Efficient access to naphthoquinon-1,3-dithioles: Formal cycloaddition and oxidation of quinones and amines with CS2

Article abstract of DOI:10.1016/j.tet.2013.04.050

An efficient strategy for one-pot synthesis of a variety of naphthoquinon-1,3-dithiole derivatives has been developed. The combined action of the formal cycloaddition and oxidation reaction of quinones and amines in the presence of CS₂ without additional oxidant produced naphthoquinon-1,3-dithiole derivatives in good yields.

Full text of DOI:10.1016/j.tet.2013.04.050

Tetrahedron 69 (2013) 5221e5226
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Tetrahedron
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Efficient access to naphthoquinon-1,3-dithioles: formal
cycloaddition and oxidation of quinones and amines with CS2
*
Huan-ming Huang, Yu-jin Li , Jian-rong Yang, Jian-hong Jia, Qing Ye, Liang Han,
*
Jian-rong Gao
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou 310032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient strategy for one-pot synthesis of a variety of naphthoquinon-1,3-dithiole derivatives has
been developed. The combined action of the formal cycloaddition and oxidation reaction of quinones and
amines in the presence of CS2 without additional oxidant produced naphthoquinon-1,3-dithiole de-
rivatives in good yields.
Received 24 January 2013
Received in revised form 26 March 2013
Accepted 11 April 2013
Available online 23 April 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
One-pot
Naphthoquinon-1,3-dithiole
Formal cycloaddition
Oxidation
Sulfur-attack
1. Introduction
containing compounds. Recently, carbon disulfide is often used as
sulfur reagent in constructing of various sulfur hetero-
During the past decade, a multicomponent reaction, offering
a straightforward route to generate complexity and diversity in
a single operation, became an extremely powerful tool in combi-
natorial chemistry and drug discovery.1 There are numerous bi-
ological active molecules with five-membered rings, containing
two heteroatoms, which have antimalarial, antibacterial, antifun-
gal, antiviral, antitumor, anti-inflammatory, and herbicidal activi-
ties.2 Compounds containing the sulfur heterocycles have shown
a wide range of pharmacological activities.1i,3 Additionally, de-
rivatives of sulfur heterocycles such as 1,3-dithiole have been
widely explored as new materials because of their super-
conducting, optical, and electronic switching properties.4 Espe-
cially, tetrathiafulvalenes (TTFs) are the most successful class of
heterocycles in terms of creating highly conducting and low-
temperature superconducting organic crystalline materials.5
What’s more, TTFequinones constitute a promising field of appli-
cations due to the interesting optoelectronic properties they
exhibit.6
cycles.1i,3b,c,4beg,7 Itoh7a reported ruthenium-catalyzed cycloaddi-
tion of 1,6-diynes with isothiocyanates and carbon disulfide. One-
pot reaction of amines, CS2, and alkyl halides under catalyst and
solvent-free to synthesize dithiocarbamates was established.7d
Nozaki reported the first successful synthesis of sulfur-rich poly-
mers with completely alternating copolymerization of episulfide
with CS2.4e Noteworthily, Ma and co-workers have utilized CS2 as
a substrate to construct 2-N-substituted benzothiazoles7h and 2-
thio-substituted benzothiazoles.4g During the past few years we
have reported the novel reactions of C60 with amino-acid esters and
CS2 affording fullerene derivatives.7b
Interest in 1,3-dithioles derivatives continues unabated due to
their wide usefulness as biologically active agents and key in-
termediates in the organic synthesis.8 At the same time, the qui-
none structure is common in numerous natural products9 and
important pharmacophores.10 Furthermore, a number of natural
occurring quinone structures are associated with anticancer, anti-
bacterial, antimalarial, and fungicidal activities.11 Based on their
biological and structural properties, we investigated a novel, one-
pot synthesis of a series of new 1,3-dithioles derivatives, which
combine quinone structures and amines.
There are few protocols for the corresponding reactions in-
volving CeS bond formation comparing to the new CeN and CeO
bond-forming technologies, despite the importance of sulfur-
In the course of our studies on the reaction of naphthoquinone
and amine, we were pleased to find that the new product 4 was
obtained in the presence of CS2. Herein we disclosed the details of
our results.
* Corresponding authors. Tel.: þ86 (0)571 88320891; fax: þ86 (0)571 88320544;
e-mail addresses: lyjzjut@zjut.edu.cn (Y.-j. Li), gdgjr@zjut.edu.cn (J.-r. Gao).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.050

5222
H.-m. Huang et al. / Tetrahedron 69 (2013) 5221e5226
Table 1
2. Results and discussion
Optimization between 1,4-naphthoquinone, CS2, and phenylalanine ethyl ester
hydrochloridesa
In this reaction, it had two possible reaction routes to the dif-
ferent products of A with sulfur-attack and B with nitrogen-attack
(Scheme 1). In order to validate the structure of product 4, the
single crystal of 4a was cultured and determined by X-ray crystal-
lographic analysis. Finally, it was unambiguously confirmed that
the structure of product 4a was A (Fig. 1).12 Therefore, it had been
identified two-step sulfur-attack to obtain 4 in this reaction system.
Entry
1/2a/3
Temperature
Solvent
Base
Yieldc (%)
1
2
3
4
5
6
7
8
1:1:3
1:1:3
1:1:3
1:1:3
1:1:3
1:1:1
1:1:5
1:1:3
1:1:3
1:1:3
1:1.2:3
rt
rt
rt
rt.
rt
rt
rt
rt
rt
Ethanol
AcOEt
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
Pyridine
Et3N
78.9
80.4
67.4
69.6
81.3
56.1
81.6
43.2
83.0
86.0
88.2
Isopropanol
Toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
9
10
0
0
ꢀC
ꢀC
Et3N
Et3N
11b
Scheme 1. Two possible reaction routes.
a
Reaction conditions: mixture of 1a (1.0 mmol), 2a (1.0 mmol), 3a (3e5 mmol),
base (1.0 mmol), and solvent (5.0 mL) was stirred for 4 h under corresponding
temperature.
b
Et3N (1.2 equiv) was added.
Yield of the isolated product.
c
With the optimized reaction conditions established, we then
examined the substrate scope of this reaction, and the results were
summarized in Tables 2 and 3.
As highlighted in Table 2, a variety of amino-acid ester hydro-
chlorides 2ae2h could react efficiently with 1a in the presence of
CS2 to give the corresponding products in good to excellent yields
(Table 2, entries 1e8). Unfortunately, the lower yields of 4c and 4d
were obtained in 54.0 and 60.3%, the reason may be that the side
reaction of urea was increased due to the small steric effect of
glycine ester (Table 2, entries 3 and 4). The 1,4-anthraquinone 1b
was also applied to this reaction and obtained the corresponding
products with middle yields in 40.3e55.8% because of the lower
activity of 1,4-anthraquinone (Table 2, entries 9e13).
With the satisfactory results of amino-acid ester hydrochloride,
we also investigated the aliphatic amines in this reaction to further
extend the applicability of this reaction. Propylamine was used in
order to establish the full scope of this interesting reaction at first.
The corresponding product 4p was only yielded in 60.1% when
propylamine was used as the reactant under the same condition
and the byproduct 2-thioxonaphtho[2,3-d][1,3]dithiole-4,9-dione
15 was found in 18.7% yield. Excitingly, the yield of 4p was im-
proved to 94.8% when propylamine hydrochloride and Et3N was
employed (Table 3, entry 3). Then, the different primary amines
(2ie2r) bearing various linear and branched chain alkyl groups,
benzyl group all yielded the corresponding products in 73.1e96.7%
yield (Table 3, entries 1e9). Cyclohexylamine was obtained in 66.8%
yield because of the low reactivity due to the steric hindrance of
cyclohexylamine. When cyclohexylamine hydrochloride was up to
3 equiv, the yield of 4w was up to 80.0%. A little byproduct 15 was
found in about 10% yield when some amines used (Table 3, entries
2, 4, 6, 7, 10). 1,4-Anthraquinone was also examined with propyl-
amine and the corresponding product (4x) was obtained in 60.1%.
Furthermore, the corresponding product was not observed, but 2-
(phenyl)amino-1,4-naphthoquinone 16 was obtained as the addi-
tion product of 1,4-naphthoquinone and phenylamine for the low
activity of phenylamine (confirmed by NMR and GCeMS).
Fig. 1. X-ray crystallography for 4a.
As indicated in Table 1, the reaction conditions such as solvent,
temperature, and bases were studied. It was found that the new
compound 4a was afforded in 78.9% yield through the reaction of
1,4-naphthoquinone (1a), phenylalanine ethyl ester hydrochloride
(2a), and CS2 (3) at room temperature and NaHCO3 as base in
ethanol (Table 1, entry 1). Encouraged by this result, we tried to
optimize the reaction condition and the results were summarized
in Table 1. The results demonstrated that the dichloromethane was
more efficient than other solvents (Table 1, entry 5). As the carbon
bisulfide was highly volatile, it was necessary to increase the ratio
of CS2 and the satisfactory yield 81.3% was obtained with 3 equiv of
CS2. However, when we tried to add more carbon bisulfide, the
yield of 4a didn’t increase remarkably (Table 1, entry 7). Next, we
screened different bases in place of NaHCO3. Product 4a was only
yielded in 43.2% when pyridine was employed as base and the yield
of 4a was raised to 83.0% when Et3N was used in this reaction (Table
1, entries 5, 8, and 9). Due to the byproduct urea produced by the
side reaction of CS2 and amine at room temperature, the yield of 4
was up to 86.0% when the temperature was dropped to 0 ꢀC (Table
1, entry 10). Finally, the quantity of 2a was increased to 1.2 equiv in
order to make sure 1a consumed completely and the yield of 4a was
88.2% (Table 1, entry 9). On the basis of these results, the optimal
condition involved the following parameters: Et3N as a base,
dichloromethane as a solvent, and reacted at 0 ꢀC.
It was the result of the combined action of the cycloaddition and
oxidationreaction toyieldtheproductof 4 intheabsenceof additional
oxidant at this reaction system. Referring to the work of Miyamura3a
and Wang,13 we considered that the oxidation process was the re-
sult of the combined oxidation with oxygen and quinone itself in this

H.-m. Huang et al. / Tetrahedron 69 (2013) 5221e5226
5223
Table 2
Extending scopes using different amino-acid ester hydrochlorides
Table 3
Extending scopes using different primary amine hydrochlorides
Entrya
1
1
R1
R2
4
Yield (%)
88.2
Entry
1
1
R1
4
Yield (%)
PhCH2e
CH3CH2e
4a
CH3e
4n
96.7
2
3
(CH3)2CHe
He
CH3e
4b
4c
75.0
54.0
2
3
4
CH3CH2e
4o
4p
4q
86.7
94.8
81.0
CH3CH2e
CH3CH2CH2e
(CH3)2CHe
4
5
6
He
(CH3)2CHe
CH3e
CH3e
CH3CH2e
CH3CH2e
4d
4e
4f
60.3
79.3
86.0
5
6
7
8
9
CH3CH2CH2CH2e
C6H13e
4r
4s
4t
4u
4v
90.7
85.5
76.0
73.1
83.3
7
CH3CH2e
4g
71.2
C10
H21e
C12H25e
PhCH2e
8
9
CH3CH2e
CH3CH2e
4h
4i
78.2
55.8
10
4w
4x
80.0a
PhCH2e
11
CH3CH2CH2e
60.1
10
He
CH3CH2e
4j
46.1
a
3.0 equiv cyclohexylamine hydrochloride and 3.0 equiv Et3N were added.
11
12
(CH3)2CHe
CH3e
CH3CH2e
CH3CH2e
4k
4l
41.1
48.1
13
CH3CH2e
4m
40.3
a
Reaction conditions: the mixture of 1a (1.0 mmol), 2 (1.2 mmol), 3a (3 mmol),
Et3N (1.2 mmol), and CH2Cl2 (5.0 mL) was stirred for about 4 h under 0 ꢀC.
Scheme 2. Control experiment.
reaction system. Some control experiments were carried out in order
to probe the mechanism of this transformation. In order to capture the
naphthol and prove the oxidation of naphthoquinone, the acetic an-
hydride was added to the reaction system at different conditions.
When 4 equiv Ac2O and Et3N were added the reaction mixture of 1a,
2o, and 3 at standard condition for 2 h, the resulting products 5 and 6
were detected by GCeMS and 1H NMR. It showed that naphthol was
produced with the oxidation of quinone. The products 5 and 6 were
5.8% and 42.9% at air atmosphere, but 48.3% and 10.0% under the ni-
trogen atmosphere [see Supplementary data]. It showed that oxygen
also has the same oxidation in this reaction (Scheme 2).
On the basis of the above results, the mechanism of this reaction
is proposed in Scheme 3. Firstly, the amine 2j added to CS2 and
formed adduct 7.7a,f,g,14 Subsequently, intermediate 7 attacked 1,4-
naphthoquinone 1a and formed the initial addition product 8 and
it’s tautomer 9, which can be oxidized by quinine itself or O2. Finally
the final product of 4o was obtained through another sulfur-attack
reaction and oxidized procedure. The byproduct 15 was detected
because the hydrogensulfide anion attacked final product 14 and
the yield of 15 was increased when sodium sulfide was added to the
reaction system [identified by NMR and GCeMS,6 see
Supplementary data]. We suspected the hydrogensulfide anion was
formed with the side reaction of urea.
Scheme 3. Proposed reaction pathway.
3. Conclusion
In conclusion, we have developed a simple, facile, and highly
efficient method for the synthesis of naphthoquinon-1,3-dithiole
derivatives, which relied on the combined action of the formal
cycloaddition and oxidation reaction of 1,4-naphthoquinone and
amines in the presence of CS2 without additional oxidant. This

5224
H.-m. Huang et al. / Tetrahedron 69 (2013) 5221e5226
approach can compliment a lot of other existing methods for
naphthoquinon-1,3-dithiole derivatives. Therefore the potential
application of these compounds will be interested in academic,
pharmaceutical, and material research. The application of this
powerful strategy to the synthesis of natural products and more
detailed mechanistic investigations are currently underway in our
laboratory. Additionally, the successful application of CS2 in syn-
thesis of sulfur-containing heterocycle will stimulate the study on
sulfur chemistry by employing these inexpensive reagents.
125 MHz): d (ppm) 176.1,175.5,168.2,161.4,144.5,142.7,134.4,134.3,
132.0 (2C),127.2,127.1, 61.6, 59.0,14.2; GCeMS m/z 333.1 [M]þ, 261.3,
260.3 (100%), 220.3,104.2, 76.2, 72.2, 50.1; HRMS (ESI-TOF) m/z calcd
for C15H12NO4S2 [MþH]þ 334.0202, found 334.0203.
4.1.4. Methyl 2-(4,9-dioxo-4,9-dihydronaphtho[2,3-d][1,3]dithiol-2-
imino)acetate (4d). Yield 60.3%; mp 196e197 ꢀC; 1H NMR
(500 MHz, CDCl3):
d
(ppm) 8.14e8.12 (m, 2H), 7.79e7.77 (m, 2H),
(ppm) 176.1,
4.05 (s, 2H), 3.82 (s, 3H); 13C NMR (CDCl3, 125 MHz):
d
175.4, 168.7, 161.6, 144.5, 142.6, 134.4, 134.3, 132.0 (2C), 127.2, 127.1,
58.8, 52.5; GCeMS m/z 319.3 [MþH]þ, 261.6, 260.6 (100%), 220.5,
191.5, 149.5, 134.5, 104.3; HRMS (ESI-TOF) m/z calcd for
C14H9NO4S2Na [MþNa]þ 341.9865, found 341.9874.
4. Experimental section
4.1. General
All chemicals were purchased from commercial vendors and
were used as received without further purification; any exceptions
are noted within the text and the vendors are noted within the
context of use. The 1H and 13C NMR spectra were recorded at 500
and 125 MHz, respectively, in CDCl3 using TMS as internal standard
4.1.5. Ethyl 2-(4,9-dioxo-4,9-dihydronaphtho[2,3-d][1,3]dithiol-2-
imino)-3-methylbutanoate (4e). Yield 79.3%; mp 132e133 ꢀC; 1H
NMR (500 MHz, CDCl3):
d (ppm) 8.12e8.09 (m, 2H), 7.77e7.76 (m,
2H), 4.24 (q, J1¼7.0 Hz, J2¼14.0 Hz, 2H), 3.49 (d, J¼6.0 Hz, 1H),
2.40e2.34 (m, 1H), 1.31 (t, J¼7.5 Hz, 3H), 1.0 (d, J¼6.0 Hz, 6H); 13C
with a Bruker AM 500 spectrometer. Chemical shifts (
d
) were re-
NMR (CDCl3, 125 MHz): d (ppm) 176.1, 175.5, 169.6, 159.7, 143.7,
ported as parts per million (ppm) and the following abbreviations
were used to identify the multiplicities: s¼singlet, d¼doublet,
t¼triplet, q¼quartet, m¼multiplet, br¼broad and all combinations
thereof can be explained by their integral parts. The GCeMS was
taken on Aglient (GC431-MS210) and elementary analysis was on
Thermo Electron Corporation Flash EA 1112. HRMS were recorded
on a Bruker MicroTOF-QII mass instrument (ESI).
142.7, 134.3, 134.2, 132.0 (2C), 127.1, 78.1, 61.3, 32.4, 19.3, 18.3, 14.2
(2C); GCeMS m/z 376.0 [MþH]þ, 332.1, 303.3, 302.3 (100%), 104.1,
76.1, 55.0. Anal. Calcd for C18H17NO4S2: C, 57.58; H, 4.56; N, 3.73; S,
17.08. Found: C, 57.75; H, 4.46; N, 3.49; S, 17.06.
4.1.6. Ethyl 2-(4,9-dioxo-4,9-dihydronaphtho[2,3-d][1,3]dithiol-2-
imino)propanoate (4f). Yield 86.0%; mp 169e170 ꢀC; 1H NMR
(500 MHz, CDCl3):
d (ppm) 8.11e8.09 (m, 2H), 7.78e7.75 (m, 2H),
4.1.1. Typical procedure for the preparation of ethyl 2-(4,9-dioxo-
4 , 9 - d i hy d ro n a p h t h o [ 2 , 3 - d ] [ 1, 3 ] - d i t h i o l - 2 - i m i n o ) - 3 -
phenylpropanoate(4a). Typically, a mixture of 1,4-naphthoquinone
(1a, 1.0 mmol, 0.158 g, 1.0 equiv), phenylalanine ethyl ester hy-
drochloride (2a, 1.2 mmol, 0.276 g, 1.2 equiv), CS2 (3a, 5 mmol,
0.381 g, 5.0 equiv), triethylamine (1.2 mmol, 0.121 g 1.2 equiv) in
CH2Cl2 (5.0 mL) was stirred at 0 ꢀC under air condition for 4 h,
determined by GCeMS and TLC. The solvent was removed under
vacuum and the resulting crude product was purified by chroma-
tography on silica gel eluted using CH2Cl2 as the eluent to afford the
desired product 4a as red solid (0.3735 g, yield 88.2%,
mp¼149e150 ꢀC).
4.23 (q, J1¼7.5 Hz, J2¼14.0 Hz, 2H), 3.81 (d, J1¼7.0 Hz, J2¼14.0 Hz,
1H), 1.52 (d, J¼7.0 Hz, 3H), 1.30 (t, J¼7.0 Hz, 3H); 13C NMR (CDCl3,
125 MHz): d (ppm) 176.0, 175.5, 170.6, 159.5, 143.9, 142.7, 134.3 (2C),
132.0, 131.9, 127.2, 127.1, 66.5, 61.5, 17.6, 14.2; GCeMS m/z 348.0
[MþH]þ, 274.1 (100%), 104.1, 86.0, 76.2, 60.0; HRMS (ESI-TOF) m/z
calcd for C16H14NO4S2 [MþH]þ 348.0359, found 348.0361.
4.1.7. Ethyl 2-(4,9-dioxo-4,9-dihydronaphtho[2,3-d][1,3]dithiol-2-
imino)-3-(4-hydroxyphenyl)propanoate (4g). Yield 71.2%; mp
163e164 ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.11e8.08 (m, 2H),
7.77e7.74 (m, 2H), 7.12e7.09 (m, 2H), 6.77e6.74 (m, 2H), 5.13 (s,
1H), 4.22 (q, J¼6.5 Hz, 2H), 3.88 (dd, J1¼5.0 Hz, J2¼8.0 Hz, 1H), 3.24
(dd, J1¼5.0 Hz, J2¼14.0 Hz, 1H), 3.06 (dd, J1¼8.0 Hz, J2¼13.5 Hz, 1H),
Yield 88.2%; mp 149e150 ꢀC; 1H NMR (500 MHz, CDCl3):
d
(ppm) 8.12e8.08 (m, 2H), 7.78e7.74 (m, 2H), 7.31e7.28 (m, 2H),
1.27 (t, J¼7.0 Hz, 3H); 13C NMR (CDCl3, 125 MHz):
d (ppm) 176.1,
7.26e7.20 (m, 3H), 4.22 (q, J¼7.0 Hz, 2H), 3.93 (dd, J1¼5.5 Hz,
J2¼8.5 Hz, 1H), 3.32 (dd, J1¼5.0 Hz, J2¼13.5 Hz, 1H), 3.14 (dd,
J1¼8.0 Hz, J2¼13.0 Hz, 1H), 1.26 (t, J¼8.0 Hz, 3H); 13C NMR (CDCl3,
175.5, 169.8, 160.7, 154.7, 143.6, 142.6, 134.3 (2C), 132.01, 132.0, 130.8
(2C), 128.6, 127.1 (2C), 115.5 (2C), 73.7, 61.7, 38.2, 14.2; EIMS m/z
440.03 [MþH]þ; HRMS (ESI-TOF) m/z calcd for C22H17NO5S2Na
[MþNa]þ 462.0440, found 462.0444.
125 MHz):
d (ppm) 176.1, 175.5, 169.6, 160.7, 143.6, 142.6, 136.6,
134.3 (2C), 132.0, 131.9, 129.6 (2C), 128.5 (2C), 127.1 (2C), 127.0, 73.4,
61.6, 39.1, 14.1; EIMS m/z 424.18 [MþH]þ. Anal. Calcd for
C18H17NO4S2: C, 62.10; H, 4.50; N, 3.29; S, 15.07. Found: C, 62.39; H,
3.97; N, 3.17; S, 14.69.
4.1.8. Ethyl 2-(4,9-dioxo-4,9-dihydronaphtho[2,3-d][1,3]dithiol-2-
imino)-2-(1H-indol-3-yl)acetate (4h). Yield 78.2%; mp 129e130
ꢀC; 1H NMR (500 MHz, CDCl3):
d (ppm) 8.20 (s, 1H), 8.00e7.96 (m,
2H), 7.68e7.65 (m, 2H), 7.22 (d, J¼7.0 Hz, 2H), 7.13e7.07 (m, 2H),
7.00 (d, J¼2.5 Hz, 1H), 4.22 (q, J¼4.5 Hz, 2H), 4.02 (t, J¼5.5 Hz, 1H),
3.45 (dd, J1¼5.5 Hz, J2¼14.5 Hz, 1H), 3.28 (dd, J1¼8.0 Hz, J2¼14.0 Hz,
4.1.2. Methyl 2-(4,9-dioxo-4,9-dihydronaphtho[2,3-d][1,3]dithiol-2-
imino)-3-methylbutanoate (4b). Yield 75.0%; mp 142e143 ꢀC; 1H
NMR (500 MHz, CDCl3):
d
(ppm) 8.13e8.11 (m, 2H), 7.79e7.76 (m,
1H), 1.26 (t, J¼7.5 Hz, 3H); 13C NMR (CDCl3, 125 MHz):
d (ppm)
2H), 3.78 (s, 3H), 3.52 (d, J¼5.5 Hz, 1H), 2.41e2.34 (m, 1H), 1.01 (d,
175.8, 175.2, 170.2, 160.6, 143.2, 142.4, 136.1, 134.2, 134.1, 131.8, 131.7,
127.4, 126.9 (2C), 123.6, 122.1, 120.0, 118.7, 111.3, 110.7, 72.9, 61.7,
28.8, 14.2; EIMS m/z 463.71 [MþH]þ; HRMS (ESI-TOF) m/z calcd for
C24H18N2O4S2Na [MþNa]þ 485.0600, found 485.0602.
J¼3.0 Hz, 3H), 0.99 (d, J¼2.5 Hz, 3H); 13C NMR (CDCl3, 125 MHz):
d
(ppm) 176.1, 175.5, 170.1, 160.0, 143.8, 142.6, 134.3, 134.3, 132.0
(2C), 127.1, 78.1, 52.2, 32.5, 19.3, 18.4 (2C). GCeMS m/z 362.3
[MþH]þ, 361.3 [M]þ, 318.4, 303.0 (100%), 104.5, 76.5, 55.3; HRMS
(ESI-TOF) m/z calcd for C17H16NO4S2 [MþH]þ 362.0515, found
362.0515.
4.1.9. Ethyl 2-(4,11-dioxo-4,11-dihydroanthra[2,3-d][1,3]dithiol-2-
imino)-3-phenylpropanoate(4i). Yield 55.8%; mp >300 ꢀC; 1H NMR
(500 MHz, CDCl3):
d
(ppm) 8.55 (d, J¼7.0 Hz, 2H), 8.02 (s, 2H), 7.70 (d,
4.1.3. Ethyl 2-(4,9-dioxo-4,9-dihydronaphtho[2,3-d][1,3]dithiol-2-
J¼4.0 Hz, 2H), 7.34e7.22 (m, 2H), 4.24 (q, J¼7.0 Hz, 2H), 3.96 (dd,
J1¼6.0 Hz, J2¼8.0 Hz, 1H), 3.35 (dd, J1¼5.0 Hz, J2¼14.0 Hz, 1H), 3.17
(dd, J1¼8.5 Hz, J2¼14.0 Hz,1H),1.28 (t, J¼6.5 Hz, 3H); 13C NMR (CDCl3,
imino)acetate (4c). Yield 54.0%; mp 159e160 ꢀC; 1H NMR
(500 MHz, CDCl3): d (ppm) 8.14e8.12 (m, 2H), 7.79e7.76 (m, 2H), 4.28
(q, J¼7.0 Hz, 2H), 4.04 (s, 2H), 1.33 (t, J¼7.5 Hz, 3H); 13C NMR (CDCl3,
125 MHz): d (ppm) 175.5, 175.0, 169.6, 160.8, 145.2, 144.2, 136.7,

H.-m. Huang et al. / Tetrahedron 69 (2013) 5221e5226
5225
134.6, 130.4, 130.3 (2C), 129.9, 129.6 (2C), 128.5 (2C), 128.0, 127.9,
127.0, 73.4, 61.7, 39.1, 14.2; EIMS m/z 472.39 [MꢁH]þ; HRMS (ESI-
TOF) m/z calcd for C26H20NO4S2 [MþH]þ 474.0827, found 474.0828.
d
(ppm) 8.09 (dd, J1¼3.5 Hz, J2¼5.0 Hz, 2H), 7.75 (dd, J1¼3.0 Hz,
J2¼5.0 Hz, 2H), 3.18 (t, J¼7.0 Hz, 2H), 1.80e1.73 (m, 2H), 1.00 (t,
J¼7.5 Hz, 3H); 13C NMR (CDCl3, 125 MHz):
d (ppm) 176.2, 175.6,
155.3, 143.9, 143.2, 134.2, 134.1, 132.1, 132.0, 127.1 (2C), 61.5, 23.3,
11.9; GCeMS m/z 289.9 [MþH]þ, 288.9 [M]þ, 261.0, 260.0 (100%),
220.0, 160.1, 132.3, 104.1; HRMS (ESI-TOF) m/z calcd for
C14H12NO2S2 [MþH]þ 290.0304, found 290.0305.
4.1.10. Ethyl 2-(4,11-dioxo-4,11-dihydroanthra-[2,3-d][1,3]dithiol-2-
imino)acetate (4j). Yield 46.1%; mp 205e206 ꢀC; 1H NMR
(500 MHz, CDCl3):
d
(ppm) 8.64 (d, J¼3.5 Hz, 2H), 8.07 (d, J¼4.5 Hz,
2H), 7.74 (d, J¼5.5 Hz, 2H), 4.31 (q, J¼6.5 Hz, 2H), 4.06 (s, 2H), 1.36 (t,
J¼7.0 Hz, 3H); 13C NMR (CDCl3,125 MHz):
d
(ppm) 175.8,175.1,168.3,
4.1.17. 2-(Isopropylimino)naphtho[2,3-d][1,3]dithiole-4,9-dione
161.6, 146.2, 144.4, 134.8 (2C), 130.5, 130.4, 130.3 (2C), 130.1 (2C),
128.1,128.0, 61.7, 59.1,14.2; EIMS m/z (%) 384.23 [MþH]þ; HRMS (ESI-
TOF) m/z calcd for C19H14NO4S2 [MþH]þ 384.0359, found 384.0368.
(4q). Yield 81.0%; mp 153e154 ꢀC; 1H NMR (500 MHz, CDCl3):
d
(ppm) 8.07 (dd, J1¼1.0 Hz, J2¼5.0 Hz, 2H), 7.73 (dd, J1¼3.5 Hz,
J2¼6.0 Hz, 2H), 3.24e3.18 (m, 1H), 1.25 (d, J¼6.5 Hz, 6H); 13C NMR
(CDCl3, 125 MHz):
d (ppm) 176.1, 175.7, 153.5, 143.6, 143.2, 134.2,
4.1.11. Ethyl 2-(4,11-dioxo-4,11-dihydroanthra-[2,3-d][1,3]dithiol-2-
134.1, 132.1, 132.0, 127.1 (2C), 61.4, 22.3; GCeMS m/z 290.2 [MþH]þ,
289.5, 274.8, 273.8, 245.7, 105.3; HRMS (ESI-TOF) m/z calcd for
C14H12NO2S2 [MþH]þ 290.0304, found 290.0311.
imino)-3-methylbutanoate(4k). Yield 41.1%; mp 199e200 ꢀC; 1H
NMR (500 MHz, CDCl3):
d
(ppm) 8.64 (d, J¼1.5 Hz, 2H), 8.08e8.06
(m, 2H), 7.75e7.73 (m, 2H), 4.26 (q, J¼7.5 Hz, 2H), 3.52 (d, J¼6.5 Hz,
1H), 2.53e2.36 (m, 1H), 1.33 (t, J¼6.5 Hz, 3H), 1.03 (d, J¼3 Hz, 3H),
4.1.18. 2-(Butylimino)naphtho[2,3-d][1,3]dithiole-4,9-dione
1.02 (d, J¼2.5 Hz, 3H); 13C NMR (CDCl3, 125 MHz):
d
(ppm) 175.8,
(4r). Yield 90.7%; mp 108e109 ꢀC; 1H NMR (500 MHz, CDCl3):
175.3, 169.7, 160.0, 145.5, 144.4, 134.8, 134.7, 130.6, 130.5, 130.4 (2C),
130.3, 130.0, 128.2, 128.1, 78.2, 61.4, 32.5, 19.3, 18.4, 14.3; EIMS m/z
424.09 [MꢁH]þ; HRMS (ESI-TOF) m/z calcd for C22H20NO4S2
[MþH]þ 426.0828, found 426.0815.
d
(ppm) 8.07 (dd, J1¼4.0 Hz, J2¼5.5 Hz, 2H), 7.74 (dd, J1¼3.0 Hz,
J2¼5.5 Hz, 2H), 3.21 (t, J¼6.5 Hz, 2H), 1.73e1.68 (m, 2H), 1.46e1.39
(m, 2H), 0.96 (t, J¼7.5 Hz, 3H); 13C NMR (CDCl3, 125 MHz):
d (ppm)
176.1, 175.5, 155.1, 143.8, 143.1, 134.2, 134.1, 132.0, 131.9, 127.1, 127.0,
59.4, 31.9, 20.5, 13.8; GCeMS m/z 303.0 [M]þ, 285.9, 270.1 (100%),
260.3, 220.2, 104.1, 76.1, 72.1, 50.0; HRMS (ESI-TOF) m/z calcd for
C15H14NO2S2 [MþH]þ 304.0461, found 304.0465.
4.1.12. Ethyl 2-(4,11-dioxo-4,11-dihydroanthra-[2,3-d][1,3]dithiol-2-
imino)propanoate(4l). Yield 48.1%; mp 232e233 ꢀC; 1H NMR
(500 MHz, CDCl3):
d
(ppm) 8.66 (d, J¼2.5 Hz, 2H), 8.10e8.07 (m,
2H), 7.76e7.74 (m, 2H), 4.26 (q, J¼6.5 Hz, 2H), 3.86 (q, J¼6.5 Hz, 1H),
4.1.19. 2-(Hexylimino)naphtho[2,3-d][1,3]dithiole-4,9-dione
1.56 (t, J¼10.0 Hz, 3H), 1.33 (t, J¼7.5 Hz, 3H); 13C NMR (CDCl3,
(4s). Yield 85.5%; mp 80e81 ꢀC; 1H NMR (500 MHz, CDCl3):
125 MHz):
d
(ppm) 175.7, 175.3, 170.8, 159.8, 145.8, 144.4, 134.8 (2C),
d
(ppm) 8.04 (dd, J1¼3.5 Hz, J2¼5.5 Hz, 2H), 7.72 (dd, J1¼3.5 Hz,
130.5, 130.4, 130.3 (2C), 130.1 (2C), 128.2, 128.1, 66.5, 61.6, 17.7, 14.2;
EIMS m/z 398.16 [MþH]þ; HRMS (ESI-TOF) m/z calcd for
C20H16NO4S2 [MþH]þ 398.0495, found 398.0631.
J2¼6.0 Hz, 2H), 3.18 (t, J¼7.0 Hz, 2H), 1.73e1.67 (m, 2H), 1.41e1.35
(m, 2H), 1.32e1.30 (m, 4H), 0.89 (t, J¼7.0 Hz, 3H); 13C NMR (CDCl3,
125 MHz):
d (ppm) 175.9, 175.4, 155.0, 143.8, 143.1, 134.7, 134.2,
134.1, 132.0, 131.9, 127.0, 126.8, 59.7, 31.6, 29.8, 27.1, 22.6, 14.1;
GCeMS m/z 331.0[M]þ, 298.2 (100%), 260.3, 247.1, 220.2, 104.1, 76.1,
41.0; HRMS (ESI-TOF) m/z calcd for C17H18NO2S2 [MþH]þ 332.0774,
found 332.0780.
4.1.13. Ethyl 2-(4,11-dioxo-4,11-dihydroanthra-[2,3-d][1,3]dithiol-2-
imino)-3-(4-hydroxyphenyl)-propanoate (4m). Yield 40.3%; mp
>300 ꢀC 1H NMR (500 MHz, CDCl3):
d
(ppm) 8.60 (d, J¼8.5 Hz, 2H),
8.06e8.04 (m, 2H), 7.13 (d, J¼8.0 Hz, 2H), 6.78 (d, J¼8.0 Hz, 2H),
5.00 (s, 1H), 4.23 (q, J¼6.5 Hz, 2H), 3.90 (q, J¼2.5 Hz, 2H), 3.26 (dd,
J1¼5.0 Hz, J2¼14.0 Hz, 1H), 3.08 (dd, J1¼8.0 Hz, J2¼14.0 Hz, 1H), 1.28
4.1.20. 2-(Decylimino)naphtho[2,3-d][1,3]dithi-ole-4,9-dione
(4t). Yield 76.0%; mp 104e105 ꢀC; 1H NMR (500 MHz, CDCl3):
(t, J¼7.0 Hz, 3H); 13C NMR (CDCl3, 125 MHz):
d
(ppm) 175.7, 175.2,
d
(ppm) 8.12 (dd, J1¼3.5 Hz, J2¼5.5 Hz, 2H), 7.76 (dd, J1¼3.0 Hz,
169.8, 161.7, 154.7, 144.3, 142.6, 135.0 (2C), 134.7 (3C), 130.7, 130.4
(2C), 130.3, 123.0, 128.1, 128.0, 115.4 (2C), 73.6, 61.6, 38.2, 14.2; EIMS
m/z 489.03 [M]þ; HRMS(ESI-TOF) m/z calcd for C26H19NO5S2Na
[MþNa]þ 512.0594, found 512.0601.
J2¼5.0 Hz, 2H), 3.23 (t, J¼7.0 Hz, 2H), 1.76e1.70 (m, 2H), 1.43e1.28
(m, 14H), 0.89 (t, J¼6.5 Hz, 3H); 13C NMR (CDCl3, 125 MHz):
d (ppm)
176.2, 175.6, 155.2, 143.9, 143.2, 134.2, 134.1 (2C), 132.0, 127.1 (2C),
59.8, 31.9, 29.9, 29.6 (2C), 29.3 (2C), 27.4, 22.7, 14.1; GCeMS m/z
387.3 [M]þ, 354.3 (100%), 316.3, 283.4, 247.2, 166.5, 76.3, 41.2. Anal.
Calcd for C21H25NO2S2: C, 65.08; H, 6.50; N, 3.61; S, 16.55. Found: C,
65.09; H, 6.60; N, 3.42; S, 17.06.
4.1.14. 2-(Methylimino)naphtho[2,3-d][1,3]dithiole-4,9-dione
(4n). Yield 96.7%; mp 182e183 ꢀC; 1H NMR (500 MHz, CDCl3):
d
(ppm) 8.11 (dd, J1¼3.5 Hz, J2¼5.5 Hz, 2H), 7.76 (dd, J1¼3.0 Hz,
J2¼5.5 Hz, 2H), 3.20 (s, 3H); 13C NMR (CDCl3, 125 MHz):
d
(ppm)
4.1.21. 2-(Dodecylimino)naphtho[2,3-d][1,3]dithiole-4,9-dione
176.2, 175.6, 157.5, 144.1, 143.1, 134.3, 134.2, 132.0 (2C), 127.1 (2C),
45.3; GCeMS m/z 262.2 [MþH]þ, 261.3 (M, 100%), 220.3, 188.3,
160.3, 104.2, 76.3, 50.2; HRMS (ESI-TOF) m/z calcd for C17H8NO2S2
[MþH]þ 261.9991, found 261.9999.
(4u). Yield 73.1%; mp 98e99 ꢀC; 1H NMR (500 MHz, CDCl3):
d
(ppm) 8.07 (dd, J1¼4.0 Hz, J2¼5.5 Hz, 2H), 7.73 (dd, J1¼4.0 Hz,
J2¼6.0 Hz, 2H), 3.50 (t, J¼6.0 Hz, 1H), 3.20 (t, J¼6.5 Hz, 2H),
1.74e1.66 (m, 3H), 1.41e1.26 (m, 16H), 0.88 (t, J¼7.0 Hz, 3H); 13C
NMR (CDCl3, 125 MHz):
d (ppm) 176.0, 175.5, 155.0, 143.7, 143.1,
4.1.15. 2-(Ethylimino)naphtho[2,3-d][1,3]dithiole-4,9-dione
134.1 (2C), 132.0, 131.9, 127.0 (2C), 59.7, 45.0, 31.9, 31.3, 30.0, 29.8,
29.6 (3C), 27.4, 22.6,14.1; EIMS m/z 416.13 [MþH]þ; HRMS (ESI-TOF)
m/z calcd for C23H30NO2S2 [MþH]þ 416.1713, found 416.1721.
(4o). Yield 86.7%; mp 199e200 ꢀC; 1H NMR (500 MHz, CDCl3):
d
(ppm) 8.09 (dd, J1¼1.0 Hz, J2¼5.5 Hz, 2H), 7.75 (dd, J1¼3.5 Hz,
J2¼5.5 Hz, 2H), 3.26 (q, J¼7.0 Hz, 2H), 1.35 (t, J¼7.0 Hz, 3H); 13C NMR
(CDCl3, 125 MHz):
d
(ppm) 176.1, 175.5, 155.3, 143.9, 143.1, 134.2,
4.1.22. 2-(Benzylimino)naphtho[2,3-d][1,3]dithiole-4,9-dione
134.1, 132.0 (2C), 127.1, 127.0, 53.9, 14.8; GCeMS m/z 276.1 [MþH]þ,
275.2, 260.4, 188.3, 160.2, 132.3, 104.2, 76.3, 50.2; HRMS (ESI-TOF)
m/z calcd for C13H10NO2S2 [MþH]þ 276.0148, found 276.0151.
(4v). Yield 83.3%; mp 162e163 ꢀC; 1H NMR (500 MHz, CDCl3):
d
(ppm) 8.14 (dd, J1¼3.0 Hz, J2¼5.5 Hz, 2H), 7.77 (dd, J1¼3.5 Hz,
J2¼6.0 Hz, 2H), 7.38e7.36 (m, 4H), 7.32e7.29 (m, 1H), 4.44 (s, 2H);
13C NMR (CDCl3, 125 MHz):
(ppm) 176.2, 175.6, 157.3, 144.2, 143.0,
d
4.1.16. 2-(Propylimino)naphtho[2,3-d][1,3]dithiole-4,9-dione
137.4, 134.3, 134.2, 132.1, 132.0, 128.7 (2C), 127.8 (2C), 127.5, 127.2
(4p). Yield 94.8%; mp 130e131 ꢀC; 1H NMR (500 MHz, CDCl3):
(2C), 62.6; GCeMS m/z 338.5 [MþH]þ, 337.5 (M, 100%), 232.6, 91.5,

5226
H.-m. Huang et al. / Tetrahedron 69 (2013) 5221e5226
65.5, 50.2; HRMS (ESI-TOF) m/z calcd for C18H12NO2S2 [MþH]þ
€
€
2000, 2, 1133; (c) Ottersbach, P. A.; Elsinghorst, P. W.; Hacker, H.-G.; Gutschow,
M. Org. Lett. 2010, 12, 3662.
338.0304, found 338.0312.
4. (a) Konstantinova, L. S.; Rakitin, O. A.; Rees, C. W. Chem. Rev. 2004, 104, 2617; (b)
Attanasi, O. A.; Crescentini, L. D.; Favi, G.; Filippone, P.; Giorgi, G.; Mantellini, F.;
Moscatelli, G.; Behalo, M. S. Org. Lett. 2009, 11, 2265; (c) Wang, F.; Cai, S.; Wang,
Z.; Xi, C. Org. Lett. 2011, 13, 3202; (d) Tanaka, K.; Wada, A.; Noguchi, K. Org. Lett.
2006, 8, 907; (e) Nakano, K.; Tatsumi, G.; Nozaki, K. J. Am. Chem. Soc. 2007, 129,
15116; (f) Hagooly, A.; Rozen, S. J. Org. Chem. 2004, 69, 8786; (g) Shi, L.; Liu, X.;
Zhang, H.; Jiang, Y.; Ma, D. J. Org. Chem. 2011, 76, 4200.
5. (a) Andreu, R.; Garín, J.; Orduna, J. Tetrahedron 2001, 57, 7883; (b) Nielsen, M. B.;
Utesch, N. F.; Moonen, N. N. P.; Boudon, C.; Gisselbrecht, J.-P.; Concilio, S.; Piotto, S.
P.; Seiler, P.; Gunter, P.; Gross, M.; Diederich, F. Chem.dEur. J. 2002, 8, 3601; (c)
4.1.23. 2-(Cyclohexylimino)naphtho[2,3-d][1,3]dithiole-4,9-dione
(4w). Yield 66.8%; mp 153e154 ꢀC; 1H NMR (500 MHz, CDCl3):
d
(ppm) 8.04 (dd, J1¼3.5 Hz, J2¼5.5 Hz, 2H), 7.72 (dd, J1¼3.5 Hz,
J2¼6.5 Hz, 2H), 2.91e2.86 (m, 1H), 1.83e1.79 (m, 4H), 1.66e1.63 (m,
1H), 1.50e1.42 (m, 2H), 1.38e1.27 (m, 3H); 13C NMR (CDCl3,
125 MHz):
d (ppm) 175.8, 175.4, 153.0, 143.4, 143.1, 134.1, 134.0,
€
131.9,131.8,129.9 (2C), 69.3, 32.1 (2C), 25.39 (2C), 24.4 (2C); GCeMS
m/z 330.3 [MþH]þ, 329.3 (M, 100%), 296.5, 141.5, 104.3, 67.3, 55.2,
41.2; HRMS (ESI-TOF) m/z calcd for C17H16NO2S2 [MþH]þ 330.0617,
found 330.0621.
Bendikov, M.; Wudl, F.; Perepichka, D. F. Chem. Rev. 2004,104, 4891; (d) Nielsen, M.
B.; Lomholt, C.; Becher, J. Chem. Soc. Rev. 2000, 29, 153; (e) Terkia-Derdra, N.;
ꢀ
Andreu, R.; Salle, M.; Levillain, E.; Orduna, J.; Garín, J.; Ortí, E.; Viruela, R.; Pou-
ꢀ
Amerigo, R.; Sahraoui, B.; Gorgues, A.; Favard, J.-F.; Riou, A. Chem.dEur. J. 2000, 6,
1199; (f) Zheng, N.; Li, B.; Ma, C.; Chen, T.; Kan, Y.; Yin, B. Tetrahedron 2012, 68,1782.
6. Dumur, F.; Gautier, N.; Gallego-Planas, N.; S¸ ahin, Y.; Levillain, E.; Mercier, N.;
Hudhomme, P.; Masino, M.; Girlando, A.; Lloveras, V.; Vidal-Gancedo, J.; Veci-
ana, J.; Rovira, C. J. Org. Chem. 2004, 69, 2164.
4.1.24. 2-(Propylimino)anthra[2,3-d][1,3]dithiole-4,11-dione
(4x). Yield 60.1%; mp 214e215 ꢀC; 1H NMR (500 MHz, CDCl3):
7. (a) Yamamoto, Y.; Takagishi, H.; Itoh, K. J. Am. Chem. Soc. 2001, 124, 28; (b)
Wang, G.-W.; Li, J.-X.; Li, Y.-J.; Liu, Y.-C. J. Org. Chem. 2005, 71, 680; (c) Zhao, Y.;
d
(ppm) 8.62 (s, 2H), 8.06e8.05 (m, 2H), 7.73e7.72 (m, 2H), 3.22 (t,
ꢀ
Perez-Segarra, W.; Shi, Q.; Wei, A. J. Am. Chem. Soc. 2005, 127, 7328; (d) Azizi, N.;
J¼6.5 Hz, 2H), 1.82e1.75 (m, 2H), 1.02 (t, J¼7.5 Hz, 3H); 13C NMR
Aryanasab, F.; Saidi, M. R. Org. Lett. 2006, 8, 5275; (e) Azizi, N.; Aryanasab, F.;
Torkiyan, L.; Ziyaei, A.; Saidi, M. R. J. Org. Chem. 2006, 71, 3634; (f) Clegg, W.;
Harrington, R. W.; North, M.; Villuendas, P. J. Org. Chem. 2010, 75, 6201; (g)
Maddani, M. R.; Prabhu, K. R. J. Org. Chem. 2010, 75, 2327; (h) Ma, D.; Lu, X.; Shi,
L.; Zhang, H.; Jiang, Y.; Liu, X. Angew. Chem., Int. Ed. 2011, 50, 1118.
(CDCl3, 125 MHz):
d (ppm) 175.8, 175.3, 155.7, 145.6, 144.8, 140.1,
137.7, 134.7, 130.6, 130.4, 130.3, 130.2, 129.9, 128.2, 128.1, 61.4, 23.3,
11.9; EIMS m/z 340.10 [MþH]þ; HRMS (ESI-TOF) m/z calcd for
C18H14NO2S2 [MþH]þ 340.0467, found 340.0460.
8. (a) Rostom, S. A. F.; El-Ashmawy, I. M.; Abd El Razik, H. A.; Badr, M. H.; Ashour,
H. M. A. Bioorg. Med. Chem. 2009, 17, 882; (b) Tenn, N.; Bellec, N.; Jeannin, O.;
ꢀ
~
Piekara-Sady, L.; Auban-Senzier, P.; Iniguez, J.; Canadell, E.; Lorcy, D. J. Am.
Chem. Soc. 2009, 131, 16961; (c) Chhabria, M.; Rathod, I.; Vala, K.; Patel, P. Med.
Chem. Res. 2011, 20, 1450; (d) Mishra, C. B.; Barodia, S. K.; Prakash, A.; Senthil
Kumar, J. B.; Luthra, P. M. Bioorg. Med. Chem. 2010, 18, 2491; (e) Fei, J.; Basu, A.;
Xue, F.; Palmore, G. T. R. Org. Lett. 2005, 8, 3; (f) Hartung, J.; Daniel, K.; Gottwald,
T.; Gro; Schneiders, N. Org. Biomol. Chem. 2006, 4, 2313.
Acknowledgements
We gratefully acknowledge the financial support from the Nat-
ural Science Foundation of China (21176223) and the Key In-
novation Team of Science and Technology in Zhejiang Province
(2010R50018).
9. (a) Klotz, L.-O.; Patak, P.; Ale-Agha, N.; Buchczyk, D. P.; Abdelmohsen, K.; Gerber,
P. A.; von Montfort, C.; Sies, H. Cancer Res. 2002, 62, 4922; (b) Tandon, V. K.; Yadav,
D. B.; Singh, R. V.; Chaturvedi, A. K.; Shukla, P. K. Bioorg. Med. Chem. Lett. 2005, 15,
5324; (c) Kumar, S.; Malachowski, W. P.; DuHadaway, J. B.; LaLonde, J. M.; Carroll,
P. J.; Jaller, D.; Metz, R.; Prendergast, G. C.; Muller, A. J. J. Med. Chem. 2008, 51,1706;
(d) Kesteleyn, B.; De Kimpe, N. J. Org. Chem. 2000, 65, 640.
Supplementary data
10. Rueping, M.; Sugiono, E.; Merino, E. Angew. Chem., Int. Ed. 2008, 47, 3046.
11. (a) Tandon, V. K.; Chhor, R. B.; Singh, R. V.; Rai, S.; Yadav, D. B. Bioorg. Med. Chem.
Lett. 2004, 14, 1079; (b) Salmon-Chemin, L.; Buisine, E.; Yardley, V.; Kohler, S.;
Debreu, M.-A.; Landry, V.; Sergheraert, C.; Croft, S. L.; Krauth-Siegel, R. L.; Da-
vioud-Charvet, E. J. Med. Chem. 2001, 44, 548; (c) Goulart, M. O. F.; Zani, C. L.;
Tonholo, J.; Freitas, L. R.; de Abreu, F. C.; Oliveira, A. B.; Raslan, D. S.; Starling, S.;
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.04.050.
References and notes
ꢀ
Chiari, E. Bioorg. Med. Chem. Lett. 1997, 7, 2043; (d) Sacau, E. P.; Estevez-Braun,
ꢀ
A.; Ravelo, A. G.; Ferro, E. A.; Tokuda, H.; Mukainaka, T.; Nishino, H. Bioorg. Med.
1. (a) Yamamoto, Y.; Hayashi, H. Tetrahedron 2007, 63, 10149; (b) Sunderhaus, J. D.;
Martin, S. F. Chem.dEur. J. 2009, 15, 1300; (c) Suero, M. G.; De la Campa, R.;
Chem. 2003, 11, 483; (e) Fujiwara, A.; Mori, T.; Iida, A.; Ueda, S.; Hano, Y.; No-
mura, T.; Tokuda, H.; Nishino, H. J. Nat. Prod. 1998, 61, 629.
ꢀ
ꢀ
Torre-Fernandez, L.; García-Granda, S.; Florez, J. Chem.dEur. J. 2012, 18, 7287;
(d) Bae, I.; Han, H.; Chang, S. J. Am. Chem. Soc. 2005, 127, 2038; (e) Mio, M. J.;
Kopel, L. C.; Braun, J. B.; Gadzikwa, T. L.; Hull, K. L.; Brisbois, R. G.; Markworth, C.
J.; Grieco, P. A. Org. Lett. 2002, 4, 3199; (f) Barral, K.; Moorhouse, A. D.; Moses, J.
E. Org. Lett. 2007, 9, 1809; (g) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem.
Rev. 2003, 103, 893; (h) Nandi, G. C.; Samai, S.; Kumar, R.; Singh, M. S. Tetra-
hedron 2009, 65, 7129; (i) Alizadeh, A.; Zohreh, N.; Sabahnoo, H.; Noaparast, Z.
Tetrahedron 2011, 67, 1709.
12. CCDC 915881 (4a) contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge Crys-
tallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
13. Jiang, C. H.; Wang, S. Z. Synlett 2009, 1099.
14. (a) Ung, G.; Mendoza-Espinosa, D.; Bouffard, J.; Bertrand, G. Angew. Chem., Int.
ꢀ
Ed. 2011, 50, 4215; (b) Dumur, F.; Guegano, X.; Gautier, N.; Liu, S.-X.; Neels, A.;
Decurtins, S.; Hudhomme, P. Eur. J. Org. Chem. 2009, 2009, 6341; (c) Guerro, M.;
Pham, N. H.; Massue, J.; Bellec, N.; Lorcy, D. Tetrahedron 2008, 64, 5285; (d)
Marcos, C. F.; Polo, C.; Rakitin, O. A.; Rees, C. W.; Torroba, T. Chem. Commun.
1997, 879.
2. Jacobine, A. M.; Posner, G. H. J. Org. Chem. 2011, 76, 8121.
3. (a) Miyamura, H.; Shiramizu, M.; Matsubara, R.; Kobayashi, S. Chem. Lett. 2008,
37, 360; (b) Wan, Y.; Kurchan, A. N.; Barnhurst, L. A.; Kutateladze, A. G. Org. Lett.