Regioselective syntheses of substituted pyridines and 2,2′- bipyridines by cobalt-catalyzed [2+2+2] cycloaddition of α,ω-diynes with nitriles

Article abstract of DOI:10.1055/s-0030-1260068

In the presence of a 1,2-bis(diphenylphosphino)ethane- cobalt(II) chloride-zinc catalyst in 1-methylpyrrolidin-2-one at room temperature to 50°C, α,ω-diynes reacted with nitriles by a [2+2+2] cycloaddition pathway to give annulated pyridines or 2,2′- bipy

Full text of DOI:10.1055/s-0030-1260068

SPECIAL TOPIC
2247
Regioselective Syntheses of Substituted Pyridines and 2,2¢-Bipyridines by
Cobalt-Catalyzed [2+2+2] Cycloaddition of a,w-Diynes with Nitriles
R
egioselective Syn
u
these
s
of Py
-
ridines
a
k
nd 2,2
¢
-Bipy
i
ridines Sugiyama, Sentaro Okamoto*
Department of Material & Life Chemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan
Fax +81(45)4139770; E-mail: okamos10@kanagawa-u.ac.jp
Received 5 April 2011
substrate (and that of the corresponding metallacycle in-
termediates) have been reported by Schreiber and co-
workers,9 Tanaka et al.,3c,10 Louie and co-workers,11 and
our research group12 for reactions catalyzed by Cp-
Abstract: In the presence of a 1,2-bis(diphenylphosphino)ethane–
cobalt(II) chloride–zinc catalyst in 1-methylpyrrolidin-2-one at
room temperature to 50 °C, a,w-diynes reacted with nitriles by a
[2+2+2] cycloaddition pathway to give annulated pyridines or 2,2¢-
bipyridines. The regioselectivity of the reaction is controlled by a Co(CO)2, cationic diphosphine–rhodium, N-heterocyclic
combination of steric and electronic effects. The reaction of diynes
carbene (NHC)–nickel, or diphosphine–cobalt systems,
with a terminal trimethylsilyl group gave the corresponding 3-(tri-
respectively. Here we report a regioselective [2+2+2]
methylsilyl)pyridines exclusively; these products could be proto- or
cycloaddition of diynes with nitriles catalyzed by a
halodesilylated to give the corresponding protonated or halogenated
1,2-bis(diphenylphosphino)ethane–cobalt(II)
chloride
pyridines or 2,2¢-bipyridines.
hexahydrate–zinc [(dppe)CoCl2·6H2O–Zn] reagent,12 and
we discuss the relationship between the selectivity and the
substrate structure.
Key words: cycloadditions, heterocycles, homogeneous catalysis,
pyridines, regioselectivity
R1
R1
ligand (6 mol%)
CoCl2⋅6H2O
(5 mol%)
The catalytic cycloaddition of alkynes and nitriles in a
[2+2+2] fashion provides a straightforward method for
preparing substituted pyridines.1,2 The regiochemistry of
the reaction and its control are important in relation to uti-
lizing the method in synthesis. Successful regiocontrol in
a fully intermolecular reaction is possible but challeng-
R3
R1
+
R2
R3
N
Z
Z
Z
N
Zn dust (10 mol%)
r.t. to 50 °C
N
R3
R2
1
2
R2
3
4
ing,3,4 whereas the regiochemistry of fully intramolecular Scheme 1
reactions can be more readily controlled by altering the
positions of the alkyne and nitrile groups or by the strain
During the course of our previous studies on alkyne cy-
cloaddition,12,13 we found that a CoCl2·6H2O/Zn reagent
catalyzed the cycloaddition of diynes and nitriles in the
presence of a diphosphine ligand. A survey of phosphine
ligands for the reaction of diyne 1 (R1 = R2 = H) in aceto-
nitrile (80 equivalents as the solvent) showed that dppe
was most effective ligand (Scheme 1; Table 1). Further-
more, we were able to reduce the amount of nitrile needed
by using 1-methylpyrrolidin-2-one (NMP) as the solvent
(runs 8 and 9).
in the intermediates or products. Pyridines with unique tri-
cyclic or spiro skeletons have been prepared by this meth-
od.5 In contrast, comprehensive data on the
regioselectivity of partially intramolecular reactions,6
such as the cycloadditions of a,w-diynes to nitriles or of
w-cyanoalkynes with alkynes, are not available.
The synthesis of pyridines by the cycloaddition of non-
symmetrical a,w-diynes 1 to nitriles 2 gives two regioiso-
mers 3 and 4 (Scheme 1). We assumed that the
regioselectivity of this reaction might be controlled by
steric or electronic effects or by the balance of the two.
The reactions of 6-substituted (1-unsubstituted) 1,6-
diynes catalyzed by CpCo(CO)27a (Cp = h5-cyclopentadi-
enyl) or Cp*RuCl(cod)3b,5b,8 (Cp* = h5-pentamethylcy-
The structures of the substrates used in this study are
shown in Figure 1.
We then investigated the reactions of alkyl- and aryl-
substituted diynes 1a–c, 1f, and 1e with the nitriles 2a–d
(Scheme 2); the results are summarized in Table 2. The
reactions of acetonitrile (2a) with diynes 1a–c and 1f,
which contain electron-donating or -withdrawing groups
at the para-position of the aryl substituent, gave the corre-
sponding 3-arylpyridines 4 predominantly, with a slight
variation in the regioselectivity (Table 2, entries 1–4). In
contrast, substituents on the nitrile had a significant effect
on the regioselectivity (entries 4–7): Aliphatic nitriles 2a
and 2b (entries 1–5) gave the 3-arylpyridines 4 as the
main products, whereas the aromatic nitriles 2c and 2d
(entries 6 and 7) gave the corresponding 2-arylpyridines
clopentadienyl; cod
=
cyclooctadienyl) gave the
corresponding 2,6-substituted pyridines predominantly
rather than the 2,3-substituted pyridines. The selectivity
of this reaction has been rationalized by considering the
steric repulsion between the metallacyclopentadiene in-
termediate and the nitrile. Several examples that might be
explained in terms of the electronic nature of the diyne
SYNTHESIS 2011, No. 14, pp 2247–2254
x
x.
x
x
.
2
0
1
1
Advanced online publication: 09.06.2011
DOI: 10.1055/s-0030-1260068; Art ID: C36211SS
© Georg Thieme Verlag Stuttgart · New York

2248
Y.-k. Sugiyama, S. Okamoto
SPECIAL TOPIC
Table 1 Survey of Phosphine Ligands (Scheme 1; R1 = R2 = H,
R = Me)
>84% regioselectivity, whereas our cobalt-catalyzed reac-
tion of 1f (R1 = Bu, R2 = Ph) with 2b gave the opposite
isomer 3fb predominantly.
Entrya
Ligand
Time (h)
Yield (%)
Table 2 Results for the Reactions Shown in Scheme 2
1
2
3
4
5
6
–
24
24
24
1
–
Entry Diyne Alkyl Aryl
2 (equiv) Ratio 3/4 Yield
2PPh-3
17
(%)
Ph-2PCH2PPh2 (dppm)
Ph-2P(CH2)2PPh2 (dppe)
Ph-2P(CH2)3PPh2 (dppp)
Ph-2P(CH2)4PPh2 (dppb)
PPh2
–
1
2
3
4
5
6
7
1a
1b
1c
1f
Bu
Bu
Bu
Bu
Bu
Bu
Me
4-MeOC6H4
2a (20)
2a (20)
2a (20)
2a (20)
2b (2)
15:85 91
12:88 89
16:84 96
15:85 96
18:82 80
61:39 75
quant.
71
4-MeC6H4
12
12
4-MeO2CC6H4
4
Ph
Ph
Ph
Ph
1f
7
12
quant.
PPh2
1f
2c (20)
2d (5)
8
9
dppe (5 equiv of 2a in NMP)b
12
1
52
96
1e
>99:1
47
dppe (20 equiv of 2a in NMP)b
a MeCN (80 equiv), r.t.
In contrast, diyne substrates containing an alkynyl or a 2-
pyridyl moiety as a terminal substituent gave the corre-
sponding 3-alkynylpyridines or 3-(2-pyridyl)pyridines 4
exclusively in all cases, irrespective of the nitrile used
(Scheme 3; Table 3). The strong electron-withdrawing
nature of the alkynyl and 2-pyridyl groups may cause dif-
ferentiation in the site reactivity of the corresponding
cobaltacyclopentadiene intermediates (see below). The
double (domino) cycloaddition of 1,6,8,12-tetrayne sub-
strates 1q and 1r gave the corresponding 2,2¢-bipyridines
exclusively. The first cycloaddition gave the 2-alkynylpy-
ridine (1q or 1r) as a single isomer and the second addi-
tion followed a 2-pyridylpyridine formation pathway with
complete selectivity.
b MeCN was replaced by NMP as the solvent.
SiMe3
H
n-Bu
Z
Z
Z
R
R
n
X
1h R = Me
1i R = n-Bu
1j R = 2-pyridyl
1k R = SIMe3
1n R = n-Bu, n = 1
1o R = Ph, n = 1
1p R = Et, n = 2
1a X = OMe
1b X = Me
1c X = CO2Me
R
Z
R
R
N
Z
Z
Z
Ph
R
1d R = H
1q R = Me
1r R = Ph
1s R = H
1e R = Me
1f R = n-Bu
1g R = SiMe3
1l R = Me
1m R = Me [Z = O]
Next, we investigated the regiochemistry of the reactions
of diynes possessing a terminal alkyne group (Scheme 4;
Table 4). The reactions with nitriles 2a–c gave the corre-
sponding 2,6-substituted pyridines 3 as the major products
with moderate-to-complete selectivities (Table 4; entries
1–9). Although the large steric influence may account for
the regioselectivity in entries 1, 5, and 8, other explana-
tions could involving cooperative steric and electronic ef-
fects are possible (see below). A similar synthesis of 2,6-
substituted pyridines has been reported for reactions cata-
lyzed by Cp*RuCl (R2 = Me, Ph, R3 = CO2Et, CH2Cl)3b
and CpCo(CO)2 (under microwaves; R2 = TMS,
R3 = alkyl).7 It has been suggested that the formation of
pyridines 4 might be disfavored by steric repulsion be-
tween R3 and R2 in the corresponding metallacyclic inter-
[unless otherwise indicated, Z = C(CO2Et)2]
2a R = Me
2d R = 2-pyridyl
2e R = (CF2)6CF3
2b R = CH2CN
2c R = Ph
R
N
Figure 1 Substrate structures
3. The extremely high selectivity in the reaction with 2-
cyanopyridine (2d) compared with that of benzonitrile
(2c) suggested that differences in the electronic nature of
the nitriles may be responsible for changes in the selectiv-
ity. Tanaka et al.3c reported that the Rh(cod)2BF4/
Segphos-catalyzed reaction of 1e (R1 = Me, R2 = Ph) with
malononitrile (2b) gave the 3-aryl derivative 4eb with
alkyl
alkyl
dppe (0.06)
CoCl2⋅6H2O (0.05)
R
alkyl
R
N
N
Zn powder (0.1)
Z
Z
Z
+
N
NMP, r.t. or 50 °C
R
aryl
Z = C(CO2Et)2
aryl
4
aryl
3
1
2a R = Me
2b R = CH2CN
2c R = Ph
2d R = 2-pyridyl
Scheme 2 Study on electronic effects in the alkynes and nitriles
Synthesis 2011, No. 14, 2247–2254 © Thieme Stuttgart · New York

SPECIAL TOPIC
Regioselective Syntheses of Pyridines and 2,2¢-Bipyridines
2249
R1
R1
H
H
R2
R3
R2
R3
R1
H
N
N
+
Z
Z
Z
+
Z
Z
Z
N
N
N
R1
R2
N
R3
Y
2a R2 = Me
2a R3 = Me
R1
R1
1
1
Y
3
Y
4
2b R2 = CH2CN
2c R2 = Ph
2b R3 = CH2CN
2c R3 = Ph
Z = C(CO2Et)2
3
4
Y =
C≡C-
2d R2 = 2-pyridyl
or
[Z = C(CO2Et)2]
Scheme 4 Reactions of substrates 1 containing a terminal alkyne
N
group
R1
double cycloaddition of tetraynes
Z
R3
R1
Table 4 Results for the Reactions Shown in Scheme 4
Z
N
N
R1
Z
2
2
Entry
1
Diyne
1i
R2
2 (equiv)
2a (20)
2a (20)
2a (80)
2a (80)
2b (2)
Ratio 3/4 Yield (%)
Z
N
R1
R3
Z
Z
Bu
Ph
95:5
66:34
>99:1
>99:1
>99:1
60:40
>99:1
98:2
78
66
87a
87a
57
48
71
58
53
78
67
78
R1
R3
[1q] or [1r]
1q or 1r
R1
2
1d
1s
3
C≡C
2-Py
Bu
Ph
Scheme 3 Reactions of alkynyl- or 2-pyridyl-substituted diynes
4
[1s]b
1i
Table 3 Results of the Reactions Shown in Scheme 3
5
Entrya Diyne R1
Y
Z
2
Ratio Yield
6
1d
1j
2b (2)
(equiv) 3/4 (%)
7
2-Py
Bu
Ph
2b (1.5)
2c (20)
2c (20)
2d (20)
2d (20)
2d (20)
1
2
3
4
5
6
7
8
9
1r
1r
1q
1l
Ph
Ph
C≡C
C≡C
C(CO2Et)2 2a (40) >99:1 90%b
C(CO2Et)2 2c (10) >99:1 86%b
8
1i
9
1d
1h
1i
>99:1
1:>99
1:>99
>99:1
Me C≡C
Me 2-Pyd C(CO2Et)2 2a (20) >99:1 81%
2-Py
C(CO2Et)2 2a (40) >99:1 90%b
Me 2-Py 2a (20) >99:1 89%
[1r]e Ph C(CO2Et)2 2c (10) >99:1 86%b
2-Py
C(CO2Et)2 2d (2)
>99:1 47%c
10
11
12
Me
Bu
Ph
[1r]e Ph
1m
1d
O
a Yield of the double cycloaddition product.
b Reaction of the intermediate in the double cycloaddition.
1m
1m
Me 2-Py
Me 2-Py
O
O
2d (5)
>99:1 69%
SiMe3
SiMe3
2e (1.5) >99:1 64%
R2
R2
N
SiMe3
N
a 20 equiv of 2a in NMP was used.
+
Z
Z
Z
N
b Yield of 2,2¢-bipyridine after double cycloaddition.
c Yield of monocyclized product (1q).
d 2-pyridyl.
R1
R2
n
n
n
R1
R1
2a R2 = Me
1
2b R2 = CH2CN
2c R2 = Ph
3
4
Z = C(CO2Et)2
e The reaction of the intermediate in the double cycloaddition.
2d R2 = 2-pyridyl
mediate. In contrast, when 2-cyanopyridine (2d) was
used, the regiochemistry of the product was completely
changed by the substituent on the diyne 1 (Table 4, entries
10–12). Once more, we observed that, in terms of the re-
gioselectivity, the relatively electron-deficient nitrile 2d
was much more sensitive to the electronic nature of the
diyne than were the other nitriles.
Scheme 5 Reactions of trimethylsilyl-substituted diynes 1
catalyzed reactions.7 With respect to the reaction of alkyl-
and silyl-substituted diynes, Louie and co-workers11 re-
ported that the Ni(cod)2/NHC-catalyzed reaction of 2a
and a diyne (R1 = Me) showed the same sense of regio-
chemistry as that of the reaction of 2a and 1n (Entry 2).
In the case of the reaction of diynes terminated with a tri-
methylsilyl group (Scheme 5; Table 5), 3-(trimethylsi-
lyl)pyridines were obtained exclusively without
exception. Note that even substrates 1 containing a termi-
nal alkyne group (R1 = H) gave the more-sterically de-
manding 3-silylpyridines 3. These results clearly showed
that the reactions were electronically controlled. Note also
that the selectivity is opposite to that observed in the
CpCo(CO)2- and the CpCo(CO)(dimethyl fumarate)-
The silyl-substituted pyridines that were obtained as the
corresponding single regioisomers are synthetically use-
ful. For instance, silylated pyridine 3oa and 2,2¢-bipy-
ridines 3od and 3nd were smoothly protodesilylated7,9 to
give the regioisomerically pure products 3da, 3dd, and
5nd (decarboxylation and saponification occurred during
the reaction) (Scheme 6). The resulting cyclopenta[c]py-
ridine 5nd had the opposite regiochemistry to that of the
Synthesis 2011, No. 14, 2247–2254 © Thieme Stuttgart · New York

2250
Y.-k. Sugiyama, S. Okamoto
SPECIAL TOPIC
the majority of the reactions presented here can be sys-
tematically rationalized by considering differences in the
electronic nature of the two alkyne groups in the diynes.
Thus, the relatively electron-rich alkyne moiety in diyne 1
bonds to the electron-deficient position (the carbon atom)
of the cyano group in nitrile 2. It is plausible that an inter-
mediate cobaltacycle of type i, derived from the corre-
sponding 1, might have a similar electronic nature,
influenced by the substituents R1 and R2, and that the re-
action proceeds by a pathway involving a [4+2] cycload-
dition (ii) and/or an insertion reaction (iii). Thus, the
regioselectivity observed here can be predicted accurately
by considering the electronic nature of alkyne substituent,
in the order TMS, alkyl, H, Ph, C≡C, 2-pyridyl (in other
words, from electron rich to electron deficient)
(Scheme 7). Overall, the regioselectivity can be altered by
such electronic effects in conjunction with cooperative or
competitive steric repulsion between the substituents of
the diyne and the nitrile, as shown in Scheme 7. Confir-
mation of the mechanism for the conversion of metallacy-
cle intermediates i into pyridines ii or iii will require
further studies. However, a consideration of the regio-
chemical trends that we observed indicates that the meth-
od is potentially useful in synthesis.
Table 5 Results of the Reactions Shown in Scheme 5
Entry Diyne R1
n
1
1
1
2
1
1
1
1
1
1
2 (Equiv) Ratio 3/4 Yield (%)
1
2
1k
1n
1o
1p
1k
1n
1o
1o
1n
1o
H
2a (20)
2a (20)
2a (20)
2a (20)
2b (20)
2b (2)
2b (2)
2c (5)
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
98:2
39
83
91
88
76
91
68
99
91
82
Bu
Ph
Et
3
4
5
H
6
Bu
Ph
Ph
Bu
Ph
7
8
>99:1
>99:1
>99:1
9
2d (2)
2d (2)
10
pyridine 3id derived from 1i and 2d. In addition, halode-
silylation of the silylated pyridines gave the correspond-
ing bromopyridines 6oa and 6od in good yields. From
these 3-bromopyridine derivatives, regiochemically pure
pyridines A can be synthesized by manipulations such as
transition metal-catalyzed coupling reactions.14 This indi-
rect method permits the production of substituted py-
ridines possessing an opposite regiochemistry to that
produced by the direct method. Studies on this reaction
are underway, and the results will be reported elsewhere.
Finally, we present some supplementary data on the
amounts (equivalents) of nitriles that should be used. For
the reaction of diynes containing a terminal alkyne group,
the use of aliphatic or aromatic nitriles such as acetonitrile
(2a), benzonitrile (2c), or 2-cyanopyridine (2d) in an ex-
cess of 80 equivalents when used as the solvent or in an
excess of 5–20 equivalents in 1-methylpyrrolidin-2-one
as the solvent is recommended for the successful synthesis
of the required pyridines. These excesses of nitrile sup-
press the competitive formation of benzenes by [2+2+2]
cycloaddition between the two diyne moieties as a side-re-
action. Because the reactions of nitriles containing a coor-
dinating group or of electron-deficient nitriles, such as
malononitrile (2b) or cyanoperfluoroalkanes,10,12b pro-
ceed selectively at high rates, 1.5–2 equivalents of these
nitriles can be used. When the two alkyne groups in
diynes 1 are internal, the benzene-forming side-reactions
are suppressed and the reactions require smaller excesses
of the nitrile (2–5 equivalents).
Me3Si
H
R2
R2
a
Z
Z
N
N
R1
R1
3oa R1 = Ph, R2 = Me
3da 88%
3dd 82%
5nd Z = CH(CO2H) 96%
3od R1 = Ph, R2 = 2-pyridyl
3nd R1 = n-Bu, R2 = 2-pyridyl
Z = C(CO2Et)2
R3
Br
R2
R2
R3M
Z
b
Z
N
R1
R1
6oa 97%
6od 95%
1H NMR spectra of samples dissolved in CDCl3 were recorded at
600, 500, and 270 MHz, whereas 13C NMR spectra were recorded
at 150, 125 and 67.5 MHz on JEOL JNM-ECA600, JNM-ECA500,
and JNM-EX270 spectrometers, respectively. Chemical shifts are
reported in ppm relative to TMS (d = 0.00) or residual CHCl3 (d =
A
Scheme 6 Protodesilylation and halodesilylation of silyl-substitu-
ted pyridines
1
7.26 for H NMR) or CDCl3 (d = 77.0 for 13C NMR). IR spectra
We postulate that the dppe–CoCl2·6H2O–Zn-catalyzed
pyridine-formation reaction might proceed through a
(dppe)CoICl complex generated by the reduction of
(dppe)CoCl2 with zinc; this complex could react with
diynes to provide cobaltacyclopentadiene intermediates i
(Scheme 7). Although there are several exceptions
(Table 1, entries 1–5; Table 4, entries 1, 5, and 7) involv-
ing reactions in which the contribution of steric factors
might be relatively large, the regioselectivity observed in
were recorded on a Fourier-transform IR spectrometer (Shimadzu,
IR Prestige-21 or JASCO FT/IR-4100). High-resolution mass spec-
tra were acquired by using a JEOL Accu TOF T-100 spectrometer
equipped for electrospray ionization. All reactions that were sensi-
tive to oxygen and/or moisture were performed under argon. Anhy-
drous THF and NMP were purchased from Kanto Chemicals
(Tokyo). All the other commercially sourced chemicals were used
as received. Starting diynes 1 were prepared by conventional proce-
dures. Data for compounds 3fa, 4fa, 3ed, 3qd, 3la, 3ma, 3md, 3me,
3ia, 3da, 4da, 3jb, 4hd, 4id, 3dd, 3ka, 3na, 3oa, 3pa, 3kb, 3nb,
Synthesis 2011, No. 14, 2247–2254 © Thieme Stuttgart · New York

SPECIAL TOPIC
Regioselective Syntheses of Pyridines and 2,2¢-Bipyridines
2251
R1
R2
sterically
disfavored
Z
R1
1
R3
R3
CoI
R1
Z
R1
N
R1
N
R3
R2
R1
2
N
>
Z
Z
>
CoIIIL
Cl
R2
Z
N
R3
R2
disfavored
R2
i
N
Z
favored
R3
R2
: relatively electron-rich position
: relatively electron-deficient position
electronically
disfavored
: a large group
electron-rich
: a small group
electron-deficient
C≡C
2-pyridyl
Ph
H
alkyl
SiMe3
Zn
diyne
(dppe)CoICl
i
(dppe)CoCl2
1/2ZnCl2
R3CN
R3
R1
R1
CoIIIL
R3
N
N
Z
CoIIIL
Z
Cl
R2
ii
Cl
R2
and/or
R1
Cl
pyridine
CoIIIL
R3
Z
R2
iii
N
Scheme 7 Summary of regioselectivity and possible routes to opposite regioisomers
3nd, 5nd, 6oa, and 2,2¢-bipyridines after the double cycloaddition
of the 1r + 2a, 1r + 2b, 1r + 2c, and 1s + 2a substrate pairs have
been published previously.12
Diethyl 1-Butyl-4-(4-methoxyphenyl)-3-methyl-5,7-dihydro-
6H-cyclopenta[c]pyridine-6,6-dicarboxylate (4aa) and Diethyl
4-Butyl-1-(4-methoxyphenyl)-3-methyl-5,7-dihydro-6H-cyclo-
penta[c]pyridine-6,6-dicarboxylate (3aa) (Table 2, Entry 1)
4aa + 3aa
Cycloaddition of Diyne 1 and Nitrile 2 Catalyzed by dppe–
CoCl2·6H2O–Zn Reagent; General Procedure
IR (neat): 2956, 2931, 2870, 1730, 1581, 1514, 1258, 1185 cm–1.
A soln of CoCl2·6H2O (6 mg, 0.025 mmol) and dppe (12 mg, 0.03
mmol) in NMP or MeCN (1 mL) at r.t. was added to a stirred mix-
ture of Zn powder (3.5 mg, 0.05 mmol), diyne 1 (0.5 mmol), and ni-
trile 2 (1.5–80 equiv). [NMP (1 mL) was also added if 80 equiv of
MeCN were used]. The mixture was then stirred at r.t. or 50 °C and
the progress of the reaction was monitored by TLC. After comple-
tion of the reaction, a small portion of EtOAc or Et2O was added,
and the mixture was passed through a pad of Celite that was washed
with EtOAc or Et2O. The filtrate was concentrated to dryness and
the residue was purified by chromatography (silica gel, hexane–
EtOAc) to separate the pyridine or bipyridine derivative(s).
13C NMR (CDCl3, 150 MHz): d = 171.3, 158.7, 155.5, 154.3, 148.9,
130.8, 130.6, 130.4, 130.1, 113.9, 113.7, 61.9, 61.8, 60.0, 40.1,
38.6, 31.5, 31.4, 23.0, 22.9, 22.7, 14.03, 13.99, 13.98, 13.95.
HRMS (ESI+, MeOH): m/z calcd for [C26H34NO5]+: 440.2437;
found: 440.2449.
4aa
1H NMR (CDCl3, 600 MHz): d = 7.15 (d, J = 8.6 Hz, 2 H, Ar), 6.97
(d, J = 8.6 Hz, 2 H, Ar), 4.24–4.13 (m, 4 H, OCH2CH3), 3.86 (s, 3
H, OCH3), 3.59 (s, 2 H, PyCH2C), 3.31 (s, 2 H, PyCH2C), 2.72 (t,
J = 7.9 Hz, 2 H, PyCH2CH2), 2.33 (s, 3 H, PyCH3), 1.71–1.65 (m, 2
Synthesis 2011, No. 14, 2247–2254 © Thieme Stuttgart · New York

2252
Y.-k. Sugiyama, S. Okamoto
SPECIAL TOPIC
H, alkyl), 1.47–1.40 (m, 2 H, alkyl), 1.23 (t, J = 7.2 Hz, 6 H,
OCH2CH3), 0.96 (t, J = 7.2 Hz, 3 H, CH2CH2CH3).
J = 8.3 Hz, 2 H, PyCH2CH2), 2.58 (s, 3 H, PyCH3), 1.75–1.64 (m, 2
H, alkyl), 1.56–1.49 (m, 2 H, alkyl), 1.23 (t, J = 6.9 Hz, 6 H,
OCH2CH3), 0.98 (t, J = 6.9 Hz, 3 H, CH2CH2CH3).
3aa
1H NMR (CDCl3, 600 MHz): d = 7.68 (d, J = 8.9 Hz, 2 H, Ar), 6.97
(d, J = 8.9 Hz, 2 H, Ar), 4.24–4.13 (m, 4 H, OCH2CH3), 3.85 (s, 3
H, OCH3), 3.73 (s, 2 H, PyCH2C), 3.55 (s, 2 H, PyCH2C), 2.61 (t,
J = 7.9 Hz, 2 H, PyCH2CH2), 2.56 (s, 3 H, PyCH3), 1.71–1.65 (m, 2
H, alkyl), 1.55–1.48 (m, 2 H, alkyl), 1.23 (t, J = 7.2 Hz, 6 H,
OCH2CH3), 0.96 (t, J = 7.2 Hz, 3 H, CH2CH2CH3).
Diethyl 1-Butyl-3-(cyanomethyl)-4-phenyl-5,7-dihydro-6H-cy-
clopenta[c]pyridine-6,6-dicarboxylate (4fb) and Diethyl 4-Bu-
tyl-3-(cyanomethyl)-1-phenyl-5,7-dihydro-6H-cyclo-
penta[c]pyridine-6,6-dicarboxylate (3fb) (Table 2, Entry 5)
4fb + 3fb
IR (neat): 2957, 2931, 2871, 2251, 1747, 1583, 1462, 1430, 1268
cm–1.
Diethyl 1-Butyl-3-methyl-4-(4-tolyl)-5,7-dihydro-6H-cyclopen-
ta[c]pyridine-6,6-dicarboxylate (4ba) and Diethyl 4-Butyl-3-
methyl-1-(4-methylphenyl)-5,7-dihydro-6H-cyclopenta[c]pyri-
dine-6,6-dicarboxylate (3ba) (Table 2, Entry 2)
4ba + 3ba
13C NMR (CDCl3, 150 MHz): d = 171.0, 170.9, 157.2, 151.4, 149.7,
146.0, 136.1, 133.6, 133.3, 131.1, 129.1, 128.7, 128.4, 128.3, 128.2,
117.6, 62.1, 62.0, 60.3, 59.9, 40.2, 39.9, 39.0, 38.5, 31.5, 30.8, 29.3,
24.8, 24.4, 23.0, 22.7, 13.99, 13.96, 13.8.
HRMS (ESI+, MeOH): m/z calcd for [C26H31N2O4]+: 435.2284;
found: 435.2289.
IR (neat): 2956, 2922, 2857, 1747, 1589, 1454, 1270 cm–1.
13C NMR (CDCl3, 150 MHz): d = 171.3, 155.4, 154.1, 148.7, 136.9,
135.2, 130.9, 130.8, 129.2, 129.0, 128.8, 128.2, 61.9, 61.8, 60.0,
38.6, 35.9, 31.5, 22.9, 22.7, 21.2, 14.0, 13.96, 13.95.
HRMS (ESI+, MeOH): m/z calcd for [C26H34NO4]+: 424.2488;
found: 424.2498.
4fb
1H NMR (CDCl3, 600 MHz): d = 7.49 (t, J = 7.6 Hz, 2 H, Ar), 7.43
(t, J = 7.6 Hz, 1 H, Ar), 7.25 (d, J = 7.6 Hz, 2 H, Ar), 4.26–4.15 (m,
4 H, OCH2CH3), 3.65 (s, 2 H, PyCH2CN), 3.63 (s, 2 H, PyCH2C),
3.33 (s, 2 H, PyCH2C), 2.76 (t, J = 7.9 Hz, 2 H, PyCH2CH2), 1.76–
1.69 (m, 2 H, alkyl), 1.48–1.40 (m, 2 H, alkyl), 1.24 (t, J = 7.2 Hz,
6 H, OCH2CH3), 0.98 (t, J = 7.9 Hz, 3 H, CH2CH2CH3).
4ba
1H NMR (CDCl3, 600 MHz): d = 7.24 (d, J = 7.9 Hz, 2 H, Ar), 7.11
(d, J = 7.9 Hz, 2 H, Ar), 4.24–4.13 (m, 4 H, OCH2CH3), 3.59 (s, 2
H, PyCH2C), 3.31 (s, 2 H, PyCH2C), 2.72 (t, J = 8.2 Hz, 2 H,
PyCH2CH2), 2.41 (s, 3 H, ArCH3), 2.32 (s, 3 H, PyCH3), 1.71–1.64
(m, 2 H, alkyl), 1.48–1.39 (m, 2 H, alkyl), 1.23 (t, J = 7.2 Hz, 6 H,
OCH2CH3), 0.97 (t, J = 7.2 Hz, 3 H, CH2CH2CH3).
3fb
1H NMR (CDCl3, 600 MHz): d = 7.79 (d, J = 7.6 Hz, 2 H, Ar), 7.51–
7.45 (m, 2 H, Ar), 7.45–7.39 (m, 1 H, Ar), 4.26–4.15 (m, 4 H,
OCH2CH3), 3.95 (s, 2 H, PyCH2CN), 3.80 (s, 2 H, PyCH2C), 3.59
(s, 2 H, PyCH2C), 2.67 (t, J = 8.2 Hz, 2 H, PyCH2CH2), 1.62–1.54
(m, 2 H, alkyl), 1.50–1.40 (m, 2 H, alkyl), 1.25 (t, J = 7.2 Hz, 6 H,
OCH2CH3), 1.00 (t, J = 6.9 Hz, 3 H, CH2CH2CH3).
3ba
1H NMR (CDCl3, 600 MHz): d = 7.61 (d, J = 8.2 Hz, 2 H, Ar), 7.25
(d, J = 8.2 Hz, 2 H, Ar), 4.24–4.13 (m, 4 H, OCH2CH3), 3.73 (s, 2
H, PyCH2C), 3.55 (s, 2 H, PyCH2C), 2.61 (t, J = 8.2 Hz, 2 H,
PyCH2CH2), 2.56 (s, 3 H, PyCH3), 2.39 (s, 3 H, ArCH3), 1.56–1.49
(m, 2 H, alkyl), 1.48–1.39 (m, 2 H, alkyl), 1.24 (t, J = 7.6 Hz, 6 H,
OCH2CH3), 0.98 (t, J = 7.9 Hz, 3 H, CH2CH2CH3).
Diethyl 1-Butyl-3,4-diphenyl-5,7-dihydro-6H-cyclopenta[c]py-
ridine-6,6-dicarboxylate (4fc) and Diethyl 4-Butyl-1,3-diphe-
nyl-5,7-dihydro-6H-cyclopenta[c]pyridine-6,6-dicarboxylate
(3fc) (Table 2, Entry 6)
3fc + 4fc
Diethyl 1-Butyl-4-[4-(methoxycarbonyl)phenyl]-3-methyl-5,7-
dihydro-6H-cyclopenta[c]pyridine-6,6-dicarboxylate (4ca) and
Diethyl 4-Butyl-1-[4-(methoxycarbonyl)phenyl]-3-methyl-5,7-
dihydro-6H-cyclopenta[c]pyridine-6,6-dicarboxylate (3ca)
(Table 2, Entry 3)
IR (neat): 2958, 2931, 2870, 1747, 1565, 1454, 1258 cm–1.
13C NMR (CDCl3, 150 MHz): d = 171.26, 171.22, 157.7, 156.3,
151.0, 150.4, 149.3, 140.9, 139.7, 132.4, 132.0, 130.6, 129.9, 129.8,
129.1, 128.5, 128.3, 128.2, 128.1, 128.0, 127.6, 127.1, 126.9, 62.0,
61.9, 60.3, 59.9, 40.3, 40.2, 39.3, 38.6, 35.8, 31.9, 31.1, 29.6, 22.81,
22.77, 14.1, 13.99, 13.98, 13.7.
4ca + 3ca
IR (neat): 2956, 2871, 1746, 1730, 1580, 1462, 1286, 1190 cm–1.
HRMS (ESI+, MeOH): m/z calcd for [C30H34NO4]: 472.2488;
found: 472.2484.
13C NMR (CDCl3, 150 MHz): d = 171.1, 166.9, 156.4, 153.5, 148.4,
143.2, 131.1, 130.0, 129.9, 129.6, 129.2, 129.1, 128.3, 62.0, 61.9,
60.0, 52.2, 39.9, 38.5, 31.4, 29.7, 23.0, 22.8, 22.7, 21.8, 14.01,
14.00, 13.97, 13.93.
HRMS (ESI+, MeOH): m/z calcd for [C27H34NO6]+: 468.2386;
found: 486.2389.
3fc
1H NMR (CDCl3, 600 MHz): d = 7.79 (d, J = 7.6 Hz, 2 H, Ar), 7.51
(d, J = 7.6 Hz, 2 H, Ar), 7.46–7.40 (m, 4 H, Ar), 7.39–7.34 (m, 1 H,
Ar), 7.18–7.14 (m, 1 H, Ar), 4.28–4.15 (m, 4 H, OCH2CH3), 3.83 (s,
2 H, PyCH2C), 3.66 (s, 2 H, PyCH2C), 2.64 (t, J = 8.2 Hz, 2 H,
PyCH2CH2), 1.50–1.43 (m, 2 H, alkyl), 1.31–1.20 (m, 2 H, alkyl),
1.27 (t, J = 7.2 Hz, 6 H, OCH2CH3), 0.83 (t, J = 7.6 Hz, 3 H,
CH2CH2CH3).
4ca
1H NMR (CDCl3, 600 MHz): d = 8.11 (d, J = 7.6 Hz, 2 H, Ar), 7.32
(d, J = 7.6 Hz, 2 H, Ar), 4.26–4.14 (m, 4 H, OCH2CH3), 3.96 (s, 3
H, OCH3), 3.60 (s, 2 H, PyCH2C), 3.28 (s, 2 H, PyCH2C), 2.74 (t,
J = 7.9 Hz, 2 H, PyCH2CH2), 2.32 (s, 3 H, PyCH3), 1.76–1.65 (m, 2
H, alkyl), 1.48–1.40 (m, 2 H, alkyl), 1.23 (t, J = 6.9 Hz, 6 H,
OCH2CH3), 0.97 (t, J = 7.2 Hz, 3 H, CH2CH2CH3).
4fc
1H NMR (CDCl3, 600 MHz): d = 7.39–7.34 (m, 2 H, Ar), 7.29–7.21
(m, 4 H, Ar), 7.17–7.14 (m, 2 H, Ar), 7.10 (d, J = 8.2 Hz, 2 H, Ar),
4.28–4.15 (m, 4 H, OCH2CH3), 3.68 (s, 2 H, PyCH2C), 3.46 (s, 2 H,
PyCH2C), 2.83 (t, J = 7.6 Hz, 2 H, PyCH2CH2), 1.80–1.74 (m, 2 H,
alkyl), 1.50–1.43 (m, 2 H, alkyl), 1.25 (t, J = 7.2 Hz, 6 H,
OCH2CH3), 0.98 (t, J = 7.6 Hz, 3 H, CH2CH2CH3).
3ca
1H NMR (CDCl3, 600 MHz): d = 8.11 (d, J = 7.6 Hz, 2 H, Ar), 7.80
(d, J = 7.6 Hz, 2 H, Ar), 4.26–4.14 (m, 4 H, OCH2CH3), 3.94 (s, 3
H, OCH3), 3.73 (s, 2 H, PyCH2C), 3.57 (s, 2 H, PyCH2C), 2.64 (t,
Synthesis 2011, No. 14, 2247–2254 © Thieme Stuttgart · New York

SPECIAL TOPIC
Regioselective Syntheses of Pyridines and 2,2¢-Bipyridines
2253
Diethyl 1-Butyl-3-(cyanomethyl)-5,7-dihydro-6H-cyclopen-
ta[c]pyridine-6,6-dicarboxylate (3ib) (Table 4, Entry 5)
IR (neat): 2959, 2933, 2871, 2252, 1729, 1600, 1455, 1265 cm–1.
1H NMR (CDCl3, 600 MHz): d = 7.16 (s, 1 H, Py), 4.23 (q, J = 7.2
Hz, 4 H, OCH2CH3), 3.86 (s, 2 H, PyCH2CN), 3.59 (s, 2 H,
PyCH2C), 3.55 (s, 2 H, PyCH2C), 2.70 (t, J = 7.6 Hz, 2 H,
PyCH2CH2), 1.68–1.60 (m, 2 H, alkyl), 1.42–1.35 (m, 2 H, alkyl),
1.27 (t, J = 7.2 Hz, 6 H, OCH2CH3), 0.94 (t, J = 7.6 Hz, 3 H,
CH2CH2CH3).
1H NMR (CDCl3, 600 MHz): d = 8.08 (d, J = 7.6 Hz, 2 H, Ar), 7.90
(d, J = 8.2 Hz, 2 H, Ar), 7.59 (s, 1 H, Py), 7.50 (t, J = 7.6 Hz, 2 H,
Ar), 7.46 (t, J = 8.2 Hz, 2 H, Ar), 7.42 (t, J = 8.2 Hz, 1 H, Ar), 7.39
(t, J = 7.6 Hz, 1 H, Ar), 4.27–4.15 (m, 4 H, OCH2CH3), 3.84 (s, 2 H,
PyCH2C), 3.69 (s, 2 H, PyCH2C), 1.27 (t, J = 7.3 Hz, 6 H,
OCH2CH3).
13C NMR (CDCl3, 150 MHz): d = 171.1, 156.0, 153.6, 151.9, 139.7,
139.5, 131.9, 128.7, 128.6, 128.5, 128.3, 127.0, 114.9, 62.0, 60.2,
40.3, 39.9, 14.0.
13C NMR (CDCl3, 150 MHz): d = 171.0, 158.3, 151.2, 148.4, 133.4,
117.4, 115.7, 62.1, 59.7, 40.3, 38.0, 35.5, 30.9, 26.4, 22.6, 14.0,
13.9.
HRMS (ESI+, MeOH): m/z calcd for [C26H26NO4]+: 416.1862;
found: 416.1865.
Diethyl 3-(Cyanomethyl)-1-phenyl-4-(trimethylsilyl)-5,7-dihy-
dro-6H-cyclopenta[c]pyridine-6,6-dicarboxylate(3ob) (Table5,
Entry 7)
HRMS (ESI+, MeOH): m/z calcd for [C20H27N2O4]: 359.1971;
found: 359.1968.
IR (KBr): 2980, 2903, 2250, 1730, 1556, 1445, 1365, 1259 cm–1.
Diethyl 3-(Cyanomethyl)-1-phenyl-5,7-dihydro-6H-cyclopen-
ta[c]pyridine-6,6-dicarboxylate (3db) and Diethyl 3-(Cyano-
methyl)-4-phenyl-5,7-dihydro-6H-cyclopenta[c]pyridine-6,6-
dicarboxylate (4db) (Table 4, Entry 6)
1H NMR (CDCl3, 600 MHz): d = 7.83 (d, J = 6.9 Hz, 2 H, Ar), 7.49
(t, J = 6.9 Hz, 2 H, Ar), 7.43 (t, J = 6.9 Hz, 1 H, Ar), 4.25–4.14 (m,
4 H, OCH2CH3), 4.03 (s, 2 H, PyCH2CN), 3.74 (s, 2 H, PyCH2C),
3.67 (s, 2 H, PyCH2C), 1.25 (t, J = 7.3 Hz, 6 H, OCH2CH3), 0.49 [s,
9 H, Si(CH3)3].
13C NMR (CDCl3, 150 MHz): d = 170.8, 158.6, 153.9, 153.0, 138.5,
132.0, 128.9, 128.5, 128.4, 127.2, 117.8, 62.1, 60.3, 42.3, 39.0,
28.7, 14.0, 1.54.
3db + 4db
IR (neat): 2956, 2930, 2859, 2230, 1715, 1605, 1495, 1454, 1272
cm–1.
HRMS (ESI+, MeOH): m/z calcd for [C22H22N2NaO4]+: 401.1477;
found: 401.1483.
HRMS (ESI+, MeOH): m/z calcd for [C25H30N2NaO4Si]+:
473.1873; found: 473.1874.
3db
1H NMR (CDCl3, 600 MHz): d = 7.75 (d, J = 6.9 Hz, 2 H, Ar), 7.49
(t, J = 6.9 Hz, 2 H, Ar), 7.43 (t, J = 6.9 Hz, 1 H, Ar), 7.31 (s, 1 H,
Py), 4.25–4.16 (m, 4 H, OCH2CH3), 3.97 (s, 2 H, PyCH2CN), 3.77
(s, 2 H, PyCH2C), 3.65 (s, 2 H, PyCH2C), 1.25 (t, J = 7.2 Hz, 6 H,
OCH2CH3).
Diethyl 1,3-Diphenyl-4-(trimethylsilyl)-5,7-dihydro-6H-cyclo-
penta[c]pyridine-6,6-dicarboxylate (3oc) (Table 5, Entry 8)
IR (neat): 2980, 2900, 1747, 1540, 1384, 1268, 1198 cm–1.
1H NMR (CDCl3, 600 MHz): d = 7.78 (d, J = 6.9 Hz, 2 H, Ar), 7.45–
7.35 (m, 8 H, Ar), 4.28–4.17 (m, 4 H, OCH2CH3), 3.79 (s, 2 H,
PyCH2C), 3.74 (s, 2 H, PyCH2C), 1.26 (t, J = 7.6 Hz, 6 H,
OCH2CH3), 0.06 [s, 9 H, Si(CH3)3].
13C NMR (CDCl3, 150 MHz): d = 170.8, 154.4, 152.8, 149.0, 138.6,
133.0, 128.9, 128.5, 128.4, 117.3, 116.8, 62.1, 60.1, 40.2, 39.7,
26.6, 14.0.
13C NMR (CDCl3, 150 MHz): d = 171.2, 157.8, 153.0, 144.5, 139.5,
130.6, 129.3, 128.7, 128.4, 128.3, 127.8, 127.79, 172.3, 62.0, 60.4,
42.4, 39.1, 14.0, 1.15.
HRMS (ESI+, MeOH): m/z calcd for [C29H34NO4Si]+: 488.2257;
found: 488.2257.
4db
1H NMR (CDCl3, 600 MHz): d = 8.46 (s, 1 H, Py), 7.51 (t, J = 6.9
Hz, 2 H, Ar), 7.45 (t, J = 6.9 Hz, 1 H, Ar), 7.26 (d, J = 6.9 Hz, 2 H,
Ar), 4.26–4.14 (m, 4 H, OCH2CH3), 3.70 (s, 2 H, PyCH2CN), 3.69
(s, 2 H, PyCH2C), 3.35 (s, 2 H, PyCH2C), 1.24 (t, J = 7.2 Hz, 6 H,
OCH2CH3).
13C NMR (CDCl3, 150 MHz): d = 170.7, 150.1, 146.4, 144.3, 136.0,
135.5, 133.4, 129.2, 128.5, 128.4, 117.2, 62.0, 60.0, 39.6, 38.3,
24.8, 13.9.
Diethyl 1-Phenyl-3-pyridin-2-yl-4-(trimethylsilyl)-5,7-dihydro-
6H-cyclopenta[c]pyridine-6,6-dicarboxylate (3od) (Table 5,
Entry 10)
IR (KBr): 2984, 2902, 1726, 1587, 1385, 1299, 1267, 1107 cm–1.
1H NMR (CDCl3, 600 MHz): d = 8.60 (d, J = 4.8 Hz, 1 H, Ar), 7.93
(d, J = 8.9 Hz, 1 H, Ar), 7.82–7.75 (m, 3 H, Ar), 7.45 (t, J = J = 7.6
Hz, 2 H, Ar), 7.39 (t, J = 7.6 Hz, 1 H, Ar), 7.30–7.27 (m, 1 H, Ar),
4.25–4.16 (m, 4 H, OCH2CH3), 3.79 (s, 2 H, PyCH2C), 3.78 (s, 2 H,
PyCH2C), 1.25 (t, J = 7.3 Hz, 6 H, OCH2CH3), 0.14 [s, 9 H,
Si(CH3)3].
13C NMR (CDCl3, 150 MHz): d = 171.0, 162.3, 160.8, 158.1, 152.9,
147.8, 139.5, 136.5, 131.6, 128.6, 128.4, 128.3, 128.2, 123.8, 122.9,
61.9, 60.4, 42.7, 39.1, 14.0, 1.69.
Diethyl 4-Butyl-3-phenyl-5,7-dihydro-6H-cyclopenta[c]pyri-
dine-6,6-dicarboxylate (3ic) (Table 4, Entry 8)
IR (neat): 2958, 2931, 2870, 1730, 1601, 1453, 1253 cm–1.
1H NMR (CDCl3, 600 MHz): d = 7.95 (d, J = 6.9 Hz, 2 H, Ar), 7.44
(t, J = 6.9 Hz, 2 H, Ar), 7.40 (s, 1 H, Py), 7.36 (t, J = 6.9 Hz, 1 H,
Ar), 4.23 (q, J = 7.2 Hz, 4 H, OCH2CH3), 3.63 (s, 2 H, PyCH2C),
3.60 (s, 2 H, PyCH2C), 2.79 (t, J = 7.6 Hz, 2 H, PyCH2CH2), 1.80–
1.73 (m, 2 H, alkyl), 1.48–1.39 (m, 2 H, alkyl), 1.26 (t, J = 7.2 Hz,
6 H, OCH2CH3), 0.97 (t, J = 7.2 Hz, 3 H, CH2CH2CH3).
13C NMR (CDCl3, 150 MHz): d = 171.3, 157.6, 156.0, 150.2, 140.0,
132.4, 128.6, 128.4, 127.0, 114.1, 62.0, 59.9, 40.5, 38.2, 35.7, 30.8,
22.7, 14.04, 14.00.
HRMS (ESI+, MeOH): m/z calcd for [C28H32NaN2O4Si]+:
511.2029; found: 511.2017.
HRMS (ESI+, MeOH): m/z calcd for [C24H30NO4]+: 396.2175;
found: 396.2173.
Diethyl 4-Bromo-1-phenyl-3-pyridin-2-yl-5,7-dihydro-6H-cy-
clopenta[c]pyridine-6,6-dicarboxylate (6od) (Scheme 6)
IR (neat): 2980, 2905, 1729, 1474, 1399, 1264, 1187 cm–1.
1H NMR (CDCl3, 600 MHz): d = 8.72 (d, J = 4.1 Hz, 1 H, Ar), 7.85–
7.74 (m, 4 H, Ar), 7.46 (t, J = 7.6 Hz, 2 H, Ar), 7.40 (t, J = 7.6 Hz,
1 H, Ar), 7.35–7.31 (m, 1 H, Ar), 4.29–4.10 (m, 4 H, OCH2CH3),
Diethyl 1,3-Diphenyl-5,7-dihydro-6H-cyclopenta[c]pyridine-
6,6-dicarboxylate (3dc) (Table 4, Entry 8)
IR (neat): 3062, 2974, 2934, 1714, 1600, 1495, 1287 cm–1.
Synthesis 2011, No. 14, 2247–2254 © Thieme Stuttgart · New York

2254
Y.-k. Sugiyama, S. Okamoto
SPECIAL TOPIC
3.93 (s, 2 H, PyCH2C), 3.77 (s, 2 H, PyCH2C), 1.27 (t, J = 7.3 Hz,
6 H, OCH2CH3).
13C NMR (CDCl3, 150 MHz): d = 170.7, 157.5, 154.9, 153.0, 152.2,
148.6, 138.4, 136.4, 134.2, 128.7, 128.43, 128.41, 124.4, 123.2,
115.1, 62.2, 59.1, 42.5, 40.9, 13.9.
HRMS (ESI+, MeOH): m/z calcd for [C25H24BrN2O4]+: 495.0919;
found: 495.0920.
Wang, H.; Kondo, Y.; Yamanaka, M.; Nakajima, K.; Kotora,
M. J. Am. Chem. Soc. 2002, 124, 5059. (c) Suzuki, D.;
Tanaka, R.; Urabe, H.; Sato, F. J. Am. Chem. Soc. 2002, 124,
3518. (d) Suzuki, D.; Yuza, A.; Watai, Y.; Tanaka, R.;
Takayama, Y.; Sato, F.; Urabe, H. J. Am. Chem. Soc. 2005,
127, 7474. (e) Takahashi, T.; Liu, Y.; Iesato, A.; Chaki, S.;
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
We thank the Scientific Frontier Research Project of the Ministry of
Education, Culture, Sports, Science and Technology (MEXT), Ja-
pan, for financial support.
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Synthesis 2011, No. 14, 2247–2254 © Thieme Stuttgart · New York