An improved Ullmann-Ukita-Buchwald-Li conditions for CuI-catalyzed coupling reaction of 2-pyridones with aryl halides

Article abstract of DOI:10.1016/j.tet.2005.01.063

An effective CuI-trans-N,N′-dimethylcyclohexane-1,2-diamine (DMCDA)-K₂CO₃-catalyzed coupling reaction of 2-pyridones with aryl halides is described. Under our conditions, DMCDA was found to be an effective catalyst that facilitates the coupling reactions even in toluene, a common industrial solvent. In addition, 3-bromopyridine could also be coupled effectively under these conditions, indicating that the catalytic reactivity of this system is high. The reaction could be applied for polymer modification and iterative oligo-pyridone synthesis.

Full text of DOI:10.1016/j.tet.2005.01.063

Tetrahedron 61 (2005) 2931–2939
An improved Ullmann–Ukita–Buchwald–Li conditions for
CuI-catalyzed coupling reaction of 2-pyridones with aryl halides
Po-Shih Wang,a,b Chih-Kai Lianga,b and Man-kit Leunga,b,
*
aDepartment of Chemistry, National Taiwan University, Taipei 106, Taiwan ROC
bInstitute of Polymer Science and Engineering, National Taiwan University, Taipei 106, Taiwan ROC
Received 20 October 2004; revised 31 December 2004; accepted 5 January 2005
Abstract—An effective CuI-trans-N,N0-dimethylcyclohexane-1,2-diamine (DMCDA)-K2CO3-catalyzed coupling reaction of 2-pyridones
with aryl halides is described. Under our conditions, DMCDA was found to be an effective catalyst that facilitates the coupling reactions even
in toluene, a common industrial solvent. In addition, 3-bromopyridine could also be coupled effectively under these conditions, indicating
that the catalytic reactivity of this system is high. The reaction could be applied for polymer modification and iterative oligo-pyridone
synthesis.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Li has recently reported a modification of the Ukita
conditions, using CuI–MeNHCH2CH2NHMe–K3PO4 in
dioxane to promote the coupling reaction.4b In his work,
detail electronic effects on pyridones as well as on the aryl
halides have been evaluated.
N-Substituted pyrid-2-ones have attracted synthetic organic
chemists because of their chemical reactivity, photo-
chemical behavior, as well as their biological activities.1,2
Direct C–N bond formation is one of the most convenient
synthetic approaches for N-alkylpyridones.3 However,
synthetic examples for N-arylpyridones are rare.4
Traditional copper-catalyzed Ullmann type C–N bond
formation often requires the use of high temperatures as
well as stoichiometric amounts of copper reagents.5
Recently, palladium catalyzed N-arylations have been
extensively explored.6 In addition, Ullmann-type copper-
catalyzed processes for C–N bond formation such as
N-arylation of amines,7 anilines,8 amides,9 imidazole,10
indoles,9 and hydrazines11 have been reported. The
reactivity of the copper catalyst strongly relies on the ligand
system used in the reaction. N,N0-Dimethylethylene-
diamines and derivatives are known effective ligands to
promote the reactions.
In this report, we noted that CuI could facilitate the coupling
of aryl halides with 2-hydroxypyridines under milder
conditions in the presence of N,N0-dimethylcyclohexane-
1,2-diamine (DMCDA) as the ligand. The reaction could
proceed in toluene instead of dioxane or DMF.12 Toluene is
a common solvent that could be used for industrial
applications.
Recently, we have attempted the synthesis of 2-amino-
pyridines.13 In one experiment, we accidentally observed
that 2 equiv of 2-bromopyridine (1) would undergo self-
condensation in the presence of CuI/DMCDA/K2CO3 as the
catalyst to give N-(pyrid-2-yl)pyrid-2-one (2) as the major
product. Although we could not conclusively differentiate
the N-arylated or O-arylated structure on the basis of the
NMR spectrum, X-ray crystallographic analysis of the self-
condensation product (4) unambiguously shows that the
pyridyl group is attached to the pyridone nitrogen atom
(Fig. 1, Scheme 1).
Ukita has recently reported the copper-catalyzed Ullmann
N-arylation of 2-hydroxypyridine.4a Copper halides, oxides,
or copper powder facilitates the reaction. However, high
temperatures of 120–150 8C in DMF are usually required.
The reaction is sensitive to steric hindrance. Ortho-
substituted aryl halides are ineffective toward the coupling
reaction.
Keywords: 2-Pyridones; Copper reagents; C–N coupling; Toluene.
* Corresponding author.; e-mail: mkleung@ntu.edu.tw
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.063

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P.-S. Wang et al. / Tetrahedron 61 (2005) 2931–2939
However, 2-chloropyridine was found to be sluggish in the
self-condensation reaction. Although no direct evidence
was obtained for the reaction mechanism, we suspect that
hydrolysis of 2-bromopyridine (1) under the reaction
conditions would occur to give 2-hydroxypyridine. The
newly generated 2-hydroxypyridine would then be further
coupled with 2-bromopyridine to give (2). Since we could
not isolate any 2-hydroxypyridine from the reaction
mixture, we proposed that the coupling of 2-hydroxy-
pyridine with 2-bromopyridine is relatively fast in
comparison to the 2-hydroxypyridine formation.
These observations suggested that cross coupling of
2-hydroxypyridine with other 2-aryl halides might be
feasible under similar reaction conditions (Table 2).
Figure 1. The ORTEP of 4.
In our initial screening experiments, 2-hydroxypyridine and
bromobenzene were used as the prototype substrates for
searching the reaction conditions. In contrast to Ukita’s
reaction conditions4a in which no reaction would occur in
mesitylene, our reaction proceeds smoothly in toluene at
reflux temperature. More surprisingly, the reaction is very
specific to 2-hydroxypyridine. Other phenolic derivatives
such as 3- and 4-hydroxypyridines, 2-hydroxypyrimidine,
and phenol or phthalimide do not couple with bromo-
benzene under the above conditions. The choice of the
ligand strongly affects the reactivity of the cross-coupling
reaction. The use of CHDA under similar conditions gave
N-phenylpyrid-2-one (5) in low yield (3%). TMEDA does
not promote the reaction.
Scheme 1.
It is noteworthy that unsubstituted or tetrasubstituted 1,2-
diamines such as trans-cyclohexane-1,2-diamine(CHDA)
or tetramethylethylene-1,2-diamine (TMEDA) do not
promote the self-condensation reaction, indicating that
DMCDA is essential for the reaction. When CHDA was
applied, no reaction occurred. On the other hand, bromo–
iodo exchange reaction occurred to give 2-iodopyridine
(20%) in the presence of TMEDA. The self-condensation
reaction could be applied to other 2-halopyridines (Table 1).
Both KOAc and K2CO3 were found to be effective as bases.
Table 1. Self-condensation of 2-halopyridines
Substrate
CuI, L (equiv)
Product (yield %)
0.2, 0.2
XZBr (56) XZI (44)a
2
0.2, 0.2
(57)b
3
0.2, 0.2
(36)b
4
0.2, 1
(7)c
2
L: trans-N,N0-Dimethyl-cyclohexane-1,2-diamine.
a 16 h.
b 20 h.
c 24 h.

P.-S. Wang et al. / Tetrahedron 61 (2005) 2931–2939
Table 2. Cross coupling of 2-hydroxypyridine with various aryl halides
2933
Entry
Aryl hailde
Product (%)
Entry
Aryl halide
Product (%)
XZBr (91)
XZ1 (84)
1
11
(59)
5
15
2
3
(89)
(70)
6
7
12
(79)
16
4
(38)
13
(68)
2
8
9
5
6
7
(82)
(61)
(81)
14
15
16
(76)
(65)
(33)
17
18
19
10
11
12
8
9
(2)a
17
18
19
(74)
(62)
(80)
20
(37)
13
14
21
22
10
(!1)
a In DMF.

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P.-S. Wang et al. / Tetrahedron 61 (2005) 2931–2939
1
aromatic H NMR signals at d 6.14 (1H), 6.42 (1H), 6.81
However, KOtBu will attack 2-bromopyridine to give
2-tert-butoxypyridine.14 The reaction will also proceed in
other solvents such as DMF or dioxane.
(2H), 7.23 (2H), and 7.41 (2H), and nine sets of sp2 13
C
NMR signals at d 105.2, 120.3, 125.9, 127.6, 138.2, 138.7,
140.0, 144.9 and 160.8 suggested the polypyridone
formation (Scheme 2).
However, the use of toluene gave the best results. The
optimized reaction conditions of 20 mol% CuI, 20 mol%
DMCDA, and 2 equiv K2CO3 were applied to the N-aryl-
ation of 2-hydroxypyridine with a number of aryl halides
(Table 2). Functional groups that are compatible with this
CuI-catalyzed N-arylation protocol include ether, thioether,
triarylamine, nitrile, nitro group, styrene, and ester. No
significant electronic effects on the aryl halides were
observed in the reaction. As can be seen, the electron-
deficient aryl bromides such as 3-NO2C6H4Br and 4-CNC6-
H4Br, as well as the electron-rich aryl bromides such as
4-MeOC6H4Br or Ph2NC6H4Br are effectively coupled in
the reaction.
Scheme 2.
Electronic effects on 2-hydroxypyridine are significant,
however. Electron-withdrawing substituents that would
reduce the nucleophilicity of 2-hydroxypyridine do retard
its reactivity toward the coupling reaction. Thus, the
reaction of 2-hydroxy-5-nitropyridine is very sluggish.
Similar results were reported in Li’s conditions.
The reaction could be extended to iterative oligo-pyridone
synthesis (Scheme 3). As mentioned before, the bromo
group of 2-bromopyridine could be replaced by tert-
butoxide in the presence of KOtBu. Thus, reaction of 25
with KOtBu afforded 26. CuI-catalyzed condensation of 2-
hydroxypyridine with 26 gave 27 in moderated yield.
The reaction could also be applied to heterocyclic aryl
halides such as pyridine, thiophene, and thiazole. In contrast
to the results of Ukita’s and Li’s conditions, our conditions
could also be applied to 3-bromopyridine to give the
corresponding pyridone 17 in high yield.
The reaction is very sensitive to the steric environment of
the aryl halides. Usually, o-substituted aryl bromides do not
show enough reactivity in the reaction. Thus, regioselective
coupling would occur at the 4-position of 2,4-dibromo-
anisole to give the para substituted product (entry 9,
Table 2).
Similarly, although 2-bromonaphthalene could react
smoothly to give the desired pyridone, as mentioned in
Ukita’s paper, 1-bromonaphthalene does not react under
these conditions (compare entries 5 and 10, Table 2). We
have applied this method for purifying 1-bromonaphtha-
lene. Commercially available 1-bromonaphthalene is
usually contaminated by a few percent of 2-bromonaphtha-
lene. Since they have similar polarity and boiling point, they
are difficult to separate. When the contaminated 1-bromo-
naphthalene was treated with 2-hydroxypyridine in the
presence of the copper catalyst, the 2-bromo impurity was
selectively converted to the more polar pyridone and
removed by liquid chromatography. No bromo–iodo
exchange was observed under these reaction conditions.
Scheme 3.
Deprotection of 27 by removal of the tert-butyl group in
TFA afforded 28 in high yield. Compound 28 is slightly
hygroscopic and has to be dried under vacuum at 110 8C
before use in order to obtain the third generation of oligo-
pyridone 29 in high yield. This iterative approach proved to
be effective. Further application of this approach to the
synthesis of tailored oligo-pyridones is ongoing (Scheme 3).
The reactivity of the reaction is so high that it could be
successfully applied to polymer modification. Treatment of
the commercially available poly(4-bromostyrene) (23) with
2-hydroxypyridine under the same conditions affords the
target polypyridone (24) in reasonable yield. The structural
assignment was supported by IR and NMR spectroscopy.
The final polymer shows characteristic IR absorption bands
of pyridone at 1663 and 1590 cmK1, along with the
disappearance of the characteristic IR absorption band of
poly(4-bromostyrene) at 1073 cmK1. In addition, five
2. Experimental
2.1. The CuI-catalyzed self-condensation of 2-bromo-
pyridine
trans-N,N0-Dimethylcyclohexane-1,2-diamine (DMCDA)

P.-S. Wang et al. / Tetrahedron 61 (2005) 2931–2939
2935
was prepared according to the supporting information in
literature.9c
2.3. General procedure for the CuI-catalyzed N-
arylation of 2-hydroxypyridine
To an oven-dried double-necked flask containing a stir-bar
was charged 2-hydroxypyridine (1 equiv), CuI (20 mol%),
and K2CO3 (2 equiv). The flask was evacuated and back-
filled with nitrogen. A solution of arylbromide in toluene
(1 M, 1 equiv) and DMCDA (20 mol%) were injected under
nitrogen. The reaction mixture was stirred and heated at
reflux temperature for the time specified. The resulting
mixture was cooled to room temperature, diluted with
dichloromethane, and filtered. The filtrate was washed with
water. The organic phase was collected, dried over
anhydrous MgSO4, and concentrated. The crude product
was purified by flash chromatography on silica gel (ethyl
acetate/dichloromethane).
2.2. General procedure
To an oven-dried double-necked flask containing a stir-bar
was charged CuI (20 mol%) and K2CO3 (2 equiv). The flask
was evacuated and backfilled with nitrogen. A solution of
2-bromopyridine in toluene (1 M, 1 equiv) and DMCDA
(20 mol%) were injected under nitrogen. The reaction
mixture was stirred and heated at reflux temperature for
the time specified. The resulting mixture was cooled to room
temperature, diluted with dichloromethane, and filtered. The
filtrate was washed with water. The organic phase was
collected, dried over anhydrous MgSO4, and concentrated.
The crude product was purified by flash chromatography on
silica gel (ethyl acetate/dichloromethane).
2.3.1. 1-Phenyl-1H-pyridin-2-one (5).17 Reaction time:
18 h, colourless solid (91%). Mp 153–154 8C (from CH2Cl2/
hexaneZ1:10); 1H NMR (400 MHz, d6-DMSO) d 7.62 (dd,
JZ7.2, 1.6 Hz, 1H), 7.47–7.52 (m, 3H), 7.44 (d, JZ7.2 Hz,
1H), 7.33–7.41 (m, 2H), 6.47 (d, JZ8.8 Hz, 1H), 6.30 (td,
JZ6.8, 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 162.1,
140.7, 139.6, 137.8, 129.1, 128.3, 126.3, 121.7, 105.8; IR
2.2.1. 1-(2-Pyridyl)-1H-pyridin-2-one (2).15 Reaction
time: 16 h, white solid (56%). Mp 53–54 8C (from hexane);
1H NMR (400 MHz, CDCl3) d 8.54 (d, JZ5.2 Hz, 1H), 7.91
(d, JZ6.8 Hz, 1H), 7.79–7.84 (m, 2H), 7.36 (ddd, JZ9.2,
6.8, 2.4 Hz, 1H), 7.29 (ddd, JZ6.8, 5.2, 1.2 Hz, 1H), 6.61
(d, JZ9.2 Hz, 1H), 6.27 (td, JZ6.8, 1.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 161.9, 151.5, 148.6, 140.0, 137.5,
135.8, 123.0, 121.8, 121.2, 106.1; IR (KBr): 3058, 2991,
1673 (C]O), 1612, 1540 cmK1; FAB (NBA) 173.1 (MCC
H); HRMS calcd for C10H9N2O 173.0715, found 173.0712
(MCCH), calcd for C10H8N2O 172.0637, found 172.0639
(MC). Anal. calcd for C10H8N2O C, 69.76; H, 4.68; N,
16.27. Found C, 69.73; H, 4.70; N, 16.26.
(KBr): 3038, 1671(C]O), 1611, 1585, 1499, 1447 cmK1
;
FAB (NBA) 172.1 (MCCH), HRMS calcd for C11H10NO
171.0762, found 172.0759 (MCCH), calcd for C11H9NO
171.0684, found 171.0686 (MC). Anal. calcd for C11H9NO:
C, 77.17; H, 5.30; N, 8.18. Found C, 77.30; H, 5.12; N, 8.11.
2.3.2. 1-(4-Methoxyphenyl)-1H-pyrid-2-one (6). Reaction
time: 20 h, white solid (89%). Mp 110–111 8C (from
1
CH2Cl2/hexaneZ1:10); H NMR (400 MHz, d6-acetone) d
7.5 (ddd, JZ7, 2.2, 0.8 Hz, 1H), 7.43 (ddd, JZ9.2, 6.7,
2.2 Hz, 1H), 7.32 (dt, JZ9.2, 2.8 Hz, 2H), 7.02 (dt, JZ9.2,
2.8 Hz, 2H), 6.42 (ddd,, JZ9.2, 1.2, 0.8 Hz, 1H), 6.24 (td,
JZ6.7, 1.6 Hz, 1H), 3.85 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 162.4, 159.1, 139.5, 138.1, 133.6, 127.4, 121.6,
114.4, 105.6, 55.5; IR (KBr): 3024, 2363, 2325, 1661
(C]O), 1599, 1499, 1435 cmK1; FAB (NBA) 202.1
(MCCH); HRMS calcd for C12H12NO2 202.0868, found
202.0865 (MCCH), calcd for C12H11NO2 201.0790, found
201.0797 (MC). Anal. calcd for C12H11NO2: C, 71.63; H,
5.51; N, 6.96. Found C, 71.93; H, 5.29; N, 6.87.
2.2.2. 1-(4-Methylpyrid-2-yl)-4-methyl-1H-pyridin-2-
one (3).15 Reaction time: 20 h, colorless solid (57%). Mp
79–81 8C (from hexane); H NMR (400 MHz, CDCl3) d
8.37 (d, JZ5.2 Hz, 1H), 7.70–7.72 (m, 2H), 7.09 (ddd, JZ
5.2, 1.2, 0.8 Hz, 1H), 6.41 (bs, 1H), 6.10 (dd, JZ7.2, 2 Hz,
1H), 2.40 (s, 3H), 2.20 (d, JZ0.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 161.9, 151.8, 151.7, 149.1, 148.2,
134.9, 124.0, 121.9, 119.9, 108.8, 21.4, 21.3; IR (CH2Cl2):
1
3044, 2922, 1670 (C]O), 1614, 1599, 1537, 1406 cmK1
;
FAB (NBA) 201.1 (MCCH), 200.1 (MC); HRMS calcd for
C12H13N2O 201.1028, found 201.1031 (MCCH), calcd for
C12H12N2O 200.0950, found 200.0951 (MC). Anal. calcd
for C12H12N2O C, 71.98; H, 6.04; N, 13.99. Found C, 71.89;
H, 6.09; N, 13.98.
2.3.3. 1-(4-Cyanophenyl)-1H-pyridin-2-one (7).18 Reac-
tion time: 12 h, white solid (70%). Mp 165–166 8C (from
CH2Cl2/hexaneZ1:10); 1H NMR (400 MHz, CDCl3) d 7.75
(d, JZ8.4 Hz, 2H), 7.51 (d, JZ8.4 Hz, 2H), 7.39 (ddd, JZ
9.2, 6.8, 2.2 Hz, 1H), 7.28 (dd, JZ7, 2.2 Hz, 1H), 6.61 (d,
JZ9.2 Hz, 1H), 6.26 (t, JZ6.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 161.5, 144.1, 140.1, 136.5, 133.0,
127.3, 121.9, 117.7, 112.1, 106.6; IR (KBr): 3100, 3038,
2362, 2325, 1673 (C]O), 1599, 1523, 1499 cmK1; FAB
(NBA) 197.0 (MCCH); HRMS calcd for C12H9N2O
197.0715, found 197.0711 (MCCH), calcd for C12H8N2O
196.0637, found 196.0643 (MC). Anal. calcd for
C12H8N2O: C, 73.46; H, 4.11; N, 14.28. Found C, 73.28;
H, 3.98; N, 14.16.
2.2.3. 1-(5-Methylpyrid-2-yl)-5-methyl-1H-pyridin-2-
one (4).16 Reaction time: 24 h, colorless solid (36%). Mp
106–107 8C (from hexane); 1H NMR (400 MHz, CD2Cl2) d
8.36 (bs, 1H), 7.72 (d, JZ8 Hz, 1H), 7.63 (dd, JZ8, 2 Hz,
1H), 7.58 (dd, JZ2.4, 0.8 Hz, 1H), 7.25 (dd, JZ9.2, 2.4 Hz,
1H), 6.48 (d, JZ9.6 Hz, 1H), 2.38 (s, 3H), 2.11 (d, JZ
1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 161.4, 149.7,
148.7, 142.7, 138.1, 133.1, 132.7, 121.4, 120.7, 115.0, 18.1,
17.3; IR (CH2Cl2): 3047, 2926, 1681 (C]O), 1614, 1593,
1530, 1498 cmK1; FAB (NBA) 201.1 (MCCH), 200.1
(MC); HRMS calcd for C12H13N2O 201.1028, found
201.1026 (MCCH), calcd for C12H12N2O 200.0950,
found 200.0946 (MC). Anal. calcd for C12H12N2O C,
71.98; H, 6.04; N, 13.99. Found C, 71.97; H, 6.07; N, 13.98.
2.3.4. 1-(Biphenyl-4-yl)-1H-pyridin-2-one (8).19 Reaction
time: 14 h, white solid (38%). Mp 226–227 8C (from
CH2Cl2/hexaneZ1:10); 1H NMR (400 MHz, CDCl3) d

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P.-S. Wang et al. / Tetrahedron 61 (2005) 2931–2939
7.68 (dd, JZ6.6, 1.8 Hz, 2H), 7.58 (d, JZ9.2 Hz, 2H),
7.34–7.46 (m, 7H), 6.68 (d, JZ9.2 Hz, 1H), 6.29 (td, JZ
6.6, 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 162.2,
141.4, 139.9, 139.8, 139.7, 137.7, 128.7, 127.9, 127.6,
127.1, 126.6, 121.7, 106.0; IR (KBr): 3062, 3024, 2363,
2337, 1661 (C]O), 1585, 1535, 1485 cmK1; FAB (NBA)
248.1 (MCCH); HRMS calcd for C17H14NO 248.1075,
found 248.1074 (MCCH), calcd for C17H13NO 247.0997,
found 247.0993 (MC). Anal. calcd for C17H13NO: C, 82.57;
H, 5.30; N, 5.66. Found C, 82.26; H,5.17; N, 5.46.
1H), 6.18 (td, JZ6.4, 1.2 Hz, 1H), 3.80 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 162.2, 154.0, 139.7, 138.8, 130.1,
129.5, 128.4, 121.7, 120.8, 112.3, 105.3, 55.9; IR (neat):
3062, 2989, 1661 (C]O), 1599, 1523, 1485 cmK1; FAB
(NBA) 202.0 (MCCH); HRMS calcd for C12H12NO2
202.0868, found 202.0868 (MCCH), calcd for
C12H11NO2 201.0790, found 201.0784 (MC).
2.3.9. 1-(3-Bromo-4-methoxyphenyl)pyridin-2-one (13).
Reaction time: 14 h, white solid (37%). Mp 146–147 8C
(from THF); 1H NMR (400 MHz, d6-DMSO) d 7.65 (d, JZ
2.8 Hz, 1H), 7.61 (dd, JZ6.8, 1.8 Hz, 1H), 7.48 (td, JZ9.2,
6.8, 2.4 Hz, 1H), 7.38 (dd, JZ8.8, 2.8 Hz, 1H), 7.21 (d, JZ
8.8 Hz, 1H), 6.45 (d, JZ9.2 Hz, 1H), 6.28 (td, JZ6.8,
1.2 Hz, 1H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3) d
162.1, 155.5, 139.7, 137.6, 133.9, 131.1, 126.5, 121.5,
111.6, 111.5, 105.8, 56.4; IR (KBr): 3100, 3062, 3024,
2988, 2939, 2363, 2337, 1661 (C]O), 1585, 1535,
1485 cmK1; FAB (NBA) 280.0 (MCCH); HRMS calcd
2.3.5. 1-(Naphthalen-2-yl)-1H-pyridin-2-one (9). Reac-
tion time: 18 h, white solid, (82%). Mp 160–161 8C (from
CH2Cl2/hexaneZ1:10); 1H NMR (400 MHz, CDCl3) d 7.92
(d, JZ8.8 Hz, 1H), 7.81–7.89 (m, 2H), 7.79 (d, JZ2 Hz,
1H), 7.48–7.54 (m, 3H), 7.37–7.43 (m, 2H), 6.68 (dd, JZ
9.8, 1.4 Hz, 1H), 6.25 (td, JZ6.8, 0.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 162.3, 139.7, 138.5, 138.0, 133.2,
132.6, 129.0, 127.9, 127.6, 126.7, 126.6, 124.7, 124.4,
121.8, 105.9; IR (KBr): 3024, 2362, 2337, 1661 (C]O),
1585, 1535, 1499, 1461 cmK1; FAB (NBA) 222.1 (MCC
H),221.1 (MC); HRMS calcd for C15H12NO 222.0919,
found 222.0921 (MCCH), calcd for C15H11NO 221.0841,
found 221.0841 (MC). Anal. calcd for C15H11NO: C, 81.43;
H, 5.01; N, 6.33. Found C, 81.16; H, 5.11; N, 6.31.
for C12H BrNO2 279.9973, found 279.9971 (MCCH),
79
11
79
10
calcd for C12H BrNO2 278.9895, found 278.9896 (MC).
Anal. calcd for C12H10BrNO2 C, 51.45; H, 3.60; N, 5.00.
Found C, 51.19; H, 3.58; N, 5.03.
2.3.10. 1-(4-(Diphenylamino)phenyl)pyrid-2-one (15).
Reaction time: 24 h, white solid (59%). Mp 220–221 8C
(from CH2Cl2/hexaneZ1:10); 1H NMR (400 MHz, d6-
acetone) d 7.56 (ddd, JZ6.4, 2.4, 0.8 Hz, 1H), 7.44 (ddd,
JZ9.2, 6.7, 2.4 Hz, 1H), 7.29–7.36 (m, 6H), 7.05–7.13 (m,
8H), 6.44 (dd, JZ9.2, 0.8 Hz, 1H), 6.26 (td, JZ6.7, 1.2 Hz,
1H); 13C NMR (100 MHz, CDCl3) d 162.3, 147.7, 147.0,
139.5, 138.0, 134.3, 129.2, 126.9, 124.8, 123.4, 122.7, 121.6,
105.9; IR (KBr): 3076, 3038, 2363, 2337, 1661 (C]O), 1585,
1485, 1473 cmK1; FAB (NBA) 339.1 (MCCH),338.1 (MC);
HRMS calcd for C23H19N2O 339.1497, found 339.1493
(MCCH), calcd for C23H18N2O 338.1419, found 338.1417
(MC). Anal. calcd for C23H18N2O: C, 81.63; H, 5.36; N, 8.28.
Found C, 81.48; H, 5.26; N, 8.41.
2.3.6. 1-(4-Vinylphenyl)-1H-pyridin-2-one (10). Reaction
time: 9 h, white solid (61%). Mp 115–116 8C (from CH2Cl2/
hexaneZ1:10); 1H NMR (400 MHz, CDCl3) d 7.49 (dt, JZ
8.4, 2 Hz, 2H), 7.36 (ddd, JZ9.2, 6.8, 2.4 Hz, 1H), 7.28–
7.34 (m, 3H), 6.72 (dd, JZ17.6, 10.8 Hz, 1H), 6.63 (d, JZ
9.2 Hz, 1H), 6.21 (td, JZ6.8, 1.6 Hz, 1H), 5.77 (dd, JZ
17.6, 0.8 Hz, 1H), 5.30 (dd, JZ10.8, 0.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) only 10 sets of 13C signals was observed
d 162.1, 140.0, 139.6, 137.6, 135.5, 126.9, 126.4, 121.8,
115.2, 105.8; IR (KBr): 3029, 1668 (C]O), 1582, 1530,
1490, 1455 cmK1; FAB (NBA) 198.1 (MCCH),197.1
(MC); HRMS calcd for C13H12NO 198.0919, found
198.0918 (MCCH), calcd for C13H11NO 197.0841, found
197.0839 (MC). Anal. calcd for C13H11NO C, 79.17; H,
5.62; N, 7.10. Found C, 79.33; H, 5.64; N, 7.28.
2.3.11. 1-(40-(Diphenylamino)biphenyl-4-yl)-1H-pyridin-
2-one (16). Reaction time: 20 h, white solid (79%). Mp
232–234 8C (from CH2Cl2/hexaneZ1:10); 1H NMR
(400 MHz, d6-DMSO) d 7.74 (dt, JZ8.8, 2.2 Hz, 2H),
7.68 (dd, JZ7, 1.4 Hz, 1H), 7.64 (dt, JZ8.8, 2.2 Hz, 2H),
7.51 (ddd, JZ8.8, 6.7, 2.2 Hz, 1H), 7.45 (dt, JZ8.8, 2.2 Hz,
2H), 7.33 (t, JZ9.2 Hz, 4H), 7.02–7.09 (m, 8H), 6.48 (d,
JZ8.8 Hz, 1H), 6.32 (td, JZ6.7, 0.8 Hz, 1H), 6.32 (td, JZ
6.7, 0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 162.3,
147.4, 147.3, 140.8, 139.7, 139.3, 137.8, 133.5, 129.2,
127.7, 127.3, 126.6, 124.5, 123.4, 123.0, 121.8, 105.9; IR
(KBr): 3076, 3038, 2363, 2337, 1661 (C]O), 1585, 1485,
1473 cmK1; FAB (NBA) 415.1 (MCCH); HRMS calcd for
C29H22N2O 414.1732, found 414.1735 (MC). Anal. calcd
for C29H22N2O: C, 84.03; H, 5.35; N, 6.76. Found C, 83.74;
H, 5.22; N, 7.08.
2.3.7. 4,40-Bis(2-oxo-2H-pyridin-1-yl)biphenyl-2,20-
dicarboxylic acid dimethyl ester (11). Reaction time:
16 h, white solid (81%). Mp 218–219 8C (from CH3CN); 1H
NMR (400 MHz, CDCl3) d 8.07 (d, JZ2.4 Hz, 2H), 7.63
(dd, JZ8, 2 Hz, 2H), 7.40–7.46 (m, 4H), 7.37 (d, JZ8.4 Hz,
2H), 6.68 (d, JZ9.2 Hz, 2H), 6.29 (t, JZ6.8 Hz, 2H), 3.66
(s, 6H); 13C NMR (100 MHz, CDCl3) d 165.7, 162.0, 142.3,
139.9, 139.7, 137.4, 131.0, 130.0, 129.6, 127.8, 121.8,
106.2, 52.1; IR (KBr): 3626, 3450, 3062, 3038, 2951, 2363,
2336, 1737 (C]O), 1661 (C]O), 1585, 1523, 1473 cmK1
;
FAB (NBA) 457.1 (MCCH), 456.1 (MC); HRMS calcd for
C26H21N2O6 457.1400, found 457.1408 (MCCH), calcd for
C26H20N2O6 456.1321, found 456.1326 (MC). Anal. calcd
for C26H20N2O6 C, 68.42; H, 4.42; N, 6.14. Found C, 68.17;
H, 4.34; N, 6.17.
2.3.12. 1-(Pyridin-3-yl)-1H-pyridinin-2-one (17).21 Reac-
tion time: 15 h, tint brown solid (76%). Mp 144–145 8C
(from CH2Cl2/hexaneZ1:10); 1H NMR (400 MHz, d6-
DMSO) d 8.61–8.63 (m, 2H), 7.91 (d, JZ8.8 Hz, 1H), 7.71
(dt, JZ6.8, 0.8 Hz, 1H), 7.50–7.57 (m, 2H), 6.51 (d, JZ
8.8 Hz, 1H), 6.35 (t, JZ6.8 Hz, 1H); 13C NMR (100 MHz,
d6-DMSO) d 160.8, 148.7, 147.2, 140.8, 138.5, 137.0,
2.3.8. 1-(2-Methoxyphenyl)-1H-pyridin-2-one (12).20
Reaction time: 16 h (in DMF), white solid (2%). Mp 86–
1
87 8C (from Et2O); H NMR (400 MHz, CDCl3) d 7.35–
7.41 (m, 2H), 7.25 (dd, JZ7.6, 1.6 Hz, 1H), 7.18 (dd, JZ
7.6, 1.6 Hz, 1H), 7.01–7.05 (m, 2H), 6.64 (d, JZ9.2 Hz,

P.-S. Wang et al. / Tetrahedron 61 (2005) 2931–2939
2937
134.4, 123.6, 120.3, 105.8; IR (KBr): 3063, 3012, 2363,
2337, 1661 (C]O), 1573, 1535 cmK1; FAB (NBA) 173.1
(MCCH); HRMS calcd for C10H9N2O 173.0715, found
173.0712 (MCCH). Anal. calcd for C10H8N2O: C, 69.76;
H, 4.68; N, 16.27. Found C, 69.63; H, 4.60; N, 15.97.
2.3.17. 1-(4-(Methylthio)phenyl)-1H-pyridin-2-one (22).
Reaction time: 5 h, white solid (80%). Mp 141–142 8C
(from CH2Cl2/hexaneZ1:10); 1H NMR (400 MHz, d6-
DMSO) d 7.60 (dd, JZ6.6, 2 Hz, 1H), 7.48 (ddd, JZ9.2,
6.6, 2 Hz, 1H), 7.30–7.38 (m, 4H), 6.45 (d, JZ9.2 Hz, 1H),
6.29 (td, JZ6.6, 1.2 Hz, 1H), 2.5 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 162.0, 139.6, 139.1, 137.6, 137.4,
126.6, 126.5, 121.5, 105.8, 15.7; IR (KBr): 3046, 2980,
2.3.13. 1-(6-(2-Oxopyridin-1(2H)-yl)pyridin-2-yl)pyri-
din-2(1H)-one (18). Reaction time: 4 h, white solid
2922, 2361, 2342, 1660 (C]O), 1591, 1525, 1487 cmK1
;
1
(65%). Mp 176–177 8C (from CH2Cl2/hexaneZ1:10); H
FAB (NBA) 218.0 (MCCH); HRMS calcd for C12H12NOS
218.0640, found 218.0642 (MCCH), calcd for C12H11NOS
217.0561, found 217.0554 (MC). Anal. calcd for
C12H11NOS: C, 66.33; H, 5.10; N, 6.45; S, 14.76. Found
C, 66.36; H, 4.96; N, 6.40; S, 14.91.
NMR (400 MHz, CDCl3) d 7.89–7.97 (m, 3H), 7.79 (dd, JZ
6.8, 2 Hz, 2H), 7.36 (ddd, JZ9.2, 6.8, 2 Hz, 2H), 6.60 (d,
JZ9.2 Hz, 2H), 6.25 (t, JZ6.8 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 161.7, 150.6, 140.1, 139.3, 135.6,
121.9, 120.4, 106.3; IR (KBr): 3100, 3051, 2363, 2337,
1673 (C]O), 1599, 1573, 1535 cmK1; FAB (NBA) 266.0
(MCCH); HRMS calcd for C15H12N3O2 266.0930, found
266.0922 (MCCH), calcd for C15H11N3O2 265.0851, found
265.0848 (MC). Anal. calcd for C15H11N3O2: C, 67.92; H,
4.18; N, 15.84. Found C, 67.66; H, 4.09; N, 15.68.
2.3.18. 5-Nitro-1-phenyl-1H-pyridin-2-one. Reaction
time: 16 h, tint yellow solid (3%). Mp 169.5–170 8C (from
CH2Cl2/hexaneZ1:10); 1H NMR (400 MHz, CDCl3) d 8.64
(d, JZ3.2 Hz, 1H), 8.14 (dd, JZ10.4, 3.2 Hz, 1H), 7.47–
7.56 (m, 3H), 7.36–7.39 (m, 2H), 6.64 (d, JZ10.4 Hz, 1H);
13C NMR (100 MHz, CDCl3) d 160.9, 139.6, 139.0, 133.3,
130.8, 129.64, 129.61, 126.1, 120.3; IR (KBr): 3085, 2361,
2333, 1667 (C]O), 1621, 1553, 1497, 1450 cmK1; FAB
(NBA) 217.0 (MCCH); HRMS calcd for C11H9N2O3
217.0613, found 217.0613 (MCCH), calcd for
C11H8N2O3 216.0535, found 216.0530 (MC). Anal. calcd
for C11H8N2O3 C, 61.11; H, 3.73; N, 12.96. Found C, 60.91;
H, 3.76; N, 12.62.
2.3.14. 1-(Thiazol-2-yl)-1H-pyridin-2-one (19). Reaction
time: 14 h, tint yellow solid (33%). Mp 85.5–86 8C (from
1
CH2Cl2/hexaneZ1:15); H NMR (400 MHz, d6-DMSO) d
8.76 (ddd, JZ7.6, 2, 0.8 Hz, 1H), 7.77 (d, JZ3.2 Hz, 1H),
7.59–7.64 (m, 2H), 6.73 (dd, JZ8, 0.8 Hz, 1H), 6.58 (td,
JZ7.6, 0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 160.1,
155.7, 139.3, 137.5, 131.6, 121.2, 118.4, 107.2; IR (KBr):
3114, 3068, 2357, 2335, 1670 (C]O), 1599, 1541,
1495 cmK1; FAB (NBA) 179.0 (MCCH); HRMS calcd
for C8H7N2OS 179.0279, found 179.0282 (MCCH), calcd
for C8H6N2OS 178.0201, found 178.0204 (MC). Anal.
calcd for C8H6N2OS: C, 53.92; H, 3.39; N, 15.72; S, 17.99.
Found C, 53.97; H, 3.40; N, 15.59; S, 17.67.
2.3.19. 2-tert-Butoxy-5-bromopyridine (26). To an oven-
dried 100 mL double-necked flask was charged a solution of
2,5-dibromopyridine (4.90 g, 21 mmol) and sodium tert-
butoxide (3.25 g, 30 mmol) in toluene (30 ml). The reaction
mixture was stirred and heated at reflux temperature for
2.5 h. The resulting suspension was cooled to room
temperature and filtered through celite. The collected
organic phase was concentrated, and purified by flash
chromatography on silica gel (hexane/dichloromethane) to
give colorless liquid (2.65 g, 56%). Note that the compound
is a slightly hygroscopic liquid and should be distilled
before use. Bp 70 8C (0.15 mmHg). 1H NMR (400 MHz, d6-
DMSO) d 8.20 (d, JZ2.4 Hz, 1H), 7.80 (dd, JZ8.8, 2.8 Hz,
1H), 6.66 (d, JZ8.8 Hz, 1H), 1.50 (s, 9H); 13C NMR
(100 MHz, CDCl3) d 162.4, 146.8, 140.5, 114.9, 111.2,
80.2, 28.6; IR (neat): 2980, 2933, 2353, 2343, 1573, 1545,
2.3.15. 1-(Thiophen-3-yl)-1H-pyridin-2-one (20).17 Reac-
tion time: 22 h, brown solid (74%). Mp 116–117 8C (from
1
CH2Cl2/hexaneZ1:15); H NMR (400 MHz, d6-DMSO) d
7.75 (dd, JZ3.2, 1.4 Hz, 1H), 7.70 (dd, JZ6.8, 2.4 Hz, 1H),
7.62 (dd, JZ5.2, 3.2 Hz, 1H), 7.47 (ddd, JZ9.2, 6.8,
2.4 Hz, 1H), 7.28 (dd, JZ5, 1.4 Hz, 1H), 6.47 (d, JZ
9.2 Hz, 1H), 6.29 (td, JZ6.8, 1.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 161.8, 139.4, 138.6, 137.4, 125.4,
124.8, 121.8, 119.6, 106.0; IR (KBr): 3112, 3066, 2361,
2333, 1661 (C]O), 1583, 1515 cmK1; FAB (NBA) 178.0
(MCCH); HRMS calcd for C9H8NOS 178.0327, found
178.0326 (MCCH). Anal. calcd for C9H7NOS: C, 60.99; H,
3.98; N, 7.90; S, 18.09. Found C, 61.00; H, 3.95; N, 7.83; S,
18.15.
1459, 1363 cmK1; HRMS (EI, 70 eV) calcd for C9H BrNO
79
12
229.0102, found 229.0097 (MC). Anal. calcd for C9H12-
BrNOC, 46.98; H, 5.26; N, 6.09. Found C, 46.93; H, 5.41;
N, 5.93.
2.3.16. 1-(3-Nitrophenyl)-1H-pyridin-2-one (21).22 Reac-
tion time: 15 h, tint yellow solid (62%). Mp 185–186 8C
(from CH2Cl2/hexaneZ1:10); 1H NMR (400 MHz, CDCl3)
d 8.27–8.27 (m, 2H), 7.79 (dt, JZ8, 1.6 Hz, 1H), 7.67
(t, JZ8 Hz, 1H), 7.43 (ddd, JZ9.2, 6.6, 2.4 Hz, 1H), 7.33
(dd, JZ6.6, 1.6 Hz, 1H), 6.67 (d, JZ9.2 Hz, 1H), 6.30 (t,
JZ6.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 161.7,
148.4, 141.4, 140.3, 136.7, 132.8, 130.0, 123.2, 122.1,
121.9, 106.7; IR (KBr): 3080, 3023, 2361, 2333, 1671
(C]O), 1593, 1525 cmK1; FAB (NBA) 217.0 (MCCH);
HRMS calcd for C11H9N2O3 217.0613, found 217.0612
(MCCH), calcd for C11H8N2O3 216.0535, found 216.0534
(MC). Anal. calcd for C11H8N2O3: C, 61.11; H, 3.73; N,
12.96. Found C, 61.30; H, 3.79; N, 12.88.
2.3.20. 1-(6-tert-Butoxypyridin-3-yl)-1H-pyridin-2-one
(27). To an oven-dried 25 mL double-necked flask was
charged 2-hydroxypyridine (1.26 g, 13.2 mmol), CuI
(20 mol%), and K2CO3 (2 equiv). The flask was evacuated
and backfilled with nitrogen. A solution of 2-tert-butoxy-5-
bromopyridine (3.03 g, 13.2 mmol) in toluene (13.2 mL)
and DMCDA (20 mol%) were injected under nitrogen. The
reaction mixture was stirred and heated at reflux tempera-
ture for 11 h. The resulting mixture was cooled to room
temperature, diluted with dichloromethane, and filtered. The
filtrate was washed with water. The collected organic phase
was dried over anhydrous MgSO4 and concentrated. The
crude product was purified by flash chromatography on

2938
P.-S. Wang et al. / Tetrahedron 61 (2005) 2931–2939
silica gel (ethyl acetate/dichloromethane) to give white solid
(2.03 g, 63%). Mp 188–189 8C (from CH2Cl2/hexaneZ
1:10); 1H NMR (400 MHz, d6-acetone) d 8.14 (d, JZ
2.8 Hz, 1H), 7.71 (dd, JZ9.2, 2.8 Hz, 1H), 7.57 (ddd, JZ
6.8, 2, 0.8 Hz, 1H), 7.47 (ddd, JZ9.2, 6.8, 2 Hz, 1H), 6.75
(d, JZ9.2 Hz, 1H), 6.45 (dt, JZ9.2, 0.8 Hz, 1H), 6.28 (td,
JZ6.8, 1.2 Hz, 1H), 1.60 (s, 9H); 13C NMR (100 MHz,
CDCl3) d 163.1, 162.2, 143.1, 139.9, 137.8, 136.5, 130.6,
121.5, 113.1, 106.0, 80.3, 28.6; IR (KBr): 3047, 2971, 2923,
2361, 2333, 1667 (C]O), 1583, 1535, 1477 cmK1; FAB
(NBA) 245.1 (MCCH); HRMS calcd for C14H17N2O2
245.1290, found 245.1289 (MCCH). Anal. calcd for
C14H16N2O2: C, 68.83; H, 6.60; N, 11.47. Found C,
68.77; H, 6.82; N, 11.40.
IR (KBr): 3055, 2970, 2361, 2333, 1679 (C]O), 1661
(C]O), 1619, 1573, 1525, 1463 cmK1; FAB (NBA) 338.2
(MCCH); HRMS calcd for C19H20N3O3 338.1505, found
338.1503 (MCCH), calcd for C19H19N3O3 337.1426, found
337.1439 (MC). Anal. calcd for C19H19N3O3 C, 67.64; H,
5.68; N, 12.45. Found C, 67.40; H, 5.63; N, 12.59.
Acknowledgements
We thank the National Science Council of Republic of
China for the financial support (NSC 93-2113-M-002-008).
2.3.21. 1-(6-Hydroxypyridin-3-yl)-1H-pyridin-2-one
(28). To an oven-dried 25 mL flask was charged 1-(6-tert-
butoxypyridin-3-yl)pyridin-2(1H)-one (0.75 g, 3.06 mmol),
CH2Cl2 (15 mL), and TFA (5%). The reaction mixture was
stirred and heated at reflux temperature for 1 h. The
resulting solution was concentrated and washed with hexane
to give white solid. Note that this compound is hygroscopic
and soluble in water. Normal extraction workup procedure
is inappropriate in this case. The white solid was dried under
vacuum at 110 8C for overnight to afford 0.57 g, 99% yield
of 28. Mp 284–285 8C (from CH2Cl2/hexaneZ1:5); 1H
NMR (400 MHz, d6-DMSO) d 12.07 (bs, 1H), 7.60–7.63
(m, 2H), 7.44–7.51 (m, 2H), 6.44 (d, JZ9.6 Hz, 1H), 6.40
(d, JZ10 Hz, 1H), 6.26 (td, JZ6.8, 1.2 Hz, 1H); 13C NMR
(100 MHz, d6-DMSO) d 161.3, 161.2, 140.6, 140.5, 139.4,
133.7, 121.7, 121.0, 118.6, 105.5; IR (KBr): 3446, 3140,
3065, 2799, 2353, 1677 (C]O), 1621, 1583, 1525,
1469 cmK1; FAB (NBA) 189.1 (MCCH); HRMS calcd
for C10H9N2O2 189.0664, found 189.0667 (MCCH), calcd
for C10H8N2O2 188.0586, found 188.0587 (MC). Anal.
calcd for C10H8N2O2: C, 63.82; H, 4.28; N, 14.89. Found C,
63.41; H, 4.57; N, 15.01.
Supplementary data
Supplementary data associated with this article can
be found, in the online version, at doi:10.1016/j.tet.2005.
01.063
References and notes
1. For reviews, see (a) Sieburth, S. McN. In The Inter- and
Intramolecular [4C4] Photocycloaddition of 2-Pyridones and
Its Application to Natural Product Synthesis; Harmata, M.,
Ed.; Advances in Cycloaddition; JAI: Greenwich, CT, 1999;
Vol. 5, p 85. (b) Mehta, G.; Singh, V. Chem. Rev. 1999, 99,
881–930. (c) Joule, J. A.; Mills, K.; Smith, G. F. Heterocyclic
Chemistry, 3rd ed.; Chapman and Hall: London, 1995; pp
87–93. (d) Kuzuya, M.; Noguchi, A. Trends Org. Chem. 1991,
2, 73.
2. (a) Kohmoto, S.; Noguchi, T.; Masu, H.; Kishikawa, K.;
Yamamoto, M.; Yamaguchi, K. Org. Lett. 2004, 6, 683–685.
(b) Tanaka, K.; Fujiwara, T.; Urbanczyk-Lipkowska, Z. Org.
Lett. 2002, 4, 3255–3257. (c) Zhu, M.; Qiu, Z.; Hiel, G. P.;
Sieburth, S.; McN J. Org. Chem. 2002, 67, 3487–3493.
(d) Ader, T. A.; Champey, C. A.; Kuznetsova, L. V.; Li, T.;
Lim, Y.-H.; Rucando, D.; Sieburth, S. McN. Org. Lett. 2001,
3, 2165–2167. (e) Lee, Y.-g.; McGee, K. F., Jr.; Chen, J.;
Rucando, D.; Sieburth, S. McN. J. Org. Chem. 2000, 65,
6676–6681. (f) Sieburth, S. McN. ; McGee, K. F., Jr.; Zhang,
F.; Chen, Y. J. Org. Chem. 2000, 65, 1972–1977. (g) Bach, T.;
Bergmann, H.; Harms, K. Org. Lett. 2001, 3, 601–603.
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2.3.22. 1-(1-(6-tert-Butoxypyridin-3-yl)-1,6-dihydro-6-
oxopyridin-3-yl)-1H-pyridin-2-one (29). To an oven-
dried 10 mL double-necked flask containing a stir-bar was
charged with 1-(6-hydroxypyridin-3-yl)-1H-pyridin-2-one
(0.19 g, 1.01 mmol), CuI (20 mol%), and K2CO3 (2 equiv).
The flask was evacuated and backfilled with nitrogen. A
solution of 2-tert-butoxy-5-bromopyridine (0.28 g,
1.21 mmol) in toluene (1 mL) and DMCDA (20 mol%)
were injected under nitrogen. The reaction mixture was
stirred and heated at reflux temperature for 12 h. The
resulting mixture was cooled to room temperature, diluted
with dichloromethane, and filtered. The filtrate was washed
with water. The collected organic phase was dried over
anhydrous MgSO4 and concentrated. The crude product was
purified by flash chromatography on silica gel (ethyl acetate/
dichloromethane/MeOH) to give white solid (0.28 g, 82%).
Mp 216–217 8C (from CH2Cl2/hexaneZ1:10); 1H NMR
(400 MHz, d6-DMSO) d 8.22 (d, JZ2.8 Hz, 1H), 8.00 (d,
JZ2.8 Hz, 1H), 7.78 (dd, JZ8.8, 2.8 Hz, 1H), 7.73 (dd, JZ
7.2, 2 Hz, 1H), 7.62 (dd, JZ10, 2.8 Hz, 1H), 7.49 (ddd, JZ
9.2, 6.8, 2 Hz, 1H), 6.80 (d, JZ8.8 Hz, 1H), 6.53 (d, JZ
10 Hz, 1H), 6.46 (d, JZ9.2 Hz, 1H), 6.29 (td, JZ6.8,
1.2 Hz, 1H), 1.60 (s, 9H); 13C NMR (100 MHz, CDCl3) d
163.4, 162.1, 161.0, 143.2, 140.3, 139.1, 137.3, 136.4,
135.5, 130.0, 122.0, 121.7, 121.5, 113.3, 106.5, 80.6, 28.6;
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