Cerium salts in the oxidative free radical reactions between 2-amino-1,4-naphthoquinones and β-dicarbonyl compounds

Article abstract of DOI:10.1016/S0040-4020(02)00864-5

The oxidative free radical reactions between 2-amino-1,4-naphthoquinones and β-dicarbonyl compounds mediated by cerium(IV) salts are described. In contrast to those mediated by manganese(III) acetate, the cerium(IV) mediated free radical reaction provides a novel method for the synthesis of benzo[f]indole-4,9-diones exclusively. This high selectivity is due to the strong oxaphilicity of the cerium salts.

Full text of DOI:10.1016/S0040-4020(02)00864-5

Tetrahedron 58 (2002) 7625–7633
Cerium salts in the oxidative free radical reactions between
2-amino-1,4-naphthoquinones and b-dicarbonyl compounds
*
Chih-Chung Tseng, Yi-Lung Wu and Che-Ping Chuang
Department of Chemistry, National Cheng Kung University, Tainan 70101, Taiwan, ROC
Received 11 March 2002; revised 20 June 2002; accepted 18 July 2002
Abstract—The oxidative free radical reactions between 2-amino-1,4-naphthoquinones and b-dicarbonyl compounds mediated by
cerium(IV) salts are described. In contrast to those mediated by manganese(III) acetate, the cerium(IV) mediated free radical reaction
provides a novel method for the synthesis of benzo[ f]indole-4,9-diones exclusively. This high selectivity is due to the strong oxaphilicity of
the cerium salts. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
nature.2,3 The oxidative addition of electrophilic carbon-
centered radicals to alkenes mediated by metal salts has
received considerable attention in the construction of
carbon–carbon bonds. Among these, manganese(III)
acetate and cerium(IV) ammonium nitrate have been used
most efficiently.1d–f,4,5 These reactions can be performed
Free radical reactions have become increasingly important
in organic synthesis in the last two decades.1 Compounds
containing the quinone group represent an important class of
biologically active molecules that are widespread in
Table 1. Free radical reactions of 2-amino-1,4-naphthoquinones
Entry
Quinone
Cerium(IV) salt
b-Dicarbonyl compound
Reaction time
Product (yield (%))
1
2
3
4
5
6
7
8
1a: R¼H
CAN
Ce(SO4)2
CAN
Ce(SO4)2
CAN
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
CAN
2a: R1¼Me, R2¼Me
2b: R1¼Et, R2¼Et
2c: R1¼i-Pr, R2¼i-Pr
40 min
3.5 h
40 min
3.5 h
40 min
3.5 h
3 h
3.5 h
3.5 h
3.5 h
3.5 h
3.5 h
30 min
3 h
40 min
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3a (76)
3a (77)
3b (53)
3b (67)
3c (39)
3c (62)
3d (64)
3e (73)
3f (57), 4a (18)
3g (61)
3h (57)
3i (60)
3j (59)
3j (76)
3k (61)
3k (69)
3l (73)
3m (61)
3n (64)
3o (58)
3p (52)
3q (66)
3r (45)
3s (44)
3t (23)
22a (48)
22b (31)
22c (52)
22d (37)
1a: R¼H
1a: R¼H
1a: R¼H
2d: R1¼Me, R2¼Ph
2e: R1¼Me, R2¼t-Bu
2f: R1¼Me, R2¼i-Bu
2a: R1¼Me, R2¼Me
2b: R1¼Et, R2¼Et
1a: R¼H
9
1a: R¼H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
1b: R¼p-Tolyl
1b: R¼p-Tolyl
1c: R¼p-Tolyl
1a: R¼H
2d: R1¼Me, R2¼Ph
2g: R1¼Me, R2¼OEt
Ce(SO4)2
CAN
1b: R¼p-Tolyl
2g: R1¼Me, R2¼OEt
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
Ce(SO4)2
1c: R¼Pr
2g: R1¼Me, R2¼OEt
2g: R1¼Me, R2¼OEt
2h: R1¼Pr, R2¼OEt
2i: R1¼i-Pr, R2¼OMe
2j: R1¼Ph, R2¼OEt
2k: R1¼MeOCH2, R2¼OMe
2h: R1¼Pr, R2¼OEt
2i: R1¼i-Pr, R2¼OMe
2j: R1¼Ph, R2¼OEt
2a: R1¼Me, R2¼Me
2d: R1¼Me, R2¼Ph
2g: R1¼Me, R2¼OEt
2h: R1¼Pr, R2¼OEt
1d: R¼i-Pr
1a: R¼H
1a: R¼H
1a: R¼H
1a: R¼H
1b: R¼p-Tolyl
1b: R¼p-Tolyl
1b: R¼p-Tolyl
21a: Ar¼Ph
21a: Ar¼Ph
21a: Ar¼Ph
21a: Ar¼Ph
4.5 h
5.5 h
6.5 h
5 h
3.5 h
5 h
5 h
Keywords: cerium salts; free radical; 2-amino-1,4-naphthoquinones; b-dicarbonyl compounds.
*
Corresponding author. Fax: þ886-6-2740552; e-mail: cpchuang@mail.ncku.edu.tw
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00864-5

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C.-C. Tseng et al. / Tetrahedron 58 (2002) 7625–7633
Scheme 1.
intermolecularly or intramolecularly. The free radical
reaction of 1,4-naphthoquinone derivatives has been
reported.5c–i,6 In this report, we wish to describe our results
on the reactions between 2-amino-1,4-naphthoquinones and
b-dicarbonyl compounds via a cerium(IV) mediated
oxidative free radical reaction.
obtained when CAN was used. Dione 12a8 generated from
the CAN oxidation of dione 8a was also produced in 20%
yield. Indole 9a was formed presumably via the reaction
routes outlined in Scheme 2. Oxidation of 8a by CAN
produces radical 11a, which undergoes intermolecular
addition to the quinone followed by oxidation to give 14a.
It undergoes further oxidation to produce 15a. Quinone 15a
undergoes either addition reaction to give 16a, followed by
retro Claisen condensation and dehydration to produce 9a
(path a) or retro Claisen condensation followed by addition
and dehydration to produce 9a (path b).9 Since dione 12a
is also produced, quinone 15a may also be produced from
the intermolecular addition of radical intermediate 13a
generated from the CAN oxidation of 12a (path c). To test
this possible reaction route, quinone 1a was treated with 12a
and CAN under similar reaction conditions and no desired
product 9a could be obtained. Based on this result, we
believe that path c is not the reaction route for the generation
of 9a. Other 1,3-cyclohexanediones 8 behaved similarly
giving the corresponding products 9 (Table 2).
2. Results and discussion
We began our studies of this free radical reaction with
2-(alkylamino)-1,4-naphthoquinone 1 and 1,3-diones.
When 2-(methylamino)-1,4-naphthoquinone (1a) was
treated with 2,4-pentanedione (2a) and CAN in methanol
at room temperature, 3a was obtained in 76% yield (Table 1,
entry 1). A possible mechanism for this reaction is shown in
Scheme 1. Initiation occurs with the cerium(IV) oxidation
of 2a to produce radical 5a (R1¼R2¼Me). This radical
intermediate 5a undergoes intermolecular addition to the
quinone ring followed by oxidation to give 7a, which
undergoes a further condensation reaction to produce 3a.
The results of this reaction are summarized in Table 1
(entries 1–12). With cerium(IV) sulfate, this reaction
proceeds at a much slower reaction rate but it gives better
results. Steric hindrance plays an important role in the final
outcome of this reaction. In most cases, the condensation
reaction occurs on the less hindered carbonyl group of the
1,3-diones (entries 7–9)7 and the reaction yield decreases as
the size of R, R1 and R2 increases.
Previously, we reported that the manganese(III) acetate
mediated reaction between 2-(alkylamino)-1,4-naphtho-
quinones 1 and b-keto esters gave 3, 19 and 20 (Eq. (1)).5h
The product distributions are highly dependent on the size
of substituents on 1 and the b-keto esters used. Treatment
of 2-(methylamino)-1,4-naphthoquinone (1a) with ethyl
acetoacetate (2g) and CAN gave indole 3j exclusively in
59% yield. With cerium(IV) sulfate, the reaction yield of 3j
can be improved to 76% (Table 1, entries 13, 14). Indole 3j
was formed via a similar reaction route as shown in Scheme
1. The effect of substituents was also studied by varying the
size of substituents on 1 and the b-keto esters. The reaction
yield decreases as the size of R and R1 increases. As
illustrated in Table 1 (entries 13–25), in all cases, indole 3 is
The reaction of 2-(methylamino)-1,4-naphthoquinone
(1a) with 1,3-cyclohexanedione 8a (R1¼R2¼Me) and
cerium(IV) sulfate in methanol at room temperature gave
9a in 18% yield and no trace of desired product 10 could be
found (Table 2, entry 2). A better result (42% yield) was
Table 2. Free radical reactions between 2-amino-1,4-naphthoquinone 1 and 1,3-cyclohexanedione 8
Entry
Quinone
Cerium(IV) salt
b-Dicarbonyl compound
8a: R1¼Me, R2¼Me
8b: R1¼Me, R2¼H
8c: R1¼Ph, R2¼H
8d: R1¼H, R2¼H
Reaction time (h)
Product (yield (%))
1
2
3
4
5
1a: R¼H
CAN
3
5
3
3
3
9a (42)
12a (20)a
Ce(SO4)2
CAN
CAN
9a (18)
9b (42)
9c (25)
9d (29)
1a: R¼H
1a: R¼H
1a: R¼H
12b (19)a
12c (21)a
12d (20)a
CAN
a
The reaction yield of 12 is based on starting 8 used.

C.-C. Tseng et al. / Tetrahedron 58 (2002) 7625–7633
7627
Scheme 2.
the only product even with N-benzyl substituted 1,4-naph-
thoquinone 1b and ethyl benzoylacetate (2j) (entry 25). In
this case, 20a (R¼p-tolyl, R2¼OEt) was obtained as the
only product by using manganese(III) acetate as oxidant.5h
was performed with manganese(III) acetate), giving the
corresponding 22 as the only product (Table 1, entries 27–29).
ð2Þ
ð1Þ
Manganese(III) acetate mediated free radical reactions
between 2-(anilino)-1,4-naphthoquinone 21 and b-dicarbo-
nyl compounds produced 22 and 23 (Eq. (2)).5h In all cases,
acridine 23 is the major product, which is derived from the
consecutive addition cyclization of radical intermediate
generated from the manganese(III) oxidation. We have
continued to study this oxidative free radical reaction with
cerium(IV) sulfate. When 2-(anilino)-1,4-naphthoquinone
(21a) was treated with 2,4-pentanedione (2a) and
cerium(IV) sulfate, indole 22a was obtained as the only
product in 48% yield and no trace of 23a could be isolated
(Table 1, entry 26). It was generated via a similar reaction
route as shown in Scheme 1. With other b-dicarbonyl
compounds, it behaved similarly (even with ethyl butyryl
acetate (2h), 23b was the only product when this reaction
This different reaction behavior of intermediate 7 can be
ascribed to the strong oxaphilicity of cerium salt, which
enhances the condensation rate of 7.10 To test this
hypothesis, we also performed this oxidative free radical
reaction with Mn(III)–Ce(III) systems. When 2-(ethyl-
amino)-1,4-naphthoquinone (1e) was treated with methyl
4-methoxyacetoacetate (2k), manganese(III) acetate and
cerium(III) nitrate in acetic acid at room temperature, 3u
and 19a were obtained in 63 and 6% yields, respectively
(Table 3, entry 2). Other examples were also shown in Table
3. In all cases, the ratios of 3/19 and 22/23 increase as the
cerium(III) nitrate is added. This result demonstrates that
the condensation rate of 7 is enhanced by the addition of
cerium salt.

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C.-C. Tseng et al. / Tetrahedron 58 (2002) 7625–7633
Table 3. Effect of cerium(III) salt in manganese(III)-based oxidative free radical reactions
Entry
Quinone
Cerium(III) salt
b-Keto ester
Product (yield (%))
1
2
3
4
5
6
7
8
9
10
1e: R¼Me
–
Ce(NO3)3
–
Ce(NO3)3
–
Ce(NO3)3
–
Ce(NO3)3
–
Ce(NO3)3
2k: R1¼MeOCH2, R2¼OMe
2k: R1¼MeOCH2, R2¼OMe
2l: R1¼ClCH2, R2¼OEt
2l: R1¼ClCH2, R2¼OEt
2h: R1¼Pr, R2¼OEt
3u (22)
19a (57)11
19a (6)
1e: R¼Me
3u (63)
3v (12)
3v (54)
3w (35)
3w (72)
22d (0)
22d (23)
22e (7)
22e (29)
1e: R¼Me
19b (59)11
19b (22)
1e: R¼Me
1e: R¼Me
19c (35)11
19c (trace)
23b (54)11
23b (22)
1e: R¼Me
2h: R1¼Pr, R2¼OEt
21a: Ar¼Ph
21a: Ar¼Ph
21b: Ar¼p-Tolyl
21b: Ar¼p-Tolyl
2h: R1¼Pr, R2¼OEt
2h: R1¼Pr, R2¼OEt
2g: R1¼Me, R2¼OEt
2g: R1¼Me, R2¼OEt
23c (45)11
23c (25)
In conclusion, radical 5 can be generated from the
cerium(IV) oxidation of b-dicarbonyl compounds and it
undergoes efficient addition to the C–C double bond of
2-amino-1,4-naphthoquinones. It proceeded at a much faster
reaction rate with CAN. This free radical reaction provides a
novel method for the synthesis of benzo[ f ]indole-4,9-dione
3, 9 and 22 exclusively from readily available 2-amino-1,4-
naphthoquinones and b-dicarbonyl compounds.
176.3 (s), 180.6 (s), 199.1 (s); anal. calcd for C16H13NO3: N,
5.24; C, 71.90; H, 4.90. Found: N, 5.18; C, 71.76; H, 4.92.
3.1.2. 2-Ethyl-1-methyl-3-propionyl-4,9-dihydro-4,9-
dioxo-1H-benzo[ f ]indole 3b. 53%; yellow crystals; mp
132–1338C; IR (CHCl3) 2985, 1660, 1595, 1470,
1255 cm21
;
1H NMR (400 MHz, CDCl3) d 1.21 (t, J¼
7.4 Hz, 3H, CH3), 1.24 (t, J¼7.3 Hz, 3H, CH3), 2.78 (q,
J¼7.4 Hz, 2H, CH2), 3.08 (q, J¼7.3 Hz, 2H, CH2), 4.07 (s,
3H, NCH3), 7.65–7.72 (m, 2H, ArH), 8.09–8.17 (m, 2H,
ArH); 13C NMR (75.5 MHz, CDCl3) d 8.5 (q), 13.5 (q), 17.8
(t), 32.6 (q), 36.7 (t), 122.0 (s), 124.7 (s), 126.1 (d), 126.4
(d), 129.8 (s), 133.0 (d), 133.1 (d), 133.2 (s), 133.4 (s),
146.2 (s), 176.1 (s), 180.5 (s), 202.7 (s); anal. calcd for
C18H17NO3: N, 4.74; C, 73.20; H, 5.80. Found: N, 4.72; C,
73.17; H, 5.88.
3. Experimental
General considerations. Melting points are uncorrected.
The NMR spectra were recorded on a Bruker AVANCE-
300, AMX-400 or AVANCE-600 spectrometer. Chemical
shifts are reported in ppm relative to TMS as internal
reference. Analytical thin-layer chromatography was per-
formed with precoated silica gel 60 F-254 plates (0.25 mm
thick) from EM Laboratories and visualized by UV.
The reaction mixture was purified by column chroma-
tography over EM Laboratories silica gel (70–230 mesh).
The starting 1,4-naphthoquinone 1 and 21 were synthesized
by literature procedure.12
3.1.3. 3-Isobutyryl-2-isopropyl-1-methyl-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 3c. 39%; yellow crystals;
mp 155–1568C; IR (CHCl3) 2980, 2940, 1660, 1595, 1455,
1
1250 cm21; H NMR (400 MHz, CDCl3) d 1.21 (d, J¼
6.9 Hz, 6H, CH3), 1.36 (d, J¼7.2 Hz, 6H, CH3), 3.24
(septet, J¼7.2 Hz, 1H, CH), 3.44 (septet, J¼6.9 Hz, 1H,
CH), 4.14 (s, 3H, NCH3), 7.61–7.72 (m, 2H, ArH), 8.05–
8.17 (m, 2H, ArH); 13C NMR (100.6 MHz, CDCl3) d 18.6
(q£2), 20.8 (q£2), 25.7 (d), 33.7 (q), 41.3 (d), 122.2 (s),
125.4 (s), 126.3 (d), 126.4 (d), 129.6 (s), 133.1 (d£2), 133.3
(s), 133.6 (s), 147.5 (s), 176.2 (s), 180.6 (s), 207.9 (s); anal.
calcd for C20H21NO3: N, 4.33; C, 74.28; H, 6.55. Found: N,
4.31; C, 73.97; H, 6.72.
3.1. Typical experimental procedure for the reaction
mediated by CAN
To a solution of 151 mg (0.80 mmol) of 2-(methylamino)-
1,4-naphthoquinone (1a) and 320 mg (3.20 mmol) of
2,4-pentanedione (2a) in 10 ml of methanol and 2 ml of
dichloromethane stirred at room temperature was added
1.54 g (2.81 mmol) of CAN in four portions at 10 min
intervals. The reaction mixture was stirred for another
10 min and then diluted with 100 ml of ethyl acetate,
washed with 50 ml of saturated aqueous sodium bisulfite,
three 50 ml portions of water, dried (Na2SO4), and
concentrated in vacuo. The residue was chromatographed
over 20 g of silica gel (eluted with 2:1 dichloromethane–
hexane) followed by recrystallization (hexane–ethyl acetate)
to give 164 mg (76%) of 3a.
3.1.4. 1,2-Dimethyl-3-ethoxycarbonyl-4,9-dihydro-4,9-
dioxo-1H-benzo[ f ]indole 3j. 59%; yellow crystals; mp
142–1438C; IR (CHCl3) 2990, 1710, 1655, 1300,
1275 cm21
;
1H NMR (400 MHz, CDCl3) d 1.43 (t, J¼
7.1 Hz, 3H, CH3), 2.47 (s, 3H, CH3), 4.03 (s, 3H, NCH3),
4.43 (q, J¼7.1 Hz, 2H, OCH2), 7.61–7.71 (m, 2H, ArH),
8.07–8.17 (m, 2H, ArH); 13C NMR (100.6 MHz, CDCl3) d
10.9 (q), 14.2 (q), 32.9 (q), 61.1 (t), 113.9 (s), 125.5 (s),
126.1 (d), 126.7 (d), 130.5 (s), 132.9 (d), 133.1 (s), 133.2
(d), 133.8 (s), 142.1 (s), 164.5 (s), 176.4 (s), 179.3 (s); anal.
calcd for C17H15NO4: N, 4.71; C, 68.68; H, 5.09. Found: N,
4.73; C, 68.63; H, 5.09.
3.1.1. 3-Acetyl-1,2-dimethyl-4,9-dihydro-4,9-dioxo-1H-
benzo[ f ]indole 3a. 76%; yellow needles; mp 180–1818C;
1
IR (CHCl3) 3010, 2960, 1655, 1595, 1465, 1270 cm21; H
3.1.5. 3-Ethoxycarbonyl-2-methyl-1-( p-methylbenzyl)-
4,9-dihydro-4,9-dioxo-1H-benzo[f]indole 3k. 61%; yellow
needles; mp 170–1718C; IR (CHCl3) 3010, 1710, 1660,
NMR (400 MHz, CDCl3) d 2.41 (s, 3H, CH3), 2.71 (s, 3H,
CH3), 4.04 (s, 3H, NCH3), 7.64–7.73 (m, 2H, ArH), 8.08–
8.17 (m, 2H, ArH); 13C NMR (75.5 MHz, CDCl3) d 10.8
(q), 31.6 (q), 32.8 (q), 122.6 (s), 124.8 (s), 126.2 (d), 126.6
(d), 130.0 (s), 133.1 (sþd), 133.3 (d), 133.5 (s), 141.9 (s),
1
1435, 1255 cm21; H NMR (400 MHz, CDCl3) d 1.43 (t,
J¼7.1 Hz, 3H, CH3), 2.30 (s, 3H, CH3), 2.41 (s, 3H, CH3),
4.44 (q, J¼7.1 Hz, 2H, OCH2), 5.77 (s, 2H, NCH2), 6.96 (d,

C.-C. Tseng et al. / Tetrahedron 58 (2002) 7625–7633
7629
J¼7.9 Hz, 2H, ArH), 7.11 (d, J¼7.9 Hz, 2H, ArH), 7.61–
7.69 (m, 2H, ArH), 8.09 (dd, J¼7.4, 1.2 Hz, 1H, ArH), 8.15
(dd, J¼7.4, 1.2 Hz, 1H, ArH); 13C NMR (100.6 MHz,
CDCl3) d 11.0 (q), 14.2 (q), 21.0 (q), 48.6 (t), 61.2 (t), 114.4
(s), 125.9 (s), 126.2 (d£2), 126.3 (d), 126.7 (d), 129.6 (d£2),
130.2 (s), 132.5 (s), 132.9 (d), 133.2 (s), 133.3 (d), 133.7 (s),
137.5 (s), 142.3 (s), 164.6 (s), 176.2 (s), 179.5 (s); anal.
calcd for C24H21NO4: N, 3.62; C, 74.40; H, 5.46. Found: N,
3.62; C, 74.31; H, 5.45.
124–1258C; IR (CHCl3) 2970, 1655, 1595, 1300,
1
1250 cm21; H NMR (400 MHz, CDCl3) d 0.96 (d, J¼
6.8 Hz, 6H, CH3), 2.19 (nontet, J¼6.8 Hz, 1H, CH), 2.38 (s,
3H, CH3), 2.99 (d, J¼6.8 Hz, 2H, CH2), 4.03 (s, 3H, NCH3),
7.64–7.73 (m, 2H, ArH), 8.08–8.17 (m, 2H, ArH); 13C
NMR (100.6 MHz, CDCl3) d 10.7 (q), 22.6 (q£2), 25.5 (d),
32.8 (q), 52.4 (t), 123.1 (s), 124.7 (s), 126.2 (d), 126.6 (d),
129.9 (s), 133.1 (d), 133.2 (sþd), 133.5 (s), 141.1 (s), 176.3
(s), 180.5 (s), 202.3 (s); anal. calcd for C19H19NO3: N, 4.53;
C, 73.77; H, 6.19. Found: N, 4.57; C, 73.88; H, 6.24.
3.2. Typical experimental procedure for the reaction
mediated by cerium sulfate
3.2.7. 3-Acetyl-2-methyl-1-(p-methylbenzyl)-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 3g. 61%; yellow crystals;
mp 197–1988C; IR (CHCl3) 3010, 1650, 1495, 1435,
To a solution of 120 mg (0.64 mmol) of 2-(methylamino)-
1,4-naphthoquinone (1a) and 256 mg (2.56 mmol) of
2,4-pentanedione (2a) in 10 ml of methanol, 2 ml of
dichloromethane and 2 ml of water was added 903 mg
(2.23 mmol) of cerium sulfate in four portions at 1 h
intervals. The reaction mixture was stirred for another
30 min. After workup as described as above, the residue was
chromatographed over 20 g of silica gel (eluted with 2:1
dichloromethane–hexane) followed by recrystallization
(hexane–ethyl acetate) to give 132 mg (77%) of 3a.
1
1270 cm21; H NMR (400 MHz, CDCl3) d 2.31 (s, 3H,
CH3), 2.36 (s, 3H, CH3), 2.73 (s, 3H, CH3), 5.78 (s, 2H,
NCH2), 6.97 (d, J¼7.7 Hz, 2H, ArH), 7.12 (d, J¼7.7 Hz,
2H, ArH), 7.61–7.75 (m, 2H, ArH), 8.04–8.22 (m, 2H,
ArH); 13C NMR (75.5 MHz, CDCl3) d 10.9 (q), 21.0 (q),
31.7 (q), 48.6 (t), 123.1 (s), 125.3 (s), 126.2 (d£2), 126.4 (d),
126.7 (d), 129.6 (d£2), 129.8 (s), 132.5 (s), 133.2 (d),
133.25 (s), 133.34 (d), 133.5 (s), 137.6 (s), 142.0 (s), 176.2
(s), 180.7 (s), 199.2 (s); anal. calcd for C23H19NO3: N, 3.92;
C, 77.29; H, 5.36. Found: N, 3.89; C, 77.22; H, 5.36.
3.2.1. 3-Acetyl-1,2-dimethyl-4,9-dihydro-4,9-dioxo-1H-
benzo[ f ]indole 3a. 77%; the spectral data for 3a was
identical to that reported earlier.
3.2.8. 2-Ethyl-1-(p-methylbenzyl)-3-propionyl-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 3h. 57%; yellow crystals;
mp 115–1168C; IR (CHCl3) 2985, 1660, 1595, 1495,
1470 cm21
;
1H NMR (400 MHz, CDCl3) d 1.13 (t, J¼
3.2.2. 2-Ethyl-1-methyl-3-propionyl-4,9-dihydro-4,9-
dioxo-1H-benzo[ f ]indole 3b. 67%; the spectral data for
3b was identical to that reported earlier.
7.5 Hz, 3H, CH3), 1.22 (t, J¼7.2 Hz, 3H, CH3), 2.31 (s, 3H,
CH3), 2.72 (q, J¼7.5 Hz, 2H, CH2), 3.11 (q, J¼7.2 Hz, 2H,
CH2), 5.77 (s, 2H, NCH2), 6.94 (d, J¼7.9 Hz, 2H, ArH),
7.12 (d, J¼7.9 Hz, 2H, ArH), 7.61–7.74 (m, 2H, ArH),
8.04–8.21 (m, 2H, ArH); 13C NMR (75.5 MHz, CDCl3) d
8.6 (q), 14.3 (q), 18.1 (t), 21.0 (q), 36.9 (t), 48.4 (t), 122.6
(s), 125.4 (s), 125.9 (d£2), 126.5 (d), 126.6 (d), 129.6 (d£2),
129.7 (s), 133.1 (s), 133.2 (d), 133.3 (d), 133.4 (s), 133.5 (s),
137.5 (s), 146.7 (s), 176.0 (s), 180.8 (s), 202.9 (s); anal.
calcd for C25H23NO3: N, 3.63; C, 77.90; H, 6.01. Found: N,
3.63; C, 77.83; H, 6.07.
3.2.3. 3-Isobutyryl-2-isopropyl-1-methyl-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 3c. 62%; the spectral data
for 3c was identical to that reported earlier.
3.2.4. 3-Benzoyl-1,2-dimethyl-4,9-dihydro-4,9-dioxo-1H-
benzo[ f ]indole 3d. 64%; yellow crystals; mp 237–2388C;
1
IR (CHCl3) 3010, 2960, 1655, 1600, 1465, 1225 cm21; H
NMR (400 MHz, CDCl3) d 2.34 (s, 3H, CH3), 4.08 (s, 3H,
NCH3), 7.35–7.48 (m, 2H, ArH), 7.48–7.70 (m, 3H, ArH),
7.88 (d, J¼7.7 Hz, 2H, ArH), 7.93 (d, J¼7.5 Hz, 1H, ArH),
8.11 (d, J¼7.5 Hz, 1H, ArH); 13C NMR (100.6 MHz,
CDCl3) d 10.7 (q), 32.9 (q), 120.8 (s), 126.1 (s), 126.3 (d),
126.6 (d), 128.4 (d£2), 129.3 (d£2), 129.8 (s), 133.1 (d£2),
133.2 (d), 133.3 (s), 133.5 (s), 138.3 (s), 140.7 (s), 176.3 (s),
179.6 (s), 193.0 (s); anal. calcd for C21H15NO3: N, 4.25; C,
76.58; H, 4.59. Found: N, 4.26; C, 76.43; H, 4.63.
3.2.9. 3-Benzoyl-2-methyl-1-(p-methylbenzyl)-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 3i. 60%; yellow crystals;
mp 244–2458C; IR (CHCl3) 3010, 1655, 1595, 1505,
1
1435 cm21; H NMR (400 MHz, CDCl3) d 2.29 (s, 3H,
CH3), 2.32 (s, 3H, CH3), 5.82 (s, 2H, NCH2), 7.04 (d,
J¼7.9 Hz, 2H, ArH), 7.15 (d, J¼7.9 Hz, 2H, ArH), 7.44 (t,
J¼7.6 Hz, 2H, ArH), 7.51–7.72 (m, 3H, ArH), 7.84–7.94
(m, 2H, ArH), 7.97 (dd, J¼7.4, 1.2 Hz, 1H, ArH), 8.13 (dd,
J¼7.4, 1.2 Hz, 1H, ArH); 13C NMR (75.5 MHz, CDCl3) d
10.8 (q), 21.1 (q), 48.7 (t), 121.2 (s), 126.3 (d£2), 126.48
(d), 126.52 (s), 126.6 (d£2), 128.4 (d), 129.3 (d£2), 129.6
(s), 129.7 (d£2), 132.6 (s), 133.1 (d£2), 133.19 (d), 133.22
(s), 133.6 (s), 137.6 (s), 138.3 (s), 140.8 (s), 176.0 (s), 179.7
(s), 193.0 (s); anal. calcd for C28H21NO3: N, 3.34; C, 80.17;
H, 5.05. Found: N, 3.28; C, 77.92; H, 5.08.
3.2.5. 1,2-Dimethyl-3-trimethylacetyl-4,9-dihydro-4,9-
dioxo-1H-benzo[ f ]indole 3e. 73%; yellow crystals;
mp 183–1848C; IR (CHCl3) 2975, 1660, 1595, 1465,
1
1250 cm21; H NMR (400 MHz, CDCl3) d 1.28 (s, 9H,
CH3), 2.24 (s, 3H, CH3), 4.03 (s, 3H, NCH3), 7.59–7.74 (m,
2H, ArH), 8.04–8.18 (m, 2H, ArH); 13C NMR (100.6 MHz,
CDCl3) d 11.1 (q), 27.1 (q£3), 32.8 (q), 45.8 (s), 122.3 (s),
125.7 (s), 126.4 (d), 126.5 (d), 129.5 (s), 133.16 (sþd),
133.19 (d), 133.8 (s), 135.9 (s), 176.0 (s), 180.3 (s), 211.8
(s); anal. calcd for C19H19NO3: N, 4.53; C, 73.77; H, 6.19.
Found: N, 4.54; C, 73.74; H, 6.21.
3.2.10. 1,2-Dimethyl-3-ethoxycarbonyl-4,9-dihydro-4,9-
dioxo-1H-benzo[ f ]indole 3j. 76%; the spectral data for
3j was identical to that reported earlier.
3.2.6. 1,2-Dimethyl-3-isopentanoyl-4,9-dihydro-4,9-
dioxo-1H-benzo[ f ]indole 3f. 57%; yellow needles; mp
3.2.11. 3-Ethoxycarbonyl-2-methyl-1-( p-methylbenzyl)-
4,9-dihydro-4,9-dioxo-1H-benzo[ f ]indole 3k. 69%; the

7630
C.-C. Tseng et al. / Tetrahedron 58 (2002) 7625–7633
spectral data for 3k was identical to that reported
earlier.
2H, OCH2), 7.37–7.46 (m, 2H, ArH), 7.46–7.56 (m, 2H,
ArH), 7.64–7.77 (m, 2H, ArH), 8.09–8.23 (m, 2H, ArH);
13C NMR (75.5 MHz, CDCl3) d 13.8 (q), 34.5 (q), 61.1 (t),
115.5 (s), 125.3 (s), 126.2 (d), 126.7 (d), 128.56 (d£2),
128.61 (s), 129.6 (d), 130.1 (d£2), 130.5 (s), 133.0 (d),
133.3 (s), 133.4 (d), 133.7 (s), 143.2 (s), 146.1 (s), 176.6 (s),
179.5 (s); anal. calcd for C22H17NO4: N, 3.90; C, 73.53; H,
4.77. Found: N, 3.89; C, 73.46; H, 4.84.
3.2.12. 1-Butyl-3-ethoxycarbonyl-2-methyl-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 3l. 73%; yellow needles; mp
93–948C; IR (CHCl3) 2975, 1715, 1655, 1470, 1275 cm21
;
1H NMR (600 MHz, CDCl3) d 0.99 (t, J¼7.6 Hz, 3H, CH3),
1.44 (t, J¼7.1 Hz, 3H, CH3), 1.39–1.53 (m, 2H, CH2), 1.74
(quintet, J¼7.6 Hz, 2H, CH2), 2.48 (s, 3H, CH3), 4.40–4.48
(m, 4H), 7.61–7.70 (m, 2H, ArH), 8.07–8.16 (m, 2H, ArH);
13C NMR (150.9 MHz, CDCl3) d 10.7 (q), 13.6 (q), 14.2 (q),
19.9 (t), 32.4 (t), 45.7 (t), 61.0 (t), 114.1 (s), 125.8 (s), 126.1
(d), 126.6 (d), 130.0 (s), 132.8 (d), 133.1 (d), 133.2 (s),
133.8 (s), 141.3 (s), 164.7 (s), 175.9 (s), 179.3 (s); anal.
calcd for C20H21NO4: N, 4.13; C, 70.78; H, 6.24. Found: N,
4.11; C, 70.74; H, 6.33.
3.2.17. 3-Methoxycarbonyl-2-methoxymethyl-1-methyl-
4,9-dihydro-4,9-dioxo-1H-benzo[f]indole 3q. 66%; yellow
crystals; mp 159–1608C; IR (CHCl3) 3015, 1715, 1660,
1
1305, 1275 cm21; H NMR (400 MHz, CDCl3) d 3.39 (s,
3H, OCH3), 3.98 (s, 3H, NCH3), 4.14 (s, 3H, OCH3), 4.68 (s,
2H, OCH2), 7.65–7.74 (m, 2H, ArH), 8.09–8.19 (m, 2H,
ArH); 13C NMR (100.6 MHz, CDCl3) d 33.7 (q), 52.4 (q),
58.2 (q), 62.7 (t), 115.6 (s), 124.9 (s), 126.3 (d), 126.8 (d),
131.5 (s), 133.1 (sþd), 133.6 (d), 133.8 (s), 139.7 (s), 167.4
(s), 176.9 (s), 179.4 (s); anal. calcd for C17H15NO5: N, 4.47;
C, 65.17; H, 4.83. Found: N, 4.44; C, 65.04; H, 4.82.
3.2.13. 3-Ethoxycarbonyl-1-isobutyl-2-methyl-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 3m. 61%; yellow needles;
mp 118–1198C; IR (CHCl3) 2975, 1715, 1660, 1470,
1
1260 cm21; H NMR (300 MHz, CDCl3) d 0.97 (d, J¼
6.9 Hz, 6H, CH3), 1.44 (t, J¼7.1 Hz, 3H, CH3), 2.17 (nontet,
J¼6.9 Hz, 1H, CH), 2.48 (s, 3H, CH3), 4.30 (d, J¼6.9 Hz,
2H, NCH2), 4.44 (q, J¼7.1 Hz, 2H, OCH2), 7.61–7.71 (m,
2H, ArH), 8.06–8.18 (m, 2H, ArH); 13C NMR (75.5 MHz,
CDCl3) d 11.3 (q), 14.2 (q), 19.8 (q£2), 29.8 (d), 52.5 (t),
61.6 (t), 114.2 (s), 126.0 (s), 126.2 (d), 126.6 (d), 130.3 (s),
132.9 (d), 133.1 (d), 133.4 (s), 133.8 (s), 141.7 (s), 164.8 (s),
176.0 (s), 179.5 (s); anal. calcd for C20H21NO4: N, 4.13; C,
70.78; H, 6.24. Found: N, 4.17; C, 70.73; H, 6.20.
3.2.18. 3-Ethoxycarbonyl-1-( p-methylbenzyl)-2-propyl-
4,9-dihydro-4,9-dioxo-1H-benzo[f]indole 3r. 45%; yellow
crystals; mp 100–1018C; IR (CHCl3) 2975, 1715, 1655,
1
1495, 1270 cm21; H NMR (400 MHz, CDCl3) d 0.94 (t,
J¼7.7 Hz, 3H, CH3), 1.44 (t, J¼7.1 Hz, 3H, CH3), 1.54
(sextet, J¼7.7 Hz, 2H, CH2), 2.30 (s, 3H, CH3), 2.78 (t,
J¼7.7 Hz, 2H, CH2), 4.45 (q, J¼7.1 Hz, 2H, OCH2), 5.77
(s, 2H, NCH2), 6.93 (d, J¼7.9 Hz, 2H, ArH), 7.11 (d, J¼
7.9 Hz, 2H, ArH), 7.57–7.70 (m, 2H, ArH), 8.06 (dd, J¼
7.2, 1.5 Hz, 1H, ArH), 8.14 (dd, J¼7.2, 1.5 Hz, 1H, ArH);
13C NMR (75.5 MHz, CDCl3) d 14.0 (q), 14.2 (q), 21.0 (q),
22.9 (t), 26.7 (t), 48.5 (t), 61.1 (t), 114.3 (s), 125.8 (d£2),
126.1 (s), 126.3 (d), 126.6 (d), 129.5 (d£2), 130.1 (s), 132.9
(d), 133.16 (s), 133.21 (d), 133.24 (s), 133.8 (s), 137.4 (s),
146.1 (s), 164.6 (s), 176.0 (s), 179.5 (s); anal. calcd for
C26H25NO4: N, 3.37; C, 75.16; H, 6.06. Found: N, 3.26; C,
74.89; H, 6.12.
3.2.14. 3-Ethoxycarbonyl-1-methyl-2-propyl-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 3n. 64%; yellow needles;
mp 82–838C; IR (CHCl3) 2975, 1715, 1660, 1595,
1465 cm21
;
1H NMR (400 MHz, CDCl3) d 1.02 (t, J¼
7.5 Hz, 3H, CH3), 1.43 (t, J¼7.1 Hz, 3H, CH3), 1.66 (sextet,
J¼7.5 Hz, 2H, CH2), 2.85 (t, J¼7.5 Hz, 2H, CH2), 4.05 (s,
3H, NCH3), 4.32 (q, J¼7.1 Hz, 2H, OCH2), 7.61–7.73 (m,
2H, ArH), 8.06–8.21 (m, 2H, ArH); 13C NMR (75.5 MHz,
CDCl3) d 13.8 (q), 14.2 (q), 22.3 (t), 26.5 (t), 32.9 (q), 61.0
(t), 113.9 (s), 125.6 (s), 126.1 (d), 126.6 (d), 130.4 (s), 132.9
(d), 133.2 (sþd), 133.8 (s), 145.7 (s), 164.6 (s), 176.4 (s),
179.4 (s); anal. calcd for C19H19NO4: N, 4.31; C, 70.14; H,
5.89. Found: N, 4.29; C, 70.10; H, 5.93.
3.2.19. 2-Isopropyl-3-methoxycarbonyl-1-( p-methyl-
benzyl)-4,9-dihydro-4,9-dioxo-1H-benzo[f]indole 3s. 44%;
yellow crystals; mp 160–1618C; IR (CHCl3) 2980, 1730,
1655, 1430, 1275 cm21; 1H NMR (400 MHz, CDCl3) d 1.25
(d, J¼7.0 Hz, 6H, CH3), 2.31 (s, 3H, CH3), 3.09 (septet,
J¼7.0 Hz, 1H, CH), 4.00 (s, 3H, OCH3), 5.82 (s, 2H,
NCH2), 6.92 (d, J¼8.0 Hz, 2H, ArH), 7.11 (d, J¼8.0 Hz,
2H, ArH), 7.58–7.72 (m, 2H, ArH), 8.03–8.18 (m, 2H,
ArH); 13C NMR (75.5 MHz, CDCl3) d 21.0 (q), 21.2 (q),
25.9 (d), 48.4 (t), 52.6 (q), 113.8 (s), 125.7 (d£2), 126.1 (s),
126.4 (d), 126.6 (d), 128.8 (s), 129.6 (d£2), 133.1 (sþd),
133.17 (d), 133.21 (s), 133.3 (s), 133.7 (s), 137.4 (s),
147.7 (s), 166.7 (s), 175.8 (s), 180.0 (s); anal. calcd for
C25H23NO4: N, 3.49; C, 74.79; H, 5.77. Found: N, 3.47; C,
74.50; H, 5.81.
3.2.15. 2-Isopropyl-3-methoxycarbonyl-1-methyl-4,9-
dihydro-4,9-dioxo-1H-benzo[ f ]indole 3o. 58%; yellow
crystals; mp 129–1308C; IR (CHCl3) 2980, 1660, 1595,
1
1275, 1245 cm21; H NMR (400 MHz, CDCl3) d 1.38 (d,
J¼7.1 Hz, 6H, CH3), 3.23 (septet, J¼7.1 Hz, 1H, CH), 3.98
(s, 3H, NCH3), 4.10 (s, 3H, OCH3), 7.61–7.72 (m, 2H,
ArH), 8.06–8.17 (m, 2H, ArH); 13C NMR (100.6 MHz,
CDCl3) d 20.6 (q£2), 25.7 (d), 32.8 (q), 52.4 (q), 113.2 (s),
125.3 (s), 126.2 (d£2), 129.1 (s), 133.0 (d£2), 133.1 (s),
133.5 (s), 146.9 (s), 166.5 (s), 175.9 (s), 179.6 (s); anal.
calcd for C18H17NO4: N, 4.50; C, 69.44; H, 5.50. Found: N,
4.53; C, 69.24; H, 5.57.
3.2.20. 3-Ethoxycarbonyl-1-( p-methylbenzyl)-2-phenyl-
4,9-dihydro-4,9-dioxo-1H-benzo[f ]indole 3t. 23%; yellow
crystals; mp 120–1218C; IR (CHCl3) 2960, 1730, 1660,
1
3.2.16. 3-Ethoxycarbonyl-1-methyl-2-phenyl-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 3p. 52%; yellow crystals;
mp 118–1198C; IR (CHCl3) 3010, 1725, 1495, 1450,
1495, 1450 cm21; H NMR (400 MHz, CDCl3) d 1.12 (t,
J¼7.2 Hz, 3H, CH3), 2.27 (s, 3H, CH3), 4.22 (q, J¼7.2 Hz,
2H, OCH2), 5.61 (s, 2H, NCH2), 6.79 (d, J¼7.6 Hz, 2H,
ArH), 7.03 (d, J¼7.6 Hz, 2H, ArH), 7.27–7.35 (m, 2H,
ArH), 7.35–7.49 (m, 3H, ArH), 7.61–7.73 (m, 2H, ArH),
1275 cm21
;
1H NMR (400 MHz, CDCl3) d 1.13 (t, J¼
7.1 Hz, 3H, CH3), 3.93 (s, 3H, NCH3), 4.23 (q, J¼7.1 Hz,

C.-C. Tseng et al. / Tetrahedron 58 (2002) 7625–7633
7631
8.03–8.15 (m, 1H, ArH), 8.15–8.23 (m, 1H. ArH); 13C
NMR (100.6 MHz, CDCl3) d 13.8 (q), 21.0 (q), 49.3 (t),
61.2 (t), 116.1 (s), 125.8 (s), 126.1 (d£2), 126.5 (d), 126.7
(d), 128.4 (d£2), 128.6 (s), 129.3 (d£2), 129.7 (d), 130.2
(d£2), 133.1 (d), 133.4 (sþd), 133.6 (s), 133.7 (s), 137.2 (s),
143.5 (s), 164.1 (s), 176.1 (s), 179.6 (s); anal. calcd for
C29H23NO4: N, 3.12; C, 77.49; H, 5.16. Found: N, 3.16; C,
77.40; H, 5.19.
3.2.25. 3-Ethoxycarbonyl-1-phenyl-2-propyl-4,9-di-
hydro-4,9-dioxo-1H-benzo[ f ]indole 22d. 37%; yellow
crystals; mp 156–1578C; IR (CHCl3) 3015, 2975, 1715,
1665, 1495, 1285 cm21; 1H NMR (400 MHz, CDCl3) d 0.81
(t, J¼7.6 Hz, 3H, CH3), 1.45 (t, J¼7.1 Hz, 3H, CH3), 1.38–
1.54 (m, 2H, CH2), 2.61 (t, J¼7.6 Hz, 2H, CH2), 4.47 (q,
J¼7.1 Hz, 2H, OCH2), 7.28–7.34 (m, 2H, ArH), 7.51–7.71
(m, 5H, ArH), 7.92–8.00 (m, 1H, ArH), 8.13–8.20 (m, 1H,
ArH); 13C NMR (100.6 MHz, CDCl3) d 13.8 (q), 14.1 (q),
22.9 (t), 26.8 (t), 61.1 (t), 113.9 (s), 125.8 (s), 126.1 (d),
126.6 (d), 127.4 (d£2), 129.4 (d£2), 129.6 (d), 131.2 (s),
133.0 (sþd), 133.2 (d), 133.7 (s), 136.7 (s), 146.5 (s), 164.5
(s), 174.9 (s), 179.6 (s); anal. calcd for C24H21NO4: N, 3.62;
C, 74.40; H, 5.46. Found: N, 3.67; C, 74.47; H, 5.50.
3.2.21. 3-Acetyl-2-isobutyl-1-methyl-4,9-dihydro-4,9-
dioxo-1H-benzo[ f ]indole 4a. 18%; yellow crystals; mp
166–1678C; IR (CHCl3) 3010, 2970, 1655, 1595, 1460,
1
1265 cm21; H NMR (300 MHz, CDCl3) d 0.96 (d, J¼
6.8 Hz, 6H, 2CH3), 1.92 (nontet, J¼6.8 Hz, 1H, CH), 2.69
(s, 3H, CH3), 2.75 (d, J¼6.8 Hz, 2H, CH2), 4.04 (s, 3H,
NCH3), 7.65–7.74 (m, 2H, ArH), 8.09–8.20 (m, 2H, ArH);
13C NMR (75.5 MHz, CDCl3) d 22.3 (q£2), 29.0 (q), 31.7
(d), 32.5 (t), 33.3 (q), 123.3 (s), 125.0 (s), 126.2 (d), 126.6
(d), 130.1 (s), 133.1 (d), 133.27 (d), 133.3 (s), 133.5 (s),
144.4 (s), 176.3 (s), 180.7 (s), 199.5 (s); anal. calcd for
C19H19NO3: N, 4.53; C, 73.77; H, 6.19. Found: N, 4.57; C,
73.84; H, 6.29.
3.3. Typical experimental procedure for the reaction of
2-amino-1,4-naphthoquinone 1 and 1,3-cyclohexane-
dione 8 mediated by CAN
To a solution of 120 mg (0.64 mmol) of 2-(methylamino)-
1,4-naphthoquinone (1a) and 362 mg (2.58 mmol) of
5,5-dimethyl-1,3-cyclohexanedione (8a) in 10 ml of
methanol and 2 ml of dichloromethane stirred at room
temperature was added 1.77 g (3.22 mmol) of CAN in five
portions at 30 min intervals. The reaction mixture was
stirred for another 30 min. After workup as described as
above, the residue was chromatographed over 20 g of silica
gel to give 96 mg (42%) of 9a (eluted with 2:1 dichloro-
methane–hexane) followed by 87 mg (20%) of 12a (eluted
with 1:1 dichloromethane–ethyl acetate).
3.2.22. 3-Acetyl-2-methyl-1-phenyl-4,9-dihydro-4,9-
dioxo-1H-benzo[ f ]indole 22a. 48%; yellow needles;
mp 170–1718C; IR (CHCl3) 3015, 1660, 1600, 1495,
1
1280 cm21; H NMR (400 MHz, CDCl3) d 2.19 (s, 3H,
CH3), 2.80 (s, 3H, CH3), 7.24–7.34 (m, 2H, ArH), 7.53–
7.61 (m, 3H, ArH), 7.61–7.73 (m, 2H, ArH), 7.99 (dd, J¼
7.0, 1.1 Hz, 1H, ArH), 8.17 (dd, J¼7.0, 1.1 Hz, 1H, ArH);
13C NMR (100.6 MHz, CDCl3) d 11.8 (q), 31.8 (q), 122.6
(s), 125.1 (s), 126.2 (d), 126.8 (d), 127.1 (d£2), 129.6 (d£3),
131.0 (s), 133.0 (s), 133.3 (d), 133.4 (d), 133.6 (s), 136.9 (s),
142.7 (s), 175.0 (s), 180.9 (s), 199.1 (s); anal. calcd for
C21H15NO3: N, 4.25; C, 76.58; H, 4.59. Found: N, 4.25; C,
76.40; H, 4.61.
3.3.1. 2-(2,2-Dimethyl-3-methoxycarbonylpropyl)-3-
methoxy-1-methyl-4,9-dihydro-4,9-dioxo-1H-benzo[ f ]-
indole 9a. 42%; orange needles; mp 128–1298C; IR
;
(CHCl3) 3010, 2970, 1730, 1645, 1465, 1270 cm21 1H
NMR (400 MHz, CDCl3) d 1.09 (s, 6H, CH3), 2.36 (s, 2H,
CH2), 2.80 (s, 2H, CH2), 3.69 (s, 3H, OCH3), 4.00 (s, 3H,
CH3), 4.01 (s, 3H, CH3), 7.59–7.70 (m, 2H, ArH), 8.06–
8.18 (m, 2H, ArH); 13C NMR (100.6 MHz, CDCl3) d 27.3
(q£2), 33.7 (t), 34.2 (q), 35.9 (s), 45.7 (t), 51.2 (q), 61.6 (q),
117.5 (s), 126.1 (d), 126.2 (d), 126.8 (s), 131.5 (s), 132.7 (d),
132.8 (d), 133.7 (s), 134.0 (s), 145.1 (s), 172.3 (s), 175.0 (s),
179.7 (s); anal. calcd for C21H23NO5: N, 3.79; C, 68.28; H,
6.28. Found: N, 3.80; C, 68.30; H, 6.32.
3.2.23. 3-Benzoyl-2-methyl-1-phenyl-4,9-dihydro-4,9-
dioxo-1H-benzo[ f ]indole 22b. 31%; yellow crystals;
mp 194–1958C; IR (CHCl3) 3015, 1660, 1600, 1500,
1
1285 cm21; H NMR (400 MHz, CDCl3) d 2.13 (s, 3H,
CH3), 7.34–7.42 (m, 2H, ArH), 7.44–7.53 (m, 2H, ArH),
7.56–7.68 (m, 6H, ArH), 7.94–8.06 (m, 4H, ArH); 13C
NMR (75.5 MHz, CDCl3) d 11.3 (q), 120.8 (s), 126.3 (d),
126.5 (s), 126.6 (d), 127.1 (d£2), 128.4 (d£2), 129.3 (d£2),
129.6 (d£3), 130.7 (s), 133.2 (d£2), 133.4 (s), 136.8 (s),
138.2 (s), 141.2 (s), 174.8 (s), 179.9 (s), 193.0 (s); anal.
calcd for C26H17NO3: N, 3.58; C, 79.78; H, 4.38. Found: N,
3.55; C, 79.64; H, 4.47.
3.3.2. 3-Methoxy-2-(3-methoxycarbonyl-2-methylpropyl)-
1-methyl-4,9-dihydro-4,9-dioxo-1H-benzo[ f ]indole 9b.
42%; orange crystals; mp 116–1178C; IR (CHCl3) 3010,
1
2960, 1730, 1650, 1465, 1270 cm21; H NMR (400 MHz,
CDCl3) d 1.02 (d, J¼6.2 Hz, 3H, CH3), 2.23–2.43 (m, 3H),
2.57 (dd, J¼14.7, 7.6 Hz, 1H, CH), 2.70 (dd, J¼14.4,
6.3 Hz, 1H, CH), 3.65 (s, 3H, OCH3), 4.02 (s, 3H, CH3),
4.05 (s, 3H, CH3), 7.60–7.70 (m, 2H, ArH), 8.10–8.18 (m,
2H, ArH); 13C NMR (75.5 MHz, CDCl3) d 19.9 (q), 29.3 (t),
29.9 (d), 33.4 (q), 40.7 (d), 51.5 (q), 61.9 (q), 117.6 (s),
126.2 (d), 126.3 (d), 126.6 (s), 132.2 (s), 132.8 (d), 132.9
(d), 133.8 (s), 134.1 (s), 144.4 (s), 173.0 (s), 175.3 (s), 179.8
(s); anal. calcd for C20H21NO5: N, 3.94; C, 67.59; H, 5.96.
Found: N, 4.02; C, 67.60; H, 6.01.
3.2.24. 3-Ethoxycarbonyl-2-methyl-1-phenyl-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 22c. 52%; yellow needles;
mp 181–1828C; IR (CHCl3) 3015, 1715, 1660, 1500,
1285 cm21
;
1H NMR (400 MHz, CDCl3) d 1.46 (t, J¼
7.1 Hz, 3H, CH3), 2.25 (s, 3H, CH3), 4.48 (q, J¼7.1 Hz, 2H,
CH2), 7.25–7.35 (m, 2H, ArH), 7.53–7.74 (m, 5H, ArH),
7.97 (dd, J¼7.5, 1.1 Hz, 1H, ArH), 8.18 (dd, J¼7.5, 1.1 Hz,
1H, ArH); 13C NMR (100.6 MHz, CDCl3) d 11.7 (q), 14.2
(q), 61.2 (t), 114.1 (s), 125.8 (s), 126.1 (d), 126.8 (d), 127.2
(d£2), 129.6 (d£3), 131.5 (s), 133.0 (s), 133.03 (d), 133.32
(d), 133.8 (s), 136.9 (s), 142.8 (s), 146.5 (s), 174.9 (s), 179.6
(s); anal. calcd for C22H17NO4: N, 3.90; C, 73.53; H, 4.77.
Found: N, 3.89; C, 73.40; H, 4.81.
3.3.3. 3-Methoxy-2-(3-methoxycarbonyl-2-phenylpropyl)-
1-methyl-4,9-dihydro-4,9-dioxo-1H-benzo[ f ]indole 9c.
25%; orange crystals; mp 152–1538C; IR (CHCl3) 3010,

7632
C.-C. Tseng et al. / Tetrahedron 58 (2002) 7625–7633
2955, 1730, 1650, 1465, 1270 cm21; H NMR (400 MHz,
CDCl3) d 2.75 (dd, J¼16.2, 7.4 Hz, 1H, CH), 2.83 (dd,
J¼16.2, 7.4 Hz, 1H, CH), 2.92 (dd, J¼14.6, 7.4 Hz, 1H,
CH), 3.02 (dd, J¼14.6, 7.4 Hz, 1H, CH), 3.46 (quintet, J¼
7.4 Hz, 1H, CH), 3.61 (s, 3H, OCH3), 3.77 (s, 3H, CH3),
3.82 (s, 3H, CH3), 7.10–7.18 (m, 2H, ArH), 7.18–7.25 (m,
1H, ArH), 7.25–7.32 (m, 2H, ArH), 7.60–7.69 (m, 2H,
ArH), 8.06–8.17 (m, 2H, ArH); 13C NMR (75.5 MHz,
CDCl3) d 29.9 (t), 33.2 (q), 39.5 (t), 41.3 (d), 51.7 (q), 61.7
(q), 117.5 (s), 126.2 (d), 126.3 (d), 126.6 (s), 127.3 (d£3),
128.8 (d£2), 131.4 (s), 132.8 (d), 132.9 (d), 133.8 (s), 134.1
(s), 142.4 (s), 144.4 (s), 172.4 (s), 175.3 (s), 179.7 (s); anal.
calcd for C25H23NO5: N, 3.36; C, 71.93; H, 5.55. Found: N,
3.33; C, 71.74; H, 5.63.
CH2), 3.70 (s, 3H, OCH3), 5.38 (s, 1H, OCH); 13C NMR
(100.6 MHz, CDCl3) d 21.1 (t), 28.7 (t), 36.6 (t), 55.5 (q),
102.2 (d), 178.6 (s), 199.6 (s); HRMS calcd for C7H10O3
m/e 142.0630, found m/e 142.0633.
1
3.4. Typical experimental procedure for the reaction
mediated by manganese(III) acetate and cerium(III)
nitrate
A solution of 121 mg (0.60 mmol) of 2-(ethylamino)-1,4-
naphthoquinone (1e), 352 mg (2.41 mmol) of methyl
4-methoxyacetoacetate (2k), 520 mg (1.20 mmol) of
cerium(III) nitrate and 802 mg (2.99 mmol) of manga-
nese(III) acetate in 10 ml of acetic acid was stirred at room
temperature for 8 h. After workup as described as above,
The residue was chromatographed over 20 g of silica gel
(eluted with 8:1 hexane–ethyl acetate) followed by
recrystallization (hexane–ethyl acetate) to give 12 mg
(6%) of 19a, followed by 124 mg (63%) of 3u.
3.3.4. 3-Methoxy-2-(3-methoxycarbonylpropyl)-1-
methyl-4,9-dihydro-4,9-dioxo-1H-benzo[ f ]indole 9d.
29%; orange crystals; mp 124–1258C; IR (CHCl3) 3010,
1
2960, 1730, 1650, 1470, 1270 cm21; H NMR (400 MHz,
CDCl3) d 1.91 (quintet, J¼7.4 Hz, 2H, CH2), 2.43 (t, J¼
7.4 Hz, 2H, CH2), 2.72 (t, J¼7.4 Hz, 2H, CH2), 3.68 (s, 3H,
OCH3), 4.01 (s, 3H, CH3), 4.05 (s, 3H, CH3), 7.61–7.71
(m, 2H, ArH), 8.08–8.20 (m, 2H, ArH); 13C NMR
(100.6 MHz, CDCl3) d 21.8 (t), 23.7 (t), 32.9 (t), 33.1
(q), 51.7 (q), 62.1 (q), 117.8 (s), 126.2 (d), 126.3 (d), 126.5
(s), 132.8 (d), 132.9 (d), 133.1 (s), 133.8 (s), 134.1 (s), 143.9
(s), 173.4 (s), 175.4 (s), 179.9 (s); anal. calcd for
C19H19NO5: N, 4.10; C, 66.85; H, 5.61. Found: N, 4.11;
C, 66.60; H, 5.66.
3.4.1. 1-Ethyl-3-methoxycarbonyl-2-methoxymethyl-4,9-
dihydro-4,9-dioxo-1H-benzo[ f ]indole 3u. 63%; the spec-
tral data of 3u has been reported.5h
3.4.2. 2-Chloromethyl-3-ethoxylcarbonyl-1-ethyl-4,9-
dihydro-4,9-dioxo-1H-benzo[ f ]indole 3v. 54%; the spec-
tral data of 3v has been reported.5h
3.4.3. 3-Ethoxycarbonyl-1-ethyl-2-propyl-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 3w. 72%; the spectral data
of 3w has been reported.5h
3.3.5. 5,5-Dimethyl-2-methoxy-1,3-cyclohexanedione
12a. 20%; pale yellow oil; IR (CHCl3) 2970, 1730, 1595,
1
1385, 1300 cm21; H NMR (400 MHz, CDCl3) d 1.08 (s,
3.4.4. 1-Ethyl-3-methoxycarbonyl-3-methoxymethyl-
2,3,4,9-tetrahydro-2,4,9-trioxo-1H-benzo[ f ]indole 19a.
6%; the spectral data of 19a has been reported.5h
6H, CH3), 2.22 (s, 2H, CH2), 2.28 (s, 2H, CH2), 3.70 (s, 3H,
OCH3), 5.37 (s, 1H, OCH); 13C NMR (100.6 MHz, CDCl3)
d 28.1 (q£2), 32.4 (s), 42.6 (t), 50.6 (t), 55.6 (q), 101.0 (d),
177.0 (s), 199.4 (s); HRMS calcd for C9H14O3 m/e
170.0943, found m/e 170.0942.
3.4.5. 3-Chloromethyl-3-ethoxylcarbonyl-1-ethyl-
2,3,4,9-tetrahydro-2,4,9-trioxo-1H-benzo[ f ]indole 19b.
22%; the spectral data of 19b has been reported.5h
3.3.6. 2-Methoxy-5-methyl-1,3-cyclohexanedione 12b.
19%; pale yellow oil; IR (CHCl3) 2960, 1730, 1610, 1380,
3.4.6. 3-Ethoxycarbonyl-1-phenyl-2-propyl-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 22d. 23%; yellow crystals;
mp 156–1578C; IR (CHCl3) 3015, 2975, 1715, 1665, 1495,
1
1250 cm21; H NMR (400 MHz, CDCl3) d 1.08 (d, J¼
6.4 Hz, 3H, CH3), 1.94–2.31 (m, 3H), 2.42 (dd, J¼16.2,
3.2 Hz, 2H, CH), 3.70 (s, 3H, OCH3), 5.36 (s, 1H,
OCH); 13C NMR (100.6 MHz, CDCl3) d 20.7 (q), 28.7
(d), 36.8 (t), 44.9 (t), 55.5 (q), 101.7 (d), 177.9 (s), 199.4 (s);
HRMS calcd for C8H12O3 m/e 156.0786, found m/e
156.0786.
1285 cm21
;
1H NMR (400 MHz, CDCl3) d 0.81 (t, J¼
7.6 Hz, 3H, CH3), 1.45 (t, J¼7.1 Hz, 3H, CH3), 1.38–1.54
(m, 2H, CH2), 2.61 (t, J¼7.6 Hz, 2H, CH2), 4.47 (q, J¼
7.1 Hz, 2H, OCH2), 7.28–7.34 (m, 2H, ArH), 7.51–7.71
(m, 5H, ArH), 7.92–8.00 (m, 1H, ArH), 8.13–8.20
(m, 1H, ArH); 13C NMR (100.6 MHz, CDCl3) d 13.8
(q), 14.1 (q), 22.9 (t), 26.8 (t), 61.1 (t), 113.9 (s), 125.8 (s),
126.1 (d), 126.6 (d), 127.4 (d£2), 129.4 (d£2), 129.6
(d), 131.2 (s), 133.0 (sþd), 133.2 (d), 133.7 (s), 136.7 (s),
146.5 (s), 164.5 (s), 174.9 (s), 179.6 (s); anal. calcd for
C24H21NO4: N, 3.62; C, 74.40; H, 5.46. Found: N, 3.67; C,
74.47; H, 5.50.
3.3.7. 2-Methoxy-5-phenyl-1,3-cyclohexanedione 12c.
21%; pale yellow oil; IR (CHCl3) 2990, 1730, 1610, 1375,
1
1250 cm21; H NMR (400 MHz, CDCl3) d 2.51–2.74 (m,
4H, CH2), 3.29–3.43 (m, 1H, CH), 3.72 (s, 3H, OCH3), 5.46
(s, 1H, OCH), 7.21–7.30 (m, 3H, ArH), 7.31–7.39 (m, 2H,
ArH); 13C NMR (100.6 MHz, CDCl3) d 36.3 (t), 39.3 (d),
43.8 (t), 55.8 (q), 102.0 (d), 126.6 (d£2), 127.0 (d), 128.7
(d£2), 142.6 (s), 177.6 (s), 198.5 (s); HRMS calcd for
C13H14O3 m/e 218.0943, found m/e 218.0943.
3.4.7. 3-Ethoxycarbonyl-2-methyl-1-(p-tolyl)-4,9-dihydro-
4,9-dioxo-1H-benzo[ f ]indole 22e. 29%; the spectral data
of 22e has been reported.5h
3.3.8. 2-Methoxy-1,3-cyclohexanedione 12d. 20%; pale
yellow oil; IR (CHCl3) 2960, 1730, 1610, 1375, 1265 cm21
;
3.4.8. 12-Ethoxycarbonyl-6,11-dihydro-6,11-dioxo-benzo-
[b ]acridine 23b. 22%; the spectral data of 23b has been
reported.5g
1H NMR (400 MHz, CDCl3) d 1.99 (quintet, J¼6.4 Hz, 2H,
CH2), 2.35 (t, J¼6.4 Hz, 2H, CH2), 2.42 (t, J¼6.4 Hz, 2H,

C.-C. Tseng et al. / Tetrahedron 58 (2002) 7625–7633
7633
5. (a) Citterio, A.; Sebastiano, R.; Carvayal, M. C. J. Org. Chem.
1991, 56, 5335. (b) Citterio, A.; Sebastiano, R.; Nicolini, M.
Tetrahedron 1993, 49, 7743. (c) Chuang, C.-P.; Wang, S.-F.
Tetrahedron Lett. 1994, 35, 4365. (d) Chuang, C.-P.; Wang,
S.-F. J. Chin. Chem. Soc. 1997, 44, 271. (e) Chuang, C.-P.;
Wang, S.-F. Tetrahedron 1998, 54, 10043. (f) Chuang, C.-P.;
Wang, S.-F. Heterocycles 1999, 50, 489. (g) Chuang, C.-P.;
Wu, Y.-L.; Jiang, M.-C. Tetrahedron 1999, 55, 11229.
(h) Jiang, M.-C.; Chuang, C.-P. J. Org. Chem. 2000, 65,
5409. (i) Wu, Y.-L.; Chuang, C.-P.; Lin, P.-Y. Tetrahedron
2001, 57, 5543.
3.4.9. 12-Ethoxycarbonyl-2-methyl-6,11-dihydro-6,11-
dioxo-benzo[b ]acridine 23c. 25%; the spectral data of
23c has been reported.5g
Acknowledgments
We are grateful to the National Science Council of the ROC
for financial support (Grant No. NSC-90-2113-M-006-014).
References
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