Ruthenium-catalyzed C-H bond functionalizations of 1,2,3-Triazol-4-yl- substituted arenes: Dehydrogenative couplings versus direct arylations

Article abstract of DOI:10.1055/s-0029-1220010

The chemoselectivity of ruthenium-catalyzed C-H bond arylations on triazol-4-yl-substituted arenes was found to depend on the substitution pattern of both substrates. While various aryl chlorides led to products stemming from direct arylations, ortho-substituted aryl halides in combination with ortho-alkylated arenes preferentially resulted in oxidative homo-couplings. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1220010

PAPER
2245
Ruthenium-Catalyzed C–H Bond Functionalizations of 1,2,3-Triazol-4-yl-
Substituted Arenes: Dehydrogenative Couplings Versus Direct Arylations
R
uthenium-Cata
u
lyzedDehy
t
drogena
z
tive
H
omo-Coup
A
lings
V
ersus Direc
c
t
A
rylation
k
s
ermann,* Petr Novák, Rubén Vicente, Valentina Pirovano, Harish K. Potukuchi
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstr. 2, 37077 Göttingen, Germany
Fax +49(551)396777; E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
Received 18 April 2010
Dedicated to the 90th birthday of Prof. Rolf Huisgen
Moreover, these studies resulted in the development of
Abstract: The chemoselectivity of ruthenium-catalyzed C–H bond
novel reaction conditions for ruthenium-catalyzed19 dehy-
arylations on triazol-4-yl-substituted arenes was found to depend on
the substitution pattern of both substrates. While various aryl chlo-
rides led to products stemming from direct arylations, ortho-substi-
drogenative homo-coupling reactions20 of disubstituted
arenes 1, which involved the use of ortho-substituted aryl
tuted aryl halides in combination with ortho-alkylated arenes halides 2 as sacrificial oxidant, and thereby provided ac-
preferentially resulted in oxidative homo-couplings.
cess to biaryl derivatives 4 (Scheme 1).
Key words: arylations, C–H activation, dehydrogenation, rutheni-
um, triazoles
R1
N
N
N
(a)
R1
R3
R2
N
N
Huisgen 1,3-dipolar cycloaddition reactions are among
the most versatile tools for the synthesis of functionalized
heterocycles.1–4 Particularly, azide–alkyne [3+2] cycload-
ditions have recently been widely employed for post-syn-
thetic modifications of biologically active compounds or
functional materials, since excellent chemoselectivity and
site-selectivity could be accomplished with copper5–7 cat-
alysts.8 Thus, considering the increasing practical impor-
tance of the resulting 1,4-disubstituted 1,2,3-triazole
scaffold for synthetic chemistry,8 we became interested in
exploiting this N-heteroaromatic moiety as directing
group for a subsequent post-synthetic functionalization,
ideally via a modular C–H bond functionalization strate-
gy. As a result, we previously disclosed ruthenium-
catalyzed9,10 direct arylations11 of arenes displaying triaz-
ol-1-yl substituents as directing groups.12–15 In continua-
tion of our research program on sustainable C–H bond
functionalizations,16,17 we probed the use of 4-aryl-substi-
tuted 1,2,3-triazoles 1 as substrates for directed arylations,
on which we wish to report herein.18 A notable feature of
this approach is represented by its site-selectivity being
complementary to copper or palladium-catalyzed15 C–H
bond functionalizations (Figure 1).
N
R2
H
cat. [Ru]
X
3
R1
N
N
1
N
(b)
R2
R3
R2
2
N
N
N
R1
4
Scheme 1 Chemoselectivity of ruthenium-catalyzed C–H bond
functionalization: (a) direct arylation versus (b) oxidative homo-
coupling
At the outset of our studies, we tested direct arylations of
4-aryl-1,2,3-triazole 1a (R1 = Oct; R2 = 2-Me) with aryl
bromide 2a in toluene as solvent (Table 1). Notably, no
reaction occurred in the absence of additives (entry 1). On
the contrary, carboxylic acid MesCO2H (5) was found to
generate an active catalyst (entries 2 and 3), which also
proved applicable to aryl iodides, and less expensive aryl
chlorides (entries 4 and 5). However, ruthenium complex-
es derived from representative phosphines 6 or N-hetero-
cyclic carbene precursor 7 only provided unsatisfactory
results, under otherwise identical reaction conditions (en-
tries 6–8).
R1
[Cu] or [Pd]
N
N
N
H
[Ru]
H
Subsequently, we tested the scope of the catalytic system
in direct arylations with differently substituted triazol-4-
yl-substituted arenes 1 employing economically attractive
aryl chlorides 2 (Scheme 2). Here, mono- or para-disub-
stituted arenes 1 as substrates delivered preferentially the
diarylated products 3.
R2
1
Figure 1 Complementary site-selectivities in post-synthetic C–H
bond functionalizations of 1,2,3-triazoles 1
However, monoarylated products 3 were obtained with
both ortho- (entries 1–10) as well as meta-substituted
arenes 1 (entry 11, Table 2). In the latter case, the direct
SYNTHESIS 2010, No. 13, pp 2245–2253
Advanced online publication: 18.05.2010
DOI: 10.1055/s-0029-1220010; Art ID: C02010SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
0

2246
L. Ackermann et al.
PAPER
Table 1 Effect of Additives on Direct Arylation of 1,2,3-Triazole 1aa
(entries 6 and 7) or ketone substituents (entries 8–11),
were well tolerated. On the contrary, the use of an ortho-
substituted aryl chloride did not allow for a conversion of
a meta-substituted arene (entry 12).
Oct
Oct
N
N
N N
N
N
OMe
[RuCl2(p-cymene)]2
X
(2.5 mol%)
L (10–30 mol%)
Table 2 Scope of Direct Arylations of Triazol-4-yl-Substituted
Arenes 1a
+
K2CO3, PhMe
20 h
OMe
R1
R1
1a
2
3a
N
N
N N
[RuCl2(p-cymene)]2
N
N
(2.5 mol%)
MesCO2H (5)
(30 mol%)
Entry
2
L
Temp (°C) Yield (%)
Cl
R3
1
2
3
4
5
6
7
8
Br (2a)
Br (2a)
Br (2a)
I (2b)
–
120
120
100
120
120
120
120
120
–
+
K2CO3, PhMe
120 °C, 20 h
R2
R2
R3
MesCO2H (5)
MesCO2H (5)
MesCO2H (5)
MesCO2H (5)
PPh3 (6a)
PCy3 (6b)
HIPrClb (7)
92
67
79
85
23c
27c
–
1
2
3
Entry R1
R3
3
Yield
(%)
Cl (2c)
Cl (2c)
Cl (2c)
Cl (2c)
Hex
N
N
N
1
2
3
4
5
6
7
Hex
H
3h 99
a Reaction conditions: 1a (1.00 mmol), 2 (1.50 mmol), [RuCl2(p-
cymene]2 (2.5 mol%), L (10–30 mol%), K2CO3 (2.00 mmol), PhMe
(4.0 mL), 120 °C, 20 h; yields of isolated products.
b HIPr = N,N¢-bis-(2,6-di-isopropylphenyl)imidazolium.
c GC conversion.
Hex
N
N
N
Hex 4-Me
Hex 4-OMe
Oct 4-CF3
Hex 4-F
3i
3j
74
68
MeO
R1
R1
N
N
N N
Hex
N
N
[RuCl2(p-cymene)]2
(2.5 mol%)
N
N
Cl
R3
R3
N
OMe
MesCO2H (5)
(30 mol%)
+
MeO
K2CO3, PhMe
120 °C, 20 h
R3
R2
R2
1
2
3
Oct
Hex
Oct
N
N
N
N
N N
N
CF3
N
N
MeO
OMe
F3C
CF3
3k 67
3b: 58%
3c: 60%
Hex
Oct
Oct
N
N
N
N
N N
O
O
N
F
3l
89
N
N
EtO2C
CO2Et
Ph
Ph
3d: 64%
3e: 78%
Hex
Hex
Oct
N
N
N
N
N N
O
O
O
O
N
CO2Et
Hex 4-CO2Et
3m 67
N
N
MeO
3f: 66%
3g: 71%
Oct
N
N
N
CO2Et
Scheme 2 Ruthenium-catalyzed direct arylations of 1,2,3-triazoles
1 with an excess of aryl chlorides 2
Oct 4-CO2Et
3n 92
functionalization took selectively place at the less sterical-
ly hindered C–H bond. Given the remarkably mild reac-
tion conditions, valuable functional groups, such as ester
Synthesis 2010, No. 13, 2245–2253 © Thieme Stuttgart · New York

PAPER
Ruthenium-Catalyzed Dehydrogenative Homo-Couplings Versus Direct Arylations
2247
Table 2 Scope of Direct Arylations of Triazol-4-yl-Substituted
Arenes 1a (continued)
aryl bromide 2k proved to be a viable additive, but ortho-
functionalized bromoarenes 2l and 2m gave less satisfac-
tory results (entries 11 and 12).
R1
R1
N
N
N N
[RuCl2(p-cymene)]2
N
N
Table 3 Influence of Aryl Halides 2 on Dehydrogenative
(2.5 mol%)
MesCO2H (5)
(30 mol%)
Cl
Arylationsa
R3
Hex
+
K2CO3, PhMe
120 °C, 20 h
N
N
R2
R2
R3
Hex
[RuCl2(p-cymene)]2
N
N
N
(2.5 mol%)
MesCO2H (5)
(30 mol%)
1
X
2
3
N
Entry R1
R3
3
Yield
(%)
+
K2CO3, PhMe
120 °C, 20 h
R3
N
Hex
N
N
N
N
O
Hex
N
1b
2
4a
8
Hex 4-C(O)Ph
3o 95
Ph
Entry
1
2
Yield (%)
67
Cl
Hex
Hex
Hex
Hex
2d
2e
N
N
N
N
N
N
9
10
11
12
Hex 3-C(O)Ph
Hex 4-C(O)Me
Hex 4-C(O)Me
Hex 4-CF3
3p 91
Cl
Ph
2
–
O
O
N
Cl
O
N
<10b
49
F3C
Cl
CF3
3
4
5
6
2f
2g
2h
2i
3q 88
N
O
N
3r
3s
51
Cl
CF3
CF3
CF3
81
I
N
53
N
–
Br
Br
Br
Br
7
8
9
73
CF3
2j
2k
2l
<10b,c
64d
a Reaction conditions: 1 (1.00 mmol), 2 (1.50 mmol), [RuCl2(p-
cymene]2 (2.5 mol%), 5 (30 mol%), K2CO3 (2.00 mmol), PhMe
(4.0 mL), 120 °C, 20 h; yields of isolated products.
10
11
12
65
Moreover, the chemoselectivity of the C–H bond func-
tionalization altered when ortho-alkylated arene 1b
served as substrate (Table 3). Hence, 2-chlorotoluene (2d)
predominantly led to the formation of product 4a through
an oxidative homo-coupling (entry 1). While more steri-
cally congested aryl chlorides 2e and 2f turned out to be
inferior (entries 2 and 3), mono-ortho-substituted aryl
chlorides 2g, and particularly 2h enabled efficient dehy-
drogenative arylations (entries 4 and 5). Notably, the oxi-
dative C–H bond functionalization was not restricted to
the use of aryl chlorides, but aryl iodide 2i or aryl bromide
2j were successfully employed as well (entries 6 and 7).
Whereas reactions did not proceed in polar solvent NMP
(entry 8), catalysis occurred conveniently under an atmo-
sphere of air (entry 9). Additionally, more electron-rich
CO2H
CN
–
2m
–
a Reaction conditions: 1b (1.00 mmol), 2 (1.50 mmol), [RuCl2(p-
cymene]2 (2.5 mol%), 5 (30 mol%), K2CO3 (2.00 mmol), PhMe
(4.0 mL), 120 °C, 20 h; yields of isolated products.
b GC conversion.
c In NMP (4.0 mL).
d Under an atmosphere of air.
Synthesis 2010, No. 13, 2245–2253 © Thieme Stuttgart · New York

2248
L. Ackermann et al.
PAPER
As to the mechanism, acetophenone was isolated as the All catalytic reactions were carried out under N2 in dry glassware,
unless otherwise noted. Toluene was freshly distilled over Na/ben-
major by-product in the reaction with 2-chloroacetophe-
zophenone. Yields refer to isolated compounds, estimated to be
none (2g) (entry 4), thus indicating that aryl halides 2
>95% pure as judged by 1H NMR and GC analyses. Flash chroma-
served as formal hydrogen acceptor21 in the dehydrogena-
tography was conducted on Macherey-Nagel silica gel 60 (70–230
mesh). NMR spectra were recorded on a Varian VXR 300, or a
tive coupling.
Varian 600 MHz NMR instrument in the solvent indicated; chemi-
cal shifts (d) are given in ppm.
With aryl chloride 2h as optimal sacrificial oxidant we
next explored oxidative homo-couplings of representative
arenes 1 bearing various directing groups (Scheme 3).
Ruthenium-Catalyzed Direct Monoarylation of Triazoles 1; 3¢-
Thus, ortho-alkylated pyrazol-1-yl- or pyridin-2-yl-sub-
Methyl-2¢-(1-n-octyl-1H-1,2,3-triazol-4-yl)biphenyl-4-carboxy-
lic Acid Ethyl Ester (3n); Representative Procedure A (Table 2,
Entry 7)
stituted arenes 1 were homo-coupled in a highly regiose-
lective fashion to yield biaryl derivatives 4b–e. However,
a more electron-deficient arene provided product 4f in sig- A suspension of [RuCl2(p-cymene)]2 (15.4 mg, 0.025 mmol, 2.5
mol%), 5 (49.2 mg, 0.30 mmol, 30 mol%), K2CO3 (276 mg, 2.00
mmol), 1-n-octyl-4-o-tolyl-1,2,3-triazole (271 mg, 1.00 mmol) and
4-chlorobenzoic acid ethyl ester (276 mg, 1.50 mmol) in PhMe (4.0
mL) was stirred at 120 °C for 20 h. EtOAc (50 mL) and H2O (50
mL) were added to the cold reaction mixture. The separated aque-
ous phase was extracted with EtOAc (2 × 50 mL). The combined
organic layers were washed with H2O (50 mL) and brine (50 mL),
dried (Na2SO4), and concentrated under vacuum. The remaining
residue was purified by column chromatography on silica gel (n-
hexane–EtOAc, 5:1) to yield 3n as a colorless oil; yield: 385 mg
(92%).
nificantly diminished yield, while ortho-alkoxy-substitut-
ed derivatives were not functionalized. Thus,
dehydrogenative homo-coupling reactions with aryl chlo-
rides 2 are restricted to electron-rich ortho-alkyl-substi-
tuted arenes, which in turn defines the scope of
ruthenium-catalyzed direct arylations.
R4
[RuCl2(p-cymene)]2
R4
N
R2
R3
N
(2.5 mol%)
MesCO2H (5)
(30 mol%)
X
R3
X
R1
R1
IR (NaCl): 2926, 2858, 1716, 1642, 1274 cm–1.
R1
2-ClC6H4(CF3) (2h)
K2CO3, PhMe
120 °C, 20 h
1H NMR (300 MHz, CDCl3): d = 7.85 (m, 2 H), 7.40–7.29 (m, 2 H),
7.24–7.11 (m, 3 H), 6.82 (s, 1 H), 4.32 (q, J = 7.1 Hz, 2 H), 4.18 (t,
J = 7.0 Hz, 2 H), 2.28 (s, 3 H), 1.71–1.61 (m, 2 H), 1.34 (t, J = 7.1
Hz, 3 H), 1.20 (m, 8 H), 1.06 (m, 2 H), 0.84 (t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 166.4 (Cq), 146.5 (Cq), 145.2 (Cq),
141.8 (Cq), 138.9 (Cq), 129.9 (CH), 129.5 (CH), 129.0 (Cq), 128.9
(CH), 128.5 (Cq), 128.4 (CH), 127.1 (CH), 122.8 (CH), 60.8 (CH2),
50.0 (CH2), 31.6 (CH2), 30.1 (CH2), 28.9 (CH2), 28.7 (CH2), 26.0
(CH2), 22.5 (CH2), 20.9 (CH3), 14.3 (CH3), 14.0 (CH3).
X
N
R4
R3
R2
R2
N
1
4
N
N
N
N
N
4b: 71%
4c: 52%
MS (EI): m/z (%) = 419 (92, [M+]), 391 (100), 219 (23).
HRMS (ESI): m/z calcd for C26H33N3O2 + H+: 420.2649; found:
420.2646.
N
N
PMB
PMB
Hex
PMB
PMB
1-(4¢-Methoxy-3-methylbiphenyl-2-yl)-4-n-octyl-1H-1,2,3-tria-
zole (3a)
N
N
Representative procedure A was followed, using 1-n-octyl-4-o-
tolyl-1,2,3-triazole (136 mg, 0.50 mmol) and 4-chloroanisole (108
mg, 0.75 mmol) at 120 °C. After 20 h, purification by chromatogra-
phy (n-hexane–EtOAc, 8:1) yielded 3a (160 mg, 85%) as a color-
less oil.
4d: 52%
4e: 56%
N
N
N
F
N
MeO
OMe
IR (NaCl): 2928, 2855, 1609, 1513, 1463, 1289, 1214, 1178, 1036,
833, 789, 758 cm–1.
PMB
PMB
N
1H NMR (300 MHz, CDCl3): d = 7.34–7.18 (m, 3 H), 7.00 (d,
J = 8.7 Hz, 2 H), 6.82 (s, 1 H), 6.71 (d, J = 8.7 Hz, 2 H), 4.21 (t,
J = 7.0 Hz, 2 H), 3.73 (s, 3 H), 2.28 (s, 3 H), 1.70 (q, J = 7.0 Hz, 2
H), 1.30–1.21 (m, 8 H), 1.15–1.08 (m, 2 H), 0.85 (t, J = 6.6 Hz, 3
H).
N
N
N
Hex
4g: ---
F
4f: 23%
Scheme 3 Scope of ruthenium-catalyzed oxidative homo-coupling
13C NMR (75 MHz, CDCl3): d = 158.3 (Cq), 145.8 (Cq), 142.4 (Cq),
138.7 (Cq), 134.1 (Cq), 130.6 (CH), 129.1 (CH), 129.0 (Cq), 128.4
(CH), 127.4 (CH), 122.8 (CH), 113.1 (CH), 55.1 (CH3), 50.0 (CH2),
31.7 (CH2), 30.2 (CH2), 29.0 (CH2), 28.9 (CH2), 26.2 (CH2), 22.6
(CH2), 21.0 (CH3), 14.1 (CH3).
MS (EI): m/z (%) = 377 (88, [M+]), 348 (100), 249 (30), 233 (21),
221 (10), 209 (65), 195 (16), 178 (14), 165 (12), 152 (7), 140 (4), 71
(25), 57 (37), 43 (42).
In summary, we have reported on the chemoselectivity of
ruthenium-catalyzed C–H bond functionalizations of tria-
zol-4-yl-substituted arenes with aryl halides. A catalytic
system derived from MesCO2H (5) enabled broadly appli-
cable direct arylations. Contrarily, oxidative homo-
couplings of electron-rich ortho-alkylated arenes prefer-
entially occurred when ortho-substituted aryl halides
were employed.
Synthesis 2010, No. 13, 2245–2253 © Thieme Stuttgart · New York

PAPER
Ruthenium-Catalyzed Dehydrogenative Homo-Couplings Versus Direct Arylations
2249
HRMS (ESI): m/z calcd for C24H31N3O + H+: 378.2540; found:
378.2539.
4-(3-Methyl-4¢-(trifluoromethyl)biphenyl-2-yl)-1-n-octyl-1H-
1,2,3-triazole (3k)
Representative procedure A was followed, using 1-n-octyl-4-o-
tolyl-1,2,3-triazole (271 mg, 1.00 mmol) and 1-chloro-4-(trifluo-
romethyl)benzene (271 mg, 1.50 mmol) at 120 °C. After 20 h, puri-
fication by chromatography (n-hexane–EtOAc, 5:1) yielded 3k
(278 mg, 67%) as a colorless oil.
1-n-Hexyl-4-(3-methylbiphenyl-2-yl)-1H-1,2,3-triazole (3h)
Representative procedure A was followed, using 1-n-hexyl-4-o-
tolyl-1,2,3-triazole (243 mg, 1.00 mmol) and chlorobenzene (169
mg, 1.50 mmol) at 120 °C. After 20 h, purification by chromatogra-
phy (n-hexane–EtOAc, 5:1) yielded 3h (316 mg, 99%) as a color-
less oil.
IR (NaCl): 2926, 2857, 2226, 1362, 1221 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.52–7.42 (m, 2 H), 7.39–7.29 (m,
2 H), 7.26–7.14 (m, 3 H), 6.89 (s, 1 H), 4.22 (t, J = 7.0 Hz, 2 H),
2.26 (s, 3 H), 1.71 (m, 2 H), 1.22 (m, 8 H), 1.09 (s, 2 H), 0.86 (t,
J = 6.8 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 146.6 (Cq), 144.9 (Cq), 140.9 (Cq),
139.1 (Cq), 131.4 (CH), 130.3 (CH), 130.3 (CH), 128.9 (Cq), 128.7
(CH), 127.0 (CH), 122.6 (CH), 118.7 (Cq), 110.3 (Cq), 50.1 (CH2),
31.6 (CH2), 30.1 (CH2), 29.0 (CH2), 28.8 (CH2), 26.1 (CH2), 22.5
(CH2), 20.8 (CH3), 14.0 (CH3).
IR (NaCl): 2928, 1711, 1642, 1456, 1222 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41–7.25 (m, 2 H), 7.25–7.13 (m,
4 H), 7.07 (m, 2 H), 6.78 (s, 1 H), 4.18 (t, J = 6.9 Hz, 2 H), 2.31 (s,
3 H), 1.73–1.57 (m, 2 H), 1.31–1.16 (m, 4 H), 1.15–1.03 (m, 2 H),
0.86 (t, J = 6.7 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 145.7 (Cq), 142.8 (Cq), 141.8 (Cq),
138.7 (Cq), 129.5 (CH), 129.4 (CH), 129.1 (Cq), 128.3 (CH), 127.7
(CH), 127.3 (CH), 126.4 (CH), 122.8 (CH), 50.0 (CH2), 31.1 (CH2),
30.2 (CH2), 25.8 (CH2), 22.4 (CH2), 21.1 (CH3), 14.0 (CH3).
MS (EI): m/z (%) = 372 (64), 344 (56), 245 (71), 44 (100).
MS (EI): m/z (%) = 319 (100, [M+]), 291 (71), 220 (78), 204 (42).
4-(4¢-Fluoro-3-methylbiphenyl-2-yl)-1-n-hexyl-1H-1,2,3-triaz-
ole (3l)
Representative procedure A was followed, using 1-n-hexyl-4-o-
tolyl-1,2,3-triazole (243 mg, 1.00 mmol) and 1-chloro-4-fluoroben-
zene (196 mg, 1.50 mmol) at 120 °C. After 20 h, purification by
chromatography (n-hexane–EtOAc, 5:1) yielded 3l (300 mg, 89%)
as a colorless oil.
HRMS (ESI): m/z calcd for C21H25N3 + H+: 320.2122; found:
320.2121.
1-n-Hexyl-4-(3-methoxy-4¢-methylbiphenyl-2-yl)-1H-1,2,3-tria-
zole (3i)
Representative procedure A was followed, using 4-o-anisyl-1-n-
hexyl-1,2,3-triazole (259 mg, 1.00 mmol) and 1-chloro-4-methyl-
benzene (190 mg, 1.50 mmol) at 120 °C. After 20 h, purification by
chromatography (n-hexane–EtOAc, 5:1) yielded 3i (259 mg, 74%)
as a colorless oil.
IR (NaCl): 2930, 1641, 1550, 1223 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.35–7.21 (m, 2 H), 7.21–7.12 (m,
1 H), 7.08–6.95 (m, 2 H), 6.92–6.73 (m, 3 H), 4.20 (t, J = 6.9 Hz, 2
H), 2.25 (s, 3 H), 1.77–1.57 (m, 2 H), 1.32–1.14 (m, 4 H), 1.08 (m,
2 H), 0.84 (t, J = 6.8 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 161.5 (1JC,F = 246 Hz, Cq), 145.4
(Cq), 141.6 (Cq), 138.6 (Cq), 137.6 (4JC,F = 3 Hz, Cq), 131.0
(3JC,F = 8 Hz, CH), 129.4 (CH), 129.1 (CH), 128.3 (CH), 127.1
(CH), 122.6 (CH), 114.4 (2JC,F = 21 Hz, CH), 49.9 (CH2), 30.9
(CH2), 30.1 (CH2), 25.7 (CH2), 22.2 (CH2), 20.8 (CH3), 13.8 (CH3).
IR (NaCl): 2923, 2855, 1699, 1642, 1459, 1366 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.45–7.32 (m, 1 H), 7.07–6.90 (m,
7 H), 4.22 (t, J = 7.0 Hz, 2 H), 3.80 (s, 3 H), 2.27 (s, 3 H), 1.69 (m,
2 H), 1.31–1.07 (m, 6 H), 0.86 (t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 158.0 (Cq), 144.0 (Cq), 142.7 (Cq),
138.2 (Cq), 136.1 (Cq), 129.4 (CH), 129.3 (CH), 128.4 (CH), 123.3
(CH), 122.4 (CH), 118.8 (Cq), 109.8 (CH), 56.0 (CH3), 50.0 (CH2),
31.1 (CH2), 30.1 (CH2), 25.9 (CH2), 22.4 (CH2), 21.0 (CH3), 14.0
(CH3).
MS (EI): m/z (%) = 337 (100, [M+]), 309 (44), 238 (89).
HRMS (ESI): m/z calcd for C21H24FN3 + H+: 338.2022; found:
MS (EI): m/z (%) = 349 (100, [M+]), 321 (45), 250 (86).
338.2025.
HRMS (ESI): m/z calcd for C22H27N3O + H+: 350.2222; found:
350.2225.
2¢-(1-n-Hexyl-1H-1,2,3-triazol-4-yl)-3¢-methoxybiphenyl-4-car-
boxylic Acid Ethyl Ester (3m)
Representative procedure A was followed, using 4-o-anisyl-1-n-
hexyl-1,2,3-triazole (259 mg, 1.00 mmol) and 4-chlorobenzoic acid
ethyl ester (277 mg, 1.50 mmol) at 120 °C. After 20 h, purification
by chromatography (n-hexane–EtOAc, 5:1) yielded 3m (273 mg,
67%) as a colorless oil.
4-(3,4¢-Dimethoxybiphenyl-2-yl)-1-n-hexyl-1H-1,2,3-triazole
(3j)
Representative procedure A was followed, using 4-o-anisyl-1-n-
hexyl-1,2,3-triazole (259 mg, 1.00 mmol) and 1-chloro-4-methoxy-
benzene (214 mg, 1.50 mmol) at 120 °C. After 20 h, purification by
chromatography (n-hexane–EtOAc, 5:1) yielded 3j (249 mg, 68%)
as a colorless oil.
IR (NaCl): 2926, 1711, 1641, 1363, 1270 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.92–7.80 (m, 2 H), 7.40 (t,
J = 8.0 Hz, 1 H), 7.23–7.13 (m, 2 H), 7.09 (s, 1 H), 6.99 (d, J = 8.0
Hz, 2 H), 4.32 (q, J = 7.1 Hz, 2 H), 4.22 (t, J = 7.0 Hz, 2 H), 3.80 (s,
3 H), 1.81–1.64 (m, 2 H), 1.34 (t, J = 7.1 Hz, 3 H), 1.29–1.02 (m, 6
H), 0.84 (t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 166.7 (Cq), 158.2 (Cq), 146.3 (Cq),
143.2 (Cq), 142.3 (Cq), 129.9 (CH), 129.7 (CH), 129.2 (CH), 128.9
(Cq), 123.7 (CH), 122.5 (CH), 119.0 (Cq), 110.7 (CH), 61.1 (CH2),
56.2 (CH3), 50.3 (CH2), 31.3 (CH2), 30.3 (CH2), 26.1 (CH2), 22.6
(CH2), 14.5 (CH3), 14.2 (CH3).
IR (NaCl): 2933, 1641, 1461, 1248, 1030 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.44–7.31 (m, 1 H), 7.08–6.88 (m,
5 H), 6.80–6.65 (m, 2 H), 4.22 (t, J = 7.1 Hz, 2 H), 3.79 (s, 3 H),
3.73 (s, 3 H), 1.84–1.65 (m, 2 H), 1.23 (s, 6 H), 0.86 (t, J = 6.7 Hz,
3 H).
13C NMR (75 MHz, CDCl3): d = 158.3 (Cq), 158.0 (Cq), 143.7 (Cq),
142.7 (Cq), 133.5 (Cq), 130.5 (CH), 129.4 (CH), 123.3 (CH), 122.3
(CH), 118.7 (Cq), 113.1 (CH), 109.6 (CH), 55.9 (CH3), 55.0 (CH3),
49.9 (CH2), 31.1 (CH2), 30.1 (CH2), 25.9 (CH2), 22.3 (CH2), 13.9
(CH3).
MS (EI): m/z (%) = 407 (95, [M+]), 379 (100), 308 (61).
MS (EI): m/z (%) = 365 (100, [M+]), 337 (63), 266 (69), 226 (71).
HRMS (ESI): m/z calcd for C24H29N3O3 + H+: 408.2282; found:
408.2281.
HRMS (ESI): m/z calcd for C22H27N3O2 + H+: 366.2176; found:
366.2175.
Synthesis 2010, No. 13, 2245–2253 © Thieme Stuttgart · New York

2250
L. Ackermann et al.
PAPER
{2¢-(1-n-Hexyl-1H-1,2,3-triazol-4-yl)-3¢-methylbiphenyl-4-
yl}(phenyl)methanone (3o)
Representative procedure A was followed, using 1-n-hexyl-4-o-
tolyl-1,2,3-triazole (243 mg, 1.00 mmol) and (4-chlorophenyl)(phe-
nyl)methanone (325 mg, 1.50 mmol) at 120 °C. After 20 h, purifi-
cation by chromatography (n-hexane–EtOAc, 5:1) yielded 3o (402
mg, 95%) as a colorless oil.
MS (EI): m/z (%) = 361 (100, [M+]), 333 (58), 220 (63), 179 (56).
HRMS (ESI): m/z calcd for C23H27N3O + H+: 362.2227; found:
362.2227.
1-{2¢-(1-n-Hexyl-1H-1,2,3-triazol-4-yl)-4¢-methylbiphenyl-3-
yl}ethanone (3r)
Representative procedure A was followed, using 1-n-hexyl-4-m-
tolyl-1,2,3-triazole (243 mg, 1.0 mmol) and 1-(4-chlorophenyl)eth-
anone (232 mg, 1.5 mmol) at 120 °C. After 20 h, purification by
chromatography (n-hexane–EtOAc, 5:1) yielded 3r (184 mg, 51%)
as a colorless oil.
IR (NaCl): 2929, 2090, 1650, 1455, 1278, 928 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.73 (dd, J = 5.2, 3.3 Hz, 2 H),
7.69–7.61 (m, 2 H), 7.55 (ddd, J = 6.6, 3.9, 1.4 Hz, 1 H), 7.50–7.28
(m, 4 H), 7.27–7.17 (m, 3 H), 6.89 (s, 1 H), 4.21 (t, J = 7.1 Hz, 2 H),
2.29 (s, 3 H), 1.78–1.61 (m, 2 H), 1.23–1.01 (m, 6 H), 0.78 (t,
J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 196.2 (Cq), 146.2 (Cq), 145.2 (Cq),
141.7 (Cq), 138.9 (Cq), 137.5 (Cq), 135.4 (Cq), 132.3 (CH), 130.0
(CH), 129.8 (CH), 129.6 (CH), 129.5 (CH), 129.0 (Cq), 128.5 (CH),
128.2 (CH), 127.2 (CH), 122.8 (CH), 50.0 (CH2), 30.9 (CH2), 30.2
(CH2), 25.8 (CH2), 22.3 (CH2), 20.9 (CH3), 13.9 (CH3).
MS (EI): m/z (%) = 423 (56, [M+]), 395 (45), 284 (7), 218 (8), 105
(100).
HRMS (ESI): m/z calcd for C28H29N3O + H+: 424.2383; found:
424.2383.
IR (NaCl): 2927, 2861, 1642, 1361, 1264, 1224 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.98–7.82 (m, 3 H), 7.38–7.27 (m,
2 H), 7.20 (m, 2 H), 6.53 (s, 1 H), 4.15 (t, J = 7.1 Hz, 2 H), 2.60 (s,
3 H), 2.43 (s, 3 H), 1.76–1.61 (m, 2 H), 1.32–1.05 (m, 6 H), 0.84 (t,
J = 6.8 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 197.5 (Cq), 146.6 (Cq), 146.0
(Cq), 138.3 (Cq), 136.2 (Cq), 135.7 (Cq), 129.8 (CH), 129.8 (CH),
129.7 (CH), 128.9 (CH), 128.8 (Cq), 128.2 (CH), 121.9 (CH), 50.2
(CH2), 31.1 (CH2), 30.2 (CH2), 26.7 (CH2), 26.0 (CH3), 22.5 (CH3),
21.2 (CH2), 14.0 (CH3).
MS (EI): m/z (%) = 361 (100, [M+]), 333 (48), 220 (98), 179 (79).
HRMS (ESI): m/z calcd for C23H27N3O + H+: 362.2233; found:
362.2231.
{2¢-(1-n-Hexyl-1H-1,2,3-triazol-4-yl)-3¢-methylbiphenyl-3-
yl}(phenyl)methanone (3p)
Representative procedure A was followed, using 1-n-hexyl-4-o-
tolyl-1,2,3-triazole (243 mg, 1.00 mmol) and (3-chlorophenyl)(phe-
nyl)methanone (325 mg, 1.50 mmol) at 120 °C. After 20 h, purifi-
cation by chromatography (n-hexane–EtOAc, 5:1) yielded 3p (385
mg, 91%) as a colorless oil.
Ruthenium-Catalyzed Direct Diarylation of Triazoles 1; 4-
{2¢,6¢-Di-(4¢¢-Ethoxycarbonylphenyl)phenyl}-1-n-octyl-1H-
1,2,3-triazole (3d); Representative Procedure B (Scheme 2)
A suspension of [RuCl2(p-cymene)]2 (15.4 mg, 0.025 mmol, 2.5
mol%), 5 (49.2 mg, 0.300 mmol, 30 mol%), K2CO3 (276 mg, 2.00
mmol), 1-n-octyl-4-phenyl-1,2,3-triazole (257 mg, 1.00 mmol) and
4-chlorobenzoic acid ethyl ester (552 mg, 3.00 mmol) in PhMe (4.0
mL) was stirred at 120 °C for 20 h. EtOAc (50 mL) and H2O (50
mL) were added to the cold reaction mixture. The separated aque-
ous phase was extracted with EtOAc (2 × 50 mL). The combined
organic layers were washed with H2O (50 mL) and brine (50 mL),
dried (Na2SO4), and concentrated under vacuum. The residue was
purified by column chromatography on silica gel (n-hexane–
EtOAc, 5:1) to yield 3d (354 mg, 64%) as a white solid; mp 133.5–
135.8 °C.
IR (NaCl): 3137, 2928, 1710, 1656, 1452, 717 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.74–7.61 (m, 3 H), 7.55 (m, 2 H),
7.45 (m, 2 H), 7.40–7.16 (m, 5 H), 6.92 (s, 1 H), 4.21 (t, J = 7.1 Hz,
2 H), 2.27 (s, 3 H), 1.80–1.60 (m, 2 H), 1.31–1.00 (m, 6 H), 0.81 (t,
J = 6.8 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 196.2 (Cq), 145.2 (Cq), 141.8 (Cq),
141.7 (Cq), 138.8 (Cq), 137.1 (Cq), 137.0 (Cq), 133.6 (CH), 132.4
(CH), 131.0 (CH), 129.8 (CH), 129.7 (CH), 129.1 (Cq), 128.4 (CH),
128.3 (CH), 128.1 (CH), 127.6 (CH), 127.2 (CH), 122.8 (CH), 50.0
(CH2), 30.9 (CH2), 30.1 (CH2), 25.8 (CH2), 22.3 (CH2), 20.9 (CH3),
13.9 (CH3).
IR (NaCl): 2925, 2855, 1706, 1642, 1270, 1108 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.87 (m, 4 H), 7.53 (dd, J = 8.6,
6.7 Hz, 1 H), 7.48–7.38 (m, 2 H), 7.28–7.17 (m, 4 H), 6.75 (s, 1 H),
4.32 (q, J = 7.1 Hz, 4 H), 4.07 (t, J = 6.9 Hz, 2 H), 1.63–1.45 (m, 2
H), 1.35 (t, J = 7.1 Hz, 6 H), 1.28–1.09 (m, 8 H), 0.95 (m, 2 H), 0.85
(t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 166.4 (Cq), 145.9 (Cq), 144.4 (Cq),
142.5 (Cq), 129.5 (CH), 129.0 (CH), 129.0 (CH), 128.8 (Cq), 128.7
(CH), 128.1 (Cq), 123.2 (CH), 60.9 (CH2), 49.9 (CH2), 31.7 (CH2),
30.1 (CH2), 28.9 (CH2), 28.6 (CH2), 25.9 (CH2), 22.5 (CH2), 14.3
(CH3), 14.0 (CH3).
MS (EI): m/z (%) = 423 (95, [M+]), 378 (37), 318 (52), 105 (100).
HRMS (ESI): m/z calcd for C28H29N3O + H+: 424.2383; found:
424.2383.
1-{2¢-(1-n-Hexyl-1H-1,2,3-triazol-4-yl)-3¢-methylbiphenyl-4-
yl}ethanone (3q)
Representative procedure A was followed, using 1-n-hexyl-4-o-
tolyl-1,2,3-triazole (243 mg, 1.00 mmol) and 1-(4-chlorophe-
nyl)ethanone (232 mg, 1.50 mmol) at 120 °C. After 20 h, purifica-
tion by chromatography (n-hexane–EtOAc, 5:1) yielded 3q (318
mg, 88%) as a colorless oil.
MS (EI): m/z (%) = 553 (13, [M+]), 525 (19), 43 (100).
IR (NaCl): 2926, 1641, 1361, 1264 cm–1.
HRMS (ESI): m/z calcd for C34H39N3O4 + H+: 554.3013; found:
554.3010.
1H NMR (300 MHz, CDCl3): d = 7.83–7.71 (m, 2 H), 7.32 (m, 2 H),
7.25–7.14 (m, 3 H), 6.86 (s, 1 H), 4.20 (t, J = 7.0 Hz, 2 H), 2.53 (s,
3 H), 2.28 (s, 3 H), 1.68 (m, 2 H), 1.19 (m, 4 H), 1.08 (m, 2 H), 0.83
(t, J = 6.7 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 197.6 (Cq), 146.8 (Cq), 145.2 (Cq),
141.6 (Cq), 138.9 (Cq), 135.1 (Cq), 130.0 (CH), 129.8 (CH), 128.9
(Cq), 128.5 (CH), 127.7 (CH), 127.1 (CH), 122.7 (CH), 50.0 (CH2),
30.9 (CH2), 30.1 (CH2), 26.5 (CH3), 25.8 (CH2), 22.3 (CH2), 20.9
(CH3), 13.9 (CH3).
4-{2¢,6¢-Di-(4¢¢-methoxyphenyl)-4¢-methylphenyl}-1-n-octyl-1H-
1,2,3-triazole (3b)
Representative procedure B was followed, using 1-n-hexyl-4-p-
tolyl-1,2,3-triazole (229 mg, 1.00 mmol) and 1-chloro-4-methoxy-
benzene (428 mg, 3.00 mmol) at 120 °C. After 20 h, purification by
chromatography (n-hexane–EtOAc, 5:1) yielded 3b (264 mg, 58%)
as a white solid; mp 78.4–80.8 °C.
IR (NaCl): 2934, 2860, 1709, 1610, 1510, 1245, 1035 cm–1.
Synthesis 2010, No. 13, 2245–2253 © Thieme Stuttgart · New York

PAPER
Ruthenium-Catalyzed Dehydrogenative Homo-Couplings Versus Direct Arylations
2251
1H NMR (300 MHz, CDCl3): d = 7.18 (s, 2 H), 7.14–7.03 (m, 4 H),
6.79–6.64 (m, 5 H), 4.10 (t, J = 6.9 Hz, 2 H), 3.73 (s, 6 H), 2.42 (s,
3 H), 1.67–1.51 (m, 2 H), 1.28–1.11 (m, 4 H), 1.00 (m, 2 H), 0.84
(t, J = 6.7 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.76 (d, J = 8.3 Hz, 4 H), 7.32–
7.14 (m, 6 H), 6.78 (s, 1 H), 4.06 (t, J = 6.8 Hz, 2 H), 2.50 (s, 6 H),
2.43 (s, 3 H), 1.63–1.46 (m, 2 H), 1.21–1.07 (m, 4 H), 0.93 (m, 2 H),
0.79 (t, J = 6.7 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 158.1 (Cq), 145.3 (Cq), 142.8
(Cq), 138.0 (Cq), 134.0 (Cq), 130.5 (CH), 129.6 (CH), 125.4 (Cq),
123.0 (CH), 112.9 (CH), 55.1 (CH3), 49.8 (CH2), 31.1 (CH2), 30.2
(CH2), 25.7 (CH2), 22.4 (CH2), 21.3 (CH3), 14.0 (CH3).
13C NMR (125 MHz, CDCl3): d = 197.2 (Cq), 146.0 (Cq), 144.1
(Cq), 142.0 (Cq), 138.4 (Cq), 135.0 (Cq), 130.0 (CH), 129.5 (CH),
127.5 (CH), 124.9 (Cq), 123.1 (CH), 49.7 (CH2), 30.8 (CH2), 29.9
(CH2), 26.4 (CH3), 25.4 (CH2), 22.2 (CH2), 21.1 (CH3), 13.8 (CH3).
MS (EI): m/z (%) = 455 (66, [M+]), 427 (100), 356 (19), 316 (45).
HRMS (ESI): m/z calcd for C31H33N3O2 + H+: 480.2646; found:
480.2645.
HRMS (ESI): m/z calcd. for C29H33N3O2 + H+: 456.2646; found:
456.2645.
4-{2¢,6¢-Di-(4¢¢-methylcarbonylphenyl)phenyl}-1-n-octyl-1H-
1,2,3-triazole (3g)
Representative procedure A was followed, using 1-n-octyl-4-phe-
nyl-1,2,3-triazole (259 mg, 1.00 mmol) and 1-(4-chlorophenyl)eth-
anone (464 mg, 3.00 mmol) at 120 °C. After 20 h, purification by
chromatography (n-hexane–EtOAc, 5:1) yielded 3g (350 mg, 71%)
as a white solid; mp 170.4–172.2 °C.
4-{2¢,6¢-Di-(4¢¢-trifluoromethyl)phenyl}-1-n-octyl-1H-1,2,3-tria-
zole (3c)
Representative procedure A was followed, using 1-n-octyl-4-phe-
nyl-1,2,3-triazole (259 mg, 1.00 mmol) and 1-chloro-4-(trifluoro-
methyl)benzene (542 mg, 3.00 mmol) at 120 °C. After 20 h,
purification by chromatography (n-hexane–EtOAc, 5:1) yielded 3c
(327 mg, 60%) as a white solid; mp 132.5–134.2 °C.
IR (NaCl): 2924, 2090, 1642, 1364, 1254 cm–1.
IR (NaCl): 2928, 2860, 1643, 1323, 1117 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.87–7.73 (m, 4 H), 7.54 (dd,
J = 8.5, 6.7 Hz, 1 H), 7.43 (dd, J = 7.6, 0.8 Hz, 2 H), 7.31–7.19 (m,
4 H), 6.77 (s, 1 H), 4.08 (t, J = 7.0 Hz, 2 H), 2.56 (s, 6 H), 1.64–1.48
(m, 2 H), 1.30–1.10 (m, 8 H), 0.96 (m, 2 H), 0.85 (t, J = 6.9 Hz, 3
H).
13C NMR (125 MHz, CDCl3): d = 197.6 (Cq), 146.1 (Cq), 144.4
(Cq), 142.4 (Cq), 135.4 (Cq), 129.8 (CH), 129.6 (CH), 128.8 (CH),
128.0 (Cq), 127.8 (CH), 123.2 (CH), 49.9 (CH2), 31.7 (CH2), 30.1
(CH2), 29.0 (CH2), 28.7 (CH2), 26.5 (CH3), 25.9 (CH2), 22.5 (CH2),
14.0 (CH3).
1H NMR (300 MHz, CDCl3): d = 7.55 (dd, J = 8.5, 6.8 Hz, 1 H),
7.45 (ddd, J = 9.4, 8.5, 0.8 Hz, 6 H), 7.29 (dd, J = 8.7, 0.8 Hz, 4 H),
6.75 (s, 1 H), 4.10 (t, J = 7.0 Hz, 2 H), 1.56 (m, 2 H), 1.31–1.08 (m,
8 H), 0.98 (m, 2 H), 0.86 (t, J = 6.9 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 144.7 (Cq), 144.2 (Cq), 142.1
(Cq), 129.4 (CH), 129.1 (CH), 128.4 (2JC,F = 33 Hz, Cq), 128.3
(CH), 127.7 (Cq), 124.7 (1JC,F = 272 Hz, Cq), 124.6 (3JC,F = 4 Hz,
CH), 122.6 (CH), 49.9 (CH2), 31.8 (CH2), 30.2 (CH2), 29.0 (CH2),
28.7 (CH2), 26.0 (CH2), 22.6 (CH2), 14.1 (CH3).
MS (EI): m/z (%) = 493 (100, [M+]), 279 (44), 239 (76).
HRMS (ESI): m/z calcd for C32H35N3O2 + H+: 494.2794; found:
MS (EI): m/z (%) = 545 (31, [M+]), 517 (25), 418 (22), 43 (100).
HRMS (ESI): m/z calcd for C30H29F6N3 + H+: 546.2338; found:
494.2802.
546.2337.
Ruthenium-Catalyzed Oxidative Homo-Coupling; 3,3¢-Dimeth-
yl-2,2¢-di(1H-pyrazol-1-yl)biphenyl (4b); Representative Proce-
dure C (Scheme 3)
4-{2¢,6¢-Di-(4¢¢-phenylcarbonylphenyl)phenyl}-1-n-octyl-1H-
1,2,3-triazole (3e)
Representative procedure A was followed, using 1-n-octyl-4-phe-
nyl-1,2,3-triazole (259 mg, 1.00 mmol) and (4-chlorophenyl)(phe-
nyl)methanone (650 mg, 3.00 mmol) at 120 °C. After 20 h,
purification by chromatography (n-hexane–EtOAc, 5:1) yielded 3e
(482 mg, 78%) as a white solid; mp 135.8–137.6 °C.
A
suspension of [RuCl2(p-cymene)]2 (7.7 mg, 0.012 mmol,
2.5 mol%), 5 (24.6 mg, 0.15 mmol, 30 mol%), K2CO3 (138 mg,
1.00 mmol), 1-o-tolyl-1H-pyrazole (79.1 g, 0.50 mmol), and 2h
(135 mg, 0.75 mmol) in PhMe (2 mL) was stirred at 120 °C for 20 h.
MTBE (25 mL) and H2O (25 mL) were added to the cold reaction
mixture. The separate aqueous phase was extracted with MTBE
(2 × 25 mL). The combined organic layers were washed with H2O
(25 mL) and brine (25 mL), dried (Na2SO4), and concentrated under
vacuum. The remaining residue was purified by column chromatog-
raphy on silica gel (n-hexane–EtOAc, 10:1 → 5:1) to yield 4b (56
mg, 71%) as a white solid; mp 146.9–147.4 °C.
IR (NaCl): 2926, 1649, 1277, 927 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.75 (dd, J = 8.0, 1.0 Hz, 4 H),
7.72–7.63 (m, 4 H), 7.63–7.52 (m, 3 H), 7.52–7.40 (m, 6 H), 7.29
(d, J = 8.1 Hz, 4 H), 6.83 (s, 1 H), 4.11 (t, J = 7.0 Hz, 2 H), 1.60 (m,
2 H), 1.21–1.06 (m, 8 H), 1.01 (m, 2 H), 0.79 (t, J = 6.8 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 196.2 (Cq), 145.6 (Cq), 144.4
(Cq), 142.5 (Cq), 137.6 (Cq), 135.7 (Cq), 132.3 (CH), 129.9 (CH),
129.6 (CH), 129.5 (2 × CH), 128.8 (Cq), 128.2 (CH), 128.1 (CH),
123.3 (CH), 49.9 (CH2), 31.6 (CH2), 30.2 (CH2), 28.9 (CH2), 28.7
(CH2), 26.0 (CH2), 22.5 (CH2), 14.0 (CH3).
IR (NaCl): 3445, 1713, 1362, 1222, 761 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.63–7.46 (m, 4 H), 7.14 (d,
J = 7.5 Hz, 2 H), 7.06 (t, J = 7.5 Hz, 2 H), 6.82 (d, J = 7.5 Hz, 2 H),
6.18 (t, J = 2.0 Hz, 2 H), 2.05 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 139.6 (CH), 138.3 (Cq), 136.6 (Cq),
136.0 (Cq), 131.9 (CH), 129.9 (CH), 127.8 (CH), 127.4 (CH), 105.6
(CH), 17.7 (CH3).
MS (EI): m/z (%) = 314 (64, [M+]), 233 (100), 191 (3).
HRMS (ESI): m/z calcd for C20H18N4 + H+: 315.1604; found:
MS (EI): m/z (%) = 617 (5, [M+]), 589 (7), 105 (100).
HRMS (ESI): m/z calcd for C42H39N3O2 + H+: 618.3115; found:
618.3112.
4-{2¢,6¢-Di-(4¢¢-methylcarbonylphenyl)-4¢-methylphenyl}-1-n-
octyl-1H-1,2,3-triazole (3f)
Representative procedure A was followed, using 1-n-hexyl-4-p-
tolyl-1,2,3-triazole (229 mg, 1.00 mmol) and 1-(4-chlorophe-
nyl)ethanone (464 mg, 3.00 mmol) at 120 °C. After 20 h, purifica-
tion by chromatography (n-hexane–EtOAc, 5:1) yielded 3f (317
mg, 66%) as a white solid; mp 163.1–165.4 °C.
315.1606.
2,2¢-Bis(1-n-hexyl-1H-1,2,3-triazol-4-yl)-3,3¢-dimethylbiphenyl
(4a)
Representative procedure C was followed using 1-n-hexyl-4-o-
tolyl-1,2,3-triazole (243 mg, 1.00 mmol) and 2h (338 mg, 1.50
IR (NaCl): 2926, 1678, 1361, 1264, 837 cm–1.
Synthesis 2010, No. 13, 2245–2253 © Thieme Stuttgart · New York

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L. Ackermann et al.
PAPER
mmol) at 120 °C. After 20 h, purification by chromatography (n-
hexane–EtOAc, 3:1) yielded 4a (192 mg, 81%) as a colorless oil.
IR (NaCl): 3448, 3131, 2928, 2861, 1710, 1456, 1049, 731 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.52 (d, J = 4.3 Hz, 2 H), 7.38 (t,
J = 7.0 Hz, 2 H), 7.17–6.94 (m, 4 H), 6.85–6.58 (m, 12 H), 3.87–
3.63 (m, 10 H), 2.07 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 159.1 (Cq), 157.5 (Cq), 148.2
(CH), 140.6 (Cq), 138.9 (Cq), 137.1 (Cq), 136.2 (Cq), 134.8 (CH),
133.7 (Cq), 129.8 (CH), 129.6 (CH), 129.2 (CH), 126.2 (CH), 121.0
(CH), 113.3 (CH), 55.1 (CH3), 38.2 (CH2), 20.8 (CH3).
1H NMR (300 MHz, CDCl3): d = 7.23 (s, 2 H), 7.14–7.01 (m, 4 H),
6.90 (dd, J = 7.2, 1.7 Hz, 2 H), 4.20 (t, J = 6.9 Hz, 4 H), 2.20 (s, 6
H), 1.76–1.59 (m, 4 H), 1.22 (m, 8 H), 1.05 (m, 4 H), 0.86 (t, J = 6.8
Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 145.1 (Cq), 142.2 (Cq), 137.8 (Cq),
129.9 (Cq), 129.0 (CH), 127.6 (CH), 127.2 (CH), 123.4 (CH), 50.0
(CH2), 31.1 (CH2), 30.1 (CH2), 25.7 (CH2), 22.4 (CH2), 21.0 (CH3),
14.0 (CH3).
MS (ESI): m/z = 577 (100%, [M+]).
HRMS (ESI): m/z calcd for C40H36N2O2 + H+: 577.2850; found:
577.2850.
5,5¢-Difluoro-3,3¢-di(4-methoxybenzyl)-2,2¢-di(pyridin-2-yl)bi-
phenyl (4f)
Representative procedure C was followed, using 2-[4-fluoro-2-(4-
methoxybenzyl)phenyl]pyridine (147 mg, 0.50 mmol) and 2h (135
mg, 0.75 mmol) at 120 °C. After 20 h, purification by chromatogra-
phy (n-hexane–EtOAc, 5:1 → 1:1) yielded 4f (34 mg, 23%) as a
green oil.
MS (EI): m/z (%) = 484 (64, [M+]), 399 (14), 385 (100), 345 (21).
HRMS (ESI): m/z calcd for C30H40N6 + H+: 485.3387; found:
485.3387.
3,3¢-Dimethyl-2,2¢-di(pyridin-2-yl)biphenyl (4c)
Representative procedure C was followed, using 2-o-tolylpyridine
(84.6 mg, 0.50 mmol) and 2h (135 mg, 0.75 mmol) at 120 °C. After
20 h, purification by chromatography (n-hexane–EtOAc, 5:1 →
1:1) yielded 4c (44 mg, 52%) as a green solid; mp 154.1–154.9 °C.
IR (NaCl): 3048, 3002, 2956, 2931, 2836, 1734, 1566, 1510, 1456,
1427, 1298, 1034, 909, 870, 819, 733, 646, 624 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.55 (s, 2 H), 7.52–7.39 (m, 2 H),
7.24–7.03 (m, 4 H), 6.84–6.64 (m, 10 H), 6.52 (dd, J = 9.2, 2.6 Hz,
2 H), 3.75 (m, 10 H).
IR (NaCl): 3445, 3053, 1710, 1584, 1462, 1029, 789, 752 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.51 (d, J = 4.4 Hz, 2 H), 7.48 (td,
J = 7.6, 1.7 Hz, 2 H), 7.25 (d, J = 7.6 Hz, 2 H), 7.01 (ddd, J = 8.5,
4.9, 2.4 Hz, 4 H), 6.88 (t, J = 7.6 Hz, 2 H), 6.72 (d, J = 7.3 Hz, 2 H),
2.04 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 159.4 (Cq), 148.7 (CH), 140.2 (Cq),
139.7 (Cq), 135.9 (Cq), 135.4 (CH), 128.8 (CH), 128.5 (CH), 126.6
(CH), 125.6 (CH), 121.1 (CH), 20.5 (CH3).
13C NMR (125 MHz, CDCl3): d = 160.9 (Cq, 1JC,F = 247 Hz), 157.7
3
(Cq), 157.5 (Cq), 148.6 (CH), 142.1 (Cq, JC,F = 9 Hz), 141.5 (Cq,
3JC,F = 9 Hz), 135.9 (Cq), 135.3 (CH), 132.2 (Cq), 129.6 (CH), 126.1
(CH), 121.6 (CH), 115.6 (CH, 2JC,F = 23 Hz), 115.2 (CH, 2JC,F = 23
Hz), 113.6 (CH), 55.23 (CH3), 38.43 (CH2).
19F NMR (285 MHz, CDCl3): d = –115.2 (s).
MS (ESI): m/z = 585 (100%, [M+]).
HRMS (ESI): m/z calcd for C38H30F2N2O2 + H+: 585.2348; found:
MS (EI): m/z (%) = 336 (77, [M+]), 335 (100), 258 (23), 168 (17).
HRMS (ESI): m/z calcd for C24H20N2 + H+: 337.1699; found:
337.1699.
585.2351.
3,3¢-Di(4-methoxybenzyl)-2,2¢-di(pyridin-2-yl)biphenyl (4d)
Representative procedure C was followed, using 2-[2-(4-methoxy-
benzyl)phenyl]pyridine (138 mg, 0.50 mmol) and 2h (135 mg, 0.75
mmol) at 120 °C. After 20 h, purification by chromatography (n-
hexane–EtOAc, 5:1 → 1:1) yielded 4d (72 mg, 52%) as a green sol-
id; mp 123.3–124.2 °C.
Acknowledgment
Support by the DFG and the Alexander von Humboldt foundation
(fellowship to R.V.) is gratefully acknowledged.
IR (NaCl): 3051, 3003, 2958, 2910, 2837, 1610, 1587, 1470, 1446,
1421, 1298, 1177, 1151, 1034, 906, 807, 792 cm–1.
References
1H NMR (300 MHz, CDCl3): d = 8.52 (s, 2 H), 7.45–7.33 (m, 2 H),
(1) Huisgen, R. Angew. Chem., Int. Ed. Engl. 1963, 2, 565.
(2) Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles,
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7.23–6.88 (m, 9 H), 6.84–6.62 (m, 9 H), 3.90–3.63 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 158.9 (Cq), 157.6 (Cq), 148.4 (CH),
140.6 (Cq), 139.9 (Cq), 139.2 (Cq), 135.0 (CH), 133.5 (Cq), 129.6
(CH), 128.9 (CH), 128.6 (CH), 126.8 (CH), 126.1 (CH), 121.2
(CH), 113.4 (CH), 55.2 (CH3), 38.4 (CH2).
MS (ESI): m/z = 549 (100%, [M+]).
HRMS (ESI): m/z calcd for C38H32N2O2 + H+: 549.2537; found:
(3) Gilchrist, T. L. Heterocyclic Chemistry, 3rd ed.; Addison
Wesley Longman Limited: Harlow, 1997.
(4) Joule, J. A.; Mills, K. Heterocyclic Chemistry, 4th ed.;
Blackwell Science Ltd: Oxford, 2000.
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549.2538.
(7) For complementary ruthenium-catalyzed cycloadditions,
see: Zhang, L.; Chen, X.; Xue, P.; Sun, H. H. Y.; Williams,
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5,5¢-Dimethyl-3,3¢-di(4-methoxybenzyl)-2,2¢-di(pyridin-2-yl)bi-
phenyl (4e)
Representative procedure C was followed, using 2-[2-(4-methoxy-
benzyl)-4-methylphenyl]pyridine (145 mg, 0.50 mmol) and 2h
(135 mg, 0.75 mmol) at 120 °C. After 20 h, purification by chroma-
tography (n-hexane–EtOAc, 5:1 → 1:1) yielded 4e (81 mg, 56%) as
a brown oil.
(8) For representative recent reviews, see the following themed
issue: Chem. Soc. Rev. 2010, 39, 1231.
(9) Ackermann, L.; Vicente, R. Top. Curr. Chem. 2010, in
press; DOI: 10.1007/128_2009_9.
IR (NaCl): 3042, 3001, 2952, 2915, 2836, 1607, 1590, 1510, 1456,
1427, 1297, 1244, 1177, 1034, 909, 866, 819, 802, 733 cm–1.
Synthesis 2010, No. 13, 2245–2253 © Thieme Stuttgart · New York

PAPER
Ruthenium-Catalyzed Dehydrogenative Homo-Couplings Versus Direct Arylations
2253
(10) For representative examples of ruthenium-catalyzed direct
arylations and alkylations with organic halides or boron-
based reagents, see: (a) Miura, H.; Wada, K.; Hosokawa, S.;
Inoue, M. Chem. Eur. J. 2010, 16, 4186. (b) Kitazawa, K.;
Kochi, T.; Sato, M.; Kakiuchi, F. Org. Lett. 2009, 11, 1951.
(c) Pozgan, F.; Dixneuf, P. H. Adv. Synth. Catal. 2009, 351,
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4966. (e) Ackermann, L.; Novak, P.; Vicente, R.; Hofmann,
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(g) Oi, S.; Funayama, R.; Hattori, T.; Inoue, Y. Tetrahedron
2008, 64, 6051. (h) Deng, G.; Zhao, L.; Li, C.-J. Angew.
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(m) Ackermann, L.; Althammer, A.; Born, R. Angew. Chem.
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(12) Ackermann, L.; Vicente, R.; Althammer, A. Org. Lett. 2008,
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(13) Ackermann, L.; Born, R.; Vicente, R. ChemSusChem 2009,
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(14) Ackermann, L.; Vicente, R. Org. Lett. 2009, 11, 4922.
(15) For select examples of copper- or palladium-catalyzed direct
arylations of the heteroaromatic moiety in 1,2,3-triazoles,
see: [Cu]: (a) Ackermann, L.; Potukuchi, H. K.; Landsberg,
D.; Vicente, R. Org. Lett. 2008, 10, 3081. [Pd]:
(b) Chuprakov, S.; Chernyak, N.; Dudnik, A. S.; Gevorgyan,
V. Org. Lett. 2007, 9, 2333. (c) Iwasaki, M.; Yorimitsu, H.;
Oshima, K. Chem. Asian J. 2007, 2, 1430. (d) Ackermann,
L.; Vicente, R.; Born, R. Adv. Synth. Catal. 2008, 350, 741.
(e) Ackermann, L.; Althammer, A.; Fenner, S. Angew.
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(16) Ackermann, L.; Born, R.; Spatz, J. H.; Althammer, A.;
Gschrei, C. J. Pure Appl. Chem. 2006, 78, 209.
(17) Recent examples: (a) Ackermann, L.; Barfüßer, S.; Pospech,
J. Org. Lett. 2010, 12, 724. (b) Ackermann, L.; Barfüßer, S.
Synlett 2009, 808.
(18) For preliminarily communicated examples of ruthenium-
catalyzed direct arylations of 4-aryl-substituted 1,2,3-
triazoles 1, which served for palladium-catalyzed
dehydrogenative arylations, see: Ackermann, L.;
Jeyachandran, R.; Potukuchi, H. K.; Novák, P.; Büttner, L.
Org. Lett. 2010, 12, 2056.
(19) Examples of palladium-catalyzed or copper-mediated
directed oxidative homo-coupling reactions: (a) Hull, K. L.;
Lanni, E. L.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128,
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(20) For ruthenium-catalyzed oxidative homo-couplings with
stoichiometric amounts of FeCl3 or methallyl acetate, see:
(a) Guo, X.; Deng, G.; Li, C.-J. Adv. Synth. Catal. 2009, 351,
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(11) Representative recent reviews: (a) Colby, D. A.; Bergman,
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(b) Ackermann, L.; Vicente, R.; Kapdi, A. Angew. Chem.
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(g) Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200.
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(21) The use of other sacrificial oxidants, such as Cu(OAc)2,
Ag2O, benzoquinone, [t-BuO]2, or allyl acetate, did not meet
with success, under otherwise identical reaction conditions.
Synthesis 2010, No. 13, 2245–2253 © Thieme Stuttgart · New York