Palladium(II)-catalyzed ortho arylation of 2-phenylpyridines with potassium aryltrifluoroborates by C-H functionalization

Article abstract of DOI:10.1055/s-0029-1217014

An efficient one-pot synthesis of ortho-arylated 2-phenylpyridine and pyridine derivatives by use of potassium aryltrifluoroborates is presented. The optimal reaction conditions are as follows: the 2-phenylpyridine or pyridine derivative is treated with 2

Full text of DOI:10.1055/s-0029-1217014

PAPER
3757
Palladium(II)-Catalyzed ortho Arylation of 2-Phenylpyridines with Potassium
Aryltrifluoroborates by C–H Functionalization
P
alladium
e
(II)-Catalyz
a
edortho
A
n
r
ylation of
2
-
H
yridines o Chu,a Shiang-Lin Tsai,b Ming-Jung Wu*a
a
Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan 804, Taiwan
Fax +886(7)5253909; E-mail: mijuwu@faculty.nsysu.edu.tw
b
Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan 807, Taiwan
Received 8 June 2009; revised 6 July 2009
To the best of our knowledge, only a few examples ex-
ploiting potassium organotrifluoroborate salts as a cou-
pling reagent in C–C bond formations via transition-
metal-catalyzed C–H bond activation have been report-
Abstract: An efficient one-pot synthesis of ortho-arylated 2-phe-
nylpyridine and pyridine derivatives by use of potassium aryltri-
fluoroborates is presented. The optimal reaction conditions are as
follows: the 2-phenylpyridine or pyridine derivative is treated with
2.5 equivalents of a potassium aryltrifluoroborate in the presence of ed.17 Considering the advantages of these salts, we antici-
10 mol% palladium(II) acetate, three equivalents of copper(II) ace-
tate, and two equivalents of p-benzoquinone in 1,4-dioxane at
pated that potassium organotrifluoroborate salts would be
superior to organoboronic acids in direct C–C bond for-
120 °C for 24 hours. p-Benzoquinone is an important co-oxidant in
mation via aryl C–H bond activation. Herein we report the
the transmetalation–reductive elimination step. The kinetic isotope
direct ortho arylation of 2-phenylpyridine and pyridine
effect (kH/kD) for the C–H bond activation was determined to be
1.09. It indicates that the C–H bond cleavage does not occur in the
rate-determining step.
derivatives using potassium aryltrifluoroborate salts and
palladium(II) acetate as the coupling reagent and catalyst,
respectively.
Key words: C–H functionalization, potassium trifluoroborate, pal-
ladium catalyst, arylations, pyridines
Our investigation began by examining the intermolecular
C–C bond formation of 2-phenylpyridine (1) with potas-
sium trifluoro(phenyl)borate (2a) via C–H bond activa-
tion (Scheme 1). A variety of oxidants and solvents were
screened, and the results are shown in Tables 1 and 2.
Copper(II) acetate and 1,4-dioxane were found to be the
best oxidant and solvent for this reaction.
Transition-metal-catalyzed functionalization of aryl C–H
bonds has received much attention recently.1 Various cou-
pling reagents, such as organosilanes,2 organotin re-
agents,3 organozinc reagents,4 olefins,5 peroxides,6 an
amide,7 a diethyl azodicarboxylate,8 and boronic acids,9
have been utilized in the atom-economic C–H bond acti-
vation and coupling reactions. Among those efficient
transformations of a C–H bond into a C–C bond, orga-
noboronic acids or -boronates are the most commonly
used reagents. The drawback of these reagents is that they
very easily undergo a homocoupling reaction to give the
undesired biaryl products10 under the reaction conditions,
and the yields of the desired products are modest to low.
Potassium organoborates were first synthesized by
Fowler and Kraus in 1940.11 Vedejs and co-workers de-
veloped a convenient synthesis of potassium organotri-
fluoroborates by the reaction of organoboronic acids or
esters with potassium hydrogenfluoride (KHF2).12 In ad-
dition, Genêt and co-workers reported the first example of
a cross-coupling reaction in which organotrifluoroborate
reagents were used.13 Later, Molander and co-workers de-
veloped a palladium-catalyzed cross-coupling reaction of
aryl halides with a variety of potassium organotrifluoro-
borates.14 To date, potassium organotrifluoroborate re-
agents have been widely used in Suzuki–Miyaura
reactions and other coupling reactions.15 These salts have
been demonstrated to be air- and moisture stable, and less
prone to protodeboronation.16
R
Pd(OAc)2 (10 mol%)
Cu(OAc)2 (3 equiv)
BQ (2 equiv)
H
+
1,4-dioxane
120 °C, 24 h
N
N
R
X
1
2a R = H; X = BF3K
3a R = H 74%
3b R = CHO 65%
3a R = H 15%
2b R = CHO; X = BF3K
4a R = H; X = B(OH)2
4b R = CHO; X = B(OH)2
3b R = CHO 17%
Scheme 1
Under the optimal reaction conditions [Ar-BF3K (2.5
equiv),18 Pd(OAc)2 (10 mol%), Cu(OAc)2 (3 equiv), BQ
(2 equiv), 1,4-dioxane, 120 °C, 24 h], the reaction of py-
ridine 1 with trifluoroborate 2a gave 3a in 74% yield
(Scheme 1). We also carried out this C–C bond-formation
reaction using phenylboronic acid (4a), and found that the
boronic acid gave the desired product 3a in only 15%
yield (Scheme 1). To double check the relative efficiency
of these two reagents (trifluoroborate and boronic acid) in
this C–C bond-formation reaction, potassium trifluoro(4-
formylphenyl)borate (2b) and 4-formylphenylboronic
acid (4b) were also compared. Trifluoroborate 2b gave
the product 3b in 65% yield and the corresponding boron-
ic acid 4b gave the desired product 3b in only 17% yield.
This demonstrated that the aryltrifluoroborate salts are su-
SYNTHESIS 2009, No. 22, pp 3757–3764
Advanced online publication: 23.09.2009
DOI: 10.1055/s-0029-1217014; Art ID: F11509SS
x
x.
x
x
.
2
0
0
9
© Georg Thieme Verlag Stuttgart · New York

3758
J.-H. Chu et al.
PAPER
the polymer. In addition, the structure of 3c was further
confirmed by a single-crystal X-ray crystallography anal-
ysis, as shown in Figure 1.19
Table 1 Reaction of 2-Phenylpyridine (1) with Potassium Trifluo-
ro(phenyl)borate (2a) in the Presence of Various Oxidantsa
Entry
Oxidant
none
Product
3a
Isolated yield (%)
Table 3 Arylation of 2-Phenylpyridine (1) with Potassium Aryltri-
fluoroborates 2a–ia
1
2
traceb
74
Cu(OAc)2
AgOAc
Ag2CO3
Ag2O
3a
Pd(OAc)2 (10 mol%)
3
3a
68
Cu(OAc)2 (3 equiv)
BQ (2 equiv)
H
Ar
4
3a
51
+
ArBF3K
N
1,4-dioxane
120 °C, 24 h
N
5
3a
45
6
AgF
3a
25
1
2a–i
3a–i
7
Oxone
3a
15
Entry ArBF3K
Product
Isolated
yield (%)
8
K2S2O8
Cu(OTf)2
Hg(OAc)2
3a
15
9
3a
traceb
traceb
10
3a
BF3K
1
74
a Reaction conditions: 1 (0.44 mmol), PhBF3K (1.10 mmol, 2.5
equiv), Pd(OAc)2 (10 mol%), oxidant (1.32 mmol, 3 equiv), p-benzo-
quinone (BQ; 0.88 mmol, 2 equiv), 1,4-dioxane (15 mL), 120 °C, 24
h.
N
2a
3a
b Analyzed by TLC.
OHC
BF3K
2
65
75
55
65
64
Table 2 Reaction of 2-Phenylpyridine (1) with Potassium Trifluo-
ro(phenyl)borate (2a) in Various Solventsa
N
CHO
2b
Entry
Solvent
1,4-dioxane
THF
Product
3a
Isolated yield (%)
3b
1
2
74
65
61
60
55
55
55
50
50
35
3a
BF3K
3
3
CH2Cl2
EtMe2COH
t-BuOH
benzene
DMF
3a
N
O2N
2c
NO2
4
3a
3c
5
3a
6
3a
MeO
BF3K
4
7
3a
N
OMe
t-Bu
F
2d
8
MeCN
3a
9
DMSO
toluene
3a
3d
10
3a
a Reaction conditions: 1 (0.44 mmol), PhBF3K (1.10 mmol, 2.5
equiv), Pd(OAc)2 (10 mol%), Cu(OAc)2 (1.32 mmol, 3 equiv), BQ
(0.88 mmol, 2 equiv), solvent (15 mL).
t-Bu
BF3K
5
N
2e
3e
perior to boronic acids in the palladium(II)-catalyzed
ortho-arylation reactions.
On the basis of the above initial results, the reactions of
various potassium aryltrifluoroborates 2a–i with 2-phe-
nylpyridine (1) were carried out under the optimal reac-
tion conditions to give the products 3a–i in 20–78% yield
(Table 3). All the reagents gave the ortho-arylation ad-
ducts in good yields except reagent 2i. We suspect that un-
desired side reactions might take place, including
polymerization of reagent 2i, although we did not isolate
F
BF3K
6
N
2f
3f
Synthesis 2009, No. 22, 3757–3764 © Thieme Stuttgart · New York

PAPER
Palladium(II)-Catalyzed ortho Arylation of 2-Phenylpyridines
3759
Table 3 Arylation of 2-Phenylpyridine (1) with Potassium Aryltri-
fluoroborates 2a–ia (continued)
Table 4. In most of the cases, the yields are from modest
to good (59–89%). Lower yields (38% and 30%, respec-
tively) were found with compounds 5d and 5f (entries 4
and 6). The poor yield obtained from 5d could be ex-
plained by the peri interaction in the palladacycle interme-
diate between the hydrogen on C8 of the quinoline, and
that would prevent the formation of the palladacycle inter-
mediate. The lower yield of compound 6f (30%) might be
due to the decreased coordinating ability of the pyridine
bearing an ortho-arylcarbonyl group, in addition to the
formation of a six-membered palladacycle intermediate,
which is considered to be less stable than a five-mem-
bered palladacycle.20 On the other hand, silver(I) acetate
was found to be a better oxidant than copper(II) acetate in
the reactions of compounds 5d and 5e with 2b (entries 4
and 5).
Pd(OAc)2 (10 mol%)
Cu(OAc)2 (3 equiv)
BQ (2 equiv)
H
Ar
+
ArBF3K
N
1,4-dioxane
120 °C, 24 h
N
1
2a–i
3a–i
Entry ArBF3K
Product
Isolated
yield (%)
Cl
BF3K
7
78
N
Cl
2g
Table 4 Arylation of Pyridine Derivatives 5a–f with Potassium Tri-
fluoro(4-formylphenyl)borate (2b)a
3g
Pd(OAc)2 (10 mol%)
Cu(OAc)2 or AgOAc (3 equiv)
BQ (2 equiv)
CHO
pyridine
products
+
Br
BF3K
8
62
20
derivatives
1,4-dioxane
120 °C, 24 h
N
Br
6a–f
5a–f
2h
BF3K
2b
3h
Entry Pyridine
derivative
Product
Isolated
yield (%)
I
BF3K
9
N
I
2i
1
62
3i
a Reaction conditions: 1 (0.44 mmol), ArBF3K (1.10 mmol, 2.5
equiv), Pd(OAc)2 (10 mol%), Cu(OAc)2 (1.32 mmol, 3 equiv), BQ
(0.88 mmol, 2 equiv), 1,4-dioxane (15 mL).
N
N
CHO
5a
6a
CHO
CHO
2
59
89
N
N
CHO
5b
6b
6c
3
N
CHO
N
5c
4
38 (28)b
N
CHO
N
Figure 1 ORTEP drawing of compound 3c
Furthermore, the reactions of pyridine derivatives 5a–f
with potassium trifluoro(4-formylphenyl)borate (2b)
were carried out, and the results are summarized in
5d
6d
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J.-H. Chu et al.
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Table 4 Arylation of Pyridine Derivatives 5a–f with Potassium Tri-
fluoro(4-formylphenyl)borate (2b)a (continued)
In addition, the kinetic isotope effect was investigated by
using 2-(o-deuteriophenyl)pyridine (1-D) to react with 2a,
to form 3a-D and 3a (Scheme 3). The kH/kD ratio for the
C–H bond activation when potassium trifluoro(phe-
nyl)borate (2a) and phenylboronic acid (4a) were used
was determined to be 1.09 and 1.03 (compared with the
standard 1H NMR spectrum of 3a), respectively. This in-
dicates that the palladium(II)-catalyzed C–H bond cleav-
age of 2-phenylpyridine (1) does not occur in the rate-
determining step. Thus, the reaction of the palladacycle
with trifluoroborates or boronic acids is still a viable op-
tion for the rate-determining step.
Pd(OAc)2 (10 mol%)
CHO
Cu(OAc)2 or AgOAc (3 equiv)
BQ (2 equiv)
pyridine
products
+
derivatives
1,4-dioxane
120 °C, 24 h
6a–f
5a–f
BF3K
2b
Entry Pyridine
derivative
Product
Isolated
yield (%)
CHO
N
55 (21)b
N
5
D
N
Pd(OAc)2 (10 mol%)
Cu(OAc)2 (3 equiv)
BQ (2 equiv)
5e
3a-D
H
D
6e
+
+
1,4-dioxane
120 °C, 24 h
CHO
N
X
O
2a R = BF3K
4a R = B(OH)2
H
1-D
O
6
30
N
N
3a
5f
N
kH/kD for 2a = 1.09
kH/kD for 4a = 1.03
6f
a Reaction conditions: 1 (0.44 mmol), PhBF3K (1.10 mmol, 2.5
equiv), Pd(OAc)2 (10 mol%), Cu(OAc)2 (1.32 mmol, 3 equiv), BQ
(0.88 mmol, 2 equiv), 1,4-dioxane (15 mL).
Scheme 3
b The yield reported first was that obtained when AgOAc (1.32 mmol,
3 equiv) was used as the oxidant, whereas the yield in the parentheses
was obtained when Cu(OAc)2 (1.32 mmol, 3 equiv) was used as the
oxidant.
Finally, a possible mechanism for the present palladi-
um(II)-catalyzed ortho arylation of 2-phenylpyridine (1)
via C–H bond activation is proposed, as shown in
Scheme 4. Coordination of 2-phenylpyridine (1) to palla-
dium(II) acetate is followed by an ortho C–H bond activa-
tion to form a pyridine palladacycle I. Subsequently, the
aryl group of potassium aryltrifluoroborate 2 bonds to the
palladium center of I via ligand exchange and release of
potassium fluoride and difluoroboron acetate.22 Benzo-
quinone could act as a ligand to coordinate with palladium
to form intermediate II.5d,21 Finally, intermediate II is fur-
ther converted into ortho-arylated product 3. In addition,
the released palladium(0) is reoxidized by copper(II) ace-
tate and p-benzoquinone to regenerate palladium(II),
which would continue the catalytic cycle.
To obtain detailed information on the catalytic mecha-
nism, we prepared the pyridine palladacycle I according
to a literature procedure,9i and carried out the reaction of I
with potassium trifluoro(phenyl)borate (2a) in the pres-
ence (or absence) of p-benzoquinone (BQ) (Scheme 2).
O
Ac
2a with
2a without
BQ
no desired
product
observed
BQ (2 equiv)
Pd
3a
2
1,4-dioxane,
120 °C, 4 h
80%
1,4-dioxane,
120 °C, 4 h
N
To further demonstrate that the reactive efficiency of a tri-
fluoroborate reagent is better than that of a boronic acid in
other C–H functionalization reactions, acetanilide (7) was
utilized to react with either potassium trifluoro(phe-
nyl)borate (2a) or phenylboronic acid (4a) to form N-(bi-
phenyl-2-yl)acetamide (8) (Scheme 5).23 The yield
obtained with trifluoroborate 2a (66%) was higher than
that achieved with boronic acid 4a (38%).
pyridine
palladacycle
I
Scheme 2
We found that 3a was obtained in 80% yield when two
equivalents of p-benzoquinone are presented in the reac-
tion mixture. However, in the absence of p-benzoquinone,
no formation of the desired product was observed. We
therefore conclude that p-benzoquinone is an essential re-
agent in the transmetalation–reductive elimination step,21
and that pyridine palladacycle I might be the key interme-
diate in the C–H bond activation process.
In summary, we have demonstrated that potassium aryltri-
fluoroborate salts are more efficient reagents than the cor-
responding boronic acids in palladium(II)-catalyzed ortho
arylation of 2-phenylpyridine and pyridine derivatives.
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PAPER
Palladium(II)-Catalyzed ortho Arylation of 2-Phenylpyridines
3761
ortho-Arylated 2-Phenylpyridine Derivatives 3a–i and 6a–f;
General Procedure
Cu(I) + hydroquinone
1
HOAc
Pd(OAc)2
A well-stirred soln of 2-phenylpyridine (1; 68.0 mg, 0.44 mmol),
the appropriate potassium aryltrifluoroborate 2 (2.5 equiv),
Cu(OAc)2 (3 equiv), BQ (2 equiv), and Pd(OAc)2 (10 mol%) in 1,4-
dioxane (15 mL) was heated to 120 °C and stirred at this tempera-
ture for 24 h. After cooling to r.t., the soln was filtered through filter
paper under vacuum and washed with H2O (2 × 5 mL). The aqueous
layer was extracted with CH2Cl2 (2 × 10 mL), and the combined or-
ganic extracts were dried (MgSO4). After filtration and evaporation
under vacuum, the residue was purified by chromatography (silica
gel, n-hexane–EtOAc, 20:1 to 5:1); this gave the appropriate ortho-
arylated 2-phenylpyridine of the series 3a–i.
Ac
O
Cu(II) + BQ
Pd
2
N
Pd(0)
R
I
BF3K
R
2
+
BQ
Pd
N
O
Yields: 3a: 75.2 mg (74%); 3b: 74.1 mg (65%); 3c: 91.1 mg (75%);
3d: 63.2 mg (55%); 3e: 82.1 mg (65%); 3f: 70.1 mg (64%); 3g: 90.9
mg (78%); 3h: 84.6 mg (62%); 3i: 31.4 mg (20%).
N
KF
+
R
O
F2BOAc
3
Under the same reaction conditions, pyridine derivatives 5a–f were
converted into pyridine derivatives 6a–f. The amounts of pyridine
derivatives 5a–f that were used are as follows: 5a: 74.4 mg, 0.44
mmol; 5b: 80.5 mg, 0.44 mmol; 5c: 90.2 mg, 0.44 mmol; 5d: 90.0
mg, 0.44 mmol; 5e: 78.8 mg, 0.44 mmol; 5f: 80.5 mg, 0.44 mmol.
II
Scheme 4 Proposed mechanism of the palladium(II)-catalyzed re-
action of 2-phenylpyridine (1) with potassium aryltrifluoroborates 2
O
O
Yields: 6a: 74.5 mg (62%); 6b: 74.5 mg (59%); 6c: 121.0 mg
(89%); 6d: 51.7 mg (38%); 6e: 68.5 mg (55%); 6f: 37.9 mg (30%).
Pd(OAc)2 (5 mol%)
Cu(OTf)2 (1 equiv)
Ag2O (1 equiv)
HN
HN
2-(Biphenyl-2-yl)pyridine (3a)1i
+
Ph
toluene, 120 °C, 24 h
White solid; mp 79–80 °C (Lit.1i 86.5–87.5 °C); Rf = 0.69 (n-hex-
ane–EtOAc, 5:2).
R
1H NMR (400 MHz, CDCl3): d = 6.88 (dt, J = 8.0, 1.0 Hz, 1 H),
7.10 (ddd, J = 7.5, 4.8, 1.2 Hz, 1 H), 7.14–7.18 (m, 2 H), 7.21–7.25
(m, 3 H), 7.38 (td, J = 7.5, 1.7 Hz, 1 H), 7.42–7.46 (m, 3 H), 7.68–
7.71 (m, 1 H), 8.63 (ddd, J = 4.8, 1.7, 1.2 Hz, 1 H).
7
8 66% (from 2a)
38% (from 4a)
2a R = BF3K
4a R = B(OH)2
Scheme 5
13C NMR (100 MHz, CDCl3): d = 121.3 (CH), 125.4 (CH), 126.7
(CH), 127.6 (CH), 128.0 (CH × 2), 128.5 (CH), 129.7 (CH × 2),
130.4 (CH), 130.5 (CH), 135.2 (CH), 139.5 (Cq), 140.6 (Cq), 141.3
(Cq), 149.4 (CH), 159.2 (Cq).
MS (EI, 70 eV): m/z (%) = 231 (27) [M+], 230 (100) [M – H+], 84
(15).
From the point of view of reagent and atom economy,
some reactions using aryl halides have the advantage of
requiring no oxidant and producing less waste.2,24 The re-
action using Ar–H (instead of Ar–M) in the presence of
oxidants still has sufficient merits,5d although the main
drawback is the use of excess amounts of oxidants
[Cu(OAc)2 (3 equiv), BQ (2 equiv)]. Therefore, the tran-
sition-metal-catalyzed C–C bond formation via C–H bond
activation can provide an efficient tool in organic synthe-
sis. At the same time, this finding suggests that potassium
aryltrifluoroborate salts could be further explored in C–C
bond formation of other substrates.
HRMS (EI): m/z [M]+ calcd for C17H13N: 231.1048; found:
231.1040.
2¢-(2-Pyridyl)biphenyl-4-carbaldehyde (3b)
Colorless viscous liquid; Rf = 0.44 (n-hexane–EtOAc, 5:2).
1H NMR (400 MHz, CDCl3): d = 6.96 (d, J = 8.0 Hz, 1 H), 7.14
(ddd, J = 7.4, 4.8, 0.8 Hz, 1 H), 7.32 (d, J = 8.4 Hz, 2 H), 7.44–7.54
(m, 4 H), 7.69–7.71 (m, 1 H), 7.75 (d, J = 8.4 Hz, 2 H), 8.60 (ddd,
J = 4.9, 1.6, 0.8 Hz, 1 H), 9.98 (s, 1 H).
Solvents were purchased from Echo, Mallinckrodt (ACS grade; n-
hexane, EtOAc, and CH2Cl2) and Scharlau (1,4-dioxane). Reagents
were purchased from Aldrich (potassium aryltrifluoroborates),
Acros [97% 2-phenylpyridine, 99% Cu(OAc)2, and 99% AgOAc],
Alfa (98+% p-benzoquinone), TCI (pyridine derivatives), and
Seedchem [Pd(OAc)2]. All the solvents and reagents were used
without further purification. 1H NMR spectra were obtained on 300-
MHz Bruker AVIII-300 and 400-MHz Varian Unity plus 400 spec-
trometers. Natural-abundance 13C NMR spectra were obtained with
the use of pulse FT on a Varian Unity plus 400 (400-MHz NMR)
spectrometer operating at 100 MHz. Chemical shifts are given rela-
tive to the solvent (usually CDCl3) peak as an internal standard. The
reference peak for 1H is TMS (d = 0.00), and for 13C it is the central
peak at d = 77.0. Low- and high-resolution mass spectrometry was
performed on a Finnigan/Thermo Quest MAT 95XL spectrometer.
Melting points were determined using a Barnstead International
Electrothermal melting point meter IA1101D.
13C NMR (100 MHz, CDCl3): d = 116.1 (CH), 121.7 (CH), 125.2
(CH), 128.5 (CH), 128.7 (CH), 129.5 (CH × 2), 130.3 (CH × 2),
130.7 (CH), 134.6 (Cq), 135.7 (CH), 139.3 (Cq), 139.6 (Cq), 147.9
(Cq), 149.5 (CH), 158.8 (Cq), 192.0 (CH).
MS (EI, 70 eV): m/z (%) = 259 (37) [M+], 258 (100) [M – H+], 84
(63).
HRMS (EI): m/z [M]+ calcd for C18H13NO: 259.0997; found:
259.0996.
2-(3¢-Nitrobiphenyl-2-yl)pyridine (3c)
White solid; mp 102–103 °C; Rf = 0.56 (n-hexane–EtOAc, 5:2).
1H NMR (400 MHz, CDCl3): d = 7.02 (dt, J = 8.0, 0.8 Hz, 1 H),
7.14 (ddd, J = 7.4, 5.0, 0.8 Hz, 1 H), 7.34–7.56 (m, 6 H), 7.67–7.70
(m, 1 H), 8.06–8.09 (m, 2 H), 8.57 (ddd, J = 4.8, 1.8, 0.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 121.6 (CH), 121.8 (CH), 124.3
(CH), 125.0 (CH), 128.7 (CH), 128.8 (CH), 128.9 (CH), 130.3
Synthesis 2009, No. 22, 3757–3764 © Thieme Stuttgart · New York

3762
J.-H. Chu et al.
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(CH), 130.7 (CH), 135.8 (CH × 2), 138.2 (Cq), 139.7 (Cq), 143.1
(Cq), 148.1 (Cq), 149.6 (CH), 158.6 (Cq).
(CH × 2), 132.8 (Cq), 135.5 (CH), 139.3 (Cq), 139.5 (Cq), 139.8
(Cq), 149.5 (CH), 159.0 (Cq).
MS (EI, 70 eV): m/z (%) = 276 (22) [M+], 275 (64) [M – H+], 229
MS (EI, 70 eV): m/z (%) = 266 (4) [M+ + 1], 264 (11) [M+ – 1], 84
(100), 202 (21), 84 (23).
(100), 47 (22).
HRMS (EI): m/z [M]+ calcd for C17H12N2O2: 276.0899; found:
HRMS (EI): m/z [M]+ calcd for C17H1235ClN: 265.0658; found:
276.0894.
265.0653.
2-(4¢-Methoxybiphenyl-2-yl)pyridine (3d)3b
Colorless viscous liquid; Rf = 0.72 (n-hexane–EtOAc, 5:2).
2-(4¢-Bromobiphenyl-2-yl)pyridine (3h)
Colorless viscous liquid; Rf = 0.69 (n-hexane–EtOAc, 5:2).
1H NMR (400 MHz, CDCl3): d = 3.78 (s, 3 H), 6.77 (d, J = 8.8 Hz,
2 H), 6.90 (d, J = 8.0 Hz, 1 H), 7.07 (d, J = 8.8 Hz, 2 H), 7.10 (ddd,
J = 7.5, 5.0, 1.2 Hz, 1 H), 7.38–7.45 (m, 4 H), 7.66–7.68 (m, 1 H),
8.64 (ddd, J = 5.0, 1.8, 1.0 Hz, 1 H).
1H NMR (400 MHz, CDCl3): d = 6.92 (dt, J = 8.2, 1.2 Hz, 1 H),
7.02 (d, J = 6.8 Hz, 2 H), 7.13 (ddd, J = 7.3, 1.2 Hz, 1 H), 7.36 (d,
J = 8.2 Hz, 2 H), 7.39–7.49 (m, 4 H), 7.66–7.68 (m, 1 H), 8.62 (ddd,
J = 4.8, 1.8, 1.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 55.2 (CH3), 113.5 (CH × 2),
121.3 (CH), 125.4 (CH), 127.3 (CH), 128.5 (CH), 130.4 (CH),
130.5 (CH), 130.8 (CH × 2), 133.7 (Cq), 135.2 (CH), 139.4 (Cq),
140.2 (Cq), 149.4 (CH), 158.5 (Cq), 159.5 (Cq).
13C NMR (100 MHz, CDCl3): d = 121.0 (Cq), 121.5 (CH), 125.2
(CH), 128.0 (CH), 128.6 (CH), 130.3 (CH), 130.6 (CH), 131.2
(CH × 2), 131.3 (CH × 2), 135.5 (CH), 139.3 (Cq), 139.4 (Cq), 140.3
(Cq), 149.5 (CH), 159.0 (Cq).
MS (EI, 70 eV): m/z (%) = 261 (14) [M+], 217 (14), 84 (100), 47
MS (EI, 70 eV): m/z (%) = 310 (24) [M+], 308 (23) [M+ – 2], 84
(26).
(100), 47 (35).
HRMS (EI): m/z [M]+ calcd for C18H15NO: 261.1154; found:
HRMS (EI): m/z [M]+ calcd for C17H12BrN: 309.0153; found:
261.1154.
309.0152.
2-(4¢-tert-Butylbiphenyl-2-yl)pyridine (3e)
Colorless viscous liquid; Rf = 0.72 (n-hexane–EtOAc, 5:2).
2-(4¢-Iodobiphenyl-2-yl)pyridine (3i)
Colorless viscous liquid; Rf = 0.69 (n-hexane–EtOAc, 5:2).
1H NMR (400 MHz, CDCl3): d = 1.29 (s, 9 H), 6.89 (d, J = 8.0 Hz,
1 H), 7.08 (d, J = 8.8 Hz, 2 H), 7.11 (ddd, J = 6.6 Hz, 1 H), 7.23–
7.26 (m, 3 H), 7.37 (td, J = 8.0, 1.6 Hz, 1 H), 7.43–7.45 (m, 2 H),
7.68–7.70 (m, 1 H), 8.64 (ddd, J = 5.0, 1.8, 1.2 Hz, 1 H).
1H NMR (400 MHz, CDCl3): d = 6.89 (d, J = 8.4 Hz, 2 H), 6.93 (d,
J = 8.0 Hz, 1 H), 7.14 (ddd, J = 7.3, 4.9, 1.2 Hz, 1 H), 7.38–7.41 (m,
1 H), 7.44–7.50 (m, 3 H), 7.56 (d, J = 8.4 Hz, 2 H), 7.66–7.68 (m, 1
H), 8.62 (ddd, J = 4.9, 1.8, 1.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 31.3 (CH3), 34.4 (Cq), 121.3
(CH), 124.9 (CH × 2), 125.5 (CH), 127.4 (CH), 128.5 (CH), 129.3
(CH × 2), 130.5 (CH × 2), 135.1 (CH), 138.2 (Cq), 139.4 (Cq), 140.5
(Cq), 149.4 (CH), 149.6 (Cq), 159.4 (Cq).
13C NMR (100 MHz, CDCl3): d = 92.6 (Cq), 121.5 (CH), 125.3
(CH), 128.0 (CH), 128.7 (CH), 130.2 (CH), 130.6 (CH), 131.5
(CH × 2), 135.5 (CH), 137.2 (CH × 2), 139.4 (Cq × 2), 140.9 (Cq),
149.5 (CH), 159.0 (Cq).
MS (EI, 70 eV): m/z (%) = 287 (50) [M+], 286 (100) [M – H+], 272
MS (EI, 70 eV): m/z (%) = 357 (39) [M+], 356 (100) [M – H+], 228
(27), 84 (67).
(53), 84 (68).
HRMS (EI): m/z [M]+ calcd for C21H21N: 287.1674; found:
HRMS (EI): m/z [M]+ calcd for C17H12IN: 357.0014; found:
287.1676.
357.0014.
2-(4¢-Fluorobiphenyl-2-yl)pyridine (3f)1i
Colorless viscous liquid; Rf = 0.69 (n-hexane–EtOAc, 5:2).
5¢-Methyl-2¢-(2-pyridyl)biphenyl-4-carbaldehyde (6a)
Colorless viscous liquid; Rf = 0.47 (n-hexane–EtOAc, 5:2).
1H NMR (400 MHz, CDCl3): d = 6.88–6.95 (m, 3 H), 7.09–7.13 (m,
3 H), 7.39–7.48 (m, 4 H), 7.66–7.68 (m, 1 H), 8.63 (ddd, J = 5.0,
1.8, 1.0 Hz, 1 H).
1H NMR (400 MHz, CDCl3): d = 2.46 (s, 3 H), 6.92 (dt, J = 8.0, 1.2
Hz, 1 H), 7.12 (ddd, J = 7.4, 4.8, 1.2 Hz, 1 H), 7.30–7.35 (m, 4 H),
7.43 (td, J = 8.2, 1.6 Hz, 1 H), 7.60 (d, J = 7.6 Hz, 1 H), 7.75 (d,
J = 8.4 Hz, 2 H), 8.58 (ddd, J = 4.8, 1.8, 1.2 Hz, 1 H), 9.98 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 21.2 (CH3), 121.5 (CH), 125.2
(CH), 129.2 (CH), 129.5 (CH × 2), 130.3 (CH × 2), 130.6 (CH),
131.0 (CH), 134.6 (Cq), 135.6 (CH), 136.8 (Cq), 138.6 (Cq), 139.2
(Cq), 148.1 (Cq), 149.4 (CH), 158.8 (Cq), 192.0 (CH).
13C NMR (100 MHz, CDCl3): d = 115.0 (d, JC-F = 20.0 Hz, CH × 2),
121.4 (CH), 125.3 (CH), 127.8 (CH), 128.6 (CH), 130.4 (d, JC-F
=
12.1 Hz, CH × 2), 131.1 (CH), 131.2 (CH), 135.4 (CH), 137.3 (d,
JC-F = 3.8 Hz, Cq), 139.5 (Cq × 2), 149.5 (CH), 159.1 (Cq), 161.9 (d,
JC-F = 240.0 Hz, Cq).
MS (EI, 70 eV): m/z (%) = 249 (14) [M+], 248 (43) [M – H+], 84
MS (EI, 70 eV): m/z (%) = 273 (40) [M+], 272 (100) [M – H+], 84
(100), 47 (26).
(53).
HRMS (EI): m/z [M]+ calcd for C17H12FN: 249.0954; found:
HRMS (EI): m/z [M]+ calcd for C19H15NO: 273.1154; found:
249.0954.
273.1154.
2-(4¢-Chlorobiphenyl-2-yl)pyridine (3g)
Colorless viscous liquid; Rf = 0.69 (n-hexane–EtOAc, 5:2)
6-(2-Pyridyl)biphenyl-3,4¢-dicarbaldehyde (6b)
Colorless viscous liquid; Rf = 0.25 (n-hexane–EtOAc, 5:2)
1H NMR (400 MHz, CDCl3): d = 6.92 (dt, J = 8.0, 1.2 Hz, 1 H),
7.08 (d, J = 8.6 Hz, 2 H), 7.13 (ddd, J = 7.5, 4.8, 1.2 Hz, 1 H), 7.21
(d, J = 8.6 Hz, 2 H), 7.39–7.50 (m, 4 H), 7.66–7.69 (m, 1 H), 8.62
(ddd, J = 5.0, 1.8, 1.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 121.5 (CH), 125.2 (CH), 127.9
(CH), 128.3 (CH × 2), 128.6 (CH), 130.3 (CH), 130.6 (CH), 130.9
1H NMR (400 MHz, CDCl3): d = 6.98 (d, J = 7.6 Hz, 1 H), 7.20
(ddd, J = 7.5, 4.9, 1.2 Hz, 1 H), 7.35 (d, J = 8.0 Hz, 2 H), 7.49 (td,
J = 7.8, 1.6 Hz, 1 H), 7.79 (d, J = 8.0 Hz, 2 H), 7.90 (d, J = 7.6 Hz,
1 H), 7.98 (d, J = 1.6 Hz, 1 H), 8.03 (dd, J = 7.6, 1.6 Hz, 1 H), 8.64
(ddd, J = 4.8, 1.6, 0.8 Hz, 1 H), 10.00 (s, 1 H), 10.14 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 122.5 (CH), 125.1 (CH), 129.5
(CH), 129.7 (CH × 2), 130.2 (CH × 2), 131.4 (CH), 131.6 (CH),
Synthesis 2009, No. 22, 3757–3764 © Thieme Stuttgart · New York

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Palladium(II)-Catalyzed ortho Arylation of 2-Phenylpyridines
3763
135.1 (Cq), 135.9 (CH), 136.3 (Cq), 140.3 (Cq), 145.1 (Cq), 146.4
(Cq), 149.8 (CH), 157.4 (Cq), 191.6 (CH), 191.8 (CH).
MS (EI, 70 eV): m/z (%) = 287 (41) [M+], 286 (100) [M – H+], 84
13C NMR (100 MHz, CDCl3): d = 123.8 (CH), 126.4 (CH), 128.0
(CH), 129.5 (CH × 2), 129.7 (CH × 4), 131.1 (CH), 134.8 (Cq),
136.6 (CH), 138.3 (Cq), 140.7 (Cq), 147.2 (Cq), 148.8 (CH), 154.2
(Cq), 191.8 (CH), 197.7 (Cq).
MS (EI, 70 eV): m/z (%) = 287 (12) [M+], 258 (24), 181 (17), 152
(19), 84 (100), 47 (23).
(97), 47 (30).
HRMS (EI): m/z [M]+ calcd for C19H13NO2: 287.0946; found:
287.0946.
HRMS (EI): m/z [M]+ calcd for C19H13NO2: 287.0946; found:
2¢-(1-Isoquinolyl)biphenyl-4-carbaldehyde (6c)
287.0946.
Colorless viscous liquid; Rf = 0.42 (n-hexane–EtOAc, 5:2).
2-Phenylpyridine Palladacycle I9i,25
1H NMR (400 MHz, CDCl3): d = 7.23 (d, J = 8.2 Hz, 2 H), 7.35
(ddd, J = 8.3, 6.9, 1.2 Hz, 1 H), 7.52 (d, J = 8.2 Hz, 2 H), 7.55–7.64
(m, 7 H), 7.76 (d, J = 8.0 Hz, 1 H), 8.51 (d, J = 5.6 Hz, 1 H), 9.81
(s, 1 H).
13C NMR (100 MHz, CDCl3): d = 120.1 (CH), 126.8 (CH), 127.1
(CH × 2), 127.3 (Cq), 128.2 (CH), 129.0 (CH), 129.2 (CH × 2),
129.7 (CH × 2), 129.9 (CH), 130.0 (CH), 130.9 (CH), 134.4 (Cq),
136.1 (Cq), 138.3 (Cq), 140.4 (Cq), 142.0 (CH), 147.5 (Cq), 160.5
(Cq), 191.9 (CH).
A well-stirred soln of 2-phenylpyridine (1) (345 mg, 2.23 mmol)
with Pd(OAc)2 (500 mg, 2.23 mmol) in AcOH (50 mL) was heated
at 100 °C for 3 h. After cooling down, the soln was filtered through
a pad of Celite. The filtrate was evaporated under reduced pressure
and the residue was recrystallized from CH2Cl2 to give 2-phenylpy-
ridine palladacycle I.
Yield: 610 mg (85%); yellow solid; mp 258–260 °C (dec).
1H NMR (300 MHz, CDCl3): d = 2.27 (s, 6 H), 6.45 (td, J = 7.2, 1.2
Hz, 2 H), 6.80–6.94 (m, 8 H), 7.08 (d, J = 8.1 Hz, 2 H), 7.36 (td,
J = 8.5, 1.5 Hz, 2 H), 7.87 (d, J = 5.7 Hz, 2 H).
MS (EI, 70 eV): m/z (%) = 309 (70) [M+], 308 (100) [M – H+], 278
(23), 84 (49).
HRMS (EI): m/z [M]+ calcd for C22H15NO: 309.1154; found:
309.1151.
Kinetic Isotope Investigation: Phenylation of 2-(o-Deuteriophe-
nyl)pyridine (1-D)26 with Trifluoroborate 2a and Boronic Acid
4a
The experimental procedure was the same as that used for ortho-
arylated 2-phenylpyridine derivatives 3a–i. The following reagents
were used: 1-D (51.0 mg, 0.33 mmol), 2a (150 mg, 0.82 mmol), 4a
(100 mg, 0.82 mmol), Pd(OAc)2 (7.30 mg, 0.03 mmol), Cu(OAc)2
(178 mg, 0.98 mmol), p-benzoquinone (70.6 mg, 0.65 mmol), 1,4-
dioxane (15 mL).
2¢-(2-Quinolyl)biphenyl-4-carbaldehyde (6d)
Colorless viscous liquid; Rf = 0.61 (n-hexane–EtOAc, 5:2).
1H NMR (400 MHz, CDCl3): d = 6.98 (d, J = 8.8 Hz, 1 H), 7.37 (d,
J = 8.0 Hz, 2 H), 7.49–7.60 (m, 4 H), 7.72 (d, J = 8.4 Hz, 2 H), 7.75
(td, J = 7.6, 1.6 Hz, 2 H), 7.84–7.87 (m, 2 H), 8.12 (dd, J = 8.4, 1.2
Hz, 1 H), 9.95 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 123.2 (CH), 126.6 (CH), 127.5
(CH), 128.0 (Cq), 128.7 (CH), 129.0 (CH), 129.5 (CH), 129.6
(CH × 3), 130.3 (CH), 130.4 (CH × 2), 131.0 (CH), 134.7 (Cq),
135.3 (CH), 139.5 (Cq), 140.0 (Cq), 147.7 (Cq), 148.2 (Cq), 159.2
(Cq), 192.0 (CH).
MS (EI, 70 eV): m/z (%) = 309 (4) [M+], 308 (7) [M – H+], 84 (100),
47 (10).
N-(Biphenyl-2-yl)acetamide (8) by Phenylation of Acetanilide
(7) with Trifluoroborate 2a and Boronic Acid 4a
The previously reported experimental procedure was followed.9g
The following reagents were used: 7 (40.0 mg, 0.30 mmol), 2a (109
mg, 0.60 mmol) or 4a (72.0 mg, 0.60 mmol), Pd(OAc)2 (3.30 mg,
0.01 mmol), Cu(OTf)2 (97.0 mg, 0.30 mmol), Ag2O (69.0 mg, 0.30
mmol), toluene (10 mL).
HRMS (EI): m/z [M]+ calcd for C22H15NO: 309.1154; found:
309.1158.
Yield (8): 41.8 mg (66%) from 2a; 24.1 mg (38%) from 4a.
N-(Biphenyl-2-yl)acetamide (8)2,27
White solid; mp 101–103 °C; Rf = 0.54 (n-hexane–EtOAc, 1:1).
4-(Benzo[H]quinolin-10-yl)benzaldehyde (6e)
Colorless viscous liquid; Rf = 0.56 (n-hexane–EtOAc, 5:2).
1H NMR (300 MHz, CDCl3): d = 2.02 (s, 3 H), 7.12–7.24 (m, 3 H),
7.34–7.52 (m, 6 H), 8.25 (d, J = 8.1 Hz, 1 H).
1H NMR (400 MHz, CDCl3): d = 7.34 (dd, J = 8.0, 4.4 Hz, 1 H),
7.50–7.52 (m, 3 H), 7.70–7.75 (m, 2 H), 7.89 (d, J = 8.8 Hz, 1 H),
7.92 (d, J = 8.4 Hz, 2 H), 7.98 (dd, J = 8.0, 1.2 Hz, 1 H), 8.11 (dd,
J = 8.2, 1.6 Hz, 1 H), 8.37 (dd, J = 8.2, 1.6 Hz, 1 H), 10.12 (s, 1 H).
Acknowledgment
13C NMR (100 MHz, CDCl3): d = 121.3 (CH), 126.2 (CH), 127.1
(CH), 127.3 (Cq), 128.2 (CH), 128.6 (CH), 128.8 (Cq), 129.1
(CH × 2), 129.4 (CH × 2), 130.8 (CH), 134.1 (Cq), 134.9 (Cq), 135.3
(CH), 140.2 (Cq), 146.3 (Cq), 146.9 (CH), 153.4 (Cq), 192.5 (CH).
We thank the National Science Council of Taiwan, R.O.C., for fi-
nancial support.
References
MS (EI, 70 eV): m/z (%) = 283 (18) [M+], 282 (52) [M – H+], 84
(100), 47 (20).
(1) (a) Özdemir, I.; Demir, S.; Cetinkaya, B.; Gourlaouen, C.;
Maseras, F.; Bruneau, C.; Dixneuf, P. H. J. Am. Chem. Soc.
2008, 130, 1156. (b) Li, B.-J.; Yang, S.-D.; Shi, Z.-J. Synlett
2008, 949. (c) Stuart, D. R.; Fagnou, K. Science 2007, 316,
1172. (d) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev.
2007, 107, 174. (e) Ackermann, L.; Born, R.; Álvarez-
Bercedo, P. Angew. Chem. Int. Ed. 2007, 46, 6364.
HRMS (EI): m/z [M]+ calcd for C20H13NO: 283.0997; found:
283.0998.
2¢-Picolinoylbiphenyl-4-carbaldehyde (6f)
Colorless viscous liquid; Rf = 0.36 (n-hexane–EtOAc, 5:2)
1H NMR (400 MHz, CDCl3): d = 7.26 (ddd, J = 7.6, 4.8, 1.2 Hz, 1
H), 7.43 (d, J = 8.0 Hz, 2 H), 7.48 (dd, J = 8.0, 1.2 Hz, 1 H), 7.55
(td, J = 7.5, 1.2 Hz, 1 H), 7.64 (td, J = 7.5, 1.2 Hz, 1 H), 7.67–7.72
(m, 4 H), 7.89 (dt, J = 7.5, 1.2 Hz, 1 H), 8.44 (ddd, J = 4.8, 1.6, 0.8
Hz, 1 H), 9.91 (s, 1 H).
(f) Ackermann, L.; Althammer, A.; Born, R. Angew. Chem.
Int. Ed. 2006, 45, 2619. (g) Kakiuchi, F.; Chatani, N. Adv.
Synth. Catal. 2003, 345, 1077. (h) Jia, C.; Kitamura, T.;
Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633. (i) Oi, S.;
Fukita, S.; Hirata, N.; Watanuki, N.; Miyano, S.; Inoue, Y.
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3764
J.-H. Chu et al.
PAPER
(12) (a) Vedejs, E.; Chapman, R. W.; Field, S. C.; Lin, S.;
Schrimpf, M. R. J. Org. Chem. 1995, 60, 3020. (b) Vedejs,
E.; Fields, S. C.; Hayashi, R.; Hitchcock, S. R.; Powell, D.
R.; Schrimpt, M. R. J. Am. Chem. Soc. 1999, 121, 2460.
(13) Darses, S.; Genêt, J.-P.; Brayer, J.-L.; Demoute, J.-P.
Tetrahedron Lett. 1997, 38, 4393.
(14) Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393.
(15) (a) Darses, S.; Genêt, J.-P. Chem. Rev. 2008, 108, 288.
(b) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40,
275. (c) Stefani, H. A.; Cella, R.; Vieira, A. S. Tetrahedron
2007, 63, 3623.
(16) Molander, G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302.
(17) (a) Zhao, J.; Zhang, Y.; Cheng, K. J. Org. Chem. 2008, 73,
7428. (b) Ge, H.; Niphakis, M. J.; Georg, G. I. J. Am. Chem.
Soc. 2008, 130, 3708. (c) Wang, D.-H.; Mei, T.-S.; Yu, J.-Q.
J. Am. Chem. Soc. 2008, 130, 17676.
(18) Four different equivalents (1, 2, 2.5, and 3) of potassium
trifluoro(phenyl)borate(2a) were examined under the
reaction conditions, and the yield of product 3a was
determined to be 52%, 68%, 74%, and 75%, respectively.
According to these results, 2.5 equivalents of potassium
aryltrifluoroborates were chosen to be the optimal amount.
(19) CCDC 715155 contains the supplementary crystallographic
data of compound 3c. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
Org. Lett. 2001, 3, 2579. (j) Dyker, G. Angew. Chem. Int.
Ed. 1999, 38, 1698.
(2) Yang, S.; Li, B.; Wan, X.; Shi, Z. J. Am. Chem. Soc. 2007,
129, 6066.
(3) (a) Chen, X.; Li, J. J.; Hao, X. S.; Goodhue, C. E.; Yu, J. Q.
J. Am. Chem. Soc. 2006, 128, 78. (b) Oi, S.; Fukita, S.;
Inoue, Y. Chem. Commun. 1998, 2439.
(4) Norinder, J.; Matsumoto, A.; Yoshikai, N.; Nakamura, E.
J. Am. Chem. Soc. 2008, 130, 5858.
(5) (a) Chiong, H. A.; Pham, Q.-N.; Daugulis, O. J. Am. Chem.
Soc. 2007, 129, 9879. (b) Stuart, D. R.; Villemure, E.;
Fagnou, K. J. Am. Chem. Soc. 2007, 129, 12072. (c) Cai,
G.; Fu, Y.; Li, Y.; Wan, X.; Shi, Z. J. Am. Chem. Soc. 2007,
129, 7666. (d) Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc.
2007, 129, 11904. (e) Dwight, T. A.; Rue, N. R.; Charyk, D.;
Josselyn, R.; DeBoef, B. Org. Lett. 2007, 9, 3137. (f) Xia,
J.-B.; You, S.-L. Organometallics 2007, 26, 4869. (g) Hull,
K. L.; Lanni, E. L.; Sanford, M. S. J. Am. Chem. Soc. 2006,
128, 14047.
(6) Zhang, Y.; Feng, J.; Li, C. J. J. Am. Chem. Soc. 2008, 130,
2900.
(7) (a) Thu, H.-Y.; Yu, W.-Y.; Che, C.-M. J. Am. Chem. Soc.
2006, 128, 9048. (b) Wasa, M.; Yu, J.-Q. J. Am. Chem. Soc.
2008, 130, 14058. (c) Tsang, W. C. P.; Munday, R. H.;
Brasche, G.; Zheng, N.; Buchwald, S. L. J. Org. Chem.
2008, 73, 7603.
(8) Yu, W. Y.; Sit, W. N.; Lai, K. M.; Zhou, Z.; Chen, A. S. C.
J. Am. Chem. Soc. 2008, 130, 3304.
(20) Li, J.-J.; Giri, R.; Yu, J.-Q. Tetrahedron 2008, 64, 6979; and
references cited therein.
(9) (a) Kirchberg, S.; Vogler, T.; Studer, A. Synlett 2008, 2841.
(b) Vogler, T.; Studer, A. Org. Lett. 2008, 10, 129.
(c) Yang, S. D.; Sun, C.-L.; Fang, Z.; Li, B.-J.; Li, Y.-Z.; Shi,
Z.-J. Angew. Chem. Int. Ed. 2008, 47, 1473. (d) Wang, D.-
H.; Wasa, M.; Giri, R.; Yu, J.-Q. J. Am. Chem. Soc. 2008,
130, 7190. (e) Shi, B.-F.; Maugel, N.; Zhang, Y.-H.; Yu, J.-
Q. Angew. Chem. Int. Ed. 2008, 47, 4882. (f) Chu, J.-H.;
Chen, C.-C.; Wu, M.-J. Organometallics 2008, 27, 5173.
(g) Shi, Z.; Li, B.; Wan, X.; Cheng, J.; Fang, Z.; Cao, B.;
Qin, C.; Wang, Y. Angew. Chem. Int. Ed. 2007, 46, 5554.
(h) Giri, R.; Maugel, N.; Li, J. J.; Wang, D. H.; Breazzano,
S. P.; Saunders, L. B.; Yu, J. Q. J. Am. Chem. Soc. 2007, 129,
3510. (i) Chen, X.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem.
Soc. 2006, 128, 12634. (j) Kakiuchi, F.; Usui, M.; Ueno, S.;
Chatani, N.; Murai, S. J. Am. Chem. Soc. 2004, 126, 2706.
(k) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.; Murai, S.
J. Am. Chem. Soc. 2003, 125, 1698.
(21) Similar phenomena were observed when p-benzoquinone or
an olefin was used to promote transmetalation–reductive
elimination; please see: (a) refs. 3a and 9i. (b) Albéniz, A.
C.; Espinet, P.; Martín-Ruiz, B. Chem. Eur. J. 2001, 7,
2481. (c) Kurosawa, H.; Emoto, M.; Ohnishi, H.; Miki, K.;
Kasai, N.; Tasumi, K.; Nakamura, A. J. Am. Chem. Soc.
1987, 109, 6333.
(22) For a possible release of potassium fluoride from a
trifluoroborate, please see: Ting, R.; Harwing, C. W.; Lo, J.;
Li, Y.; Adam, M. J.; Ruth, T. J.; Perrin, D. M. J. Org. Chem.
2008, 73, 4662; and references cited therein, as well as ref.
17a.
(23) The optimal reaction conditions reported in the literature
were followed; see ref. 9g.
(24) Kalyani, D.; Deprez, N. R.; Desai, L. V.; Sanford, M. S.
J. Am. Chem. Soc. 2005, 127, 7330.
(25) Aiello, I.; Crispini, A.; Ghedini, M.; Deda, M. L.;
Barigelletti, F. Inorg. Chim. Acta 2000, 308, 121.
(26) For the preparation of compound 1-D, the literature
procedure was followed; see: Chen, X.; Hao, X.-S.;
Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128,
6790.
(10) (a) Wong, M. S.; Zhang, X. L. Tetrahedron Lett. 2001, 42,
4087. (b) Moreno-Manas, M.; Perez, M.; Pleixats, R. J. Org.
Chem. 1996, 61, 2346.
(11) Fowler, D. L.; Kraus, C. A. J. Am. Chem. Soc. 1940, 62,
1143.
(27) Chauhan, K. K.; Frost, C. G.; Love, I.; Waite, D. Synlett
1999, 1743.
Synthesis 2009, No. 22, 3757–3764 © Thieme Stuttgart · New York