An efficient one-pot three-component synthesis of tetrahydrofuro[3,4-b] quinoline-1,8(3H,4H)-dione derivatives catalyzed by L-proline

Article abstract of DOI:10.1002/jhet.782

L-Proline is found to be an efficient catalyst for the synthesis of tetrahydrofuro[3,4-b]quinoline- 1,8(3H,4H)-dione derivatives. This protocol is novel and has the advantages of mild condition, high yield, and easy operation.

Full text of DOI:10.1002/jhet.782

January 2012
An Efficient One-Pot Three-Component Synthesis of
Tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H)-dione Derivatives
Catalyzed by L-Proline
125
Chun-Ling Shi,a Hui Chen,b and Daqing Shib*
aSchool of Chemistry and Chemical Engineering, Xuzhou Institute of Technology, Xuzhou
221008, People’s Republic of China
bCollege of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Organic
Synthesis of Jiangsu Province, Soochow University, Suzhou 215123, People’s Republic of China
*E-mail: dqshi@suda.edu.cn
Received September 20, 2010
DOI 10.1002/jhet.782
Published online 15 October 2011 in Wiley Online Library (wileyonlinelibrary.com).
L-Proline is found to be an efficient catalyst for the synthesis of tetrahydrofuro[3,4-b]quinoline-
1,8(3H,4H)-dione derivatives. This protocol is novel and has the advantages of mild condition, high
yield, and easy operation.
J. Heterocyclic Chem., 49, 125 (2012).
INTRODUCTION
Alzheimer’s disease, and chemosensitizer in tumor ther-
apy [24–27]. These examples clearly indicate the
remarkable potential of novel dihydropyridine deriva-
tives as a source of valuable drug candidates. Among
these compounds, furo[3,4-b]quinoline-1,8(3H,4H)-dione
(podophyllotoxin) derivatives, which inhibits microtu-
bule assembly as an antitumor ligand, have attracted
attention in recent decade [28–30]. Extensive structural
modifications have been performed to obtain more
potent and less toxic anticancer agents [31–33]. For
example, Takeya and coworkers [34,35] reported the
synthesis of aza-podophyllotoxin via condensation,
cyclization, and reduction. This method was less effi-
cient. Tratrat et al. [36] also reported the synthesis of
aza-podophyllotoxin by one-pot reaction of aldehyde,
tetronic acid, and aniline in refluxing ethanol with the
limitation that aniline must be substituted in the metapo-
sition by electron-donating groups. Tu et al. [37] also
reported a three-component reaction for one-pot synthe-
sis of 4-aza-podophyllotoxin derivatives in water under
microwave irradiation conditions, with the wide applica-
ble scope of aldehydes and anilines. The main drawback
of this method is the need of a special reaction instru-
ment and high temperature.
The replacement of current chemical process with
more environmentally benign alternatives is an increas-
ingly attractive goal in organic synthesis. Recently,
organic reaction catalyzed by small organic molecules
has been studied more and more extensively. A lot of
small organic molecules such as cinchona alkaloids, L-
proline, and its derivatives have been used in various
transformations with excellent yields [1–3]. Direct cata-
lytic asymmetric aldol [4,5], Mannich [6,7], Michael
[8,9], Diels-Alder [10,11], a-amination reactions, and
Knoevenagel-type reaction [12] using L-proline as a cat-
alyst have also been reported. Recently, L-proline and its
derivatives have been used in multicomponent unsym-
metrical Biginelli [13,14] and Hantzsch reactions[15].
More recently, we have reported the synthesis of furo[3-
,40:5,6]pyrido[2,3-c]pyrazole derivatives catalyzed by
organocatalysts [16] and 3,30-benzylidenebis[4-hydroxy-
6-methylpyridin-2(1H)-one] derivatives catalyzed by
L-proline [17].
1,4-Dihydropyridine compounds are well known as
calcium channel modulators and have emerged as one of
the most important classes of drugs for the treatment of
cardiovascular diseases [18,19]. 1,4-Dihydropyridine
derivatives possess a variety of biological activities such
as vasodilator, bronchodilator, antitumor, and antidia-
betic activity [20–23]. Extensive studies have revealed
that these compounds exhibit various medicinal func-
tions such as neuroprotectant, platelet antiaggregatory
activity, cerebral antischemic activity in the treatment of
RESULTS AND DISCUSSION
As a consequence of our interest in organic synthesis
catalyzed by L-proline, we describe a mild and highly
efficient protocol for the synthesis of tetrahydrofuro[3,4-
C
V
2011 HeteroCorporation

126
C.-L. Shi, H. Chen, and D. Shi
Vol 49
Scheme 1
Table 2
Temperature optimization for synthesis of 4d in EtOH catalyzed
by 10 mol % L-proline.
Reaction
temperature (ꢀC)
Reaction
time (h)
Isolated
yield (%)
Entries
1
2
3
4
r.t.
40
60
80
5
4
30
59
72
95
b]quinoline-1,8(3H,4H)-dione derivatives via three-com-
ponent reaction of 5,5-dimethyl-3-aminocyclohex-2-
enone 1, aldehyde 2, and tetronic acid 3 in EtOH
(2 mL) catalyzed by 10 mol % L-proline (Scheme 1).
First, the synthesis of compound 4d was chosen as a
model to find an appropriate solvent. The 10 mol % L-pro-
line catalyzed reaction of 3-(4-fluorophenylamino)-5,5-
dimethylcyclohex-2-enone 1d, 4-methoxybenzaldehyde
2d, and tetronic acid 3 was examined using EtOH, DMF,
CH3CN, HOAc, CHCl3, and H2O as solvents, respec-
tively. The results are summarized in Table 1. It can be
seen from Table 1 that the reaction using EtOH as solvent
resulted in the excellent yield and shortest time. There-
fore, EtOH was chosen as the solvent of this reaction.
To optimize the reaction temperature, the synthesis
of compound 4d was carried out in EtOH at r.t, 40,
60, and 80ꢀC, respectively. The results are shown in
Table 2. We found that the reaction time was shortest
and yield highest at 80ꢀC. Therefore, the most reaction
temperature should be 80ꢀC.
3
1.5
significantly. Therefore, it was concluded that L-proline
was the best among the six catalysts in this study.
To optimize the catalyst loading, 5, 10, 15, and 20
mol % of L-proline was tested, respectively. The results
are summarized in Table 4. A 10-mol % loading of L-
proline was sufficient to push the reaction forward, and
5 mol % of L-proline was not enough. Higher amounts
of L-proline did not lead to significant change in the
reaction yields.
Under these optimized reaction conditions (2 mL
EtOH, 80ꢀC, 10 mol % L-proline), a series of tetrahydro-
furo[3,4-b]quinoline-1,8(3H,4H)-dione derivatives (4)
were synthesized. The results are summarized in Table 5.
As shown in Table 5, this protocol can be applied not
only to the aromatic aldehydes with either electron-with-
drawing groups (such as nitro and halide groups) or
electron-donating groups (such as hydroxyl and alkoxyl
groups) but also to aliphatic aldehydes under the same
conditions. The substituted groups on nitrogen atom
may be aromatic and aliphatic. Therefore, this reaction
can be applied in a wide range.
The catalytic efficiency of other organocatalysts in
this reaction was also studied. In all cases, 10 mol % of
the catalyst was used, and the reaction was carried out
in refluxing ethanol. As shown in Table 3, the catalytic
effects of 5a, 5b, and 5c were similar, whereas 5d, 5e,
and 5f gave lower yields. The presence of a secondary
nitrogen and carboxylic acid at 2-position in the cata-
lysts led to good yields of products, whereas DL-phenyl-
glycine (5d) with a primary amino group, and (þ)-cin-
chonine (5e), cinchonidine (5f) with a tertiary amino
group, respectively, gave lower yields. These results
indicate that the presence of secondary nitrogen may be
essential for better catalytic activity. Replacing CH2
(5a) by S (5b) and with CHOH (5c) did not affect yields
In conclusion, we have developed a novel three-
component reaction of 5,5-dimethyl-3-aminocyclohex-2-
enone, aldehyde, and tetronic acid in EtOH (2 mL)
catalyzed by 10 mol % L-proline for the synthesis of
tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H)-dione deriva-
tives. This new method has the advantages of good
yields, convenient procedure and the use of environmen-
tally friendly catalyst and solvent.
EXPERIMENTAL
Melting points are uncorrected. Infrared spectra were
recorded on a Varian 1000 FTIR spectrometer in KBr with
Table 1
Solvent optimization for the synthesis of 4d catalyzed by
10 mol % L-proline.
1
absorption in cmꢁ1. H NMR spectra were recorded on a Var-
ian Invoa-400 MHz superconductive NMR spectrometer as
DMSO-d6 solution. J values are in Hz. Chemical shifts are
expressed in d downfield from internal tetramethylsilane. Mass
spectra were obtained using TOF-MS instrument.
Typical procedure for the synthesis of tetrahydro-
furo[3,4-b]quinoline-1,8(3H,4H)-diones 4. A mixture of 5,5-
dimethyl-3-aminocyclohex-2-enone 1 (1 mmol), aldehyde 2 (1
mmol), and tetronic acid 3 (2 mmol) was suspended in EtOH
(2 mL) using 10 mol % L-proline (0.0115 g) as catalyst and
Entries Solvents Temperature (ꢀC) Time (h) Yield (%)
1
2
3
4
5
6
EtOH
DMF
CH3CN
HOAc
CHCl3
H2O
80
100
70
1.5
1.5
3
95
78
79
78
82
60
100
65
100
2.5
2.5
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2012
An Efficient One-Pot Three-Component Synthesis of Tetrahydrofuro[3,4-b]
quinoline-1,8(3H,4H)-dione Derivatives Catalyzed by L-Proline
127
Table 3
Table 4
Catalytic efficiency of different organocatalysts over the reaction
synthesizing 4da
The effect about amounts of L-proline for the synthesis of 4d in
ethanol at 80ꢀC.
Reaction
time (h)
Isolated
yield (%)
Amounts of L-proline
(mol %)
Entries
1
Catalysts
None
Entries
Time (h)
Yield (%)
2
68
95
1
2
3
4
5
0
5
3
2
61
83
95
95
96
10
15
20
1.5
1.5
1.5
1.5
2
3
1.5
1.5
2
90
87
63
2.18–2.23 (2H, m, CH2), 2.26 (3H, s, CH3), 4.51 (1H, d, J ¼
16.4 Hz, CH2), 4.57 (1H, d, J ¼ 16.4 Hz, CH2), 4.73 (1H, s,
CH), 7.09 (2H, d, J ¼ 7.6 Hz, ArH), 7.22 (2H, d, J ¼ 7.6 Hz,
ArH), 7.44 (2H, t, J ¼ 8.0 Hz, ArH), 7.62–7.65 (2H, m, ArH);
IR (KBr, m, cmꢁ1): 3070, 2981, 2880, 1751, 1687, 1578, 1510,
1366, 1223; HRMS [Found: m/z 417.1738 (Mþ), Calcd for
C26H24NO3F: M, 417.1740].
9-(4-Chlorophenyl)-4-(4-fluorophenyl)-6,6-dimethyl-5,6,7,9-
tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H)-dione (4b). M.p.
297–299ꢀC; H NMR (DMSO-d6, d, ppm): 0.85 (3H, s, CH3),
4
5
1
0.93 (3H, s, CH3), 2.03–2.10 (2H, m, CH2), 2.19–2.25 (2H, m,
CH2), 4.52 (1H, d, J ¼ 16.4Hz, CH2), 4.59 (1H, d, J ¼ 16.4
Hz, CH2), 4.78 (1H, s, CH), 7.35 (4H, dd, J1 ¼ 8.4 Hz, J2 ¼
15.2 Hz, ArH), 7.44 (2H, s, ArH), 7.65 (2H, s, ArH); IR (KBr,
m, cmꢁ1): 3298, 3062, 2960, 2882, 1754, 1689, 1580, 1510,
1367, 1224; HRMS [Found: m/z 437.1184 (Mþ), Calcd for
C25H21NO3F35Cl: M, 437.1194].
6
2
51
9-(4-Bromophenyl)-4-(4-fluorophenyl)-6,6-dimethyl-5,6,7,9-
tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H)-dione (4c). M.p.
1
283–285ꢀC; H NMR (DMSO-d6, d, ppm): 0.86 (3H, s, CH3),
0.93 (3H, s, CH3), 2.03–2.10 (2H, m, CH2), 2.19–2.25 (2H, m,
CH2), 4.52 (1H, d, J ¼ 16.4 Hz, CH2), 4.59 (1H, d, J ¼ 16.4
Hz, CH2), 4.76 (1H, s, CH), 7.31 (2H, d, J ¼ 8.4 Hz, ArH),
7.44–7.48 (4H, m, ArH), 7.66 (2H, s, ArH); IR (KBr, m,
cmꢁ1): 3081, 2960, 2881, 1755, 1690, 1578, 1510, 1367,
1224; HRMS [Found: m/z 481.0692 (Mþ), Calcd for
C25H21NO3F79Br: M, 481.0689].
7
2
49
Table 5
Synthesis of N-substituted furo[3,4-b]quinoline derivatives catalyzed
by 10 mol% L-proline in ethanol at 80ꢀC.
a Reaction conditions: 3-(4-fluorophenylamino)-5,5-dimethylcyclo-
hex-2-enone (1 mmol), 4-methoxybenzaldehyde (1 mmol), and tetronic
acid (1 mmol), catalyst 10 mol %, EtOH, 80ꢀC
Time Yield
(%)
Products
R1
R
(h)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4-FC6H4
4-FC6H4
4-FC6H4
4-CH3C6H4
4-ClC6H4
4-BrC6H4
2
92
91
93
95
91
95
94
91
94
92
93
2
stirred at 80ꢀC for 1.5–3 h. The reaction was monitored by
TLC. After completion of the reaction, the reaction mixture
was allowed to cool to room temperature and was poured into
the water. The precipitate was collected by suction and recrys-
tallized from ethanol to give products 4 with high purity.
Spectroscopy data. 4-(4-Fluorophenyl)-6,6-dimethyl-9-p-
tolyl-5,6,7,9-tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H)-dione
(4a). M.p. 281–283ꢀC; 1H NMR (DMSO-d6, d, 400 ppm):
0.86 (3H, s, CH3), 0.94 (3H, s, CH3), 1.99–2.08 (2H, m, CH2),
1.5
1.5
3
1.5
2
4-FC6H4
4-CH3OC6H4
3,4,5-(CH3O)3C6H2
4-CH3C6H4
4-CH3OC6H4
n-Propyl
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
3-Cl-4-CH3C6H3
n-Butyl
3
4-BrC6H4
4-HOC6H4
4-BrC6H4
2
4j
4k
3
2.5
n-Butyl
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

128
C.-L. Shi, H. Chen, and D. Shi
Vol 49
(1H, m, ArH), 7.73–7.83 (1H, m, ArH); IR (KBr, m, cmꢁ1):
2959, 2933, 1749, 1683, 1583, 1494, 1366, 1270, 1194;
4-(4-Fluorophenyl)-9-(4-methoxyphenyl)-6,6-dimethyl-5,6,7,9-
tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H)-dione (4d). M.p.
[Found: m/z 511.0560 (Mþ),
Calcd
for
1
266–268ꢀC; H NMR (DMSO-d6, d, ppm): 0.86 (3H, s, CH3),
HRMS
C26H23NO335Cl79Br: M, 511.0550].
0.93 (3H, s, CH3), 2.01–2.05 (2H, m, CH2), 2.19–2.25 (2H, m,
CH2), 3.72 (3H, s, OCH3), 4.51 (1H, d, J ¼ 15.6 Hz, CH2),
4.58 (1H, d, J ¼ 16.0 Hz, CH2), 4.72 (1H, s, CH), 6.84 (2H,
d, J ¼ 8.4 Hz, ArH), 7.25 (2H, d, J ¼ 8.4 Hz, ArH), 7.42–
7.46 (2H, m, ArH), 7.62–7.65 (2H, m, ArH); IR (KBr, m,
cmꢁ1): 3070, 2962, 2888, 1751, 1685, 1578, 1510, 1365,
1223; HRMS [Found: m/z 433.1708 (Mþ), Calcd for
C26H24NO4F: M, 433.1689].
6,6-Dimethyl-4-p-tolyl-9-(3,4,5-trimethoxyphenyl)-5,6,7,9-tet-
rahydrofuro[3,4-b]quinoline-1,8(3H,4H)-dione (4e). M.p. 221–
223ꢀC; 1H NMR (DMSO-d6, d, ppm): 0.93 (6H, d, J ¼ 4.8
Hz, 2 ꢂ CH3), 2.02–2.13 (2H, m, CH2), 2.23–2.28 (2H, m,
CH2), 2.40 (3H, s, CH3), 3.62 (3H, s, OCH3), 3.77 (6H, s, 2 ꢂ
OCH3), 4.50 (1H, d, J ¼ 16.4 Hz, CH2), 4.55 (1H, d, J ¼ 16.4
Hz, CH2), 4.72 (1H, s, CH), 6.56 (2H, s, ArH), 7.40 (4H, s,
ArH); IR (KBr, m, cmꢁ1): 2962, 1750, 1679, 1589, 1511,
1422, 1367, 1227, 1124, 1001; HRMS [Found: m/z 489.2156
(Mþ), Calcd for C29H31NO6: M, 489.2151].
6,6-Dimethyl-4,9-dip-tolyl-5,6,7,9-tetrahydrofuro[3, 4-b]quino-
line-1,8(3H,4H)-dione (4f). M.p. 263–264ꢀC; 1H NMR
(DMSO-d6, d, ppm): 0.83 (3H, s, CH3), 0.91 (3H, s, CH3),
2.00–2.06 (2H, m, CH2), 2.18–2.22 (2H, m, CH2), 2.25 (3H, s,
CH3), 2.40 (3H, s, CH3), 4.48 (1H, d, J ¼ 16.0 Hz, CH2), 4.56
(1H, d, J ¼ 15.6 Hz, CH2), 4.71 (1H, s, CH), 7.08 (2H, d, J ¼
8.0 Hz, ArH), 7.20 (2H, d, J ¼ 8.0 Hz, ArH), 7.40 (4H, d, J
¼ 6.0 Hz, ArH); IR (KBr, m, cmꢁ1): 2957, 2932, 1754, 1682,
1577, 1510, 1369, 1274; HRMS [Found: m/z 413.2010 (Mþ),
Calcd for C27H27NO3: M, 413.1991].
4-Butyl-9-(4-hydroxyphenyl)-6,6-dimethyl-5,6,7,9-tetrahydro-
furo[3,4-b]quinoline-1,8(3H,4H)-dione (4j). M.p. 237–238ꢀC;
1H NMR (DMSO-d6, d, ppm): 0.94–0.97 (6H, m, 2 ꢂ CH3),
1.06 (3H, s, CH3), 1.33–1.39 (2H, m, CH2), 1.61–1.64 (2H, m,
CH2), 2.07 (1H, d, J ¼ 16.0 Hz, CH2), 2.21 (1H, d, J ¼ 16.4
Hz, CH2), 2.58 (1H, d, J ¼ 17.6 Hz, CH2), 2.66 (1H, d, J ¼
17.6 Hz, CH2), 3.40–3.44 (1H, m, CH2), 3.61–3.68 (1H, m,
CH2), 4.58 (1H, s, CH), 5.01 (1H, d, J ¼ 16.0 Hz, CH2), 5.09
(1H, d, J ¼ 15.6 Hz, CH2), 6.60 (2H, d, J ¼ 8.0 Hz, ArH),
6.93 (2H, d, J ¼ 8.4 Hz, ArH), 9.11 (1H, br., s, OH); IR
(KBr, m, cmꢁ1): 3473, 3158, 2955, 1750, 1686, 1583, 1543,
1511, 1428, 1392, 1220; HRMS [Found: m/z 381.1949 (Mþ),
Calcd for C23H27NO4: M, 381.1940].
9-(4-Bromophenyl)-4-butyl-6,6-dimethyl-5,6,7,9-tetrahydro-
furo[3,4-b]quinoline-1,8(3H,4H)-dione (4k). M.p. 249–250ꢀC;
1H NMR (DMSO-d6, d, ppm): 0.94–0.97 (6H, m, 2 ꢂ CH3),
1.07 (3H, s, CH3), 1.31–1.40 (2H, m, CH2), 1.59–1.69 (2H, m,
CH2), 2.08 (1H, d, J ¼ 16.0 Hz, CH2), 2.22 (1H, d, J ¼ 15.6
Hz, CH2), 2.61 (1H, d, J ¼ 17.6 Hz, CH2), 2.68 (1H, d, J ¼
17.2 Hz, CH2), 3.38–3.47 (1H, m, CH2), 3.59–3.67 (1H, m,
CH2), 4.67 (1H, s, CH), 5.05 (1H, d, J ¼ 16.0 Hz, CH2), 5.11
(1H, d, J ¼ 16.4 Hz, CH2), 7.11 (2H, d, J ¼ 8.4 Hz, ArH),
7.43 (2H, d, J ¼ 8.4 Hz, ArH); IR (KBr, m, cmꢁ1): 2956,
1755, 1675, 1643, 1568, 1429, 1368, 1219, 1147; HRMS
[Found: m/z 443.1094 (Mþ), Calcd for C23H26NO379Br: M,
443.1096].
Acknowledgments. The authors are grateful to the Scientific
Research Item of Xuzhou Institute of Technology (grant No.
XKY2009114) for financial support.
9-(4-Methoxyphenyl)-6,6-dimethyl-4-p-tolyl-5,6,7,9-tetrahydro-
furo[3,4-b]quinoline-1,8(3H,4H)-dione (4g). M.p. 254–256ꢀC
1
(Lit 256–257ꢀC38); H NMR (DMSO-d6, d, ppm): 0.83 (3H, s,
CH3), 0.91 (3H, s, CH3), 1.99–2.06 (2H, m, CH2), 2.18–2.25
(2H, m, CH2), 2.40 (3H, s, CH3), 3.71 (3H, s, OCH3), 4.48
(1H, d, J ¼ 16.4 Hz, CH2), 4.56 (1H, d, J ¼ 16.0 Hz, CH2),
4.70 (1H, s, CH), 6.84 (2H, d, J ¼ 8.8 Hz, ArH), 7.23 (2H, d,
J ¼ 8.4 Hz, ArH), 7.40 (4H, d, J ¼ 6.0 Hz, ArH); IR (KBr, m,
cmꢁ1): 2956, 2937, 1753, 1681, 1579, 1509, 1371, 1244,
1026; HRMS [Found: m/z 429.1926 (Mþ), Calcd for
C27H27NO4: M, 429.1940].
6,6-Dimethyl-9-propyl-4-p-tolyl-5,6,7,9-tetrahydrofuro[3,4-
b]-quinoline-1,8(3H,4H)-dione (4h). M.p. 213–215ꢀC; 1H
NMR (DMSO-d6, d, ppm): 0.87 (3H, t, J ¼ 7.6 Hz, CH3),
0.93 (6H, d, J ¼ 6.0Hz, 2 ꢂ CH3), 1.26–1.33 (2H, m, CH2),
1.43–1.55 (2H, m, CH2), 1.92 (1H, d, J ¼ 17.6 Hz, CH2), 2.15
(1H, d, J ¼ 17.2 Hz, CH2), 2.19–1.29 (2H, m, CH2), 2.39 (3H,
s, CH3), 3.77 (1H, t, J ¼ 4.4 Hz, CH), 4.43 (1H, d, J ¼ 16.4
Hz, CH2), 4.52 (1H, d, J ¼ 16.0 Hz, CH2), 7.27–7.29 (1H, m,
ArH), 7.36 (3H, d, J ¼ 8.0 Hz, ArH); IR (KBr, m, cmꢁ1):
3256, 2982, 2869, 1745, 1679, 1575, 1511, 1422, 1373, 1232;
HRMS [Found: m/z 365.1973 (Mþ), Calcd for C23H27NO3: M,
365.1991].
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1
272–274ꢀC; H NMR (DMSO-d6, d, ppm): 0.85 (3H, s, CH3),
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An Efficient One-Pot Three-Component Synthesis of Tetrahydrofuro[3,4-b]
quinoline-1,8(3H,4H)-dione Derivatives Catalyzed by L-Proline
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