Approach to trisubstituted 3-Aminopyrrole derivatives by Yb(OTf) 3-catalyzed [4+1] annulation of 2-Azadiene with Me3SiCN

Article abstract of DOI:10.1002/ejoc.201000241

In the present study, we found a novel approach to the simple and practical synthesis of 3-aminopyrrole derivatives through the four-component coupling reaction of a functionalized silane, a nitrile, an aldehyde, and trimethylsilyl cyanide by Yb(OTf)₃-catalyzed annulation of a 2-azabutadiene with trimethylsilyl cyanide. In this paper, we also disclose a single-step transformation of the 3-aminopyrrole framework into the pyrrolo[3,4-b]pyridin-4- one skeleton.

Full text of DOI:10.1002/ejoc.201000241

FULL PAPER
DOI: 10.1002/ejoc.201000241
Approach to Trisubstituted 3-Aminopyrrole Derivatives by Yb(OTf)3-Catalyzed
[4+1] Annulation of 2-Azadiene with Me3SiCN
Toshiaki Sasada,[a] Takuya Sawada,[a] Reiko Ikeda,[a] Norio Sakai,[a] and
Takeo Konakahara*[a]
Keywords: Multicomponent reactions / Nitrogen heterocycles / Annulation / Ytterbium
In the present study, we found a novel approach to the simple
and practical synthesis of 3-aminopyrrole derivatives
through the four-component coupling reaction of a function-
alized silane, a nitrile, an aldehyde, and trimethylsilyl cyan-
ide by Yb(OTf)3-catalyzed annulation of a 2-azabutadiene
with trimethylsilyl cyanide. In this paper, we also disclose a
single-step transformation of the 3-aminopyrrole framework
into the pyrrolo[3,4-b]pyridin-4-one skeleton.
Introduction
3-Aminopyrrole derivatives are found in many natural
products and in a variety of biologically active substances,[1]
such as distamycin A[2] and netropsin,[3] and they are useful
building blocks in synthetic chemistry.[4] To date, a number
of approaches to the construction of the pyrrole skeleton
have been reported by many organic and pharmaceutical
chemists,[5–9] and general synthetic methods for the synthe-
sis of 3-aminopyrrole derivatives are shown in Scheme 1:
(i) functional group transformation of pyrrole derivatives
such as 3-hydroxypyrroles,[10] 3-nitropyrroles,[11] 3-arylazo-
pyrroles,[12] and pyrrol-3-carboxylic acids[13] (path a);
(ii) 2,3-bond-forming[14] or 3,4-bond-forming[15] cyclization
(paths b and c); and (iii) 1,2- and 2,3-bond-forming,[16] 2,3-
and 4,5-bond-forming,[17] 1,5- and 2,3-bond-forming,[18]
and 1,5- and 3,4-bond-forming[19] annulation (paths d–g).
To the best of our knowledge, there are few examples of the
preparation of a 3-aminopyrrole derivative by 2,3- and 3,4-
bond-forming annulation (path h).[20] Moreover, the pre-
vious methods require two equivalents of TiCl4 as an addi-
tive,[20a] unavailable reagents such as a tungsten carbene
Scheme 1. Approach to the synthesis of 3-aminopyrrole derivative.
formed 2-azabutadiene with trimethylsilyl cyanide to pro-
duce the desired 3-aminopyrrole derivative (Scheme 2).
Herein, we report the efficient and facile synthesis of 3-ami-
nopyrrole derivatives by a four-component coupling reac-
tion from a functionalized silane, a nitrile, an aldehyde, and
trimethylsilyl cyanide. We also disclose a novel approach to
the single-step synthesis of pyrrolo[3,4-b]pyridin-4-one de-
complex[20b] and
a a
multifunctionalized triazine,[20c]
multistep synthesis, and low temperature,[20a] which lead to
low selectivity and a decline in product yields.
Thus, on the basis of our previous work,[21] we envi-
sioned a facile and efficient approach for the preparation
of 3-aminopyrrole derivatives, in which the intermolecular
coupling reaction of a functionalized silane, a nitrile, and an
aldehyde would initially form a 2-azabutadiene derivative
followed by the Lewis acid catalyzed annulation of the
[a] Department of Pure and Applied Chemistry, Faculty of Science
and Technology, Tokyo University of Science (RIKADAI),
Noda, Chiba 278-8510, Japan
Fax: +81-4-7123-9326
E-mail: konaka@rs.noda.tus.ac.jp
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000241.
Scheme 2. This work.
Eur. J. Org. Chem. 2010, 4237–4244
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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T. Sasada, T. Sawada, R. Ikeda, N. Sakai, T. Konakahara
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rivatives starting from the 3-aminopyrrole containing an Table 1. Examination of synthesis of 3-aminopyrrole 6a.
isoxazole group by the reductive ring-opening reaction of
the isoxazole ring.
Results and Discussion
On the basis of our previous work, we first examined the
one-pot, three-component coupling reaction of a function-
Entry Lewis acid (equiv.)
Solvent
Time [h] Yield [%][a]
alized silane, an aromatic nitrile, and an aromatic aldehyde,
leading to the preparation of 2-azabutadiene derivatives
(Scheme 3).[22,23] For example, when the reaction of 3-
methyl-5-(trimethylsilyl)methylisoxazole (1a) with benzoni-
trile (2a) was carried out in THF at –70 °C for 1 h in the
presence of nBuLi, followed by the addition of benzalde-
hyde (3a), desired 2-azadiene 4a was obtained in 53% yield.
The structure of the 2-azadiene framework was unambigu-
ously determined by spectroscopy and by X-ray structure
analysis of isolated compound 4d.
1
2
none
InCl3 (0.2)
THF
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
PhMe
24
24
24
24
24
24
24
48
12
24
24
NR
30
31
trace
20
53
(75)
76
72
68
65
3
4
5
ZnCl2 (0.2)
Cu(OTf)2 (0.2)
AlCl3 (0.2)
6
7
8
9
10
11
Hf(OTf)4 (0.2)
Yb(OTf)3 (0.2)
Yb(OTf)3 (0.1)
Yb(OTf)3 (0.4)
Yb(OTf)3 (0.2)
Yb(OTf)3 (0.2)
[a] NMR yield (isolated yield); NR = no reaction.
produced the corresponding pyrrole derivatives 6e–i in good
yields (Table 2, Entries 5–9). On the other hand, 2-azabuta-
diene 4j, with a pyridin-3-yl group as R3, gave desired
product 6j, but the yield was low (Table 2, Entry 10). Sur-
prisingly, when 2-azabutadiene 4k having a pyridin-4-yl
group instead of a 3-methylisoxazol-5-yl group as R1 was
employed, the reaction was complete in the presence of only
0.05 equiv. of Yb(OTf)3 within only 2 h to give pyrrole 6k
in 83% yield (Table 2, Entry 11).
Scheme 3. One-pot synthesis of 2-azadiene 4a.
The annulation of prepared 2-azabutadiene 4a with tri-
methylsilyl cyanide (Me3SiCN) to afford 3-aminopyrrole
derivative 6a was examined, and the results are summarized
in Table 1. When the model reaction was performed with-
out a Lewis acid catalyst, desired pyrrole derivative 6a was
not obtained (Table 1, Entry 1). Addition of a typical Lewis
acid as an additive, such as InCl3, ZnCl2, Cu(OTf)2, and
AlCl3, promoted the annulation to give desired product 6a,
but the yields were rather low (Table 1, Entries 2–5). The
structure of the pyrrole skeleton was unambiguously deter-
mined by X-ray diffraction of crystallized compound 6g. To
enhance the yield, when Yb(OTf)3 was employed, the prod-
uct yield was drastically increased (Table 1, Entries 7–9).
Because both Et2O and toluene gave a slightly decent yield,
THF was the most suitable reaction solvent (Table 1, En-
tries 10 and 11). Consequently, the reaction described in
Entry 7 proved to be the optimal conditions for annulation,
as shown in Table 1.
Table 2. Single-step synthesis of 3-aminopyrrole 6.
To extend the scope of the Yb(OTf)3-catalyzed annu-
lation, we next examined the reaction of various 2-azabuta-
dienes with trimethylsilyl cyanide, leading to 3-aminopyr-
role derivatives under our optimal conditions. These results
are summarized in Table 2. When R3 was a 4-chlorophenyl
group, desired pyrrole derivative 6b was produced in excel-
lent yield (Table 2, Entry 2). By contrast, when R3 was a 4-
methoxyphenyl group, the desired reaction proceeded, but
[a] Isolated yield. [b] Reaction time = 2 h; Yb(OTf)3 = 0.05 equiv.
To apply the four-component coupling reaction using a
the yield of product 6c was moderate (Table 2, Entry 3). functionalized silane, a nitrile, an aldehyde, and trimethyl-
Similarly, the use of 2-azabutadienes 4e–i, containing a 4- silyl cyanide, we next attempted the one-pot synthesis of 3-
methoxyphenyl group or a 4-chlorophenyl group as R2, aminopyrrole derivative 6 (Scheme 4). When the reaction
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Eur. J. Org. Chem. 2010, 4237–4244

Yb(OTf)3-Catalyzed [4+1] Annulation of 2-Azadiene with Me3SiCN
was carried out under the above optimal conditions, the of azadiene 4a with Me3SiCN was treated with a catalytic
desired reaction successfully proceeded to give pyrrole de- amount of Yb(OTf)3, intermediate 9a was isolated in 70%
rivatives 6a and 6b in 53 and 41% yield, respectively.
yield.[24] Yb(OTf)3-catalyzed intramolecular cyclization of
intermediate 9 then occurred to produce corresponding in-
termediate 10 with a shift of the silyl group.[25] Finally, aro-
matization of intermediate 10 worked as the driving force
to produce the desired 3-aminopyrrole derivative after con-
ventional aqueous workup.
Conclusions
Thus far, we have outlined the process for a novel, simple,
and practical synthesis of 3-aminopyrrole derivatives
through the Yb(OTf)3-catalyzed annulation of 2-azabutadi-
ene with trimethylsilyl cyanide, and the four-component
coupling reaction of a functionalized silane, a nitrile, an
aldehyde, and trimethylsilyl cyanide. Also detailed is the
transformation of 3-aminopyrroles with an isoxazolyl group
into pyrrolo[3,4-b]pyridin-4-one derivatives through a re-
ductive ring-opening reaction and subsequent intramolecu-
lar cyclization.
Scheme 4. One-pot synthesis of 3-aminopyrrole 6.
Finally, to illustrate the utility of an isoxazole group, we
examined the skeletal transformation of prepared 3-amino-
pyrroles 6 into pyrrolo[3,4-b]pyridin-4-one derivatives 8
(Scheme 5). When product 6a was treated with 0.5 equiv.
of Mo(CO)6,[21f] rather than expected pyrrole derivative 7a,
pyrrolopyridine derivative 8a was obtained in 88% yield
through the reductive ring opening of the isoxazole fol-
lowed by intramolecular cyclization.
Experimental Section
General Methods: Column chromatography was performed by
using Silica gel 60 and aluminum oxide 90 active neutral. THF,
Et2O, and toluene were distilled from sodium–benzophenone and
dried with 5 Å MS or 4 Å MS. Prior to use, 3,5-dimethylisoxazole,
trimethylsilyl chloride, benzonitrile, and benzaldehyde were dis-
tilled. Other materials were commercially available and were used
without further purification. Using a previously reported pro-
cedure,[26] 4-(trimethylsilyl)methylpyridine (1b) was prepared. All
reactions were carried out under a nitrogen atmosphere, unless
otherwise noted. 1H NMR spectra were measured at 500 or
300 MHz by using tetramethylsilane as an internal standard. 13C
NMR spectra were measured at 125 or 75 MHz by using the center
peak of chloroform (δ =77.0 ppm) as an internal standard. High-
resolution mass spectra were measured by using NBA (3-nitro-
benzyl alcohol) as a matrix.
Scheme 5. Synthesis of pyrrolo[3,4-b]pyridin-4-ones 8.
1b:[26] Colorless liquid. B.p. 76 °C/5 Torr (ref.[27] 73–74 °C/4.5 Torr).
A plausible mechanism for the Yb(OTf)3-catalyzed annu-
lation is shown in Scheme 6. First, coordination of Yb-
(OTf)3 to the nitrogen atom of the 2-azadiene facilitated the 2.03 (s, 2 H, Ar-CH2-SiMe3), 6.84 (d, JH,H = 4.5 Hz, 2 H, Ar-H),
attack of the azadiene by a cyanide ion, which led to the
CDCl3, 25 °C): δ = –2.1, 27.3, 123.4, 149.2, 150.1 ppm. MS (FA):
formation of intermediate 9. Practically, when the reaction
1H NMR (300 MHz, CDCl3, 25 °C): δ = –0.05 (s, 9 H, -SiMe3),
3
3
8.32 (d, JH,H = 4.5 Hz, 2 H, Ar-H) ppm. 13C NMR (75 MHz,
m/z (%) = 166 (100) [M + H].
Procedure for the Synthesis of 1a: To a THF solution (120 mL)
of diisopropylamine (55.6 g, 0.550 mol) was added nBuLi (1.5  in
hexane, 0.550 mol) at –70 °C, and the mixture was stirred at the
same temperature. After 30 min, 3,5-dimethylisoxazole (48.6 g,
0.500 mol) was added dropwise, and the mixture was stirred for 1 h
at –70 °C. Trimethylsilyl chloride (54.3 g, 0.500 mol) was gradually
added to the solution at –70 °C, and the mixture was stirred for
1 h at the same temperature and then for 1 h at room temperature.
To quench the reaction, a saturated aqueous solution of NH4Cl
was added to the mixture. The mixture was extracted several times
with Et2O, and the combined organic extracts were dried with
Na2SO4, filtered, and then concentrated under reduced pressure.
The residue was purified by distillation under reduced pressure to
Scheme 6. A plausible mechanism.
give 3-methyl-5-(trimethylsilyl)methylisoxazole (1a; 68.6 g, 81%) as
Eur. J. Org. Chem. 2010, 4237–4244
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T. Sasada, T. Sawada, R. Ikeda, N. Sakai, T. Konakahara
FULL PAPER
a colorless liquid. B.p. 109–110 °C/32 Torr (ref.[28] 43 °C/0.6 Torr).
1H NMR (500 MHz, CDCl3, 25 °C): δ = 0.03 (s, 9 H, -SiMe3), 2.12
(s, 2 H, Ar-CH2-SiMe3), 2.18 (s, 3 H, Ar-Me), 5.57 (s, 1 H, Ar-H)
3
2 H, Ar-H), 7.86 (d, JH,H = 8.5 Hz, 2 H, Ar-H), 8.23 (s, 1 H,
-N=CH-Ar) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 11.4,
101.3, 103.8, 128.1, 128.9, 129.4, 130.2, 133.7, 135.2, 135.4, 138.6,
ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = –1.8, 11.3, 17.6, 152.3, 159.8, 162.8, 167.1 ppm. MS (FA): m/z (%) = 358 (100) [M
99.9, 159.7, 171.9 ppm. MS (FA): m/z (%) = 170 (100) [M + H].
+ H]+. C19H14Cl2N2O (357.23): calcd. C 63.88, H 3.95, N 7.84;
found C 63.95, H 3.97, N 7.80.
General Procedure for the Synthesis of 2-Azadienes 4a–j: To a THF
solution (15 mL) of 1a (847 mg, 5.00 mmol) was added nBuLi
(1.5  in hexane, 5.50 mmol) at –70 °C, and the reaction mixture
was stirred at the same temperature. After 1 h, benzonitrile (2a;
516 mg, 5.00 mmol) was added to the solution by syringe, and the
solution was further stirred for 1 h at –70 °C, then for 1 h at room
temperature. Benzaldehyde (3a; 531 mg, 5.00 mmol) was added to
the solution at –70 °C, and the mixture was stirred for 1 h at the
same temperature, then for 1 h at room temperature. To quench the
reaction, water (30 mL) was added to the mixture at 0 °C. The mix-
ture was extracted several times with AcOEt, and the combined
organic extracts were dried with Na2SO4, filtered, and then concen-
trated under reduced pressure. The residue was purified by neutral
Al2O3 chromatography (hexane/AcOEt) to give 4a (764 mg, 53%)
as a yellow solid (CHCl3/hexane).
4f: Yield: 759 mg, 43%, yellow solid (CHCl3/hexane). M.p. 158.7–
160.1 °C. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 2.24 (s, 3 H, Ar-
Me), 3.90 (s, 3 H, Ar-OMe), 6.11 (s, 1 H), 6.40 (s, 1 H), 7.03 (d,
3
3JH,H = 8.7 Hz, 2 H, Ar-H), 7.35 (d, JH,H = 8.7 Hz, 2 H, Ar-H),
3
3
7.45 (d, JH,H = 8.7 Hz, 2 H, Ar-H), 7.88 (d, JH,H = 8.7 Hz, 2 H,
Ar-H), 8.17 (s, 1 H, -N=CH-Ar) ppm. 13C NMR (75 MHz, CDCl3,
25 °C): δ = 11.5, 55.5, 100.8, 103.5, 114.5, 128.2, 128.8, 130.9,
135.0, 135.8, 152.8, 159.8, 163.1, 163.3, 167.5 ppm. MS (FA): m/z
(%) = 353 (100) [M + H]+. C20H17ClN2O2 (352.81): calcd. C 68.09,
H 4.86, N 7.94; found C 67.76, H 4.93, N 7.86.
4g: Yield: 796 mg, 50%, yellow solid (CHCl3/hexane). M.p. 123.8–
124.9 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 2.22 (s, 3 H, Ar-
Me), 3.84 (s, 3 H, Ar-OMe), 6.05 (s, 1 H), 6.38 (s, 1 H), 6.91 (d,
3
3JH,H = 8.5 Hz, 2 H, Ar-H), 7.46 (d, JH,H = 8.5 Hz, 2 H, Ar-H),
4a: M.p. 87.2–87.4 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ =
7.51–7.57 (m, 3 H, Ar-H), 7.94 (d, JH,H = 7.0 Hz, 2 H, Ar-H),
3
2.14 (s, 3 H, Ar-Me), 6.04 (s, 1 H), 6.35 (s, 1 H), 7.26–7.31 (m, 3 8.28 (s, 1 H, -N=CH-Ar) ppm. 13C NMR (75 MHz, CDCl3, 25 °C):
3
H, Ar-H), 7.40–7.48 (m, 5 H, Ar-H), 7.84 (d, JH,H = 6.5 Hz, 2 H,
Ar-H), 8.18 (s, 1 H, -N=CH-Ar) ppm. 13C NMR (125 MHz,
CDCl3, 25 °C): δ = 11.5, 101.0, 103.6, 127.0, 128.7, 129.0, 129.1,
δ = 11.5, 55.3, 99.0 103.0, 114.1, 128.3, 129.0, 129.0, 129.5, 132.2,
135.5, 153.6, 159.8, 160.4, 163.9, 167.9 ppm. MS (FA): m/z (%) =
319 (100) [M + H]+. HRMS (FAB): calcd. for C20H19N2O2 [M +
132.2, 135.4, 137.1, 153.7, 159.8, 163.9, 167.6 ppm. MS (FA): m/z H]+ 319.1447; found 319.1467.
(%) = 288 (100) [M]+. C19H16N2O (288.34): calcd. C 79.14, H 5.59,
4h: Yield: 529 mg, 30%, yellow solid (CHCl3/hexane). M.p. 178.7–
N 9.72; found C 79.06, H 5.50, N 9.73.
179.3 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 2.23 (s, 3 H, Ar-
Me), 3.84 (s, 3 H, Ar-OMe), 6.01 (s, 1 H), 6.36 (s, 1 H), 6.92 (d,
4b: Yield: 662 mg, 41%, yellow solid (CHCl3/hexane). M.p. 120.1–
121.0 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 2.25 (s, 3 H, Ar-
Me), 6.09 (s, 1 H), 6.44 (s, 1 H), 7.38–7.42 (m, 3 H, Ar-H) 7.41–
3
3JH,H = 8.5 Hz, 2 H, Ar-H), 7.43 (d, JH,H = 8.5 Hz, 2 H, Ar-H),
3
3
7.50 (d, JH,H = 8.5 Hz, 2 H, Ar-H), 7.87 (d, JH,H = 8.5 Hz, 2 H,
3
7.51 (m, 4 H, Ar-H), 7.87 (d, JH,H = 8.0 Hz, 2 H, Ar-H), 8.25 (s,
Ar-H), 8.25 (s, 1 H, -N=CH-Ar) ppm. 13C NMR (125 MHz,
1 H, -N=CH-Ar) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = CDCl3, 25 °C): δ = 11.5, 55.4, 99.4, 103.1, 114.1, 128.3, 129.3,
11.5, 101.4, 103.7, 127.0, 128.7, 129.2, 129.4, 130.1, 133.9, 137.0,
138.4, 153.4, 159.8, 164.5, 167.4 ppm. MS (FA): m/z (%) = 323
(100) [M + H]+. C19H15ClN2O (322.79): calcd. C 70.70, H 4.68, N
8.68; found C 70.83, H 4.62, N 8.62.
129.4, 130.1, 133.9, 138.4, 153.3, 159.8, 160.5, 162.4, 167.7 ppm.
MS (FA): m/z (%) = 353 (100) [M + H]+. C20H17ClN2O2 (352.81):
calcd. C 68.09, H 4.86, N 7.94; found C 67.99, H 5.18, N 7.94.
4i: Yield: 610 mg, 35%, yellow oil. 1H NMR (500 MHz, CDCl3,
4c: Yield: 1.10 g, 69%, yellow solid (CHCl3/hexane). M.p. 119.5– 25 °C): δ = 2.22 (s, 3 H, Ar-Me), 3.82 (s, 3 H, Ar-OMe), 3.89 (s, 3
3
120.7 °C. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 2.24 (s, 3 H, Ar-
H, Ar-OMe), 6.05 (s, 1 H), 6.35 (s, 1 H), 6.90 (d, JH,H = 9.0 Hz,
3
3
Me), 3.90 (s, 3 H, Ar-OMe), 6.13 (s, 1 H), 6.43 (s, 1 H), 7.03 (d, 2 H, Ar-H), 7.03 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 7.45 (d, JH,H
=
3JH,H = 9.0 Hz, 2 H, Ar-H), 7.37–7.39 (m, 3 H, Ar-H), 7.49–7.53
9.0 Hz, 2 H, Ar-H), 7.88 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 8.18 (s, 1
3
(m, 2 H, Ar-H), 7.88 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 8.19 (s, 1 H, H, -N=CH-Ar) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ =
3
-N=CH-Ar) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 11.5, 11.4, 55.3, 55.4, 98.8, 102.7, 114.0, 114.4, 128.2, 128.4, 129.7, 130.7,
55.5, 100.9, 103.4, 114.5, 127.1, 128.4, 128.7, 129.0, 130.8, 137.4,
154.0, 159.8, 163.0, 163.0, 167.8 ppm. MS (FA): m/z (%) = 319
(100) [M + H]+. C20H18N2O2 (318.37): calcd. C 75.45, H 5.70, N
8.80; found C 75.45, H 5.71, N 8.80.
153.9, 159.7, 160.3, 162.9, 168.0 ppm. MS (FA): m/z (%) = 349
(100) [M + H]+. HRMS (FAB): calcd. for C21H20N2O3 [M]+
348.1474; found 348.1501.
4j: Yield: 477 mg, 33%, yellow oil. 1H NMR (500 MHz, CDCl3,
4d: Yield: 775 mg, 48%, yellow solid (CHCl3/hexane). M.p. 92.8–
25 °C): δ = 2.25 (s, 3 H, Ar-Me), 6.15 (s, 1 H), 6.44 (s, 1 H), 7.38–
1
3
92.9 °C. H NMR (500 MHz, CDCl3, 25 °C): δ = 2.23 (s, 3 H, Ar-
7.42 (m, 3 H, Ar-H), 7.46–7.49 (m, 3 H, Ar-H), 8.31 (td, JH,H
=
3
Me), 6.11 (s, 1 H), 6.42 (s, 1 H), 7.35 (d, JH,H = 8.5 Hz, 2 H, Ar- 8.0 Hz, 4JH,H = 2.0 Hz, 1 H, Ar-H), 8.34 (s, 1 H, -N=CH-Ar), 8.76
3
3
4
4
H), 7.44 (d, JH,H = 8.5 Hz, 2 H, Ar-H), 7.52–7.59 (m, 3 H, Ar- (dd, JH,H = 4.5 Hz, JH,H = 2.0 Hz, 1 H, Ar-H), 9.05 (d, JH,H
=
3
H), 7.93 (d, JH,H = 7.5 Hz, 2 H, Ar-H), 8.27 (s, 1 H, -N=CH-Ar)
2.0 Hz, 1 H, Ar-H) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ
ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 11.4, 100.9, 103.7, = 11.3, 102.1, 104.0, 123.9, 126.9, 128.6, 129.1, 130.9, 135.1, 136.6,
128.1, 128.9, 129.0, 129.0, 132.4, 135.1, 135.2, 135.5, 152.5, 159.8,
164.2, 167.2 ppm. MS (FA): m/z (%) = 323 (100) [M + H]+.
C19H15ClN2O (322.79): calcd. C 70.70, H 4.68, N 8.68; found C
70.84, H 4.71, N 8.69.
150.8, 152.6, 153.0, 159.6, 161.1, 167.0 ppm. MS (FA): m/z (%) =
290 (100) [M + H]+. HRMS (FAB): calcd. for C18H16N3O [M +
H]+ 290.1293; found 290.1289.
Procedure for the Synthesis of 2-Azadiene 4k: To a THF solution
(15 mL) of 4-(trimethylsilyl)methylpyridine (1b, 457 mg,
5.00 mmol) was added MeLi (1  in Et2O, 5.50 mmol) at room
4e: Yield: 679 mg, 38%, yellow solid (CHCl3/hexane). M.p. 174.1–
175.1 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 2.24 (s, 3 H, Ar-
3
Me), 6.07 (s, 1 H), 6.40 (s, 1 H), 7.36 (d, JH,H = 8.5 Hz, 2 H, Ar- temperature, and the reaction mixture was heated at 60 °C. After
3
3
H), 7.43 (d, JH,H = 8.5 Hz, 2 H, Ar-H), 7.50 (d, JH,H = 8.5 Hz,
1 h, anisonitrile (666 mg, 5.00 mmol) was added to the solution by
4240
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4237–4244

Yb(OTf)3-Catalyzed [4+1] Annulation of 2-Azadiene with Me3SiCN
3
syringe at room temperature, and the solution was stirred at the
same temperature. After 1 h, benzaldehyde (531 mg, 5.00 mmol)
was added to the mixture, and the reaction mixture was stirred for
1 h at room temperature. To quench the reaction, water (30 mL)
was added to the mixture at 0 °C. The mixture was extracted several
times with AcOEt, and the combined organic extracts were dried
with Na2SO4, filtered, and then concentrated under reduced pres-
sure. The residue was purified by neutral Al2O3 chromatography
(hexane/AcOEt) to give 4k (629 mg, 40%) as a yellow solid (CHCl3/
hexane). M.p. 191.2–192.4 °C. 1H NMR (500 MHz, CDCl3, 25 °C):
δ = 3.84 (s, 3 H, Ar-OMe), 6.24 (s, 1 H, Ar-CH=CAr-), 6.92 (d,
3JH,H = 9.0 Hz, 2 H, Ar-H), 7.42–7.45 (m, 4 H, Ar-H), 7.49–7.54
3JH,H = 7.5 Hz, 2 H, Ar-H), 7.52 (d, JH,H = 7.5 Hz, 2 H, Ar-H),
7.97 (br., 1 H, -NH-) ppm. 13C NMR (125 MHz, [D6]DMSO,
25 °C): δ = 11.0, 101.2, 101.3, 116.5, 124.8, 125.0, 128.2, 128.6,
128.6, 129.5, 129.8, 130.8, 131.7, 132.4, 159.4, 165.4 ppm. MS (FA):
m/z (%) = 349 (100) [M]+. C20H16ClN3O (349.81): calcd. C 68.67,
H 4.61, N 12.01; found C 68.53, H 4.38, N 11.70.
6e: Yield: 140 mg, 73%, pale-yellow solid (CHCl3/hexane). M.p.
233.8–234.0 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 2.26 (s, 3
H, Ar-Me), 3.85 (br., 2 H, Ar-NH2), 5.83 (s, 1 H, Ar-H), 7.37–7.41
3
(m, 6 H, Ar-H), 7.45 (d, JH,H = 8.5 Hz, 2 H, Ar-H), 7.98 (br., 1
H, -NH-) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 11.4,
100.4, 102.4, 115.5, 125.9, 129.1, 129.1, 129.5, 129.5, 129.7, 130.3,
130.6, 131.4, 134.2, 159.8, 166.1 ppm. MS (FA): m/z (%) = 383
(100) [M]+. C20H15Cl2N3O (384.26): calcd. C 62.51, H 3.93, N
10.94; found C 62.31, H 3.78, N 10.81.
3
(m, 3 H, Ar-H), 7.89 (d, JH,H = 6.0 Hz, 2 H, Ar-H), 8.26 (s, 1 H,
3
-N=CH-Ar), 8.47 (d, JH,H = 6.0 Hz, 2 H, Ar-H) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 55.3, 112.6, 114.0, 123.9, 128.6,
128.9, 129.0, 130.7, 132.0, 135.7, 144.2, 149.5, 153.9, 160.1,
163.3 ppm. MS (FA): m/z (%) = 315 (100) [M + H]+. C21H18N2O
(314.38): calcd. C 80.23, H 5.77, N 8.91; found C 80.04, H 6.15, N
8.75.
6f: Yield: 152 mg, 80%, pale-yellow solid (CHCl3/hexane). M.p.
199.7–200.5 °C. H NMR (500 MHz, [D6]DMSO, 25 °C): δ = 2.22
(s, 3 H, Ar-Me), 3.78 (s, 3 H, Ar-OMe), 4.01 (br., 2 H, Ar-NH2),
1
3
6.22 (s, 1 H, Ar-H), 6.99 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 7.39 (d,
General Procedure for the Synthesis of 3-Aminopyrrole 6: To a THF
(1 mL) solution of 2-azadiene 4 (0.500 mmol) and trimethylsilyl cy-
anide (5, 59.5 mg, 0.600 mmol) was added Yb(OTf)3 (62.0 mg,
0.100 mmol) at room temperature, and the reaction mixture was
stirred for 24 h at the same temperature. To quench the reaction, a
saturated aqueous solution of NaHCO3 (5 mL) was added to the
mixture. The mixture was extracted several times with CHCl3, and
the combined organic extracts were dried with anhydrous Na2CO3,
filtered, and then concentrated under reduced pressure. The crude
product was purified by SiO2 column chromatography (hexane/Ac-
OEt) to afford 6 in the yields shown in Table 2.
3
3JH,H = 9.0 Hz, 2 H, Ar-H), 7.44 (d, JH,H = 9.0 Hz, 2 H, Ar-H),
3
7.59 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 11.09 (br., 1 H, -NH-) ppm.
13C NMR (125 MHz, CDCl3, 25 °C): δ = 11.0, 55.1, 101.2, 101.2,
114.1, 116.8, 125.1, 126.6, 127.7, 128.2, 128.6, 129.3, 131.0, 131.5,
157.0, 159.4, 165.6 ppm. MS (FA): m/z (%) = 380 (100) [M + H]+.
C21H18ClN3O2 (379.84): calcd. C 66.40, H 4.78, N 11.06; found C
66.02, H 4.54, N 10.77.
6g: Yield: 130 mg, 75%, pale-yellow solid (CHCl3/hexane). M.p.
195.3–195.6 °C. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 2.23 (s, 3
H, Ar-Me), 3.84 (s, 3 H, Ar-OMe), 3.91 (br., 2 H, Ar-NH2), 5.77
(s, 1 H, Ar-H), 6.94 (d, JH,H = 7.5 Hz, 2 H, Ar-H), 7.23 (t, JH,H
= 7.5 Hz, 1 H, Ar-H), 7.36–7.44 (m, 4 H, Ar-H), 7.50 (d, JH,H
3
3
6a: Yield: 118 mg, 75%, colorless solid (CHCl3/hexane). M.p.
157.9–158.0 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 2.20 (s, 3
H, Ar-Me), 3.83 (br., 2 H, Ar-NH2), 5.79 (s, 1 H, Ar-H), 7.20 (t,
3
=
7.5 Hz, 2 H, Ar-H), 7.99 (br., 1 H, -NH-) ppm. 13C NMR (75 MHz,
CDCl3, 25 °C): δ = 12.4, 55.3, 99.6, 101.7, 114.2, 115.5, 124.5,
124.6, 125.6, 129.0, 129.2, 129.4, 130.6, 132.4, 159.6, 166.9 ppm.
MS (FA): m/z (%) = 346 (100) [M + H]+. HRMS (FAB): calcd. for
C21H20N3O2 [M + H]+ 346.1556; found 346.1585.
3
3JH,H = 7.5 Hz, 1 H, Ar-H), 7.33 (t, JH,H = 7.5 Hz, 1 H, Ar-H),
7.36–7.45 (m, 6 H, Ar-H), 7.50 (t, 3JH,H = 7.5 Hz, 2 H, Ar-H), 8.24
(br., 1 H, -NH-) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ =
11.3, 100.0, 101.8, 116.1, 124.8, 125.7, 127.9, 128.0, 128.7, 129.1,
129.2, 130.5, 132.1, 132.2, 159.6, 166.7 ppm. MS (FA): m/z (%) =
315 (100) [M]+. HRMS (FAB): calcd. for C20H17N3O [M]+
315.1372; found 315.1380.
6h: Yield: 158 mg, 83%, pale-yellow solid (CHCl3/hexane). M.p.
212.5–212.9 °C. H NMR (500 MHz, [D6]DMSO, 25 °C): δ = 2.20
(s, 3 H, Ar-Me), 3.78 (s, 3 H, Ar-OMe), 4.20 (br., 2 H, Ar-NH2),
1
3
6.08 (s, 1 H, Ar-H), 6.97 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 7.34 (d,
6b: Yield: 152 mg, 87%, pale-yellow solid (CHCl3/hexane). M.p.
165.7–165.8 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 2.21 (s, 3
H, Ar-Me), 3.86 (br., 2 H, Ar-NH2), 5.79 (s, 1 H, Ar-H), 7.33–7.45
(m, 9 H, Ar-H), 8.16 (br., 1 H, -NH-) ppm. 13C NMR (125 MHz,
CDCl3, 25 °C): δ = 11.3, 100.1, 102.1, 115.2, 125.8, 127.9, 128.2,
128.8, 129.3, 129.5, 130.7, 130.9, 131.1, 131.9, 159.7, 166.5 ppm.
MS (FA): m/z (%) = 349 (100) [M]+. C20H16ClN3O (349.81): calcd.
C 68.67, H 4.61, N 12.01; found C 68.51, H 4.61, N 12.01.
3
3JH,H = 9.0 Hz, 2 H, Ar-H), 7.41 (d, JH,H = 9.0 Hz, 2 H, Ar-H),
3
7.68 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 11.03 (br., 1 H, -NH-) ppm.
13C NMR (125 MHz, [D6]DMSO, 25 °C): δ = 11.0, 55.1, 100.6,
100.7, 113.7, 114.3, 124.3, 126.0, 128.4, 128.4, 129.4, 130.1, 130.8,
131.6, 158.8, 159.2, 165.9 ppm. MS (FA): m/z (%) = 379 (100)
[M]+. C21H18ClN3O2 (379.84): calcd. C 66.40, H 4.78, N 11.06;
found C 66.13, H 4.57, N 10.79.
6i: Yield: 116 mg, 62%, pale-yellow sold (CHCl3/hexane). M.p.
158.7–160.0 °C. H NMR (500 MHz, [D6]DMSO, 25 °C): δ = 2.20
6c: Yield: 88.1 mg, 51%, green solid (CHCl3/hexane). M.p. 148.0–
148.7 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 2.19 (s, 3 H, Ar-
Me), 3.75 (br., 2 H, Ar-NH2), 3.80 (s, 3 H, Ar-OMe), 5.79 (s, 1 H,
Ar-H), 6.94 (d, 3JH,H = 8.5 Hz, 2 H, Ar-H), 7.30 (t, 3JH,H = 7.5 Hz,
1
(s, 3 H, Ar-Me), 3.77 (s, 3 H, Ar-OMe), 3.78 (s, 3 H, Ar-OMe), 3.99
3
(br., 2 H, Ar-NH2), 6.08 (s, 1 H, Ar-H), 6.96 (d, JH,H = 9.0 Hz, 2
3
3
3
H, Ar-H), 6.98 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 7.33 (d, JH,H
=
1 H, Ar-H), 7.36 (t, JH,H = 7.5 Hz, 2 H, Ar-H), 7.40–7.43 (m, 4
9.0 Hz, 2 H, Ar-H), 7.58 (d, 3JH,H = 9.0 Hz, 2 H, Ar-H), 10.91 (br.,
1 H, -NH-) ppm. 13C NMR (125 MHz, [D6]DMSO, 25 °C): δ =
11.0, 55.1, 55.1, 100.3, 100.5, 113.7, 114.0, 115.6, 124.7, 125.5,
126.3, 128.2, 129.3, 129.3, 156.7, 158.6, 159.1, 166.3 ppm. MS (FA):
m/z (%) = 375 (100) [M]+. C22H21N3O3 (375.42): calcd. C 70.38, H
5.64, N1 1.19; found C 70.01, H 5.52, N 10.88.
H, Ar-H), 8.25 (br., 1 H, -NH-) ppm. 13C NMR (125 MHz, CDCl3,
25 °C): δ = 11.3, 55.3, 100.0, 101.8, 114.6, 116.3, 124.9, 126.4,
127.8, 127.8, 128.0, 128.7, 129.7, 132.2, 157.8, 159.6, 166.8 ppm.
MS (FA): m/z (%) = 345 (100) [M]+. C21H19N3O2 (345.39): calcd.
C 73.03, H 5.54, N 12.17; found C 73.03, H 5.76, N 12.08.
6d: Yield: 135 mg, 77%, pale-yellow solid (CHCl3/hexane). M.p.
234.3–234.4 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 2.27 (s, 3
H, Ar-Me), 3.87 (br., 2 H, Ar-NH2), 5.85 (s, 1 H, Ar-H), 7.24 (t,
3JH,H = 8.0 Hz, 1 H, Ar-H), 7.36–7.40 (m, 4 H, Ar-H), 7.44 (t,
6j: Yield: 47.5 mg, 30%, pale-yellow solid (CHCl3/hexane). M.p.
1
242.4–142.5 °C. H NMR (500 MHz, [D6]DMSO, 25 °C): δ = 2.21
(s, 3 H, Ar-Me), 4.33 (br., 2 H, Ar-NH2), 6.16 (s, 1 H, Ar-H), 7.32–
Eur. J. Org. Chem. 2010, 4237–4244
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4241

T. Sasada, T. Sawada, R. Ikeda, N. Sakai, T. Konakahara
FULL PAPER
7.43 (m, 5 H, Ar-H), 8.03 (d, JH,H = 8.0 Hz, 1 H, Ar-H), 8.32 (d,
(100) [M + H]+. HRMS (FAB): calcd. for C20H16ClN2O [M +
3
3JH,H = 5.0 Hz, 1 H, Ar-H), 8.92 (s, 1 H, Ar-H), 11.24 (br 1 H, H]+ 335.0951; found 335.0956.
-NH-) ppm. 13C NMR (125 MHz, [D6]DMSO, 25 °C): δ = 11.0,
8c: Yield: 164 mg, 99%, pale-yellow solid (CHCl3/hexane). M.p.
101.1, 101.2, 113.1, 123.5, 127.5, 128.0, 128.3, 128.7, 131.0, 131.2,
131.4, 131.8, 145.2, 145.9, 159.3, 165.5 ppm. MS (FA): m/z (%) =
317 (100) [M]+. C19H16N4O (316.36): calcd. C 72.13, H 5.10, N
17.71; found C 71.91, H 4.90, N 17.46.
1
256.6–257.0 °C. H NMR (500 MHz, [D6]DMSO, 25 °C): δ = 2.26
(s, 3 H, Ar-Me), 3.79 (s, 3 H, Ar-OMe), 5.45 (s, 1 H, Ar-H), 6.94
3
3
(d, JH,H = 8.5 Hz, 2 H, Ar-H), 7.26 (t, JH,H = 7.5 Hz, 1 H, Ar-
3
3
H), 7.46 (t, JH,H = 7.5 Hz, 2 H, Ar-H), 7.67 (d, JH,H = 7.5 Hz, 2
3
6k: Yield: 142 mg, 83%, yellow solid (CHCl3/hexane). M.p. 219.4–
H, Ar-H), 7.99 (d, JH,H = 8.5 Hz, 2 H, Ar-H), 10.37 (br., 1 H,
1
-NH-), 11.88 (br., 1 H, -NH-) ppm. 13C NMR (125 MHz, [D6]-
DMSO, 25 °C): δ = 19.4, 55.1, 106.3, 112.9, 113.1, 124.4, 125.7,
126.6, 127.5, 127.6, 128.6, 130.3, 131.1, 148.8, 158.3, 176.6 ppm.
MS (FA): m/z (%) = 331 (100) [M + H]+. HRMS (FAB): calcd. for
C21H19N2O2 [M + H]+ 331.1447; found 331.1449.
220.0 °C. H NMR (500 MHz, CDCl3, 25 °C): δ = 3.35 (br., 2 H,
3
Ar-NH2), 3.80 (s, 3 H, Ar-OMe), 6.83 (d, JH,H = 8.0 Hz, 2 H, Ar-
H), 7.20–7.22 (m, 3 H, Ar-H), 7.26–7.28 (m, 2 H, Ar-H), 7.44 (t,
3JH,H = 8.0 Hz, 2 H, Ar-H), 7.55 (d, JH,H = 8.0 Hz, 2 H, Ar-H),
3
3
8.12 (br., 1 H, -NH-), 8.50 (d, JH,H = 5.0 Hz, 2 H, Ar-H) ppm.
13C NMR (125 MHz, [D6]DMSO, 25 °C): δ = 55.1, 111.0, 113.9,
116.0, 124.3, 124.4, 124.7, 124.8, 128.5, 128.9, 129.0, 129.1, 133.1,
143.3, 149.6, 158.2 ppm. MS (FA): m/z (%) = 342 (100) [M + H]+.
HRMS (FAB): calcd. for C22H20N3O [M + H]+ 342.1606; found
342.1607.
Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental procedures and characterization data
for novel compounds, ORTEP diagram of 4d and 6g, X-ray data
1
for 4d and 6g, and copies of the H and 13C NMR spectra of the
novel products.
General Procedure for the One-pot Synthesis of 3-Aminopyrrole 6:
To a THF solution (5 mL) of 1a (339 mg, 2.00 mmol) was added
nBuLi (1.5  in hexane, 2.20 mmol) at –70 °C, and the reaction
mixture was stirred at the same temperature. After 1 h, benzonitrile
(2a, 206 mg, 2.00 mmol) was added to the solution by syringe, and
the solution was further stirred for 1 h at –70 °C, then for 1 h at
room temperature. Aldehyde 3 (2.00 mmol) was added to the solu-
tion at –70 °C, and the mixture was stirred for 1 h at the same
temperature, then for 1 h at room temperature. Trimethylsilyl cya-
nide (5, 59.5 mg, 0.600 mmol) and Yb(OTf)3 (62.0 mg, 0.100 mmol)
were added to the mixture at room temperature, and the reaction
mixture was stirred for 24 h at the same temperature. To quench
the reaction, a saturated aqueous solution of NaHCO3 (10 mL)
was added to the mixture. The mixture was extracted several times
with CHCl3, and the combined organic extracts were dried with
anhydrous Na2CO3, filtered, and then concentrated under reduced
pressure. The crude product was purified by SiO2 column
chromatography (hexane/AcOEt) to afford 6a and 6b in 53 and
41% yield, respectively.
Acknowledgments
This work was partially supported by a grant from the Japan Pri-
vate School Promotion Foundation (2008 and 2009) and a Grant-
in-Aid for Scientific Research from Ministry of Education, Culture,
Sports, Science and Technology (MEXT) (16550148, 2004–2005;
21590025, 2009–2011) and a fund for the High-Tech Research Cen-
ter Project for Private Universities, which is a matching fund sub-
sidy from MEXT (2000–2004 and 2005–2007).
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Am. Chem. Soc. 2008, 130, 6859–6866; e) K. Schneider, S. Kel-
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K. W. Johnson, M. I. Gross, M. Iwamoto, P. Jones, D. Lofland,
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i) T. Bando, A. Narita, I. Saito, H. Sugiyama, J. Am. Chem.
Soc. 2003, 125, 3471–3485; j) J. A. Kaizerman, M. I. Gross, Y.
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R. D. Tanaka, H. E. Moser, R. W. Buerli, J. Med. Chem. 2003,
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Cozzi, N. Bianchi, R. Gambari, R. Romagnoli, Bioorg. Med.
Chem. 2003, 11, 965–975.
General Procedure for the Synthesis of Pyrrolo[3,4-b]pyridin-4-ones
8: To an MeCN (9 mL) and H2O (1 mL) solution of pyrrole 5
(0.500 mmol) was added Mo(CO)6 (66.0 mg, 0.250 mmol). The
mixture was stirred at 100 °C. After 2.5 h, the volatile compounds
were removed by evaporation in vacuo. The residue was purified
by SiO2 column chromatography (AcOEt) to give 8.
8a: Yield: 132 mg, 88%, pale-yellow solid (CHCl3/hexane). M.p.
1
188.6–189.7 °C. H NMR (300 MHz, [D6]DMSO, 25 °C): δ = 2.28
(s, 3 H Ar-Me), 5.49 (s, 1 H, Ar-H), 7.24–7.49 (m, 6 H, Ar-H), 7.69
3
3
(d, JH,H = 7.5 Hz, 2 H, Ar-H), 8.04 (d, JH,H = 7.5 Hz, 2 H, Ar-
H), 10.46 (br., 1 H, -NH-), 12.04 (br., 1 H, -NH-) ppm. 13C NMR
(75 MHz, [D6]DMSO, 25 °C): δ = 19.4, 106.4, 113.5, 114.1, 126.1,
126.6, 126.8, 127.3, 127.5, 127.8, 128.6, 129.0, 131.0, 131.7, 149.0,
176.5 ppm. MS (FA): m/z (%) = 301 (100) [M + H]+. HRMS
(FAB): calcd. for C20H17N2O [M + H]+ 301.1341; found 301.1347.
8b: Yield: 151 mg, 90%, pale-yellow solid (CHCl3/hexane). M.p.
292 °C (decomp.). 1H NMR (500 MHz, [D6]DMSO, 25 °C): δ =
[2] F. Arcamone, S. Penco, P. Orezzi, V. Nicolella, A. Pirelli, Na-
ture 1964, 203, 1064–1065.
[3] A. C. Finlay, F. A. Hochstein, B. A. Sobin, F. X. Murphy, J.
Am. Chem. Soc. 1951, 73, 341–343.
[4] For selected recent papers, see: a) D. M. Chenoweth, D. A.
Harki, P. B. Dervan, J. Am. Chem. Soc. 2009, 131, 7175–7181;
b) F. Brucoli, P. W. Howard, D. E. Thurston, J. Comb. Chem.
2009, 11, 576–586; c) A. Gangjee, W. Li, J. Yang, R. L. Kisliuk,
J. Med. Chem. 2008, 51, 68–76; d) G. Fridkin, W. D. Lubell,
3
2.27 (s, 3 H, Ar-Me), 5.48 (s, 1 H, Ar-H), 7.27 (t, JH,H = 8.0 Hz,
3
3
1 H, Ar-H), 7.38 (t, JH,H = 8.0 Hz, 2 H, Ar-H), 7.51 (d, JH,H
=
3
8.0 Hz, 2 H, Ar-H), 7.69 (d, JH,H = 8.0 Hz, 2 H, Ar-H), 8.01 (d,
3JH,H = 8.0 Hz, 2 H, Ar-H), 10.45 (br., 1 H, -NH-), 12.07 (br., 1
H, -NH-) ppm. 13C NMR (125 MHz, [D6]DMSO, 25 °C): δ = 19.4,
106.6, 112.8, 113.4, 126.8, 127.4, 127.8, 128.1, 128.4, 128.5, 129.0,
129.8, 130.3, 131.6, 148.9, 176.3 ppm. MS (FA): m/z (%) = 335
4242
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4237–4244

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4243

T. Sasada, T. Sawada, R. Ikeda, N. Sakai, T. Konakahara
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Received: February 22, 2010
Published Online: June 9, 2010
4244
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4237–4244