Iodine mediated reaction of quinones and N-substituted amino esters to 2-substituted benzo[f]isoindole-4,9-diones

Article abstract of DOI:10.1039/c3ra44095h

A novel and efficient synthesis of benzo[f]isoindole-4,9-diones through the I₂-promoted cyclization reaction of N-substituted amino acid esters and quinones has been realized successfully via an unprecedented 1,3-dipolar cycloaddition using KF as the base. Different substituted amino esters were found able to react with quinones through a cycloaddition reaction to afford 2-substituted benzo[f]isoindole-4,9-diones. The unexpected, short, attractive and direct synthesis of these interesting compounds is important and relevant, and provides an extremely preferable method for the synthesis of 2-substituted benzo[f]isoindole-4,9-diones.

Full text of DOI:10.1039/c3ra44095h

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PAPER
Iodine mediated reaction of quinones and N-substituted
amino esters to 2-substituted benzo[f]isoindole-4,9-
diones†
Cite this: RSC Adv., 2013, 3, 25840
*
Yu-jin Li, Huan-ming Huang, Jie Ju, Jian-hong Jia, Liang Han, Qing Ye, Wu-bin Yu
*
and Jian-rong Gao
A novel and efficient synthesis of benzo[f]isoindole-4,9-diones through the I2-promoted cyclization
reaction of N-substituted amino acid esters and quinones has been realized successfully via an
unprecedented 1,3-dipolar cycloaddition using KF as the base. Different substituted amino esters were
found able to react with quinones through a cycloaddition reaction to afford 2-substituted benzo[f]
isoindole-4,9-diones. The unexpected, short, attractive and direct synthesis of these interesting
compounds is important and relevant, and provides an extremely preferable method for the synthesis of
2-substituted benzo[f]isoindole-4,9-diones.
Received 1st August 2013
Accepted 19th September 2013
DOI: 10.1039/c3ra44095h
www.rsc.org/advances
alkylation and bromomethylation of 1,4-naphthoquinone,9
CAN-mediated oxidation of 2,3-bis(aminomethyl)-1,4-dime-
Introduction
thoxynaphthalene,11a and acyl radical addition of quinone
derivates.16
Heterocycles are an important class of organic compounds found
in a wide range of natural products and medicinal agents. Among
the numerous methods for the preparation of heterocycles,
organic transformations catalyzed by an iodine source have
attracted considerable attention in recent years.1 Iodine, a non-
toxic, inexpensive and readily available catalyst for various organic
transformations, has attracted the interest of numerous chemists.2
It has been used extensively in the synthesis of substituted
isoquinolines,1h quinazolines,3 quinolines,2c acetophenones,2h 2,2-
bisindolyl-1-aryl ethanones,4 azaanthraquinones,2a etc. Also,
numerous reactions can be initiated by iodine such as 5-endo5 and
6-endo cyclizations,2a,6 cross-dehydrogenative coupling reactions,2e,7
iodolactonizations,8 etc.
Due to the signicant biological activity of benzo[f]isoindole-
4,9-diones, several pathways have been developed for their
synthesis, among which, a general and efficient method for the
synthesis of benzo[f]isoindole-4,9-diones from simple and
readily available precursors is of great value. We herein report a
single-step approach to 2-substituted benzo[f]isoindole-4,9-
diones via the I2 triggered reaction of quinones and
N-substituted amino esters. To the best of our knowledge, few
reports in the literature describe the direct synthesis of iso-
indoles from the reaction of quinones with N-substituted acid
esters induced by iodine.
Isoindoles are the core structure of natural products
exhibiting important biological activity.9 They exist in many
bioactive molecules such as GR30921 X,10 bhimamycin C and
bhimamycin D,9,11 shown in Fig. 1. Since the general appli-
cation of 1,3-dipoles in organic chemistry was rst estab-
lished by the systematic studies by Huisgen in the 1960s,12 it
has been the main strategy to synthesize benzo[f]isoindole-
4,9-diones.13 Other methods have also been used in
the construction of these structures. For instance, by
Friedel–Cras acylation,14 photochemical addition,15 radical
Results and discussion
Recently, we reported the addition reaction of 1,4-
naphthoquinone with amines.17 With a continuous interest
in the derivatization of heterocyclic compounds containing
quinone,18 we have focused on the reaction of 1,4-
naphthoquinone with N-substituted amino esters. Typi-
cally, the addition reaction of 1,4-naphthoquinone 1a with
sarcosine ethyl ester 2a initiated by iodine was investigated.
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology,
Zhejiang University of Technology, Hangzhou and 310032, P. R. China. E-mail:
lyjzjut@zjut.edu.cn; gdgjr@zjut.edu.cn; Fax: +86-0571-88320544; Tel: +86-0571-
88320891
† Electronic supplementary information (ESI) available: X-ray structural data (CIF)
of compound 3d, as well as copies of the 1H and 13C NMR spectra of the products
3a–3r, 4, and 5. CDCC 915884. For crystallographic data in CIF or other electronic
format see DOI: 10.1039/c3ra44095h
Fig. 1 Representative examples of isoindole natural products.
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However, an unexpected reaction product, 2-substituted
benzo[f]isoindole-4,9-dione 3a, was obtained, albeit in low
yields (Table 1, entry 1). This unexpected product prompted
us to undertake further investigation to elucidate the reac-
tion of quinone and the N-substituted amino ester and the
mechanism for the formation of 3a. Interestingly, no matter
what kind of N-substituted alkyl was used, products with a
structure similar to 3 were obtained (Scheme 1).
Scheme 1 The unexpected reaction between quinones 1 and N-substituted
amino esters 2.
The absolute conformation of 3 was unequivocally proven by
X-ray single crystal structure analysis of product 3d (Fig. 2).19
To further conrm these results, 3a was also synthesized
through the classic 1,3-dipolar cycloaddition reaction of 1,4-
naphthoquinone, sarcosine ethyl ester 2a and para-
formaldehyde as the starting materials (Scheme 2).
In order to get a better yield of the desired product and
make the reaction synthetically valuable, the reaction condi-
tions such as solvent, base and ratio of reactants were opti-
mized. As shown in Table 1, the amount of iodine was
rst screened in CH3CN with NaHCO3 as the base. In the
presence of 0.1 equivalents of iodine, the reaction of 1,4-
naphthoquinone with sarcosine ethyl ester resulted in a 12%
yield of 3a along with 4 and 5 in 28% and 47% yield, respec-
tively. The yield of 3a was increased to 41% when the number
of equivalents of iodine was increased (Table 1, entries 1 and
2). Further increase of the amount of iodine led to a decrease
in the yield of 3a due to the generation of other byproducts.
Various inorganic and organic bases were also screened for
this reaction. Interestingly, the yield of 3a increased to 50%
when KF was employed as the base (Table 1, entry 8). Other
bases, such as pyridine, Et3N, K2CO3 and CsF, were not
effective for the formation of the benzo[f]isoindole-4,9-dione
(Table 1, entries 4–7). Several solvents, besides CH3CN, were
investigated for this reaction. As it has been summarized in
Table 1, the use of CH3NO2, DMSO, THF, CH2Cl2, C2H5OH and
toluene did not lead to any improvements in the yield (Table 1,
entries 9–14). Various additives such as KI, AIBN and NIS were
added to the reaction together with the base, however, the
yield of the desired product 3a did not increase (Table 1,
entries 15–17). Although a better yield was obtained when KF
was used as the base, product 3a was always accompanied by
small amounts of unreacted 1a whether the reaction was
performed for an extended period of time or with larger
amounts of KF and 2a. Finally, it was found that a higher yield
(75%) of 3a could be achieved by further addition of KF and 2a
(up to 4 equiv.) (Table 1, entry 18). As a result, the desirable
conditions were established and an isolated yield of 72% 3a
was obtained under the optimized conditions.
Table 1 Optimization of the reaction conditions
We then focused our attention into the investigation of the
scope of this reaction under optimal reaction conditions. A
variety of N-alkyl amino esters (2a–2h) were found to react
with 1,4-naphthoquinone 1a and 1,4-anthraquinone 1b. The
results are summarized in Table 2. Products with a similar
structure to 3 were obtained from the reaction of N-alkyl
amino esters (2a–2h) with different carbon chain lengths, but
the yield of 3 decreased when substrates with a long group on
the N atom were used (Table 2, entries 1–4). We speculated
that it might be more difficult for the amine with a large group
to leave from the intermediate during the reaction, thus
making the yield of 3 decrease. It is worth noting that when
Iodine source
Entrya Base (equiv.) (equiv.)
Solvent
Yieldf (3a/4/5, %)
1
2
3
4
5
6
7
8
NaHCO3 (3)
NaHCO3 (3)
NaHCO3 (3)
Pyridine (3)
Et3N (3)
K2CO3 (3)
CsF (3)
KF (3)
I2 (0.1)
I2 (1.0)
I2 (1.5)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
12/28/47
41/29/30
28/18/32
33/19/37
25/10/43
40/15/40
43/10/15
50/8/10
9
KF (3)
I
2 (1.0)
I2 (1.0)
2 (1.0)
CH3NO2 19/2.6/4.3
DMSO
THF
10b
11
12
13
14
15c
16d
17
18e
KF (3)
KF (3)
KF (3)
KF (3)
KF (3)
KF (3)
KF (3)
KF (3)
14/2/77
4.3/5.4/47
I
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
NIS (1.0)
I2 (1.0)
C2H5OH 10/20/60
CH2Cl2
Toluene
CH3CN
CH3CN
CH3CN
CH3CN
30/15/50
23/15/30
30/15/30
23/25/50
18/11/33
75/3/18
KF (4)
a
Reaction conditions: 1a (1.0 mmol), 2a (3.0 mmol), base (3.0 mmol),
iodine (0.1–2.0 mmol) in solvent (5.0 mL) for 6 h at reuxing
b
c
d
temperature. At 80 ꢀC. 1 equiv. KI was added. 0.2 equiv. AIBN
was added. 1a (1.0 mmol) 2a (2.0 mmol), KF (2.0 mmol), iodine (0.5
e
mmol) for 3 h in CH3CN at reuxing temperature, then 2 equiv. 2a, 2
f
equiv. KF and 0.5 equiv. I2 were added for another 3 h. The yield
from HPLC.
Fig. 2 X-ray crystal structure of 3d.
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Scheme 2 The classic 1,3-dipolar cycloaddition reaction.
Table 2 Substrate scope for the unexpected reaction
Scheme 4 Reaction of 1a and N-benzylglycine ethyl ester 2j.
molecules in the literature.9,11,20 In order to match the
natural products, several substituted 1,4-naphthoquinones
were used to react with sarcosine ethyl ester. Products 3s
and 3s0 were obtained in a 30.1% total yield with two
isomers (3s and 3s0) in a 1 : 1 ratio as determined by 1H NMR
spectroscopy when 5-hydroxy-1,4-naphthoquinone 1c
was employed. A similar result was obtained with a 33.8%
total yield in the case of 5-nitro-1,4-naphthoquinone 1d
(Scheme 5).
2
Entrya
1
2
R1
R2
3
Yield of 3a (%)
Several control experiments were conducted to gain
insight into the mechanism of this I2-mediated cycloaddi-
tion reaction. In order to conrm the intermediates of the
reaction and elucidate the mechanism for the formation of
3a, the reaction mixture under the above conditions and
that of the amino ester with iodine were detected by GC-MS.
The yield of 3a decreased to 45.7% under N2 even aer 6 h,
suggesting the possible oxidation with O2. It was reported
that an enamine can be produced by treating an amine with
iodine.2e,7 Combining the literature ndings and the afore-
mentioned experimental results, we envision that an
enamine probably forms in this system and reacts with the
quinone by a 1,3-dipolar cycloaddition. The proposed
mechanism is summarized in Scheme 6. Initially, the
sarcosine ethyl ester 1a reacts with I2 to afford the inter-
mediate a-iodo sarcosine ethyl ester 6.4,21 Subsequently, the
iodine in intermediate 6 is eliminated to form an iminium
ion which then adds 2a to form 8. The 1,3-dipole 9, which is
in equilibrium with 90 by hydrogen transfer, can be formed
from the C–C bond rupture of 8. The 1,3-dipole 9 reacts
with 1a through a 1,3-dipolar addition, affording the inter-
mediate 10 along with its isomer by aromatization, which is
unstable and easy to oxidize by O2 and I2.22 The product 3a
is then formed with the release of one molecule of methyl-
amine. The GC-MS analysis of the reaction mixture of 1a and
2a with a stoichiometric amount of I2 showed the formation
of the corresponding dimer 8 (molecular ion peak at 232.3
[M]+), the enamine 9 (molecular ion peak at 158.1 [M]+), and
the 1,3-dipolar addition product 10 (molecular ion
peak at 316.2 [M]+). The mechanism was also subsequently
supported by the successful capture of methylamine
(see ESI†).
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
Me
Et
Et
Et
Et
Et
3a
3b
3c
3d
3e
3f
72
64
54
48
53
38
38
44
n-Pr
n-Bu
Me
Me
Me
Me
n-Pr
n-Bu
Isopentyl
i-Pr
2g
2h
3g
3h
9
2a
2b
2c
2d
2e
2f
Me
Et
Et
Et
Et
Et
3i
3j
51
44
40
35
40
32
30
31
10
11
12
13
14
15
16
n-Pr
n-Bu
Me
Me
Me
Me
3k
3l
3m
3n
3o
3p
n-Pr
n-Bu
Isopentyl
i-Pr
2g
2h
a
Isolated yield.
N-phenylglycine ethyl ester 2i was used (Scheme 3), the cor-
responding product benzo[f]isoindole-4,9-dione 3q was not
obtained. The reason for this may lie in that the conjugating
action of the aromatic ring makes it difficult to remove phe-
nylamine. Moreover, in the case of N-benzylglycine ethyl ester
2j, only traces of the desired product 3r were found by GC-MS.
Some other products were produced instead, which could not
be separated and characterized (Scheme 4). Besides 1,4-
naphthoquinone 1a, 1,4-anthraquinone 1b was also used in
this coupling reaction resulting in slightly lower yields of 30–
51% (Table 2, entries 9–16) due to the lower reactivity of 1b
compared to that of 1a.
Hydroxy-substituted or amino-substituted moieties are
crucial in most of the bioactive benzo[f]isoindole-4,9-dione
Scheme 3 Reaction of 1a and N-phenylglycine ethyl ester 2i.
25842 | RSC Adv., 2013, 3, 25840–25848
Scheme 5 Reaction of substituted 1,4-naphthoquinones.
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Ethyl 2-methyl-2H-benzo[f]isoindole-4,9-dione-1-carboxylate
(3a)
Scheme 6 Possible reaction mechanism.
Yield 72% (0.205 g), mp 152–153 ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.26–8.24 (m, 1H), 8.23–8.21 (m, 1H), 7.74–7.69 (m, 2H),
7.48 (s, 1H), 4.52 (q, J ¼ 8.0 Hz, 2H), 3.95 (s, 3H), 1.50 (t, J ¼ 7.0
Hz, 3H); 13C NMR (CDCl3, 125 MHz): d (ppm) 180.1, 178.7,
160.9, 135.9, 134.3, 133.4, 133.1, 130.0, 127.4, 126.6, 125.8,
123.6, 122.6, 62.1, 37.5, 14.12; GC-MS m/z 283.9 [M + H]+, 283.0,
239.2, 211.2, 183.0, 170.1, 113.2, 50.0. Anal. calcd for
Conclusion
In conclusion, an efficient I2-promoted cyclization reaction
of N-substituted amino esters and quinones for the
synthesis of benzo[f]isoindole-4,9-diones has been estab-
lished successfully via an unprecedented 1,3-dipolar cyclo-
addition with KF as the base. The unexpected, short and
direct synthesis of these interesting compounds is impor-
tant and relevant as the reaction described here is mild,
general and efficient. Future studies will focus on the
application of this method to synthesize more complex
benzo[f]isoindole-4,9-dione compounds such as bhimamy-
cin C and bhimamycin D.
C
16H13NO4: C, 67.84; H, 4.63; N, 4.94. Found: C, 67.71; H, 4.73;
N, 4.75%.
Ethyl 2-ethy-2H-benzo[f]isoindole-4,9-dione-1-carboxylate (3b)
Experimental section
General information
Yield 64% (0.192 g), mp 143–144 ꢀC; 1H NMR (500 MHz,
CDCl3): d (ppm) 8.26–8.22 (m, 2H), 7.74–7.69 (m, 2H), 7.55 (s,
1H), 4.52 (q, J ¼ 6.5 Hz, 2H), 4.31 (q, J ¼ 7.0 Hz, 2H), 1.53–
1.49 (m, 6H); 13C NMR (CDCl3, 125 MHz): d (ppm) 180.3,
178.8, 161.2, 136.0, 134.4, 133.4, 133.1, 127.4 (2C), 126.7,
126.0, 123.3, 122.7, 62.2, 45.1, 16.5, 14.1; GC-MS m/z 298.2 [M
+ H]+, 297.2, 268.3, 253.3, 225.3, 197.2, 140.2, 113.2. Anal.
calcd for C17H15NO4: C, 68.68; H, 5.09; N, 4.71. Found: C,
68.41; H, 5.18; N, 4.48%.
All solvents were puried and dried using standard methods
prior to use. Commercially available reagents were used without
1
further purication. H NMR spectra were recorded on a NMR
instrument operated at 500 MHz. Chemical shis are reported
in ppm with the solvent resonance as the internal standard
(CDCl3: d 7.26 ppm). 13C NMR spectra were recorded on a NMR
instrument operated at 125 MHz with complete proton decou-
pling. Chemical shis are reported in ppm with the solvent
resonance as the internal standard (CDCl3: d 77.1 ppm). MS and
HRMS were measured in EI or ESI mode and the mass analyzer
of the HRMS was TOF. Thin layer chromatography was per-
formed on pre-coated glass back plates and visualized with UV
light at 254 nm. Flash column chromatography was performed
on silica gel.
Ethyl 2-propy-2H-benzo[f]isoindole-4,9-dione-1-carboxylate
(3c)
Representative procedure for the synthesis of 2-substituted
benzo[f]isoindole-4,9-diones 3
Typically, a mixture of 1,4-naphthoquinone (1a, 1.0 mmol,
0.158 g, 1.0 equiv.), sarcosine ethyl ester (2a, 2.0 mmol, 0.234
g, 2.0 equiv.), KF (2.0 mmol, 0.116 g, 2.0 equiv.) and iodine (0.5 Yield 54% (0.169 g), mp 115–116 ꢀC; 1H NMR (500 MHz,
mmol, 0.127 g, 0.5 equiv.) in CH3CN (5.0 mL) was stirred at CDCl3): d (ppm) 8.25–8.21 (m, 2H), 7.74–7.69 (m, 2H), 7.52 (s,
reuxing temperature for 3 h. Then, sarcosine ethyl ester (2a, 1H), 4.52 (q, J ¼ 8.0 Hz, 2H), 4.23 (q, J ¼ 7.5 Hz, 2H), 1.91–
2.0 mmol, 0.234 g, 2.0 equiv.), KF (2.0 mmol, 0.116 g, 2.0 1.84 (m, 2H), 1.50 (t, J ¼ 6.5 Hz, 3H), 0.97 (t, J ¼ 7.5 Hz, 3H);
equiv.) and iodine (0.5 mmol, 0.127 g, 0.5 equiv.) were added 13C NMR (CDCl3, 125 MHz): d (ppm) 180.2, 179.0, 161.0,
for another 3 h and analyzed by GC-MS and TLC. The solvent 135.9, 134.4, 133.4, 133.1, 127.4, 126.8, 126.6, 125.6, 123.3,
was removed under vacuum and the resulting crude product 122.5, 62.2, 51.6, 24.5, 14.1, 11.0; GC-MS m/z 311.8 [M + H]+,
was puried by chromatography on silica gel with CH2Cl2 as 310.8, 281.8, 265.9, 264.0, 250.0, 238.2, 224.0, 211.1; HRMS
the eluent to afford the desired product 3a as a yellow solid (ESI-TOF) m/z calcd for C18H17NO4Na [M + Na]+ 334.1050,
ꢀ
(0.205 g, 72%, mp 152–153 C).
found 334.1052.
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Ethyl 2-butyl-2H-benzo[f]isoindole-4,9-dione-1-carboxylate
Isopentyl 2-methyl-2H-benzo[f]isoindole-4,9-dione-1-
(3d)
carboxylate (3g)
Yield 48% (0.154 g), mp 162–163 ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.26–8.22 (m, 2H), 7.74–7.69 (m, 2H), 7.52 (s, 1H), 4.52
(q, J ¼ 7.0 Hz, 2H), 4.26 (t, J ¼ 7.5 Hz, 2H), 1.85–1.79 (m, 2H),
1.50 (t, J ¼ 7.0 Hz, 3H), 1.41–1.33 (m, 2H), 0.97 (t, J ¼ 7.0 Hz, 3H);
13C NMR (CDCl3, 125 MHz): d (ppm) 180.2, 178.9, 161.1, 136.0,
134.4, 133.4, 133.1, 127.4, 126.7 (2C), 125.7, 123.3, 122.6, 62.2,
49.8, 33.2, 19.8, 14.1, 13.6; GC-MS m/z 326.6 [M + H]+, 325.7,
279.8, 251.8 (100%), 210.0; HRMS (ESI-TOF) m/z calcd for
Yield 38% (0.122 g), mp 119–120 ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.26–8.24 (m, 1H), 8.23–8.21 (m, 1H), 7.75–7.69 (m, 2H),
7.49 (s, 1H), 4.48 (t, J ¼ 7.0 Hz, 2H), 3.95 (s, 3H), 1.87–1.81 (m,
1H), 1.79–1.75 (m, 2H), 1.01 (d, J ¼ 6.5 Hz, 6H); 13C NMR (CDCl3,
125 MHz): d (ppm) 180.0, 178.5, 160.9, 135.9, 134.2, 133.4, 133.0,
128.0, 127.4, 126.5, 125.7, 123.5, 122.5, 64.8, 37.5, 37.1, 25.1,
22.5 (2C); GC-MS m/z 326.2 [M + H]+, 325.3, 256.2, 238.3, 170.3,
113.2, 41.0; HRMS (ESI-TOF) m/z calcd for C19H19NO4Na [M +
Na]+ 348.1206, found 348.1216.
C
19H19NO4Na [M + Na]+ 348.1206, found 348.1209.
Propyl 2-methy-2H-benzo[f]isoindole-4,9-dione-1-carboxylate
(3e)
Isopropyl 2-methyl-2H-benzo[f]isoindole-4,9-dione-1-
carboxylate (3h)
Yield 53% (0.157 g), mp 121–122 ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.26–8.24 (m, 1H), 8.23–8.21 (m, 1H), 7.74–7.69 (m, 2H),
7.49 (s, 1H), 4.41 (t, J ¼ 7.0 Hz, 2H), 4.00 (s, 3H), 1.94–1.86 (m,
2H), 1.09 (t, J ¼ 8.0 Hz, 3H); 13C NMR (CDCl3, 125 MHz): d (ppm)
180.1, 178.7, 161.0, 136.0, 134.3, 133.5, 133.0, 128.0, 127.5,
126.6, 125.8, 123.6, 122.7, 67.7, 37.6, 22.0, 10.5; GC-MS m/z 298.1
[M + H]+, 297.1, 255.1, 239.3, 238.3, 211.2, 170.2, 41.0; HRMS
(ESI-TOF) m/z calcd for C17H15NO4Na [M + Na]+ 320.0893, found
320.0898.
Yield 44% (0.130 g), mp 133–134 ꢀC; 1H NMR (500 MHz,
CDCl3): d (ppm) 8.26–8.24 (m, 1H), 8.22–8.20 (m, 1H), 7.74–
7.69 (m, 2H), 7.46 (s, 1H), 5.39–5.34 (m, 1H), 3.94 (s, 3H), 1.49
(d, J ¼ 6.0 Hz, 6H); 13C NMR (CDCl3, 125 MHz): d (ppm) 180.2,
178.7, 160.4, 136.0, 134.8, 134.4, 133.5, 133.1, 127.7, 127.5,
126.6, 126.5, 123.4, 122.6, 70.3, 37.4, 21.8; GC-MS m/z 298.1 [M
+ H]+, 297.1, 239.2, 211.2, 183.2, 170.3, 154.2, 43.0; HRMS (ESI-
TOF) m/z calcd for C17H16NO4 [M + H]+ 298.1079, found
298.1080.
Butyl 2-methyl-2H-benzo[f]isoindole-4,9-dione-1-carboxylate
(3f)
Ethyl 2-methyl-2H-naphtho[2,3-f]isoindole-4,11-dione-1-
carboxylate (3i)
Yield 38% (0.118 g), mp 120–121 ꢀC; 1H NMR (500 MHz, CDCl3): Yield 51% (0.171 g), mp 202–203 ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.25–8.23 (m, 1H), 8.21–8.20 (m, 1H), 7.73–7.68 (m, 2H), d (ppm) 8.73 (d, J ¼ 13.5 Hz, 2H), 8.04–8.02 (m, 2H), 7.65–7.63
7.48 (s, 1H), 4.44 (t, J ¼ 7.0 Hz, 2H), 3.94 (s, 3H), 1.87–1.82 (m, (m, 2H), 7.52 (s, 1H), 4.53 (q, J ¼ 7.0 Hz, 2H), 3.95 (s, 3H), 1.52 (t,
2H), 1.56–1.48 (m, 2H), 1.01 (t, J ¼ 7.5 Hz, 3H); 13C NMR (CDCl3, J ¼ 7.0 Hz, 3H); 13C NMR (CDCl3, 125 MHz): d (ppm) 180.0,
125 MHz): d (ppm) 180.0, 178.6, 161.0, 135.9, 134.3, 133.4, 133.0, 178.6, 160.9, 134.9, 134.6, 132.3, 139.9, 129.9 (2C), 129.5, 129.0
128.0, 127.4, 126.6, 125.8, 123.5, 122.6, 65.9, 37.5, 30.6, 19.2, (2C), 128.7, 128.0, 125.9, 124.3, 123.5, 62.1, 37.5, 14.1; GC-MS m/
13.7; GC-MS m/z 312.4 [M + H]+, 311.5, 239.5, 238.5, 211.5, 170.5, z 333.1 [M]+, 289.2, 262.2, 261.3 (100%), 220.2, 163.3, 42.1;
113.5, 41.2; HRMS (ESI-TOF) m/z calcd for C18H17NO4Na [M + HRMS (ESI-TOF) m/z calcd for C20H15NO4Na [M + Na]+ 356.0893,
Na]+ 334.1050, found 334.1052.
found 356.0900.
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Ethyl 2-ethyl-2H-naphtho[2,3-f]isoindole-4,11-dione-1-
Propyl 2-methyl-2H-naphtho[2,3-f]isoindole-4,11-dione-1-
carboxylate (3j)
carboxylate (3m)
Yield 40% (0.139 g), mp 127–128 ꢀC; 1H NMR (500 MHz, CDCl3): d
(ppm) 8.71 (d, J ¼ 3.5 Hz, 2H), 8.02 (dd, J1 ¼ 3.5 Hz, J2 ¼ 6.0 Hz,
2H), 7.63 (dd, J1 ¼ 3.5 Hz, J2 ¼ 6.5 Hz, 2H), 7.51 (s, 1H), 4.42 (t, J ¼
7.0 Hz, 2H), 3.94 (s, 3H), 1.92 (q, J ¼ 7.5 Hz, 2H), 1.12 (t, J ¼ 8.0 Hz,
3H); 13C NMR (CDCl3, 125 MHz): d (ppm) 179.9, 178.5, 161.1, 134.9,
134.6, 132.3, 130.9, 129.9 (2C), 129.5, 129.0 (2C), 128.6, 128.1,
125.9, 124.3, 123.5, 67.7, 37.5, 22.0, 10.5; GC-MS m/z 348.0 [M + H]+,
347.1, 289.2, 275.3, 262.2, 261.3, 163.3, 41.0; HRMS (ESI-TOF) m/z
calcd for C21H17NO4Na [M + Na]+ 370.1050, found 370.1058.
Yield 44% (0.154 g), mp 187–188 ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.77 (d, J ¼ 7.5 Hz, 2H), 8.07–8.05 (m, 2H), 7.68–7.64 (m,
2H), 7.61 (s, 1H), 4.55 (q, J ¼ 7.0 Hz, 2H), 4.33 (q, J ¼ 7.0 Hz, 2H),
1.55–1.52 (m, 6H); 13C NMR (CDCl3, 125 MHz): d (ppm) 179.8,
178.5, 161.0, 134.8, 134.5, 132.2, 130.9, 129.8 (2C), 129.3, 128.9
(2C), 128.6, 126.1, 125.5, 123.9, 123.4, 62.0, 44.8, 16.3, 14.0; GC-
MS m/z 348.0 [M + H]+, 347.1, 303.3, 286.3, 275.3, 247.3, 190.3,
163.3, 120.0; HRMS (ESI-TOF) m/z calcd for C21H17NO4Na [M +
Na]+ 370.1050, found 370.1058.
Ethyl 2-propyl-2H-naphtho[2,3-f]isoindole-4,11-dione-1-
Butyl 2-methyl-2H-naphtho[2,3-f]isoindole-4,11-dione-1-
carboxylate (3k)
carboxylate (3n)
Yield 40% (0.144 g), mp 176–177 ꢀC; 1H NMR (500 MHz, CDCl3): d
(ppm) 8.78 (d, J ¼ 6.5 Hz, 2H), 8.08–8.05 (m, 2H), 7.68–7.65 (m, 2H),
7.58 (s, 1H), 4.55 (q, J ¼ 7.0 Hz, 2H), 4.25 (t, J ¼ 6.5 Hz, 2H), 1.94–
Yield 32% (0.117 g), mp 147–148 ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.74 (d, J ¼ 13.5 Hz, 2H), 8.05 (dd, J1 ¼ 3.5 Hz, J2 ¼ 6.5
Hz, 2H), 7.65 (dd, J1 ¼ 3.5 Hz, J2 ¼ 6.5 Hz, 2H), 7.53 (s, 1H), 4.47
(t, J ¼ 7.5 Hz, 2H), 3.96 (s, 3H), 1.91–1.85 (m, 2H), 1.59–1.51 (m,
2H), 1.03 (t, J ¼ 7.5 Hz, 3H); 13C NMR (CDCl3, 125 MHz): d (ppm)
180.0, 178.5, 161.1, 134.9, 134.6, 132.3, 130.9, 129.9 (2C), 129.5,
129.0 (2C), 128.7, 128.0, 125.95, 124.3, 123.5, 66.0, 37.5, 30.6,
19.2, 13.8; GC-MS m/z 362.0 [M + H]+, 361.0, 289.0, 262.2, 261.2,
220.2, 207.2, 73.0; HRMS (ESI-TOF) m/z calcd for C22H19NO4Na
[M + Na]+ 384.1206, found 384.1215.
1.86 (m, 2H), 1.53 (t, J ¼ 7.0 Hz, 3H), 0.99 (t, J ¼ 7.5 Hz, 3H); 13
C
NMR (CDCl3, 125 MHz): d (ppm) 180.2, 178.8, 161.2, 135.0, 134.7,
132.4, 131.1, 130.0 (2C), 129.5, 129.1, 129.0, 128.8, 125.9, 124.1,
123.4, 62.2, 51.6, 24.5, 14.1, 11.0; GC-MS m/z 362.5 [M + H]+, 361.5,
317.7, 290.5, 289.8, 261.8, 190.5, 163.5, 126.5; HRMS (ESI-TOF) m/z
calcd for C22H19NO4Na [M + Na]+ 384.1206, found 384.1208.
Ethyl 2-butyl-2H-naphtho[2,3-f]isoindole-4,11-dione-1-
carboxylate (3l)
Isopentyl 2-methyl-2H-naphtho[2,3-f]isoindole-4,11-dione-1-
carboxylate (3o)
Yield 35% (0.132 g), mp 156–157 ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.74 (d, J ¼ 7.0 Hz, 2H), 8.05–8.04 (m, 2H), 7.65–7.63 (m,
2H), 7.56 (s, 1H), 4.54 (q, J ¼ 7.0 Hz, 2H), 4.26 (t, J ¼ 7.5 Hz, 2H), Yield 30% (0.113 g), mp 100–101 ꢀC; 1H NMR (500 MHz, CDCl3):
1.90–1.80 (m, 2H), 1.52 (t, J ¼ 7.0 Hz, 3H), 1.41–1.34 (m, 2H), d (ppm) 8.75 (d, J ¼ 12.5 Hz, 2H), 8.06–8.05 (m, 2H), 7.66 (dd, J1
0.97 (t, J ¼ 3.5 Hz, 3H); 13C NMR (CDCl3, 125 MHz): d (ppm) ¼ 3.0 Hz, J2 ¼ 6.0 Hz, 2H), 7.55 (s, 1H), 4.50 (t, J ¼ 7.5 Hz, 2H),
183.9, 180.2, 161.3, 135.0, 134.8, 132.4, 131.2, 130.0 (2C), 129.5, 3.97 (s, 3H), 1.88–1.83 (m, 1H), 1.82–1.77 (m, 2H), 1.02 (d, J ¼ 6.5
129.1 (2C), 128.8, 126.8, 126.0, 124.1, 123.5, 62.2, 49.8, 33.2, Hz, 6H); 13C NMR (CDCl3, 125 MHz): d (ppm) 180.1, 178.6,
19.8, 14.2, 13.6; GC-MS m/z 376.0 [M + H]+, 375.1, 304.2, 302.2 161.2, 135.0, 134.7, 132.4, 131.0, 130.0 (2C), 129.6, 129.1, 129.1,
(100%), 274.2, 190.2, 155.2, 126.3; HRMS (ESI-TOF) m/z calcd for 128.8, 128.1, 126.1, 124.4, 123.6, 65.0, 37.6, 30.3, 25.3, 22.6 (2C);
C
23H21NO4Na [M + Na]+ 398.1363, found 398.1371.
GC-MS: m/z 376.5 [M + H]+, 375.5, 306.5, 289.7, 288.7, 261.8,
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163.6, 41.3; HRMS (ESI-TOF) m/z calcd for C23H21NO4Na [M + 177.4, 176.3, 176.0, 175.3, 160.2, 160.1, 149.8, 149.1, 137.0,
Na]+ 398.1363, found 398.137.
135.5, 134.0, 133.5, 129.8, 129.2, 128.6, 127.8, 127.4, 126.7,
126.3, 125.1, 123.1, 122.6, 122.2, 121.7, 121.3, 62.3, 62.2, 37.8,
37.6, 14.1, 13.8; GC-MS m/z, 328.0[M]+, 298.1, 284.1, 267.1,
256.1, 253.2, 226.2, 198.2, 127.2; HRMS (ESI-TOF) m/z calcd for
Isopropyl 2-methyl-2H-naphtho[2,3-f]isoindole-4,11-dione-1-
carboxylate (3p)
C
16H12N2O6Na [M + Na]+ 351.0587, found 351.0596.
2-(Methylamino)-1,4-naphthoquinone (4)23
Yield 31% (0.107 g), mp 192–193 ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.79 (s, 1H), 8.76 (s, 1H), 8.07 (dd, J1 ¼ 3.5 Hz, J2 ¼ 6.0
Hz, 2H), 7.66 (dd, J1 ¼ 3.5 Hz, J2 ¼ 6.0 Hz, 2H), 7.54 (s, 1H), 1.52
(d, J ¼ 6.5 Hz, 6H); 13C NMR (CDCl3, 125 MHz): d (ppm) 179.9,
178.4, 160.5, 134.9, 134.6, 132.2, 130.9, 129.9 (2C), 129.4, 129.0,
128.9, 128.6, 127.8, 126.5, 124.0, 123.3, 70.2, 37.3, 21.7 (2C); GC-
MS m/z, 348.0 [M + H]+, 346.9, 289.0, 261.2 (100%), 220.2, 41.0;
HRMS (ESI-TOF) m/z calcd for C21H17NO4Na [M + Na]+ 370.1050,
found 370.1057.
1
Red needle crystals: mp 221–222 C (lit.24 mp 220–223 C); H
NMR (CDCl3, 500 MHz): d (ppm) 8.12 (d, J ¼ 7.5 Hz, 1H), 8.06 (d,
J ¼ 7.5 Hz, 1H), 7.76–7.73 (m, 1H), 7.65–7.61 (m, 1H), 5.95 (s,
1H), 5.74 (s, 1H), 2.95 (d, J ¼ 5.0 Hz, 3H); GC-MS m/z 187.2 [M]+,
146.2, 130.3, 105.2, 89.2, 76.2, 50.1.
ꢀ
ꢀ
Ethyl 2-((1,4-dioxo-1,4-dihydronaphthalen-2-yl)(methyl)
amino)acetate (5)
Ethyl 8-hydroxy-2-methyl-2H-benzo[f]isoindole-4,9-dione-1-
carboxylate (3s) and ethyl 5-hydroxy-2-methyl-2H-benzo[f]
isoindole-4,9-dione-1-carboxylate (3s0)
Red solid, mp 99–100 ꢀC; 1H NMR (CDCl3, 500 MHz): (ppm) 7.99
(dd, J1 ¼ 1.0 Hz, J2 ¼ 1.5 Hz, 1H), 7.92 (dd, J1 ¼ 1.0 Hz, J2 ¼ 1.0
Hz, 1H), 7.66–7.63 (m, 1H), 7.58–7.55 (m, 1H), 5.89 (s, 1H), 4.44
(s, 2H), 4.20 (q, J ¼ 7.5 Hz, 2H), 3.08 (s, 3H), 1.26 (t, J ¼ 6.5 Hz,
3H). 13C NMR (CDCl3, 125 MHz): d (ppm) 183.2, 183.1, 169.4,
151.0, 133.9, 132.2, 132.1, 126.5, 125.3, 108.4, 61.3, 55.8, 42.3,
14.1; EI-MS m/z 273.01 [M]+, 200.1, 172.1, 115.1, 75.1; HRMS
(ESI-TOF) m/z calcd for C15H15NO4Na [M + Na]+ 296.0899, found
296.0901.
Yield 30% (0.090 g); 1H NMR (500 MHz, CDCl3): d (ppm) 12.94
(s, 1H), 12.67 (s, 1H), 7.77–7.74 (m, 2H), 7.61–7.57 (m, 2H),
7.48–7.46 (m, 2H), 7.25–7.20 (m, 2H), 4.54–4.49 (m, 4H), 3.96
(s, 3H), 3.94 (s, 3H), 1.51–1.48 (m, 6H); 13C NMR (CDCl3, 125
MHz): d (ppm) 185.7, 185.0, 179.1, 177.8, 162.9, 162.4, 160.5,
160.5, 136.0, 135.9, 135.6, 134.5, 128.1, 128.0, 126.3, 126.2,
124.1, 123.4 (2C), 122.5, 122.4, 121.8, 119.6, 118.8, 117.6,
116.5, 62.2, 62.1, 37.5, 37.4, 14.1, 14.0; GC-MS m/z, 300.0 [M +
H]+, 299.0, 253.1, 227.3, 225.3, 170.2, 142.2, 63.0; HRMS (ESI-
TOF) m/z calcd for C16H13NO5Na [M + Na]+ 322.0686, found
322.0689.
Acknowledgements
We gratefully acknowledge the nancial support by the Natural
Science Foundation of China (21176223), the National Natural
Science Foundation of Zhejiang (LY13B020016) and the Key
Innovation Team of Science and Technology in Zhejiang Prov-
ince (2010R50018).
Ethyl 8-nitro-2-methyl-2H-benzo[f]isoindole-4,9-dione-1-
carboxylate (3t) and ethyl 5-nitro-2-methyl-2H-benzo[f]
isoindole-4,9-dione-1-carboxylate (3t0)
Notes and references
1 (a) V. V. Zhdankin and P. J. Stang, Chem. Rev., 2008, 108,
5299–5358; (b) X. Zhang, S. Sarkar and R. C. Larock, J. Org.
Chem., 2006, 71, 236–243; (c) P. T. Parvatkar,
P. S. Parameswaran and S. G. Tilve, Chem.–Eur. J., 2012, 18,
5460–5489; (d) H. Togo and S. Iida, Synlett, 2006, 2159–
2175; (e) M. J. Mphahlele, Molecules, 2009, 14, 4814–4837;
(f) B. P. Bandgar and K. A. Shaikh, Tetrahedron Lett., 2003,
1
Yield 34% (0.111 g); H NMR (500 MHz, CDCl3): d (ppm) 8.45–
8.39 (m, 2H), 7.85–7.80 (m, 2H), 7.77–7.64 (m, 2H), 7.64–7.51
(m, 2H), 4.54–4.49 (m, 2H), 4.47–4.43 (m, 2H), 1.52–1.49 (m,
3H), 1.45–1.42 (m, 3H); 13C NMR (CDCl3, 125 MHz): d (ppm)
25846 | RSC Adv., 2013, 3, 25840–25848
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44, 1959–1961; (g) S. V. More, M. N. V. Sastry, C.-C. Wang and
RSC Advances
3 Y. Yan, Y. Zhang, C. Feng, Z. Zha and Z. Wang, Angew. Chem.,
Int. Ed., 2012, 51, 8077–8081.
4 Y.-P. Zhu, M.-C. Liu, F.-C. Jia, J.-J. Yuan, Q.-H. Gao, M. Lian
and A.-X. Wu, Org. Lett., 2012, 14, 3392–3395.
5 I. Kim, H. K. Won, J. Choi and G. H. Lee, Tetrahedron, 2007,
63, 12954–12960.
C.-F. Yao, Tetrahedron Lett., 2005, 46, 6345–6348; (h)
D. Fischer, H. Tomeba, N. K. Pahadi, N. T. Patil, Z. Huo
and Y. Yamamoto, J. Am. Chem. Soc., 2008, 130, 15720–
15725; (i) Y. Yamamoto, H. Hayashi, T. Saigoku and
H. Nishiyama, J. Am. Chem. Soc., 2005, 127, 10804–10805;
¨
(j) F. C. Kupper, M. C. Feiters, B. Olofsson, T. Kaiho,
6 Y.-X. Xie, Z.-Y. Yan, D.-Z. Wang, L.-Y. Wu, B. Qian,
X.-Y. Liu and Y.-M. Liang, Eur. J. Org. Chem., 2009,
2283–2288.
7 (a) T. Nobuta, N. Tada, A. Fujiya, A. Kariya, T. Miura and
A. Itoh, Org. Lett., 2013, 15, 574–577; (b) J. Dhineshkumar,
M. Lamani, K. Alagiri and K. R. Prabhu, Org. Lett., 2013,
15, 1092–1095.
8 S. Ma and L. Lu, J. Org. Chem., 2005, 70, 7629–7633.
9 J. Deblander, S. V. Aeken, J. Jacobs, N. D. Kimpe and
K. A. Tehrani, Eur. J. Org. Chem., 2009, 4882–4892.
S. Yanagida, M. B. Zimmermann, L. J. Carpenter,
G. W. Luther, Z. Lu, M. Jonsson and L. Kloo, Angew. Chem.,
Int. Ed., 2011, 50, 11598–11620; (k) Y. Kita, K. Morimoto,
M. Ito, C. Ogawa, A. Goto and T. Dohi, J. Am. Chem. Soc.,
2009, 131, 1668–1669; (l) M. Uyanik, H. Okamoto, T. Yasui
and K. Ishihara, Science, 2010, 328, 1376–1379; (m)
M. Uyanik, D. Suzuki, T. Yasui and K. Ishihara, Angew.
Chem., Int. Ed., 2011, 50, 5331–5334; (n) M. Scheideman,
G. Wang and E. Vedejs, J. Am. Chem. Soc., 2008, 130, 8669–
´
~
8676; (o) J. A. Souto, P. Becker, A Iglesias and K. Muniz, 10 E. Boven, A. M. C. Erkelens, M. Luning and H. M. Pinedo, Br.
J. Am. Chem. Soc., 2012, 134, 15505–15511; (p) S. H. Cho, J. Cancer, 1990, 61, 709–711.
J. Yoon and S. Chang, J. Am. Chem. Soc., 2011, 133, 5996– 11 (a) S. Claessens, J. Jacobs, S. V. Aeken, K. A. Tehrani and
6005; (q) T. Yao, M. A. Campo and R. C. Larock, Org. Lett.,
2004, 6, 2677–2680; (r) R. D. Richardson, M. Desaize and
T. Wirth, Chem.–Eur. J., 2007, 13, 6745–6754; (s)
G. Ramachandran, N. S. Karthikeyan, P. Giridharan and
K. I. Sathiyanarayanan, Org. Biomol. Chem., 2012, 10, 5343–
N. D. Kimpe, J. Org. Chem., 2008, 73, 7555–7559; (b)
N. Pongprom, H. Bachitsch, A. Bauchinger, H. Ettefagh,
T. Haider, M. Hofer, H. Kna, R. Slanz, M. Waismeyer,
F. Wieser and H. Spreitzer, Monatsh. Chem., 2010, 141,
53–62.
5346; (t) C. Hempel, N. M. Weckenmann, C. Maichle- 12 R. Huisgen, Angew. Chem., 1963, 75, 604–637.
Moessmer and B. J. Nachtsheim, Org. Biomol. Chem., 2012, 13 (a) J. A. Myers, L. D. Moore, W. L. Whitter, S. L. Council,
10, 9325–9329.
R. M. Waldo, J. L. Lanier and B. U. Omoji, J. Org. Chem.,
1980, 45, 1202–1206; (b) M. Schubert-Zsilavecz,
W. Likussar, D. Gusterhuber and A. Michelitsch, Monatsh.
Chem., 1991, 122, 383–387; (c) T. Mitsumori, M. Bendikov,
2 (a) N. Fei, Q. Hou, S. Wang, H. Wang and Z.-J. Yao, Org.
Biomol. Chem., 2010, 8, 4096–4103; (b) S. Ali, H.-T. Zhu,
X.-F. Xia, K.-G. Ji, Y.-F. Yang, X.-R. Song and Y.-M. Liang,
Org. Lett., 2011, 13, 2598–2601; (c) H. Batchu,
S. Bhattacharyya and S. Batra, Org. Lett., 2012, 14, 6330–
6333; (d) B. Alcaide, P. Almendros, G. Cabrero, R. Callejo,
´
J. Sedo and F. Wudl, Chem. Mater., 2003, 15, 3759–3768; (d)
´
S. Zhao, M. G. P. M. S. Neves, A. C. Tome, A. M. S. Silva
and J. A. S. Cavaleiro, Tetrahedron Lett., 2005, 46, 5487–
5490; (e) M. Gał¸ezowski and D. T. Gryko, J. Org. Chem.,
2006, 71, 5942–5950; (f) A. M. G. Silva, P. S. S. Lacerda,
´
M. P. Ruiz, M. Arno and L. R. Domingo, Adv. Synth. Catal.,
2010, 352, 1688–1700; (e) W.-B. Wu and J.-M. Huang, Org.
Lett., 2012, 14, 5832–5835; (f) Y.-X. Li, K.-G. Ji,
H.-X. Wang, S. Ali and Y.-M. Liang, J. Org. Chem., 2011,
76, 744–747; (g) Y.-X. Li, H.-X. Wang, S. Ali, X.-F. Xia and
Y.-M. Liang, Chem. Commun., 2012, 48, 2343–2345; (h)
T. Nobuta, S.-i. Hirashima, N. Tada, T. Miura and A. Itoh,
Org. Lett., 2011, 13, 2576–2579; (i) K. G. Guggenheim,
H. Toru and M. J. Kurth, Org. Lett., 2012, 14, 3732–3735;
(j) Y.-X. Xie, Z.-Y. Yan, B. Qian, W.-Y. Deng, D.-Z. Wang,
L.-Y. Wu, X.-Y. Liu and Y.-M. Liang, Chem. Commun.,
2009, 5451–5453; (k) W.-C. Gao, S. Jiang, R.-L. Wang and
´
A. C. Tome, M. G. P. M. S. Neves, A. M. S. Silva,
J. A. S. Cavaleiro, E. A. Makarova and E. A. Lukyanets,
J. Org. Chem., 2006, 71, 8352–8356; (g) L. S. H. P. Vale,
J. F. B. Barata, C. I. M. Santos, M. G. P. M. S. Neves,
´
M. A. F. Faustino, A. C. Tome, A. M. S. Silva, F. A. A. Paz
and J. A. S. Cavaleiro, J. Porphyrins Phthalocyanines, 2009,
´
13, 358–368; (h) A. S. F. Farinha, A. C. Tome and
J. A. S. Cavaleiro, Tetrahedron, 2010, 66, 7595–7599; (i)
C. Yu, Y. Zhang, S. Zhang, H. Li and W. Wang, Chem.
Commun., 2011, 47, 1036–1038.
C. Zhang, Chem. Commun., 2013, 49, 4890–4892; (l) 14 D. V. Nightingale and J. A. Gallagher, J. Org. Chem., 1959, 24,
A. K. Verma, T. Aggarwal, V. Rustagi and R. C. Larock, 501–504.
Chem. Commun., 2010, 46, 4064–4066; (m) X. Yang and 15 P. Gilgen, B. Jackson, H.-J. Hansen, H. Heimgartner and
P. Knochel, Chem. Commun., 2006, 2170–2172; (n) H. Schmid, Helv. Chim. Acta, 1974, 57, 2634–2643.
A. R. Vaino and W. A. Szarek, Chem. Commun., 1996, 16 Z.-Y. Lin, Y.-L. Chen, C.-S. Lee and C.-P. Chuang, Eur. J. Org.
2351–2352; (o) J. D. Panarese and S. P. Waters, Org. Chem., 2010, 3876–3882.
Biomol. Chem., 2013, 11, 3428–3431; (p) G. Yin, L. Fan, 17 H.-M. Huang, Y.-J. Li, Y.-P. Dai, W.-B. Yu, Q. Ye and J.-R. Gao,
T. Ren, C. Zheng, Q. Tao, A. Wu and N. She, Org. Biomol. J. Chem. Res., 2013, 37, 34–37.
Chem., 2012, 10, 8877–8883; (q) R. Fan, W. Li and 18 H.-M. Huang, Y.-J. Li, J.-R. Yang, J.-H. Jia, Q. Ye, L. Han and
B. Wang, Org. Biomol. Chem., 2008, 6, 4615–4621; (r) J.-R. Gao, Tetrahedron, 2013, 69, 5221–5226.
H.-C. Wu, C.-W. Yang, L.-C. Hwang and M.-J. Wu, Org. 19 CDCC 915884 (3d) contains the supplementary
Biomol. Chem., 2012, 10, 6640–6648.
crystallographic data for this paper.†
This journal is ª The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 25840–25848 | 25847

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RSC Advances
Paper
20 W. R. Ashcro, L. Dalton, M. G. Beal, G. L. Humphrey and
J. A. Joule, J. Chem. Soc., Perkin Trans. 1, 1983, 2409–2412.
21 (a) W.-M. Shu, Y. Yang, D.-X. Zhang, L.-M. Wu, Y.-P. Zhu,
G.-D. Yin and A.-X. Wu, Org. Lett., 2013, 15, 456–459; (b)
Y.-P. Zhu, F.-C. Jia, M.-C. Liu, L.-M. Wu, Q. Cai, Y. Gao
and A.-X. Wu, Org. Lett., 2012, 14, 5378–5381; (c)
S. Stanley, E. Kazyanskaya, D. Hung and J. L. Wood, Org.
Lett., 2012, 14, 4534–4536; (h) T. Kawasaki, M. Shinada,
M. Ohzono, A. Ogawa, R. Terashima and M. Sakamoto, J.
Org. Chem., 2008, 73, 5959–5964; (i) C. L. Martin,
L. E. Overman and J. M. Rohde, J. Am. Chem. Soc., 2008,
130, 7568–7569.
Y.-P. Zhu, Z. Fei, M.-C. Liu, F.-C. Jia and A.-X. Wu, Org. 22 (a) C. Jiang and S. Wang, Synlett, 2009, 1099–1102; (b)
Lett., 2013, 15, 378–381; (d) M. Lian, Q. Li, Y. Zhu, G. Yin
and A. Wu, Tetrahedron, 2012, 68, 9598–9605; (e)
H. Miyamura, M. Shiramizu, R. Matsubara and
S. Kobayashi, Chem. Lett., 2008, 37, 360–361.
M. Lamani and K. R. Prabhu, Chem.–Eur. J., 2012, 18, 23 B. J. Josey, E. S. Inks, X. Wen and C. J. Chou, J. Med. Chem.,
14638–14642; (f) M. B. Donald, K. X. Rodriguez, H. Shay, 2013, 56, 1007–1022.
P.-W. Phuan, A. S. Verkman and M. J. Kurth, Bioorg. 24 U. Lohmann and K. Hartke, Arch. Pharm., 1984, 317, 313–
Med. Chem., 2012, 20, 5247–5253; (g) T. C. McMahon, 323.
25848 | RSC Adv., 2013, 3, 25840–25848
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