Chlorophyll-Catalyzed Visible-Light-Mediated Synthesis of Tetrahydroquinolines from N,N-Dimethylanilines and Maleimides

Article abstract of DOI:10.1021/acs.joc.6b03034

Natural pigment chlorophyll was used as a green photosensitizer for the first time in a visible-light photoredox catalysis for the efficient synthesis of tetrahydroquinolines from N,N-dimethylanilines and maleimides in an air atmosphere. The reaction involves direct cyclization via an sp³ C-H bond functionalization process to afford products in moderate to high yields (61-98%) from a wide range of substrates with a low loading of chlorophyll under mild conditions. This work demonstrates the potential benefits of chlorophyll as photosensitizer in visible light catalysis.

Full text of DOI:10.1021/acs.joc.6b03034

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Featured Article
Chlorophyll-Catalyzed Visible-Light-Mediated Synthesis of
Tetrahydroquinolines from N,N-Dimethylanilines and Maleimides
Jun-Tao Guo, Da-Cheng Yang, Zhi Guan, and Yan-Hong He
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b03034 • Publication Date (Web): 20 Jan 2017
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Chlorophyll-Catalyzed Visible-Light-Mediated Synthesis of
Tetrahydroquinolines from N,N-Dimethylanilines and Maleimides
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Jun-Tao Guo, Da-Cheng Yang, Zhi Guan* and Yan-Hong He*
Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering,
Southwest University, Chongqing 400715, PR China
E-mails: guanzhi@swu.edu.cn (for Z. Guan); heyh@swu.edu.cn (for Y.-H. He)
Abstract: Natural pigment chlorophyll was used as a green photosensitizer for the first time in a
visible light photoredox catalysis for the efficient synthesis of tetrahydroquinolines from
N,N-dimethylanilines and maleimides in an air atmosphere. The reaction involves direct
3
cyclization via sp C–H bond functionalization process to afford products in moderate to high
yields (61-98%) from a wide range of substrates with a low loading of chlorophyll under mild
conditions. This work demonstrates the potential benefits of chlorophyll as photosensitizer in
visible light catalysis.
3
Key words: chlorophyll; photosensitizer; visible light catalysis; sp C-H bond functionalization;
tetrahydroquinolines
1
. Introduction
1
Light is an inexpensive, abundant and endlessly renewable source of clean energy. Thus,
visible light photoredox catalysis as an effective and versatile method has become a powerful and
promising tool. It has been productively used to drive chemical transformations in the field of
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organic synthesis. Since photo-induced electron transfer (PET) reactions can be used to construct
molecular architectures that would otherwise be difficult to produce, photochemistry would
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significantly impact multiple aspects of chemical synthesis.
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Photosynthesis is one of the most famous chemical reactions in nature, in which plants use
2 2
sunlight as their energy source to convert CO and H O to sugars. Chlorophyll is the most
abundant natural visible light photocatalyst on the earth. It is the principal photoacceptor in the
chloroplasts of most green plants. In 2015, Boyer et al. utilized the electron transfer mechanism of
4
chlorophyll under light to control radical polymerization. As a green, environmentally friendly
and widespread photosensitizer, chlorophyll has been rarely applied in photo-driven synthesis.
Inspired by the leading role of chlorophyll playing in photosynthesis, we envisaged that if it was
possible to use chlorophyll as a highly efficient photosensitizer in visible light catalysis for
organic synthesis.
Tetrahydroquinoline moiety is an important structural feature of various natural products and
pharmaceutical agents that have exhibited a broad range of biological activities such as
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antibacterial, neuroprotectant and anti-arrhythmic etc. Owing to their ubiquitous distribution in
natural products and medicinal agents, tetrahydroquinolines have become important synthetic
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2 2
targets for chemists. In 2011, Miura etal. used CuCl /O to catalyze N-methylanilines and
maleimides for the synthesis of the tetrahydroquinolines in moderate yields. Because tertiary
amines have low oxidation potentials, many reported PET processes make use of these molecules
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as electron donors. The photoredox reactions were also employed to develop the
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tetrahydroquinolines using tertiary amines and maleimides. Ru(bpy)
3
Cl
2 2
, Eosin Y, TiO ,
1
2
13
[Cu(dap)
2
]Cl and conjugated nanoporous polymers, have been used as photosensitizers in the
visible light mediated photoredox reactions for the synthesis of tetrahydroquinoline derivatives.
Herein, we wish report the first example of natural pigment chlorophyll being used as a
green and efficient photosensitizer in a visible light photoredox catalysis for the synthesis of
tetrahydroquinolines from N,N-dimethylanilines and maleimides in an air atmosphere. This work
demonstrated that chlorophyll can act as visible-light photoredox catalyst to initiate organic
transformations. This novel process provides an example for exploring environmentally friendly,
simple and convenient synthetic route utilizing chlorophyll and light energy in organic chemistry.
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2. Results and Discussion
Initially, the cyclization reaction between N,N-dimethyl-p-toluidine (1a, 0.50 mmol) and
N-phenylmaleimide (2a, 0.25 mmol) in DMF (1.0 mL) under an air atmosphere (with no air
bubbling) was chosen as the model reaction system. Firstly, key control experiments were
performed to establish that both visible light and chlorophyll are necessary for the reaction.
Without visible light and chlorophyll no reaction was observed (Table 1, entry 1). The reaction in
the absence of either visible light or chlorophyll only gave a trace amount of product (Table 1,
entries 2 and 3). Gratifyingly, when the model reaction was carried out with 0.16 mg of
chlorophyll (30 mg of chlorophyll powder preparation, in which total chlorophyll content is 0.52%)
under irradiation with a 23 W fluorescent lamp, the desired product tetrahydroquinoline 3a was
obtained with 80% yield after 36 h (Table 1, entry 4). The results indicated that both visible light
and chlorophyll are necessary for the model reaction. In order to check if oxygen is necessary in
this reaction, the model reaction was conducted in the absence of oxygen under nitrogen, and
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product 3a was only obtained in a low yield of 8% (Table 1, entry 5). This result indicated that
oxygen plays a key role in this reaction. Furthermore, to verify if a radical process is involved in
this reaction,
a
test experiment was performed with
a
free radical scavenger,
(2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl (TEMPO). Only a trace amount of product 3a was
observed when TEMPO was added to the model reaction (Table 1, entry 6), indicating the
involvement of a radical mechanism.
a
Table 1. Control experiments
Visible light (irradiation with a 23 W
fluorescent lamp)
Chlorophyll (0.16
mg)
TEMPO (0.50
mmol)
b
Entry
1
Yield (%)
c
-
-
-
no reaction
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trace
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trace
a
Reaction conditions: a mixture of 1a (0.50 mmol) and 2a (0.25 mmol) in DMF (1.0 mL) was stirred for 36 h.
b
Yield of the isolated product after silica gel chromatography.
c
d
e
“
-”means the corresponding substance was not used.
“+”means the corresponding substance was used.
Nitrogen protection without oxygen.
It is well known that chlorophyll can generate singlet oxygen upon irradiation in oxygenated
1
4
solution. In order to verify the existence of singlet oxygen, we did some control experiments
under optimal reaction conditions (details of the optimizations were described hereafter in Table 3
and the Supporting information Table S1). When 0.25 mmol (1 equiv) of
1
5
1
,4-diazabicyclo[2.2.2]octane (DABCO), which is known as a quencher of singlet oxygen, was
added to the model reaction, no product 3a was observed within the first 18 h. The reaction rate
was largely suppressed during all the reaction time. A much lower yield of 12% was obtained in
the presence of DABCO after 48 h compared to the yield of 97% (under optimal reaction
conditions) without DABCO (Figure 1). The results suggested that singlet oxygen must be
involved in the reaction mechanism.
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chlorophyll
chlorophyll+DABCO
4
2
0
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Time (h)
Figure 1. Influence of DABCO on the model reaction
The natural pigment chlorophyll we used was purchased from Tokyo Chemical Industry
(TCI). This is a mixture powder of chlorophyll, lactose and dry gum Arabic, in which the total
chlorophyll from plants is 0.52% (the mass percentage) (For more information about this
chlorophyll preparation, please see the Supporting information, Materials). In order to exclude the
effects of lactose and dry gum arabic on the model reaction, some comparison experiments were
performed. In the model reaction described in Table 1, entry 4, 0.16 mg of chlorophyll (30 mg of
chlorophyll powder preparation, in which total chlorophyll content is 0.52%) was used. Thus, as a
comparison, lactose (30 mg), gum arabic (30 mg) and lactose/gum arabic=1/1 mixture (30 mg)
were used instead of chlorophyll to catalyze the reaction, respectively. It can be seen that lactose,
gum arabic and the mixture of lactose and gum arabic displayed a low degree of catalytic effect on
the model reaction, giving 3a with the yield ranged from 7-28% (Table 2, entries 1, 4 and 7). To
understand this phenomenon, we performed some control experiments. Firstly, we measured the
visible light absorption of gum arabic and lactose, and found that none of them showed obvious
absorption in the visible light range (For details, please see the Supporting information Figures S2
and S3). Next, when a free radical scavenger, (2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl
(
TEMPO) (2 equiv) (Table 2, entries 2, 5 and 8) and a singlet oxygen quencher
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1,4-diazabicyclo[2.2.2]octane (DABCO) (1 equiv) (Table 2, entries 3, 6 and 9) were added into
the reaction system separately, only a trace amount of product 3a was observed. Based on the
above results, we can draw conclusion that the additives (lactose and gum arabic) in commercial
chlorophyll preparation can catalyze the model reaction; a free radical process and singlet oxygen
may be involved in these reactions. However, the catalysis degree of these additives was much
lower than chlorophyll. The results confirmed that chlorophyll plays a leading role in this
photocatalytic reaction. Chlorophyll a is the mostly distributed form of chlorophyll in plants, and
its structure is shown in Figure 2.
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Table 2. Comparison experiments
Lactose
Gum arabic
(30 mg)
Lactose/gum arabic=1/1
mixture (30 mg)
TEMPO
DABCO
Yield
Entry
b
(30 mg)
(0.50 mmol)
(0.25 mmol)
(%)
c
d
1
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-
+
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trace
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+
a
Reaction conditions: A mixture of 1a (0.50 mmol), 2a (0.25 mmol) in DMF (1.0 mL) was irradiated with a 23 W
fluorescent lamp for 36 h.
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b
Yield of the isolated product after silica gel chromatography.
c
“
“
-”means the corresponding substance was not used.
d
+”means the corresponding substance was used.
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Figure 2. Structure of chlorophyll a
Next, we optimized the reaction conditions with respect to solvents and catalyst dosages.
DMF was found to be the best solvent among DMF, DMSO, MeCN, MeOH, THF, DCM and H
Table 3, entries 1-7). Then, the catalyst dosage was screened. When increasing the amount of
2
O
(
chlorophyll from 0.05 mg to 0.16 mg, the yield of product 3a increased significantly (Table 3,
entries 1, 8 and 9). When the amount of chlorophyll was further increased from 0.16 mg to 0.21
mg, the yield of 3a was almost remained unchanged (Table 3, entries 1 and 10). Therefore, DMF
and 0.16 mg of catalyst dosage were chosen as the suitable conditions for the model reaction.
Additionally, the influences of molar ratio, solvent volume, wattage of lamp and reaction time
were investigated. Based on the experiment results, 1a:2a = 2:1, 2.0 mL of DMF and 23 W
fluorescent lamp were chosen as the optimum conditions for the model reaction. (For details,
please see the Supporting information Table S1).
a
Table 3. Screening of solvents and catalyst dosages
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b
Entry
Chlorophyll (mg)
Solvent
Yield (3a) %
1
2
3
4
5
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8
9
0.16
0.16
0.16
0.16
0.16
0.16
0.16
0.05
0.10
0.21
DMF
DMSO
MeCN
MeOH
THF
80
76
23
23
19
CH
2
Cl
2
10
H
2
O
trace
37
DMF
DMF
DMF
55
1
0
76
a
Reaction conditions: A mixture of 1a (0.50 mmol), 2a (0.25 mmol), 0.05-0.21 mg of chlorophyll (10-40 mg of
chlorophyll powder preparation, in which total chlorophyll content is 0.52%) in a solvent (1.0 mL) was irradiated
with a 23 W fluorescent lamp for 36 h.
b
Yield of the isolated product after silica gel chromatography.
With the optimized conditions in hand, the substrate scope of this photoreaction was
investigated (Table 4). A series of N,N-dimethylanilines 1 with a range of substituents on the
benzene ring and maleimides 2 with different substituents on the N atom were examined. It can be
seen that N,N-dimethylanilines with either electron-donating groups (4-Me) or
electron-withdrawing groups (4-F, 4-Cl, 4-Br) reacted well with N-alkyl maleimides and N-aryl
maleimides to give the corresponding products in good yields (Table 4, entries 1-3, 5-9, 11-24 and
2
6). Wherein the N-tert-butyl maleimide was used, a relatively low yields (61-66%) (Table 4,
entries 4, 10, 25) were obtained after 48 h; this is probably due to the larger steric hindrance. The
highest yield of 98% was achieved (Table 4, entries 13 and 17). 13 new tetrahydroquinoline
1
13
derivatives were obtained, and their structures were confirmed by HRMS, H NMR and C NMR.
In addition, second amine N-methyl-phenylamine and hetero-aromatic tertiary amine
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4-dimethylaminopyridine were also tested, but no reaction was detected (the data are not shown in
Table 4). This may be due to second amine and electron-defect pyridine could not stabilize amine
cation radical, which is generated in the photoredox process.
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a
Table 4. Substrate scope
1
2
b
Entry
R
R
Product No.
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
4-Me
4-Me
4-Me
4-Me
4-Me
H
Ph
Me
Et
3a
3b
3c
3d
3e
3f
36
36
36
48
36
36
30
36
36
48
36
36
30
36
36
36
36
30
36
36
36
36
36
36
48
36
89
74
72
62
83
93
97
93
87
66
95
97
98
89
84
69
98
97
79
73
80
96
86
90
61
75
t-Bu
Bn
Ph
H
H
3g
3h
3i
H
Me
Et
H
1
1
1
1
0
1
2
3
H
t-Bu
Bn
Ph
H
3j
H
3k
3l
4-F
4-F
3m
3n
3o
3p
3q
3r
3s
14
4-F
Me
Et
1
1
5
6
4-F
4-F
Bn
Ph
H
17
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Br
4-Br
4-Br
4-Br
4-Br
1
1
8
9
Me
Et
20
3t
2
2
1
2
Bn
Ph
Me
Et
3u
3v
3w
3x
3y
3z
23
2
2
4
5
t-Bu
Bn
26
a
Reaction conditions: A mixture of 1 (0.50 mmol), 2 (0.25 mmol) and 0.16 mg of chlorophyll (30 mg of
chlorophyllpowder preparation, in which total chlorophyll content is 0.52%) in DMF (2.0 mL) was irradiated with
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a 23W fluorescent lamp.
b
Yield of the isolated product after silica gel chromatography.
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-13
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0
Based on our control experiments above and previous work, we believe that the formation
of tetrahydroquinolines involves the addition of α-aminoalkyl radicals to the double bond and
subsequent free radical cyclization as the key steps, and singlet oxygen was involved in the
reaction mechanism. Thus, a plausible reaction pathway for this visible light induced cyclization
reaction catalyzed by chlorophyll is proposed in Scheme 1. The absorption of a photon excites the
*
chlorophyll from its ground state to its excited state (chlorophyll ). The excited state
*
photosensitizer (chlorophyll ) transfers its energy to the ground state oxygen, forming the singlet
oxygen. Meanwhile, the excited state of the photosensitizer goes back to the ground state. Asingle
electron transfer (SET) from the tertiary amine 1 to the singlet oxygen leads to the amine cation
radical 4. At the same time, singlet oxygen accepts an electron to form superoxide anion radicals.
Proton transfer from the amine cation radical 4 to the superoxide anion radical gives the
α-aminoalkyl radical 5. Radical addition of 5 to the maleimide 2 generates 6, and subsequent
intramolecular cyclization leads to intermediate 7. SET oxidation of 7 by oxygen forms a
carbocation 8, which followed by deprotonation to furnish the desired product 3. In this process,
-
the protonation of superoxide radical anion would generate the HOO and then to H
2
O
2
.
1
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Scheme 1: Proposed reaction mechanism.
3
. Conclusion
In conclusion, we have developed a green, facile and efficient method for the synthesis of
tetrahydroquinolines from N,N-dimethylanilines and maleimides. The protocol is significantly
green because it utilizes visible light and atmospheric oxygen as the greenest reagents, and natural
pigment chlorophyll as the photosensitizer to deliver the product at room temperature in a simple
3
procedure. This methodology provides a direct cyclization via sp C–H bond functionalization
process to afford tetrahydroquionoline frameworks of importance in medicinal and pharmaceutical
chemistry. Moderate to high yields (61-98%) were obtained from a wide range of substrates under
mild conditions. This novel process provides an example for exploring environmentally friendly,
simple and convenient synthetic route utilizing chlorophyll and light energy in organic chemistry.
4
. Experimental section
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4.1 General procedure for the synthesis of tetrahydroquinolines
A round-bottom flask was charged with 0.16 mg of chlorophyll (30 mg of chlorophyll powder
preparation, in which total chlorophyll content is 0.52%), N,N-dimethylaniline 1 (0.50 mmol),
maleimide 2 (0.25 mmol) and DMF (2.0 mL). The resultant mixture was stirred under irradiation
of a 23 W fluorescent lamp (the parallel distance between the lamp and the reaction flask is 2 cm)
at room temperature for the specified reaction time and monitored by TLC. The reaction mixture
was filtered (with 40 mm Buchner funnel and qualitative filter paper) to remove lactose and gum
arabic, which could not dissolve well in DMF. The ethyl acetate was employed to wash the residue
on the filter paper to assure that products obtained were all dissolved in the filtrate. The filtrate
0
1
2
3
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8
9
0
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2
3
4
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7
8
9
0
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9
0
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3
4
5
6
7
8
9
0
2 4
was washed with water for three times, and then dried over anhydrous Na SO . The organic
solvent was then removed under reduced pressure. The crude products were purified by silica gel
column chromatography with petroleum ether/ethyl acetate as eluent (VPE /VEA = 2:1 to 12:1).
5,8-Dimethyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3a)
7
,9-11
(Table 4, entry 1).
o
White solid: yield 67.7 mg, 89%; mp 193-195 C; R
f
= 0.31 (petroleum ether/ethyl acetate 6:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.43 - 7.40 (m, 2H), 7.35 - 7.33 (m, 2H), 7.27 - 7.24 (m, 2H),
7.07 (d, J = 8.2 Hz, 1H), 6.68 (d, J = 8.2 Hz, 1H), 4.14 (d, J = 9.4 Hz, 1H), 3.61 (dd, J = 11.4, 2.5
Hz, 1H), 3.54 (ddd, J = 9.4, 4.4, 2.5 Hz, 1H), 3.09 (dd, J = 11.4, 4.4 Hz, 1H), 2.84 (s, 3H), 2.33 (s,
1
3
3
3H). C NMR (150 MHz, CDCl ) δ = 177.7, 175.8, 146.4, 132.1, 130.8, 129.2, 129.0, 128.9,
128.5, 126.4, 118.5, 112.5, 51.0, 43.6, 42.2, 39.5, 20.4.
2,5,8-Trimethyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3b) (Table 4,
7
,10-11
entry 2).
o
White solid: yield 45.2 mg, 74%; mp 171-174 C; R
f
= 0.35 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.32 (s, 1H), 7.03 (d, J = 8.3 Hz, 1H), 6.63 (d, J = 8.3 Hz, 1H),
3.97 (d, J = 9.4 Hz, 1H), 3.53 (dd, J = 11.4, 2.3 Hz, 1H), 3.35 (ddd, J = 9.4, 4.5, 2.3 Hz, 1H), 3.01
1
3
(s, 3H), 2.95 (dd, J = 11.4, 4.5 Hz, 1H), 2.78 (s, 3H), 2.32 (s, 3H). C NMR (150 MHz, CDCl
3
) δ
= 178.8, 176.8, 146.3, 130.7, 129.1, 128.9, 118.7, 112.5, 50.8, 43.6, 42.1, 39.5, 25.3, 20.4.
2-Ethyl-5,8-dimethyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(3c)
(
Table 4, entry 3).
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o
White solid: yield 46.5 mg, 72%; mp 117-119 C; R
f
= 0.36 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.32 (s, 1H), 7.03 (d, J = 8.2 Hz, 1H), 6.63 (d, J = 8.2 Hz, 1H),
3.94 (d, J = 9.4 Hz, 1H), 3.56 (m, 2H), 3.49 (dd, J = 11.4, 2.6 Hz, 1H), 3.33 (dd, J = 9.4, 4.6 Hz,
1
3
10
11
12
13
14
15
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59
60
1H), 2.99 (dd, J = 11.4, 4.6 Hz, 1H), 2.78 (s, 3H), 2.32 (s, 3H), 1.16 (t, J = 7.2 Hz, 3H). C NMR
(150 MHz, CDCl
3
) δ = 178.8, 176.8, 146.3, 130.7, 129.1, 128.9, 118.7, 112.5, 50.8, 43.6, 42.1,
+
39.5, 25.3, 20.4, 12.9. HRMS (ESI-TOF) calc. for C15
281.1264.
H
18
N
2
O
2
(M+Na) : 281.1260, found:
2-(tert-Butyl)-5,8-dimethyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(3d) (Table 4, entry 4).
Yellowish oil: yield 44.1 mg, 62%; R
f
= 0.29 (petroleum ether/ethyl acetate 12:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.03 (d, J = 8.2 Hz, 1H), 6.63 (d, J = 8.2 Hz, 1H), 6.54 (s, 1H),
3.81 (d, J = 9.7 Hz, 1H), 3.42 (dd, J = 11.3, 3.3 Hz, 1H), 3.20 (ddd, J = 9.7, 4.6, 3.3 Hz, 1H), 2.96
1
3
3
(dd, J = 11.3, 4.6 Hz, 1H), 2.79 (s, 3H), 2.32 (s, 3H), 1.57 (s, 9H). C NMR (150 MHz, CDCl ) δ
= 179.6, 177.9, 133.9, 130.8, 128.9, 119.2, 112.3, 58.7, 51.3, 43.2, 42.2, 39.5, 28.4, 20.4. HRMS
+
(ESI-TOF) calc. for C17
H
22
N
2
O
2
(M+Na) : 309.1573, found: 309.1582.
2-Benzyl-5,8-dimethyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3e)
7
,9,11
(Table 4, entry 5).
o
White solid: yield 66.5 mg, 83%; mp 120-122 C; R
f
= 0.33 (petroleum ether/ethyl acetate 8:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.34 - 7.27 (m, 6H), 7.05 (d, J = 8.2 Hz, 1H), 6.65 (d, J = 8.2 Hz,
1H), 4.71 (d, J = 14.4 Hz, 1H), 4.64 (d, J = 14.4 Hz, 1H), 3.96 (d, J = 9.4 Hz, 1H), 3.50 (dd, J = 11.4,
2.5 Hz, 1H), 3.40 (ddd, J = 9.4, 4.5, 2.5 Hz, 1H), 3.01 (dd, J = 11.4, 4.5 Hz, 1H), 2.80 (s, 3H),
1
3
3
2.33 (s, 3H). C NMR (150 MHz, CDCl ) δ = 178.4, 176.5, 146.3, 135.7, 130.8, 129.1, 129.0,
128.6, 128.3, 127.8, 118.9, 112.4, 51.1, 43.7, 42.8, 42.2, 39.4, 20.4.
5-Methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(3f)
7
,9-12
(
Table 4, entry 6).
o
White solid: yield 67.9 mg, 93%; mp 203-205 C; R
f
= 0.27 (petroleum ether/ethyl acetate 6:1);
) δ = 7.57 - 7.31(m, 4H), 7.30 - 7.27 (m, 3H), 6.95 (d, J = 8.2 Hz, 1H),
6.78 (d, J = 8.2 Hz, 1H), 4.17 (d, J = 9.6 Hz, 1H), 3.63 (dd, J = 11.5, 2.6 Hz, 1H), 3.56 (ddd, J =
1
H NMR (600 MHz, CDCl
3
1
3
3
9.6, 4.4, 2.6 Hz, 1H), 3.14 (dd, J = 11.5, 4.4 Hz, 1H), 2.87 (s, 3H). C NMR (150 MHz, CDCl ) δ
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= 177.6, 175.7, 148.5, 132.1, 130.4, 129.0, 128.7, 128.5, 126.4, 119.7, 118.6, 112.5, 50.7, 43.6,
42.2, 39.4.
5-Methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3g) (Table 4, entry
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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7
8
9
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2
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8
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1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7).
o
White solid: yield 52.6 mg, 97%; mp 77-79 C; R
f
= 0.18 (petroleum ether/ethyl acetate 2:1);
1
H NMR (600 MHz, DMSO-d
6
) δ = 11.30 (br, 1H), 7.30 (d, J = 7.4 Hz, 1H), 7.17 - 7.15 (m, 1H),
6.83 - 6.81 (m, 1H), 6.73 (d, J = 7.4 Hz, 1H), 4.01 (d, J = 9.4 Hz, 1H), 3.45 (ddd, J = 9.4, 4.7, 2.3
1
3
Hz, 1H), 3.33 (dd, J = 11.5, 2.3 Hz, 1H), 2.87 (dd, J = 11.5, 4.7 Hz, 1H), 2.72 (s, 3H). C NMR
(150 MHz, DMSO-d
6
) δ = 180.6, 178.6, 148.9, 130.4, 128.3, 120.1, 119.2, 112.7, 50.8, 44.4, 43.3,
+
39.7. HRMS (ESI-TOF) calc. for C12
H
12
N
2
O
2
(M+H) : 217.0972, found: 217.0976.
2,5-Dimethyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3h) (Table 4,
1
0-11
entry 8).
o
White solid: yield 53.3 mg, 93%; mp 171-173 C; R
f
= 0.24 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.50 (d, J = 7.5 Hz, 1H), 7.24 - 7.21 (m, 1H), 6.91 (m, 1H), 6.72
(d, J = 7.5 Hz, 1H), 4.01 (d, J = 9.4 Hz, 1H), 3.55 (dd, J = 11.5, 2.4 Hz, 1H), 3.38 (ddd, J = 9.4,
1
3
4.5, 2.4 Hz, 1H), 3.06 (dd, J = 11.5, 4.5 Hz, 1H), 3.00 (s, 3H), 2.82 (s, 3H). C NMR (150 MHz,
CDCl ) δ = 178.7, 176.8, 148.4, 130.2, 128.6, 119.6, 118.7, 112.5, 50.5, 43.6, 42.0, 39.4, 25.3.
3
2-Ethyl-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3i) (Table
4, entry 9).
Yellowish oil: yield 53.3 mg, 87%; R
f
= 0.32 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.50 (d, J = 7.5 Hz, 1H), 7.24 - 7.21 (m, 1H), 6.91 (m, 1H), 6.72
(d, J = 7.5 Hz, 1H), 3.98 (d, J = 9.4 Hz, 1H), 3.62 - 3.53 (m, 2H), 3.52 (d, J = 9.4 Hz, 1H), 3.37 -
1
3
3.35 (m, 1H), 3.07 - 3.04 (m, 1H), 2.82 (s, 3H), 1.16 (t, J = 7.2 Hz, 3H). C NMR (150 MHz,
CDCl
3
) δ = 178.4, 176.5, 148.4, 130.2, 128.5, 119.6, 118.9, 112.4, 50.7, 43.5, 42.0, 39.4, 34.2,
+
12.9. HRMS (ESI-TOF) calc. for C14
H
16
N
2
O
2
(M+Na) : 267.1104, found: 267.1107.
2-(tert-Butyl)-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3j)
1
1
(
Table 4, entry 10).
o
White solid: yield 44.8 mg, 66%; mp 77-79 C; R
f
= 0.29 (petroleum ether/ethyl acetate 12:1);
1
H NMR (600 MHz, CDCl3) δ = 7.47 (d, J = 7.5 Hz, 1H), 7.23 (m, 1H), 6.90 (m, 1H), 6.73 (d, J =
7
.5 Hz, 1H), 3.85 (d, J = 9.7 Hz, 1H), 3.45 (dd, J = 11.4, 2.9 Hz, 1H), 3.23 (ddd, J = 9.7, 4.5, 2.9
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1
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Hz,1H), 3.03 (dd, J = 11.4, 4.5 Hz, 1H), 2.83 (s, 3H), 1.57 (s, 9H). C NMR (150 MHz, CDCl
3
) δ
= 179.5, 177.8, 148.3, 130.3, 128.4, 119.3, 119.2, 112.3, 58.7, 50.9, 43.2, 42.1, 39.3, 28.4.
2-Benzyl-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(3k)
1
1-12
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(Table 4, entry 11).
o
White solid: yield 72.5 mg, 95%; mp 126-128 C; R
f
= 0.30 (petroleum ether/ethyl acetate 8:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.50 (d, J = 7.5 Hz, 1H), 7.34 - 7.23 (m, 6H), 6.93 (m, 1H), 6.74
(d, J = 7.5 Hz, 1H), 4.71 (d, J = 14.4 Hz, 1H), 4.65 (d, J = 14.4 Hz, 1H), 4.00 (d, J = 9.4 Hz, 1H),
3.52 (dd, J = 11.5, 2.6 Hz, 1H), 3.37 (ddd, J = 9.4, 4.5, 2.6 Hz, 1H), 3.07 (dd, J = 11.5, 4.5 Hz,
1
3
3
1H), 2.83 (s, 3H). C NMR (150 MHz, CDCl ) δ = 178.3, 176.4, 148.5, 135.6, 130.3, 128.6,
128.5, 128.3, 127.8, 119.7, 118.9, 112.4, 50.8, 43.7, 42.8, 42.1, 39.3.
8-Fluoro-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
9
,11
(3l) (Table 4, entry 12).
o
White solid: yield 75.4 mg, 97%; mp 171-173 C; R
f
= 0.31 (petroleum ether/ethyl acetate 9:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.41 - 7.38 (m, 2H), 7.33 - 7.31 (m, 1H), 7.22 - 7.21 (m, 3H),
6.90 - 6.88 (m, 1H), 6.64 - 6.62 (m, 1H), 4.09 (d, J = 9.4 Hz, 1H), 3.54 (dd, J = 11.4, 2.6 Hz, 1H),
1
3
3.50 (ddd, J = 9.4, 3.9, 2.6 Hz, 1H), 3.03 (dd, J = 11.4, 3.9 Hz, 1H), 2.77 (s, 3H). C NMR (150
1
MHz, CDCl
3
) δ = 177.4, 175.2, 156.5 (d, JC-F = 237.0 Hz), 145.0 (d, J = 1.7 Hz), 131.9, 129.0,
128.5, 126.3, 120.1 (d, J = 7.6 Hz), 116.9 (d, J = 23.2 Hz), 114.9 (d, J = 21.9 Hz), 113.3 (d, J = 7.6
Hz), 51.0, 43.4, 42.2, 39.7.
8-Fluoro-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(Table 4, entry 13).
(3m)
Yellowish oil: yield 57.5 mg, 98%; R
f
= 0.25 (petroleum ether/ethyl acetate 2:1);
) δ = 8.57 (br, 1H), 7.21 - 7.20 (m, 1H), 6.94 - 6.83 (m, 1H), 6.68 -
6.66 (m, 1H), 4.01 (d, J = 9.5 Hz, 1H), 3.50 (dd, J = 11.5, 2.6 Hz, 1H), 3.43 (ddd, J = 9.5, 4.3, 2.6
1
H NMR (600 MHz, CDCl
3
13
Hz, 1H), 3.01 (dd, J = 11.5, 4.3 Hz, 1H), 2.81 (s, 3H). C NMR (150 MHz, CDCl
3
) δ = 178.3,
1
1
75.9, 156.6 (d, JC-F = 237.4 Hz), 144.9 (d, J = 2.0 Hz), 119.9(d, J = 7.4 Hz), 116.7(d, J = 23.2
Hz), 115.0(d, J = 21.9 Hz), 113.4 (d, J = 7.6 Hz), 50.8, 44.6, 43.3, 39.7. HRMS (ESI-TOF) calc.
+
for C12
H11 FN
2
O
2
(M+H) : 235.0877, found: 235.0884.
8-Fluoro-2,5-dimethyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3n)
Table 4, entry 14).
(
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5
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6
o
White solid: yield 55.4 mg, 89%; mp 136-138 C; R
f
= 0.23 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.24 - 7.22 (m, 1H), 6.93 - 6.90 (m, 1H), 6.64 - 6.62 (m, 1H),
3.97 (d, J = 9.4 Hz, 1H), 3.51 (dd, J = 11.5, 2.5 Hz, 1H), 3.37 (ddd, J = 9.4, 4.5, 2.5 Hz, 1H), 3.01
1
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
(s, 3H), 2.99 (d, J = 4.5 Hz, 1H), 2.78 (s, 3H). C NMR (150 MHz, CDCl ) δ = 178.4, 176.1,
1
157.4, 155.8 (d, JC-F = 237.1 Hz), 144.8 (d, J = 1.9 Hz), 120.1 (d, J = 7.5 Hz), 116.8(d, J = 23.1
Hz), 114.8(d, J = 21.2 Hz), 113.3 (d, J = 7.5 Hz), 50.9, 43.4, 42.1, 39.7, 25.4. HRMS (ESI-TOF)
+
calc. for C13
H13 FN
2
O
2
(M+H) : 249.1034, found: 249.1036.
2-Ethyl-8-fluoro-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(3o) (Table 4, entry 15).
o
White solid: yield 55.0 mg, 84%; mp 122-124 C; R
f
= 0.30 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.25 - 7.23 (m, 1H), 6.94 - 6.90 (m, 1H), 6.65 - 6.63 (m, 1H),
3.94 (d, J = 9.4 Hz, 1H), 3.56 (m, 2H), 3.49 (dd, J = 11.5, 2.7 Hz, 1H), 3.35 (ddd, J = 9.4, 4.6, 2.7
1
3
Hz, 1H), 3.01 (dd, J = 11.5, 4.6 Hz, 1H), 2.79 (s, 3H), 1.16 (t, J = 7.2 Hz, 3H). C NMR (150
1
MHz, CDCl
3
) δ = 178.1, 175.9, 156.6 (d, JC-F = 237.1 Hz), 144.9 (d, J = 1.7 Hz), 120.3 (d, J =
7.6 Hz), 116.8 (d, J = 23.1 Hz), 114.8 (d, J = 21.8 Hz), 113.2 (d, J = 7.6 Hz), 51.0, 43.3, 42.1, 39.7,
+
34.3, 12.9. HRMS (ESI-TOF) calc. for C14
H
15FN
2
O
2
(M+H) : 263.1190, found: 263.1193.
2-Benzyl-8-fluoro-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(3p) (Table 4, entry 16).
o
White solid: yield 56.1 mg, 69%; mp 123-125 C; R
f
=0.33 (petroleum ether/ethyl acetate 10:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.36 - 7.26 (m, 5H), 7.24 - 7.21 m, 1H), 6.94 - 6.92 (m, 1H), 6.66
- 6.64 (m, 1H), 4.71 (d, J = 14.4 Hz, 1H), 4.65 (d, J = 14.4 Hz, 1H), 3.96 (d, J = 9.4 Hz, 1H), 3.49
(dd, J = 11.5, 2.7 Hz, 1H), 3.37 (ddd, J = 9.4, 4.6, 2.7 Hz, 1H), 3.02 (dd, J = 11.5, 4.6 Hz, 1H),
1
3
1
2.79 (s, 3H). C NMR (150 MHz, CDCl ) δ = 178.0, 175.8, 156.6, (d, JC-F = 237.2 Hz), 144.9 (d,
3
J = 1.8 Hz), 135.5, 128.6, 128.3, 127.8, 120.3 (d, J = 7.6 Hz), 116.9 (d, J = 23.1Hz), 114.9(d, J =
21.8 Hz), 113.2 (d, J = 7.6 Hz), 51.1, 43.5, 42.9, 42.2, 39.6. HRMS (ESI-TOF) calc. for
+
C
19
H17FN
2
O
2
(M+Na) : 347.1166, found: 347.1170.
8-Chloro-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
9
,11
(3q) (Table 4, entry 17).
o
White solid: yield 79.9 mg, 98%; mp 157-159 C; R
f
= 0.29 (petroleum ether/ethyl acetate 3:1);
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H NMR (600 MHz, CDCl
3
) δ = 7.48 - 7.24 (m, 6H), 7.15 (d, J = 8.8 Hz, 1H), 6.64 (d, J = 8.8 Hz,
1H), 4.08 (d, J = 9.6 Hz, 1H), 3.58 (dd, J = 11.5, 2.7 Hz, 1H), 3.52 (ddd, J = 9.6, 4.4, 2.7 Hz, 1H),
1
3
3
3.08 (dd, J = 11.6, 4.4 Hz, 1H), 2.81 (s, 3H). C NMR (150 MHz, CDCl ) δ = 177.2, 175.1, 147.1,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
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131.9, 129.9, 129.0, 128.6, 128.5, 126.3, 124.4, 120.0, 113.7, 50.5, 43.3, 41.9, 39.4.
8-Chloro-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(3r)
(Table 4, entry 18).
o
White solid: yield 60.9 mg, 97%; mp 177-179 C; R
f
= 0.25 (petroleum ether/ethyl acetate 2:1);
1
3
H NMR (600 MHz, CDCl ) δ = 9.56 (br, 1H), 7.40 (d, J = 2.2 Hz, 1H), 7.14 (dd, J = 8.7, 2.2 Hz,
1H), 6.62 (d, J = 8.7 Hz, 1H), 3.95 (d, J = 9.5 Hz, 1H), 3.47 (dd, J = 11.6, 2.7 Hz, 1H), 3.39 (ddd,
1
3
J = 9.5, 4.5, 2.7 Hz, 1H), 2.99 (dd, J = 11.6, 4.5 Hz, 1H), 2.79 (s, 3H). C NMR (150 MHz,
CDCl
3
) δ = 178.8, 176.5, 147.0, 129.7, 128.3, 124.3, 120.1, 113.6, 50.3, 44.4, 43.0, 39.4. HRMS
-
(ESI-TOF) calc. for C12
H10ClN
2
O
2
(M-H) : 249.0425, found: 249.0428.
8-Chloro-2,5-dimethyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3s)
1
6
(Table 4, entry 19).
o
White solid: yield 52.5 mg, 79%; mp 174-177 C; R
f
= 0.30 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.46 (d, J = 2.1 Hz, 1H), 7.15 (dd, J = 8.7, 2.1 Hz, 1H), 6.62 (d, J
= 8.7 Hz, 1H), 3.95 (d, J = 9.4 Hz, 1H), 3.53 (dd, J = 11.6, 2.5 Hz, 1H), 3.37 (ddd, J = 9.4, 4.5, 2.5
1
3
3
Hz, 1H), 3.03 (dd, J = 11.6, 4.5 Hz, 1H), 3.00 (s, 3H), 2.79 (s, 3H). C NMR (150 MHz, CDCl ) δ
= 178.2, 176.1, 147.0, 129.8, 128.4, 124.4, 120.2, 113.7, 50.4, 43.3, 41.8, 39.4, 25.4.
8-Chloro-2-ethyl-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(3t) (Table 4, entry 20).
o
White solid: yield 51.1 mg, 73%; mp 121-123 C; R
f
= 0.29 (petroleum ether/ethyl acetate 4:1);
1
3
H NMR (600 MHz, CDCl ) δ = 7.47 (d, J = 2.3 Hz, 1H), 7.16 (dd, J = 8.7, 2.3 Hz, 1H), 6.63 (d, J
= 8.7 Hz, 1H), 3.93 (d, J = 9.4 Hz, 1H), 3.57 - 3.56 (m, 2H), 3.50 (dd, J = 11.5, 2.8 Hz, 1H), 3.35
(ddd, J = 9.4, 4.6, 2.8 Hz, 1H), 3.04 (dd, J = 11.5, 4.6 Hz, 1H), 2.80 (s, 3H), 1.16 (t, J = 7.2 Hz,
1
3
3H). C NMR (150 MHz, CDCl
3
) δ = 177.9, 175.8, 147.0, 129.8, 128.3, 124.4, 120.3, 113.6, 50.5,
+
43.2, 41.7, 39.4, 34.4, 12.9. HRMS (ESI-TOF) calc. for C14
279.0901.
H15ClN
2
O
2
(M+H) : 279.0895, found:
2-Benzyl-8-chloro-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
3u) (Table 4, entry 21).
(
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6
o
White solid: yield 68.2 mg, 80%; mp 141-143 C; R
f
= 0.34 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.47 (d, J = 2.0 Hz, 1H), 7.35 - 7.24 (m, 5H), 7.17 (dd, J = 8.7,
2.0 Hz, 1H), 6.64 (d, J = 8.7 Hz, 1H), 4.70 (d, J = 14.3 Hz, 1H), 4.64 (d, J = 14.3 Hz, 1H), 3.93 (d, J
= 9.4 Hz, 1H), 3.49 (dd, J = 11.5, 2.7 Hz, 1H), 3.36 (ddd, J = 9.4, 4.6, 2.7 Hz, 1H), 3.05 (dd, J =
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
3
11.5, 4.6 Hz, 1H), 2.80 (s, 3H). C NMR (150 MHz, CDCl ) δ = 177.9, 175.7, 147.1, 135.5, 129.9,
128.6, 128.4, 128.3, 127.9, 124.5, 120.3, 113.6, 50.7, 43.4, 42.9, 41.9, 39.4. HRMS (ESI-TOF)
+
calc. for C19
H17ClN
2
O
2
(M+Na) : 363.0871, found: 363.0876.
8-Bromo-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
9
,11,12
(3v) (Table 4, entry 22).
o
White solid: yield 89.0 mg, 96%; mp 157-159 C; R
f
= 0.28 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.66 - 7.65 (m, 1H), 7.46 - 7.44 (m, 2H), 7.41 - 7.37 (m, 1H),
7.36 - 7.32 (m, 1H), 7.32 - 7.25 (m, 2H), 6.63 - 6.61 (m, 1H), 4.09 (d, J = 9.5 Hz, 1H), 3.61 (ddd,
J = 11.3, 4.9, 2.8 Hz, 1H), 3.53 (dd, J = 9.5, 2.8 Hz 1H), 3.11 (dd, J = 11.3, 4.9 Hz, 1H), 2.83 (s,
1
3
3
3H). C NMR (150 MHz, CDCl ) δ = 177.2, 175.1, 147.5, 132.7, 132.0, 131.4, 129.0, 128.6,
126.3, 120.5, 114.2, 111.6, 50.4, 43.3, 41.8, 39.4.
8-Bromo-2,5-dimethyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3w)
1
0,11
(Table 4, entry 23).
o
White solid: yield 66.1 mg, 86%; mp 187-189 C; R
f
= 0.26 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.60 (s, 1H), 7.28 (d, J = 8.7 Hz, 1H), 6.57 (d, J = 8.7 Hz, 1H),
3.95 (d, J = 9.4 Hz, 1H), 3.53 (dd, J = 11.6, 2.2 Hz, 1H), 3.37 (ddd, J = 9.4, 4.5, 2.2 Hz, 1H), 3.04
1
3
(dd, J = 11.6, 4.5 Hz, 1H), 3.00 (s, 3H), 2.79 (s, 3H). C NMR (150 MHz, CDCl
176.1, 147.4, 132.6, 131.3, 120.6, 114.1, 111.6, 50.3, 43.3, 41.7, 39.4, 25.4.
8-Bromo-2-ethyl-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
3x) (Table 4, entry 24).
White solid: yield 72.8mg, 90%; mp 128-130 C; R
3
) δ = 178.2,
(
o
f
= 0.31 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.58 - 7.57 (m, 1H), 7.28 - 7.27 (m, 1H), 6.57 – 6.56 (m, 1H),
3.91 (d, J = 9.4 Hz, 1H), 3.59 – 3.51 (m, 2H), 3.48 (dd, J = 11.6, 2.7 Hz, 1H), 3.34 (ddd, J = 9.4,
1
3
4.6, 2.7 Hz, 1H), 3.03 (dd, J = 11.6, 4.6 Hz, 1H), 2.78 (s, 3H), 1.14 (t, J = 7.2 Hz, 3H). C NMR
(150 MHz, CDCl
3
) δ = 177.9, 175.8, 147.4, 132.6, 131.2, 120.8, 114.1, 111.5, 50.4, 43.2, 41.6,
+
3
9.4, 34.3, 12.9. HRMS (ESI-TOF) calc. for C14
H15BrN
2
O
2
(M+Na) : 345.0209, found: 345.0211.
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8-Bromo-2-(tert-butyl)-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-di
one (3y) (Table 4, entry 25).
o
White solid: yield 53.8 mg, 61%; mp 115-117 C; R
f
=0.29 (petroleum ether/ethyl acetate 10:1);
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
H NMR (600 MHz, CDCl
3
) δ = 7.57 - 7.56 (m, 1H), 7.29 - 7.28 (m, 1H), 6.59 - 6.57 (m, 1H),
3.79 (d, J = 9.7 Hz, 1H), 3.43 (dd, J = 11.5, 3.1 Hz, 1H), 3.22 (ddd, J = 9.7, 4.6, 3.1 Hz, 1H), 3.01
1
3
3
(dd, J = 11.5, 4.6 Hz, 1H), 2.80 (s, 3H), 1.56 (s, 9H). C NMR (150 MHz, CDCl ) δ = 179.0,
177.0, 147.3, 132.7, 131.1, 121.1, 114.0, 111.3, 58.9, 50.6, 42.8, 41.8, 39.4, 28.3. HRMS
+
(ESI-TOF) calc. for C16
H19BrN
2
O
2
(M+Na) : 373.0522, found: 373.0525.
2-Benzyl-8-bromo-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
1
1
(3z) (Table 4, entry 26).
o
White solid: yield 72.5 mg, 75%; mp 148-150 C; R
f
= 0.23 (petroleum ether/ethyl acetate 3:1);
1
H NMR (600 MHz, CDCl
3
) δ = 7.60 - 7.59 (m, 1H), 7.35 - 7.25 (m, 6H), 6.59 - 6.58 (m, 1H),
4.70 (d, J = 14.3 Hz, 1H), 4.64 (d, J = 14.3 Hz, 1H), 3.93 (d, J = 9.4 Hz, 1H), 3.49 (dd, J = 11.5, 2.8
1
3
Hz, 1H), 3.37 (ddd, J = 9.4, 4.6, 2.8 Hz, 1H), 3.05 (dd, J = 11.5, 4.6 Hz, 1H), 2.80 (s, 3H).
C
NMR (150 MHz, CDCl ) δ = 177.8, 175.7, 147.5, 135.5, 132.7, 131.3, 128.6, 128.3, 127.9, 120.7,
3
114.1, 111.7, 50.6, 43.4, 42.9, 41.7, 39.3.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
Materials, analytical methods, extra information for optimization of reaction conditions,
1
13
UV-visible absorption of chlorophyll, gum arabic and lactose, H NMR, C NMR and HRMS
spectra.
AUTHOR INFORMATION
Corresponding Authors
*E-mail for Y.-H.H.: heyh@swu.edu.cn ;
*E-mail for Z.G.: guanzhi@swu.edu.cn.
Notes
The authors declare no competing financial interest.
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Acknowledgements
This work was financially supported by the National Natural Science Foundation of China (No.
1472152 and No.21672174), and the Basic and Frontier Research Project of Chongqing
cstc2015jcyjBX0106).
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