The synthesis of imidazo[1,5-a]quinolines via a decarboxylative cyclization under metal-free conditions

Article abstract of DOI:10.1039/c8ra03786h

An iodine-mediated decarboxylative cyclization was developed from α-amino acids and 2-methyl quinolines under metal-free conditions, affording a variety of imidazo[1,5-a]quinolines with moderate to good yields.

Full text of DOI:10.1039/c8ra03786h

RSC Advances
View Article Online
View Journal | View Issue
PAPER
The synthesis of imidazo[1,5-a]quinolines via
a decarboxylative cyclization under metal-free
Cite this: RSC Adv., 2018, 8, 23058
conditions†
a
b
a
a
a
*
*
Zicong Yan, Changfeng Wan, Yu Yang, Zhenggen Zha and Zhiyong Wang
Received 3rd May 2018
Accepted 15th June 2018
An iodine-mediated decarboxylative cyclization was developed from a-amino acids and 2-methyl
quinolines under metal-free conditions, affording a variety of imidazo[1,5-a]quinolines with moderate to
good yields.
DOI: 10.1039/c8ra03786h
rsc.li/rsc-advances
heterocycles.12 Recently, a series of cascade decarboxylative
reactions involving azomethine ylides have been developed to
construct C–C and C–N bonds.13 As a facile, stable and cheap
starting materials, amino acids has long been neglected in
organic synthesis.14 Our group also developed some decarbox-
ylative cyclization reactions from amino acids.15 As our
continuing interest in the decarboxylative reaction for the
synthesis of N-heterocycles, herein we report a new decarbox-
ylative cascade reaction for the synthesis of imidazo[1,5-a]
quinolines starting from readily available materials under
metal-free condition (Scheme 1c and d).
Introduction
The imidazo[1,5-a]quinoline moiety is an important class of
fused N-heterocyclic compounds such as skeletons of NK1
receptor ligands,1 antitumor drug C-1311,2 potential antimi-
crobial natural product cribrostatin 6,3 inhibitor targeting
phosphodiesterase 10A4 and highly efficient ligands of central
benzodiazepine receptors.5 As the structure for the precursors
of N-heterocyclic carbene6 and other transformations,7 much
effort has been done for the synthesis of imidazo[1,5-a]quino-
lines. The previous strategies mainly focused in Vilsmeier-type
cyclizations using N-2-pyridylmethylamides as starting mate-
rials.8 Subsequently, various new protocols have also been
developed to synthesize these compounds.9 Recently, Zeng and
Xu groups independently reported copper-catalyzed imidazole
synthesis via the oxidative C–H amination reactions (Scheme 1a
and b).10 These elegant protocols led to new reactivity pathways
and made great progress in imidazole synthesis. However, these
reported methods still suffered from the usage of transition-
metal catalysts. Our group also developed previously some
oxidative C–H amination reactions for imidazole synthesis
under metal-free conditions.11 The main drawbacks are the
narrow scope of the substrates and the difficulty of the available
starting materials. Therefore, a more environmental-friendly
methodology with readily available starting materials for the
preparation of imidazo[1,5-a]quinolines is also highly desirable.
On the other hand, decarboxylative reactions were widely
used in organic synthesis, especially in pericyclic reactions for
Results and discussion
Initially, we employed 2-methylquinoline (1a) and valine (2a) as
model substrates. The results are summarized in Table 1.
Firstly, the reaction of 1 equiv. of 1a and 1.5 equiv. of 2a was
carried out in the presence of 1 equiv. of I2 in N,N-dime-
thylformamide (DMF) at 80 ꢀC for 3 h to give rise to a 20% yield
of the expected product 1-isopropylimidazo[1,5-a]quinoline
(3aa) (Entry 1, Table 1). Then the inuence of oxidants on this
reaction was investigated (Entries 2–6, Table 1). It was found
that the yield could be improved to 84% by using 3 equiv. of tert-
butyl hydroperoxide (TBHP) while the other oxidants, such as
di-tert-butyl peroxide (DTBP), dioxygen and peroxysulfates had
little inuence on the reaction or deteriorated the reaction.
Aerwards several solvents were also examined (Entries 7–
16, Table 1). N,N-Dimethylacetamide (DMA) had a little negative
inuence on the reaction (Entry 7, Table 1) while dimethyl
sulfoxide (DMSO) reduced the reaction yield remarkably. Other
solvents, such as ethyl nitrile, toluene, tetrahydrofuran (THF),
aHefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of
So Matter Chemistry & Center for Excellence in Molecular Synthesis of Chinese
Academy of Sciences, Collaborative Innovation Center of Suzhou Nano Science and methanol, 1,4-dioxane and water would result in the failure of
Technology & School of Chemistry and Materials Science, University of Science and
the reaction (Entries 9–14, Table 1). The mixed solvents deteri-
orated the reaction either (Entries 15–16, Table 1). Subsequently
Technology of China, 230026, Hefei, Anhui, P. R. China. E-mail: zwang3@ustc.edu.cn;
Tel: +86-551-6360-3185
the different temperature was examined for this reaction. When
the reaction temperature was increased to 100 ꢀC, the corre-
sponding product can be obtained with a yield of 83%. (Entry
19, Table 1). Further increase of the temperature could not
bCollege of Chemistry and Chemical Engineering, Jiangxi Normal University, 330022,
Nanchang, P. R. China. E-mail: wanfeng@jxnu.edu.cn
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c8ra03786h
23058 | RSC Adv., 2018, 8, 23058–23065
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
Table 1 Optimization of reaction conditionsa
Entry
Oxidant
Solvent
Temp. (ꢀC)
Yieldb (%)
1
2
3
4
5
6
7
8
—
TBHP
O2
DMF
DMF
DMF
DMF
DMF
DMF
DMA
DMSO
H2O
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
25
50
100
120
80
80
20
84
84
18
DTBP
K2S2O8
(NH4)2S2O8
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
0
Trace
81
57
n. d.
n. d.
Trace
n. d.
n. d.
n. d.
37
49
25
43
83
83
0
17
9
10
11
12
13
14
15
16
17
18
19
20
21c
22d
Tol.
MeCN
MeOH
THF
1,4-Dioxane
DMF/H2O
DMF/MeOH
DMF
DMF
DMF
DMF
DMF
Scheme 1 Previous study and this work for the synthesis of imidazo
[1,5-a]quinolines.
DMF
a
Reaction conditions: 1a (1.0 equiv., 0.2 mmol), 2a (1.5 equiv., 0.3
b
mmol), I2 (1.0 equiv.), oxidant (3 equiv.) in solvent (0.5 mL). Isolated
c
d
yield. The reaction was carried out without I2. The reaction was
carried out with 20% of I2.
improve the yield (Entry 20, Table 1). The product 3aa was ob-
tained with the yields of 25% and 43% when the reactions were
carried out at 25 ꢀC and 50 ꢀC, respectively (Entry 17–18, Table
1). This indicated that reducing the reaction temperature would
destroy this reaction. The reaction could not proceed without I2
and the yield of the product decreased to 17% while only 20% of
the I2 was added (Entries 21–22, Table 1). Finally, the optimized
reaction conditions were obtained as described in entry 2 of
Table 1: 1.0 equiv. of 2-methyl quinoline 1a and 1.5 equiv. of a-
amino acid 2a as the reaction substrates, 1.0 equiv. of iodine
and 3.0 equiv. of TBHP as the oxidants, the reaction being
the same. However, the 8-methoxyl product was obtained with
an abnormal yield of 79% (3ha, 3ja and 3ka). This implied that
steric hindrance had little inuence on the reaction when 2-
methyl-8-phenylquinoline was employed (3ia vs. 3la). The 2-
ethylquinoline showed lower reactivity. We could not obtain the
desired product under the standard conditions but only the
corresponding ketone was obtained. The desired imidazo[1,5-a]
quinoline can be obtained with a yield of 50% when the reaction
temperature was increased to 120 ꢀC (3ma). Agreeing with
former reports,11b an electron-withdrawing substituent on the
carbon of methyl at 2-position favoured the reaction (3na). 1-
Methylisoquinoline could also converted to the desired product
well under standard conditions (3oa).
On the other hand, the scope of the amino acids were
investigated (Table 3). Alkyl amino acids worked well in this
reaction to afford the desired products with moderate to good
yields (3ab–3ah), while the aromatic amino acids, such as
phenylglycine and phenylalanine, can also be employed as the
substrate to afford the corresponding products with lower yields
(3aj–3ak). This may be due to the fact that under these condi-
tions, aromatic amino acids are more active and some side
reactions can occur. For instance, part of the amino acids might
ꢀ
carried out in 0.5 mL of DMF at 80 C for 3 h.
With the optimized conditions in hand, we explored the
scope of the reaction substrates. Firstly, different substrates
with groups on R1 and R2 were examined, and the results were
listed in Table 2. Generally, 6-substituted 2-methylquinolines
could be converted to the corresponding products in moderate
to good yields (3ba–3ia). The substrates with electron-
withdrawing groups presented more efficient than that with
the electron-donating groups in this reaction. For example, 2-
methyl-6-methoxylquinoline only afforded the product (3ha)
with 44% yield while 2-methyl-6-nitroquinoline gave the
product with a high yield of 81% (3ga). Subsequently, the
substitution position of methoxyl group was investigated. The
yields between 4-methoxyl and 6-methoxyl product were almost
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 23058–23065 | 23059

View Article Online
RSC Advances
Paper
Table 2 Substrate scope of various quinolinesa
Table 3 Substrate scope of various amino acidsa
a
Reaction conditions: 2b–2o (1.0 equiv., 0.2 mmol), 2a (1.5 equiv., 0.3
b
mmol), I2 (1.0 equiv.), oxidant (3 equiv.) in solvent (0.5 mL). Isolated
yield. c This reaction was carried out at 120 ꢀC.
ꢀ
[1,5-a]quinoline (3ai) can be obtained at 120 C by virtue of
this method, which was challenging from other methods.9a,11a
To get an insight into the mechanism of this process, we
conducted several control experiments (Scheme 2). Firstly, only
2-methylquinoline (1a) was employed under the standard
conditions and quinoline-2-carbaldehyde (1aa) was obtained
with a yield of 95%. The yield decreased when TBHP was absent
with 55% of 1a recovered, and no corresponding aldehyde was
found without iodine (Scheme 2a). Besides, the aldehyde (1aa)
and 2-(iodomethyl) quinoline (1ab) could be detected at 15
minutes of the model reaction (Scheme 2b). Moreover, 2-
(iodomethyl) quinoline (1ab) was employed under the standard
conditions without I2 and 1aa was obtained with a yield of 60%
(Scheme 2c). When quinoline-2-carbaldehyde (1aa) and valine
a
Reaction conditions: 1a–1o (1.0 equiv., 0.2 mmol), 2a (1.5 equiv., 0.3
b
mmol), I2 (1.0 equiv.), oxidant (3 equiv.) in solvent (0.5 mL). Isolated
c
d
yield. This reaction was carried out at 120 ꢀC. This product was
obtained with the starting material of 1-methylisoquinoline so the
structure was different from 3 as shown.
be decarboxylated rst, which could not convert to desired
products. As for tyrosine, the phenolic hydroxyl group could
tolerate the reaction conditions to give the desired product
with good yield (3al). To our delight, non-substituted imidazo
23060 | RSC Adv., 2018, 8, 23058–23065
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
(2a) were used as the reaction substrates under standard
conditions, 90% of 3aa could be afforded. It should be noted
that the yield decreased slightly when TBHP was absent, but no
corresponding product 3aa was detected without iodine
(Scheme 2d). These experiments indicated that 1aa might be an
intermediate of this reaction under the promotion of iodine and
TBHP. In the subsequent transformation, TBHP might not be
important but I2 is needed.
Based on the experimental results above and the previous
reports,10c,11a a possible reaction pathway was proposed as
shown in Scheme 3. Initially, 2-methylquinoline (1a) is quickly
substituted with iodine to afford 2-(iodomethyl) quinoline (1ab)
and subsequently oxidized to quinoline-2-carbaldehyde (1aa).
Thereaer, 1aa produces imine A with the amino acid 2a. The
imine A goes through N-iodination process, generating inter-
mediate B. Aerward, the intermediate B undergoes a decar-
boxylative pathway to generate intermediate
C at high
temperature. Finally, C transforms to D and then cyclization
happens easily through an intramolecular nucleophilic attack
to give the nal product 3aa.
Conclusions
In summary, we developed a facile decarboxylative cyclization to
construct imidazo[1,5-a]quinolines with readily available start-
ing material under metal-free condition. Compared to previous
reports, the substrate scope of the primary a-amino acid was
largely extended. In particular, the synthesis avoids the metal
residues in the products, which provides a useful method for
the pharmaceutical synthesis.
Scheme 2 Control experiments.
Experimental
Materials and methods
Products were puried by ash chromatography on 200–300
mesh silica gels using petroleum ether/ethyl acetate as eluent.
NMR spectra were recorded on 400 MHz (101 MHz for 13C NMR)
Bruker NMR spectrometer with CDCl3 or DMSO-d6 as the
solvent and tetramethylsilane (TMS) as the internal standard.
High resolution mass spectra (ESI) were recorded on a Waters™
Q-TOF Premier. Melting points were determined on a melting
point apparatus and are uncorrected.
General procedure for the synthesis of imidazo[1,5-a]
quinolines (3)
2-Methyl quinoline (1a, 28 mg, 0.2 mmol), valine (2a, 35 mg, 0.3
mmol) and iodine (51 mg, 0.2 mmol) were added to 0.5 mL of
N,N-dimethylformamide. Then 60 mL of tert-butyl hydroper-
oxide was added and the solution was kept at 80 ꢀC for 3 h. Aer
the reaction was nished, the reaction mixture was washed and
extracted by CH2Cl2. The organic phase was dried by Na2SO4
and then evaporated under reduced pressure. The resulting
residue was puried by silica gel column chromatography (PE/
EtOAc) to afford the desired product 3.
Scheme 3 The proposed reaction mechanism.
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 23058–23065 | 23061

View Article Online
RSC Advances
Paper
give the product as a yellow oil. Silica gel TLC Rf ¼ 0.15
(PE : EtOAc ¼ 10 : 1); 1H NMR (400 MHz, CDCl3) d 8.03 (m, 1H),
7.75–7.74 (d, J ¼ 2.3 Hz, 1H), 7.60–7.57 (m, 1H), 7.39 (s, 1H),
7.29–7.27 (m, 1H), 6.83–6.80 (m, 1H), 3.80–3.69 (sept, J ¼ 6.6 Hz,
1H), 1.56–1.54 (d, J ¼ 6.6 Hz, 6H); 13C NMR (101 MHz, CDCl3)
d 149.5, 131.9, 130.9, 130.3, 130.0, 127.9, 121.3, 119.3, 118.8,
118.5, 117.8, 30.0, 21.3; HRMS (ESI) m/z calcd for C14H14N2Br [M
+ H]+ 289.0340, found 289.0340.
1-Isopropyl imidazo[1,5-a]quinoline (3aa)
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a yellow oil. Silica gel TLC Rf ¼ 0.6
(PE : EtOAc ¼ 3 : 1); 1H NMR (400 MHz, CDCl3) d 8.07–8.05 (d, J
¼ 8.5 Hz, 1H), 7.52–7.50 (d, J ¼ 7.7 Hz, 1H), 7.41–7.37 (t, J ¼
7.9 Hz, 1H), 7.27–7.24 (m, 2H), 7.15–7.12 (d, J ¼ 9.6 Hz, 1H),
6.81–6.79 (d, J ¼ 9.3 Hz, 1H), 3.77–3.67 (sept, J ¼ 6.6 Hz, 1H),
1.47–1.45 (d, J ¼ 6.6 Hz, 6H). 13C NMR (101 MHz, CDCl3) d 149.3,
133.1, 130.2, 128.7, 127.7, 126.0, 124.8, 120.6, 117.5, 116.9, 30.0,
21.6; HRMS (ESI) m/z calcd for C14H15N2 [M + H]+ 211.1235,
found 211.1236.
1-Isopropyl-7-(triuoromethyl)-imidazo[1,5-a]quinoline (3fa)
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a yellow needle solid. Silica gel TLC Rf ¼ 0.5
(PE : EtOAc ¼ 3 : 1); mp ¼ 60–62 ꢀC; 1H NMR (400 MHz, CDCl3)
d 8.27–8.24 (d, J ¼ 8.9 Hz, 1H), 7.88 (s, 1H), 7.74–7.72 (d, J ¼
8.9 Hz, 1H), 7.41 (s, 1H), 7.34–7.32 (d, J ¼ 9.3 Hz, 1H), 6.95–6.92
(d, J ¼ 9.3 Hz, 1H), 3.84–3.74 (sept, J ¼ 6.6 Hz, 1H), 1.57 (d, J ¼
6.6 Hz, 6H); 13C NMR (101 MHz, CDCl3) d 150.0, 135.0, 130.2,
1-Isopropyl-7-methyl-imidazo[1,5-a]quinoline (3ba)
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a brown oil. Silica gel TLC Rf ¼ 0.45
(PE : EtOAc ¼ 3 : 1); 1H NMR (400 MHz, CDCl3) d 8.06–8.04 (d, J
¼ 8.6 Hz, 1H), 7.40 (s, 1H), 7.35 (s, 1H), 7.31–7.29 (d, J ¼ 8.6 Hz,
1H), 7.21 (d, J ¼ 8.1 Hz, 1H), 6.86–6.84 (d, J ¼ 9.4 Hz, 1H), 3.85–
3.75 (sept, J ¼ 6.7 Hz, 1H), 2.44 (s, 3H), 1.56–1.54 (d, J ¼ 6.7 Hz,
6H); 13C NMR (101 MHz, CDCl3) d 149.0, 134.4, 131.0, 130.0,
128.7, 128.7, 126.0, 120.5, 117.4, 116.8, 29.8, 21.5, 20.7; HRMS
(ESI) m/z calcd for C15H17N2 [M + H]+ 225.1392, found 225.1390.
1
127.8, 125.1, 122.4, 119.7 (q, JCF ¼ 272.0 Hz), 127.4, 127.0,
126.7, 126.4 (q, 2JCF ¼ 33.0 Hz), 126.1, 125.8, 125.7, 125.7, 125.7
(q, JCF ¼ 3.9 Hz), 124.2, 124.2, 124.1, 124.1 (q, JCF ¼ 3.4 Hz),
121.5, 119.9, 119.1, 117.4, 30.1, 21.4; HRMS (ESI) m/z calcd for
C
15H14N2F3 [M + H]+ 279.1109, found 279.1107.
1-Isopropyl-7-nitro-imidazo[1,5-a]quinoline (3ga)
7-Flouro-1-isopropyl-imidazo[1,5-a]quinoline (3ca)
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as an orange needle solid. Silica gel TLC Rf ¼
0.45 (PE : EtOAc ¼ 3 : 1); mp ¼ 190–192 ꢀC; 1H NMR (400 MHz,
CDCl3) d 8.47–8.24 (m, 3H), 7.44–7.43 (d, J ¼ 4.8 Hz, 1H), 7.40–
7.36 (dd, J ¼ 9.3, 5.5 Hz, 1H), 7.00–6.96 (m, 1H), 3.79–3.74 (sept,
J ¼ 6.4 Hz, 1H), 1.57 (d, J ¼ 6.5, 6H); 13C NMR (101 MHz, CDCl3)
d 150.5, 143.9, 136.7, 130.2, 126.5, 123.8, 122.3, 122.1, 120.0,
119.8, 117.6, 30.2, 21.4; HRMS (ESI) m/z calcd for C14H14N3O2
[M + H]+ 256.1086, found 256.1083.
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a yellow solid. Silica gel TLC Rf ¼ 0.6
(PE : EtOAc ¼ 3 : 1); mp ¼ 74–76 ꢀC; 1H NMR (400 MHz, CDCl3)
d 8.16–8.12 (dd, J ¼ 9.1, 4.4 Hz, 1H), 7.40 (s, 1H), 7.31–7.27 (m,
2H), 7.25–7.20 (m, 1H), 6.87–6.84 (d, J ¼ 9.3 Hz, 1H), 3.81–3.71
(sept, J ¼ 6.7 Hz, 1H), 1.56 (d, J ¼ 6.7 Hz, 6H); 13C NMR (101
1
MHz, CDCl3) d 160.4, 157.9 (d, JCF ¼ 251.5 Hz), 149.2, 129.9,
4
3
129.5, 129.5 (d, JCF ¼ 2.2 Hz), 127.9, 127.8 (d, JCF ¼ 8.3 Hz),
121.2, 119.7, 119.7 (d, 4JCF ¼ 2.7 Hz), 118.8, 118.6, 118.5 (d, 3JCF
¼ 8.5 Hz), 115.0, 114.8 (d, 2JCF ¼ 23.5 Hz), 114.0, 113.7 (d, 2JCF
¼
1-Isopropyl-7-methoxy-imidazo[1,5-a]quinoline (3ha)
22.3 Hz), 29.9, 21.4; HRMS (ESI) m/z calcd for C14H14N2F [M +
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a brown oil. Silica gel TLC Rf ¼ 0.30
(PE : EtOAc ¼ 3 : 1); 1H NMR (400 MHz, CDCl3) d 8.11–8.08 (d, J
¼ 8.8 Hz, 1H), 7.37 (s, 1H), 7.26–7.24 (d, J ¼ 9.6 Hz, 1H), 7.10–
7.08 (m, 2H), 6.88–6.86 (d, J ¼ 9.3 Hz, 1H), 3.90 (s, 3H), 3.84–3.74
(sept, J ¼ 6.7 Hz, 1H), 1.56 (d, J ¼ 6.7 Hz, 6H); 13C NMR (101
MHz, CDCl3) d 156.3, 148.7, 129.9, 127.4, 127.3, 120.6, 120.4,
118.2, 118.0, 115.1, 111.2, 55.5, 29.8, 21.5; HRMS (ESI) m/z calcd
for C15H17N2O [M + H]+ 241.1341, found 241.1342.
H]+ 229.1141, found 229.1138.
7-Chloro-1-isopropyl-imidazo[1,5-a]quinoline (3da)
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a yellow oil. Silica gel TLC Rf ¼ 0.6
(PE : EtOAc ¼ 2 : 1) 1H NMR (400 MHz, CDCl3) d 8.10–8.08 (d, J
¼ 9.0 Hz, 1H), 7.59 (s, 1H), 7.46–7.44 (d, J ¼ 9.0 Hz, 1H), 7.39 (s,
1H), 7.30–7.27 (d, J ¼ 9.6 Hz, 1H), 6.84–6.82 (d, J ¼ 9.4 Hz, 1H),
3.80–3.70 (sept, J ¼ 6.7 Hz, 1H), 1.57–1.55 (d, J ¼ 6.7 Hz, 6H); 13
C
NMR (101 MHz, CDCl3) d 149.5, 131.5, 130.17, 130.0, 127.8,
127.5, 127.5, 121.3, 119.4, 118.8, 118.3, 30.0, 21.4; HRMS (ESI)
m/z calcd for C14H14N2Cl [M + H]+ 245.0846, found 245.0844.
1-Isopropyl-7-phenyl-imidazo[1,5-a]quinoline (3ia)
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a yellow oil. Silica gel TLC Rf ¼ 0.15
(PE : EtOAc ¼ 10 : 1); 1H NMR (400 MHz, CDCl3) d 8.24–8.22 (d, J
7-Bromo-1-isopropyl-imidazo[1,5-a]quinoline (3ea)
The title compound was prepared according to the general ¼ 8.8 Hz, 1H), 7.82 (s, 1H), 7.75–7.73 (d, J ¼ 8.8 Hz, 1H), 7.67–
working procedure and puried by column chromatography to 7.65 (d, J ¼ 7.5 Hz, 4H), 7.50–7.46 (t, J ¼ 7.5 Hz, 2H), 7.40–7.37
23062 | RSC Adv., 2018, 8, 23058–23065
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
(m, 2H), 7.28–7.26 (t, J ¼ 6.8 Hz, 1H), 6.98–6.96 (d, J ¼ 9.3 Hz, CDCl3) d 148.0, 133.3, 128.6, 128.5, 127.5, 126.2, 126.1, 124.6,
2H), 3.90–3.80 (sept, J ¼ 6.6 Hz, 1H), 1.59 (d, J ¼ 6.6 Hz, 6H); 13
C
118.8, 117.1, 116.9, 29.7, 21.7, 12.5; HRMS (ESI) m/z calcd for
C
15H17N2 [M + H]+ 225.1392, found 225.1390.
NMR (101 MHz, CDCl3) d 149.4, 139.7, 137.6, 130.2, 128.9, 127.6,
127.0, 126.8, 126.5, 126.4, 120.8, 120.7, 117.9, 117.3, 30.0, 21.5.
HRMS (ESI) m/z calcd for C20H19N2 [M + H]+ 287.1548, found
287.1550.
Ethyl 1-isopropyl-imidazo[1,5-a]quinoline-3-carboxylate (3na)
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a pale yellow solid. Silica gel TLC Rf ¼ 0.2
1-Isopropyl-5-methoxy-imidazo[1,5-a]quinoline (3ja)
The title compound was prepared according to the general (PE : DCM ¼ 2 : 1); mp ¼ 118–120 ꢀC; 1H NMR (400 MHz,
working procedure and puried by column chromatography to CDCl3) d 8.30–8.28 (d, J ¼ 8.5 Hz, 1H), 8.15–8.13 (d, J ¼ 9.3 Hz,
give the product as a green oil. Silica gel TLC Rf ¼ 0.50 1H), 7.77–7.75 (d, J ¼ 7.5 Hz, 1H), 7.65–7.61 (t, J ¼ 7.6 Hz, 1H),
(PE : EtOAc ¼ 3 : 1); 1H NMR (400 MHz, CDCl3) d 8.15–8.12 (d, J 7.57–7.41 (t, J ¼ 7.4 Hz, 1H), 7.33–7.31 (d, J ¼ 9.5 Hz, 1H), 4.51–
¼ 8.7 Hz, 1H), 8.08–8.06 (d, J ¼ 8.1 Hz, 1H), 7.57–7.53 (m, 1H), 4.46 (q, J ¼ 7.0 Hz, 2H), 3.93–3.83 (sept, J ¼ 6.3 Hz, 1H), 1.64–
7.42–7.38 (m, 1H), 7.17 (s, 1H), 6.50 (s, 1H), 3.94 (m, 3H), 3.80– 1.62 (d, J ¼ 6.4 Hz, 6H), 1.48–1.45 (t, J ¼ 7.0 Hz, 3H); 13C NMR
3.71 (sept, J ¼ 6.5 Hz, 1H), 1.54 (d, J ¼ 6.6 Hz, 6H); 13C NMR (101 (101 MHz, CDCl3) d 163.8, 150.0, 134.6, 132.8, 129.2, 128.9,
MHz, CDCl3) d 148.5, 147.9, 133.4, 130.1, 128.5, 124.4, 123.4, 125.8, 125.7, 125.6, 121.9, 118.1, 117.3, 60.6, 30.3, 21.5, 14.6;
121.3, 117.9, 116.7, 91.9, 55.3, 30.0, 21.5; HRMS (ESI) m/z calcd HRMS (ESI) m/z calcd for C17H18N2O2Na [M + Na]+ 305.1266,
for C15H17N2O [M + H]+ 241.1341, found 241.1338.
found 305.1265.
1-Isopropyl-9-methoxy-imidazo[1,5-a]quinoline (3ka)
3-Isopropyl-imidazo[5,1-a]isoquinoline (3oa)
The title compound was prepared according to the general The title compound was prepared according to the general
working procedure and puried by column chromatography to working procedure and puried by column chromatography to
give the product as a green oil. Silica gel TLC Rf ¼ 0.55 give the product as a pale yellow solid, mp ¼ 73–75 ꢀC, silica gel
1
1
(PE : EtOAc ¼ 3 : 1) H NMR (400 MHz, CDCl3) d 7.41 (s, 1H), TLC Rf ¼ 0.3 (PE : EtOAc ¼ 3 : 1); H NMR (400 MHz, CDCl3)
7.33–7.29 (m, 1H), 7.18–7.16 (d, J ¼ 8.3 Hz, 2H), 7.00–6.98 (d, J ¼ d 8.00–7.98 (d, J ¼ 7.9 Hz, 1H), 7.77 (s, 1H), 7.65–7.63 (d, J ¼
8.1 Hz, 1H), 6.79–6.77 (d, J ¼ 9.2 Hz, 1H), 3.92 (m, 3H), 3.75–3.65 7.5 Hz, 1H), 7.57–7.55 (d, J ¼ 7.7 Hz, 1H), 7.52–7.48 (t, J ¼ 7.5 Hz,
(sept, J ¼ 6.7 Hz, 1H), 1.36 (d, J ¼ 6.7 Hz, 6H); 13C NMR (101 1H), 7.42–7.38 (t, J ¼ 7.4 Hz, 1H), 6.82–6.80 (d, J ¼ 7.4 Hz, 1H),
MHz, CDCl3) d 154.6, 149.7, 130.5, 129.1, 125.7, 122.7, 121.6, 3.41–3.31 (sept, J ¼ 6.8 Hz, 1H), 1.48 (d, J ¼ 6.8 Hz, 6H); 13C
119.7, 118.0, 109.9, 55.3, 30.2, 22.9; HRMS (ESI) m/z calcd for NMR (101 MHz, CDCl3) d 146.0, 128.4, 128.1, 127.0, 127.7, 126.6,
C
15H17N2O [M + H]+ 241.1341, found 241.1345.
125.1, 122.3, 119.5, 118.2, 113.5, 26.1, 20.8; HRMS (ESI) m/z
calcd for C14H15N2 [M + H]+ 211.1235, found 211.1235.
1-Isopropyl-9-phenyl-imidazo[1,5-a]quinoline (3la)
1-Propyl-imidazo[1,5-a]quinoline (3ab)
The title compound was prepared according to the general
working procedure and puried by column chromatography to The title compound was prepared according to the general
give the product as a yellow oil. Silica gel TLC Rf ¼ 0.35 (PE: working procedure and puried by column chromatography to
EtOAc ¼ 10: 1); 1H NMR (400 MHz, CDCl3) d 7.56–7.53 (m, 1H), give the product as a yellow oil. Silica gel TLC Rf ¼ 0.40
7.45–7.43 (d, J ¼ 9.2 Hz, 3H), 7.40–7.36 (t, J ¼ 7.4 Hz, 2H), 7.32– (PE : EtOAc ¼ 2 : 1); 1H NMR (400 MHz, CDCl3) d 8.15–8.13 (d, J
7.28 (t, J ¼ 7.4 Hz, 1H), 7.26–7.24 (d, J ¼ 9.4 Hz, 1H), 7.20–7.18 ¼ 8.1 Hz, 1H), 7.65–7.63 (d, J ¼ 7.5 Hz, 1H), 7.54–7.50 (m, 1H),
(d, J ¼ 6.9 Hz, 2H), 6.92–6.90 (d, J ¼ 9.2 Hz, 1H), 2.83–2.73 (sept, 7.41–7.36 (m, 2H), 7.27–7.25 (m, 1H), 6.94–6.92 (d, J ¼ 9.5 Hz,
J ¼ 6.7 Hz, 1H), 0.69–0.67 (d, J ¼ 6.7 Hz, 6H); 13C NMR (101 1H), 3.38–3.34 (t, J ¼ 7.4 Hz, 2H), 2.07–1.99 (m, 2H), 1.17–1.13 (t,
MHz, CDCl3) d 154.5, 141.0, 133.0, 131.0, 130.9, 129.5, 129.2, J ¼ 7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 144.1, 133.2, 130.3,
129.0, 127.60, 127.6, 126.5, 125.6, 122.1, 120.3, 117.7, 29.8, 21.3; 128.7, 127.7, 125.9, 124.8, 120.6, 117.4, 116.6, 34.3, 20.6, 14.0;
HRMS (ESI) m/z calcd for C20H19N2 [M + H]+ 287.1548, found HRMS (ESI) m/z calcd for C14H15N2 [M + H]+ 211.1235, found
287.1552.
211.1230.
1-Isopropyl-3-methyl-imidazo[1,5-a]quinoline (3ma)
1-Butyl-imidazo[1,5-a]quinoline (3ac)
The title compound was prepared according to the general The title compound was prepared according to the general
working procedure except the temperature was 120 ꢀC and working procedure and puried by column chromatography to
puried by column chromatography to give the product as give the product as an orange oil. Silica gel TLC Rf ¼ 0.65
a yellow solid. Silica gel TLC Rf ¼ 0.25 (PE : EtOAc ¼ 5 : 1); mp ¼ (PE : EtOAc ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 8.14–8.12 (d, J
110–112 ꢀC; 1H NMR (400 MHz, CDCl3) d 8.13–8.11 (d, J ¼ ¼ 8.5 Hz, 1H), 7.63–7.61 (d, J ¼ 7.7 Hz, 1H), 7.53–7.49 (t, J ¼
8.5 Hz, 1H), 7.60–7.58 (d, J ¼ 7.6 Hz, 1H), 7.49–7.45 (t, J ¼ 7.4 Hz, 7.8 Hz, 1H), 7.40–7.35 (m, 2H), 7.25–7.23 (m, 1H), 6.92–6.90 (d, J
1H), 7.36–7.33 (t, J ¼ 7.4 Hz, 1H), 7.20–7.17 (d, J ¼ 9.4 Hz, 1H), ¼ 9.4 Hz, 1H), 3.38–3.35 (t, J ¼ 7.7 Hz, 2H), 2.02–1.95 (m, 2H),
6.84–6.81 (d, J ¼ 9.4 Hz, 1H), 3.86–3.76 (sept, J ¼ 6.7 Hz, 1H), 1.61–1.54 (m, 2H), 1.05–1.00 (t, J ¼ 7.3 Hz, 3H); 13C NMR (101
2.49 (s, 3H), 1.57–1.55 (d, J ¼ 6.7 Hz, 6H); 13C NMR (101 MHz, MHz, CDCl3) d 144.2, 133.2, 130.3, 128.7, 127.7, 125.9, 124.8,
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 23058–23065 | 23063

View Article Online
RSC Advances
Paper
120.6, 120.6, 117.5, 116.6, 32.1, 29.3, 22.6, 13.9; HRMS (ESI) m/z
1-Methyl-imidazo[1,5-a]quinoline (3ah)
calcd for C15H17N2 [M + H]+ 225.1392, found 225.1391.
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a yellow oil. Silica gel TLC Rf ¼ 0.30
(PE : EtOAc ¼ 6 : 1); 1H NMR (400 MHz, CDCl3) d 8.23–8.21 (d, J
¼ 8.5 Hz, 1H), 7.65–7.63 (dd, J ¼ 7.7, 1.4 Hz, 1H), 7.54–7.49 (m,
1H), 7.41–7.37 (m, 1H), 7.33 (s, 1H), 7.26–7.24 (m, 1H), 6.95–6.92
(d, J ¼ 9.4 Hz, 1H), 3.09 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 140.0, 133.3, 130.3, 128.6, 127.7, 125.7, 124.9, 120.6, 120.5,
117.3, 116.2, 19.6; HRMS (ESI) m/z calcd for C12H11N2 [M + H]+
183.0922, found 183.0923.
1-Isobutyl-imidazo[1,5-a]quinoline (3ad)
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a yellow oil. Silica gel TLC Rf ¼ 0.25
(PE : EtOAc ¼ 5 : 1); 1H NMR (400 MHz, CDCl3) d 8.13–8.10 (d, J
¼ 8.5 Hz, 1H), 7.65–7.63 (d, J ¼ 7.7 Hz, 1H), 7.54–7.50 (t, J ¼
7.8 Hz, 1H), 7.41–7.37 (m, 2H), 7.27–7.25 (m, 1H), 6.95–6.92 (d, J
¼ 9.4 Hz, 1H), 3.28–3.26 (d, J ¼ 7.0 Hz, 2H), 2.47–2.35 (m, 1H),
1.10–1.09 (d, J ¼ 6.6 Hz, 6H); 13C NMR (101 MHz, CDCl3) d 143.5,
133.1, 130.3, 128.7, 127.7, 125.9, 124.9, 120.6, 120.6, 117.5,
116.6, 41.1, 26.6, 22.6; HRMS (ESI) m/z calcd for C15H17N2 [M +
H]+ 225.1392, found 225.1393.
Imidazo[1,5-a]quinoline (3ai)
The title compound was prepared according to the general
working procedure except the temperature was 120 ꢀC and
puried by column chromatography to give the product as
1
a brown oil. Silica gel TLC Rf ¼ 0.15 (PE : EtOAc ¼ 3 : 1); H
1-(sec-Butyl)-imidazo[1,5-a]quinoline (3ae)
NMR (400 MHz, CDCl3) d 8.65 (s, 1H), 7.98–7.96 (d, J ¼ 8.3 Hz,
1H), 7.68–7.66 (d, J ¼ 7.8 Hz, 1H), 7.58–7.54 (m, 1H), 7.48–7.41
(m, 2H), 7.34–7.32 (d, J ¼ 9.5 Hz, 1H), 7.05–7.03 (d, J ¼ 9.5 Hz,
1H); 13C NMR (101 MHz, CDCl3) d 130.9, 128.8, 128.6, 127.8,
125.6, 124.2, 122.4, 121.3, 116.8, 114.6; HRMS (ESI) m/z calcd for
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a brown oil. Silica gel TLC Rf ¼ 0.70
(PE : EtOAc ¼ 3 : 1); 1H NMR (400 MHz, CDCl3) d 8.15–8.13 (d, J
¼ 8.6 Hz, 1H), 7.63–7.61 (d, J ¼ 7.7 Hz, 1H), 7.52–7.49 (t, J ¼
7.9 Hz, 1H), 7.38–7.35 (m, 2H), 7.27–7.23 (m, 1H), 6.92–6.89 (d, J
¼ 9.3 Hz, 1H), 3.64–3.56 (m, 1H), 2.24–2.14 (m, 1H), 1.86–1.75
(m, 1H), 1.55–1.53 (d, J ¼ 6.7 Hz, 3H), 1.05–1.01 (t, J ¼ 7.4 Hz,
3H); 13C NMR (101 MHz, CDCl3) d 148.7, 133.2, 130.1, 128.7,
127.6, 126.1, 124.7, 120.7, 120.5, 117.5, 116.9, 36.7, 28.5, 18.9,
11.9; HRMS (ESI) m/z calcd for C15H17N2 [M + H]+ 225.1392,
found 225.1396.
C
11H9N2 [M + H]+ 169.0766, found 169.0765.
1-Phenyl-imidazo[1,5-a]quinoline (3aj)
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a pale yellow solid. Silica gel TLC Rf ¼ 0.30
(PE : EtOAc ¼ 6 : 1); mp ¼ 113–115 ꢀC; 1H NMR (400 MHz,
CDCl3) d 7.66–7.60 (m, 3H), 7.54–7.50 (m, 5H), 7.34–7.26 (m,
2H), 7.19–7.14 (m, 1H), 7.03–7.00 (d, J ¼ 9.4 Hz, 1H); 13C NMR
(101 MHz, CDCl3) d 142.3, 133.7, 132.3, 130.5, 129.5, 129.2,
128.7, 128.6, 127.3, 125.5, 125.1, 122.3, 121.4, 117.4, 117.1;
HRMS (ESI) m/z calcd for C17H13N2 [M + H]+ 245.1079, found
245.1082.
1-(tert-Butyl)-imidazo[1,5-a]quinoline (3af)
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a yellow oil. Silica gel TLC Rf ¼ 0.55
(PE : EtOAc ¼ 3 : 1); 1H NMR (400 MHz, CDCl3) d 8.42–8.40 (d, J
¼ 8.7 Hz, 1H), 7.63–7.61 (d, J ¼ 7.7 Hz, 1H), 7.54–7.50 (t, J ¼ 1-Benzyl-imidazo[1,5-a]quinoline (3ak)
7.9 Hz, 1H), 7.40–7.37 (m, 2H), 7.28–7.26 (d, J ¼ 9.1 Hz, 1H),
The title compound was prepared according to the general
6.95–6.92 (d, J ¼ 9.3 Hz, 1H), 1.75 (s, 9H); 13C NMR (101 MHz,
CDCl3) d 151.5, 133.2, 131.8, 128.7, 126.7, 126.5, 124.8, 120.8,
120.4, 120.3, 117.9, 34.8, 30.5; HRMS (ESI) m/z calcd for
working procedure except the temperature was 120 ꢀC and
puried by column chromatography to give the product as
a pale yellow solid. Silica gel TLC Rf ¼ 0.40 (PE : EtOAc ¼ 3 : 1);
C
15H17N2 [M + H]+ 225.1392, found 225.1391.
1
ꢀ
mp ¼ 95–97 C; H NMR (400 MHz, CDCl3) d 8.00–7.98 (d, J ¼
7.7 Hz, 1H), 7.61–7.59 (m, 1H), 7.47 (s, 1H), 7.35–7.25 (m, 5H),
7.23–7.15 (m, 3H), 6.98–6.96 (d, J ¼ 9.4 Hz, 1H), 4.83 (s, 2H); 13
C
1-Ethyl-imidazo[1,5-a]quinoline (3ag)
NMR (101 MHz, CDCl3) d 141.4, 136.9, 132.6, 130.7, 128.9, 128.5,
128.2, 127.8, 126.7, 125.7, 125.0, 121.2, 121.0, 117.3, 116.9, 37.8;
HRMS (ESI) m/z calcd for C18H15N2 [M + H]+ 259.1235, found
259.1230.
The title compound was prepared according to the general
working procedure and puried by column chromatography to
give the product as a brown oil. Silica gel TLC Rf ¼ 0.35
(PE : EtOAc ¼ 10 : 1); 1H NMR (400 MHz, CDCl3) d 8.18–8.16 (d, J
¼ 8.5 Hz, 1H), 7.64–7.62 (d, J ¼ 7.9 Hz, 1H), 7.53–7.50 (t, J ¼
7.8 Hz, 1H), 7.41–7.37 (m, 2H), 7.27–7.25 (m, 1H), 6.95–6.92 (d, J
4-(Imidazo[1,5-a]quinolin-1-ylmethyl)-phenol (3al)
¼ 9.1 Hz, 1H), 3.44–3.39 (q, J ¼ 6.9 Hz, 2H), 1.60–1.56 (t, J ¼ The title compound was prepared according to the general
7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 145.1, 133.2, 130.4, working procedure and puried by column chromatography to
ꢀ
128.7, 127.8, 125.9, 124.9, 120.7, 120.5, 117.4, 116.6, 25.8, 11.8; give the product as a brown solid, mp ¼ 224–225 C. Silica gel
HRMS (ESI) m/z calcd for C13H13N2 [M + H]+ 197.1079, found TLC Rf ¼ 0.55 (DCM : MeOH ¼ 10 : 1); 1H NMR (400 MHz,
197.1079.
DMSO) d 9.26 (s, 1H), 8.09–8.07 (d, J ¼ 8.2 Hz, 1H), 7.75–7.74 (d,
23064 | RSC Adv., 2018, 8, 23058–23065
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
´
´
˜
J ¼ 7.4 Hz, 1H), 7.47–7.38 (m, 4H), 7.12–7.10 (d, J ¼ 9.1 Hz, 1H),
6.91–6.89 (d, J ¼ 8.1 Hz, 2H), 6.66–6.64 (d, J ¼ 8.0 Hz, 2H), 4.68
(s, 2H); 13C NMR (101 MHz, DMSO) d 155.9, 141.9, 131.8, 130.2,
129.0, 128.5, 128.0, 127.1, 125.1, 125.08, 121.0, 120.6, 117.4,
117.0, 115.5, 36.1; HRMS (ESI) m/z calcd for C18H15N2O [M + H]+
275.1184, found 275.1185.
B. Perez, F. J. Luque, R. Gamez-Montano and R. Lavilla,
Angew. Chem., Int. Ed., 2016, 55, 8994; (d) H. Erguven,
D. C. Leitch, E. N. Keyzer and B. A. Arndtsen, Angew.
Chem., Int. Ed., 2017, 56, 6078.
7 (a) D. S. Roman, V. Poiret, G. Pelletier and A. B. Charette, Eur.
J. Org. Chem., 2015, 67; (b) Z. Tan, H. Zhao, C. Zhou, H. Jiang
and M. Zhang, J. Org. Chem., 2016, 81, 9939; (c) S.-S. Wu,
C.-T. Feng, D. Hu, Y.-K. Huang, Z. Li, Z.-G. Luo and
S.-T. Ma, Org. Biomol. Chem., 2017, 15, 1680.
Conflicts of interest
There are no conicts to declare.
8 (a) J. D. Bower and G. R. Ramage, J. Chem. Soc., 1955, 2834;
(b) K. Winterfeld and H. Franzke, Angew. Chem., 1963, 75,
1101.
9 (a) D. C. Mohan, S. N. Rao, C. Ravi and S. Adimurthy, Org.
Biomol. Chem., 2015, 13, 5602; (b) Z. Li, S.-S. Wu, Z.-G. Luo,
W.-K. Liu, C.-T. Feng and S.-T. Ma, J. Org. Chem., 2016, 81,
4386.
10 (a) M. Li, Y. Xie, Y. Ye, Y. Zou, H. Jiang and W. Zeng, Org.
Lett., 2014, 16, 6232; (b) H. Wang, W. Xu, Z. Wang, L. Yu
and K. Xu, J. Org. Chem., 2015, 80, 2431; (c) H. Wang,
W. Xu, L. Xin, W. Liu, Z. Wang and K. Xu, J. Org. Chem.,
2016, 81, 3681.
Acknowledgements
We are grateful to the nancial support from the National
Natural Science Foundation of China (21432009, 21672200,
21472177 and 21772185), and the assistance of the product
characterization from the Chemistry Experiment Teaching
Center of University of Science and Technology of China. This
work was supported by the Strategic Priority Research Program
of the Chinese Academy of Sciences, Grant No. XDB20000000.
11 (a) Q. Wang, S. Zhang, F. Guo, B. Zhang, P. Hu and Z. Wang,
J. Org. Chem., 2012, 77, 11161; (b) Y. Yan, Y. Zhang, Z. Zha
and Z. Wang, Org. Lett., 2013, 15, 2274.
Notes and references
1 A. Cappelli, G. Giuliani, M. Anzini, D. Riitano, G. Giorgi and
S. Vomero, Bioorg. Med. Chem., 2008, 16, 6850.
´
12 (a) N. Rodrıguez and L. J. Goossen, Chem. Soc. Rev., 2011, 40,
´
2 A. Wisniewska, A. Chrapkowska, A. Kot-Wasik, J. Konopa and
5030; (b) Y. Wei, P. Hu, M. Zhang and W. Su, Chem. Rev.,
2017, 117, 8864.
Z. Mazerska, Acta Biochim. Pol., 2007, 54, 831.
3 (a) G. R. Pettit, J. C. Collins, J. C. Knight, D. L. Herald,
R. A. Nieman, M. D. Williams and R. K. Pettit, J. Nat. Prod.,
2003, 66, 544; (b) M. D. Markey and T. R. Kelly, J. Org.
Chem., 2008, 73, 7441; (c) D. Knueppel and S. F. Martin,
Angew. Chem., Int. Ed., 2009, 48, 2569; (d) M. Mohamed,
T. P. Gonçalves, R. J. Whitby, H. F. Sneddon and
D. C. Harrowven, Chem.–Eur. J., 2011, 17, 13698.
4 M. S. Malamas, Y. Ni, J. Erdei, H. Stange, R. Schindler,
H.-J. Lankau, C. Grunwald, K. Y. Fan, K. Parris, B. Langen,
U. Egerland, T. Hage, K. L. Marquis, S. Grauer, J. Brennan,
R. Navarra, R. Graf, B. L. Harrison, A. Robichaud,
T. Kronbach, M. N. Pangalos, N. Hoefgen and
N. J. Brandon, J. Med. Chem., 2011, 54, 7621.
13 (a) D. Seidel, Acc. Chem. Res., 2015, 48, 317; (b) L. Zheng,
F. Yang, Q. Dang and X. Bai, Org. Lett., 2008, 10, 889; (c)
H.-P. Bi, L. Zhao, Y.-M. Liang and C.-J. Li, Angew. Chem.,
Int. Ed., 2009, 48, 792; (d) C. Zhang and D. Seidel, J. Am.
Chem. Soc., 2010, 132, 1798; (e) H.-P. Bi, Q. Teng, M. Guan,
W.-W. Chen, Y.-M. Liang, X. Yao and C.-J. Li, J. Org. Chem.,
2010, 75, 783; (f) Y. Kang and D. Seidel, Org. Lett., 2016, 18,
4277; (g) D. Singh, V. Kumar, N. Devi, C. C. Malakar,
R. Shankar and V. Singh, Adv. Synth. Catal., 2017, 359, 1213.
14 (a) D. Zhao, T. Wang, Q. Shen and J.-X. Li, Chem. Commun.,
2014, 50, 4302; (b) K. Xu, Z. Wang, J. Zhang, L. Yu and J. Tan,
Org. Lett., 2015, 17, 4476; (c) A. Joshi, D. C. Mohan and
´
S. Adimurthy, Org. Lett., 2016, 18, 464; (d) P. Olsen,
5 A. Cappelli, M. Anzini, F. Castriconi, G. Grisci, M. Paolino,
C. Braile, S. Valenti, G. Giuliani, S. Vomero, A. D. Capua,
L. Betti, G. Giannaccini, A. Lucacchini, C. Ghelardini,
L. D. C. Mannelli, M. Frosini, L. Ricci, G. Giorgi,
M. P. Mascia and G. Biggio, J. Med. Chem., 2016, 59, 3353.
˚
M. Oschmann, E. V. Johnston and B. Akermark, Green
Chem., 2018, 20, 469; (e) P. Peng, J. Xiong, B. Li, G. Mo,
R. Chen and Z. Wang, Chin. J. Org. Chem., 2013, 33, 1891.
15 (a) Z. Zhang, J. Zhang, J. Tan and Z. Wang, J. Org. Chem.,
2008, 73, 5180; (b) Q. Wang, C. Wan, Y. Gu, J. Zhang,
L. Gao and Z. Wang, Green Chem., 2011, 13, 578; (c) Y. Yan
and Z. Wang, Chem. Commun., 2011, 47, 9513; (d) Y. Li,
F. Guo, Z. Zha and Z. Wang, Sustainable Chem. Processes,
2013, 1, 8.
´
6 (a) M. Alcarazo, S. J. Roseblade, A. R. Cowley, R. Fernandez,
J. M. Brown and J. M. Lassaletta, J. Am. Chem. Soc., 2005,
127, 3290; (b) F. E. Hahn, Angew. Chem., Int. Ed., 2006, 45,
1348; (c) K. G. Kishore, O. Ghashghaei, C. Estarellas,
M. M. Mestre, C. Monturiol, N. Kielland, J. M. Kelly,
˜
A. F. Francisco, S. Jayawardhana, D. Munoz-Torrero,
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 23058–23065 | 23065