% yield. After additional
2.2. Substrate scope
With the optimized condition in hand, we then investigated the
substrate scope of this condition. As shown in Fig. 1, similar to those
reported in previous studies by others, the results of our substrate
scope showed that aryl iodides underwent our modified Ullmann
reactions more efficiently than the corresponding aryl bromides. In
many cases, these aryl iodides furnished the desired products in
higher yields while requiring significantly shorter reaction times
Table 1
Screening conditions for Cu(0)-Cu(I)-mediated Ullmann reaction of 3
Entry
Cu(0) (equiv)
Cu(I) (equiv)
Pd(0)a (equiv)
Solventb
Temp (ꢀC)
Time (h)
Yield (%)c
1
2
3
4
5
6
7
8
0.2
10
10
10
10
10
10
10
10
10
10
10
15
5
10
10
10
10
10
5
None
None
None
CuI (2)
CuI (2)
CuI (2)
CuI (2)
CuI (2)
CuI (2)
CuI (2)
CuI (5)
CuI (10)
CuI (2)
0.05
None
0.05
0.05
0.05
DMF or DMSO
DMF or DMSO
DMSO
DMF or DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
NMP
NMP
110
65 or 110
65
65
65
6e72
24e72
72
24
48
Trace
10e25
35
25
38
0.05
0.05
65
72
58
65 or 110d
25
0.1e1
72e96
72
72
72
72
72
72
72
72
72
72
72
72
72
72
72
Trace
Trace
47
62
49
55
41
44
39
47
79
63
56
62
53
46
0
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None or 0.05
None
None
9
110
65
65
65
65
65
65
65
65
110
170
65
110
170
65
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
CuI (2)
CuBr (2)
CuCl (2)
CuTC (2)
CuTC (2)
CuTC (2)
CuTC (1)
CuTC (1)
CuTC (1)
CuI (2) or CuTC (2)
CuTC (2)
CuTC (2)
5
5
None
10
10
25
65
72
72
0
0
a
Pd(PPh3)4 was used as a source of Pd(0).
b
c
DMF¼N,N-dimethylformamide; DMSO¼dimethyl sulfoxide; NMP¼N-methyl-2-pyrrolidone.
Isolated yield.
d
Microwave heating was employed.

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K. Yasamut et al. / Tetrahedron 72 (2016) 5994e6000
(only about 15 h instead of 72 h). The biaryls 5e7 were obtained
from the corresponding aryl iodides in 58e91% yields which were
significantly higher than those of the products from the aryl bro-
mides (trace up to 49%). In addition, good to excellent yields
(56e98%) of the products could be obtained from the substrates
bearing electron-withdrawing groups such as aldehyde, ketone,
ester, and nitro ortho to the halide (8e13). For substrates containing
electron-donating groups such as methoxy, better yields were ob-
tained if these groups were meta or para to the halide (5e7). In-
When more than one electron-donating and/or electron-
withdrawing group was simultaneously present, the results largely
depended on both the position and number of these groups. 4-
Bromo-2-methoxybenzaldehyde, despite having the methoxy group
meta and formyl group para to the bromine, did not give the dia-
ldehyde 21. On the other hand, the dialdehyde 22 was obtained from
2-bromo-5-methoxybenzaldehyde, withthemethoxygroupparaand
the formyl group ortho to the bromine, in 69% yield. Interestingly, in
case of the biaryls 23e25, subtle differences of the electron-donating/
withdrawing substituents at the same position could facilitate or
hamper the Ullmann reaction under the developed conditions. Thus,
when compared with the starting bromobenzaldehyde 3, an addi-
tional electron-donating methoxy group meta to the aldehyde ren-
dered compound 26 not suitable for the Ullmann reaction. Only the
debrominated product i.e., veratraldehyde was obtained from the
reaction in 67% yield. Changing this methoxy group to an electron-
withdrawing acetoxy group (27) gave the corresponding biaryl 24
albeit in low yield (19%) along with the debrominated by-product (ca.
50%). Finally, changing this methoxygroup to a methyl carbonate (28)
which is a less electron-withdrawing group than the acetoxy group
could provide the biaryl product 26 in 76% yield.
terestingly,
compound
14
bearing
a
coordinating
hydroxymethylene group on the ortho position was also obtained
from the corresponding 2-iodobenzyl alcohol in moderate yield
(56%). Such hydroxy group of the 2-iodobenzyl alcohol could be
converted to the corresponding acetate or methyl ether; however,
neither underwent the Ullmann reaction to furnish the corre-
sponding products. In addition, the presence of a cinnamate group
proved to be incompatible with the reaction conditions as no
product 15 could be obtained. However, direct Horner-Wittig re-
action of 11 provided 15 in good yield (77%), mostly as the trans,
trans isomer. The presence of the b-nitrostyrene did not hamper the
reaction; the corresponding product 16 was obtained in moderate
yield (47%). Both benzamide and acetamide functional groups at
the ortho position of the aryl iodides could be tolerated under re-
action conditions; the corresponding biaryls 17 and 18 were ob-
tained in 46 and 45% yields, respectively. Both biphenyl 19 and
binaphthol 20, without any electronically biased group on any
position of the aromatic ring, were also obtained in moderate yields
of 50% and 48%, respectively.
In addition to the homo-biaryl coupling, it is also possible to
affect the hetero-biaryl cross-coupling reactions under the de-
veloped conditions. Thus, after some experimentation, aldehyde 3
and 2-bromobenzaldehyde underwent the modified Ullmann re-
action to give the corresponding product 29 in 31% yield (Fig. 2).
Similarly,
aldehyde
3
could
react
with
2-bromo-5-
methoxybenzaldehyde to furnish 30 in 36% yield.
Fig. 1. Substrate scope of the modified Cu(0)-CuTC Ullmann Caryl-Caryl homo-biaryl coupling reactions.

K. Yasamut et al. / Tetrahedron 72 (2016) 5994e6000
5997
some cases, aryl bromides could be employed as substrates al-
though the use of aryl iodides usually gave better yields and re-
quired shorter reaction times. Various functional groups could be
tolerated. Cross-coupling reactions of different aryl halides as
substrates could be performed under similar reaction conditions
albeit giving the desired cross-coupling products in low yields
(<36%) and the homo-coupling products in 50e60% yields. The use
of CuTC under our developed conditions facilitated the Ullmann-
type Caryl-Caryl biaryl coupling by lowering the required tempera-
ture to be as low as 65 ꢀC. Some substrates which do not undergo
the Ullmann reactions when Cu(0) powder or CuTC was employed
alone could be converted smoothly to the corresponding biaryl
products in good to excellent yields (up to 98%). Applications of this
developed method towards the synthesis of the biaryl core struc-
tures of biologically active compounds are currently pursued in our
laboratory and will be reported in due course.
Fig. 2. Cross-coupling reactions of 3.
It should be noted that the desired cross-coupling products 29
and 30 were obtained along with significant amount of homo-
coupling products 11 and 22, respectively (50e60%).
2.3. Mechanistic implications
Although the exact mechanism for this modified Cu(0)-CuTC-
mediated Caryl-Caryl biaryl coupling reactions has not yet been
fully delineated, there is some important experimental evidence
which suggests, for the first time, that both Cu(0) and CuTC are
necessary. In fact, when we carried out reactions using the sub-
strates for the biaryls 6e7, 10e12, and 25 under the reaction con-
ditions reported by Liebeskind (CuTC (2.5e3 equiv), NMP as solvent
at room temperature or 65 ꢀC for 0.5e48 h),14 they either gave no
desired products or in much lower yields than those obtained from
our developed conditions. For these substrates, only 2-
iodoacetophenone gave 12, under Liebeskind conditions, in 37%
yield, with some starting materials remaining; other substrates
gave no desired product. While the exact role of Cu(0) powder is
still debatable, Cu(0) could serve as a stoichiometric reductant or
a surface for the Ullmann-type coupling reactions to take place or
both. Interestingly, besides obtaining the biaryl 6 as the product
either from 3-bromoanisole or 3-iodoanisole, the reactions also
produced anisole (10e20%) and 31 (15e20%) with a thiophene
carboxylate (TC) on the benzene ring replacing the halogen (Br or I)
as shown in Fig. 3. Additional experiments were performed to in-
vestigate the nature of the transfer of the TC moiety. This TC for Br/I
substitution could take place only when CuTC was employed. When
CuTC was used alone in the reaction, 31 was obtained from 3-
bromoanisole in 43% yield. In the presence of thiophene carbox-
ylic acid as a separate ligand under our modified Ullmann reaction
conditions without CuTC, Cu(0) or other Cu(I) salts such as CuI
could not mediate the CaryleO bond formation to generate 31. This
suggested that the transfer of the TC moiety was more likely to take
place from CuTC directly following its complexation with the sub-
strate. For some substrates, this pathway probably competes with
other pathway(s) under our reaction conditions.
4. Experimental section
4.1. General experimental methods
Unless otherwise noted, reactions were run in oven-dried
round-bottomed flasks. Tetrahydrofuran (THF) was distilled from
sodium benzophenone ketyl or purified by the solvent purification
system while dichloromethane (DCM) was also purified by the
solvent purification system prior to use. All other compounds were
used as received from the suppliers. The crude reaction mixtures
were concentrated under reduced pressure by removing organic
solvents on rotary evaporator. Column chromatography was per-
formed using silica gel 60 (particle size 0.06e0.2 mm;
70e230 mesh ASTM). Analytical thin-layer chromatography (TLC)
was performed with silica gel 60 F254 aluminum sheets. Chemical
shifts for 1H nuclear magnetic resonance (NMR) spectra were re-
ported in parts per million (ppm,
d) downfield from tetrame-
thylsilane. Splitting patterns are described as singlet (s), doublet
(d), triplet (t), quartet (q), septet (sept), multiplet (m), broad (br),
and doublet of doublet (dd). Resonances for infrared (IR) spectra
were reported in wavenumbers (cmꢁ1). High resolution (HRMS)
mass spectra were obtained using time-of-flight (TOF) via the
atmospheric-pressure chemical ionization (APCI) or electrospray
ionization (ESI). Melting points were uncorrected.
4.2. General procedure for the modified Cu(0)-Cu(I)- medi-
ated Ullmann biaryl coupling
A mixture of aryl halide (1 equiv), Cu(0) powder (10 equiv), and
CuTC (2 equiv) in DMSO (0.2 mL/mmol of aryl halide) was stirred at
65e70 ꢀC for 15e72 h. Water and EtOAc were added, and the two
phases were separated. The aqueous layer was extracted twice with
EtOAc. The combined organic layers were washed with brine, dried
over Na2SO4, filtered, and concentrated under reduced pressure to
give the crude product which was further purified by preparative
TLC (EtOAc/hexanes) to furnish the desired product.
Fig. 3. Structure of 31, a CuTC-mediated CaryleO by-product.
From our experiments, the use of CuTC in combination with
Cu(0) powder appeared to effect the biaryl coupling reactions by
lowering the required high temperature normally in a range of
170e220 ꢀC to be as low as 65 ꢀC. However, long reaction time up to
72 h is still a drawback for using some aryl bromides as substrates.
4.2.1. 5,50-Dimethoxy-[1,10-biphenyl]-2,20-dicarbaldehyde
(4). Following the general procedure and purification by pre-
parative TLC (20% EtOAc/hexanes), the product was obtained as
a pale yellow solid (0.061 g, 0.23 mmol, 69%) mp (EtOAc/hexanes)
119e120 ꢀC. Rf (20% EtOAc/hexanes) 0.53. IR (UATR): nmax 1021,
1206, 1236, 1563, 1590, 1681, 2841, 2942 cmꢁ1. 1H NMR (300 MHz,
3. Conclusion
In summary, the co-utilization of Cu powder as Cu(0) and CuTC
as Cu(I) for the Caryl-Caryl Ullmann coupling reactions was de-
veloped for the first time. Use of Cu powder (10 equiv) and CuTC
(2 equiv) in DMSO as solvent at 65 ꢀC were our optimized condi-
tions. Our method showed a relatively wide substrate scope. In
CDCl3):
d
3.89 (s, 6H), 6.82 (d, J¼2.4 Hz, 2H), 7.06 (dd, J¼8.7, 2.4 Hz,
2H), 8.01 (d, J¼9.0 Hz, 2H), 9.66 (s, 2H). 13C NMR (75 MHz, CDCl3):
d
55.7, 114.6, 116.3, 128.2, 130.6, 143.6, 163.4, 189.6. LRMS (EI) m/z

5998
K. Yasamut et al. / Tetrahedron 72 (2016) 5994e6000
(rel intensity) 270 (Mþ, 12), 241 (100), 198 (19). TOF-HRMS calcd for
C
the product was obtained as a yellow solid (0.037 g, 0.15 mmol,
75%) mp (EtOAc/hexanes) 234e235 ꢀC (lit.¼238 ꢀC). Rf (40% EtOAc/
hexanes) 0.74. IR (UATR): nmax 1340, 1510, 1598, 2923 cmꢁ1. 1H NMR
16H14O4Na (MþNaþ) 293.0784, found 293.0783.
4.2.2. 2,20-Dimethoxy-1,10-biphenyl (5).18 Following the general
procedure and purification by preparative TLC (40% EtOAc/hex-
anes), the product was obtained as a yellow solid (0.027 g,
(300 MHz, CDCl3):
d
7.80 (dd, J¼6.0, 3.0 Hz, 4H), 8.37 (dd, J¼6.0,
3.0 Hz, 4H). 13C NMR (75 MHz, CDCl3):
d 29.7, 124.4, 128.4, 145.0.
TOF-HRMS calcd for C12H8O4 (Mþ) 244.0490, found 244.0481.
These spectroscopic data are in accordance with those reported
previously.
0.12
mmol,
58%)
mp
(EtOAc/hexanes)
152e153
ꢀC
(lit.¼154e155 ꢀC). Rf (40% EtOAc/hexanes) 0.84. IR (UATR): nmax
1022, 1237, 1255, 1429, 1456, 1482, 1591, 2929, 2963, 3026 cmꢁ1. 1H
NMR (300 MHz, CDCl3):
d
3.76 (s, 3H), 6.96e7.02 (m, 4H), 7.24 (dd,
4.2.8. [1,10-Biphenyl]-2,20-dicarbaldehyde (11). Following the gen-
eral procedure and purification by preparative TLC (40% EtOAc/
hexanes), the product was obtained as an orange sticky gum
(0.89 g, 0.42 mmol, 98%). Rf (40% EtOAc/hexanes) 0.68. IR (UATR):
J¼9.0, 3.0 Hz, 2H), 7.29e7.35 (m, 2H). 13C NMR (75 MHz, CDCl3):
d
55.6, 111.0, 120.3, 127.8, 128.6, 131.4, 157.0. LRMS (EI) m/z (rel in-
tensity) 214 (Mþ, 100), 171 (14). TOF-HRMS calcd for C14H15O2
(MþHþ) 215.1067, found 215.1065. These spectroscopic data are in
accordance with those reported previously.
nmax 1196, 1247, 1574, 1595, 1690, 2848 cmꢁ1 1H NMR (300 MHz,
.
CDCl3):
d
7.36 (dd, J¼7.5, 1.2 Hz, 2H), 7.56e7.70 (m, 4H), 8.06 (dd,
J¼7.5, 1.2 Hz, 2H), 9.83 (s, 2H). 13C NMR (75 MHz, CDCl3):
d 128.6,
4.2.3. 3,30-Dimethoxy-1,10-biphenyl (6).19 Following the general
procedure and purification by preparative TLC (40% EtOAc/hex-
anes), the product was obtained as a light brown solid (0.099 g,
0.46 mmol, 72%) mp (EtOAc/hexanes) 36e37 ꢀC (lit.¼36e37 ꢀC). Rf
(40% EtOAc/hexanes) 0.68. IR (UATR): nmax 1030, 1232, 1475, 1575,
128.8, 131.7, 133.4, 134.6, 141.2, 191.0. LRMS (EI) m/z (rel intensity)
210 (Mþ, 3), 181 (100), 152 (23). TOF-HRMS calcd for C14H10O2Na
(MþNaþ) 233.0573, found 233.0568.
4.2.9. 1,10-([1,10-Biphenyl]-2,20-diyl)diethanone (12). Following the
general procedure and purification by preparative TLC (40% EtOAc/
hexanes), the product was obtained as a brown amorphous solid
(0.125 g, 0.53 mmol, 86%). Rf (40% EtOAc/hexanes) 0.53. IR (UATR):
nmax 1245, 1272, 1354, 1435, 1594, 1685, 2854, 2924 cmꢁ1. 1H NMR
1597, 2835, 2938 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
3.78 (s, 6H),
6.85 (dd, J¼8.1, 2.4 Hz, 2H), 7.13 (t, J¼6.6 Hz, 4H), 7.30 (t, J¼8.1 Hz,
2H). 13C NMR (75 MHz, CDCl3):
d 55.3, 112.9, 113.2, 119.8, 129.9,
142.7, 160.1. LRMS (EI) m/z (rel intensity) 214 (Mþ, 100), 199 (53).
TOF-HRMS calcd for C14H14O2 (Mþ) 214.0988, found 214.0983.
These spectroscopic data are in accordance with those reported
previously.
(300 MHz, CDCl3):
d
2.25 (s, 6H), 7.16 (d, J¼9.0 Hz, 2H), 7.40e7.49
(m, 4H), 7.73 (dd, J¼9.0, 3.0 Hz, 2H). 13C NMR (75 MHz, CDCl3):
d
29.3, 127.7, 128.6, 130.8, 131.1, 138.7, 140.7, 201.1. LRMS (EI) m/z (rel
intensity) 238 (Mþ, 0.04), 195 (100), 196 (15). TOF-HRMS calcd for
4.2.4. 4,40-Dimethoxy-1,10-biphenyl (7).20 Following the general
procedure and purification by preparative TLC (40% EtOAc/hex-
anes), the product was obtained as yellow solid (0.125 g, 0.58 mmol,
91%) mp (EtOAc/hexanes) 169e170 ꢀC (lit.¼171e172 ꢀC). Rf (40%
EtOAc/hexanes) 0.63. IR (UATR): nmax 1041, 1183, 1250, 1274, 1501,
C
16H14O2Na (MþNaþ) 261.0886, found 261.0895.
4.2.10. Dimethyl [1,10-biphenyl]-2,20-dicarboxylate (13).14 Following
the general procedure and purification by preparative TLC (40%
EtOAc/hexanes), the product was obtained as a white solid (0.14 g,
0.53 mmol, 87%) mp (EtOAc/hexanes) 73e74 ꢀC. Rf (40% EtOAc/
hexanes) 0.74. IR (UATR): nmax 1082, 1126, 1253, 1289, 1432, 1598,
1606, 2840, 2958 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 3.83 (s, 6H),
6.96 (d, J¼9.0 Hz, 4H), 7.47 (d, J¼9.0 Hz, 4H). 13C NMR (75 MHz,
CDCl3):
d
55.4, 114.2, 127.8, 133.5, 158.7. LRMS (EI) m/z (rel intensity)
1726, 2951 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 3.60 (s, 6H), 7.19 (d,
214 (Mþ, 100), 199 (54). TOF-HRMS calcd for C14H14O2 (Mþ)
214.0988, found 214.0990. These spectroscopic data are in accor-
dance with those reported previously.
J¼6.0 Hz, 2H), 7.41 (t, J¼9.0 Hz, 2H), 7.52 (t, J¼9.0 Hz, 2H), 8.00 (d,
J¼6.0 Hz, 2H). 13C NMR (75 MHz, CDCl3):
d 51.5, 127.2, 129.4, 129.9,
130.2, 131.5, 143.3, 167.4. LRMS (EI) m/z (rel intensity) 270 (Mþ, 2),
211 (100), 196 (15). TOF-HRMS calcd for C16H14O4Na (MþNaþ)
293.0784, found 293.0782. These spectroscopic data are in accor-
dance with those reported previously.
4.2.5. 2,20-Dinitro-1,10-biphenyl (8).21 Following the general pro-
cedure and purification by preparative TLC (40% EtOAc/hexanes),
the product was obtained as
a red brown solid (0.049 g,
0.199 mmol, 98%) mp (EtOAc/hexanes) 122e123 ꢀC. Rf (40% EtOAc/
4.2.11. [1,10-Biphenyl]-2,20-diyldimethanol (14).14 Following the
general procedure and purification by preparative TLC (40% EtOAc/
hexanes), the product was obtained as a pale yellow solid (0.026 g,
0.12 mmol, 56%) mp (EtOAc/hexanes) 104e105 ꢀC. Rf (40% EtOAc/
hexanes) 0.24. IR (UATR): nmax 1032, 1194, 1251, 1340, 1424, 1444,
hexanes) 0.61. IR (UATR): nmax 1348, 1515, 1527, 1606 cmꢁ1. 1H NMR
(300 MHz, CDCl3):
d
7.30 (dd, J¼6.0, 1.5 Hz, 2H), 7.57 (t, J¼6.0 Hz,
2H), 7.68 (t, J¼6.0 Hz, 2H), 8.19 (dd, J¼6.0, 1.5 Hz, 2H). 13C NMR
(75 MHz, CDCl3): d 124.6, 129.1, 130.9, 133.4, 134.1, 147.1. TOF-HRMS
calcd for C12H8N2O4 (Mþ) 244.0490, found 244.0498. These spec-
troscopic data are in accordance with those reported previously.
1478, 2920, 3256, 3349 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
4.28 (s,
4H), 7.12 (d, J¼6.0 Hz, 2H), 7.25e7.39 (m, 4H), 7.45 (d, J¼6.0 Hz, 2H).
13C NMR (75 MHz, CDCl3):
d 62.7, 127.6, 128.1, 129.6, 129.7, 138.6,
4.2.6. 3,30-Dinitro-1,10-biphenyl (9).22 Following the general pro-
cedure and purification by preparative TLC (40% EtOAc/hexanes),
the product was obtained as a pale brown solid (0.082 g, 0.34 mmol,
56%) mp (EtOAc/hexanes) 199e200 ꢀC. Rf 40% EtOAc/hexanes) 0.47.
140.0. LRMS (EI) m/z (rel intensity) 214 (Mþ, 0.22), 196 (100), 195
(74), 181 (39), 178 (46), 167 (46), 165 (55) 152 (26). TOF-HRMS calcd
for C14H14O2Na (MþNaþ) 237.0886, found 237.0888. These spec-
troscopic data are in accordance with those reported previously.
IR (UATR): nmax 1269, 1347, 1526, 2922, 3089 cmꢁ1 1H NMR
.
(300 MHz, CDCl3):
d
7.71 (t, J¼7.5 Hz, 2H), 7.98 (d, J¼6.0 Hz, 2H),
4.2.12. (2E,20E)-Diethyl
3,30-([1,10-biphenyl]-2,20-diyl)diacrylate
8.31 (d, J¼6.0 Hz, 2H), 8.50 (t, J¼3.0 Hz, 2H). 13C NMR (75 MHz,
(15). To a stirred solution of (carbethoxymethylene) triphenyl-
phosphorane (0.15 g, 0.44 mmol) in dry CH2Cl2 (1.0 mL) at 0 ꢀC
under argon was added a solution of 11 (0.037 g, 0.18 mmol) in
CH2Cl2 (0.5 mL). The reaction mixture was stirred at 0 ꢀC to room
temperature until all starting material was consumed as monitored
by TLC. Water (2 mL) and CH2Cl2 (1 mL) were added, and the two
phases were separated. The aqueous layer was extracted with
CH2Cl2 (5 mLꢂ2). The combined organic layers were washed with
CDCl3):
d 122.1, 123.3, 130.3, 133.1, 140.3, 148.9. LRMS (EI) m/z (rel
intensity) 244 (Mþ, 55), 178 (62), 149 (100). TOF-HRMS calcd for
C
12H8N2O4 (Mþ) 244.0490, found 244.0498. These spectroscopic
data are in accordance with those reported previously.
4.2.7. 4,40-Dinitro-1,10-biphenyl (10).23 Following the general pro-
cedure and purification by preparative TLC (40% EtOAc/hexanes),

K. Yasamut et al. / Tetrahedron 72 (2016) 5994e6000
5999
brine (2 mL), dried over Na2SO4, filtered, and concentrated under
reduced pressure to give the crude product. Following purification
by column chromatography on silica (20% EtOAc/hexanes), the
product was obtained as a pale yellow sticky gum (0.049 g,
0.139 mmol, 77%). Rf (20% EtOAc/hexanes) 0.37. IR (UATR): nmax
1175, 1313, 1634, 1714, 2854, 2925 cmꢁ1. 1H NMR (300 MHz, CDCl3):
(Mþ, 100), 253 (93), 252 (81), 239 (34). TOF-HRMS calcd for C20H14
(Mþ) 254.1090, found 254.1095.
4.2.18. 4,40-Dimethoxy-[1,10-biphenyl]-2,20-dicarbaldehyde
(22). Following the general procedure and purification by pre-
parative TLC (20% EtOAc/hexanes), the product was obtained as
a pale yellow solid (0.061 g, 0.226 mmol, 69%) mp (EtOAc/hexanes)
122e123 ꢀC. Rf (20% EtOAc/hexanes) 0.53. IR (UATR): nmax 1163,
1225, 1276, 1484, 1602, 1687, 2844 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
1.24 (t, J¼7.0 Hz, 6H), 4.15 (q, J¼14.3, 6.5 Hz, 4H), 6.32 (d,
J¼15.9 Hz, 2H), 7.20e7.23 (m, 2H), 7.34e7.44 (m, 6H), 7.71e7.74 (m,
2H). 13C NMR (75 MHz, CDCl3):
14.2, 60.3,119.5,126.5,128.3,129.7,
d
131.1, 133.4, 140.5, 142.7, 166.7. LRMS (EI) m/z (rel intensity) 350
(Mþ, 0.56), 203 (100), 178 (65), 85 (91), 71 (100), 57 (91) TOF-HRMS
calcd for C22H22O4Na (MþNaþ) 373.1410, found 373.1420.
d
3.93 (s, 6H), 7.19e7.28 (m, 4H), 7.55 (d, J¼3.0 Hz, 2H), 9.80 (s, 2H).
13C NMR (75 MHz, CDCl3):
d 55.7, 110.8, 120.9, 133.5, 133.7, 135.9,
159.8, 191.1. TOF-HRMS calcd for C16H14O4Na (MþNaþ) 293.0784,
found 293.0789.
4.2.13. 2,20-Bis((E)-2-nitrovinyl)-1,10-biphenyl (16). Following the
general procedure and purification by preparative TLC (40% EtOAc/
hexanes), the product was obtained as an orange solid (0.092 g,
0.31 mmol, 47%) mp (EtOAc/hexanes) 53e54 ꢀC. Rf (40% EtOAc/
hexanes) 0.84. IR (UATR): nmax 1370, 1455, 1497, 1552, 1725,
4.2.19. 2,20-Diformyl-5,50-dimethoxy-[1,10-biphenyl]-4,40-diyl diac-
etate (24). Following the general procedure and purification by
preparative TLC (40% EtOAc/hexanes), the product was obtained as
a pale yellow solid (0.02 g, 0.052 mmol, 19%) mp (EtOAc/hexanes)
179e180 ꢀC. Rf (40% EtOAc/hexanes) 0.29. IR (UATR): nmax 1016,
2926 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 7.44e7.60 (m,10H), 7.99 (d,
J¼15.0 Hz, 2H). 13C NMR (75 MHz, CDCl3):
d
129.3, 129.5, 130.1,
1104, 1178, 1499, 1598, 1681, 1768, 2853, 2925 cmꢁ1
(300 MHz, CDCl3):
2H), 9.68 (s, 2H). 13C NMR (75 MHz, CDCl3):
.
1H NMR
2.37 (s, 6H), 3.91 (s, 6H), 6.91 (s, 2H), 7.76 (s,
20.6, 56.5,114.6,122.6,
132.3, 137.2, 139.2. TOF-HRMS calcd for C16H11N2O4 (MꢁHþ)
d
295.0724, found 295.0736.
d
128.2, 133.6, 140.5, 155.2, 168.7, 188.8. LRMS (EI) m/z (rel intensity)
386 (Mþ, 4), 273 (64), 73 (100). TOF-HRMS calcd for C20H18O8Na
(MþNaþ) 409.0894, found 409.0896.
4.2.14. N,N0-([1,10-Biphenyl]-2,20-diyl)dibenzamide (17). Following
the general procedure and purification by centrifugation at
5000 rpm, room temperature for 15 min to remove Cu(0) and CuTC
before crystallization in diethyl ether, the product was obtained as
a white solid (0.084 g, 0.22 mmol, 46%) mp 190e191 ꢀC. Rf (40%
EtOAc/hexanes) 0.50. IR (UATR): nmax 1054, 1243, 1448, 1553, 1618,
4.2.20. 2,20-Diformyl-5,50-dimethoxy-[1,10-biphenyl]-4,40-diyl
di-
methyl dicarbonate (25). Following the general procedure and pu-
rification by preparative TLC (40% EtOAc/hexanes), the product was
obtained as a pale yellow solid (0.074 g, 0.192 mmol, 76%) mp
(EtOAc/hexanes) 160e161 ꢀC. Rf (40% EtOAc/hexanes) 0.26. IR
(UATR): nmax 1119, 1146, 1254, 1440, 1501, 1602, 2683, 1765, cmꢁ1. 1H
1729, 2856, 2927, 3063 cmꢁ1.1H NMR (300 MHz, CDCl3):
(m, 4H), 7.51e7.55 (m, 6H), 7.57e7.60 (m, 2H), 7.76e7.80 (m, 2H),
8.25e8.28 (m, 4H). 13C NMR (75 MHz, CDCl3):
110.6, 120.0, 124.6,
d 7.33e7.38
d
125.1, 127.2, 127.6, 128.9, 131.6, 142.1, 150.8, 163.1. LRMS (EI) m/z (rel
intensity) 392 (Mþ, 0.71), 129 (48), 73 (91), 57 (100). TOF-HRMS
calcd for C13H10NO ([M/2]þ) 196.0756, found 196.0757.
NMR (300 MHz, CDCl3):
d
2.59 (s, 6H), 3.88 (s, 6H), 6.72 (s, 2H), 7.42
40.3, 56.1, 112.9,
(s, 2H), 9.53 (s, 2H). 13C NMR (75 MHz, CDCl3):
d
113.7, 128.7, 135.3, 146.6, 151.9, 190.6. LRMS (EI) m/z (rel intensity)
418 (Mþ, 0.67), 389 (100), 331 (32). TOF-HRMS calcd for C20H22NO10
(MþNHþ4 ) 436.1238, found 436.1226.
4.2.15. N,N0-([1,10-Biphenyl]-2,20-diyl)diacetamide (18).14 Following
the general procedure and purification by preparative TLC (40%
EtOAc/hexanes), the product was obtained as a yellow sticky gum
(0.035 g, 0.132 mmol, 45%). Rf (40% EtOAc/hexane) 0.58. IR (UATR):
4.2.21. 5-Methoxy-[1,10-biphenyl]-2,20-dicarbaldehyde
(29). Following the general procedure and purification by pre-
parative TLC (40% EtOAc/hexanes), the product was obtained as
a brown sticky gum (0.031 g, 0.127 mmol, 31%). Rf (40% EtOAc/
hexanes) 0.63. IR (UATR): nmax 1016, 1217, 1251, 1565, 1593, 1688,
nmax 1025, 1178, 1219, 1361, 1380, 1733 cmꢁ1 1H NMR (300 MHz,
.
CDCl3):
d 1.96 (s, 6H), 7.06 (br s, 2H), 7.19e7.47 (m, 4H), 7.41e7.47
(m, 2H), 8.06 (d, J¼9.0 Hz, 2H). 13C NMR (75 MHz, CDCl3):
d 24.1,
123.6, 125.3, 129.3, 130.6, 135.4, 169.3. LRMS (EI) m/z (rel intensity)
268 (Mþ, 0.2), 178 (100), 111 (70). These spectroscopic data are in
accordance with those reported previously.
2843, 2931 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
3.90 (s, 3H), 6.81, (d,
J¼2.4 Hz, 1H), 7.07e7.10 (m, 1H), 7.37 (dd, J¼7.2, 0.9 Hz, 1H),
7.57e7.69 (m, 2H), 8.02e8.07 (m, 2H), 9.67 (s, 1H), 9.85 (s, 1H). 13
NMR (75 MHz, CDCl3): 55.7, 114.5, 116.6, 128.1, 128.3, 128.8, 131.0,
C
d
4.2.16. 1,10-Biphenyl (19).23 Following the general procedure and
purification by preparative TLC (40% EtOAc/hexanes), the product
was obtained as a yellow solid (0.057 g, 0.37 mmol, 50%) mp
(EtOAc/hexanes) 62e63 ꢀC (lit.¼67e69 ꢀC). Rf (40% EtOAc/hexanes)
131.3, 133.4, 134.6, 141.2, 143.6, 163.3, 189.6, 191.0. TOF-HRMS calcd
for C15H12O3Na (MþNaþ) 263.0679, found 263.0669.
4.2.22. 4,50-Dimethoxy-[1,10-biphenyl]-2,20-dicarbaldehyde
(30). Following the general procedure and purification by pre-
parative TLC (40% EtOAc/hexanes), the product was obtained as
a yellow sticky gum (0.03 g, 0.113 mmol, 36%). Rf (40% EtOAc/hex-
anes) 0.45. IR (UATR): nmax 1012, 1233, 1254, 1297, 1485, 1593,
0.71. IR (UATR): nmax 1482, 1597, 2851, 2925, 3028 cmꢁ1 1H NMR
.
(300 MHz, CDCl3):
d
7.33 (t, J¼7.5 Hz, 2H), 7.43 (t, J¼7.5 Hz, 4H), 7.59
(d, J¼9.0 Hz, 4H). 13C NMR (75 MHz, CDCl3):
d 127.2, 127.3, 128.8,
141.3. LRMS (EI) m/z (rel intensity) 154 (MþHþ, 8), 123 (40), 57, (46).
TOF-HRMS calcd for C12H10 (Mþ) 154.0777, found 154.0783.
1685 cmꢁ1 1H NMR (300 MHz, CDCl3):
. d 3.0 (s, 3H), 3.93 (s, 3H),
6.80 (d, J¼2.7 Hz, 1H), 7.07 (dd, J¼8.7, 2.7 Hz, 1H), 7.21 (dd, J¼8.4,
2.7 Hz, 1H), 7.29 (d, J¼8.4 Hz, 1H), 7.54 (d, J¼2.7 Hz, 1H), 8.03 (d,
J¼9.0 Hz, 1H), 9.69 (s, 1H), 9.80 (s, 1H). 13C NMR (75 MHz, CDCl3):
4.2.17. 1,10-Binaphthalene (20).23 Following the general procedure
and purification by preparative TLC (20% EtOAc/hexanes), the
product was obtained as a dark green sticky gum (0.89 g,
0.35 mmol, 48%). Rf (20% EtOAc/hexanes) 0.76. IR (UATR): nmax 1386,
d
55.6, 55.7, 110.6, 114.4, 117.0, 120.8, 128.7, 130.8, 132.6, 133.9, 135.5,
143.3, 159.8, 163.3, 189.8, 190.8. LRMS (EI) m/z (rel intensity) 270
(Mþ, 3), 241 (100), 198 (21). TOF-HRMS calcd for C16H14O4Na
(MþNaþ) 293.0784, found 293.0791.
1505, 1590, 3044 cmꢁ1 1H NMR (300 MHz, CDCl3):
. d 7.23 (t,
J¼7.5 Hz, 2H), 7.43e7.56 (m, 4H), 7.73 (t, J¼7.5 Hz, 6H), 8.21 (d,
J¼9.0 Hz, 2H). 13C NMR (75 MHz, CDCl3):
d 122.8, 125.2, 125.4, 125.6,
125.8,126.0,126.2,126.4,126.6,126.7, 127.1, 127.3, 127.7, 127.8, 127.9,
4.2.23. 4-Bromo-5-formyl-2-methoxyphenyl acetate (27). To a stir-
128.2, 128.3, 128.4, 129.9, 138.4. LRMS (EI) m/z (rel intensity) 254
red solution of 2-bromo-4-hydroxy-5-methoxybenzaldehyde

6000
K. Yasamut et al. / Tetrahedron 72 (2016) 5994e6000
(0.30 g, 1.30 mmol) in CH2Cl2 (13 mL) at room temperature was
added acetic anhydride (0.25 mL, 2.60 mmol), DMAP (0.16 g,
1.30 mmol) and Et3N (0.18 mL, 1.30 mmol). The reaction mixture
was stirred until all of the starting material was consumed as
monitored by TLC. Water (5 mL) and CH2Cl2 (5 mL) were added, and
the two phases were separated. The aqueous layer was extracted
with CH2Cl2 (10 mLꢂ2). The combined organic layers were washed
with brine (10 mL), dried over Na2SO4, filtered, and concentrated
under reduced pressure to give the crude product. Following pu-
rification by column chromatography on silica (40% EtOAc/hex-
anes), the product was obtained as a pale brown solid (0.35 g,
1.27 mmol, 98%) mp 95e96 ꢀC. Rf (EtOAc/hexane) 0.53. IR (UATR):
file and InChiKey of the most important compounds described in
this article.
References and notes
1. Krause, N. In Modern Organocopper Chemistry; Wiley-VCH: Dortmund, Ger-
many, 2003.
2. Allen, S. E.; Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M. C. Chem. Rev. 2013,
113, 6234e6458 and references cited therein.
3. Mao, Z. F.; Wang, Z.; Xu, Z. Q.; Huang, F.; Yu, Z. K.; Wang, R. Org. Lett. 2012, 14,
3854e3857.
4. Zheng, J.; Huang, L.; Huang, C.; Wu, W.; Jiang, H. J. Org. Chem. 2015, 80,
1235e1242.
5. Asahara, H.; Nishiwaki, N. J. Org. Chem. 2014, 79, 11735e11739.
6. For seminal work, see: (a) Ullmann, F.; Bielecki, J. Ber. 1901, 34, 2174e2185; (b)
Ullmann, F. Ann. 1904, 332, 38e81; (c) Ullmann, F. Ber. 1903, 36, 2382e2384; (d)
Ullmann, F.; Sponagel, P. Ber. 1905, 38, 2211e2212.
7. For reviews, see: (a) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. Engl. 2003,
42, 5400e5449 and references cited therein; (b) Hassan, J.; Sevignon, M.; Gozzi,
C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359e1469 and references cited
therein; (c) Sambiagio, C.; Marsden, S. P.; Blacker, A. J.; McGowan, P. C. Chem.
Soc. Rev. 2014, 43, 3525e3550 and references cited therein.
nmax 1013, 1135, 1182, 1217, 1271, 1369, 1497, 1595, 1679, 1751 cmꢁ1
1H NMR (300 MHz, CDCl3):
2.31 (s, 3H), 3.92 (s, 3H), 7.17 (s, 1H),
7.62 (s, 1H), 10.17 (s, 1H). 13C NMR (75 MHz, CDCl3):
20.4, 56.5,
.
d
d
116.8, 123.7, 125.6, 126.8, 139.6, 156.3, 168.3, 189.9. LRMS (EI) m/z
(rel intensity) 232 (M[81Br]-OAcþHþ, 99), 230 (M[79Br]-OAcþHþ,
81
100), 229 (53). TOF-HRMS calcd for C
H
BrO4 (M[81Br]þHþ)
10 10
79
274.9738, found 274.9737; for C
found 272.9748.
H
10 10
BrO4 (M[79Br]þHþ) 272.9757,
8. Nelson, T. D.; Crouch, R. D. Org. React. 2004, 63, 265e555.
9. For CarylsbndCaryl bond, see: (a) Kelly, T. R.; Xie, R. L. J. Org. Chem. 1998, 63,
8045e8048; (b) Degnan, A. P.; Meyers, A. I. J. Am. Chem. Soc. 1999, 121,
2762e2769; (c) Stark, L. M.; Lin, X.-F.; Flippin, L. A. J. Org. Chem. 2000, 65,
3227e3230.
10. For Caryl-heteroatom bond, see: (a) Boger, D. L.; Sakya, S. M.; Yohannes, D. J. Org.
Chem. 1991, 56, 4204e4207; (b) Nicolaou, K. C.; Boddy, C. N. C.; Natarajan, S.;
Yue, T. Y.; Li, H.; Braese, S.; Ramanjulu, J. M. J. Am. Chem. Soc. 1997, 119,
3421e3422; (c) Evans, D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett. 1998, 39,
2937e2940; (d) Wipf, P.; Jung, J.-K. J. Org. Chem. 2000, 65, 6319e6337; (e) Ma,
D.; Xia, C. Org. Lett. 2001, 3, 2583e2586; (f) Uchiro, H.; Kato, R.; Arai, Y.; Ha-
segawa, M.; Kobayakawa, Y. Org. Lett. 2011, 13, 6268e6271; (g) Theppawong, A.;
Ploypradith, P.; Chuawong, P.; Ruchirawat, S.; Chittchang, M. Chem.dAsian J.
2015, 10, 2631e2650.
11. (a) Kwong, F. Y.; Klapars, A.; Buchwald, S. L. Org. Lett. 2002, 4, 581e584; (b)
Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2002, 4, 4309e4312; (c) Ma, D.;
Cai, Q. Org. Lett. 2003, 5, 3799e3802; (d) Cristau, H.-J.; Cellier, P. P.; Hamada, S.;
Spindler, J.-F.; Taillefer, M. Org. Lett. 2004, 6, 913e916; (e) Chen, Y.-J.; Chen, H.-H.
Org. Lett. 2006, 8, 5609e5612; (f) Wolf, C.; Liu, S.; Mei, X.; August, A. T.; Casimir,
M. D. J. Org. Chem. 2006, 71, 3270e3273; (g) Thasana, N.; Worayuthakarn, R.;
Kradanrat, P.; Hohn, E.; Young, L.; Ruchirawat, S. J. Org. Chem. 2007, 72,
9379e9382; (h) Altman, R. A.; Shafir, A.; Lichtor, P. A.; Buchwald, S. L. J. Org.
Chem. 2008, 73, 284e286; (i) Niu, J.; Zhou, H.; Li, Z.; Xu, J.; Hu, S. J. Org. Chem.
2008, 73, 7814e7817; (j) Zhang, Q.; Wang, D.; Wang, X.; Ding, K. J. Org. Chem.
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Chem. 2015, 39, 31e37.
4.2.24. 4-Bromo-5-formyl-2-methoxyphenyl
(28). To stirred solution of
methyl
2-bromo-4-hydroxy-5-
carbonate
a
methoxybenzaldehyde (1.00 g, 4.33 mmol) in CH2Cl2 (40 mL) at
room temperature was added methyl chloroformate (0.40 mL,
5.19 mmol), DMAP (0.026 g, 0.22 mmol) and Et3N (0.60 mL,
4.33 mmol). The reaction mixture was stirred until all of the
starting material was consumed as monitored by TLC. Water
(20 mL) and CH2Cl2 (10 mL) were added, and the two phases were
separated. The aqueous layer was extracted with CH2Cl2 (20 mLꢂ2).
The combined organic layers were washed with brine (20 mL),
dried over Na2SO4, filtered, and concentrated under reduced pres-
sure to give the crude product. Following purification by column
chromatography on silica (40% EtOAc/hexanes), the product was
obtained as a white solid (1.25 g, 4.32 mmol, 99%). Rf (40% EtOAc/
hexane) 0.58. IR (UATR): nmax 1022, 1194, 1260, 1438, 1501, 1601,
1683, 1766, 2851, 2959 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 3.92 (s,
3H), 3.95 (s, 3H), 7.19 (s, 1H), 7.72 (s, 1H), 10.18 (s, 1H). 13C NMR
(75 MHz, CDCl3): d 55.9, 56.7, 110.0, 123.3, 125.8, 126.8, 139.9, 153.1,
156.3, 189.8. LRMS (EI) m/z (rel intensity) 290 (M[81Br]þHþ, 63) 288
(M[79Br]þHþ, 65), 243 (100), 94 (94). TOF-HRMS calcd for
12. (a) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev. 2004, 248, 2337e2364;
(b) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108, 3054e3131; (c)
Wu, Q.; Wang, L. Synthesis 2008, 2007e2012; (d) Monnier, F.; Taillefer, M.
Angew. Chem., Int. Ed. Engl. 2008, 47, 3096e3099; (e) Monnier, F.; Taillefer, M.
81
C
C
H
H
BrO5Na (M[81Br]þNaþ) 312.9505, found 312.9540; for
BrO5Na (M[79Br]þNaþ) 310.9526, found 310.9524.
10
9
79
9
10
€
€
Angew. Chem., Int. Ed. Engl. 2009, 48, 6954e6971; (f) Nullen, M. P.; Gottlich, R.
Synthesis 2011, 1249e1254.
4.2.25. 3-Methoxyphenyl thiophene-2-carboxylate (31). Following
the general procedure and purification by preparative TLC (40%
EtOAc/hexanes), the product was obtained as a colorless sticky gum
(0.16 g, 0.69 mmol, 43%). Rf (40% EtOAc/hexanes) 0.55. IR (UATR):
13. (a) Chen, C.; Yang, L.-M. J. Org. Chem. 2007, 72, 6324e6327; (b) Fors, B. P.;
Watson, D. A.; Biscoe, M. R.; Buchwald, S. L. J. Am. Chem. Soc. 2008, 130,
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11049e11061; (e) Xie, X.; Ni, G.; Ma, F.; Ding, L.; Xu, S.; Zhang, Z. Synlett 2011,
955e958; (f) Ackermann, L.; Sandmann, R.; Song, W. Org. Lett. 2011, 13,
1784e1786; (g) Raghuvanshi, D. S.; Gupta, A. K.; Singh, K. N. Org. Lett. 2012, 14,
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3734e3737; (i) Green, R. A.; Hartwig, J. F. Org. Lett. 2014, 16, 4388e4391.
14. Zhang, S.; Zhang, D.; Liebeskind, L. S. J. Org. Chem. 1997, 62, 2312e2313.
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Ray, J. K.; Willis, A. C. Tetrahedron 2010, 66, 9252e9262; (b) Banwell, M. G.;
Jones, M. T.; Reekie, T. A. Chem. New Zeal. 2011, 75, 122e127; (c) Ma, X.; Vo, Y.;
Banwell, M. G.; Willis, A. C. Asian J. Org. Chem. 2012, 1, 160e165; (d) Tang, F.;
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Tetrahedron 2014, 70, 6789e6795.
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nmax 1057, 1133, 1245, 1314, 1490, 1608, 1722 cmꢁ1
.
1H NMR
(300 MHz, CDCl3):
d
3.81 (s, 3H), 6.77e6.83 (m, 3H), 7.16 (dd, J¼5.1,
3.8 Hz, 1H), 7.31 (dd, J¼8.1, 7.8 Hz, 1H), 7.65 (dd, J¼5.1, 1.2 Hz, 1H),
7.97 (dd, J¼3.8, 1.2 Hz, 1H). 13C NMR (75 MHz, CDCl3):
d 55.5, 107.6,
112.0, 113.9, 128.1, 129.9, 133.6, 134.7, 151.5, 160.5. LRMS (EI) m/z (rel
intensity) 234 (Mþ, 18), 111 (100). TOF-HRMS calcd for C12H10SO3Na
(MþNaþ) 257.0243, found 257.0233.
Acknowledgements
Financial support from the Thailand Research Fund
(BRG5980010 for P.P.) is gratefully acknowledged.
Supplementary data
Supplementary data (General methods and copies of 1H and 13
C
NMR of all new compounds.) related to this article can be found at
http://dx.doi.org/10.1016/j.tet.2016.07.063. These data include MOL