Ligand-free and heterogeneous palladium on carbon-catalyzed hetero-suzuki-miyaura cross-coupling

Article abstract of DOI:10.1002/adsc.200900638

A ligand-free and heterogeneous palladium on carbon (Pd/C)-catalyzed hetero-SuzukiMiyaura coupling reaction has been developed. The protocol enables the construction of both heterocyclic-alicyclic and heterocyclic-heterocyclic biaryl derivatives in good to excellent yields. Furthermore, Pd/C could be reused. The time-course study clarified that palladium was leached into the reaction media as the reaction proceeded and then completely deposited on the carbon support.

Full text of DOI:10.1002/adsc.200900638

FULL PAPERS
DOI: 10.1002/adsc.200900638
Ligand-Free and Heterogeneous Palladium on Carbon-Catalyzed
Hetero-Suzuki–Miyaura Cross-Coupling
Yoshiaki Kitamura,a,b Satoko Sako,a Azusa Tsutsui,a Yasunari Monguchi,a
Tomohiro Maegawa,c Yukio Kitade,b and Hironao Sajikia,*
a
Laboratory of Organic Chemistry, Department of Organic and Medicinal Chemistry, Gifu Pharmaceutical University,
5-6-1 Mitahora-higashi, Gifu 502-8585, Japan
Fax : (+81)-58-237-5979; e-mail: sajiki@gifu-pu.ac.jp
Department of Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
Current address: Graduate School of Pharmaceutical Sciences, Osaka University, 1–6 Yamada-oka, Suita, Osaka
b
c
565-0871, Japan
Received: September 14, 2009; Revised: January 4, 2010; Published online: February 19, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900638.
Abstract: A ligand-free and heterogeneous palladi- fied that palladium was leached into the reaction
um on carbon (Pd/C)-catalyzed hetero-Suzuki– media as the reaction proceeded and then complete-
Miyaura coupling reaction has been developed. The ly deposited on the carbon support.
protocol enables the construction of both heterocy-
clic-alicyclic and heterocyclic-heterocyclic biaryl de-
rivatives in good to excellent yields. Furthermore, Keywords: C C coupling; heterocycles; heterogene-
Pd/C could be reused. The time-course study clari- ous catalysis; palladium; Suzuki–Miyaura reaction
À
Introduction
hetero
ACHTUNGTRENaNUNG ryl halides and heteroarylboronic acids or het-
eroaryl trifluoroborates.[3] However, these methods
The palladium-catalyzed Suzuki–Miyaura coupling re- utilized homogeneous palladium catalysts in the pres-
action is one of the most valuable synthetic methods ence of phosphine ligands. A few ligand-free Suzuki–
for preparing biaryls, which play an important role as Miyaura coupling reactions of heterocycle-containing
partial structures of pharmaceuticals, natural products, substrates catalyzed by a homogeneous palladium cat-
agrochemicals and functional materials.[1] The key ad- alyst were recently reported.[4,5] Li and co-workers
vantages of the Suzuki–Miyaura coupling reaction are found that the Suzuki–Miyaura couplings between
the high tolerance toward functional groups, the com- aryl halides and arylboronic acids worked when using
mercial availability and low toxicity of reagents, the the PdACTHNUTRGENUN(G OAc)2/NaOMe catalytic system without any li-
stability of boronic acids toward heat, oxygen, and gands and promoters at room temperature, but the
water, and the ease of handling and separation of the protocol required the use of a strong base such as
boron-containing by-products from the reaction mix- NaOMe, and the coupling between the heteroaryl hal-
tures. These desirable features make the Suzuki– ides and heteroarylboronic acids was not very effi-
Miyaura coupling reaction a popular and effective cient.[4] Bryce and co-workers succeeded in the syn-
tool. Numerous research groups have developed effi- theses of functionalized heteroarylpyridines by the
cient palladium catalytic systems for use in the Suzuki–Miyaura coupling reactions in the absence of
Suzuki–Miyaura coupling reaction, but most protocols any ligands and additives, but only particularly substi-
are mainly limited to the construction of the simple tuted boronic acids worked well for the smooth reac-
non-heteroaryl-aryl units, and are usually difficult to tion.[5] Furthermore, homogeneous catalysts were dif-
apply to the synthesis of heterocyclic biaryl deriva- ficult to recover and reuse, and the residual Pd metal
tives due to the potential binding nature of heterocy- in the products could induce serious problems in the
cle-containing substrates to the metal center.[2]
synthesis of bioactive and/or functional substrates. To
Recently, highly active catalytic protocols have overcome these concerns, the application of reusable
been developed for the cross-coupling between and recoverable heterogeneous catalysts has recently
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Ligand-Free and Heterogeneous Palladium on Carbon-Catalyzed Hetero-Suzuki–Miyaura Cross-Coupling
Table 1. Optimization of reaction conditions.
attracted much attention due to the increasing world-
wide momentum for the development of environmen-
tally friendly reactions in terms of green chemistry.[6]
Palladium on carbon (Pd/C) is one of the most suita-
ble catalysts with the advantages of being inexpensive,
stable, removable, and reusable.[7] Although some in-
teresting results of the Pd/C-catalyzed Suzuki–
Miyaura coupling reactions of heteroaryl compounds
including a ligand-free version were reported,[8] they
are not very applicable to a wide variety of substrates.
Only a single example of heteroaryl-heteroaryl cou-
pling has been reported to date.[9]
We recently reported the mild and efficient ligand-
free Pd/C-catalyzed Suzuki–Miyaura coupling reac-
tion at room temperature in the presence of a mild in-
organic base in aqueous and/or alcoholic media, such
as NaHCO3/MeOH, Na2CO3/50% EtOH, and
Na3PO4/50% i-PrOH.[10] These methods are applicable
to the coupling between a wide variety of arylboronic
acids or boronic esters and aryl halides with excellent
yields, although the coupling of heteroaromatic (het-
Entry 10% Pd/C
[mol%]
Temperature
[8C]
Time
[h]
Yield
[%][a]
1
2
3
4
0.5
3.5
3.5
3.5
r.t.
r.t.
80
24
24
24
3
0[b]
2[b]
77
80
98[c]
[a]
[b]
[c]
Isolated yield.
2-bromopyridine remained unchanged.
1.5 equiv. of 4-methoxyphenylboronic acid were used.
eroaryl) bromides and/or halides did not proceed. As nylboronic acids with 2-bromopyridine, the desired
part of our ongoing studies, we communicated the heterobiaryl products were obtained in good to excel-
preliminary results of the ligand-free Pd/C-catalyzed lent yields (entries 1–4). In contrast, the use of 3- and
hetero-Suzuki–Miyaura coupling reaction for the syn- 4-bromopyridines, 5-bromopyrimidine and 3-bromo-
thesis of heterobiaryl derivatives during heating at quinoline as the substrates instead of 2-bromopyridine
808C.[11] Herein, we report the full details of these gave the corresponding coupled products in low to
studies, which provide an efficient and practical moderate yields (entries 6–9). In the case of 2-bromo-
hetero-Suzuki–Miyaura coupling method between pyridine, the coordination of the nitrogen lone pair of
heteroaryl halides and boronic acids including the 2-bromopyridine to the Pd metal facilitated the ap-
À
effect of the reaction parameters, such as solvent, proach to the adjacent C Br bond at the ortho-posi-
base, temperature, catalytic activity of commercial Pd/ tion, and the subsequent oxidative addition of the Pd
C and the reusability of Pd/C and Pd leaching tests.
to the aryl bromide easily took place. Such a coordi-
native activation effect cannot be expected for other
heteroaryl bromides (entries 6–9).
Results and Discussion
To explore the scope of this method, the coupling
of non-heteroaryl bromides with heteroarylboronic
Our first attempts to develop the ligand-free Pd/C- acids was investigated (Table 3). Various non-hetero-
catalyzed hetero-Suzuki–Miyaura coupling were made aryl bromides and iodide-bearing electron-withdraw-
by reacting 2-bromopyridine and 4-methoxyphenyl- ing and electron-donating groups efficiently coupled
boronic acid (1.1 equiv.) in the presence of with 4-dibenzofuranboronic acid and 2-benzofuran-
Na3PO4·12H2O (3.5 equiv.) and 10% Pd/C in 50% i- boronic acid in good to excellent yields within 1–2 h
PrOH (Table 1). While the coupling reaction hardly (entries 1, 2 and 8–12). It is noteworthy that the pres-
took place at room temperature under the efficient ent protocol is applicable even to the sulfur-contain-
reaction conditions for the Pd/C-catalyzed Suzuki– ing boronic acid (entry 3), for which a lot of problems
Miyaura reaction of the previously reported for non- and limitations, such as protodeboronation[3a,g,12] and
heteroaromatic substrates[10] (entries 1 and 2), the re- catalyst poisoning based on the sulfur atom have been
action smoothly proceeded by applying heat (808C) reported in the literature.[13] The coupling using pyri-
(entry 3). Furthermore, the desired coupling product dineboronic acids bearing no other substitutent on
was quantitatively obtained using 1.5 equiv. of 4-me- the pyridine ring did not occur and 4-bromonitroben-
thoxyphenylboronic acid (entry 4).
zene was quantitatively recovered (entries 4 and 5),
First, hetero-Suzuki–Miyaura couplings of heteroar- whereas 2-methoxy-5-pyridineboronic acid or 2,6-di-
yl bromides and non-heteroarylboronic acids methoxy-3-pyridineboronic acid was successfully cou-
(1.5 equiv.) were carried out using 10% Pd/C pled to give the corresponding heterobiaryl com-
(3.5 mol% of Pd metal) and Na3PO4·12H2O pound. The reaction was completed within 1 h (en-
(3.5 equiv.) in 50% i-PrOH at 808C (Table 2). In cases tries 6, 7 and 13). In our previous studies on the cou-
of a series of electron-neutral and electron-rich phe- pling of non-heteroaryl bromides with non-heteroaryl-
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Table 2. Pd/C-catalyzed hetero-Suzuki–Miyaura coupling between heteroaryl bromides and non-heteroarylboronic acids.
Yield [%][a]
À
À
Entry
Ar Br
Ar B(OH)2
Time [h]
1
2
3
24
5
94
97
98
3
4
5
6
5
96
42
27
24
24
7[b]
24
59
8
6
79
24
9
24
[a]
Isolated yield.
[b]
4-Bromopyridine hydrogen chloride was used as a substrate together with 4.5 equiv. of Na3PO4·12H2O.
boronic acids (esters), we found that aryl boronic moquinoline with 2-benzofuranboronic acid gave
acids (esters) possessing an electron-withdrawing sub- comparable results (entries 3 and 4).
stituent on the aromatic ring are less reactive com-
Therefore, we again explored in detail the reaction
pared with electron-neutral and -rich arylboronic parameters to enhance the reactivity. Initially, the sol-
acids (esters).[10] For the 3-pyridineboronic acid and 4- vent effect was examined more closely using 3-bromo-
pyridineboronic acid, the electron-deficient pyridine qunoline and 2-benzofuranboronic acid as the sub-
ring strongly affected the poor reactivity because of strates. The use of non-aqueous alcoholic solvents, es-
the low electron density on the boronate complex pecially EtOH, i-PrOH, and t-BuOH, gave excellent
(entries 4 and 5). In fact, a significant enhancement of results (Table 5, entries 2, 4 and 5). On the other
the reactivity was observed by introducing electron- hand, MeOH and 50% i-PrOH, which were quite suit-
donating methoxy groups on the pyridine ring and the able solvents for the Suzuki–Miyaura coupling reac-
desired coupling products were efficiently obtained.
tions between non-heteroaryl bromides and boronic
We further attempted to apply the present method acids,[10] and aprotic polar solvents, such as THF,
to the coupling between heteroaryl bromides and het- DMF, and 1,4-dioxane, which are commonly used for
eroarylboronic acids. In the case of the reactions of 2- the homogeneous palladium-catalyzed Suzuki–
bromopyridine and 3-bromoquinoline with 4-dibenzo- Miyaura coupling reactions, gave poor results
furanboronic acid, the deboronation of 4-dibenzofur- (Table 5, entries 1 and 3, 6–8). Hence, non-aqueous i-
anboronic acid was mainly observed accompanied by PrOH was finally selected as the solvent for the reac-
a minor homo-coupling reaction and only 1% and 5% tion because it is less expensive and readily available.
of the desired hetero-Suzuki–Miyaura coupling prod-
Our next studies focused on the effect of bases
ucts were obtained (Table 4, entries 1 and 2). Further- (Table 6). Na3PO4·12H2O and Na2CO3 gave satisfac-
more, the couplings of 5-bromopyrimidine and 3-bro- tory results (entries 1 and 4), whereas the significant
depression of the reactivity was observed using the
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Ligand-Free and Heterogeneous Palladium on Carbon-Catalyzed Hetero-Suzuki–Miyaura Cross-Coupling
corresponding potassium, lithium, and cesium salts reaction was incomplete even after 24 h at 608C
(entries 2, 3, 5 and 6). Although these results are in- (entry 2), the complete conversion was observed even
teresting, the correlation of the reactivity with the within 0.5 h at 808C (entry 3).
counter anion of the base is not clear.
Among the key factors for the reaction progress,
The efficiency of the coupling between heteroaryl the use of Pd/C (Pd metal) and Na3PO4·12H2O is also
bromides and heteroarylboronic acids was tempera- important. The use of 10% Pd/C as catalyst could be
ture-dependently enhanced (Table 7). Although the reduced to 1.0 mol% without any significant reduc-
Table 3. Pd/C-catalyzed hetero-Suzuki–Miyaura coupling between non-heteroaryl halides and heteroarylboronic acids.
Yield [%][a]
98
À
À
Entry
1
Ar X
Ar B(OH)2
Time [h]
1
2
3
1
98
72
12
4
5
24
24
– (87[b])
– (98[b])
6
7
1
1
96
96
8
1
97
9
1
2
1
96
83
85
10
11
12
1
1
98
91
13
[a]
Isolated yield.
The yield of recovered 4-bromonitrobenzene.
[b]
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Table 4. Pd/C-catalyzed hetero-Suzuki–Miyaura coupling between heteroaryl bromides and heteroarylboronic acids.
Yield [%][a]
1 (64[b], 4[c])
À
À
Entry
1
Ar Br
Ar B(OH)2
2
3
5 (86[b], 4[c])
15 (14[d])
34 (9[d])
4
[a]
Isolated yield.
The yield of dibenzofuran.
The yield of 4,4’-bisdibenzofuran.
The yield of 2,2’-bibenzofuran.
[b]
[c]
[d]
Table 5. Effect of solvents on the hetero-Suzuki–Miyaura
coupling reaction.
Table 6. Effect of bases on the hetero-Suzuki–Miyaura cou-
pling reaction.
Entry
Solvent
Yield [%][a]
Entry
Base
Yield [%][a]
1
2
3
4
5
6
7
8
MeOH
EtOH
50% i-PrOH
i-PrOH
t-BuOH
THF
55
97
34
100
100
30
21
87
1
2
3
4
5
6
Na3PO4·12H2O
K3PO4·nH2O
Li2CO3
Na2CO3
K2CO3
100
1
50
97
47
3
Cs2CO3
DMF
1,4-dioxane
a) Yields were determined by GC.
[a]
Yields were determined by GC.
ring (entry 11), proceeded smoothly (entries 1–7 and
10–13). Unfortunately, the reaction using 3-pyridine-
tion in the reactivity (Table 8, entries 1–5), and the boronic acid or 4-pyridineboronic acid as a substrate
use of Na3PO4·12H2O could be decreased to did not proceed due to the electron deficiency as
1.0 equiv. (entries 6–10).
noted in Table 3, entries 4 and 5.
We next explored the scope and limitations of the
We further explored the improvement in efficiency
substrates under the optimized reaction conditions for the coupling using low reactive combinations of
[10% Pd/C (1.0 mol% of Pd metal) and heteroaryl bromides with non-heteroarylboronic acids
Na3PO4·12H2O (1.0 equiv.) in i-PrOH at 808C] and non-heteroaryl bromides with heteroarylboronic
(Table 9). The coupling reaction between the hetero- acids by utilizing non-aqueous i-PrOH as the solvent
aryl bromides and heteroarylboronic acids, even those (Table 10). Although the coupling between 2-bromo-
possessing an unprotected NH function on the indole pyridine and 4-chloroboronic acid was incomplete
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Ligand-Free and Heterogeneous Palladium on Carbon-Catalyzed Hetero-Suzuki–Miyaura Cross-Coupling
Table 7. Effect of temperature on the hetero-Suzuki–
Miyaura coupling reaction.
onic acid was extremely accelerated in i-PrOH and
the corresponding cross-coupling product was nearly
quantitatively obtained within 1 h (Table 10, entry 6
vs. Table 3, entry 3).
Regarding the hetero-Suzuki–Miyaura coupling re-
acton, the use of non-aqueous i-PrOH is more suita-
ble than that of 50% i-PrOH (Table 4, Table 5,
Table 9 and Table 10). Based on these results, we ex-
amined the effect of water more closely.
Several reaction conditions containing different
ratios of water were examined (Table 11). The reac-
tion efficiency was enhanced with the progressive re-
duction in the water content, although further remov-
al of a trace amount of water by the distillation of i-
PrOH or the use of anhydrous Na3PO4 instead of
Na3PO4·12H2O had no effect on the reaction (en-
tries 1–3 and 5–7). However, the addition of a drop of
water, which is equivalent to the crystal water of
Na3PO4·12H2O, into the reaction mixture containing
anhydrous Na3PO4 led to a decrease in the reaction
efficiency (compare entries 2 and 4). In addition,
when anhydrous Na3PO4 was used as a base, the fur-
ther loss of reactivity was observed under strictly an-
hydrous conditions using distilled (anhydrous) i-
PrOH and flame-dried Na3PO4 (entries 6 and 7). The
addition of a small amount of water would accelerate
the reaction due to the formation of the correspond-
ing active boronate complex, while the excessive
water would cause the protodeboronation.[14,15] Based
on these results, we believe that a trace amount of
water is required for the efficient cross-coupling reac-
tion, and the crystal water in Na3PO4·12H2O plays a
crucial role.
10% Pd/C (K type) manufactured by N.E. Chem-
cat, which was the most efficient catalyst for the non-
hetero-Suzuki–Miyaura coupling reactions in our pre-
vious studies,[10] was also suitable for the present
hetero-Suzuki–Miyaura coupling reactions. The cata-
lyst activity of Pd/C, being unrelated to the supplier,
is favorable as a synthetic application. The supplier-
dependent catalyst activity of Pd/C was examined for
the coupling reaction between 5-bromopyrimidine
and 2-benzofuranboronic acid. The Pd/C obtained
from Aldrich and Acros gave nearly equivalent re-
Entry
Temperature [8C]
Time [h]
Yield [%][a]
1
2
3
r.t.
60
80
24
24
0.5
2
81
100
[a]
Yields were determined by GC.
Table 8. Optimization of the dosages of Pd/C and bases.
Entry 10% Pd/C
[mol%]
Na3PO4·12H2O
[equiv.]
Time Yield
[h]
[%][a]
1
2
3
4
5
6
7
8
9
10
3.5
1.5
1.0
0.5
–
1.0
1.0
1.0
1.0
1.0
3.5
3.5
3.5
3.5
3.5
3.0
2.5
1.5
1.0
0.5
0.5
0.5
0.5
1
100
100
100
100
1
100
100
99
24
0.5
0.5
0.5
0.5
24
98
68
[a]
Yields were determined by GC.
even after a 24-h reaction time in 50% aqueous i- sults to the K type 10% Pd/C of N.E. Chemcat Co.
PrOH (Table 2, entry 5), the drawback of the coupling (Table 12, entries 1, 3 and 4).[16] Since the use of dry-
reaction was solved by the use of non-aqueous i- type Pd/C is problematic in process chemistry due to
PrOH, and then the reaction was successfully com- its flammable nature, wet-type Pd/C would be desira-
pleted within 24 h (Table 10, entry 1). Similarly, the ble as a catalyst when considering industrial applica-
reactions between 4-methoxyphenylboronic acid and tions. The wet-type Pd/C [N.E. Chemcat (K type),
3-bromopyridine, 4-bromopyridine, 5-bromopyrimi- containing 50 weight% of water]-catalyzed hetero-
dine or 3-bromoquinoline in i-PrOH also gave the de- Suzuki–Miyaura coupling reaction gave totally com-
sired coupling products in excellent yields, although parable results to that of the dry-type Pd/C (compare
the use of 3.5 mol% of 10% Pd/C and 3.5 equiv. of entries 1 and 2).
Na3PO4·12H2O was essential (Table 10, entries 2–5 vs.
The reusability of Pd/C is a great advantage from
Table 2, entries 6–9). Furthermore, the coupling reac- cost reduction and environmental viewpoints. Pd/C
tion of 4-bromonitrobenzene and 2-benzothienylbor- could be successfully reused at least until the fifth run
Adv. Synth. Catal. 2010, 352, 718 – 730
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Table 9. Pd/C-catalyzed hetero-Suzuki–Miyaura coupling between heteroaryl bromides and heteroarylboronic acids.
Yield [%][a]
78
À
À
Entry
1
Ar Br
Ar B(OH)2
Time [h]
24
2
3
7
3
90
98
4
12
75
5
6
7
8
0.5
24
24
24
100
83
91
– (97[b])
9
120
– (82[b])
10
11
24
24
71
70
12
1
91
97
13
24
[a]
Isolated yield.
The yield of recovered 3-bromoquinoline is indicated.
[b]
without any reduction of the catalyst activity 20, 25, 30 min or 24 h), and the filtrate was extracted
(Table 13). with EtOAc and water and separated into organic
The time-course analyses of both the palladium and aqueous layers (Scheme 1). The leached palladi-
leaching and reaction progress in the cross-coupling um in each layer was analyzed by inductively coupled
between 3-bromoquinoline and 2-benzofuranboronic plasma atomic emission spectrometry (ICP-AES),[17]
acid using 10% Pd/C and Na3PO4·12H2O in i-PrOH and the yield of the cross-coupled product was deter-
at 808C were carried out (Figure 1). The hot reaction mined by the GC analysis of the organic layer. The
mixture was filtered without cooling through a palladium leaching increased with the reaction prog-
0.45 mm membrane disk at the given time (5, 10, 15, ress and the Pd concentration in the filtrate was
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Ligand-Free and Heterogeneous Palladium on Carbon-Catalyzed Hetero-Suzuki–Miyaura Cross-Coupling
Table 10. Pd/C-catalyzed cross-coupling between heteroaryl bromides and arylboronic acids, and between aryl bromides and
heteroarylboronic acids.
Yield [%][a]
95
À
À
Entry
1
Ar Br
Ar B(OH)2
Time [h]
24
2
6
3
1
98
97
98
3[b]
4
5
6
1
99
95
6[c]
[a]
Isolated yield.
[b]
[c]
4-Bromopyridine hydrogen chloride was used as a substrate together with 4.5 equiv. of Na3PO4·12H2O.
1.0 mol% of 10% Pd/C and 1.0 equiv. of Na3PO4·12H2O were used.
Table 11. Effect of water on the Suzuki–Miyaura coupling
reaction.
Table 12. Catalyst activity of 10% Pd/C toward the hetero-
Suzuki–Miyaura coupling reaction.
Yield [%][b]
Entry
Supplier of 10% Pd/C
Time [h]
Yield [%][a]
Entry Base
Solvent
1
N.E. Chemcat (K type)
N.E. Chemcat (K type)
Aldrich (205699-50G)
Acros (19503-0100)
3
3
4
3
98
99
97
97
1
2
Na3PO4·12H2O 50% i-PrOH (58)[a] 18
2[b]
3
Na3PO4·12H2O i-PrOH (16)[a]
Na3PO4·12H2O i-PrOH (16)[a]
77
77
66
68
63
55
3[c]
4[d]
5
i-PrOH (16)[a]
i-PrOH (<1)[a]
i-PrOH (<1)[a]
i-PrOH (ꢀ0)[a]
4
Na3PO4
Na3PO4
Na3PO4
Na3PO4
[a]
Isolated yield.
Wet-type Pd/C was used.
6[c]
7[c,e]
[b]
[a]
The water content in the reaction mixture (v/v%) includ-
ing the amount of the crystal water of Na3PO4·12H2O.
Isolated yield.
Distilled i-PrOH was used.
Water corresponding to the crystal water of
Na3PO4·12H2O was added.
reached a maximum when the conversion yield was
achieved around 50–80% (20–25 min), and then time-
dependently decreased below the detection limit
(<0.25 ppm, 24 h). These results clearly indicate that
the process of the “release and capture” of the Pd
metal on the activated carbon would be involved
during the reaction.[18]
[b]
[c]
[d]
[e]
Flame dried (anhydrous) Na3PO4 was used.
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Yoshiaki Kitamura et al.
FULL PAPERS
Table 13. Recycling of used Pd/C on hetero-Suzuki–Miyaura
coupling reaction.
catalyzed hetero-Suzuki–Miyaura coupling reaction.
The methods allow for the preparation of a wide vari-
ety of heterocyclic biaryl derivatives involved in
hetero-heterobiaryl coupling in good to excellent
yields. Furthermore, Pd/C was recoverable and reusa-
ble. These advantages make the process highly valua-
ble from synthetic and environmental points of view.
Experimental Section
Entry
Run
Time [h]
Yield [%][a]
General Methods
1
2
3
4
5
1
2
3
4
5
3
3
3
4
4
98
100
97
99
98
Unless otherwise stated, all the reactions were carried out
under argon, and commercially obtained materials were
used without further purification. The aryl bromides were
purchased from Aldrich Chemical Co., Inc., Tokyo Chemi-
cal Industry Co., Ltd. or Wako Pure Chemical Industries,
Ltd. The arylboronic acids were purchased from Aldrich
Chemical Co., Inc., Tokyo Chemical Industry Co., Ltd. or
Wako Pure Chemical Industries, Ltd. Pd/C was purchased
from Acros Organics, Aldrich Chemical Co., Inc. or re-
ceived as a gift from the N.E. Chemcat Co. Bases and sol-
vents (HPLC grade) were purchased from Aldrich Chemical
Co., Inc., Nacalai Tasque, Inc. or Wako Pure Chemical In-
dustries, Ltd. and used without any further purification. The
1H and 13C NMR spectra were recorded on a JEOL JNM
EX-400 or a JEOL JNM AL-400 spectrometer (400 MHz
a) Isolated yield.
1
for H NMR and 100 MHz for 13C NMR), and CDCl3 was
used as the solvent. Low and high-resolution mass spectra
were taken on a JEOL JMS-SX102A instrument. Elemental
analyses were performed using a YANACO MT-5 instru-
ment. Flash column chromatography was performed using
Kanto Chemical Co., Inc., silica gel 60N, spherical neutral
(63–210 mm).
General Procedure for the Synthesis of Heteroaryl-
Non-Heteroaryl Derivatives using the
Na3PO4·12H2O/50% i-PrOH System (Table 2 and
Table 3)
Figure 1. Kinetic investigation and palladium leaching for
the Suzuki–Miyaura reaction of 3-bromoquinoline with 2-
benzofuranboronic acid: ( ) yield of 2-(3’-quinolyl)benzofur-
&
*
an; ( ) leached palladium in the reaction mixture.
To a test-tube containing a stir bar were added the aryl bro-
mide (250 mmol), arylboronic acid (375 mmol),
Na3PO4·12H2O (333 mg, 875 mmol), 10% Pd/C (9.3 mg,
8.75 mmol), H2O (0.5 mL), and i-PrOH (0.5 mL), and the
system was then sealed with a septum. The air inside was re-
placed with argon (balloon) by three vacuum/argon ex-
Conclusions
In conclusion, we have developed mild and efficient
protocols for the ligand-free and heterogeneous Pd/C- change cycles and the mixture was stirred at 808C. After a
Scheme 1. Analysis of leached palladium.
726
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 718 – 730

Ligand-Free and Heterogeneous Palladium on Carbon-Catalyzed Hetero-Suzuki–Miyaura Cross-Coupling
certain period, the mixture was diluted with H2O (25 mL)
and EtOAc (or Et2O) (25 mL), and passed through a mem-
brane filter (Millipore, Millexꢁ-LH, 0.45 mm). The filtrate
was separated into two layers and the aqueous layer was ex-
tracted with EtOAc (or Et2O) (2ꢂ25 mL). The combined
organic layers were then washed with brine (25 mL), dried
over Na2SO4 (or MgSO4), and concentrated under vacuum.
The residue was purified by flash column chromatography
on silica gel to give the corresponding biaryl.
J=7.4 Hz, 1H), 7.52 (s, 1H), 7.48 (d, J=8.4 Hz, 1H), 7.16
(dd, J=7.4 Hz, 4.8 Hz, 1H), 6.89 (d, J=8.4 Hz, 1H), 6.00 (s,
2H); 13C NMR: d=156.8, 149.4, 148.4, 148.2, 136.6, 133.8,
121.6, 120.8, 119.9, 108.3, 107.3, 101.2; MS (EI): m/z=199
(M+, 100%); HR-MS (EI): m/z=199.0640, calcd. for
C12H9NO2 (M+): 199.0633; anal. calcd. for C12H9NO2·1/
9H2O: C 71.63, H 4.62, N 6.96; found: C 71.78, H 4.59, N
6.93.
2-(4’-Chlorophenyl)pyridine:[19] Colorless oil; 1H NMR:
d=8.69 (d, J=4.0 Hz, 1H), 7.94 (d, J=8.6 Hz, 2H), 7.75(t,
J=7.6 Hz, 1H), 7.69 (d, J=7.6 Hz, 1H), 7.45 (d, J=8.6 Hz,
2H), 7.02 (dd, J=7.6 Hz, 4.0 Hz, 1H); 13C NMR: d=156.9,
150.4, 138.5, 137.5, 135.8, 129.6, 128.8, 123.0, 121.0; MS (EI):
m/z=189 (M+, 100%); HR-MS (EI): m/z=189.0347, calcd.
for C11H8ClN (M+): 189.0345.
General Procedure for the Synthesis of Heteroaryl-
Non-Heteroaryl Derivatives using the
Na3PO4·12H2O/i-PrOH System (Table 10)
i-PrOH (1.0 mL) was used instead of H2O (0.5 mL) and i-
PrOH (0.5 mL) in the above procedure.
3-(4’-Methoxyphenyl)pyridine:[19]
Colorless
solid;
1H NMR: d=8.83 (s, 1H), 8.55 (d, J=4.7 Hz, 1H), 7.82 (d,
J=7.7 Hz, 1H), 7.50 (d, J=8.6 Hz, 2H), 7.32 (dd, J=4.7 Hz,
7.7 Hz, 1H), 7.00 (d, J=8.6 Hz, 2H), 3.84 (s, 3H);
13C NMR: d=159.7, 147.5, 147.4, 136.3, 133.9, 130.0, 128.1,
123.5, 114.5, 55.2; MS (EI): m/z=185 (M+, 100%); HR-MS
(EI): m/z=185.0832, calcd. for C12H11NO (M+): 185.0841.
General Procedure for the Synthesis of Heteroaryl-
Hetero/Non-Heteroaryl Derivatives using the
Na3PO4·12H2O/i-PrOH System (Table 9)
To a test tube containing a stir bar were added the aryl bro-
mide (500 mmol), arylboronic acid (750 mmol),
Na3PO4·12H2O (190 mg, 500 mmol), 10% Pd/C (5.3 mg,
5.00 mmol), and i-PrOH (2.0 mL), and the system was then
sealed with a septum. The air inside was replaced with
argon (balloon) by three vacuum/argon exchnage cycles and
the mixture was stirred at 808C. After a certain period, the
mixture was diluted with H2O (50 mL) and EtOAc (50 mL),
and passed through a membrane filter (Millipore, Millexꢁ-
LH, 0.45 mm). The filtrate was separated into two layers and
the aqueous layer was extracted with EtOAc (2ꢂ50 mL).
The combined organic layers were then washed with brine
(50 mL), dried over Na2SO4 (or MgSO4), and concentrated
under vacuum. The residue was purified by flash column
chromatography on silica gel to give the corresponding
biaryl.
4-(4’-Methoxyphenyl)pyridine:[19]
Colorless
solid;
1H NMR: d=8.62 (d, J=5.8 Hz, 2H), 7.57 (d, J=8.8 Hz,
2H), 7.45 (d, J=5.8 Hz, 2H), 6.98 (d, J=8.8 Hz, 2H), 3.84
(s, 3H); 13C NMR: d=160.5, 149.7, 147.9, 130.1, 128.0, 121.0,
114.5, 55.3; MS (EI): m/z=185 (M+, 100%); HR-MS (EI):
m/z=185.0831, calcd. for C12H11NO (M+): 185.0841.
5-(4’-Methoxyphenyl)pyrimidine:[20]
Colorless
solid;
1H NMR: d=9.16 (s, 1H), 8.92 (s, 2H), 7.52 (d, J=8.4 Hz,
2H), 7.04 (d, J=8.4 Hz, 2H), 3.87 (s, 3H); 13C NMR: d=
160.4, 156.7, 154.3, 133.8, 128.0, 126.4, 114.8, 55.3; MS (EI):
m/z=186 (M+, 100%); HR-MS (EI): m/z=186.0798, calcd
for C11H10N2O (M+): 186.0793.
3-(4’-Methoxyphenyl)quinoline:[21]
Colorless
solid;
1H NMR: d=9.16 (s, 1H), 8.23 (s, 1H), 8.12 (d, J=8.4 Hz,
1H), 7.85 (d, J=8.4 Hz, 1H), 7.69 (t, J=8.4 Hz, 1H), 7.65
(d, J=8.8 Hz, 2H), 7.55 (t, J=8.4 Hz, 1H), 7.05 (d, J=
8.4 Hz, 2H), 3.87 (s, 3H); 13C NMR (CDCl3): d=159.8,
149.8, 147.0, 133.5, 132.3, 130.3, 129.2, 129.0, 128.5, 128.1,
127.8, 126.9, 114.7, 55.4; MS (EI): m/z=235 (M+, 100%);
HR-MS (EI): m/z=235.0991, calcd. for C16H13NO (M+):
235.0997.
4-(4’-Nitrophenyl)dibenzofuran: Yellow solid; mp 174–
1768C; 1H NMR: d=8.34 (d, J=8.8 Hz, 2H), 8.06 (d, J=
8.8 Hz, 2H), 8.00 (d, J=7.6 Hz, 1H), 7.99 (d, J=7.6 Hz,
1H), 7.60 (d, J=8.2 Hz, 1H), 7.59 (d, J=8.2 Hz, 1H), 7.49
(t, J=8.2 Hz, 1H), 7.45 (t, J=8.2 Hz, 1H), 7.38 (t, J=
7.6 Hz, 1H); 13C NMR: d=156.1, 153.1, 147.0, 142.9, 129.4,
127.7, 126.7, 125.4, 123.8, 123.7, 123.4, 123.3, 123.2, 121.3,
120.8, 111.8; MS (EI): m/z=289 (M+, 100%); HR-MS (EI):
m/z=289.0744, calcd. for C18H11NO3 (M+): 289.0739; anal.
calcd. for C18H11NO3·1/3H2O: C 73.21, H 3.98, N 4.74;
found: C 73.25, H 4.04, N 4.63.
Analytical Data for the Suzuki–Miyaura Coupling
Products
2-(4’-Methoxyphenyl)pyridine:[19] Colorless solid; 1H NMR:
d=8.63 (d, J=4.8 Hz, 1H), 7.94 (d, J=8.8 Hz, 2H), 7.68–
7.62ACHTUNGTRENNUNG(m, 2H), 7.15–7.11 (m, 1H), 7.02 (d, J=8.8 Hz, 2H),
3.82 (s, 3H); 13C NMR: d=160.4, 157.0, 149.4, 136.5, 131.9,
128.0, 121.3, 119.6, 114.0, 55.2; MS (EI): m/z=185 (M+,
100%); HR-MS (EI): m/z=185.0838, calcd. for C11H11NO
(M+): 185.0841.
1
2-Phenylpyridine:[19] Colorless oil; H NMR: d=8.65–8.64
(m, 1H), 7.99–7.96 (m, 2H), 7.63–7.57 (m, 2H), 7.44–7.33
(m, 3H), 7.22–7.08 (m, 1H); 13C NMR: d=157.1, 149.4,
139.1, 136.4, 128.7, 128.5, 126.6, 121.8, 120.2; MS (EI): m/z=
155 (M+, 100%); HR-MS (EI): m/z=155.07447, calcd for
C11H9N (M+): 155.0735.
1
2-(4’-Tolyl)pyridine:[19] Colorless oil; H NMR: d=8.66 (d,
2-(4’-Nitrophenyl)benzofuran:[22] Yellow solid; 1H NMR:
d=8.30 (d, J=8.8 Hz, 2H), 7.99 (d, J=8.8 Hz, 2H), 7.64 (d,
J=8.0 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.37 (t, J=8.0 Hz,
1H), 7.30–7.23 (m, 2H); 13C NMR: d=155.4, 153.2, 147.3,
136.3, 128.6, 125.8, 125.2, 124.3, 123.5, 121.6, 111.5, 105.1;
MS (EI): m/z=239 (M+, 100%); HR-MS (EI): m/z=
239.0588, calcd for C14H9NO3 (M+) 239.0583.
J=4.8 Hz, 1H), 7.88 (d, J=8.0 Hz, 2H), 7.68–7.67 (m, 2H),
7.26 (d, J=8.0 Hz, 2H), 7.18–7.14 (m, 1H), 2.38 (s, 3H);
13C NMR: d=157.4, 149.5, 138.8, 136.6, 136.5, 129.4, 126.7,
121.7, 120.1, 21.2; MS (EI): m/z=169 (M+, 100%); HR-MS
(EI): m/z=169.0897, calcd. for C12H11N (M+): 169.0892.
1
2-(3’,4’-Methylenedioxy)pyridine: Colorless oil; H NMR:
d=8.63 (d, J=4.8 Hz, 1H), 7.68 (t, J=7.4 Hz, 1H), 7.61 (d,
Adv. Synth. Catal. 2010, 352, 718 – 730
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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727

Yoshiaki Kitamura et al.
FULL PAPERS
2-(4’-Nitrophenyl)benzothiophene:[23]
Yellow
solid;
2-Methoxy-5-(4’-methoxyphenyl)pyridine:[24]
Colorless
solid; 1H NMR (CDCl3): d=8.34 (d, J=2.4 Hz, 1H), 7.73
(dd, J=8.4 Hz, 2.4 Hz, 1H), 7.44 (d, J=8.8 Hz, 2H), 6.97 (d,
J=8.8 Hz, 2H), 6.78 (d, J=8.4 Hz, 1H), 3.97 (s, 3H), 3.83
(s, 3H); 13C NMR (CDCl3): d=163.2, 159.1, 144.4, 137.1,
130.4, 129.7, 127.7, 114.4, 110.6, 55.3, 53.4; MS (EI): m/z=
215 (M+, 100%); HR-MS (EI): m/z=215.0951, calcd. for
C13H13NO2 (M+): 215.0946.
1H NMR: d=8.27 (d, J=8.8 Hz, 2H), 7.87–7.84 (m, 4H),
7.70 (s, 1H), 7.42–7.38 (m, 2H); 13C NMR: d=147.2, 141.2,
140.6, 140.3, 140.2, 126.8, 125.6, 125.1, 124.4, 124.3, 122.4,
122.4; MS (EI): m/z=255 (M+, 100%); HR-MS (EI): m/z=
255.0360, calcd. for C14H9NO2S (M+): 255.0354.
2-Methoxy-5-(4’-nitrophenyl)pyridine: Yellow solid; mp
1
166–1688C; H NMR (CDCl3): d=8.44 (s, 1H), 8.29 (d, J=
8.8 Hz, 2H), 7.83 (d, J=8.8 Hz, 1H), 7.68 (d, J=8.8 Hz,
2H), 6.87 (d, J=8.8 Hz, 1H), 3.98 (s, 3H); 13C NMR
(CDCl3): d=164.6, 147.1, 145.6, 144.4, 137.3, 127.6, 127.1,
124.3, 111.3, 53.7; MS (EI): m/z=230 (M+, 100%); HR-MS
(EI): m/z=230.0698, calcd. for C12H10N2O3 (M+): 230.0692;
anal. calcd. for C12H10N2O3: C 62.60, H 4.38, N 12.17; found:
C 62.70, H 4.45, N 12.11.
2,6-Dimethoxy-3-(4’-nitrophenyl)pyridine: Yellow solid;
mp 158–1608C; 1H NMR (CDCl3): d=8.22 (d, J=8.8 Hz,
2H), 7.70 (d, J=8.8 Hz, 2H), 7.62 (d, J=8.2 Hz, 1H), 6.44
(d, J=8.2 Hz, 1H), 4.00 (s, 3H), 3.98 (s, 3H); 13C NMR
(CDCl3): d=163.3, 159.4, 146.2, 143.8, 141.4, 129.4, 123.4,
113.1, 102.0, 53.7, 53.6; MS (EI): m/z=260 (M+, 100%);
HR-MS (EI): m/z=260.0805, calcd. for C13H12N2O4 (M+):
260.0797; anal. calcd. for C13H12N2O4: C 60.00, H 4.65, N
10.76; found: C 60.16, H 4.88, N 10.45.
4-(2’-Pyridyl)dibenzofuran:[25] Colorless oil; 1H NMR
(CDCl3): d=8.80 (d, J=6.0 Hz, 1H), 8.41 (d, J=8.0 Hz,
1H), 8.27 (d, J=8.0 Hz, 1H), 8.00 (d, J=8.0 Hz, 1H), 7.99
(d, J=8.0 Hz, 1H), 7.89 (t, J=8.0 Hz, 1H), 7.64 (d, J=
8.0 Hz, 1H), 7.49 (t, J=8.0 Hz, 2H), 7.37 (t, J=8.0 Hz, 1H),
7.30(dd, J=8.0 Hz, 6.0 Hz, 1H); 13C NMR (CDCl3): d=
156.1, 153.8, 153.7, 149.7, 136.6, 127.3, 125.1, 124.3, 124.2,
124.0, 123.3, 122.9, 122.4, 121.2, 120.7, 111.8, 113.7; MS (EI):
m/z=245 (M+, 100%); HR-MS (EI): m/z=245.0839, calcd.
for C17H11NO (M+): 245.0841.
4-(3’-Quinolyl)dibenzofuran: Colorless solid; mp 145–
1478C; 1H NMR (CDCl3): d=9.46 (d, J=2.0 Hz, 1H),
8.59(d, J=2.0 Hz, 1H), 8.18 (d, J=7.5 Hz, 1H), 7.91 (t, J=
7.5 Hz, 2H), 7.87 (d, J=7.5 Hz, 1H), 7.71 (t, J=7.4 Hz,
1H), 7.66 (d, J=7.4 Hz, 1H), 7.58–7.54 (m, 2H), 7.50–7.40
(m, 2H), 7.34 (t, J=7.5 Hz, 1H); 13C NMR (CDCl3): d=
156.0, 153.3, 150.6, 147.3, 135.0, 129.5, 129.2, 129.1, 128.0,
127.8, 127.3, 126.8, 126.5, 125.0, 123.8, 123.3, 122.8, 122.2,
120.6, 120.4, 111.7; MS (EI): m/z=295 (M+, 100%); HR-MS
(EI): m/z=295.0986, calcd. for C21H13NO (M+): 295.0997;
anal. calcd for C21H13NO·1/11H2O: C 84.93, H 4.47, N 4.72;
found: C 84.98, H 4.60, N 4.71.
4-(4’-Acetylphenyl)dibenzofuran:
Colorless
solid;
1H NMR: d=8.08 (d, J=8.0 Hz, 2H), 7.98 (d, J=8.0 Hz,
2H), 7.96 (d, J=8.0 Hz, 1H), 7.94 (d, J=8.0 Hz, 1H), 7.59
(d, J=8.0 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.45 (t, J=
8.0 Hz, 1H), 7.40 (t, J=8.0 Hz, 1H), 7.35 (t, J=8.0 Hz, 1H),
2.64 (s, 3H); 13C NMR: d=197.6, 156.1, 153.3, 141.1, 136.1,
128.8, 128.6, 127.4, 126.7, 125.1, 124.5, 123.9, 123.2, 122.9,
120.7, 120.5, 111.8, 26.6; MS (EI): m/z=286 (M+, 81%);
HR-MS (EI): m/z=286.0987, calcd. for C20H14O2 (M+):
286.0994; anal. calcd. for C20H14O2: C 83.90, H 4.93; found:
C 83.75, H 5.08.
2-(5’-Pyrimidyl)benzofuran:[26] Colorless solid; 1H NMR
(CDCl3): d=9.15 (s, 1H), 9.10 (s, 1H), 7.57 (d, J=7.8 Hz,
2H), 7.51 (d, J=7.8 Hz, 2H), 7.32 (t, J=7.8 Hz, 1H), 7.24
(t, J=7.8 Hz, 1H); 13C NMR (CDCl3): d=157.6, 155.0,
152.4, 149.4, 128.0, 125.4, 124.6, 123.4, 121.2, 111.2, 103.9;
MS (EI): m/z=196 (M+, 100%); HR-MS (EI): m/z=
196.0642, calcd. for C12H8N2O (M+): 196.0637.
1
2-(4’-Acetylphenyl)benzofuran: Colorless solid; H NMR:
d=8.00 (d, J=8.6 Hz, 2H), 7.90 (d, J=8.6 Hz, 2H), 7.59 (d,
J=8.4 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.32 (t, J=8.4 Hz,
1H), 7.22 (t, J=8.4 Hz, 1H), 2.60 (s, 3H); 13C NMR: d=
197.2, 155.2, 154.5, 136.5, 134.5, 128.9, 125.1, 124.7, 123.2,
121.3, 111.3, 103.6, 26.6; MS (EI): m/z=236 (M+, 90%);
HR-MS (EI): m/z=236.0830, calcd. for C16H12O2 (M+):
236.0837; anal. calcd. for C16H12O2·1/7H2O: C 80.46, H 5.18;
Found: C 80.85, H 5.26.
2-(3’-Quinolyl)benzofuran: Colorless solid; mp 134–
1
1368C; H NMR (CDCl3): d=9.31 (s, 1H), 8.50 (s, 1H), 8.10
(d, J=8.2 Hz, 1H), 7.84 (d, J=8.2 Hz, 1H), 7.68 (t, J=
8.2 Hz, 1H), 7.60 (d, J=7.8 Hz, 1H), 7.55–7.51 (m, 2H),
7.31 (t, J=7.8 Hz, 1H), 7.24 (t, J=7.8 Hz, 1H), 7.17 (s, 1H);
13C NMR (CDCl3): d=155.1, 153.1, 147.6, 147.5, 130.7,
129.7, 129.3, 128.8, 128.1, 127.7, 127.3, 125.0, 123.6, 123.3,
121.2, 111.2, 102.9; MS (EI): m/z=245 (M+, 100%); HR-MS
(EI): m/z=245.0835, calcd. for C17H11NO (M+): 245.0841;
anal. calcd. for C17H11NO: C 83.25, H 4.52, N 5.71; found: C
82.97, H 4.77, N 5.62.
1
4-(2’-Tolyl)dibenzofuran: Colorless oil; H NMR: d=7.97
(d, J=7.8 Hz, 1H), 7.94 (d, J=7.8 Hz, 1H) 7.50 (d, J=
7.8 Hz, 1H), 7.43–7.31 (m, 8H), 2.24 (s, 3H); 13C NMR: d=
156.2, 153.6, 136.8, 136.4, 130.3, 130.2, 128.3, 128.1, 127.1,
126.3, 125.7, 124.3, 124.2, 122.7, 122.7, 120.7, 119.6, 111.8,
20.2; MS (EI): m/z=258 (M+, 100%); HR-MS (EI): m/z=
258.1055, calcd. for C19H14O (M+): 258.1045; anal. calcd. for
C19H14O: C 88.34, H 5.46; found: C 88.10, H 5.68.
2-(3’-Pyridyl)benzofuran:[27] Colorless solid; 1H NMR
(CDCl3): d=9.07 (d, J=1.6 Hz, 1H), 8.53 (dd, J=4.6,
1.6 Hz, 1H), 8.02 (dt, J=8.0, 1.6 Hz, 1H), 7.55 (dd, J=7.7,
0.6 Hz, 1H), 7.49 (dd, J=8.2, 0.6 Hz, 1H), 7.30–7.20 (m,
3H), 7.02 (s, 1H); 13C NMR (CDCl3): d=154.4, 152.2, 148.6,
145.7, 131.1, 128.1, 125.9, 124.3, 122.9, 122.6, 120.5, 110.6,
102.1; MS (EI): m/z=195 (M+, 100%); HR-MS (EI): m/z=
195.0690, calcd. for C13H9NO (M+): 195.0684.
4-(4’-Methoxyphenyl)dibenzofuran:
Colorless
solid;
1H NMR: d=7.97 (d, J=8.0 Hz, 1H), 7.89–7.85 (m, 3H),
7.59 (d, J=8.0 Hz, 2H), 7.56 (d, J=8.0 Hz, 2H), 7.45 (t, J=
8.0 Hz, 1H), 7.39 (t, J=8.0 Hz, 1H), 7.34 (t, J=8.0 Hz, 1H),
3.88 (s, 3H); 13C NMR: d=159.3, 156.1, 153.3, 129.9, 128.8,
127.1, 126.4, 125.5, 124.8, 124.3, 123.1, 122.7, 120.6, 119.0,
114.1, 111.8, 55.3; MS (EI): m/z=289 (M+, 100%); HR-MS
(EI): m/z=274.0998, calcd. for C19H14O2 (M+): 274.0994;
anal. calcd. for C19H14O2·1/6.5H2O: C 82.36, H 5.20; found:
C 82.36, H 5.21.
3-(2’-Thienyl)quinoline:[20] Colorless solid; 1H NMR
(CDCl3): d=9.17 (s, 1H), 8.21 (s, 1H), 8.07 (d, J=8.2 Hz,
1H), 7.77 (d, J=8.2 Hz, 1H), 7.65 (t, J=8.2 Hz, 1H), 7.51
(t, J=8.2 Hz, 1H), 7.45 (d, J=3.6 Hz, 1H), 7.35 (d, J=
5.2 Hz, 1H), 7.12 (dd, J=5.2 Hz, 3.6 Hz, 1H); 13C NMR
(CDCl3): d=148.6, 147.3, 140.8, 131.4, 129.3, 129.3, 128.4,
728
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Adv. Synth. Catal. 2010, 352, 718 – 730

Ligand-Free and Heterogeneous Palladium on Carbon-Catalyzed Hetero-Suzuki–Miyaura Cross-Coupling
127.9, 127.8, 127.6, 127.3, 126.1, 124.4; MS (EI): m/z=211
(M+, 100%); HR-MS (EI): m/z=211.0461, calcd. for
C13H9NS (M+): 211.0456.
Mei, S. P. Nolan, Chem. Eur. J. 2006, 12, 5142–5148;
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3-(6-Methoxypyridin-3-yl)quinoline:[28] Colorless solid;
1H NMR (CDCl3): d=9.10 (s, 1H), 8.50 (s, 1H), 8.19 (s,
1H), 8.13 (d, J=8.4 Hz, 1H), 7.87 (d, J=8.4 Hz, 1H), 7.84
(d, J=8.4 Hz, 1H), 7.70 (t, J=8.4 Hz, 1H), 7.56 (t, J=
8.4 Hz, 1H), 6.88 (d, J=8.4 Hz, 1H), 4.00 (s, 3H); 13C NMR
(CDCl3): d=164.0, 149.2, 147.2, 145.3, 137.3, 132.5, 130.6,
129.3, 129.2, 127.8, 127.8, 127.0, 126.7, 111.2, 53.5; MS (EI):
m/z=236 (M+, 100%); HR-MS (EI): m/z=236.0955, calcd.
for C15H12N2O (M+): 236.0950.
2-(5’-Indoyl)benzofuran: Colorless solid; mp 156–1588C;
1H NMR: d=8.18 (s, 1H), 8.05 (brs, 1H), 7.68 (d, J=8.8 Hz,
1H), 7.54 (d, J=7.2 Hz, 1H), 7.52 (d, J=7.2 Hz, 1H), 7.35
(d, J=8.8 Hz, 1H), 7.26–7.18 (m, 3H), 7.15 (t, J=7.2 Hz,
1H), 6.93 (s, 1H), 6.60–6.59 (m, 1H); 13C NMR: d=157.6,
154.7, 135.9, 129.7, 128.1, 125.1, 123.5, 122.7, 122.6, 120.4,
119.7, 117.6, 111.4, 110.9, 103.3, 99.4; MS (EI): m/z=233
(M+, 100%); HR-MS (EI): m/z=233.0835, calcd. for
C16H11NO (M+): 233.0841; anal. calcd. for C16H11NO·1/
3H2O: C 80.32, H 4.91, N 5.85; found: C 80.46, H 4.90, N
5.82.
4-[2’-(5’-Methyl)thienyl]dibenzofuran: Colorless solid; mp
76–788C; 1H NMR (CDCl3): d=7.87 (d, J=8.0 Hz, 1H),
7.73 (d, J=8.0 Hz, 1H), 7.68 (d, J=3.4 Hz, 1H), 7.58 (d, J=
8.0 Hz, 2H), 7.41 (t, J=8.0 Hz, 1H), 7.28 (t, J=8.0 Hz, 1H),
7.25 (t, J=8.0 Hz, 1H), 6.80 (d, J=3.4 Hz, 1H), 2.51 (s,
3H); 13C NMR (CDCl3): d=156.0, 151.9, 140.0, 136.1, 127.2,
126.6, 126.2, 124.9, 124.5, 124.0, 123.0, 122.8, 120.6, 119.7,
118.7, 111.8, 15.3; MS (EI): m/z=264 (M+, 100%); HR-MS
(EI): m/z=264.0604, calcd. for C17H12OS (M+): 264.0609;
anal. calcd. for C17H12OS: C 77.24, H 4.58; found: C 77.27,
H 4.73.
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2-[2’-(5’-Methyl)thienyl]benzofuran: Colorless solid; mp
1
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Bryce, B. Tarbit, Eur. J. Org. Chem. 2008, 1458–1463;
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[6] a) For review, see: R. A. Sheldon, I. Arends, U. Hane-
feld, Green Chemistry and Catalysis, Wiley-VCH, Wein-
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85–878C; H NMR: d=7.48 (d, J=7.0 Hz, 1H), 7.45 (d, J=
7.0 Hz, 1H), 7.25 (d, J=4.0 Hz, 1H), 7.23–7.18 (m, 2H),
6.73 (s, 1H), 6.72 (d, J=4.0 Hz, 1H), 2.48 (s, 3H);
13C NMR: d=154.4, 151.5, 140.8, 130.9, 129.2, 126.1, 124.6,
123.9, 123.0, 120.5, 110.9, 100.2, 15.3; MS (EI): m/z=214
(M+, 100%); HR-MS (EI): m/z=214.0444, calcd. for
C13H10OS (M+): 214.0452; anal. calcd. for C13H10OS: C
72.87, H 4.70; found: C 72.92, H 4.81.
Acknowledgements
[7] S. Nishimura, Handbook of Heterogeneous Catalytic
Hydrogenation for Organic Synthesis, Wiley-VCH, New
York, NY, 2001.
We thank the N. E. Chemcat Corporation for the gift of 10%
Pd/C and measurement of the leached amount of palladium.
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