N-arylation of pyridin-2(1H)-ones with pentavalent organobismuth reagents under copper-free conditions

Article abstract of DOI:10.1246/bcsj.79.761

An efficient method for the N-arylation of pyridin-2(1H)-ones and the related heteroaromatic lactams has been established via ligand-coupling reactions using tri- or tetra-aryl organobismuth(V) reagents such as triarylbismuth dichlorides. Also, N-alkenylation of pyridin-2(1H)-one was achieved similarly by using alkenyltriarylbismuth(V) reagents.

Full text of DOI:10.1246/bcsj.79.761

Ó 2006 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 79, No. 5, 761–767 (2006)
761
N-Arylation of Pyridin-2(1H)-ones with Pentavalent Organobismuth
Reagents under Copper-Free Conditions
ꢀ1;3
Kazuhiro Ikegai,1;2 Yuzo Nagata,1 and Teruaki Mukaiyama
1The Kitasato Institute, Center for Basic Research, 6-15-5 (TCI) Toshima, Kita-ku, Tokyo 114-0003
2Astellas Pharma Inc., Miyukigaoka Research Center, 21 Miyukigaoka, Tsukuba 305-8585
3Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
Received October 31, 2005; E-mail: mukaiyam@abeam.ocn.ne.jp
An efficient method for the N-arylation of pyridin-2(1H)-ones and the related heteroaromatic lactams has been es-
tablished via ligand-coupling reactions using tri- or tetra-aryl organobismuth(V) reagents such as triarylbismuth dichlo-
rides. Also, N-alkenylation of pyridin-2(1H)-one was achieved similarly by using alkenyltriarylbismuth(V) reagents.
N-Arylated derivatives of pyridin-2(1H)-ones and the relat-
ed heterocyclic lactams such as quinolin-2(1H)-ones are im-
portant components in many active pharmaceuticals and are
frequently employed for the investigation of their structure–
activity relationships.1
lectivity can be rationalized by assuming a mechanism that
involves the formation of covalently bonded Ar3XBiV–OPh
complexes that undergo ligand-coupling reactions via a con-
certed intramolecular aryl transfer (see Scheme 1). On the oth-
er hand, the facile N-arylation of amines and amides by bis-
muth reagents required the presence of copper catalysts such
as metallic copper and Cu(OAc)2 (Barton-modified Ullmann
reaction).2b,14,15 However, we expected that copper-free N-aryl-
ation of heteroaromatic lactams such as pyridin-2(1H)-one (or
2-hydroxypyridine) may proceed by ligand coupling via cova-
lent bismuth(V)–OPy intermediates based on the analogy with
C-arylation of phenols (Scheme 1).
In this article, we would like to report on a new and efficient
method for copper-free N-arylation and -alkenylation of pyri-
din-2(1H)-ones by using pentavalent organobismuth reagents
such as triarylbismuth dichlorides, providing various N-aryl
(or -alkenyl) pyridin-2(1H)-ones in moderate-to-high yields.16
The development of direct N-arylation reactions of nitrogen-
containing substrates such as primary or secondary amines,
amides, and heterocycles is an important issue in organic syn-
thesis. The classical copper-mediated Ullmann (or Goldberg-
modified Ullmann) condensation reactions2 were commonly
carried out under harsh reaction conditions (high temperatures,
use of strong bases and stoichiometric amounts of copper
or copper salts, and long reaction times) and the N-arylation
reactions of amides were usually sluggish compared to those
of amines due to their lower nucleophilicities. Recently,
Avendan˜o described the N-arylation of carbostyrils with cata-
lytic copper(II) acetate (Cu(OAc)2) and p-tolyllead triacetate
at elevated temperatures.3 Ukita et al.4 and Renger5 reported
Goldberg–Ullmann condensation of various heteroaromatic
lactams and aryl halides with copper(I) iodide (CuI) or copper
on silica (Cu/SiO2) at elevated temperatures. More recently,
Chan and Lam reported on the modified Ullmann-arylation of
a wide range of NH substrates, including poorly nucleophilic
substrates such as heteroaromatic amides, by using arylboronic
acids as aryl donors in the presence of Cu(OAc)2 and either tri-
ethylamine or pyridine at room temperature.6 Researchers at
Merck applied the Chan–Lam’s condition to direct N-arylation
of pyridin-2(1H)-ones in a program for the discovery of novel
and potent Factor Xa inhibitors.7 Li and Dixon also reported
that N-arylation of pyridin-2(1H)-ones with aryl halides pro-
ceeded smoothly by employing the Buchwald’s CuI–diamine
ligand system.1a
Results and Discussion
At first, pyridin-2(1H)-one (2.0 equiv) was treated succes-
sively with a base (2.0 equiv) and tri-o-tolylbismuth dichloride
OH
Base
O
OH
Ar
+
Ar
Ar
Bi Ar
Cl
C-Arylation
(Barton et al.)
Ar BiCl
2
Ar BiCl
3
2
N
H
O
The arylation of organic substrates by pentavalent bismuth
reagents8 has been known since 1980.9 Various poly-arylbis-
muth(V) compounds such as Ph3BiCl2, Ph3BiCO3, Ph4BiOTs,
and Ph5Bi are efficient reagents for the regioselective C-aryla-
tion of phenols,10 active methylene, or methine compounds,11
metal–enolates,12 and enones.14 The C-arylation of phenols
takes place preferentially at the ortho position.10 The regiose-
N
Ar
+
O
N
Base
O
Ar
Ar
N-Arylation
(This work)
Bi Ar
Cl
Ar BiCl
2
Scheme 1. Working hypothesis for N-arylation of pyridin-
2(1H)-ones.
Published on the web May 12, 2006; DOI: 10.1246/bcsj.79.761

762 Bull. Chem. Soc. Jpn. Vol. 79, No. 5 (2006)
N-Arylation of Pyridin-2(1H)-ones
Table 2. N-o-Tolylation of Substituted Pyridin-2-onesaÞ
Table 1. Effect of Bases on N-o-Tolylation of Pyridin-2-
oneaÞ
R
t-BuOK
(o-Tol)3BiCl2
H
Base
(2.0 equiv.)
(o-Tol)3BiCl2
(1.0 equiv.)
H
O
N
(2.0 equiv.)
(1.0 equiv.)
O
N
N
O
N
O
Me
Me
THF
rt, 10 min
Temp., 3 h
THF
rt, 3 h
R
1
(2.0 equiv.)
1a
(2.0 equiv.)
rt, 10 min
Yield/%bÞ
Entry Substrate
Temp/ꢁC Yield/%bÞ Product
Entry
Base
H
1
2
3
R ¼ Me
R ¼ Br
rt
reflux
reflux
95
93
78
1b
1c
1d
1
2
3
4
5
6
7
t-BuOLi
n-BuLi
t-BuONa
NaH
t-BuOK
NDdÞ
NDdÞ
72
O
N
R ¼ NO2
R
O
75
95 ð40Þ
H
N
cÞ
4
5
R ¼ H
rt
reflux
90
89
1e
1f
1,1,3,3-Tetramethylguanidine
Et3N
69
NDdÞ
R ¼ NO2
R
Me
a) All reactions were carried out with pyridin-2(1H)-one (0.6
mmol), t-BuOK (0.6 mmol), and (o-Tol)3BiCl2 (0.3 mmol) in
THF (3 mL) at rt. b) Isolated yields. c) The yield in the case
when the reaction was carried out with equimolar amounts
of the reagents (0.3 mmol) in THF (3 mL). d) Not detected.
6
7
8
9
R ¼ Cl
R ¼ Br
reflux
reflux
79
51
86
85
1g
1h
1i
H
N
O
R ¼ CO2Et reflux
R
R
R ¼ NO2
reflux
1j
H
N
10
11
O R ¼ Me
R ¼ Cl
reflux
reflux
42
NDcÞ
1k
—
(1.0 equiv) in tetrahydrofuran (THF) at room temperature in
order to attempt the N-arylation reaction as shown in Table 1.
The desired N-o-tolylated product 1a was formed most effec-
tively in the case when potassium t-butoxide (t-BuOK) was
used (Table 1, Entry 5). The use of sodium hydride (NaH)
or sodium t-butoxide (t-BuONa) was found moderately effec-
tive to give 1a in 72–75% yields, while lithium bases did not
afford the arylated product (Table 1, Entries 1–4). In the case
when 1,1,3,3-tetramethylguanidine (TMG) was used as an
organic base, 1a was obtained in 69% yield (Table 1, Entry 6).
Thus, we decided to use t-BuOK as the base in the following
experiments. It is important to note that the yield of 1a de-
creased to 40% when the reaction was carried out by using
equimolar amounts of pyridin-2(1H)-one, t-BuOK, and (o-
Tol)3BiCl2, and that the addition of t-BuOK (2.0 equiv) to
the THF solution of pyridin-2(1H)-one (2.0 equiv) and (o-
Tol)3BiCl2 (1.0 equiv) gave 1a only in 70% yield.
Next, o-tolylation of substituted pyridin-2(1H)-ones was
tried under the above-mentioned conditions of using (o-Tol)3-
BiCl2 and t-BuOK (Table 2). Various 1-(2-methylphenyl)pyr-
idin-2(1H)-one derivatives were successfully synthesized in
moderate-to-high yields under mild and copper-free condi-
tions. It should be noted that these o-tolylated products were
not formed by the copper-catalyzed Ullmann reactions be-
tween pyridin-2(1H)-ones and 2-halotoluene because of the
steric hindrance of the o-tolyl group.1 N-o-Tolylation of 3- or
4-methylpyridin-2(1H)-one proceeded smoothly at room tem-
perature (Table 2, Entries 1 and 4), although refluxing condi-
tions were required when substrates having electron-withdraw-
ing substituents such as halogen, carboxylic ester, and nitro
groups were used (Table 2, Entries 2, 3, and 5–9). N-o-Tolyl-
ation of sterically hindered 6-methylpyridin-2(1H)-one gave
1k in modest yield under refluxing conditions (Table 2,
Entry 10), while the 6-chloro derivative never afforded the de-
sired product (Table 2, Entry 11). Thus, the present condition
showed broad substrate generality in the o-tolylation of sub-
stituted pyridin-2(1H)-ones. According to Li and Dixon’s re-
a) All reactions were carried out with a substrate (0.6 mmol),
t-BuOK (0.6 mmol), and (o-Tol)3BiCl2 (0.3 mmol) in THF
(3 mL). b) Isolated yields. c) Not detected.
port,1a arylation of 5-nitropyridin-2(1H)-one and 6-methylpyri-
din-2(1H)-one with aryl halides afforded trace amounts of the
desired products by the CuI–diamine system.
N-o-Tolylation of various heteroaromatic lactams was also
studied (see Table 3). Pyrimidin-4(3H)-one, quinolin-2(1H)-
one, and quinazolin-4(3H)-one were arylated regioselectively
and gave 1l, 1m, and 1o in good yields (Table 3, Entries 1,
3, and 5). In the case of the reaction with quinoxalin-2(1H)-
one (Table 3, Entry 4), the N-tolylated product 1n was formed
along with a small amount of the O-tolylated product 2n (82
and 10%, respectively). The reactions with pyrimidin-2(1H)-
one, phthalazin-1(2H)-one, and phthalimide did not afford
the arylated products under the same conditions (Table 3,
Entries 2, 6, and 7).
We next focused on the substituent effects on migratory ap-
titudes of aryl ligands attached to the bismuth(V) center17 and
the arylation of pyridin-2(1H)-one was examined by using var-
ious substituted triarylbismuth dichlorides (Table 4). ortho-
Substituted phenyl groups as well as an unsubstituted phenyl
one were transferred to the nitrogen atom of pyridin-2(1H)-
one. Importantly, triphenylbismuth dichloride (Ph3BiCl2) and
tri(p-Tol)bismuth dichloride ((p-Tol)3BiCl2) were less reac-
tive in the aryl transfer in comparison with sterically congested
(o-Tol)3BiCl2, and the N-arylated products 1p and 1q were
produced only when the reactions were carried out under re-
fluxing conditions (Table 4, Entries 1 and 2). The similar reac-
tivity differences between Ph3BiCl2 and (o-Tol)3BiCl2 in the
oxidation of alcohols were reported by Matano and co-work-
ers.18 They explained the reasons for the result by considering
that the introduction of a methyl group to the ortho position
may have weakened the C–BiV bonds in the transition states

K. Ikegai et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 5 (2006)
763
Table 3. N-o-Tolylation of Various Heteroaromatic Lac-
tamsaÞ
Table 4. Substituent Effects on Aryl LigandsaÞ
R1
Entry
1
Substrate
Product
Yield/%bÞ
77
R2
BiCl2
H
R1
t-BuOK
(2.0 equiv.)
O
N
3
H
1l
—
N
N
O
N
(1.0 equiv.)
N
N
Me
O
O
THF
Temp., 3 h
O
R2
H
N
(2.0 equiv.)
rt, 10 min
1
O
O
2
3
—
N
NDcÞ
71
N
Entry
R1
R2
Temp/ꢁC Yield/%bÞ
Product
H
N
1
2
3
4
5
6
7
8
9
H
H
H
H
Me
Cl
OMe
H
Cl
OMe
H
reflux
reflux
rt
reflux
rt
rt
rt
rt
reflux
71
62
69
81
95
91
1p
1q
1r
1s
1a
1t
1u (2u)
1v
1w (2w)
1m
Me
Me
H
Me
Me
Me
CF3
OMe
1n
2n
1o
—
82
10
N
+
H
N
O
cÞ
N
38 ð47Þ
O
O
4
71
47 ð9Þ
Me
N
cÞ
H
N
a) All reactions were carried out with pyridin-2(1H)-one
(0.6 mmol), t-BuOK (0.6 mmol), and a bismuth reagent
(0.3 mmol) in THF (3 mL). b) Isolated yields. c) Yields of
the corresponding O-arylated products 2.
N
O
O
NH
5
6
N
76
Me
N
O
N
Me
MeO
OMe
N
O
N
O
—
NDcÞ
NH
N
2u
2w
O
Table 5. Phenylation of Pyridin-2(1H)-one by Using Vari-
ous Organobismuth(V) Reagents
NDcÞ
NH
7
—
—
O
H
a) All reactions were carried out with a substrate (0.6 mmol),
t-BuOK (0.6 mmol), and (o-Tol)3BiCl2 (0.3 mmol) in reflux-
ing THF (3 mL). b) Isolated yields. c) Not detected.
V
N
O
O
t-BuOK
Bi reagents
N
THF
reflux, 3 h
rt, 10 min
1p
due to the steric hindrance, which increased the rate of the
aryl migration. The use of (p-MeO-C6H4)3BiCl2 led to regio-
selective N-arylation to afford 1s in 81% yield, while the use
of sterically hindered (o-MeO-C6H4)3BiCl2 and (4-MeO-2-
Me-C6H3)3BiCl2 afforded the desired products with modest
N-/O-selectivities (Table 4, Entries 4, 7, and 9).
Entry
Reagent
Yield/% Entry
Reagent
Yield/%
1aÞ Ph3BiCl2
2aÞ Ph3BiF2
3aÞ Ph3Bi(OAc)2
71
73
0
4aÞ Ph3BiCO3
5bÞ Ph4BiF
ꢂ
6bÞ [Ph4Biþ][BF4
]
0
68
51
a) Reactions were carried out with pyridin-2(1H)-one (0.6
mmol), t-BuOK (0.6 mmol), and a bismuth reagent (0.3 mmol)
in refluxing THF (3 mL). b) Reactions were carried out with
equimolar amounts of pyridin-2(1H)-one, t-BuOK, and a bis-
muth reagent (0.3 mmol) in refluxing THF (3 mL).
Next, N-phenylation of pyridin-2(1H)-one was investigated
by using various tri- or tetra-phenylbismuth(V) reagents (see
Table 5). Triphenylbismuth difluoride (Ph3BiF2) showed high
reactivity comparable to that of Ph3BiCl2, affording 1p in 73%
yield (Table 5, Entry 2). The desired product was not formed
with Ph3Bi(OAc)2 or Ph3BiCO3 (Table 5, Entries 3 and 4).
This indicates that the leaving groups on the bismuth center in-
fluence the formation of the covalent BiV–OPy intermediate.
When tetraphenylbismuth(V) reagents such as Ph4BiF12a and
pated that the use of the tetra-coordinated bismuthonium salt
4a, which is a useful reagent for C-alkenylation of phenols
and 1,3-dicarbonyl compounds,19b would give the N-styrylpyri-
din-2(1H)-one (3) only in 19% yield and the unreacted pyridin-
2(1H)-one would be recovered. The decrease in yield compared
to the N-phenylation with [Ph4Biþ][BF4ꢂ] can be explained by
considering the decomposition of 4a via ꢀ-proton abstraction
and subsequent vinylidene carbene generation.20 Based on this
consideration, the use of the un-ionized, penta-coordinated
styryltri-p-tolylbismuth fluoride 4b was then tried, and 3 and
1q were produced in high total yield, but the selectivity of
alkenyl vs aryl transfer was quite lower in the N-alkenylation
[Ph4Biþ][BF4
]
were allowed to react with an equimolar
ꢂ
19a
amount of the amide, 1p was obtained in reasonable yields
(68 and 51% yields, respectively) together with considerable
amounts of triphenylbismuthane (Table 5, Entries 5 and 6).
As shown in Table 6, N-alkenylation of pyridin-2(1H)-one
was next tried by using styryltri-p-tolylbismuth(V) reagents
4a19b and 4b,12a which were prepared from (p-Tol)3BiF2 ac-
cording to Matano and Maruoka’s procedure. It was unantici-

764 Bull. Chem. Soc. Jpn. Vol. 79, No. 5 (2006)
N-Arylation of Pyridin-2(1H)-ones
Table 6. N-Alkenylation with Alkenyltriarylbismuth Re-
agentsaÞ
N
K
O
BiV reagents
(1.1 equiv.)
N
O
N
O
t-BuOK
(1.0 equiv.)
O
H
(2 equiv.)
O
N
Ph
(1)
(2)
Ph
Ph
Ph
+
Ph2BiOPy
Bi
O
N
(X=Y = Cl, F)
1q
+
rt, 2 h
THF
rt, 10 min
Py
X
(1.0 equiv.)
3
Ph
Ph
Bi Ph
Yield/%
Y
N
K
O
Entry
Reagent
[(p-Tol)3BiþCH=CHPh][BF4
(p-Tol)3Bi(F)CH=CHPh
3
1q
N
O
N
Ph
+
O
(1 equiv.)
ꢂ
1
2
]
4a
4b
19
44
trace
42
Ph
Ph
Bi
X= F, BF4
Y= Ph
Ph
Ph3Bi
a) Reactions were carried out with pyridin-2(1H)-one (0.2
mmol), t-BuOK (0.2 mmol), and a bismuth reagent (0.22
mmol) in THF (2 mL) at rt.
Scheme 2. Postulated mechanisms.
(o-Tol) BiCl
t-BuOK
Me
3
2
Me
O
(2.0 equiv.)
(1.0 equiv.)
N
HN
+
N
reflux, 3 h
THF
O
O
rt, 10 min
(2.0 equiv.)
5 (42%)
(0%)
N
KCl
O
o-Tol
o-Tol
Bi
O
Me
(4-Py)
Scheme 3. O-Selective tolylation of pyridin-4(1H)-one.
of pyridin-2(1H)-one compared to the case of C-alkenylation of
1,3-dicarbonyl compounds19b and enol silyl ethers.12a
by the thermal degradation of (p-nitrophenyloxy)tetraphenyl-
bismuth was reported by Barton et al.10a It is considered, there-
fore, that the imidate-type structure of BiV–O–C(R)=N(R)
in the above-mentioned (pyridin-2-yloxy)–BiV complexes are
likely to induce N-arylation via a concerted reaction through
a weakly polarized, cyclic transition state.
A postulated reaction mechanism of the present arylation re-
actions is described in Scheme 2. In the cases of the reactions
with triarylbismuth dichlorides, two-fold amounts of the potas-
sium salt of pyridin-2(1H)-one were needed so as to attain bet-
ter results. Therefore, it is considered that the two molecules of
the substrate were initially replaced at the bismuth(V) center
and the corresponding adduct, namely Ar3Bi(OPy)2, was gen-
erated as a key intermediate. The adduct in turn thermally de-
composed via the reductive elimination of trivalent bismuth de-
rivatives, affording the desired N-arylated product (Scheme 2,
Eq. 1). The N-phenylation with tetraphenylbismuth(V) re-
agents were analogously explained by considering the Ph4Bi-
(OPy) adduct, which was transformed into N-phenylpyridin-
2(1H)-one and triphenylbismuthane (Scheme 2, Eq. 2).
In order to prove the importance of the postulated imidate-
like structure of BiV–O–C(R)=N(R) in the above BiV com-
plexes, the arylation of pyridin-4(1H)-one with (o-Tol)3BiCl2
was then tried (Scheme 3). Surprisingly, O-selective arylation
took place at elevated temperatures and 4-(2-methylphenoxy)-
pyridine (5) was formed predominantly in 42% yield. The re-
sult was in contrast to facile N-arylation of pyridin-2(1H)-one
at room temperature. The O-arylation proceeded probably via
the ligand coupling from the (pyridin-4-yloxy)–bismuth(V) in-
termediate. A similar O-selective phenylation of p-nitrophenol
Conclusion
It was demonstrated here that copper-free, facile N-arylation
of various types of structurally and electrically diverse pyridin-
2(1H)-ones and the related heteroaromatic lactams such as
pyrimidin-4(3H)-one, quinolin-2(1H)-one, quinazolin-4(3H)-
one, and quinoxalin-2(1H)-one was accomplished by a novel
arylation system using a combination of tri- or tetra-arylbis-
muth(V) reagents and potassium t-butoxide. The arylation re-
actions usually took place at a nitrogen atom of the amide moi-
eties in a regioselective manner, and various functionalities
such as halogen, carboxylic ester, and nitro groups on pyri-
din-2(1H)-one were tolerated under the mild conditions. In a
similar fashion, N-alkenylation of pyridin-2(1H)-one with the
alkenyltriarylbismuth fluoride 4b was also achieved with a
moderate selectivity of alkenyl vs aryl transfer. To the best
of our knowledge, this is the first example of efficient N-aryl-
ation of amide substrates with pentavalent bismuth reagents
under copper-free conditions.

K. Ikegai et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 5 (2006)
765
13C NMR (68 MHz, CDCl3) ꢁ 158.0, 141.8, 139.8, 137.4, 134.6,
130.9, 129.1, 126.9, 126.7, 117.1, 105.7, 17.5. Anal. Calcd for
C12H10BrNO: C, 54.57; H, 3.82; N, 5.30; Br, 30.25%. Found:
C, 54.43; H, 3.90; N, 5.24; Br, 30.00%.
Experimental
General. All melting points were determined on a Yanagimoto
micro melting point apparatus (Yanaco MP-S3) and remain uncor-
rected. Infrared (IR) spectra were recorded by an attenuated total
reflection (ATR) method on a SensIR Technologies TravelIRÔ
spectrometer. 1H NMR spectra were recorded on a JEOL JNM-
EX270L (270 MHz) spectrometer; chemical shifts (ꢁ) are reported
in parts per million relative to tetramethylsilane. Splitting patterns
are designated as s, singlet; d, doublet; t, triplet; q, quartet; m,
multiplet; and br, broad. 13C NMR spectra were recorded on a
JEOL JNM-EX270L (68 MHz) spectrometer with complete proton
decoupling. Chemical shifts are reported in parts per million rela-
tive to tetramethylsilane with the solvent resonance as the internal
standard (CDCl3; ꢁ ¼ 77:0 ppm). High resolution mass spectra
(HRMS) were recorded on a JEOL JMS-700T or a Thermo Elec-
tron Finnigan TSQ Quantum ultra AM mass spectrometer. Ele-
mental analysis were performed on a vario EL III analyzer. Ana-
lytical TLC was performed on Merck precoated TLC plates (silica
gel 60 GF254, 0.25 mm). Preparative thin-layer chromatography
(PTLC) was carried out on silica gel Wakogel B-5F. All reactions
were carried out under an argon atmosphere in dried glassware,
unless otherwise noted. Triarylbismuth dichlorides18 (or difluo-
rides21), Ph4BiBF4,19a Ph4BiF,12a 4a,19b and 4b12a were prepared
according to the reported procedures. Ph3BiCO3, Ph3Bi(OAc)2,
and t-BuOK were purchased from Tokyo Kasei Kogyo and used
without any purification. Pyridin-2(1H)-one derivatives and other
amides were purchased from Tokyo Kasei Kogyo or Aldrich, and
used without any purification. Dehydrated THF was purchased
from Kanto Chemical Co., Inc.
Typical Experimental Procedure for the Synthesis of N-
Arylpyridin-2(1H)-ones Using Ar3BiCl2 and t-BuOK. To a so-
lution of pyridin-2(1H)-one (57.1 mg, 0.6 mmol) in anhydrous
THF (3.0 mL) was added potassium t-butoxide (67.3 mg, 0.6
mmol) at room temperature. After 10 min, triarylbismuth dichlo-
ride (0.3 mmol) was added to the resulting suspension and the solu-
tion was allowed to stand at the temperatures shown in Tables 1–5.
After 2 h, the mixture was diluted with ethyl acetate and washed
successively with 1 M HCl, 2 M NaOH, and brine, then dried over
Na2SO4. After concentration, the crude was purified by preparative
thin-layer chromatography (eluent: hexane/EtOAc, the range from
3/2 to 2/3) to afford the desired arylated product.
3-Nitro-1-(2-methylphenyl)pyridin-2(1H)-one (1d): Yellow
solid. mp 103–105 ꢁC. IR (ATR, cmꢂ1) 1676, 1594, 1518, 1487,
1
1334, 1261, 1246, 768, 748. H NMR (270 MHz, CDCl3) ꢁ 8.40
(dd, J ¼ 7:6, 2.1 Hz, 1H), 7.61 (dd, J ¼ 6:6, 2.1 Hz, 1H), 7.50–
7.25 (m, 3H), 7.16 (d, J ¼ 6:8 Hz, 1H), 6.41 (dd, J ¼ 7:6, 6.6 Hz,
1H), 2.15 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 153.7, 144.5,
139.2, 139.0, 138.6, 134.5, 131.1, 129.7, 127.1, 126.6, 103.3, 17.5.
Anal. Calcd for C12H10N2O3: C, 62.60; H, 4.38; N, 12.17%.
Found: C, 62.41; H, 4.36; N, 12.09%.
4-Methyl-1-(2-methylphenyl)pyridin-2(1H)-one (1e): White
solid. mp 140–141 ꢁC. IR (ATR, cmꢂ1) 1658, 1579, 1527, 1272,
1
848, 790, 776. H NMR (270 MHz, CDCl3) ꢁ 7.38–7.10 (m, 4H),
7.07 (d, J ¼ 6:9 Hz, 1H), 6.46 (s, 1H), 6.08 (d, J ¼ 6:9 Hz, 1H),
2.23 (s, 3H), 2.15 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 161.8,
151.4, 139.9, 136.6, 134.9, 130.8, 128.7, 127.0, 126.8, 119.8,
108.2, 21.3, 17.6. Anal. Calcd for C13H13NO: C, 78.36; H, 6.58;
N, 7.03%. Found: C, 78.07; H, 6.58; N, 6.91%.
4-Methyl-1-(2-methylphenyl)-5-nitropyridin-2(1H)-one (1f):
Yellow solid. mp 140–143 ꢁC. IR (ATR, cmꢂ1) 1677, 1607, 1530,
1490, 1433, 1341, 1315, 1272, 1240, 1214, 1091, 927, 882, 772,
722. 1H NMR (270 MHz, CDCl3) ꢁ 8.51 (s, 1H), 7.48–7.11 (m,
4H), 6.47 (s, 1H), 2.60 (s, 3H), 2.17 (s, 3H). 13C NMR (68 MHz,
CDCl3) ꢁ 160.0, 146.0, 140.6, 138.1, 134.6, 132.2, 131.2, 129.9,
127.3, 126.7, 120.8, 21.5, 17.6. Anal. Calcd for C13H12N2O3: C,
63.93; H, 4.95; N, 11.47%. Found: C, 63.97; H, 5.05; N, 11.52%.
5-Chloro-1-(2-methylphenyl)pyridin-2(1H)-one (1g): White
solid. mp 94–96 ꢁC. IR (ATR, cmꢂ1) 1661, 1588, 1527, 1492,
1268, 824, 743. 1H NMR (270 MHz, CDCl3) ꢁ 7.41–7.23 (m, 5H),
7.17 (d, J ¼ 6:9 Hz, 1H), 6.64 (d, J ¼ 9:7 Hz, 1H), 2.17 (s, 3H).
13C NMR (68 MHz, CDCl3) ꢁ 160.3, 140.9, 139.3, 135.3, 134.8,
131.1, 129.3, 127.1, 126.8, 122.4, 112.2, 17.6. Anal. Calcd for
C12H10ClNO: C, 65.61; H, 4.59; N, 6.38; Cl, 16.14%. Found: C,
65.40; H, 4.63; N, 6.28; Cl, 16.22%.
5-Bromo-1-(2-methylphenyl)pyridin-2(1H)-one (1h): White
solid. mp 97–99 ꢁC. IR (ATR, cmꢂ1) 1681, 1589, 1521, 1492,
1279, 822, 731. 1H NMR (270 MHz, CDCl3) ꢁ 7.44 (d, J ¼ 9:7
Hz, 1H), 7.40–7.24 (m, 4H), 7.16 (d, J ¼ 7:1 Hz, 1H), 6.59 (d, J ¼
9:7 Hz, 1H), 2.17 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 160.3,
142.9, 139.2, 137.6, 134.8, 131.1, 129.3, 127.1, 126.8, 122.8, 97.8,
17.6. Anal. Calcd for C12H10BrNO: C, 54.57; H, 3.82; N, 5.30; Br,
30.25%. Found: C, 54.42; H, 3.91; N, 5.28;þBr, 29.83%; HRMS
(FABþ): Calcd for C12H11BrNO: ½M þ Hꢃ 264.0024. Found:
m=z 264.0034.
1-(2-Methylphenyl)pyridin-2(1H)-one (1a): White solid. mp
74–75 ꢁC. IR (ATR, cmꢂ1) 1657, 1572, 1527, 1274, 1253, 1135,
759. 1H NMR (270 MHz, CDCl3) ꢁ 7.48–7.24 (m, 4H), 7.23–7.12
(m, 2H), 6.65 (dd, J ¼ 9:5, 0.7 Hz, 1H), 6.23 (ddd, J ¼ 6:8, 6.6,
1.3 Hz, 1H), 2.15 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 161.8,
139.9, 139.8, 137.7, 134.7, 130.8, 128.8, 126.9, 126.8, 121.5,
105.6, 17.5. Anal. Calcd for C12H11NO: C, 77.81; H, 5.99; N,
7.56%. Found: C, 77.31; H, 6.00; N, 7.43%.
Ethyl 1-(2-Methylphenyl)-6-oxo-1,6-dihydropyridine-3-car-
boxylate (1i): Colorless oil. IR (ATR, cmꢂ1) 1712, 1667, 1538,
1
1438, 1262, 1239, 1098, 770, 727. H NMR (270 MHz, CDCl3) ꢁ
3-Methyl-1-(2-methylphenyl)pyridin-2(1H)-one (1b): White
solid. mp 95–98 ꢁC. IR (ATR, cmꢂ1) 1650, 1592, 1546, 1493,
1266, 764. 1H NMR (270 MHz, CDCl3) ꢁ 7.36–7.22 (m, 4H),
7.16 (d, J ¼ 6:4 Hz, 1H), 7.07 (dd, J ¼ 6:8, 1.3 Hz, 1H), 6.15 (t,
J ¼ 6:8 Hz, 1H), 2.19 (s, 3H), 2.13 (s, 3H). 13C NMR (68 MHz,
CDCl3) ꢁ 162.2, 140.3, 136.8, 135.1, 134.8, 130.8, 130.6, 128.6,
126.9, 126.8, 105.3, 17.6, 17.3. Anal. Calcd for C13H13NO: C,
78.36; H, 6.58; N, 7.03%. Found: C, 78.34; H, 6.61; N, 6.89%.
3-Bromo-1-(2-methylphenyl)pyridin-2(1H)-one (1c): White
solid. mp 85–87 ꢁC. IR (ATR, cmꢂ1) 1650, 1596, 1578, 1492,
1260, 748. 1H NMR (270 MHz, CDCl3) ꢁ 7.81 (d, J ¼ 7:1 Hz,
1H), 7.40–7.08 (m, 5H), 6.15 (t, J ¼ 7:1 Hz, 1H), 2.13 (s, 3H).
8.10 (dd, J ¼ 2:6, 0.5 Hz, 1H), 7.96 (dd, J ¼ 9:7, 2.6 Hz, 1H),
7.43–7.28 (m, 3H), 7.20 (d, J ¼ 6:9 Hz, 1H), 6.65 (d, J ¼ 9:6 Hz,
1H), 4.32 (q, J ¼ 7:1 Hz, 2H), 2.16 (s, 3H), 1.34 (t, J ¼ 7:1 Hz,
3H). 13C NMR (68 MHz, CDCl3) ꢁ 163.9, 161.7, 143.0, 139.3,
138.9, 134.7, 131.1, 129.4, 127.1, 126.8, 120.3, 110.0, 61.0, 17.5,
14.3. HRMS (FABþ): Calcd for C15H16NO3: ½M þ Hꢃþ 258.1130.
Found: m=z 258.1115.
1-(2-Methylphenyl)-5-nitropyridin-2(1H)-one (1j): Yellow
oil. IR (ATR, cmꢂ1) 1677, 1616, 1555, 1500, 1336, 1271, 1241,
1102, 829, 732. 1H NMR (270 MHz, CDCl3) ꢁ 8.54 (d, J ¼ 3:0
Hz, 1H), 8.18 (dd, J ¼ 10:1, 3.0 Hz, 1H), 7.48–7.30 (m, 3H),
7.20 (d, J ¼ 7:6 Hz, 1H), 6.65 (d, J ¼ 10:2 Hz, 1H), 2.18 (s, 3H).

766 Bull. Chem. Soc. Jpn. Vol. 79, No. 5 (2006)
N-Arylation of Pyridin-2(1H)-ones
13C NMR (68 MHz, CDCl3) ꢁ 160.6, 139.8, 138.4, 134.5,
133.5, 131.3, 130.6, 130.0, 127.4, 126.6, 120.2, 17.6. HRMS
(FABþ): Calcd for C12H11N2O3: ½M þ Hꢃþ 231.0770. Found:
m=z 231.0753.
6-Methyl-1-(2-methylphenyl)pyridin-2(1H)-one (1k): White
solid. mp 93–95 ꢁC. IR (ATR, cmꢂ1) 1657, 1579, 1545, 813, 767,
722. 1H NMR (270 MHz, CDCl3) ꢁ 7.41–7.24 (m, 4H), 7.13–7.04
(m, 1H), 6.54 (d, J ¼ 9:2 Hz, 1H), 6.12 (d, J ¼ 6:8 Hz, 1H), 2.08
(s, 3H), 1.88 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 163.2, 146.1,
139.5, 137.8, 134.9, 131.2, 128.9, 127.5, 127.2, 118.4,þ106.0, 21.1,
17.3. HRMS (FABþ): Calcd for C13H14NO: ½M þ Hꢃ 200.1075.
Found: m=z 200.1087.
13C NMR (68 MHz, CDCl3) ꢁ 162.3, 139.6, 138.2 (ꢄ2), 137.9,
129.7, 126.1, 121.6, 105.6, 21.1. HRMS (FABþ): Calcd for
C12H12NO: ½M þ Hꢃþ 186.0919. Found: m=z 186.0930.
1-(4-Chlorophenyl)pyridin-2(1H)-one (1r): White solid. mp
132–134 ꢁC. IR (ATR, cmꢂ1) 1658, 1575, 1531, 1487, 1275,
1085, 997, 841, 820, 757, 732. 1H NMR (270 MHz, CDCl3) ꢁ
7.53–7.22 (m, 6H), 6.64 (d, J ¼ 9:2 Hz, 1H), 6.25 (t, J ¼ 6:6
Hz, 1H). 13C NMR (68 MHz, CDCl3) ꢁ 162.0, 139.9, 139.2,
137.4, 134.2, 129.4, 127.8, 121.9, 106.1. HRMS (FABþ): Calcd
for C11H9ClNO: ½M þ Hꢃþ 206.0373. Found: m=z 206.0379.
1-(4-Methoxyphenyl)pyridin-2(1H)-one (1s): White solid.
mp 106–108 ꢁC. IR (ATR, cmꢂ1) 1657, 1582, 1507, 1248, 827,
1
3-(2-Methylphenyl)pyrimidin-4(3H)-one (1l): Colorless oil.
1
774, 763. H NMR (270 MHz, CDCl3) ꢁ 7.43–7.24 (m, 4H), 6.98
IR (ATR, cmꢂ1) 1670, 1521, 1246, 985, 835, 754. H NMR (270
(d, J ¼ 8:7 Hz, 2H), 6.64 (d, J ¼ 9:2 Hz, 1H), 6.21 (t, J ¼ 6:6 Hz,
1H), 3.84 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 162.5, 159.2,
139.6, 138.1, 133.7, 127.5, 121.7, 114.4, þ105.6, 55.5. HRMS
(FABþ): Calcd for C12H12NO2: ½M þ Hꢃ 202.0868. Found:
m=z 202.0869.
1-(4-Chloro-2-methylphenyl)pyridin-2(1H)-one (1t): White
solid. mp 124–126 ꢁC. IR (ATR, cmꢂ1) 1649, 1585, 1531, 1486,
1286, 1135, 998, 849, 835, 775. 1H NMR (270 MHz, CDCl3) ꢁ
7.43 (ddd, J ¼ 9:2, 6.6, 2.0 Hz, 1H), 7.36–7.23 (m, 2H), 7.20–7.08
(m, 2H), 6.66 (ddd, J ¼ 9:2, 1.3, 0.8 Hz, 1H), 6.26 (ddd, J ¼ 6:8,
6.6, 1.3 Hz, 1H), 2.14 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ
161.8, 140.0, 138.5, 137.5, 136.9, 134.5, 130.8, 128.3, 127.1,
121.7, 106.0, 17.6. Anal. Calcd for C12H10ClNO: C, 65.61; H,
4.59; N, 6.38; Cl, 16.14%. Found: C, 65.49; H, 4.58; N, 6.30;
Cl, 16.22%.
1-(4-Methoxy-2-methylphenyl)pyridin-2(1H)-one (1u): White
solid. mp 116–117 ꢁC. IR (ATR, cmꢂ1) 1649, 1579, 1500, 1236,
1053, 701. 1H NMR (270 MHz, CDCl3) ꢁ 7.41 (ddd, J ¼ 9:1, 6.4,
2.0 Hz, 1H), 7.19 (ddd, J ¼ 6:8, 2.0, 0.7 Hz, 1H), 7.10 (dd, J ¼
7:7, 1.3 Hz, 1H), 6.89–6.78 (m, 2H), 6.66 (ddd, J ¼ 9:1, 1.3, 0.7
Hz, 1H), 6.22 (ddd, J ¼ 6:8, 6.4, 1.3 Hz, 1H), 3.82 (s, 3H), 2.12 (s,
3H). 13C NMR (68 MHz, CDCl3) ꢁ 162.3, 159.5, 139.8, 138.3,
136.1, 133.0, 127.9, 121.7, 116.1, 112.2, 105.6, 55.4, 17.9. Anal.
Calcd for C13H13NO2: C, 72.54; H, 6.09; N, 6.51%. Found: C,
72.51; H, 6.08; N, 6.52%.
MHz, CDCl3) ꢁ 8.04 (s, 1H), 7.96 (d, J ¼ 6:6 Hz, 1H), 7.48–7.28
(m, 3H), 7.18 (d, J ¼ 7:4 Hz, 1H), 6.56 (d, J ¼ 6:6 Hz, 1H), 2.18
(s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 160.0, 153.3, 151.0, 136.0,
135.2, 131.2, 129.8, 127.2 (ꢄ2), 116.5, 17.6. HRMS (FABþ):
Calcd for C11H11N2O: ½M þ Hꢃþ 187.0871. Found: m=z 187.0859.
1-(2-Methylphenyl)quinolin-2(1H)-one (1m): White solid.
mp 142–145 ꢁC. IR (ATR, cmꢂ1) 1658, 1589, 1557, 1489, 1444,
1
1401, 1292, 1245, 828, 768. H NMR (270 MHz, CDCl3) ꢁ 7.99
(d, J ¼ 9:4 Hz, 1H), 7.60 (dd, J ¼ 7:7, 1.3 Hz, 1H), 7.47–7.27 (m,
4H), 7.24–7.11 (m, 2H), 6.80 (d, J ¼ 9:4 Hz, 1H), 6.55 (d, J ¼ 8:4
Hz, 1H), 2.02 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 161.6, 140.2,
139.7, 136.3, 136.0, 131.4, 130.2, 129.1, 128.5, 128.2, 127.6,
122.2, 122.1, 120.2, 115.3, 17.3. Anal. Calcd for C16H13NO: C,
81.68; H, 5.57; N, 5.95%. Found: C, 81.30; H, 5.64; N, 5.87%.
1-(2-Methylphenyl)quinoxalin-2(1H)-one (1n): White solid.
mp 114–116 ꢁC. IR (ATR, cmꢂ1) 1653, 1586, 1458, 754, 741.
1H NMR (270 MHz, CDCl3) ꢁ 8.41 (s, 1H), 7.93 (d, J ¼ 7:6 Hz,
1H), 7.51–7.25 (m, 5H), 7.17 (d, J ¼ 6:9 Hz, 1H), 6.60 (d, J ¼
7:7 Hz, 1H), 2.04 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 154.0,
150.8, 135.7, 134.1, 133.3, 133.1, 131.6, 130.8, 130.0, 129.7,
128.0, 127.7, 123.8, 115.1, 17.4. Anal. Calcd for C15H12N2O: C,
76.25; H, 5.12; N, 11.86%. Found: C, 76.36; H, 5.27; N, 11.99%.
2-(2-Methylphenoxy)quinoxaline (2n): White solid. mp 82–
84 ꢁC. IR (ATR, cmꢂ1) 1569, 1492, 1392, 1300, 1214, 1175, 750.
1H NMR (270 MHz, CDCl3) ꢁ 8.71 (s, 1H), 8.11–8.00 (m, 1H),
7.79–7.53 (m, 3H), 7.38–7.10 (m, 4H), 2.21 (s, 3H). 13C NMR
(68 MHz, CDCl3) ꢁ 156.7, 151.1, 140.1, 139.4, 138.7, 131.3,
130.5, 130.2, 128.8, 127.7, 127.2, 127.0, 125.6, 121.8, 16.6.
HRMS (FABþ): Calcd for C15H13N2O: ½M þ Hꢃþ 237.1028.
Found: m=z 237.1043.
2-(4-Methoxy-2-methylphenoxy)pyridine (2u):
Colorless
oil. IR (ATR, cmꢂ1) 1592, 1498, 1464, 1426, 1238, 1197, 1041,
1
865, 776. H NMR (270 MHz, CDCl3) ꢁ 8.20–8.12 (m, 1H), 7.63
(ddd, J ¼ 8:2, 7.1, 2.0 Hz, 1H), 6.98 (d, J ¼ 8:6 Hz, 1H), 6.95–
6.88 (m, 1H), 6.86–6.72 (m, 3H), 3.79 (s, 3H), 2.14 (s, 3H).
13C NMR (68 MHz, CDCl3) ꢁ 163.9, 156.5, 147.6, 145.5, 139.1,
131.7, 122.6, 117.6, 116.3, 112.0, 110.2,þ55.5, 16.7. HRMS
(FABþ): Calcd for C13H14NO2: ½M þ Hꢃ 216.1025. Found:
m=z 216.1029.
3-(2-Methylphenyl)quinazolin-4(3H)-one (1o): Colorless oil.
IR (ATR, cmꢂ1) 1670, 1607, 1602, 1469, 1295, 1264, 913, 769.
1H NMR (270 MHz, CDCl3) ꢁ 8.37 (d, J ¼ 7:6 Hz, 1H), 7.99 (s,
1H), 7.87–7.72 (m, 2H), 7.60–7.29 (m, 4H), 7.25 (d, J ¼ 7:1 Hz,
1H), 2.20 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 160.2, 147.9,
146.2, 136.5, 135.6, 134.4, 131.2, 129.6, 127.7, 127.5, 127.4,
127.2, 127.0, 122.3, 17.8. HRMS (FABþ): Calcd for C15H13N2O:
½M þ Hꢃþ 237.1028. Found: m=z 237.1043.
1-[2-(Trifluoromethyl)phenyl]pyridin-2(1H)-one (1v): White
solid. mp 100–102 ꢁC. IR (ATR, cmꢂ1) 1663, 1583, 1530, 1316,
1
1161, 1114, 1061, 763. H NMR (270 MHz, CDCl3) ꢁ 7.87–7.54
(m, 3H), 7.48–7.33 (m, 2H), 7.18 (ddd, J ¼ 6:9, 1.0, 0.8 Hz, 1H),
6.64 (ddd, J ¼ 9:2, 1.3, 0.8 Hz, 1H), 6.23 (ddd, J ¼ 6:8, 6.6,
1.3 Hz, 1H). 13C NMR (68 MHz, CDCl3) ꢁ 162.3, 140.2, 138.3
(d, J ¼ 2 Hz), 137.8, 133.1, 130.1, 129.4, 127.5 (q, J ¼ 31 Hz),
127.3 (q, J ¼ 5 Hz), 122.7 (q, J ¼ 273 Hz), 121.5, 105.1. HRMS
(FABþ): Calcd for C12H9F3NO: ½M þ Hꢃþ 240.0636. Found:
m=z 240.0636.
1-(2-Methoxyphenyl)pyridin-2(1H)-one (1w): White solid.
mp 127–129 ꢁC. IR (ATR, cmꢂ1) 1658, 1580, 1524, 1503, 1291,
1270, 1236, 759. 1H NMR (270 MHz, CDCl3) ꢁ 7.46–7.33 (m,
2H), 7.31–7.15 (m, 2H), 7.11–6.98 (m, 2H), 6.65 (ddd, J ¼ 9:2,
1.3, 0.8 Hz, 1H), 6.19 (ddd, J ¼ 6:8, 6.6, 1.3 Hz, 1H), 3.81 (s,
1-Phenylpyridin-2(1H)-one4,5 (1p): White solid. mp 126–
128 ꢁC (lit.4 mp 129 ꢁC). IR (ATR, cmꢂ1) 1654, 1579, 1526,
1
1491, 1276, 1255, 1139, 759, 690. H NMR (270 MHz, CDCl3) ꢁ
7.53–7.28 (m, 7H), 6.65 (d, J ¼ 9:2 Hz, 1H), 6.19 (dt, J ¼ 6:8,
1.3 Hz, 1H). 13C NMR (68 MHz, CDCl3) ꢁ 162.1, 140.7, 139.7,
137.8, 129.1, 128.3, 126.3, 121.7, 105.8.
1-(4-Methylphenyl)pyridin-2(1H)-one7 (1q): White solid.
mp 131–133 ꢁC. IR (ATR, cmꢂ1) 1657, 1580, 1525, 1506, 1275,
1
816, 760. H NMR (270 MHz, CDCl3) ꢁ 7.41–7.20 (m, 6H), 6.64
(d, J ¼ 9:2 Hz, 1H), 6.21 (t, J ¼ 6:6 Hz, 1H), 2.39 (s, 3H).

K. Ikegai et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 5 (2006)
767
3H). 13C NMR (68 MHz, CDCl3) ꢁ 162.1, 154.0, 139.7, 138.8,
130.1, 129.5, 128.4, 121.6, 120.8, 112.3, 105.2, 55.9. Anal. Calcd
for C12H11NO2: C, 71.63; H, 5.51; N, 6.96%. Found: C, 71.13; H,
5.61; N, 6.80%.
Combs, Tetrahedron Lett. 1998, 39, 2941. c) P. Y. S. Lam, S.
Deudon, E. Hauptman, C. G. Clark, Tetrahedron Lett. 2001, 42,
2427. d) P. Y. S. Lam, G. Vincent, C. G. Clark, S. Deudon, P. K.
Jadhav, Tetrahedron Lett. 2001, 42, 3415. e) P. Y. S. Lam, C. G.
Clark, S. Saubern, J. Adams, K. M. Averill, D. M. T. Chan, A.
Combs, Synlett 2000, 674.
2-(2-Methoxyphenoxy)pyridine (2w): White solid. mp 89–
90 ꢁC. IR (ATR, cmꢂ1) 1595, 1569, 1496, 1467, 1427, 1270,
1
1241, 1174, 1109, 1023, 746. H NMR (270 MHz, CDCl3) ꢁ 8.14
7
W. W. K. R. Mederski, M. Lefort, M. Germann, D. Kux,
Tetrahedron 1999, 55, 12757.
For reviews on organobismuth chemistry, see: a) R. A.
(ddd, J ¼ 4:9, 2.0, 0.8 Hz, 1H), 7.65 (ddd, J ¼ 8:2, 7.3, 2.0 Hz,
1H), 7.20 (ddd, J ¼ 8:4, 7.3, 1.8 Hz, 1H), 7.14 (dd, J ¼ 7:7, 1.5
Hz, 1H), 7.06–6.88 (m, 4H), 3.77 (s, 3H). 13C NMR (68 MHz,
CDCl3) ꢁ 163.5, 151.6, 147.3, 142.4, 138.9, 125.8, 122.9, 120.9,
117.8, 112.8, 110.5, 55.8. HRMS (FABþ): Calcd for C12H12NO2:
½M þ Hꢃþ 202.0868. Found: m=z 202.0872.
8
Abramovitch, D. H. R. Barton, J.-P. Finet, Tetrahedron 1988,
44, 3039. b) J.-P. Finet, Chem. Rev. 1989, 89, 1487. c) Y. Matano,
H. Suzuki, Bull. Chem. Soc. Jpn. 1996, 69, 267. d) H. Suzuki, T.
Ikegami, Y. Matano, Synthesis 1997, 249. e) N. Komatsu, In
Organobismuth Chemistry, ed. by H. Suzuki, Y. Matano, Elsevier,
New York, 2001, Chap. 5, p. 371. f) G. I. Elliott, J. P. Konopelski,
Tetrahedron 2001, 57, 5683.
A Typical Procedure for the N-Alkenylation of Pyridine-
2(1H)-one. Synthesis of 1-Styrylpyridin-2(1H)-one (3): To
a solution of pyridine-2(1H)-one (19.0 mg, 0.2 mmol) in anhy-
drous THF (2.0 mL) was added potassium t-butoxide (22.4 mg,
0.2 mmol) and the mixture was stirred for 10 min at room temper-
ature. The styryltri-p-tolylbismuth reagent 4a or 4b (0.22 mmol)
was added to the mixture, and the mixture was stirred for an addi-
tional 2 h at rt. The reaction was quenched with 1 M HCl and the
mixture was extracted with ethyl acetate, and the combined organ-
ic layer was dried over Na2SO4. The solution was concentrated in
vacuo and the residue was subjected to thin-layer chromatography
on silica gel (hexane/EtOAc = 1/1) to give 3 as a white solid. 3;
mp 135–137 ꢁC. IR (ATR, cmꢂ1) 1657, 1585, 1530, 1264, 957,
751, 690. 1H NMR (270 MHz, CDCl3) ꢁ 8.00 (d, J ¼ 14:8 Hz,
1H), 7.63 (d, J ¼ 6:9 Hz, 1H), 7.53–7.20 (m, 6H), 6.74–6.56 (m,
2H), 6.26 (t, J ¼ 6:8 Hz, 1H). 13C NMR (68 MHz, CDCl3) ꢁ
161.3, 139.3, 134.6, 132.6, 128.7, 128.1, 126.6, 125.8, 121.5,
121.1, 106.7. HRMS (FABþ): Calcd for C13H12NO: ½M þ Hꢃþ
198.0919. Found: m=z 198.0922.
9
D. H. R. Barton, D. J. Lester, W. B. Motherwell, M. T. B.
Papoula, J. Chem. Soc., Chem. Commun. 1980, 246.
10 a) D. H. R. Barton, N. Y. Bhatnagar, J.-C. Blazejewski, B.
Charpiot, J.-P. Finet, D. J. Lester, W. B. Motherwell, M. T. B.
Papoula, S. P. Stanforth, J. Chem. Soc., Perkin Trans. 1 1985,
2657. b) D. H. R. Barton, N. Y. Bhatnagar, J.-P. Finet, J. Khamsi,
W. B. Motherwell, S. P. Stanforth, Tetrahedron 1987, 43, 323.
11 a) D. H. R. Barton, J.-C. Blazejewski, B. Charpiot, J.-P.
Finet, W. B. Motherwell, M. T. B. Papoula, S. P. Stanforth,
J. Chem. Soc., Perkin Trans. 1 1985, 2667. b) R. S. Fornicola, E.
Oblinger, J. Montgomery, J. Org. Chem. 1998, 63, 3528. c) K. C.
Santhosh, K. K. Balasubramanian, J. Chem. Soc., Chem. Commun.
1992, 224.
12 a) T. Ooi, R. Goto, K. Maruoka, J. Am. Chem. Soc. 2003,
125, 10494. b) T. Arnauld, D. H. R. Barton, J. Org. Chem. 1999,
64, 6915.
4-(2-Methylphenoxy)pyridine (5): Colorless oil. IR (ATR,
cmꢂ1) 1573, 1486, 1250, 1204, 1179, 1110, 881, 814, 775, 743,
714. 1H NMR (270 MHz, CDCl3) ꢁ 8.43 (d, J ¼ 5:9 Hz, 2H),
7.33–6.10 (m, 3H), 7.01 (d, J ¼ 7:6 Hz, 1H), 6.74 (d, J ¼ 5:9 Hz,
2H), 3.77 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢁ 164.5, 151.7,
151.2, 131.7, 130.6, 127.5, 125.7, 121þ.2, 111.3, 16.0. HRMS
(FABþ): Calcd for C12H12NO: ½M þ Hꢃ 186.0919. Found: m=z
186.0931.
13 P. K. Koech, M. J. Krische, J. Am. Chem. Soc. 2004, 126,
5350.
14 a) T. Arnauld, D. H. R. Barton, E. Doris, Tetrahedron
1997, 53, 4137. b) D. H. R. Barton, J.-P. Finet, J. Khamsi, Tetra-
hedron Lett. 1989, 30, 937. c) D. H. R. Barton, J.-P. Finet,
J. Khamsi, Tetrahedron Lett. 1986, 27, 3615.
15 A few examples of N-phenylation with organobismuth
compounds in the absence of copper catalysts were reported.
a) D. H. R. Barton, J.-P. Finet, W. B. Motherwell, C. Pichon,
J. Chem. Soc., Perkin Trans. 1 1987, 251. b) D. H. R. Barton,
J.-P. Finet, C. Pichon, J. Chem. Soc., Chem. Commun. 1986, 65.
c) D. H. R. Barton, J.-C. Blazejewski, B. Charpiot, D. J. Lester,
W. B. Motherwell, M. T. B. Papoula, J. Chem. Soc., Chem.
Commun. 1980, 827. d) M. S. Akhtar, W. J. Brouillette, D. V.
Waterhous, J. Org. Chem. 1990, 55, 5222.
This study was supported in part by the Grant of the 21st
Century COE Program, Ministry of Education, Culture, Sports,
Science and Technology (MEXT). The authors wish to thank
Astellas Pharma Inc. for their help with high-resolution mass
spectrometry analysis and elemental analysis.
16 K. Ikegai, T. Mukaiyama, Chem. Lett. 2005, 34, 1496.
17 D. H. R. Barton, N. Y. Bhatnagar, J.-P. Finet, W. B.
Motherwell, Tetrahedron 1986, 42, 3111.
18 Y. Matano, T. Hisanaga, H. Yamada, S. Kusakabe, H.
Nomura, H. Imahori, J. Org. Chem. 2004, 69, 8676; Y. Matano,
H. Nomura, Angew. Chem., Int. Ed. 2002, 41, 3028.
19 a) Y. Matano, S. A. Begum, T. Miyamatsu, H. Suzuki,
Organometallics 1998, 17, 4332. b) Y. Matano, H. Imahori, J.
Org. Chem. 2004, 69, 5505.
20 Y. Matano, M. Yoshimune, N. Azuma, H. Suzuki, J. Chem.
Soc., Perkin Trans. 1 1996, 1971.
21 a) F. Challenger, J. F. Wilkinson, J. Chem. Soc., Trans.
1922, 121, 91. b) Y. Matano, N. Azuma, H. Suzuki, J. Chem.
Soc., Perkin Trans. 1 1994, 1739.
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