Copper(I)-catalyzed tandem cyclization/condensation reaction to novel 4,5-dihydropyrazolo[1,5-a]quinolines and pyrazolo[1,5-a]indoles

Article abstract of DOI:10.1080/00397911.2010.517892

A facile copper(I)-catalyzed tandem reaction for the synthesis of 4,5-dihydropyrazolo[1,5-a]quinolines and pyrazolo[1,5-a]indoles is reported here. High efficiency and good yields are displayed in this transformation under mild reaction conditions.

Full text of DOI:10.1080/00397911.2010.517892

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Copper(I)-Catalyzed Tandem Cyclization/
Condensation Reaction to Novel 4,5-
Dihydropyrazolo[1,5-a]quinolines and
Pyrazolo[1,5-a]indoles
Chenchen Hang a , Qiulian Li a , Yongming Zhu a & Hajime Katayama
b
a College of Pharmacy, Soochow University , Suzhou , China
b College of Pharmacy, Kinjo Gakuin University, Ohmori, Moriyama-
ku , Nagoya-City , Japan
Published online: 26 Jul 2011.
To cite this article: Chenchen Hang , Qiulian Li , Yongming Zhu & Hajime Katayama (2011)
Copper(I)-Catalyzed Tandem Cyclization/Condensation Reaction to Novel 4,5-Dihydropyrazolo[1,5-
a]quinolines and Pyrazolo[1,5-a]indoles, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:22, 3318-3324, DOI:
10.1080/00397911.2010.517892
To link to this article: http://dx.doi.org/10.1080/00397911.2010.517892
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Synthetic Communications1, 41: 3318–3324, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.517892
COPPER(I)-CATALYZED TANDEM CYCLIZATION/
CONDENSATION REACTION TO NOVEL
4,5-DIHYDROPYRAZOLO[1,5-a]QUINOLINES
AND PYRAZOLO[1,5-a]INDOLES
Chenchen Hang,1 Qiulian Li,1 Yongming Zhu,1 and
Hajime Katayama2
1College of Pharmacy, Soochow University, Suzhou, China
2College of Pharmacy, Kinjo Gakuin University, Ohmori, Moriyama-ku,
Nagoya-City, Japan
GRAPHICAL ABSTRACT
Abstract A facile copper(I)-catalyzed tandem reaction for the synthesis of 4,5-
dihydropyrazolo[1,5-a]quinolines and pyrazolo[1,5-a]indoles is reported here. High
efficiency and good yields are displayed in this transformation under mild reaction conditions.
Keywords Copper(I); 4,5-dihydropyrazolo[1,5-a]quinolines; 1,3-diketones; pyrazolo[1,5-
a]indoles
INTRODUCTION
DNA topoisomerases are key enzymes that allow DNA strands or double
helices to pass through each other, and they can solve all of the topological problems
of DNA in replication, transcription, and other cellular transactions.[1] Hence, a
number of anticancer agents take DNA topoisomerases as their targets.[2] It was first
reported by Katayama that some quaternary salts of pyrazolo[1,5-a]indole deriva-
tives, as represented by the structure A (Fig. 1), have fairly strong inhibitory activity
against DNA topoisomerases I and II and have strong cytotoxic activity against
cancer cells.[3] The structure–activity relationship (SAR) in these derivatives was
briefly investigated, and the results showed that the size and polarity of the substitu-
ents were crucial for the activity and that poisonous activities against enzyme might
be the reason for growth inhibition.[4] We have been involved in the synthesis of
pyrazolo[1,5-a]indole derivatives,[5] as represented by the structure B (Fig. 1). The
Received February 10, 2010.
Address correspondence to Yongming Zhu, College of Pharamacy, Soochow University, Suzhou
215123, China. E-mail: zhuyongming@suda.edu.cn
3318

DIHYDROPYRAZOLO[1,5-a]QUINOLINES
3319
Figure 1. The active compounds and the designed skeleton.
in vitro antitumor activity of B was examined with leukemia K562 and HL-60 cells
respectively. It showed that B can kill both leukemia K562 and HL-60 cells, with
IC50 of 5.56 mg=ml for K562 cells and 1.33 mg=ml for HL-60 cells. The strong antic-
ancer activity of B prompted us to figure out the structure of 4,5-dihydropyrazolo
[1,5-a]quinoline C (Fig. 1) as a possible candidate with the hope to discover new bio-
logically active compounds. There are few synthetic routes to 4,5-dihydropyrazolo
[1,5-a]quinolines,[6–8] but their syntheses was cumbersome with poor yields of the
products and harsh reaction conditions.
It is well recognized that the development of tandem reactions is an important
pursuit from the view of operational simplicity and assembly efficiency.[9] We noticed
that 1,3-diketones were converted in situ into pyrazoles by the addition of hydrazine
easily,[10] but the difficulties exist in isolation and purification of pyrazoles. Also, in
the past few years, the elaboration of heterocycles through copper-catalyzed coup-
ling reactions has been well developed.[11] Inspired by these findings, we planned
to explore a novel and facile method to construct pyrazoloheterocycles starting with
1,3-diketones via tandem process (Scheme 1). The method may fit the preparation of
4,5-dihydropyrazolo[1,5-a]quinoline as well as pyrazolo[1,5-a]indole derivatives as
shown in Scheme 1.
Our group has been involved in the studies of copper(I)-catalyzed coupling
reactions and has reported some intramolecular amination reactions via copper(I)
catalysis.[5,12,13] Compound 1a was used as a model to achieve and optimize the
desired tandem reaction for the formation of 3a. The results are summarized in
Table 1. As a base, K2CO3 provided better yield than Cs2CO3. Ligand is essential,
and 1,10-phenanthroline (PHAN) was found to be better than ethylenediamine
(EDA). As a catalyst, CuBr was usable but yield was less than with CuI. Without
catalyst, no reaction was observed. The optimal reaction condition for the coupling
of pyrazole 2a required CuI, PHAN, and K2CO3 in dioxane as a solvent. To have an
effective tandem reaction, the conversion of 1,3-diketones to pyrazoles should be
Scheme 1. The tandem reaction route.

3320
C. HANG ET AL.
Table 1. Screening of reaction conditions for the tandem reactions of 1aa
Entry
Solvent (mL)
Temp (ꢀC)b
R Time (h)b
Catalystb
Ligandc
Base
Yield (%)d
1
2
3
4
5
6
7
8
9
Dioxane (2)
Dioxane (2)
rtb
6
6
1
1
1
1
1
1
1
CuI
CuI
CuI
CuI
CuI
CuBr
CuI
CuI
—
PHAN
PHAN
PHAN
PHAN
EDA
K2CO3
K2CO3
K2CO3
CsCO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
39
73
92
79
44
83
38
40
0
100
100
100
100
100
100
100
100
Dioxane (0.5)
Dioxane (0.5)
Dioxane (0.5)
Dioxane (0.5)
Toluene (0.5)
Dioxane (0.5)
Dioxane (0.5)
PHAN
PHAN
—
PHAN
aReaction conditions: 1a (1 mmol) and N2H4 ꢁ H2O (1.2 mmol) were dissolved in solvent and stirred for
1 h. Then catalyst (0.05 mmol), ligand (0.1 mmol), and base (2.5 mmol) were added subsequently, and the
reaction mixture was refluxed for 20 h.
bTemp., reaction temperature; rt, room temperature.
cIsolated yields after silica-gel chromatography.
dPHAN, 1,10-phenanthroline; EDA, ethylenediamine, 0.3 mmol.
completed prior copper(I)-catalyzed intramolecular C-N coupling reaction, but it
was reported that pyrazoles could be formed in aqueous conditions from 1,3-dioke-
tones and hydrazine in the presence of dodeca-tungstophosphoric acid.[14] Thus, the
effect of a dehydrating agent at the initial stage of the tandem reaction was investi-
gated as follows. When 5-(2-bromophenyl)-1-phenylpentane-1,3-diketone 1a
(1 mmol) and hydrazine hydrate (1.2 equiv) in 1,4-dioxane (2 mL) were reacted in
the presence of molecular sieves 4A (330 mg) and MgSO4 (1 equiv) at room tempera-
ture, the yield of the desired product 2a was low (as monitored by thin-layer chro-
matography, TLC), but temperature elevation up to 100 ꢀC increased the yield of
2a with longer reaction time (6 h). When the solvent was reduced to 0.5 mL, the
tandem reaction completed within 1 h, and the isolated yield of 2-phenyl-4,5-
dihydropyrazolo[1,5-a]quinoline 3a became 92%. This result indicated that solvent
volume and temperature were crucial to the desired tandem reaction. The optimal
reaction conditions were applied to the synthesis of a variety of 4,5-dihydropyra-
zolo[1,5-a]quinolines. We have found that our method is versatile and the yields
were generally good to excellent. This method was also applicable for the synthesis
of pyrazolo[1,5-a]indoles. The results are summarized in Table 2.
A wide range of functional groups in both rings A and C were tolerated in the
reaction. The yields of 4,5-dihydropyrazolo[1,5-a]quinolines (entries 1–9) were in
general better those that of pyrazolo[1,5-a]indoles (entries 10–18), presumably
because of the steric reason. Methyl substituent ortho to bromine atom required
prolonged reaction time (entries 4 and 18). Yields were insensitive to the introduc-
tion of substitution at ring C.

DIHYDROPYRAZOLO[1,5-a]QUINOLINES
3321
Table 2. Synthesis of 4,5-dihydropyrazolo[1,5-a]quinolines and pyrazolo[1,5-a]indoles via
copper-catalyzed tandem reactiona
a
Entry
Starting materialc
N
R1
R2
R3
Yield (%)d
1
2
1a
1b
1c
1d
1e
1f
2
2
2
2
2
2
2
2
2
1
1
1
1
1
1
1
1
1
H
5-MeO
5-F
H
H
H
H
H
H
Ph
Ph
3a (92)
3b (93)
3c (91)
3d (80)e
3e (86)
3f (94)
3g (87)
3h (89)
3i (74)
3j (90)
3k (91)
3l (89)
3m (79)
3n (89)
3o (85)
3p (86)
3q (70)
3r (55)d
3
Ph
Ph
4
3-Me
H
5
4-MeOC6H4
4-NO2C6H4
-(CH2)4-
-(CH2)4-
-(CH2)4-
Ph
6
H
7
1g
1h
1i
H
8
5-MeO
5-F
9
10
11
12
13
14
15
16
17
18
1j
H
H
H
H
H
H
1k
1l
5-MeO
5-F
Ph
Ph
1m
1n
1o
1p
1q
1r
H
4-MeOC6H4
4-NO2C6H4
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)4-
H
H
5-MeO
5-F
3-Me
aReaction conditions: A solution of 1 (1 mmol) and N2H4 H2O (1.2 mmol) in 0.5 mL dioxane was stirred
for 1 h. Then CuI (0.05 mmol), PHAN (0.1 mmol), K2CO3 (2.5 mmol), and dioxane (2 mL) were added,
and the resulting solution was refluxed for 20 h.
bPHAN, 1,10-phenanthroline.
cThe structure of 1,3-diketone is not keto-form but enol-form, as indicated by the spectral data.
dIsolated yields after silica-gel chromatography.
eReaction time was prolonged to 40 h.
In summary, a novel method for the synthesis of 4,5-dihydropyrazolo[1,5-a]
quinolines and pyrazolo[1,5-a]indoles has been developed by
a
tandem
copper(I)-catalyzed cyclization=condensation reaction of 1,3-diketones. This method
provides a general, facile, and convenient route to the synthesis of pharmacologically
attractive compounds. High efficiency and good yields are displayed in this trans-
formation under mild reaction conditions. A more detailed investigation on the
potential biologically active compounds is ongoing in our laboratory.
EXPERIMENTAL
A solution of compound 1 (1.0 mmol) and hydrazine monohydrate (0.058 mL,
60 mg, 1.2 mmol) in anhydrous 1,4-dioxane (0.5 mL) was stirred at 100 ꢀC for 1 h.
Then, CuI (10 mg, 0.05 mmol), 1,10-phenanthroline (18 mg, 0.1 mmol), K2CO3
(345 mg, 2.5 mmol), and anhydrous 1,4-dioxane (2 mL) were added. The mixture
was refluxed at 110 ꢀC for 20 h under the protection of argon and filtered through

3322
C. HANG ET AL.
a pad of celite. After the filtrate was evaporated under reduced pressure, the residue
was purified by chromatography (silica gel H 10 g, solvents: petroleum ether=ethyl
acetate) to give 3 as a solid.
SPECTRAL DATA
2-Phenly-4,5-dihydropyrazolo[1,5-a]quinoline 3a
White solid (EtOAc), mp 77.7–78.7 ꢀC. 1H NMR (400 MHz, CDCl3): d
3.01–2.93 (m, 2H), 3.09-3.01 (m, 2H), 6.48 (s, 1H), 7.17–7.11 (m, 1H), 7.24 (d,
J ¼ 6.87 Hz, 1H), 7.38–7.30 (m, 2H), 7.46–7.38 (m, 2H), 7.91 (d, J ¼ 7.62 Hz, 2H),
8.01 (d, J ¼ 7.95 Hz, 1H). 13C NMR (100 MHz, CDCl3): d 17.0, 21.1, 97.1, 111.5,
120.5, 121.4 (ꢂ2), 122.2, 123.5, 123.9, 124.2 (ꢂ2), 129.0, 132.2, 135.4, 147.6, 153.3.
HRMS (EI): calcd. for C17H14N2 246.1157 [Mþ]; found 246.1159.
7-Methoxy-2-phenyl-4,5-dihydropyrazolo[1,5-a]quinoline 3b
White solid (EtOAc), mp 111.1–112.6 ꢀC. 1H NMR (400 MHz, CDCl3): d 2.95
(t, J ¼ 7.58 Hz, 2H), 3.04 (t, J ¼ 7.52 Hz, 2H), 3.83 (s, 3H), 6.46 (s, 1H), 6.80 (s, 1H),
6.87 (d, J ¼ 8.78 Hz, 1H), 7.36–7.29 (m, 1H), 7.46–7.38 (m, 2H), 7.95-7.86 (m, 3H).
13C NMR (100 MHz, CDCl3): d 21.7, 26.2, 55.8, 101.4, 112.7, 114.2, 117.3, 125.9
(ꢂ2), 128.0, 128.2, 128.8 (ꢂ2), 130.9, 133.7, 139.3, 151.7, 157.2. HRMS (ESI): calcd.
for C18H17N2O 276.1263 [Mþ]; found 276.1258.
7-Fluoro-2-phenyl-4,5-dihydropyrazolo[1,5-a]quinoline 3c
White solid (EtOAc), mp 111.7–112.9 ꢀC. 1H NMR (400 MHz, CDCl3): d 2.96
(t, J ¼ 7.67 Hz, 2H), 3.05 (t, J ¼ 7.73 Hz, 2H), 6.47 (s, 1H), 6.96 (dd, J ¼ 2.18,
8.63 Hz, 1H), 7.04 (dt, J ¼ 2.30, 8.62 Hz, 1H), 7.37–7.29 (m, 1H), 7.47-7.38 (m,
2H), 7.88 (d, J ¼ 7.85 Hz, 2H), 7.99–7.92 (m, 1H). 13C NMR (100 MHz, CDCl3): d
21.5, 26.0, 101.7, 114.4 and 114.7, 115.2 and 115.5, 117.7 and 117.8, 126.0 (ꢂ2),
128.2, 128.6 and 128.7, 128.9 (ꢂ2), 133.2 and 133.5, 139.5, 152.2, 158.6 and 161.8.
HRMS (ESI): calcd. for C17H13FN2 264.1063 [Mþ]; found 264.1055.
9-Methyl-2-phenyl-4,5-dihydropyrazolo[1,5-a]quinoline 3d
1
White solid (EtOAc), mp 99.1–100.8 ꢀC. H NMR (400 MHz, CDCl3): d 2.86
(s, 3H), 2.95–2.89 (m, 2H), 3.01–2.95 (m, 2H), 6.47 (s, 1H), 7.07–7.01 (m, 1H),
7.10 (d, J ¼ 7.04 Hz, 1H), 7.19 (d, J ¼ 7.42 Hz, 1H), 7.35–7.28 (m, 1H), 7.46–7.39
(m, 2H), 7.90 (d, J ¼ 7.61 Hz, 2H). 13C NMR (100 MHz, CDCl3): d 22.0, 22.1,
27.5, 100.1, 124.9, 125.5 (ꢂ2), 126.1, 127.7, 128.4, 128.6 (ꢂ2), 129.0, 131.8, 133.6,
135.4, 141.7, 150.5. HRMS (ESI): calcd. for C18H16N2 260.1313 [Mþ]; found 260.1301.
2-(4-Methoxyphenyl)-4,5-dihydropyrazolo[1,5-a]quinoline 3e
White solid (EtOAc), mp 125.1–126.0 ꢀC. 1H NMR (400 MHz, CDCl3): d
3.01–2.94 (m, 2H), 3.10–3.01 (m, 2H), 3.85 (s, 3H), 6.41 (s, 1H), 6.96 (d, J ¼ 8.75 Hz,

DIHYDROPYRAZOLO[1,5-a]QUINOLINES
3323
2H), 7.17–7.08 (m, 1H), 7.28–7.21 (m, 1H), 7.39-7.30 (m, 1H), 7.83 (d, J ¼ 8.75 Hz,
2H), 7.98 (d, J ¼ 7.99 Hz, 1H). 13C NMR (100 MHz, CDCl3): d 21.5, 25.6, 55.3,
101.0, 114.0 (ꢂ2), 115.8, 124.7, 126.1, 126.3, 127.0 (ꢂ2), 127.7, 128.2, 136.7, 139.7,
151.9, 159.5. HRMS (ESI): calcd. for C18H16N2O 276.1263 [Mþ]; found 276.1257.
2-(4-Nitrophenyl)-4,5-dihydropyrazolo[1,5-a]quinoline 3f
1
Yellow solid (EtOAc), mp 174.2–175.6 ꢀC. H NMR (400 MHz, CDCl3): d
3.05–2.97 (m, 2H), 3.12–3.05 (m, 2H), 6.57 (s, 1H), 7.22–7.16 (m, 1H), 7.32–7.24
(m, 1H), 7.43–7.34 (m, 1H), 8.01 (d, J ¼ 7.95 Hz, 1H), 8.05 (d, J ¼ 8.91 Hz, 2H),
8.28 (d, J ¼ 8.92 Hz, 2H). 13C NMR (100 MHz, CDCl3): d 21.6, 25.7, 102.5, 116.3,
124.2 (ꢂ2), 125.9, 126.3 (ꢂ2), 126.8, 128.1, 128.6, 136.5, 139.9, 140.6, 147.3, 149.7.
HRMS (EI): calcd. for C17H13N3O2 291.1008 [Mþ]; found 291.1006.
5,6,7,8,9,10-Hexahydroindazolo[2,3-a]quinoline 3g
White solid (EtOAc), mp 72.7–73.8 ꢀC. 1H NMR (400 MHz, CDCl3): d
1.89–1.75 (m, 4H), 2.50 (t, J ¼ 5.80 Hz, 2H), 2.79 (t, J ¼ 5.94 Hz, 2H), 2.98–2.83
(m, 4H), 7.11–7.06 (m, 1H), 7.21 (d, J ¼ 7.40 Hz, 1H), 7.33–7.27 (m, 1H), 7.86 (d,
J ¼ 7.95 Hz, 1H). 13C NMR (100 MHz, CDCl3): d 15.5, 15.5, 18.8, 18.9, 19.1, 21.1,
108.8, 110.8, 119.7, 121.5, 123.1, 123.7, 130.1, 132.3, 146.1. HRMS (EI): calcd. for
C15H16N2 224.1313 [Mþ]; found 224.1315.
2-Methoxy-7,8,9,10,11,12-hexahydroquinoline[1,2-b]indazole 3h
White solid (EtOAc), mp 78.5–79.8 ꢀC. 1H NMR (400 MHz, CDCl3): d
1.88–1.72 (m, 4H), 2.47 (t, J ¼ 5.98 Hz, 2H), 2.75 (t, J ¼ 6.11 Hz, 2H), 2.92–2.79
(m, 4H), 3.79 (s, 3H), 6.75 (d, J ¼ 2.65 Hz, 1H), 6.81 (dd, J ¼ 8.75, 2.74 Hz, 1H),
7.72 (d, J ¼ 8.75 Hz, 1H). 13C NMR (100 MHz, CDCl3): d 20.5, 20.5, 23.8, 23.9,
24.0, 26.4, 55.9, 112.6, 113.3, 114.5, 116.7, 128.1, 131.3, 134.4, 150.5, 156.8. HRMS
(EI): calcd. for C16H18N2O 254.1419 [Mþ]; found 254.1419.
2-Fluoro-7,8,9,10,11,12-hexahydroquinoline[1,2-b]indazole 3i
White solid (EtOAc), mp 101.1–101.9 ꢀC. 1H NMR (400 MHz, CDCl3): d
1.91–1.73 (m, 4H), 2.48 (t, J ¼ 5.97 Hz, 2H), 2.77 (t, J ¼ 6.06 Hz, 2H), 2.96-2.83
(m, 4H), 6.93 (dd, J ¼ 2.61, 8.64 Hz, 1H), 6.98 (dt, J ¼ 2.73, 8.61 Hz, 1H),
7.83–7.77 (m, 1H). 13C NMR (100 MHz, CDCl3): d 15.3, 15.5, 18.7, 18.9, 19.0,
21.1, 108.8, 109.4 and 109.7, 110.4 and 110.7, 112.1 and 112.2, 123.4 and 123.5,
128.6 and 128.6, 129.6, 146.1, 153.4 and 156.6. HRMS (ESI): calcd. for
C15H15FN2 242.1219 [Mþ]; found 242.1226.
REFERENCES
1. Wang, J. C. Cellular roles of DNA topoisomerases: A molecular perspective. Nat. Rev.
Mol. Cell Bio. 2002, 3, 430–440.

3324
C. HANG ET AL.
2. (a) Pontmesil, M.; Kohn, K. W. DNA Topoisomerases in Cancer; Oxford University Press:
New York, 1991; (b) Halicka, H. D.; Ozkaynak, M. F.; Levendoglu-Tugal, O.; Sandoval,
C.; Seiter, K.; Kajstura, M.; Traganos, F.; Jayabose, S.; Darzynkiewicz, Z. DNA damage
response as a biomarker in treatment of leukemias. Cell Cycle 2009, 8, 1720–1724; (c)
Ishimaru, C.; Yonezawa, Y.; Kuriyama, I.; Nishida, M.; Yoshida, H.; Mizushina, Y.
Inhibitory effects of cholesterol derivatives on DNA polymerase and topoisomerase
activities, and human cancer cell growth. Lipids 2008, 43, 373–382.
3. Katayama, H.; Kawada, Y.; Kaneko, K.; Oshiyama, T.; Takatsu, N. Synthetic inhibitors
of DNA topoisomerase I and II. Chem. Pharm. Bull. 1999, 47, 48–53.
4. (a) Katayama, H.; Kiryu, Y.; Kaneko, K.; Ohshima, R. Anti-cancer activities of pyra-
zolo[1,5-a]indole derivatives. Chem. Pharm. Bull. 2000, 48, 1628–1633 (b) Umemura,
K.; Mizushima, T.; Katayama, H.; Kiryu, Y.; Yamori, T.; Andoh, T. Inhibition of
DNA topoisomerases II and=or I by pyrazolo[1,5-a]indole derivatives and their growth
inhibitory activities. Mol. Pharmacol. 2002, 62, 873–880.
5. Zhu, Y.-M.; Qin, L.-N.; Liu, R.; Ji, S.-J.; Katayama, H. Synthesis of pyrazolo[1,5-
a]indoles via copper(I)-catalyzed intramolecular amination. Tetrahedron Lett. 2007, 48,
6262–6266.
6. Deshayes, C.; Gelin, S. Photocyclization of 5-(1-alkenyl)-1-phenylpyrazoles: A convenient
synthesis of 4,5-dihydropyrazolo[1,5-a]quinolines. Tetrahedron Lett. 1983, 24, 4679–4682.
7. Gotthardt, H.; Reiter, F. Lichtinduzierte reaktionen der sydnone in gegenwart von mehr-
fachbindungssystemen. Chem. Ber. 1979, 112, 1206–1225.
8. Winters, G.; Odasso, G.; Conti, M.; Tarzia, G.; Galliani, G. Synthesis and pregnancy termi-
nating activity of pyrazolo[1,5-a]indoles and quinolines. Eur. J. Med. Chem. 1984, 19, 215–218.
9. (a) Eilbracht, P.; Barfacker, L.; Buss, C.; Hollman, C.; Kitsos-Rzychon, B. E.;
Kranemann, C. L.; Rische, T.; Roggenbuck, R.; Schmidt, A. Tandem reaction sequences
under hydroformylation conditions: New synthetic applications of transition metal cataly-
sis. Chem. Rev. 1999, 99, 3329–3365; (b) Ji, K.-G.; Shu, X.-Z.; Chen, J.; Zhao, S.-C.;
Zheng, Z.-J.; Lu, L.; Liu, X.-Y.; Liang, Y.-M. PtCl2-catalyzed tandem triple migration
reaction toward (Z)-1,5-dien-2-yl eaters. Org. Lett. 2008, 10, 3919–3922; (c) Kabalka,
G. W.; Tejedor, D.; Li, N.-S.; Malladi, R. R.; Trotman, S. An unprecedented, tandem
aldol–Grob reaction sequence. J. Org. Chem. 1998, 63, 6438–6439; (d) Liu, Y.-K.; Ma,
C.; Jiang, K.; Liu, T.-Y.; Chen, Y.-C. Asymmetric tandem Michael addition–Witting reac-
tion to cyclohexenone annulation. Org. Lett. 2009, 11, 2848–2851.
10. Heller, S. T.; Natarajan, S. R. 1,3-Diketones from acid chlorides and ketones: A rapid and
general one-pot synthesis of pyrazoles. Org. Lett. 2006, 8, 2675–2678.
11. (a) Maiti, D.; Buchwald, S. T. Orthogonal Cu- and Pd-based catalyst systems for the
O- and N-arylation of aminophenols. J. Am. Chem. Soc. 2009, 131, 17423–17429; (b)
Kwong, F. Y.; Buchwald, S. T. Mild and efficient copper-catalyzed amination of aryl bro-
mides with primary alkylamines. Org. Lett. 2003, 5, 793–796; (c) Yuan, Q.-L.; Ma, D.-W.
A one-pot coupling=hydrolysis=condensation process to pyrrolo[1,2-a]quinoxaline. J.
Org. Chem. 2008, 73, 5159–5162; (d) Liu, F.; Ma, D.-W. Assembly of conjugated enynes
and substituted indoles via CuI=amino acid-catalyzed coupling of 1-alkynes with vinyl
iodides and 2-bromotrifluoroacetanilides. J. Org. Chem. 2007, 72, 4844–4850.
12. Liu, R.; Zhu, Y.-M.; Qin, L.-N.; Ji, S.-J. Efficient synthesis of 1-aryl-1H-indazole deriva-
tives via copper(I)-catalyzed intramolecular amination reaction. Synth. Commun. 2008, 38,
249–254.
13. Liu, R.; Zhu, Y.-M.; Qin, L.-N.; Ji, S.-J.; Katayama, H. Synthesis of 2-aryl-2H-indazoles
via copper(I)-catalyzed intramolecular amination reaction. Heterocycles 2007, 71, 1755–1763.
14. Chen, X.; She, J.; Shang, Z.; Wu, J.; Wu, H.; Zhang, P. Synthesis of pyrazoles, diazepines,
enaminones, and enamino esters using 12-tungstophosphoric acid as a reusable catalyst in
water. Synthesis 2008, 21, 3478–3486.