[RuCl3(H2O)n]-catalyzed direct arylations

Article abstract of DOI:10.1016/j.tet.2008.01.050

Catalytic amounts of economically attractive [RuCl₃(H₂O)_n] allow for direct arylations via C-H bond functionalization with aryl bromides under phosphine ligand-free reaction conditions. Thereby, a variety of functionalized

Full text of DOI:10.1016/j.tet.2008.01.050

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 6115e6124
www.elsevier.com/locate/tet
[RuCl3(H2O)n]-catalyzed direct arylations
*
Lutz Ackermann , Andreas Althammer, Robert Born
Institut fuer Organische und Biomolekulare Chemie, Georg-August-Universitaet Goettingen, Tammannstraße 2, D-37077 Goettingen, Germany
Received 23 September 2007; received in revised form 17 October 2007; accepted 18 October 2007
Available online 16 January 2008
Abstract
Catalytic amounts of economically attractive [RuCl3(H2O)n] allow for direct arylations via CeH bond functionalization with aryl bromides
under phosphine ligand-free reaction conditions. Thereby, a variety of functionalized (hetero)aryl bromides, bearing either electron-withdrawing
or electron-releasing substituents, can be employed for direct arylations of pyridine, oxazoline, pyrazole, or ketimine derivatives as pronucleo-
philes.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
use of (temporarily installed) directing groups, which enable
highly regioselective intermolecular arylation reactions.7
For these chelation-assisted CeH bond functionalization re-
actions of arenes either organometallic reagents (Scheme 1, b),
arenes (Scheme 1, c), or organic (pseudo)halides (Scheme 1, d)
Modern methodologies for regioselective C(sp2)eC(sp2)
bond forming reactions employ largely transition metal-cata-
lyzed cross-coupling reactions between organic(pseudo)halides
and organometallic reagents.1,2 The prerequisite organometallic
compounds are often commercially unavailable or relatively
expensive, and their use gives rise to the formation of undesired
side-product. Direct arylation reactions via cross-coupling of
CeH bonds with organic electrophiles represent an ecologically
benign and economically attractive alternative.3e6
In contrast to more traditional cross-coupling reactions with
organometallic reagents (Scheme 1, a), pronucleophilic sub-
strates for direct CeH bond arylation reactions do not display
a single reactive functional group. Therefore, the regioselective
arylation of a specific CeH bond in a given molecule constitutes
a major objective for the development of preparatively useful
direct arylation methodologies.7 Intramolecular transforma-
tions proceed often with good regioselectivities, and so do direct
arylations of various heteroarenes.8e10 However, the develop-
ment of regioselective intermolecular direct arylations of (elec-
tronically non-activated) arenes represents a notable challenge
(Scheme 1, bed).7 A solution to this problem is found in the
M
R2
R1
cat. [TM]
R2
R2
R2
R2
a
+
+
+
+
R1
- MHal
Hal
H
H
H
R2
R2
R2
R1
R1
R1
cat. [TM]
b
c
d
- MH
R1
R1
R1
M
cat. [TM]
- H2
H
cat. [TM]
- HHal
* Corresponding author.
address:
Hal
E-mail
Ackermann).
lutz.ackermann@chemie.uni-goettingen.de
(L.
Scheme 1. Strategies for intermolecular C(sp2)eC(sp2) bond formation.
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.050

6116
L. Ackermann et al. / Tetrahedron 64 (2008) 6115e6124
can be employed as arylating reagents. Transformations using
stoichiometric amounts of organometallic reagents encounter
similar drawbacks as traditional cross-coupling reactions (vide
supra, and Scheme 1, a). Oxidative direct arylations of arenes
rely on the use of stoichiometric amounts of oxidants, such as
oxone, benzoquinone, or copper salts,11 which give rise to stoi-
chiometric amounts of economically and environmentally unde-
sired side-products. More importantly, regioselectivity is even
more difficult to achieve in such intermolecular cross-coup-
ling12 reactions.13,14 Hence, a significant amount of research ef-
fort has been devoted to the development of direct arylation
reactions using organic (pseudo)halides as electrophiles.5,7
In addition to valuable rhodium- and palladium-catalyzed
processes,15 ruthenium catalysts stabilized by phosphorus-
based ligands proved effective and versatile for direct arylation
reactions with organic halides.16e18 In this context, we reported
on the use of air-stable secondary phosphine oxides19 as preli-
gands for ruthenium-catalyzed direct arylation reactions
employing readily available, inexpensive chlorides20 or tosyl-
ates21 as electrophiles. During mechanistic studies on regio-
and diastereoselective ruthenium-catalyzed direct arylations
of alkenes with aryl chlorides,22 we noted that simple ruthenium
compounds, such as [RuCl3(H2O)n] (1) and [RuCl2(p-cym-
ene)]2 (2), could be used as catalysts for direct arylation reac-
tions without the need for an additional phosphorus-based
(pre)ligand. While simple palladium salts, such as Pd(OAc)2,
had been shown previously to allow for direct arylation reactions
with aryl halides,5,23 effective ruthenium catalysts for regiose-
lective direct arylation reactions relied thus far entirely on the
use of phosphorus-based stabilizing (pre)ligands. Hence, we
felt attracted by the possibility of employing commercially
available and inexpensive ruthenium compounds for direct aryl-
ation reactions via CeH bond functionalization. Herein, we
wish to provide a full account24 on the scope and limitations
of this economically attractive and simple catalytic system.
While a significant product formation was noted, aryl chlo-
rides 4aec were converted only sluggishly (Scheme 2).
More generally speaking, it is noteworthy that these ruthe-
nium-catalyzed direct arylations of alkenes22 are distinct
from simple palladium-catalyzed Heck reactions, as substrates
not bearing a directing group, such as stilbene, were not
converted.
R
N
N
R
5.0 mol% 1
+
K2CO3, NMP,120 °C, 22 h
Cl
R = C(O)Me: 4a
R = CO2Et: 4b
R = OMe: 4c
R = C(O)Me: 5a 53%
3
R = CO2Et: 5b
R = OMe: 5c
21%
27%
Scheme 2. Direct arylation of alkene 3a with aryl chlorides 4.
Low isolated yields were also obtained when using an arene
as pronucleophile. Thus, arylation of pyridine derivative 6
with aryl chloride 4a provided the desired product 7a in
only 31% yield (Scheme 3).
Me
O
O
O
N
N
5.0 mol% 1
Me
Me
+
K2CO3, NMP,
120 °C, 22 h
Cl
4a
7a
31%
6
Scheme 3. Direct arylation of pyridine 6.
2.2. [RuCl3(H2O)n]-catalyzed direct arylation with aryl
tosylates
2. Results and discussion
Amongarylhalides, chloridesarearguablythemostattractive
class of electrophiles for coupling reactions, due to their lower
price and higher availability. In traditional cross-coupling reac-
tions of organometallic reagents, the use of stabilizing ligands
is necessary in order to funtionalize such electrophiles.25,26 Gen-
erally applicable methods for intermolecular direct arylation
reactions employingaryl chlorideswere, untilrecently, notavail-
able.20,27,28 We reported on the use of ruthenium complexes de-
rived from different phosphorus-based (pre)ligands for direct
arylation reactions employing aryl chlorides20 with ample scope.
To simplify our approach further we turned our attention to phos-
phorus-based ligand-free ruthenium catalyst in direct arylations
using inexpensive aryl chlorides as electrophiles.
The possibility of using tosylates as electrophiles in cross-
coupling chemistry is attractive, since they can be prepared
from readily available phenols or ketones with reagents that
are less expensive than those used to prepare the correspond-
ing triflates. Further, tosylates are more convenient to use, be-
ing more stable to water than triflates and highly crystalline.
However, this greater stability makes tosylates less reactive
in transition metal-catalyzed processes. Methods for tradi-
tional cross-coupling reactions between aryl tosylates and
organometallic reagents are known.29 In contrast, catalytic, di-
rect arylation reactions through CeH bond activation using
tosylates were not reported until recently. Thus, we disclosed
the use of a ruthenium catalyst for unprecedented direct aryl-
ation reactions with tosylates.21 Consequently, we explored,
within the present study, the use of economically attractive
[RuCl3(H2O)n] (1) as catalyst for direct arylations using aryl
tosylates as electrophiles. Interestingly, significant product for-
mation was noted. Thus, arene 8 was regioselectively arylated
in 47% yield (Scheme 4).
2.1. [RuCl3(H2O)n]-catalyzed direct arylation with aryl
chlorides
First, we probed the catalytic activity of [RuCl3(H2O)n] (1)
in the regioselective CeH bond functionalization of alkene 3.

L. Ackermann et al. / Tetrahedron 64 (2008) 6115e6124
6117
Table 1
Direct arylations of pyridine 6 employing [RuCl3(H2O)n] (1)a
OMe
O
N
O
N
OMe
5.0 mol% 1
+
Me
Me
K2CO3, NMP,
120 °C, 22 h
R
N
+
N
5.0 mol% 1
OTs
R
R
K2CO3,
NMP,120 °C, 22 h
8
9a
10a
47%
Br
6
11
7
Scheme 4. Direct arylation of arene 8 with tosylate 9a.
Entry
1
R
Product 7
Yield (%)
O
O
N
N
N
N
N
N
O
Me
Me
Me
O
4-C(O)Me
4-CO2Et
4-CN
7a 90
7b 94
7c 85
7d 69
7e 95
7f 51
N
N
5.0 mol% 2
K2CO3, NMP,120 °C, 22 h
Me
+
OTs
9b
EtO2C
NC
CO2Et
CN
3
5a
40 %
2
3
4
5
6
Scheme 5. Direct arylation of alkene 3 with tosylate 9b.
Furthermore, catalytic amounts of complex 2 allowed for
a regioselective arylation of alkene 3 (Scheme 5).
2.3. [RuCl3(H2O)n]-catalyzed direct arylation of pyridine
derivatives with aryl bromides
Cl
Cl
4-Cl
Since [RuCl3(H2O)n]-catalyzed direct arylations with aryl
chlorides 4 and tosylates 9 provided generally rather unsatis-
factory isolated yields, we turned our attention to the use of
aryl bromides 11 as electrophiles (Table 1).
3-CO2Et
EtO2C
CO2Et
Interestingly, catalytic amounts of commercially available
[RuCl3(H2O)n] (1) enabled generally applicable direct aryl-
ation reactions of pyridine 6 with a variety of bromides 11
(Table 1). Importantly, a high catalytic activity was not only
observed when using electron-deficient aryl bromides and
iodides, thereby for an oxidative addition electronically acti-
vated (entries 1e6), but also for electron-rich aryl bromides
(entries 7 and 9) and iodides (entry 8). Further, a number of
valuable functional groups were tolerated, including an enoliz-
able ketone (entry 1), ester (entries 2 and 5), nitriles (entry
3 and 6), and a chloride (entry 4). Also a more sterically
hindered ortho-substituted aryl bromide could be converted
with satisfactory isolated yield (entry 9). Additionally, it is
noteworthy that catalytic amounts of [RuCl3(H2O)n] (1) al-
lowed an efficient direct arylation reaction of 2-phenyl pyri-
dine (6) even at the lower reaction temperature of 100 ꢀC
(Scheme 6).
Cross-coupling reactions of heteroaromatic (pseudo)halides
are of utmost importance, because heterocycles are often in-
dispensable substructures of naturally occurring products and
biologically active compounds in pharmaceuticals, as well as
agrochemicals. However, only a single heteroaromatic halide
was thus far employed in ruthenium-catalyzed direct arylation
reactions via CeH bond functionalization.18 Consequently, we
probed the efficacy of our catalytic system in the conversion of
furan 12 and thiophene 14. The functionalized bromide 12 was
3-CN
NC
CN
MeO
N
OMe
7
8
4-OMe
61
7g
73
4-OMeb
N
9
2-OMe
7h 65
OMe
OMe
a
Isolated yields.
Using 4-MeOC6H4I as electrophile.
b
efficiently converted with catalytic amounts of [RuCl3(H2O)n]
(1), yielding mono-arylated product 13 in a good isolated yield
(Scheme 7).
On the contrary, thiophene 14 provided an inseparable
mixture of the mono- and di-arylated products 15 and 16 in
a combined isolated yield of only 45% (Scheme 8).

6118
L. Ackermann et al. / Tetrahedron 64 (2008) 6115e6124
Table 2
Catalytic direct arylations of oxazoline 8a
Me
O
O
O
N
N
N
N
5.0 mol% 1
Me
Me
+
R
O
N
O
N
K2CO3,
NMP, 100 °C, 22 h
5.0 mol% [RuCl3(H2O)n] (1)
+
R
Me
Me
K2CO3,
NMP,120 °C, 22 h
Br
11a
Br
6
7a
54%
8
11
10
Scheme 6. Direct arylation of pyridine 6 at 100 ꢀC.
Entry
1
R
Product 10
Yield (%)
68
O
O
N
Me
4-C(O)Me
4-CO2Me
4-CN
10b
10c
10d
10e
10f
Me
N
10.0 mol% 1
+
CO2Et
Br
CO2Et
K2CO3,
O
O
NMP,120 °C, 22 h
O
N
CO2Me
2
3
4
5
6
7
8
68
59
77
46
62
51
65
6
12
13
Me
64%
Scheme 7. Direct arylation with furane 12.
O
N
CN
Me
N
N
10.0 mol% (1)
+
+
O
N
Br
K2CO3,
NMP,130 °C, 22 h
45%
S
S
S
S
3-CO2Me
3,5-(CF3)2
2-Cl
Me
CO2Me
CF3
6
14
15
16
:
2
1
O
N
Scheme 8. Direct arylation with thiophene 14.
Me
CF3
2.4. [RuCl3(H2O)n]-catalyzed direct arylation of oxazolines
with aryl bromides
O
N
10g
10h
10a
Me
O
Cl
Since 2-oxazolinyl substituents can be easily converted to
valuable functional groups, such as the corresponding carb-
oxylic acids,30 we studied next the scope of [RuCl3(H2O)n]
(1) in the catalytic direct arylation of oxazoline 8 (Table 2).
Catalytic amounts of [RuCl3(H2O)n] (1) enabled efficient
direct arylations with a variety of aryl bromides 11 as electro-
philes. Thus, aryl bromides 11 with both electron-withdrawing
and electron-releasing substituents proved to be suitable sub-
strates. This allowed for the synthesis of oxazolines 10 with
different functional groups, such as an enolizable ketone (en-
try 1), ester (entries 2 and 4), a nitrile (entry 3), alkyl (entry 5)
as well as aryl halides (entry 6), and a terminal alkene (entry
7). On the contrary, an oxazoline, displaying a 2-bromophenyl
substituent, gave as pronucleophile an unselective reaction
with bromide 11a.
N
4-CH]CH2
Me
O
N
OMe
4-OMe
Me
O
N
9
2-OMe
10i
51
Me
OMe
a
Isolated yields.
2.5. [RuCl3(H2O)n]-catalyzed direct arylations of pyrazoles
and ketimines with aryl bromides
pronucleophiles. Thus, pyrazoles 18aec were obtained in
good isolated yields (Scheme 9).
[RuCl3(H2O)n]-catalyzed direct arylations with bromoar-
enes are not restricted to pyridines or oxazoline derivatives,
but can also be applied to the regioselective arylation of other
Further, N-aryl-substituted ketimine 19 was arylated
employing catalytic amounts of [RuCl3(H2O)n] (1) (Scheme
10). The corresponding products were conveniently isolated

L. Ackermann et al. / Tetrahedron 64 (2008) 6115e6124
6119
R
unless otherwise stated. Flash chromatography: Merck silica
1
N
N
R
R
gel 60 (230e400 mesh). NMR: H was recorded on a Varian
5.0 mol% [RuCl3(H2O)n] (1)
N
N
+
Unity 300, Bruker AC 300, or AMX 600, 13C was recorded on
a Varian Mercury 300, Unity 300, Bruker AC 300, or AMX
600, and 19F was recorded on a Mercury 300 in the solvent indi-
cated; chemical shifts (d) are given in parts per million, coupling
constants (J) in hertz.
K2CO3,
NMP,120 °C, 22 h
Br
R = C(O)Me: 18a
R = CO2Me: 18b
R = OMe: 18c
64%
52%
55%
17 R = C(O)Me: 11a
R = CO2Me: 11b
R = OMe: 11c
Scheme 9. Direct arylation of pyrazole 17.
4.1.1. Representative procedure for [RuCl3(H2O)n]-
catalyzed direct arylations: 1-(4-acetyl-20-pyridin-2-yl-
[1,10:300,100]-terphenyl-400-yl)ethanone (7a)20
after hydrolysis as their acetophenone derivatives 20aec. Gen-
erally, arylation reactions proceeded well with functionalized
electron-deficient as well as with electron-rich aryl bromides
11. Contrary to pyridine, oxazoline or pyrazole derivatives,
ketimines 19 yielded selectively the mono-arylated products
20, as also observed previously for a phosphine-based ruthe-
nium catalyst.20
A suspension of 1 (12.6 mg, 0.05 mmol, 5.0 mol %),
K2CO3 (415 mg, 3.00 mmol), 6 (160 mg, 1.03 mmol), and
11a (438 mg, 2.20 mmol) in dry NMP (2.0 mL) was stirred
for 22 h at 120 ꢀC under N2. After the reaction mixture was
cooled to ambient temperature, Et2O (50 mL) and H2O
(40 mL) were added. The separated aqueous phase was ex-
tracted with Et2O (3ꢁ50 mL). The combined organic layers
were washed with H2O (50 mL) and brine (50 mL), dried
over Na2SO4, and concentrated in vacuo. The remaining resi-
due was purified by column chromatography on silica gel
(n-pentane/Et2O, 3:1/2:1/1:1/1:2/1:3) to yield 7a
OMe
R
1) 5.0 mol% [RuCl3(H2O)n] (1)
K2CO3, NMP,120 °C, 22 h
2) 1 N HCl (aq), 3 h
Me
N
Me
O
R
+
1
(361 mg, 90%, mp: 200.5e201.5 ꢀC) as a yellow solid. H
NMR (300 MHz, CDCl3): d¼8.30 (d, J¼5.0 Hz, 1H), 7.75
(d, J¼8.1 Hz, 4H), 7.56 (dd, J¼8.6, 6.4 Hz, 1H), 7.50e7.45
(m, 2H), 7.31 (dt, J¼7.7, 1.8 Hz, 1H), 7.18 (d, J¼8.1 Hz,
4H), 6.94 (ddd, J¼7.5, 4.8, 0.9 Hz, 1H), 6.86 (d, J¼7.7 Hz,
1H), 2.56 (s, 6H). 13C NMR (75 MHz, CDCl3): d¼197.7
(Cq), 157.9 (Cq), 148.7 (CH), 146.3 (Cq), 140.9 (Cq), 138.3
(Cq), 135.3 (CH), 135.1 (CH), 129.8 (CH), 129.7 (CH),
128.5 (CH), 127.8 (CH), 126.6 (CH), 121.4 (CH), 26.5
(CH3). IR (ATR): 3053, 2919, 1680, 1605, 1268, 958, 809.
MS (EI) m/z (relative intensity): 391 (68) [Mþ], 390 (100),
348 (13). HRMS (EI) m/z: calcd for C27H21NO2, 391.1572;
found, 391.1550.
Br
R = C(O)Me: 20a
R = CO2Et: 20b
R = OMe: 20c
68%
65%
56%
19 R = C(O)Me: 11a
R = CO2Et: 11b
R = OMe: 11c
Scheme 10. Direct arylation of ketimine 19.
3. Conclusions
In summary, we report herein on the scope and limitations
of economically attractive direct arylation reactions catalyzed
by [RuCl3(H2O)n] (1). While aryl chlorides and tosylates as
electrophiles gave rather sluggish product formation, aryl bro-
mides proved suitable substrates. Thus, electron-deficient as
well as electron-rich aryl bromides, displaying a variety of
valuable functional groups, were converted with high efficacy.
Further, heteroaryl bromides could be also employed with our
phosphine-free catalyst. The scope of this transformation was
not only broad with respect to the electrophile. Hence, various
pronucleophiles, such as pyridines, oxazolines, pyrazoles, and
ketimines, proved applicable for regioselective direct arylation
reactions.
4.1.2. 1-[4-(2-Pyridin-2-ylcyclohex-1-enyl)phenyl]ethanone
(5a)22
The representative procedure was followed, using 3
(80.0 mg, 0.502 mmol) and 4a (93.1 mg, 0.602 mmol). After
22 h, purification by chromatography (n-pentane/Et2O, 5:1/
3:1/1:1/1:2) yielded 5a (74 mg, 53%) as a brown solid
(mp: 61.1e62.1 ꢀC). 1H NMR (600 MHz, CDCl3): d¼8.49
(dq, J¼4.9, 0.9 Hz, 1H), 7.69 (md, J¼8.4 Hz, 2H), 7.25 (mt,
J¼7.9 Hz, 1H), 7.06 (dt, J¼8.4, 1.8 Hz, 2H), 6.95 (ddd,
J¼7.5, 4.8, 1.3 Hz, 1H), 6.66 (md, J¼7.5 Hz, 1H), 2.61e2.59
(m, 2H), 2.49 (s, 3H), 2.46e2.44 (m, 2H), 1.86e1.83 (m, 4H).
13C NMR (150 MHz, CDCl3): d¼197.7 (Cq), 161.1 (Cq),
148.9 (CH), 148.6 (Cq), 137.0 (Cq), 136.4 (Cq), 135.4 (CH),
134.9 (Cq), 129.0 (CH), 127.9 (CH), 124.8 (CH), 121.0 (CH),
31.5 (CH2), 30.0 (CH2), 26.4 (CH3), 22.9 (CH2), 22.7 (CH2).
IR (ATR): 2930, 2864, 1674, 1599, 1583, 1563, 1460, 1429,
1402, 1358, 1265 cmꢂ1. MS (EI) m/z (relative intensity): 277
(41) [Mþ], 276 (100), 262 (4), 248 (9), 234 (4), 204 (4), 43
(3). HRMS (EI) m/z: calcd for C19H19NO, 277.1467; found,
277.1432.
4. Experimental
4.1. General
All catalytic reactions were carried out under N2 using pre-
dried glassware. Chemicals were obtained from commercial
sources, and were used without further purification. NMP (extra
dry) was obtained from Acros Organics, and was used without
further purification. Yields refer to isolated compounds, esti-
1
mated to be >95% pure as determined by H NMR and GC,

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L. Ackermann et al. / Tetrahedron 64 (2008) 6115e6124
4.1.3. 4-(2-Pyridin-2-ylcyclohex-1-enyl)benzoic acid ethyl
ester (5b)22
450 (100), 422 (11), 394 (17). HRMS (EI) m/z: calcd for
C29H25NO4, 451.1784; found, 451.1773.
The representative procedure was followed, using 3
(83.3 mg, 0.523 mmol) and 4b (108 mg, 0.585 mmol). After
22 h, purification by chromatography (n-pentane/Et2O, 5:1/
3:1/2:1/1:1) yielded 5b (34 mg, 21%) as a yellow solid
(mp: 88.0e89.0 ꢀC). 1H NMR (600 MHz, CDCl3): d¼8.50
(md, J¼4.8 Hz, 1H), 7.78 (md, J¼8.4 Hz, 2H), 7.24 (dt, J¼
7.8, 1.8 Hz, 1H), 7.05 (md, J¼8.3 Hz, 2H), 6.95 (ddd, J¼7.5,
4.9, 0.9 Hz, 1H), 6.66 (d, J¼7.9 Hz, 1H), 4.31 (q, J¼7.1 Hz,
2H), 2.62e2.59 (m, 2H), 2.47e2.45 (m, 2H), 1.85 (quint,
J¼3.1 Hz, 4H), 1.34 (t, J¼7.1 Hz, 3H). 13C NMR (150 MHz,
CDCl3): d¼166.5 (Cq), 161.2 (Cq), 148.9 (CH), 148.3 (Cq),
136.9 (Cq), 136.5 (Cq), 135.4 (CH), 129.1 (CH), 128.8 (CH),
128.1 (Cq), 124.8 (CH), 121.0 (CH), 60.7 (CH2), 31.5 (CH2),
30.0 (CH2), 23.0 (CH2), 22.7 (CH2), 14.3 (CH3). IR (KBr):
2936, 1714, 1604, 1585, 1562, 1427, 1272, 1256, 1181, 1110,
1101, 770, 706 cmꢂ1. MS (EI) m/z (relative intensity): 307
(33) [Mþ], 306 (100), 278 (22), 262 (3), 250 (4), 204 (3).
HRMS (EI) m/z: calcd for C20H21NO2, 307.1572; found,
307.1553.
4.1.6. 20-Pyridin-2-yl-[1,10;30,100]-terphenyl-4,400-
dicarbonitrile (7c)
The representative procedure was followed, using pyridine 6
(155 mg, 1.00 mmol) and 4-bromobenzonitrile (400 mg,
2.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/1:1) yielded 7c (304 mg, 85%) as a colorless
solid (mp: 164.5e165.2 ꢀC). 1H NMR (600 MHz, CDCl3):
d¼8.33 (d, J¼4.8 Hz, 1H), 7.59 (t, J¼7.5 Hz, 1H), 7.48e7.44
(m, 6H), 7.36 (t, J¼7.7 Hz, 1H), 7.19e7.17 (m, 4H), 7.00 (d,
J¼6.0 Hz, 1H), 6.82 (d, J¼7.8 Hz, 1H). 13C NMR (75 MHz,
CDCl3): d¼157.3 (Cq), 149.0 (CH), 145.9 (Cq), 140.3 (Cq),
138.3 (Cq), 135.5 (CH), 131.5 (CH), 130.2 (CH), 130.0 (CH),
128.8 (CH), 126.5 (CH), 121.7 (CH), 118.7 (Cq), 110.4 (Cq).
IR (ATR): 3056, 2230, 1675, 1463, 775, 703 cmꢂ1. MS (EI)
m/z (relative intensity): 358 (12), 357 (62) [Mþ], 356 (100).
HRMS (EI) m/z: calcd for C25H15N3, 357.1266; found,
357.1267.
4.1.7. 2-(4,400-Dichloro-[1,10;30,100]-terphenyl-20-yl)
pyridine (7d)
4.1.4. 2-[2-(4-Methoxyphenyl)cyclohex-1-enyl]pyridine (5c)
The representative procedure was followed, using 3
(83.3 mg, 0.523 mmol) and 4c (86.4 mg, 0.606 mmol). After
22 h, purification by chromatography (n-pentane/Et2O, 7:1/
The representative procedure was followed, using pyridine 6
(155 mg, 1.00 mmol) and bromo-4-chlorobenzene (421 mg,
2.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/2:1) yielded 7d (259 mg, 69%) as a colorless
1
5:1/3:1/1:1) yielded 5c (38 mg, 27%) as a yellow oil. H
NMR (600 MHz, CDCl3): d¼8.50 (md, J¼4.9 Hz, 1H), 7.26e
7.23 (m, 1H), 6.94e6.92 (m, 1H), 6.90 (md, J¼8.5 Hz, 2H),
6.68 (md, J¼7.9 Hz, 1H), 6.65 (md, J¼8.6 Hz, 2H), 3.71 (s, 3H),
2.60e2.58 (m, 2H), 2.45e2.43 (m, 2H), 1.83 (quint, J¼3.1 Hz,
4H). 13C NMR (150 MHz, CDCl3): d¼162.0 (Cq), 157.9 (Cq),
148.7 (CH), 136.8 (Cq), 135.7 (Cq), 135.1 (CH), 135.0 (Cq),
129.9 (CH), 125.1 (CH), 120.5 (CH), 113.2 (CH), 55.1 (CH3),
32.0 (CH2), 29.9 (CH2), 23.2 (CH2), 22.9 (CH2). IR (ATR):
2929, 2857, 2833, 1606, 1585, 1508, 1463, 1428, 1289, 1243,
1176, 1034 cmꢂ1. MS (EI) m/z (relative intensity): 265 (32)
[Mþ], 264 (100), 250 (7), 236 (5), 221 (2), 193 (2). HRMS
(EI) m/z: calcd for C18H19NO, 265.1467; found, 265.1451.
1
oil. H NMR (600 MHz, CDCl3): d¼8.35 (d, J¼4.6 Hz, 1H),
7.52 (t, J¼7.9 Hz, 1H), 7.42 (d, J¼7.7 Hz, 2H), 7.35 (t, J¼
7.7 Hz, 1H), 7.13 (d, J¼8.3 Hz, 4H), 7.02 (d, J¼8.3 Hz, 4H),
6.97 (t, J¼6.1 Hz, 1H), 6.85 (d, J¼7.8 Hz, 1H). 13C NMR
(150 MHz, CDCl3): d¼158.3 (Cq), 148.8 (CH), 140.7 (Cq),
138.8 (Cq), 138.4 (Cq), 135.2 (CH), 132.5 (Cq), 130.8 (CH),
129.6 (CH), 128.4 (CH), 127.9 (CH), 126.6 (CH), 121.2 (CH).
IR (ATR): 3072, 3018, 1603, 1450, 1012, 743 cmꢂ1. MS (EI)
m/z (relative intensity): 376 (78), 375 (64) [Mþ], 374 (100),
338 (20), 152 (21). HRMS (EI) m/z: calcd for C23H15Cl2N,
375.0582; found, 375.0602.
4.1.5. 20-Pyridin-2-yl-[1,10:30,100]-terphenyl-4,400-
dicarboxylic acid diethylester (7b)20
4.1.8. 20-Pyridin-2-yl-[1,10;30,100]-terphenyl-3,300-
dicarboxylic acid diethylester (7e)
The representative procedure was followed, using pyridine 6
(155 mg, 1.00 mmol) and 4-bromoethyl benzoate (504 mg,
2.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/1:1) yielded 7b (424 mg, 94%) as a colorless
solid (mp: 160.2e161.1 ꢀC). 1H NMR (300 MHz, CDCl3):
d¼8.30 (d, J¼4.9 Hz, 1H), 7.84 (d, J¼8.5 Hz, 4H), 7.56 (dd,
J¼8.7, 6.3 Hz, 1H), 7.50e7.45 (m, 2H), 7.31 (dt, J¼7.7,
1.7 Hz, 1H), 7.16 (d, J¼8.5 Hz, 4H), 6.94 (ddd, J¼7.4, 4.8,
1.0 Hz, 1H), 6.86 (d, J¼7.7 Hz, 1H), 4.33 (q, J¼7.1 Hz, 4H),
1.36 (t, J¼7.1 Hz, 6H). 13C NMR (75 MHz, CDCl3): d¼166.4
(Cq), 157.9 (Cq), 148.7 (CH), 146.0 (Cq), 141.0 (Cq), 138.3
(Cq), 135.3 (Cq), 129.8 (CH), 129.5 (CH), 128.9 (CH), 128.5
(CH), 128.4 (CH), 126.7 (CH), 121.4 (CH), 60.9 (CH2), 14.3
(CH3). IR (ATR): 3060, 2981, 1714, 1609, 1277, 1101, 1021,
769 cmꢂ1. MS (EI) m/z (relative intensity): 451 (75) [Mþ],
The representative procedure was followed, using pyridine 6
(160 mg, 1.03 mmol) and 3-bromoethyl benzoate (504 mg,
2.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/2:1) yielded 7e (440 mg, 95%) as a yellow oil.
1H NMR (300 MHz, CDCl3): d¼8.31 (d, J¼4.8 Hz, 1H), 7.84e
7.82 (m, 4H), 7.57e7.55 (m, 1H), 7.49 (d, J¼7.6 Hz, 2H), 7.30
(dt, J¼7.7, 1.6 Hz, 1H), 7.26e7.24 (m, 2H), 7.20 (t, J¼7.8 Hz, 2H),
6.91e6.87 (m, 2H), 4.30 (q, J¼4.3 Hz, 4H), 1.33 (t, J¼7.1 Hz,
6H). 13C NMR (75 MHz, CDCl3): d¼166.4 (Cq), 158.2 (Cq),
148.7 (CH), 141.5 (Cq), 140.9 (Cq), 138.6 (Cq), 135.1 (CH),
133.9 (CH), 130.6 (CH), 130.1 (Cq), 129.7 (CH), 128.5 (CH),
127.7 (CH), 127.6 (CH), 126.8 (CH), 121.1 (CH), 60.8 (CH2),
14.3 (CH3). IR (ATR): 2941, 2223, 1675, 1602, 1485, 1300,
1255, 1213, 1152, 1013, 833 cmꢂ1. MS (EI) m/z (relative inten-
sity): 452 (24), 451 (100) [Mþ], 450 (79), 422 (30), 406 (10), 404

L. Ackermann et al. / Tetrahedron 64 (2008) 6115e6124
6121
(12), 394 (12). HRMS (EI) m/z: calcd for C29H25NO4, 451.1784;
found, 451.1780.
MS (EI) m/z (relative intensity): 367 (5) [Mþ], 337 (69), 336
(100), 320 (20). HRMS (EI) m/z: calcd for C25H21NO2,
367.1572; found, 367.1571.
4.1.9. 20-Pyridin-2-yl-[1,10:30,100]-terphenyl-3,300-
dicarbonitrile (7f)20
4.1.12. 5-(2-Pyridin-2-yl-phenyl)furan-2-carboxylic acid
ethyl ester (13)
The representative procedure was followed, using pyridine 6
(145 mg, 0.93 mmol) and 3-bromobenzonitrile (400 mg,
2.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/1:1) yielded 6a (169 mg, 51%) as a colorless
solid (mp: 144.6e145.1 ꢀC). 1H NMR (300 MHz, CDCl3):
d¼8.30 (d, J¼4.9 Hz, 1H), 7.84 (d, J¼8.5 Hz, 4H), 7.56 (dd,
J¼8.7, 6.3 Hz, 1H), 7.50e7.45 (m, 2H), 7.31 (dt, J¼7.7,
1.7 Hz, 1H), 7.16 (d, J¼8.5 Hz, 4H), 6.94 (ddd, J¼7.4, 4.8,
1.0 Hz, 1H), 6.86 (d, J¼7.7 Hz, 1H), 4.33 (q, J¼7.1 Hz, 4H),
1.36 (t, J¼7.1 Hz, 6H). 13C NMR (75 MHz, CDCl3): d¼166.4
(Cq), 157.9 (Cq), 148.7 (CH), 146.0 (Cq), 141.0 (Cq), 138.3
(Cq), 135.3 (Cq), 129.8 (CH), 129.5 (CH), 128.9 (CH), 128.5
(CH), 128.4 (CH), 126.7 (CH), 121.4 (CH), 60.9 (CH2), 14.3
(CH3). IR (ATR): 3066, 2230, 1583, 1426, 795, 698 cmꢂ1. MS
(EI) m/z (relative intensity): 357 (56) [Mþ], 356 (100), 354
(6). HRMS (EI) m/z: calcd for C25H15N3, 357.1266; found,
357.1233.
The representative procedure was followed, using pyridine 6
(155 mg, 1.00 mmol) and 12 (482 mg, 2.20 mmol). After 22 h,
purification by chromatography (n-pentane/Et2O, 3:1/2:1)
yielded 13 (189 mg, 64%) as a brown oil. 1H NMR (600 MHz,
CDCl3): d¼8.61e8.59 (m, 1H), 7.80e7.77 (m, 1H), 7.63 (dt,
J¼7.8, 1.9 Hz, 1H), 7.45e7.38 (m, 3H), 7.25e7.20 (m, 2H),
6.95 (d, J¼3.8 Hz, 1H), 5.79 (d, J¼3.5 Hz, 1H), 4.22 (q, J¼
7.1 Hz, 2H), 1.25 (t, J¼7.1 Hz, 3H). 13C NMR (150 MHz,
CDCl3): d¼159.0 (Cq), 158.6 (Cq), 156.3 (Cq), 149.1 (Cq),
143.6 (Cq), 138.8 (Cq), 136.5 (CH), 130.4 (CH), 128.9 (CH),
128.7 (CH), 128.3 (CH), 128.1 (CH), 124.4 (CH), 122.3 (CH),
119.2 (CH), 110.6 (CH), 60.7 (CH2), 14.3 (CH3). IR (ATR):
3040, 2872, 2238, 1678, 1120, 904, 814 cmꢂ1. MS (EI) m/z (rel-
ative intensity): 294 (12), 293 (21) [Mþ], 220 (100), 191 (38),
163 (7). HRMS (EI) m/z: calcd for C18H15NO3, 293.1052;
found, 293.1024.
4.1.10. 2-(4,400-Dimethoxy-[1,10:30,100]-terphenyl-20-yl)-
pyridine (7g)20
The representative procedure was followed, using pyridine
4.1.13. 2-(40-Methoxy-3-methyl-biphenyl-2-yl)-4,5-dihydro-
oxazole (10a)21
The representative procedure was followed, using oxazoline
6
(145 mg, 0.93 mmol) and 4-bromoanisole (411 mg,
8
(161 mg, 1.00 mmol) and 4-bromoanisole (224 mg,
2.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 5:1/1:1) yielded 7g (208 mg, 61%) as a colorless
solid (mp: 163.1e163.9 ꢀC). 1H NMR (300 MHz, CDCl3):
d¼8.36 (d, J¼4.5 Hz, 1H), 7.48 (dd, J¼8.9, 6.2 Hz, 1H),
7.45e7.35 (m, 2H), 7.33 (dt, J¼7.8, 1.6 Hz, 1H), 7.01 (d, J¼
8.5 Hz, 4H), 6.92 (dd, J¼7.6, 5.1 Hz, 1H), 6.88 (d, J¼7.9 Hz,
1H), 6.70 (d, J¼8.5 Hz, 4H), 3.74 (s, 6H). 13C NMR (75 MHz,
CDCl3): d¼159.2 (Cq), 158.2 (Cq), 148.5 (CH), 141.4 (Cq),
138.4 (Cq), 135.0 (CH), 134.0 (CH), 130.6 (CH), 129.1 (CH),
128.1 (CH), 126.7 (CH), 113.1 (CH), 55.1 (CH3). IR (ATR):
3037, 1609, 1582, 1513, 1233, 1183, 1040, 806 cmꢂ1. MS
(EI) m/z (relative intensity): 367 (95) [Mþ], 366 (100), 353
(21), 352 (92). HRMS (EI) m/z: calcd for C25H21NO2,
367.1572; found, 367.1552.
1.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/1:1) yielded 10a (174 mg, 65%) as a yellow
oil. 1H NMR (300 MHz, CDCl3): d¼7.37e7.28 (m, 3H), 7.18
(md, J¼8.1 Hz, 2H), 6.90 (md, J¼8.8 Hz, 2H), 4.15 (t,
J¼9.3 Hz, 2H), 3.91e3.81 (m, 5H), 2.40 (s, 3H). 13C NMR
(75 MHz, CDCl3): d¼164.6 (Cq), 158.8 (Cq), 141.5 (Cq),
137.4 (Cq), 133.6 (Cq), 129.5 (CH), 129.4 (CH), 128.5 (CH),
128.1 (Cq), 127.1 (CH), 113.4 (CH), 67.1 (CH2), 55.2 (CH3),
55.0 (CH2), 19.7 (CH3). IR (ATR): 3062, 2933, 1884, 1666,
1610, 1514, 1461, 1346, 1291, 1248, 1180, 937 cmꢂ1. MS
(EI) m/z (relative intensity): 267 (17) [Mþ], 266 (100), 222
(4), 152 (2). HRMS (EI) m/z: calcd for C17H17NO2, 267.1225;
found, 267.1259.
4.1.14. 1-(20-(4,5-Dihydro-oxazol-2-yl)-30-methyl-biphenyl-
4-yl)ethanone (10b)21
4.1.11. 2-(2,200-Dimethoxy-[1,10;30,100]-terphenyl-20-yl)-
pyridine (7h)
The representative procedure was followed, using pyridine
The representative procedure was followed, using oxazoline
8 (166 mg, 1.03 mmol) and 4-bromoacetophenone (239 mg,
1.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/1:1) yielded 10b (197 mg, 68%) as a yellow
solid (mp: 88.7e89.1 ꢀC). 1H NMR (300 MHz, CDCl3):
d¼7.96 (md, J¼8.6 Hz, 2H), 7.50 (md, J¼8.6 Hz, 2H), 7.42e
7.33 (m, 1H), 7.30e7.18 (m, 2H), 4.15 (t, J¼8.6 Hz, 2H), 3.85
(t, J¼8.7 Hz, 2H), 2.62 (s, 3H), 2.42 (s, 3H). 13C NMR
(75 MHz, CDCl3): d¼197.8 (Cq), 164.1 (Cq), 146.2 (Cq),
140.8 (Cq), 137.8 (Cq), 135.8 (Cq), 129.7 (CH), 129.6 (CH),
128.6 (CH), 128.1 (CH), 128.0 (Cq), 127.0 (CH), 67.2 (CH2),
55.1 (CH2), 25.6 (CH3), 19.8 (CH3). IR (ATR): 3064, 2878,
1679, 1606, 1402, 1357, 1269, 1253, 1186, 1045, 932,
844 cmꢂ1. MS (EI) m/z (relative intensity): 279 (17) [Mþ],
6
(157 mg, 1.01 mmol) and 2-bromoanisole (411 mg,
2.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/2:1) yielded 7h (241 mg, 65%) as a colorless
solid (mp: 186.2e187.3 ꢀC). 1H NMR (600 MHz, CDCl3): d¼
8.15 (d, J¼4.2 Hz, 1H), 7.49 (t, J¼7.5 Hz, 1H), 7.40 (d, J¼
7.7 Hz, 2H), 7.21 (t, J¼7.8 Hz, 2H), 7.19e7.14 (m, 3H), 6.94
e6.85 (m, 3H), 6.78 (t, J¼7.4 Hz, 1H), 6.65 (br s, 2H), 3.43
(br s, 6H). 13C NMR (150 MHz, CDCl3): d¼159.5 (Cq), 156.0
(Cq), 147.4 (CH), 140.2 (CH), 137.9 (Cq), 133.5 (CH), 131.9
(CH), 130.8 (CH), 130.0 (CH), 128.1 (CH), 127.5 (Cq), 125.6
(Cq), 120.2 (CH), 120.1 (CH), 110.0 (CH), 54.8 (CH3). IR
(ATR): 3042, 2213, 1593, 1467, 1245, 1185, 1178, 823 cmꢂ1
.

6122
L. Ackermann et al. / Tetrahedron 64 (2008) 6115e6124
278 (100), 234 (3), 165 (3). HRMS (EI) m/z: calcd for
C18H17NO2, 279.1259; found, 279.1197.
(EI) m/z (relative intensity): 295 (23) [Mþ], 294 (100), 250
(6), 178 (4), 165 (8). HRMS (EI) m/z: calcd for C18H17NO3,
295.1208; found, 295.1174.
4.1.15. 20-(4,5-Dihydro-oxazol-2-yl)-30-methyl-biphenyl-4-
carboxylic acid methyl ester (10c)21
4.1.18. 2-(3-Methyl-30,50-bis-trifluoromethyl-biphenyl-2-yl)-
4,5-dihydro-oxazole (10f)
The representative procedure was followed, using oxazoline
8 (161 mg, 1.00 mmol) and 4-bromomethyl benzoate (258 mg,
1.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 1:1/1:2) yielded 10c (236 mg, 68%) as a yellow
solid (mp: 116.5e117.1 ꢀC). 1H NMR (300 MHz, CDCl3):
d¼7.96 (md, J¼8.6 Hz, 2H), 7.50 (md, J¼8.6 Hz, 2H), 7.41e
7.33 (m, 1H), 7.29e7.17 (m, 2H), 4.15 (t, J¼9.4 Hz, 2H), 3.85
(t, J¼9.4 Hz, 2H), 2.62 (s, 3H), 2.42 (s, 3H). 13C NMR
(75 MHz, CDCl3): d¼167.0 (Cq), 164.1 (Cq), 146.2 (Cq),
140.8 (Cq), 137.8 (Cq), 135.7 (Cq), 129.7 (CH), 129.6 (CH),
129.4 (Cq), 128.6 (CH), 128.1 (CH), 127.0 (CH), 67.2 (CH2),
55.1 (CH2), 29.6 (CH3), 19.8 (CH3). IR (ATR): 3064, 2878,
1726, 1666, 1610, 1460, 1436, 1314, 1280, 1196, 1042, 932,
856 cmꢂ1. MS (EI) m/z (relative intensity): 295 (17) [Mþ],
294 (100), 264 (3), 250 (4), 191 (2), 165 (3). HRMS (EI) m/z:
calcd for C18H17NO3, 295.1208; found, 295.1182.
The representative procedure was followed, using oxazoline
8 (161 mg, 1.00 mmol) and 3,5-bis(trifluoromethyl)bromobenz-
ene (352 mg, 1.20 mmol). After 22 h, purification by chroma-
tography (n-pentane/Et2O, 3:1/2:1) yielded 10f (170 mg,
1
46%) as a colorless oil. H NMR (600 MHz, CDCl3): d¼7.91
(s, 2H), 7.84 (s, 1H), 7.43 (t, J¼7.5 Hz, 1H), 7.33e7.32 (m,
1H), 7.27e7.25 (m, 1H), 4.20 (t, J¼9.7 Hz, 2H), 3.87 (t, J¼
9.7 Hz, 2H), 2.25 (s, 3H). 13C NMR (150 MHz, CDCl3):
d¼163.9 (Cq), 143.3 (Cq), 138.9 (Cq), 138.6 (Cq), 131.6 (q, J¼
33.2 Hz, Cq), 130.7 (CH), 130.4 (q, J¼68.7 Hz, CH), 130.2
(CH), 128.9 (CH), 128.6 (Cq), 127.2 (CH), 123.6 (q, J¼
272.7 Hz, Cq), 121.1 (q, J¼3.8 Hz, CH), 67.5 (CH2), 55.5
(CH2), 20.0(CH3). 19F NMR (282 MHz, CDCl3): d¼ꢂ63.56 (s).
IR (ATR): 2874, 1694, 1453, 1367, 1265, 1148, 1111, 1021, 956,
867 cmꢂ1. MS (EI) m/z (relative intensity): 373 (100) [Mþ], 324
(21), 317 (23), 233 (17). HRMS (EI) m/z: calcd for C18H13F6NO,
373.0901; found, 373.0917.
4.1.16. 20-(4,5-Dihydro-oxazol-2-yl)-30-methyl-biphenyl-4-
carbonitrile (10d)21
The representative procedure was followed, using oxazoline
8 (165 mg, 1.02 mmol) and 4-bromobenzonitrile (218 mg,
1.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/1:3) yielded 10d (158 mg, 59%) as a brown
solid (mp: 102.2e103.4 ꢀC). 1H NMR (300 MHz, CDCl3):
d¼7.66 (md, J¼8.6 Hz, 2H), 7.51 (d, J¼8.6 Hz, 2H), 7.44e
7.34 (m, 1H), 7.32e7.25 (m, 1H), 7.21e7.14 (m, 1H), 4.17 (t,
J¼9.5 Hz, 2H), 3.87 (t, J¼9.4 Hz, 2H), 2.43 (s, 3H). 13C
NMR (75 MHz, CDCl3): d¼163.9 (Cq), 146.0 (Cq), 140.1
(Cq), 138.0 (Cq), 131.8 (CH), 130.1 (CH), 129.7 (CH), 129.2
(CH), 128.0 (Cq), 126.9 (CH), 118.9 (Cq), 111.0 (Cq), 67.3
(CH2), 55.1 (CH2), 19.8 (CH3). IR (ATR): 2885, 2231, 1651,
1459, 1346, 1255, 1047, 969, 932, 848, 790, 758 cmꢂ1. MS
(EI) m/z (relative intensity): 262 (18) [Mþ], 261 (100), 217
(13), 190 (11), 177 (3), 151 (2). HRMS (EI) m/z: calcd for
C17H14N2O, 262.1106; found, 262.1085.
4.1.19. 2-(20-Chloro-3-methyl-biphenyl-2-yl)-4,5-dihydro-
oxazole (10g)
The representative procedure was followed, using oxazoline
8 (161 mg, 1.00 mmol) and bromo-2-chlorobenzene (230 mg,
1.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 5:1/2:1) yielded 10g (167 mg, 62%) as a yellow
oil. 1H NMR (300 MHz, CDCl3): d¼7.31e7.28 (m, 4H),
7.22e7.11 (m, 3H), 4.12 (t, J¼9.1 Hz, 2H), 3.82 (t, J¼9.1 Hz,
2H), 2.36 (s, 3H). 13C NMR (75 MHz, CDCl3): d¼164.5
(CH), 141.0 (CH), 139.9 (Cq), 137.9 (Cq), 134.2 (CH), 133.5
(CH), 133.4 (CH), 132.2 (Cq), 131.3 (Cq), 130.0 (CH), 129.8
(Cq), 129.6 (Cq), 128.4 (Cq), 127.3 (Cq), 67.7 (CH2), 55.4
(CH2), 19.8 (CH3). IR (ATR): 3056, 1654, 1489, 1351, 1265,
1003, 943, 856, 767 cmꢂ1. MS (EI) m/z (relative intensity):
271 (21), [Mþ], 270 (100), 242 (14), 161 (17), 104 (9). HRMS
(EI) m/z: calcd for C16H14ClNO, 271.0764; found, 271.0765.
4.1.17. 20-(4,5-Dihydro-oxazol-2-yl)-30-methyl-biphenyl-3-
carboxylic acid methyl ester (10e)
4.1.20. 2-(3-Methyl-40-vinylbiphenyl-2-yl)-4,5-dihydro-
oxazole (10h)
The representative procedure was followed, using oxazoline
The representative procedure was followed, using oxazoline
8 (163 mg, 1.01 mmol) and 3-bromomethyl benzoate (258 mg,
1.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/1:3) yielded 10e (230 mg, 77%) as a colorless
8
(160 mg, 0.993 mmol) and 4-bromostyrene (226 mg,
1.23 mmol). After 22 h, purification by chromatography (n-hex-
ane/EtOAc, 5:1/3:1) yielded 10h (133 mg, 51%) as a yellow
oil. 1H NMR (600 MHz, CDCl3): d¼7.43e7.34 (m, 5H),
7.23e7.21 (m, 2H), 6.75 (dd, J¼17.6, 10.9 Hz, 1H), 5.78 (d,
J¼17.6 Hz, 1H), 5.27 (d, J¼10.9 Hz, 1H), 4.16 (t, J¼9.5 Hz,
2H), 3.88 (t, J¼9.5 Hz, 2H), 2.42 (s, 3H). 13C NMR
(150 MHz, CDCl3): d¼164.4 (Cq), 141.6 (Cq), 140.7 (Cq),
137.5 (Cq), 136.5 (CH), 136.3 (Cq), 129.5 (CH), 129.0 (CH),
128.6 (CH), 128.1 (Cq), 127.1 (CH), 125.9 (CH), 113.8
(CH2), 67.2 (CH2), 55.1 (CH2), 19.8 (CH3). IR (ATR): 1667,
1
oil. H NMR (600 MHz, CDCl3): d¼8.06 (s, 1H), 7.95 (d,
J¼7.6 Hz, 1H), 7.52 (d, J¼7.8 Hz, 1H), 7.52 (d, J¼7.8 Hz,
1H), 7.39e7.35 (m, 1H), 7.32e7.28 (m, 1H), 7.20e7.15 (m,
1H), 4.09 (t, J¼9.5 Hz, 2H), 3.84 (s, 3H), 3.78 (t, J¼9.5 Hz,
2H), 2.35 (s, 3H). 13C NMR (75 MHz, CDCl3): d¼167.0 (Cq),
164.2 (Cq), 141.4 (Cq), 140.8 (Cq), 137.7 (Cq), 132.9 (CH),
130.0 (Cq), 129.6 (CH), 129.4 (CH), 128.3 (CH), 128.2 (Cq),
128.1 (CH), 128.1 (CH), 127.1 (CH), 67.2 (CH2), 55.2 (CH2),
52.1 (CH3), 19.8 (CH3). IR (ATR): 3064, 2952, 1723, 1664,
1581, 1437, 1347, 1313, 1256, 1121, 1044, 972 cmꢂ1. MS
1460, 1342, 1251, 1234, 1041, 933, 895, 849, 794, 762 cmꢂ1
MS (EI) m/z (relative intensity): 263 (18) [Mþ], 262 (100),
.

L. Ackermann et al. / Tetrahedron 64 (2008) 6115e6124
6123
234 (2), 218 (6), 205 (2), 191 (3), 178 (3), 165 (2). HRMS (EI) m/
z: calcd for C18H16NO, 262.1232; found, 262.1242.
4.1.24. 1-(4,400-Dimethoxy-[1,10:30,100]-terphenyl-20-yl)-1H-
pyrazole (18c)21
The representative procedure was followed, using 17
(148 mg, 1.03 mmol) and 11c (411 mg, 2.20 mmol). After
22 h, purification by chromatography (n-pentane/Et2O, 4:1/
1:1) yielded 18c (200 mg, 55%) as a colorless solid (mp:
132.4e133.1 ꢀC). 1H NMR (300 MHz, CDCl3): d¼7.55e7.50
(m, 1H), 7.45e7.42 (m, 3H), 7.09 (d, J¼2.4, 0.6 Hz, 1H), 7.03
(dt, J¼9.6, 2.5 Hz, 4H), 6.76 (dt, J¼9.6, 2.5 Hz, 4H), 6.10e
6.09 (m, 1H), 3.77 (s, 6H). 13C NMR (75 MHz, CDCl3):
d¼158.8 (Cq), 140.1 (Cq), 139.2 (CH), 136.2 (Cq), 132.4
(CH), 131.1 (Cq), 129.6 (CH), 129.3 (CH), 129.0 (CH), 113.5
(CH), 106.0 (CH), 55.1 (CH3). IR (ATR): 1608, 1515, 1462,
1280, 1241, 1183, 1039, 1030, 843, 835, 800, 762 cmꢂ1. MS
(EI) m/z (relative intensity): 355 (100) [MꢂHþ], 341 (6), 311
(4), 297 (2), 269 (2). HRMS (EI) m/z: calcd for C23H20N2O2,
356.1525; found, 356.1537.
4.1.21. 2-(20-Methoxy-3-methyl-biphenyl-2-yl)-4,5-dihydro-
oxazole (10i)21
The representative procedure was followed, using oxazoline
8
(161 mg, 1.00 mmol) and 2-bromoanisole (224 mg,
1.20 mmol). After 22 h, purification by chromatography (n-pen-
tane/Et2O, 3:1/1:1) yielded 10i (136 mg, 51%) as a yellow oil.
1H NMR (300 MHz, CDCl3): d¼7.37e7.17 (m, 5H), 6.99e6.89
(m, 2H), 4.05 (t, J¼9.3 Hz, 2H), 3.84e3.73 (m, 5H), 2.43 (s,
3H). 13C NMR (75 MHz, CDCl3): d¼164.5 (Cq), 156.5 (Cq),
138.7 (Cq), 137.2 (Cq), 130.7 (CH), 130.2 (Cq), 129.0 (CH),
128.9 (CH), 128.8 (CH), 128.5 (CH), 128.2 (CH), 120.1 (CH),
110.6 (CH), 66.9 (CH2), 55.5 (CH3), 55.1 (CH2), 20.1 (CH3).
IR (ATR): 3063, 2891, 1667, 1496, 1432, 1340, 1234, 1078,
1035, 1020, 935, 894, 761 cmꢂ1. MS (EI) m/z (relative inten-
sity): 266 (10) [MꢂHþ], 237 (15), 236 (100), 192 (13), 165
(5). HRMS (EI) m/z: calcd for C17H17NO2, 267.1259; found,
267.1251.
4.1.25. 2-(40-Acetylphenyl)phenylethanone (20a)20
The representative procedure was followed, using 19
(225 mg, 1.00 mmol) and 11a (229 mg, 1.20 mmol). After
22 h, purification by chromatography (n-pentane/Et2O, 8:1/
2:1) yielded 20a (162 mg, 68%) as a light yellow oil. 1H NMR
(300 MHz, CDCl3): d¼7.99 (d, J¼8.3 Hz, 2H), 7.58 (dd, J¼
7.5, 1.5 Hz, 1H), 7.52 (dt, J¼7.5, 1.4 Hz, 1H), 7.45 (dd, J¼
7.5, 1.4 Hz, 1H), 7.41 (d, J¼7.5, 1.3 Hz, 2H), 7.35 (dd, J¼7.5,
1.3 Hz, 1H), 2.62 (s, 3H), 2.11 (s, 3H). 13C NMR (75 MHz,
CDCl3): d¼203.5 (Cq), 197.5 (Cq), 145.6 (Cq), 140.3 (Cq),
139.4 (Cq), 136.1 (Cq), 130.9 (CH), 130.2 (CH), 128.9 (CH),
128.5 (CH), 128.1 (CH), 128.0 (CH), 30.2 (CH3), 26.5 (CH3).
IR (ATR): 3070, 2945, 1690, 1623, 1476, 1300, 1179, 1035,
771 cmꢂ1. MS (EI) m/z (relative intensity): 238 (78) [Mþ],
223 (100), 195 (25), 181 (45), 152 (27). HRMS (EI) m/z: calcd
for C16H14O2, 238.0994; found, 238.0981.
4.1.22. 1-(4-Acetyl-20-pyrazol-1-yl-[1,10;30,100]-terphenyl-
400-yl)ethanone (18a)
The representative procedure was followed, using 17
(148 mg, 1.03 mmol) and 11a (438 mg, 2.20 mmol). After
22 h, purification by chromatography (n-pentane/Et2O, 3:1/
1:1) yielded 18a (232 mg, 64%) as an off-white solid (mp:
1
164.2e165.1 ꢀC). H NMR (300 MHz, CDCl3): d¼7.83 (dt,
J¼8.4, 1.8 Hz, 4H), 7.65e7.52 (m, 3H), 7.37 (d, J¼1.8 Hz,
1H), 7.20 (dt, J¼8.4, 1.8 Hz, 4H), 7.06 (d, J¼2.3 Hz, 1H),
6.08 (t, J¼2.2 Hz, 1H), 2.57 (s, 6H). 13C NMR (75 MHz,
CDCl3): d¼197.6 (Cq), 143.3 (Cq), 139.9 (CH), 139.4 (Cq),
136.4 (Cq), 135.9 (Cq), 132.3 (CH), 130.5 (CH), 129.4 (CH),
128.4 (CH), 128.1 (CH), 106.7 (CH), 26.6 (CH3). IR (ATR):
1675, 1607, 1267, 847, 834, 811, 754, 705, 626, 608, 601,
591 cmꢂ1. MS (EI) m/z (relative intensity): 380 (48) [Mþ],
379 (100), 365 (6), 337 (10), 293 (5), 175 (7), 146 (5), 43 (7).
HRMS (EI) m/z: calcd for C25H20N2O2, 380.1525; found,
380.1498.
4.1.26. 4-(20-Acetylphenyl)benzoic acid ethyl ester (20b)20
The representative procedure was followed, using 19
(225 mg, 1.00 mmol) and 11b (275 mg, 1.20 mmol). After
22 h, purification by chromatography (n-pentane/Et2O, 4:1/
1
3:1) yielded 20b (173 mg, 65%) as a yellow oil. H NMR
4.1.23. 20-Pyrazol-1-yl-[1,10;30,100]-terphenyl-4,400-
dicarboxylic acid dimethyl ester (18b)
(300 MHz, CDCl3): d¼8.10 (d, J¼8.2 Hz, 2H), 7.59 (dd, J¼
7.5, 1.5 Hz, 1H), 7.51 (dt, J¼7.4, 1.6 Hz, 1H), 7.45 (dd, J¼
7.4, 1.4 Hz, 1H), 7.40 (d, J¼8.2 Hz, 2H), 7.38 (d, J¼1.4 Hz,
1H), 4.30 (q, J¼7.1 Hz, 2H), 2.08 (s, 3H), 1.41 (t, J¼7.1 Hz,
3H). 13C NMR (75 MHz, CDCl3): d¼203.8 (Cq), 166.2 (Cq),
154.4 (Cq), 140.5 (Cq), 139.5 (Cq), 130.9 (CH), 130.2 (CH),
129.8 (Cq), 129.7 (CH), 128.8 (CH), 128.1 (CH), 128.0 (CH),
61.1 (CH2), 30.4 (CH3), 14.3 (CH3). IR (ATR): 3059, 2988,
1716, 1656, 1244, 1100, 1028, 790 cmꢂ1. MS (EI) m/z (relative
intensity): 268 (60) [Mþ], 267 (18), 239 (21), 223 (33), 181
(100). HRMS (EI) m/z: calcd for C17H16O3, 268.1099; found,
268.1087.
The representative procedure was followed, using 17
(144 mg, 1.00 mmol) and 11b (473 mg, 2.20 mmol). After
22 h, purification by chromatography (n-pentane/Et2O, 3:1/
2:1) yielded 18b (214 mg, 52%) as an off-white solid (mp:
1
144.2e145.6 ꢀC). H NMR (600 MHz, CDCl3): d¼7.92 (d,
J¼8.2 Hz, 4H), 7.60 (t, J¼8.0 Hz, 1H), 7.55e7.50 (m, 2H),
7.36 (s, 1H), 7.16 (d, J¼8.1 Hz, 4H), 7.05 (s, 1H), 6.06 (s,
1H), 1.34 (s, 6H). 13C NMR (150 MHz, CDCl3): d¼164.0
(Cq), 143.0 (CH), 140.7 (CH), 137.5 (Cq), 137.2 (Cq), 134.1
(Cq), 130.0 (CH), 128.2 (Cq), 127.0 (CH), 125.9 (CH), 106.6
(CH), 104.3 (CH), 120.9 (CH3). IR (ATR): 1719, 1609, 1435,
1401, 1313, 1277, 1188, 1103, 1018, 770, 708 cmꢂ1. MS (EI)
m/z (relative intensity): 412 (43) [Mþ], 411 (100), 381 (5),
351 (6), 292 (4), 265 (2), 175 (2), 147 (2). HRMS (EI) m/z: calcd
for C25H20N2O4, 412.1423; found, 412.1408.
4.1.27. 2-(40-Methoxyphenyl)phenylethanone (20c)20
The representative procedure was followed, using 19
(225 mg, 1.00 mmol) and 11c (224 mg, 1.20 mmol). After
22 h, purification by chromatography (n-pentane/Et2O, 4:1/

6124
L. Ackermann et al. / Tetrahedron 64 (2008) 6115e6124
Organometallic Chemistry; Tsuji, J., Ed.; Springer: Berlin, Heidelberg,
New York, NY, 2005; Vol. 14, pp 55e83; (g) Kawamura, Y.; Satoh, T.;
Miura, M.; Nomura, M. Chem. Lett. 1999, 961e962; (h) Kametani, Y.;
Satoh, T.; Miura, M.; Nomura, M. Tetrahedron Lett. 2000, 41, 2655e
2658; (i) Terao, Y.; Kametani, Y.; Wakui, H.; Satoh, T.; Miura, M.;
Nomura, M. Tetrahedron 2001, 57, 5967e5974; (j) Campeau, L.-C.;
Parisien, M.; Jean, A.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 581e590;
(k) Kalyani, D.; Deprez, N. R.; Desai, L. V.; Sanford, M. S. J. Am. Chem.
Soc. 2005, 127, 7330e7331; (l) Hull, K. L.; Lanni, E. L.; Sanford, M. S.
J. Am. Chem. Soc. 2006, 128, 14047e14049; (m) Daugulis, O.; Zaitsev,
V. G. Angew. Chem., Int. Ed. 2005, 44, 4046e4048; (n) Zaitsev, V. G.;
Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2005, 127, 13154e13155;
(o) Chiong, H. A.; Pham, Q.-N.; Daugulis, O. J. Am. Chem. Soc. 2007,
129, 9879e9884 and references cited therein.
3:1) yielded 20c (196 mg, 56%) as a colorless solid (mp: 83.4e
84.5 ꢀC). 1H NMR (300 MHz, CDCl3): d¼7.45e7.35 (m, 2H),
7.31e7.25 (m, 2H), 7.16 (d, J¼8.5 Hz, 2H), 6.86 (d,
J¼8.5 Hz, 2H), 3.74 (s, 3H), 1.91 (s, 3H). 13C NMR (75 MHz,
CDCl3): d¼205.5 (Cq), 159.5 (Cq), 140.8 (Cq), 140.0 (Cq),
132.9 (CH), 130.6 (CH), 130.0 (CH), 129.9 (CH), 127.7 (CH),
126.9 (CH), 114.0 (CH), 55.2 (CH3), 30.3 (CH3). IR (ATR):
3055, 2981, 1683, 1600, 1267, 1013, 840 cmꢂ1. MS (EI) m/z
(relative intensity): 268 (10) [Mþ], 253 (65), 211 (100).
HRMS (EI) m/z: calcd for C15H14O2, 226.0994; found,
226.0987.
16. Kakiuchi, F.; Chatani, N. Ruthenium Catalysts and Fine Chemistry;
Bruneau, C., Dixneuf, P. H., Eds.; Springer: Berlin, Heidelberg, 2004;
Vol. 11, pp 45e79.
Acknowledgements
Support by the DFG, Sanofi-Aventis, the Fonds der Chemi-
schen Industrie, the Dr. Otto Rohm Gedachtnisstiftung, and
the Georg-August-Universitaet Goettingen is gratefully
acknowledged. We thank BASF AG for the donation of NMP.
17. Kakiuchi, F.; Chatani, N. Ruthenium in Organic Synthesis; Murahashi,
S.-I., Ed.; Wiley-VCH: Weinheim, 2004; pp 219e255.
¨
¨
18. (a) Oi, S.; Fukita, S.; Hirata, N.; Watanuki, N.; Miyano, S.; Inoue, Y. Org.
Lett. 2001, 3, 2579e2581; (b) Oi, S.; Ogino, Y.; Fukita, S.; Inoue, Y. Org.
Lett. 2002, 4, 1783e1785; (c) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.;
Murai, S. J. Am. Chem. Soc. 2003, 125, 1698e1699; (d) Oi, S.; Sakai, K.;
Inoue, Y. Org. Lett. 2005, 7, 4009e4011; (e) Oi, S.; Aizawa, E.; Ogino,
Y.; Inoue, Y. J. Org. Chem. 2005, 70, 3113e3119; (f) Ueno, S.; Chatani,
N.; Kakiuchi, F. J. Am. Chem. Soc. 2007, 129, 6098e6099 and references
cited therein.
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19. For a review on the use of secondary phosphine oxides in catalysis, see:
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20. Ackermann, L. Org. Lett. 2005, 7, 3123e3125.
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22. Ackermann, L.; Born, R.; Alvarez Bercedo, P. Angew. Chem., Int. Ed.
4. Godula, K.; Sames, D. Science 2006, 312, 67e72.
ꢀ
5. Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174e238.
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