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

Article abstract of DOI:10.1021/om100494p

An efficient synthesis of ortho-arylated 2-phenoxypyridines catalyzed by palladium acetate is described. Treatment of 2-phenoxypyridines with two and a half equivalents of potassium aryltrifluoroborate and 10 mol % of Pd(OAc) ₂ in the presence of two equivalents of Ag₂CO₃, one equivalent of p-benzoquinone (BQ), and four equivalents of DMSO with (or without) H₂O at 130-140 °C for 48 h in dried CH ₂Cl₂ gave the ortho-arylated 2-phenoxypyridines in modest to excellent yields. p-Benzoquinone is found to be an important ligand and co-oxidant for the transmetalation reductive elimination step in the catalytic reaction. The investigation of kinetic isotope effect (k_H/k _D) is determined to be 5.25, which indicates that C-H bond cleavage occurs in the rate-determining step. One of the arylated compounds, 2-(4′-nitrobiphenyl-2-yloxy)pyridine, was treated with methyl trifluoromethanesulfonate and subsequently sodium methoxide to give the 2-(4-nitrophenyl)phenol in 79% yield, demonstrating that pyridine is a removable directing group.

Full text of DOI:10.1021/om100494p

4058 Organometallics 2010, 29, 4058–4065
DOI: 10.1021/om100494p
Palladium(II)-Catalyzed Ortho Arylation of 2-Phenoxypyridines with
Potassium Aryltrifluoroborates via C-H Functionalization
Jean-Ho Chu, Pi-Shan Lin, and Ming-Jung Wu*
Department of Chemistry, National Sun Yat-sen University, Kaohsiung, Taiwan 804, Republic of China
Received May 19, 2010
An efficient synthesis of ortho-arylated 2-phenoxypyridines catalyzed by palladium acetate is
described. Treatment of 2-phenoxypyridines with two and a half equivalents of potassium aryltri-
fluoroborate and 10 mol % of Pd(OAc)2 in the presence of two equivalents of Ag2CO3, one
equivalent of p-benzoquinone (BQ), and four equivalents of DMSO with (or without) H2O at
130-140 °C for 48 h in dried CH2Cl2 gave the ortho-arylated 2-phenoxypyridines in modest to
excellent yields. p-Benzoquinone is found to be an important ligand and co-oxidant for the
transmetalation reductive elimination step in the catalytic reaction. The investigation of kinetic
isotope effect (kH/kD) is determined to be 5.25, which indicates that C-H bond cleavage occurs in the
rate-determining step. One of the arylated compounds, 2-(40-nitrobiphenyl-2-yloxy)pyridine, was
treated with methyl trifluoromethanesulfonate and subsequently sodium methoxide to give the 2-(4-
nitrophenyl)phenol in 79% yield, demonstrating that pyridine is a removable directing group.
Introduction
Miyaura cross-coupling reaction).3 Nevertheless, direct
C-H functionalization needs only one or no pre-existing
functional groups of starting reagents instead of the conven-
tional protocol. Concurrently, the methodology can also
improve the synthetic efficiency and atom economy. To date,
many papers have demonstrated that arenes containing so-
called directing group (such as pyridine,4 pyridine N-oxide,5
oxazoline,6 isoxazole,7 oxime,8 imine,9 amide,10 urea,11 carboxylic
Recently, transition metal-catalyzed direct functionaliza-
tion of organic molecules via carbon-hydrogen (C-H)
bond activation has received great attention.1 Selective
C-H bond activation/functionalization emerged as an
efficient strategy for the synthesis of natural products
and pharmaceutical compounds.2 Traditional methods of
carbon-carbon (C-C) bond formation usually require
two prefunctionalized arenes (Ar-X/Ar-M) as starting
materials to generate a new C-C bond (e.g., Suzuki-
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*To whom correspondence should be addressed. Fax: þ886-7-
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pubs.acs.org/Organometallics
Published on Web 08/25/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 18, 2010 4059
acid,12 hydroxy,13 ester,14 ketone,15 and O-carbamate16) can be
regioselectively functionalized by a variety of coupling reagents in
the presence of transition metal catalysts. In the literature, rare
examples utilizing C-H bond activation/functionalization were
investigated toward 2-aryloxypyridine compounds.17 On the
other hand, herbicidal and antimycobacterial activities of arylox-
ypyridine derivatives have been systematically investigated,18
whereas the structure-activity relationship of phenoxypyridine
and its analogues in the investigation of thyroid hormone was also
studied.19 We herein present palladium(II)-catalyzed direct ortho
arylation of 2-phenoxypyridine and its derivatives with potassium
aryltrifluoroborates via C-H bond activation and demon-
strated that the pyridines can be further removed to produce
ortho-arylated phenols.
Table 1. Oxidant and Solvent Effect on the Reaction of 2-Phe-
noxypyridine (1) with Potassium Phenyltrifluoroborate (2a)
entry
oxidant
solventb
product
yield (%)a
1
2
3
4
5
6
7
8
absence
Ag2CO3
AgOAc
Ag2O
K2S2O8
Oxone
Cu(OAc)2
Cu(OTf)2
Hg(OAc)2
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
0
63 (39)c
46
27
22
0
Results and Discussion
DCM
Screens of Oxidants and Solvents for the Reaction of
2-Phenoxypyridine with Potassium Phenyltrifluoroborate.
Our investigation on the ortho arylation of 2-phenoxypyridine
with potassium phenyltrifluoroborate was initiated by screening
of the oxidants and solvents. Thus, a variety of oxidants and
solvents were used in this study, and the results are shown in Table
1. In our previous study,4a copper acetate and silver acetate are the
optimal oxidants and 1,4-dioxane is the best solvent in the ortho
arylation of 2-phenylpyridines. However, on the basis of experi-
mental results, silver(I) carbonate and dichloromethane appear to
be the optimal oxidant and solvent for the reaction of 2-phenox-
ypyridine (1) with potassium phenyltrifluoroborate (2a), respec-
tively.
0
0
0
9
10
11
12
13
14
15
16
17
18
19
DCE
TCE
benzene
toluene
xylene
acetonitrile
tert-butanol
1,4-dioxane
DMF
60
58
56
40
27
14
13
11
8
Ag2CO3
THF
0
a Product yield was determined by 1H NMR spectroscopy. b DCM =
dichloromethane; DCE=1,2-dichloroethane; TCE=1,1,2,2-tetrachlo-
roethane; DMF = N,N-dimethylformamide; THF = tetrahydrofuran.
c Yield in parentheses was obtained by using 1 equiv of Ph-BF3K (2a).
(10) (a) Li, B.-J.; Yang, S.-D.; Shi, Z.-J. Synlett 2008, 949–957. (b) Shi,
Z.; Li, B.; Wan, X.; Cheng, J.; Fang, Z.; Cao, B.; Qin, C.; Wang, Y. Angew.
Chem., Int. Ed. 2007, 46, 5554–5558.
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Tyler, S. N. G.; Gagne, M. R.; Lloyd-Jones, G. C.; Booker-Milburn,
K. I. Angew. Chem., Int. Ed. 2009, 48, 1830–1833. (b) Houlden, C. E.;
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Catalytic Reaction of 2-Phenoxypyridine and Its Deriva-
tives with Various Potassium Aryltrifluoroborates. On the basis
of optimal reaction conditions (2.5 equiv of Ar-BF3K, 10
mol % Pd(OAc)2, 2 equiv of Ag2CO3, 1 equiv of p-benzoqui-
none (BQ),20 and 4 equiv of DMSO21 with (or without) 8 equiv
of H2O22 at 130-140 °Cfor48hindryCH2Cl2), we carried out
the reaction of 2-phenoxypyridine (1) with various potassium
aryltrifluoroborates, 2a-m.Aseriesofortho-arylated 2-phenoxy-
pyridines, 3a-m, were obtained in 0-95% yields (Table 2).
According to the experimental results, we found the reac-
tion of 1 with potassium aryltrifluoroborates 2a-g (Table 2,
entries 1-7) resulted in modest to excellent yields (50-95%).
In addition, the reaction of 1 with potassium 4-iodophenyl
trifluoroborate (2h) gave compound 3h in only 7% yield
(Table 2, entry 8). The low yield might be due to the side
reactions, including possible self-polymerization of 2h by
Suzuki coupling reaction, although we did not isolate the
corresponding polymers. In the above entries, we found that
adding a small amount of water could increase the reaction
rate and produce better chemical yields. After tuning the
amount of water, adding eight equivalents of water into
the reaction mixture turned out to yield the best result. On
the other hand, low yields (34-48%, Table 2, entries 9-11)
(14) Ishiyama, T; Isou, H.; Kikuchi, T.; Miyaura, N. Chem. Commun.
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Chem. 2010, 75, 208–210.
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Chem. 2009, 7, 4853–4857. (b) Xiao, B.; Fu, Y.; Xu, J.; Gong, T.-J.; Dai, J.-J.;
Yi, J.; Liu, L. J. Am. Chem. Soc. 2010, 132, 468–469. (c) Zhao, X.; Yeung,
C. S.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 5837–5844.
(17) Gu, S.; Chao, C.; Chen, W. J. Org. Chem. 2009, 74, 7203–7206.
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T. J.; Boyne, M.; Xu, H.; Gegina, Y.; Knudson, D. L.; Johnson, F.;
Peloquin, C. A.; Slayden, R. A.; Tonge, P. J. Bioorg. Med. Chem. Lett.
2008, 18, 3029–3033. (b) Fujikawa, K.; Kondo, K.; Yokomichi, I.; Kimura,
F.; Haga, T.; Nishiyama, R. Agric. Biol. Chem. 1970, 34, 68–79.
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(20) Fresh p-benzoquinone through sublimation was used.
(21) Catalytic system of Pd(II)/DMSO, see: (a) Steinhoff, B. A.;
Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 4348–4355, and references
therein. DMSO might slow catalyst decomposition and Pd(0) aggregation
and further increase the product yield; see: (b) Hull, K. L.; Sanford, M. S.
J. Am. Chem. Soc. 2007, 129, 11904–11905. (c) Hull, K. L.; Sanford, M. S.
J. Am. Chem. Soc. 2009, 131, 9651–9653. (d) Zierkiewicz, W.; Privalov, T.
Organometallics 2005, 24, 6019–6028.
(22) The yield of 2-(biphenyl-2-yloxy)pyridine (3a) in the reaction of
2-phenoxypyridine (1) with potassium phenyltrifluoroborate (2a) was
determined to be 21%, 63%, 62%, and 12% in the presence of 0, 8, 16,
and 32 equivalents of water, respectively. Trifluoroborate salts might
undergo hydrolysis to afford boronic acids and further participate in the
transmetalation-reductive elimination with palladacycle I. See: Bulters,
M.; Harvey, J. M.; Jover, J.; Lennox, A, J. J.; Lloyd-Jones, G. C.; Murray,
P. M. Angew. Chem., Int. Ed. DOI: 10.1002/anie.201001522.

4060 Organometallics, Vol. 29, No. 18, 2010
Table 2. Ortho Arylation of 2-Phenoxypyridine (1) with Potassium Aryltrifluoroborate 2a-ma
Chu et al.
a 8 equiv of H2O was added in entries 1-8, 12, and 13, and no water was added in entries 9-11. b All yields were determined by 1H NMR spectroscopy.
c Yield in parentheses was obtained by using 1.0 mmol scale of 2-phenoxypyridine (1).
were observed by using potassium aryltrifluoroborates 2i-k,
bearing electron-donating groups (tBu, Me, and OMe). No
water was added in these three cases because we found that
the self-coupling reactions of aryltrifluoroborates took place
faster than the ortho arylation reactions by adding water into
the reaction mixture. The reaction of potassium o-methoxy-
carbonylphenyltrifluoroborate (2l) (Table 2, entry 12) and
potassium 1-naphthyltrifluoroborate (2m) (Table 2, entry
13) with 2-phenoxypyridine (1) led to compounds 3l and 3m
in 18% and 0% yields, respectively. The poor yields could be
due to the steric hindrance interfering with the C-C bond
formation.
In addition to 2-phenoxypyridine (1), we also carried out
the reactions of pyridine derivatives 4a-g with potassium
4-formylphenyl trifluoroborate (2d). The ortho-arylated pro-
ducts 5a-g were obtained in 0 to 84% yields (Table 3). The
isoquinoline group of 1-phenoxyisoquinoline (4a) can also
be utilized as a directing group. Reaction of 4a with 2d under
the optimal reaction conditions gave compound 5a in 73%
yield (Table 3, entry 1). On the other hand, reaction of 4a
with 2d led to the formation of three products, 5b, 5b0, and
5b00, in a ratio of 60:25:15, and the total yield is 72% (Table 3,
entry 2). When the reaction of 2-(naphthalen-1-yloxy)-
pyridine (4c) and 2-(phenanthren-9-yloxy)pyridine (4d) was

Article
Organometallics, Vol. 29, No. 18, 2010 4061
Table 3. Ortho Arylation of Pyridine Derivatives 4a-g with Potassium 4-Formylphenyl Trifluoroborate (2d)
a,b Yields and product ratio were all determined by 1H NMR spectroscopy.
carried out to react with 2d under the described reaction condi-
tions, both reactions produced a single product, 5c and 5d,
respectively. No other regioisomer was found in these two
reactions (Table 3, entries 3 and 4). The high regioselectivity for
both reactions could be explained by the formation of the six-
membered palladacycles, which are more stable than the seven-
membered palladacycles. The structure of 5c was unambiguously
determined by X-ray crystallography analysis, as shown in
Figure 1. In addition to substrates 4a-d, we also carried out the
reaction of 2-phenoxypyridines 4e-g, bearing either an electron-
donating or withdrawing group on the phenyl ring, with 2d,
which led to 5e-g in 33%, 34%, and 0% yields, respectively.
The result shows that when 2-phenoxypyridine bears a strong
electron-withdrawing group, such as a nitro group, the reaction
took place very slowly and led to no coupling product. The low
yields obtained by the reaction of 4e and 4f may be due to the
steric effect that destabilizes the palladacycles, which would not
be efficiently transformed into the desired products.
In order to understand the detailed information on the
reaction mechanism, we independently synthesized the impor-
tant intermediate 2-phenoxypyridine palladacycle I (which
was first reported by Steel and co-workers in 1999, but they
did not obtain its X-ray crystal structure23) by treatment of
2-phenoxypyridine (1) with a stoichiometric amount of Pd-
(OAc)2 in dichloromethane. The structure of intermediate I
(a head-to-tail geometric structure) was confirmed by X-ray
crystallographic analysis, as shown in Figure 2.
With this intermediate in hand, we carried out the reac-
tion of I with potassium phenyltrifluoroborate (2a) with or
(23) de Geest, D. J.; O’Keefe, B. J.; Steel, P. J. J. Organomet. Chem.
1999, 579, 97–105.

4062 Organometallics, Vol. 29, No. 18, 2010
Chu et al.
without two equivalents of BQ (eq 1). These controlled
experiments indicated that 2-(biphenyl-2-yloxy)pyridine (3a)
was obtained in 69% yield only in the presence of BQ. In the
absence of BQ, no 3a was observed. According to these results,
we believe that BQ is an important ligand and co-oxidant in
the reductive elimination step of the catalytic reaction.24
Figure 1. ORTEP drawing of compound 5c (where all hydro-
gen atoms are omitted for clarity).
of KF) is bound to the Pd center of I via ligand exchange with
release of F2BOAc.25 p-Benzoquinone (BQ) herein is an im-
portant ligand and co-oxidant to coordinate with Pd to form
intermediate II. Eventually, intermediate II is further trans-
formed to ortho-arylated product 3. The released Pd(0) is
reoxidized by Ag2CO3 and p-benzoquinone to regenerate
Pd(II), which would continue the catalytic cycle.
Synthesis of 40-Nitrobiphenyl-2-ol (6b) through Depyridiny-
lation of Compound 3b. To demonstrate the utility of pyridine
as a removable directing group that would direct the C-H
bond activation/functionalization and could be removed to
form a variety of biphenyl alcohols from ortho-arylated
2-phenoxypyridines, herein compound 3b was treated
with methyl trifluoromethanesulfonate (MeOTf) to form
1-methyl-2-(40-nitrobiphenyl-2-yloxy)pyridinium in toluene.
Subsequently, crude 1-methyl-2-(40-nitrobiphenyl-2-yloxy)-
pyridinium was added into a refluxing Na/MeOH solution to
generate 40-nitrobiphenyl-2-ol (6b) in 79% yield in two steps
(eq 3).
Investigation of Kinetic Isotope Effect. The kinetic isotope
effect (kH/kD) of the catalytic reaction was carried out by the
reaction of ortho monodeutero-2-phenoxypyridine (1-D)
with potassium 4-formylphenyl trifluoroborate (2d) to give
the products 3d-D and 3d, respectively (eq 2). The kinetic
isotope effect (kH/kD) was determined to be 5.25 (compared
with the standard H NMR spectrum of compound 3d).
This indicates that ortho C-H bond cleavage occurs in the
rate-determining step.
1
Conclusion
Proposed Mechanism for the Reaction of 2-Phenoxypyri-
dine with Potassium Aryltrifluoroborates. A possible mecha-
nism for the present palladium(II)-catalyzed ortho arylation
of 2-phenoxypyridine (1) via C-H bond activation is pro-
posed as shown in Figure 3. First of all, coordination of
2-phenoxypyridine (1) to Pd(OAc)2 following an ortho C-H
bond activation would form a pyridine palladacycle I. Sub-
sequently, the aryl group of aryldifluoroborane 2-BF2
(generated from potassium aryltrifluoroborate 2 by a release
We have developed the reaction conditions for the synth-
esis of ortho-arylated 2-phenoxypyridines with potassium
aryltrifluoroborates via C-H bond activation using
palladium(II) acetate as a catalyst. The products can further
be converted to biphenyl alcohols in good yield by the
treatment of methyl trifluoromethanesulfonate then sodium
methoxide in methanol solution. The presented methodol-
ogy provides a useful tool in organic synthesis.
(24) Similar phenomena were observed by using the p-benzoquinone
or olefin to promote transmetalation reductive elimination in the
literature; see: (a) References 4g and 6c. (b) Kurosawa, H.; Emoto,
M.; Ohnishi, H.; Miki, K.; Kasai, N.; Tasumi, K.; Nakamura, A. J. Am.
Experimental Section
General Procedure for Synthesis of Starting Materials 1 and
4a-g.26 A well-stirred solution of 2-iodopyridine (500 mg, 2.44
mmol) or 1-bromoisoquinoline (208 mg, 1.00 mmol) with a
€
€
Chem. Soc. 1987, 109, 6333–6340. (c) Backvall, J. E.; Bystrom, S. E.;
€
Nordberg, R. E. J. Org. Chem. 1984, 49, 4619–4631. (d) Backvall, J. E.;
ꢀ
ꢀ
Gogoll, A. Tetrahedron Lett. 1988, 29, 2243–2246. (e) Kalman, K. J.
Organometallics 1998, 17, 1677–1686.
(25) (a) Molander, G. A.; Cavalcanti, L. N.; Canturk, B.; Pan, P.-S.;
Kennedy, L. E. J. Org. Chem. 2009, 74, 7364–7369. (b) Ting, R.; Harwing,
C. W.; Lo, J.; Li, Y.; Adam, M. J.; Ruth, T. J.; Perrin, D. M. J. Org. Chem.
2008, 73, 4662–4670.
(26) Starting materials 1 and 4a-g can be synthesized by following
the literature procedure: D’Angelo, N. D.; Peterson, J. J.; Booker, S. K.;
Fellows, I.; Dominguez, C.; Hungate, R.; Reider, P. J.; Kim, T.-S.
Tetrahedron Lett. 2006, 47, 5045–5048.

Article
Organometallics, Vol. 29, No. 18, 2010 4063
Figure 2. (a) Face view and (b) side view of ORTEP drawing of 2-phenoxypyridine palladacycle I. All hydrogen atoms are omitted
˚
for clarity. Selected bond lengths (A): Pd1-Pd2 = 2.9122(13); Pd1-N1 = 1.896(14); Pd1-C11 = 2.08(3); Pd1-O2 = 2.099(4);
Pd1-O5 = 2.097(4); Pd2-N2 = 1.907(17); Pd2-C26 = 2.138(17); Pd2-O3 = 2.110(4); Pd2-O4 = 2.090(4).
and the organic layers were combined, dried over MgSO4, filtered,
and evaporated under vacuum. The residue was purified by silica
gel chromatography using n-hexane/ethyl acetate (20/1 to 5/1) as
the eluent to give a series of ortho-arylated 2-phenoxypyridines,
3a-m. All yields are as follows: 3a, 63% (14 mg, 0.055 mmol); 3b,
95% (25 mg, 0.084 mmol); 3c, 90% (23 mg, 0.079 mmol); 3d, 75%
(18 mg, 0.066 mmol); 3e, 80% (19 mg, 0.070 mmol); 3f, 50%
(13 mg, 0.044 mmol); 3g, 65% (19 mg, 0.057 mmol); 3h, 41%
(14 mg, 0.036 mmol); 3i, 48% (13 mg, 0.042 mmol); 3j, 40% (9.2
mg, 0.035 mmol); 3k, 34% (8.3 mg, 0.030 mmol); 3l, 18% (4.8 mg,
0.016 mmol); 3m, 0% (0 mg, 0 mmol). The general procedure for
the synthesis of pyridine derivatives 5a-g was the same as that of
ortho-arylated pyridine derivatives 3a-m. The amounts used of
pyridine derivatives 4a-g are as follows: 4a, 15 mg, 0.068 mmol;
4b, 15 mg, 0.068 mmol; 4c, 15 mg, 0.068 mmol; 4d, 15 mg, 0.055
mmol; 4e, 15 mg, 0.075 mmol; 4f, 15 mg, 0.081 mmol; 4g, 15 mg,
0.069 mmol. All yields are as follows (note: three equivalents of
potassium 4-formylphenyl trifluoroborate 2d was used): 5a, 73%
Figure 3. Proposed mechanism of palladium(II)-catalyzed
2-phenoxypyridine (1) with potassium aryltrifluoroborates 2.
(16 mg, 0.050 mmol); 5b, 43% (9.4 mg, 0.029 mmol); 5b0, 18% (4.2
mg, 0.012 mmol); 5b00, 11% (3 mg, 0.007 mmol); 5c, 84% (19 mg,
variety of phenols (344 mg, 3.66 mmol for 1; 141 mg, 1.50 mmol
0.057 mmol); 5d, 61% (13 mg, 0.034 mmol); 5e, 29% (6.9 mg,
for 4a; 527 mg, 3.66 mmol for 4b,c; 710 mg, 3.66 mmol for 4d;
0.023 mmol); 5f, 34% (8.0 mg, 0.027 mmol); 5g, 0% (0 mg,
0 mmol).
454 mg, 3.66 mmol for 4e; 395 mg, 3.66 mmol for 4f; 501 mg, 3.66
mmol for 4g), copper powder (16 mg, 0.24 mmol for 1 and 4b-g;
6.4 mg, 0.1 mmol for 4a), and cesium carbonate (2.39 g, 7.32
General Procedure for Synthesis of 2-(40-Nitrophenyl) Phenol
(6b). To a well-stirred solution of compound 3b (36 mg, 0.13
mmol for 1 and 4b-g; 978 mg, 3.00 mmol for 4a) in N,N-
mmol) in dry toluene (5 mL) was added MeOTf (21 μL, 0.19
dimethylformamide (5 mL) was heated at 100 °C for 18 h. After
cooling to room temperature, water (20 mL) was added into the
mmol) at 100 °C for 2 h under nitrogen gas. After cooling to
room temperature, the solution was evaporated under vacuum.
solution, and the solution was further extracted by dichloro-
Without purification, the crude product was subsequently
methane (15 mL ꢀ 3). The organic layer was dried over MgSO4,
added into a Na (73.9 mg, 3.21 mmol)/MeOH (5 mL) solution,
heated to reflux, and stirred for a further 15 min. After cooling to
room temperature, the solvent was evaporated under vacuum
and water (15 mL) was added to the residue. The aqueous
solution was extracted by ethyl acetate (10 mL ꢀ 3), and the
organic layers were combined, dried over MgSO4, filtered, and
evaporated under vacuum. The residue was further purified by
silica gel chromatography using n-hexane/ethyl acetate (20/1 to
5/1) as the eluent to give 2-(40-nitrophenyl) phenol (6b) (22.1 mg,
0.103 mmol) in 79% yield.
filtered, and evaporated under vacuum. The residue was further
purified by silica gel chromatography using n-hexane/ethyl
acetate (35/1 to 20/1) as eluent to give 1 and 4a-g. All yields
are as follows: 1, 91% (380 mg, 2.22 mmol); 4a, 85% (188 mg,
0.850 mmol); 4b, 70% (377 mg, 1.71 mmol); 4c, 88% (475 mg,
2.15 mmol); 4d, 40% (264 mg, 0.970 mmol); 4e, 85% (427 mg,
2.13 mmol); 4f, 85% (384 mg, 2.10 mmol); 4g, 15% (78.8
mg, 0.365 mmol).
General Procedure for Synthesis of ortho-Arylated 2-Phenoxy-
pyridine Derivatives 3a-m. A well-stirred solution of 2-phenoxy-
pyridine (15 mg, 0.088 mmol) with potassium aryltrifluorobo-
rates (2.5 equiv), Ag2CO3 (2 equiv), BQ (1 equiv), DMSO
(4 equiv), and H2O (8 or 0 equiv) using 10 mol % Pd(OAc)2 as a
catalyst in dry CH2Cl2 (5 mL) was heated at 130-140 °C for 48 h
(note: a Teflon container sealed with a steel cylinder is used). After
cooling to room temperature, the crude solution was filtered
through a pad of Celite and washed by water (5 mL ꢀ 2). The
aqueous layer was then extracted by dichloromethane (5 mL ꢀ 2),
2-(Biphenyl-2-yloxy)pyridine (3a): colorless, viscous liquid;
Rf = 0.45 (n-hexane/ethyl acetate, 5/1); H NMR (300 MHz,
1
CDCl3) δ 6.74 (d, J=9.0 Hz, 1 H), 6.88 (dd, J=7.2, 5.4 Hz, 1 H),
7.18 (dd, J = 8.1, 1.1 Hz, 1 H), 7.26-7.42 (m, 5 H), 7.45-7.49
(m, 3 H), 7.56 (td, J=7.2, 2.1 Hz, 1 H), 8.11 (dd, J = 4.8, 1.5 Hz,
1 H); 13C NMR (100 MHz, CDCl3) δ 111.3 (CH), 118.0 (CH),
122.6 (CH), 125.3 (CH), 127.1 (CH), 128.0 (CH ꢀ 2), 128.6
(CH), 129.1 (CH ꢀ 2), 131.2 (CH), 134.7 (Cq), 137.8 (Cq), 139.2

4064 Organometallics, Vol. 29, No. 18, 2010
Chu et al.
(CH), 147.6 (CH), 150.9 (Cq), 163.8 (Cq); MS (EI, m/z) 247
(Mþ, 9), 246 (Mþ - Hþ, 17), 230 (13), 84 (100), 47 (17); HRMS
m/z calcd for C17H13NO 247.0997, found 247.1001.
122.8 (CH), 125.4 (CH), 129.0 (CH), 130.7 (CH ꢀ 2), 130.9
(CH), 131.2 (CH), 133.6 (Cq), 136.7 (Cq), 139.3 (CH), 147.6
(CH), 150.8 (Cq), 163.6 (Cq); MS (EI, m/z) 326 (Mþ þ 1, 1), 324
(Mþ - 1, 1), 84 (100), 47 (20); HRMS m/z calcd for
C17H1279BrNO 325.0102, found 325.0108.
2-(40-Nitrobiphenyl-2-yloxy)pyridine (3b): pale yellow solid;
mp 76-77 °C; Rf = 0.43 (n-hexane/ethyl acetate, 5/2); 1H NMR
(300 MHz, CDCl3) δ 6.79 (d, J = 8.1 Hz, 1 H), 6.92 (dd, J = 8.1,
4.5 Hz, 1 H), 7.21 (d, J = 8.1 Hz, 1 H), 7.31-7.36 (m, 1 H),
7.44-7.50 (m, 2 H), 7.60 (td, J = 8.4, 2.1 Hz, 1 H), 7.65 (d, J =
8.7 Hz, 2 H), 8.09 (dd, J = 4.8, 1.8 Hz, 1 H), 8.16 (d, J = 8.7 Hz,
2 H); 13C NMR (100 MHz, CDCl3) δ 111.4 (CH), 118.5 (CH),
122.9 (CH), 123.3 (CH ꢀ 2), 125.6 (CH), 129.9 (CH ꢀ 2), 130.1
(CH), 130.8 (CH), 132.5 (Cq), 139.5 (CH), 144.7 (Cq), 146.9
(Cq), 147.6 (CH), 151.0 (Cq), 163.3 (Cq); MS (EI, m/z) 292 (Mþ,
71), 291 (Mþ - Hþ, 100), 275 (63), 217 (46), 139 (32), 84 (78), 78
(32); HRMS m/z calcd for C17H12N2O3 292.0848, found
292.0840.
2-(40-Iodobiphenyl-2-yloxy)pyridine (3h): pale brown, viscous
1
liquid; Rf = 0.40 (n-hexane/ethyl acetate, 5/1); H NMR (300
MHz, CDCl3) δ 6.76 (d, J = 8.4 Hz, 1 H), 6.91 (dd, J = 6.6, 5.1
Hz, 1 H), 7.17 (d, J = 7.8 Hz, 1 H), 7.22 (d, J = 8.4 Hz, 2 H), 7.30
(d, J = 8.0 Hz, 1 H), 7.37-7.43 (m, 2 H), 7.59 (td, J = 7.8, 2.1
Hz, 1 H), 7.63 (d, J = 8.4 Hz, 2 H), 8.11 (dd, J = 5.4, 1.8 Hz,
1 H); 13C NMR (150 MHz, CDCl3) δ 93.1 (Cq), 111.3 (CH),
118.3 (CH), 122.8 (CH), 125.4 (CH), 129.0 (CH), 130.9 (CH),
131.0 (CH x 2), 133.6 (Cq), 137.2 (CH ꢀ 2), 137.4 (Cq), 139.3
(CH), 147.6 (CH), 150.8 (Cq), 163.6 (Cq); MS (EI, m/z) 373
(Mþ, 1), 84 (100), 47 (17); HRMS m/z calcd for C17H12INO
372.9964, found 372.9967.
2-(50-Nitrobiphenyl-2-yloxy)pyridine (3c): pale yellow solid;
mp 84-85 °C; Rf = 0.33 (n-hexane/ethyl acetate, 5/1); 1H NMR
(300 MHz, CDCl3) δ 6.80 (d, J = 8.7 Hz, 1 H), 6.91 (dd, J = 6.9,
5.4 Hz, 1 H), 7.23 (d, J = 7.8 Hz, 1 H), 7.32-7.37 (m, 1 H),
7.44-7.50 (m, 3 H), 7.60 (td, J = 6.6, 1.8 Hz, 1 H), 7.83 (d, J =
7.8 Hz, 1 H), 8.08-8.12 (m, 2 H), 8.37-8.38 (m, 1 H); 13C NMR
(150 MHz, CDCl3) δ 111.4 (CH), 118.5 (CH), 122.0 (CH), 122.9
(CH), 124.1 (CH), 125.6 (CH), 128.9 (CH), 129.9 (CH), 130.8
(CH), 132.3 (Cq), 135.2 (CH), 139.5 (CH þ Cq), 147.6 (CH),
148.1 (Cq), 151.0 (Cq), 163.3 (Cq); MS (EI, m/z) 292 (Mþ, 15),
291 (Mþ - Hþ, 14), 88 (29), 70 (89), 61 (100); HRMS m/z calcd
for C17H12N2O3 292.0848, found 292.0855.
2-(40-tert-Butylbiphenyl-2-yloxy)pyridine (3i): colorless, vis-
1
cous liquid; Rf = 0.45 (n-hexane/ethyl acetate, 5/1); H NMR
(300 MHz, CDCl3) δ 1.30 (s, 9 H), 6.77 (d, J = 8.1 Hz, 1 H), 6.89
(dd, J = 7.1, 5.4 Hz, 1 H), 7.15 (dd, J = 8.1, 0.9 Hz, 1 H),
7.26-7.36 (m, 4 H), 7.41 (d, J = 8.4 Hz, 2 H), 7.47 (dd, J = 7.5,
1.8 Hz, 1 H), 7.57 (td, J = 7.4, 1.8 Hz, 1 H), 8.14 (dd, J = 5.1, 1.8
Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ 31.3 (CH3 ꢀ 3), 34.5
(Cq), 111.5 (CH), 118.0 (CH), 122.5 (CH), 125.0 (CH ꢀ 2), 125.2
(CH), 128.3 (CH), 128.7 (CH ꢀ 2), 131.2 (CH), 134.4 (Cq), 134.7
(Cq), 139.1 (CH), 147.7 (CH), 149.9 (Cq), 151.1 (Cq), 163.9
(Cq); MS (EI, m/z) 303 (Mþ, 10), 302 (Mþ - Hþ, 12), 84 (100),
47 (24); HRMS m/z calcd for C21H21NO 303.1623, found
303.1629.
20-(Pyridin-2-yloxy)biphenyl-4-carbaldehyde (3d): pale orange
solid; mp 72-73 °C; Rf = 0.43 (n-hexane/ethyl acetate, 5/2); 1H
NMR (300 MHz, CDCl3) δ 6.77 (d, J = 8.1 Hz, 1 H), 6.89 (dd,
J = 6.6, 5.7 Hz, 1 H), 7.20 (d, J = 8.1 Hz, 1 H), 7.30-7.35 (m,
1 H), 7.42-7.49 (m, 2 H), 7.57 (td, J = 8.1, 1.5 Hz, 1 H), 7.65 (d,
J = 8.1 Hz, 2 H), 7.82 (d, J = 8.1 Hz, 2 H), 8.09 (d, J = 4.2 Hz,
1 H), 9.98 (s, 1 H); 13C NMR (75 MHz, CDCl3) δ 111.3 (CH),
118.3 (CH), 122.8 (CH), 125.4 (CH), 129.4 (CH ꢀ 2), 129.6
(CH), 129.7 (CH ꢀ 2), 130.9 (CH), 133.4 (Cq), 135.0 (Cq), 139.3
(CH), 144.2 (Cq), 147.6 (CH), 151.0 (Cq), 163.4 (Cq), 192.0
(CH); MS (EI, m/z) 275 (Mþ, 61), 274 (Mþ - Hþ, 100), 258 (81),
170 (27), 78 (19); HRMS m/z calcd for C18H13NO2 275.0946,
found 275.0938.
2-(40-Methylbiphenyl-2-yloxy)pyridine (3j): colorless, viscous
1
liquid; Rf = 0.45 (n-hexane/ethyl acetate, 5/1); H NMR (300
MHz, CDCl3) δ 2.32 (s, 3 H), 6.75 (d, J = 8.7 Hz, 1 H), 6.89 (dd,
J = 7.1, 4.8 Hz, 1 H), 7.12 (d, J = 7.8 Hz, 2 H), 7.16 (dd, J = 7.8,
0.9 Hz, 1 H), 7.29 (dd, J = 7.7, 1.4 Hz, 1 H), 7.34-7.39 (m, 3 H),
7.46 (dd, J = 7.5, 1.8 Hz, 1 H), 7.56 (td, J = 7.2, 1.8 Hz, 1 H),
8.13 (dd, J = 4.8, 1.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ
21.1 (CH3), 111.3 (CH), 118.0 (CH), 122.6 (CH), 125.3 (CH),
128.4 (CH), 128.8 (CH ꢀ 2), 128.9 (CH ꢀ 2), 131.2 (CH), 134.7
(Cq), 134.8 (Cq), 136.8 (Cq), 139.1 (CH), 147.6 (CH), 150.9
(Cq), 163.9 (Cq); MS (EI, m/z) 261 (Mþ, 8), 260 (Mþ - Hþ, 13),
244 (11), 84 (100), 47 (21); HRMS m/z calcd for C18H15NO
261.1154, found 261.1148.
2-(40-Fluorobiphenyl-2-yloxy)pyridine (3e): colorless, viscous
1
liquid; Rf = 0.50 (n-hexane/ethyl acetate, 5/1); H NMR (300
2-(40-Methoxybiphenyl-2-yloxy)pyridine (3k): colorless, vis-
MHz, CDCl3) δ 6.74 (d, J = 8.4 Hz, 1 H), 6.89 (dd, J = 6.9, 5.4
Hz, 1 H), 6.95-7.01 (m, 2 H), 7.17 (dd, J = 8.1, 0.9 Hz, 1 H),
7.29-7.46 (m, 5 H), 7.57 (td, J = 8.6, 2.0 Hz, 1 H), 8.11 (dd, J =
5.0, 1.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 111.2 (CH),
114.9 (d, JC-F = 21.2 Hz, CH x 2), 118.1 (CH), 122.7 (CH),
125.4 (CH), 128.8 (CH), 130.7 (d, JC-F = 8.3 Hz, CH ꢀ 2), 131.1
(CH), 133.8 (Cq), 139.2 (CH), 147.6 (CH), 150.9 (Cq), 162.1 (d,
1
cous liquid; Rf = 0.33 (n-hexane/ethyl acetate, 5/1); H NMR
(300 MHz, CDCl3) δ 3.78 (s, 3 H), 6.74 (d, J = 8.7 Hz, 1 H), 6.84
(d, J = 8.7 Hz, 2 H), 6.88 (td, J = 8.0, 5.1 Hz, 1 H), 7.15 (dd, J =
7.8, 1.5 Hz, 1 H), 7.26-7.46 (m, 5 H), 7.56 (td, J = 7.5, 1.8 Hz,
1 H), 8.12 (dd, J = 4.8, 1.8 Hz, 1 H); 13C NMR (100 MHz,
CDCl3) δ 55.2 (CH3), 111.2 (CH), 113.5 (CH ꢀ 2), 118.0 (CH),
122.7 (CH), 125.4 (CH), 128.2 (CH), 129.9 (Cq), 130.2 (CH ꢀ
2), 131.1 (CH), 134.4 (Cq), 139.2 (CH), 147.6 (CH), 155.4
(Cq), 158.8 (Cq), 163.8 (Cq); MS (EI, m/z) 277 (Mþ, 2), 291
(Mþ - Hþ, 2), 84 (100), 47 (23); HRMS m/z calcd for C18H15-
NO2 277.1103, found 277.1108.
J
C-F = 244.8 Hz, Cq), 163.6 (Cq); MS (EI, m/z) 265 (Mþ, 11),
264 (Mþ - Hþ, 19), 84 (100), 47 (17); HRMS m/z calcd for
C17H12NFO 265.0903, found 265.0901.
2-(40-Chlorobiphenyl-2-yloxy)pyridine (3f): colorless, viscous
liquid; Rf = 0.40 (n-hexane/ethyl acetate, 5/1); H NMR (300
1
Methyl 20-(pyridin-2-yloxy)biphenyl-2-carboxylate (3l): color-
less, viscous liquid; Rf = 0.43 (n-hexane/ethyl acetate, 5/2); 1H
NMR (300 MHz, CDCl3) δ 3.68 (s, 3 H), 6.69 (d, J = 8.1 Hz, 1
H), 6.82 (dd, J = 6.9, 4.8 Hz, 1 H), 7.18 (d, J = 7.8 Hz, 1 H),
7.28-7.43 (m, 6 H), 7.49 (td, J = 8.1, 1.8 Hz, 1 H), 7.81 (d, J =
8.1 Hz, 1 H), 8.02 (dd, J = 4.8, 1.8 Hz, 1 H); 13C NMR (100
MHz, CDCl3) δ 51.9 (CH3), 111.4 (CH), 118.0 (CH), 121.6
(CH), 125.0 (CH), 127.2 (CH), 128.8 (CH), 129.6 (CH), 130.4
(CH), 131.0 (Cq), 131.3 (CH), 131.4 (CH), 134.4 (Cq), 138.2
(Cq), 139.0 (CH), 147.2 (CH), 150.7 (Cq), 163.2 (Cq), 168.4
(Cq); MS (EI, m/z) 305 (Mþ, 1), 304 (Mþ - Hþ, 2), 211 (14), 84
(100), 47 (18); HRMS m/z calcd for C19H15NO3 305.1052, found
305.1046.
MHz, CDCl3) δ 6.75 (d, J = 8.4 Hz, 1 H), 6.90 (dd, J = 7.1, 5.4
Hz, 1 H), 7.17 (dd, J = 7.8, 0.9 Hz, 1 H), 7.26-7.37 (m, 3 H),
7.40-7.44 (m, 4 H), 7.58 (td, J = 7.5, 1.8 Hz, 1 H), 8.11 (dd, J =
5.0, 1.8 Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ 111.3 (CH),
118.2 (CH), 122.7 (CH), 125.4 (CH), 128.2 (CH ꢀ 2), 129.0
(CH), 130.4 (CH ꢀ 2), 131.0 (CH), 133.2 (Cq), 133.5 (Cq), 136.3
(Cq), 139.3 (CH), 147.6 (CH), 150.9 (Cq), 163.6 (Cq); MS (EI,
m/z) 282 (Mþ þ 1, 1), 291 (Mþ - 2, 3), 84 (100), 47 (23); HRMS
m/z calcd for C17H1235ClNO 281.0607, found 281.0600.
2-(40-Bromobiphenyl-2-yloxy)pyridine (3g): pale brown, vis-
1
cous liquid; Rf = 0.40 (n-hexane/ethyl acetate, 5/1); H NMR
(300 MHz, CDCl3) δ 6.76 (d, J = 8.7 Hz, 1 H), 6.90 (dd, J = 7.0,
5.4 Hz, 1 H), 7.17 (d, J = 8.1 Hz, 1 H), 7.29-7.44 (m, 7 H), 7.59
(td, J = 7.5, 1.8 Hz, 1 H), 8.11 (dd, J = 5.3, 1.5 Hz, 1 H); 13
C
20-(Isoquinolin-1-yloxy)biphenyl-4-carbaldehyde (5a):white solid;
mp 140-141 °C; Rf = 0.43 (n-hexane/ethyl acetate, 5/2); 1H NMR
NMR (100 MHz, CDCl3) δ 111.3 (CH), 118.2 (CH), 121.4 (Cq),

Article
Organometallics, Vol. 29, No. 18, 2010 4065
(300 MHz, CDCl3) δ7.22 (d, J = 5.7 Hz, 1 H), 7.32-7.39 (m, 2 H),
7.46-7.58 (m, 3 H), 7.64-7.73 (m, 6 H), 7.87 (d, J = 6.0 Hz, 1 H),
8.27 (d, J = 8.4 Hz, 1 H), 9.88 (s, 1 H); 13C NMR (100 MHz,
CDCl3) δ 116.4 (CH), 119.5 (Cq), 123.5 (CH), 123.9 (CH), 125.7
(CH), 126.2 (CH), 127.2 (CH), 129.4 (CH ꢀ 2), 129.6 (CH ꢀ 2),
130.8 (CH), 130.9 (CH), 133.7 (Cq), 134.9 (Cq), 138.3 (Cq), 139.6
(CH), 144.3 (Cq), 150.7 (Cq), 160.3 (Cq), 192.0 (CH); MS (EI,
m/z) 325 (Mþ, 66), 324 (Mþ - Hþ, 37), 308 (100), 220 (32), 128
(18), 84 (13); HRMS m/z calcd for C22H15NO2 325.1103, found
325.1098.
4-(3-(Pyridin-2-yloxy)naphthalen-2-yl)benzaldehyde (5b): pale
yellow solid; mp 148-149 °C; Rf = 0.45 (n-hexane/ethyl acetate,
5/2); 1H NMR (300 MHz, CDCl3) δ 6.80 (d, J = 8.4 Hz, 1 H),
6.88 (t, J = 6.6 Hz, 1 H), 7.48-7.60 (m, 3 H), 7.65 (s, 1 H), 7.75
(d, J = 8.1 Hz, 2 H), 7.80-7.91 (m, 4 H), 7.95 (s, 1 H), 8.06 (dd,
J = 4.8, 1.5 Hz, 1 H), 10.00 (s, 1 H); 13C NMR (100 MHz,
CDCl3) δ 111.4 (CH), 118.4 (CH), 119.4 (CH), 125.9 (CH), 126.9
(CH), 127.2 (CH), 128.0 (CH), 129.5 (CH ꢀ 2), 130.0 (CH ꢀ 2),
130.6 (CH), 131.2 (Cq), 133.4 (Cq), 133.9 (Cq), 135.0 (Cq), 139.3
(CH), 144.4 (Cq), 147.6 (CH), 149.2 (Cq), 163.6 (Cq), 192.1
(CH); MS (EI, m/z) 325 (Mþ, 2), 324 (Mþ - Hþ, 2), 84 (100),
47 (21); HRMS m/z calcd for C22H15NO2 325.1103, found
325.1098.
4-(1-(Pyridin-2-yloxy)naphthalen-2-yl)benzaldehyde (5b0):brown,
viscous liquid; Rf = 0.50 (n-hexane/ethyl acetate, 5/2); 1H NMR
(300 MHz, CDCl3) δ 6.71 (d, J = 8.1 HZ, 1 H), 6.91 (dd, J = 7.1,
5.0 Hz, 1 H), 7.36 (d, J = 9.0 Hz, 1 H), 7.41-7.58 (m, 6 H), 7.89 (d,
J = 8.1 Hz, 2 H), 7.88-7.97 (m, 4 H), 8.10 (dd, J = 4.5, 1.8 Hz,
1 H), 10.05 (s, 1 H); 13C NMR (100 MHz, CDCl3) δ 111.3 (CH),
118.3 (CH), 122.0 (CH), 125.4 (CH ꢀ 2), 126.7 (CH), 128.3 (CH),
129.2 (Cq), 129.4 (CH ꢀ 2), 129.8 (CH), 131.4 (CH ꢀ 2), 133.0
(Cq), 135.3 (Cq), 139.3 (CH), 142.4 (Cq), 147.5 (CH), 148.3 (Cq),
163.8 (Cq), 192.1 (CH); MS (EI, m/z) 325(Mþ, 19), 324 (Mþ - Hþ,
9), 220 (38), 84 (100), 47 (22); HRMS m/z calcd for C22H15NO2
325.1103, found 325.1099.
4,40-(2-(Pyridin-2-yloxy)naphthalene-1,3-diyl)dibenzaldehyde
(5b00): brown, viscous liquid; Rf = 0.30 (n-hexane/ethyl acetate,
5/2); 1H NMR (300 MHz, CDCl3) δ 6.40 (d, J = 8.4 Hz, 1 H),
6.68 (dd, J = 7.1, 5.1 Hz, 1 H), 7.30 (td, J = 7.5, 1.8 Hz, 1 H),
7.41-7.56 (m, 5 H), 7.76 (d, J = 8.1 Hz, 2 H), 7.82 (d, J =
8.1 Hz, 2 H), 7.85-7.87 (m, 3 H), 7.97 (d, J = 7.8 Hz, 1 H),
8.01 (s, 1 H), 9.95 (s, 1 H), 10.03 (s, 1 H); 13C NMR (150
MHz, CDCl3) δ 110.8 (CH), 117.8 (CH), 125.5 (CH), 126.1
(CH), 127.2 (CH), 128.5 (CH), 129.3 (CH ꢀ 2), 129.4 (CH ꢀ 2),
130.0 (CH ꢀ 2), 130.7 (CH), 130.9 (Cq), 131.3 (CH ꢀ 2),
131.6 (Cq), 132.9 (Cq), 134.0 (Cq), 135.0 (Cq), 135.3 (Cq),
139.0 (CH), 142.4 (Cq), 144.4 (Cq), 145.7 (Cq), 146.9 (CH),
163.1 (Cq), 192.0 (CH), 192.1 (CH); MS (EI, m/z) 429 (Mþ, 3),
207 (100), 91 (44); HRMS m/z calcd for C29H19NO3 429.1365,
found 429.1359.
4-(10-(Pyridin-2-yloxy)phenanthren-9-yl)benzaldehyde (5d):
white solid; mp (dec) 171-172 °C; Rf = 0.33 (n-hexane/ethyl
acetate, 5/1); 1H NMR (300 MHz, CDCl3) δ 6.69 (d, J = 8.1 Hz,
1 H), 6.84 (dd, J = 7.1, 4.7 Hz, 1 H), 7.47-7.41 (m, 8 H), 7.86
(d, J = 8.4 Hz, 2 H), 7.96-7.98 (m, 2 H), 8.78 (d, J = 8.4 Hz,
2 H), 10.03 (s, 1 H); 13C NMR (100 MHz, CDCl3) δ 110.2 (CH),
118.0 (CH), 122.9 (CH ꢀ 2), 123.4 (CH), 126.3 (CH), 126.5
(CH), 127.0 (CH), 127.2 (CH), 127.3 (Cq), 127.4 (CH), 128.0
(Cq), 129.1 (Cq), 129.4 (CH ꢀ 2), 131.3 (CH ꢀ 2), 131.6 (Cq),
131.7 (Cq), 135.3 (Cq), 139.2 (CH), 142.9 (Cq), 144.8 (Cq), 147.5
(CH), 163.9 (Cq), 192.1 (CH); MS (EI, m/z) 375 (Mþ, 18), 374
(Mþ - Hþ, 9), 270 (29), 84 (100); HRMS m/z calcd for C26H17-
NO2 375.1259, found 375.1266.
50-Methoxy-20-(pyridin-2-yloxy)biphenyl-4-carbaldehyde (5e):
colorless, viscous liquid; Rf = 0.18 (n-hexane/ethyl acetate, 5/1);
1H NMR (300 MHz, CDCl3) δ 3.85 (s, 3 H), 6.73 (d, J = 8.4 Hz,
1 H), 6.86 (dd, J = 6.9, 5.4 Hz, 1 H), 6.96-7.00 (m, 2 H), 7.14 (d,
J = 9.6 Hz, 1 H), 7.54 (td, J = 7.8, 2.0 Hz, 1 H), 7.64 (d, J = 8.1
Hz, 2 H), 7.80 (d, J = 8.1 Hz, 2 H), 8.07 (dd, J = 4.8, 1.8 Hz,
1 H), 9.97 (s, 1 H); 13C NMR (100 MHz, CDCl3) δ 55.6 (CH3),
110.9 (CH), 114.9 (CH), 115.7 (CH), 124.0 (CH), 129.5 (CH ꢀ
2), 129.6 (CH ꢀ 2), 134.3 (Cq), 135.0 (Cq), 139.2 (CH), 144.1
(Cq), 144.2 (Cq), 147.5 (CH), 156.8 (Cq), 163.8 (Cq), 192.0
(CH); MS (EI, m/z) 305 (Mþ, 8), 304 (Mþ - Hþ, 10), 84 (100), 47
(23); HRMS m/z calcd for C19H15NO3 305.1052, found
305.1045.
50-Methyl-20-(pyridin-2-yloxy)biphenyl-4-carbaldehyde (5f):
colorless, viscous liquid; Rf = 0.33 (n-hexane/ethyl acetate, 5/1);
1H NMR (300 MHz, CDCl3) δ 2.42 (s, 3 H), 6.75 (d, J = 8.4 Hz,
1 H), 6.87 (dd, J = 7.1, 5.4 Hz, 1 H), 7.10 (d, J = 8.1 Hz, 1 H),
7.24-7.28 (m, 2 H), 7.56 (td, J = 7.8, 1.8 Hz, 1 H), 7.64 (d, J =
8.1 Hz, 2 H), 7.81 (d, J = 8.1 Hz, 2 H), 8.09 (dd, J = 5.3, 1.7 Hz,
1 H), 9.97 (s, 1 H); 13C NMR (100 MHz, CDCl3) δ 20.9 (CH3),
111.2 (CH), 118.1 (CH), 122.8 (CH), 129.5 (CH ꢀ 2), 129.7 (CH
ꢀ 2), 130.3 (CH), 131.4 (CH), 133.1 (Cq), 134.9 (Cq), 135.2 (Cq),
139.3 (CH), 144.4 (Cq), 147.6 (CH), 148.6 (Cq), 163.7 (Cq),
192.0 (CH); MS (EI, m/z) 289 (Mþ, 17), 288 (Mþ - Hþ, 29),
272 (23), 84 (100), 47 (24); HRMS m/z calcd for C19H15NO2
289.1103, found 289.1092.
2-Phenoxypyridine palladacycle I:23 yellow crystal; mp (dec)
>210 °C (lit. mp 226-228 °C); 1H NMR (300 MHz, CDCl3) δ
2.11 (s, 6 H), 6.59-6.68 (m, 6 H), 6.81-6.90 (m, 6 H), 7.54 (td,
J = 8.0, 1.5 Hz, 2 H), 8.03 (dd, J = 6.2, 1.7 Hz, 2 H).
2-(20-Deutero)phenoxypyridine (1-D): colorless, viscous liquid;
1H NMR (300 MHz, CDCl3) δ 6.92-7.25 (m, 4 H), 7.39-7.45 (m,
2 H), 7.67-7.73 (m, 1 H), 8.22 (dd, J = 5.0, 2.1 Hz, 1 H).
2-(40-Nitrophenyl)phenol (6b):27 yellow solid; mp 107-108 °C;
1
Rf = 0.24 (n-hexane/ethyl acetate, 5/1); H NMR (300 MHz,
CDCl3) δ 5.06 (bs, 1 H), 6.95 (dd, J = 8.7, 1.2 Hz, 1 H), 7.05 (td,
J = 7.8, 1.2 Hz, 1 H), 7.29-7.34 (m, 2 H), 7.73 (d, J = 8.9 Hz,
2 H), 8.31 (d, J = 8.9 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ
116.5 (CH), 121.5 (CH), 123.8 (CH ꢀ 2), 126.2 (Cq), 130.1 (CH
ꢀ 2), 130.3 (CH), 130.5 (CH), 144.6 (Cq), 147.3 (Cq), 152.5 (Cq);
MS (EI, m/z) 215 (Mþ, 100), 185 (23), 168 (30), 141 (36), 115
(43); HRMS m/z calcd for C12H9NO3 215.0582, found 215.0574.
4-(2-(Pyridin-2-yloxy)naphthalen-1-yl)benzaldehyde (5c): pale
yellow solid; mp 131-132 °C; Rf = 0.45 (n-hexane/ethyl acetate,
5/2); 1H NMR (300 MHz, CDCl3) δ 6.77 (d, J = 8.4 Hz, 1 H),
6.82 (dd, J = 6.8, 5.7 Hz, 1 H), 7.47-7.60 (m, 4 H), 7.73 (d, J =
8.4 Hz, 2 H), 7.83 (d, J = 8.4 Hz, 2 H), 7.87 (d, J = 8.4 Hz, 1 H),
7.91-7.98 (m, 3 H), 9.98 (s, 1 H); 13C NMR (100 MHz, CDCl3) δ
110.1 (CH), 118.0 (CH), 122.7 (CH), 126.0 (CH), 126.8 (CH),
127.6 (CH), 128.0 (CH), 128.1 (Cq), 129.5 (CH ꢀ 2), 129.7 (Cq),
130.0 (CH ꢀ 2), 134.7 (Cq), 134.9 (Cq), 139.3 (CH), 144.6 (Cq),
146.2 (Cq), 147.7 (CH), 163.7 (Cq), 192.0 (CH); MS (EI, m/z)
325 (Mþ, 85), 324 (Mþ - Hþ, 71), 308 (100), 296 (29), 220 (55),
189 (40), 84 (33); HRMS m/z calcd for C22H15NO2 325.1103,
found 325.1107.
Acknowledgment. We thank theNational Science Council
of the Republic of China for financial support.
Supporting Information Available: This material is available
free of charge via the Internet at http://pubs.acs.org.
(27) Colbert, J. C.; Lacy, R. M. J. Am. Chem. Soc. 1946, 68, 270–271.