Solvent effects on the oxidative free radical reactions of 2-amino-1,4-naphthoquinones

Article abstract of DOI:10.1016/j.tet.2004.10.029

Solvent effects on the manganese (III) initiated oxidative free radical reactions of 2-amino-1,4-naphthoquinones are described. This free radical reaction provides a novel method for the synthesis of benzo[f]indole-4,9-diones, benzo[f]indole-2,4,9-triones, benzo[b]carbazole-6,11-diones and benzo[b]acridine-6,11-diones. High chemoselectivity was observed in different solvents. Graphical Abstract

Full text of DOI:10.1016/j.tet.2004.10.029

Tetrahedron 60 (2004) 12249–12260
Solvent effects on the oxidative free radical reactions of
2
-amino-1,4-naphthoquinones
*
Chao-Ming Tseng, Yi-Lung Wu and Che-Ping Chuang
Department of Chemistry, National Cheng Kung University, Tainan 70101, Taiwan, ROC
Received 18 August 2004; accepted 5 October 2004
Available online 28 October 2004
Abstract—Solvent effects on the manganese (III) initiated oxidative free radical reactions of 2-amino-1,4-naphthoquinones are described.
This free radical reaction provides a novel method for the synthesis of benzo[f]indole-4,9-diones, benzo[f]indole-2,4,9-triones,
benzo[b]carbazole-6,11-diones and benzo[b]acridine-6,11-diones. High chemoselectivity was observed in different solvents.
q 2004 Elsevier Ltd. All rights reserved.
6
h
1. Introduction
acid gave 3 and 4 (Eq. 1). The product distributions are
highly dependent on the substituents of b-keto ester 2.
Indoles 3 and 4 were formed presumably via the reaction
route outlined in Scheme 1. Initiation occurs with the
manganese (III) acetate oxidation of 2 to produce radical 5.
This radical intermediate 5 undergoes intermolecular
addition to the quinone ring followed by oxidation to give
6, which undergoes either condensation to generate 3 (path a)
or oxidation to produce radical 7 (path b). Radical 7
undergoes intramolecular cyclization followed by oxidation
Carbon–carbon bond forming reactions mediated by radical
have received considerable attention in organic synthesis
during the last two decades. Naturally occurring quinones
1
such as mitosenes, kinamycins, murrayaquinones, etc.
represent an important class of biologically significant natural
products. A common building block to these compounds is
2
the indoloquinone unit. The development of new synthetic
methodologies for the synthesis of indolequinone ring system
3
,4
1
is therefore important. The oxidative free radical reaction
mediated by metal salts has been developed into a versatile
protocol for the formation of highly functionalized products
to produce 9, which subsequently undergoes alkyl group (R )
migration to produce 4. On the contrary, when 1 and 2 were
treated with cerium (IV) sulfate in methanol, indole 3 was
1
d–f,5–7
6
j
from simple precursors.
Among these, manganese (III)
obtained as the only product. This different reaction
behavior of intermediate 6 can be ascribed to the presence
of cerium salt, which acts as a Lewis acid and the
acetate and cerium (IV) ammonium nitrate have been used
most efficiently. The solvent effects play an important role in
this oxidative free radical reaction. The free radical reaction
8
1
0
condensation rate of 6 was enhanced. Based on these
results, we believe that the acidity of the reaction medium
would affect the production distributions of this reaction. To
test this hypothesis, this oxidative free radical reaction was
performed in various solvents. When a solution of 2-(methyl-
amino)-1,4-naphthoquinone (1a) in formic acid was treated
with ethyl butyrylacetate (2a) and manganese (III) acetate at
6
c–j,9
of 1,4-naphthoquinones has been reported.
In this report,
we wish to describe the solvent effects on the oxidative free
radical reaction between 2-amino-1,4-naphthoquinones and
carbonyl compounds.
2
. Results and discussion
0
(
8C for 30 min, 3a was obtained exclusively in 85% yield
Table 1, entry 1). Other b-keto ester 2 behaved similarly
giving only the corresponding condensation product 3
entries 2–5). It is well known that Brønsted acid can also
2.1. The oxidative free radical reactions of 2-(alkyl-
amino)-1,4-naphthoquinones
(
catalyze the condensation reaction of carbonyl compounds.
These results demonstrate that the higher acidity of formic
acid enhances the condensation rate of 6 and path a is the only
reaction route. We next performed this reaction in less acidic
or neutral solvents. Treatment of 1a and 2a with manganese
We reported previously that the manganese (III)
acetate mediated reaction between 2-(alkylamino)-1,4-
naphthoquinones 1 and b-keto ester 2 (R ZOR) in acetic
2
Keywords: Manganese (III) acetate; Free radical; 2-Amino-1,4-naphtho-
quinones; Solvent effects.
(III) acetate in CF CH OH at 80 8C for 16 h resulted in the
3 2
formation of 3a (12%) and 4a (63%). Results of this reaction
between 1a and 2a in different solvents are summarized in
*
Corresponding author. Fax: C886 6 274 0552;
e-mail: cpchuang@mail.ncku.edu.tw
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.10.029

12250
C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
Table 1 (entries 7–10). In all cases, it gave higher 4a/3a ratio
than those performed in acetic acid (entry 6). This could
account for the rate of condensation (path a) decreasing as the
acidity of reaction medium decreases and the oxidation of 6
to produce radical 7 became the major route (path b). The
scope of this reaction was explored using a variety of b-keto
esters and the results are also illustrated in Table 1 (entries
Manganese (III) acetate mediated free radical reaction
between 2-(alkylamino)-1,4-naphthoquinone 1 and simple
ketone 10 in acetic acid produced 11 as the only product
6
i
(Eq. 2). Indole 11 was formed presumably via a similar
reaction route as shown in Scheme 1 (path a). Due to the
instability of 1 in acidic medium, we expected that the radical
reaction between 1 and 10 in neutral solvents would give 11
in better result. Indeed, when 1a and acetone (10a) were
reacted with manganese (III) acetate in acetonitrile at 80 8C
for 39 h, 11a was isolated in a better reaction yield (85%,
Table 2, entry 1) than that performed in acetic acid (73%).
The results of this reaction with a variety of simple ketones in
different solvents are summarized in Table 2 (entries 1–11).
In all cases, indole 11 was obtained in a better reaction yield
than those performed in acetic acid. This reaction can also be
performed with corresponding ketones as solvent and 11 was
obtained in a similar (better) result. The regioselectivity of
1
1–14). In all cases, 4 is the major product.
1
this reaction was also studied. With butanone (10e: R ZH,
2
R ZMe), 11e and 12a were obtained in 37 and 57% yields,
respectively (entry 12). These two products are derived from
(1)
Scheme 1.
Table 1. Free radical reactions between 2-(methylamino)-1,4-naphthoquinone (1a) and b-keto esters
Entry
b-Keto ester
Solvent time
Reaction
Product (yield (%))
1
2
1
2
3
4
5
6
7
8
9
2a: R Zn-Pr, R ZOEt
HCO
HCO
HCO
HCO
HCO
2
2
2
2
2
H
H
H
H
H
30 min
30 min
30 min
30 min
30 min
16 h
16 h
16 h
16 h
16 h
3a (85)
3b (75)
3c (76)
3d (66)
3e (63)
3a (54)
3a (12)
3a (13)
3a (8)
3a (8)
3b (8)
3c (11)
3d (6)
1
2
2b: R Zi-Pr, R ZOMe
1
2
2c: R ZEt, R ZOMe
1
2
2d: R ZClCH
2
, R ZOEt
1
2
2e: R ZMeOCH
2
, R ZOMe
1
2
a
2a: R Zn-Pr, R ZOEt
HOAc
CF CH
CH
4a (21)
4a (63)
4a (48)
4a (56)
4a (52)
1
2
2a: R Zn-Pr, R ZOEt
3
2
OH
1
2
2a: R Zn-Pr, R ZOEt
3
CN
1
2
2a: R Zn-Pr, R ZOEt
C
6
H
CHCl
6
1
2
10
11
12
13
14
2a: R Zn-Pr, R ZOEt
3
1
2
2b: R Zi-Pr, R ZOMe
CF
3
CF
3
CF
3
CF
3
CH
CH
CH
CH
2
2
2
2
OH
OH
OH
OH
16 h
16 h
16 h
16 h
4b (79)
4c (62)
4d (72)
4e (73)
1
2
2c: R ZEt, R ZOMe
1
2
2d: R ZClCH
2
, R ZOEt
1
2
2e: R ZMeOCH
2
, R ZOMe
a
6h
The result has been reported previously.

C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
12251
Table 2. Free radical reactions between 2-(methylamino)-1,4-naphthoquinone (1a) and simple ketones
Entry
Ketone
Solvent
Reaction time
Product (yield (%))
1
2
1
2
3
4
5
6
7
8
9
10a: R ZH, R ZH
CH
3
CN
39 h
42 h
16 h
30 min
16 h
41 h
16 h
16 h
24 h
22 h
26 h
21 h
41 h
11a (85)
11a (86)
11a (80)
11a (0)
1
2
10a: R ZH, R ZH
C
6
H
6
1
2
10a: R ZH, R ZH
CHCl
2
HCO H
3
1
2
10a: R ZH, R ZH
1
2
a
a
a
a
10a: R ZH, R ZH
11a (90)
11b (72)
11b (91)
11c (90)
11c (87)
11d (38)
11d (38)
11e (37)
11f (70)
1
2
10b: R ZMe, R ZMe
CH
CH
CH
3
3
3
CN
CN
CN
1
2
10b: R ZMe, R ZMe
1
2
10c: R CR ZCH
2
CH
CH
CH
CH
2
2
CH
CH
2
1
2
10c: R CR ZCH
2
2
1
2
10
11
12
13
10d: R CR ZCH
2
2
1
2
10d: R CR ZCH
2
2
1
2
10e: R ZH, R ZMe
CH
CH
3
CN
CN
12a (57)
12b (17)
1
2
10f: R ZH, R Zi-Pr
3
a
The reaction was performed in corresponding ketone.
the intermolecular addition of radical 13a and 14a. The
regioselectivity increases as the size of R increases (entry 13).
(15a) (4 equiv) and manganese (III) acetate (5 equiv) in
acetonitrile at 80 8C for 43 h gave indole 16a in 31% yield
2
(
1
Table 3, entry 1). Using 10 equiv of 15a, the desired indole
6a was afforded in 58% yield (entry 2). We also performed
this reaction in various solvents. In benzene, the yield of 16a
is 52% (35 h, 80 8C). In CF CH OH, the reaction rate is much
3
2
slower. After heated at 80 8C for 86 h, the yield of 16a is 35%
based on 71% conversion of 1a. In acetic acid, it proceeded in
a much faster reaction rate (26 h, 45 8C), however, 16a was
obtained in a much poor yield (13%) and an uncharacterized
product was also obtained. The results are summarized in
Table 3 (entries 1–5). Best yields are obtained in acetonitrile.
Indole 16a was generated via a similar reaction route as
shown in Scheme 1 (path a). The scope of this oxidative
annulation process with other 4-aryl-3-buten-2-one 15 are
also illustrated in Table 3 (entries 6–10). To study the steric
effect on the reactivity of enone 15, we also examined this
reaction with 15f and 15g. On the reaction of 15f with 1a,
indole 16f was produced though in a slower reaction rate.
After heated for 71 h, 16f was obtained in 65% yield (entry
11). With 15g, indole 16g was also produced effectively via
this oxidative annulation process (entry 12). These obser-
(
2)
0
Unsaturated a -keto radical can be generated regioselec-
tively from the manganese (III) oxidation of a,b-unsaturated
ketones. We next studied the free radical reaction of
-(alkylamino)-1,4-naphthoquinone 1 with a,b-unsaturated
ketone 15 (Eq. 3). Treatment of 2-(methylamino)-1,4-
naphthoquinone (1a) with trans-4-phenyl-3-buten-2-one
4
7
vations demonstrate that the bulkiness of substituent R has
little effect on this reaction. In order to test the regioselec-
tivity of this reaction, butenone 15i was allowed to react with
1a and 16i was obtained as the only product (entry 14). This
2
Table 3. Free radical reactions of 2-(methylamino)-1,4-naphthoquinone (1a) and a,b-unsaturated ketones
Entry
a,b-Unsaturated ketone
Solvent
Reaction time (h)
Product (yield(%))
1
2
3
4
a
1
2
3
4
5
6
7
8
9
15a: R ZH, R ZC
6
6
6
6
6
H
H
H
H
H
5
5
5
5
5
, R ZH, R ZH
CH
CH
3
CN
CN
43
41
35
26
86
45
24
46
66
45
71
64
17
28
68
45
40
17
16a (31)
1
2
3
4
15a: R ZH, R ZC
, R ZH, R ZH
3
16a (58)
16a (52)
16a (13)
1
2
3
4
15a: R ZH, R ZC
, R ZH, R ZH
C
6
H
6
1
2
3
4
15a: R ZH, R ZC
, R ZH, R ZH
HOAc
CF CH
CH
1
2
3
4
b
15a: R ZH, R ZC
, R ZH, R ZH
3
2
OH
16a (35)
1
2
3
4
15b: R ZH, R Z4-Cl(C
6
6
2
H
H
C(C
4
), R ZH, R ZH
), R ZH, R ZH
3
CN
16b (63)
16b (39)
16c (64)
16d (37)
16e (59)
16f (65)
16g (68)
16h (59)
16i (50)
16j (41)
16k (32)
20a (76)
20b (66)
1
2
3
4
15b: R ZH, R Z4-Cl(C
4
C
6
H
6
1
2
3
4
15c: R ZH, R Z4-MeO
6
H
4
), R ZH, R ZH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
3
3
3
3
CN
1
2
3
4
15d: R ZH, R Z4-MeO(C
6
H
4
), R ZH, R ZH
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
1
2
3
4
10
11
12
13
14
15
16
17
18
15e: R ZH, R Z2-thienyl, R ZH, R ZH
1 2 3 4
6 5
15f: R ZH, R ZC H , R ZH, R ZMe
3 4
1
2
15g: R ZH, R ZC H , R ZH, R Zi-Pr
6 5
1
2
3 4
15h: R ZH, R ZCO Me, R ZH, R ZH
2
1
2
3 4
15i: R ZH, R ZMe, R ZMe, R ZH
1
2
3
4
15j: R ZMe, R ZMe, R ZH, R ZH
1
2
3
4
15k: R CR ZCH
2
CH
2
CH
2
CH
2
, R ZH, R ZH
1
19a: R ZPh
1
19b: R ZEt
a
The reaction was conducted with 4 equiv of 15a.
Based on 71% conversion of 1a.
b

12252
C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
product 16i was formed via the intermolecular addition of an
a -keto radical 17 to the quinone ring. No product derived
21, the corresponding carbazole 23 was afforded effectively
under identical conditions (entries 3–6). As shown in
Table 4, benzene proved superior to acetonitrile as a
reaction solvent. With 3-methyl-2-cyclohexenone (21d), in
0
from the addition of a g-keto radical 18 to the quinone ring
can be detected. Similarly, reaction of enones 15j and 15k
with manganese (III) acetate gave annulation products 16j
1
2
contrast to 22a, the dehydrogenation of 22f (R ZH, R Z
0
3
and 16k, respectively via the addition of a similar a -keto
Me, R ZH) proceeded in a much slower reaction rate. After
radical (entries 15 and 16). Notably, butynone 19 behaved
similarly, giving the corresponding annulation product 20
effectively (entries 17 and 18).
heating in benzene for 16 h, carbazoles 22f and 23f were
obtained in 45 and 43% yields, respectively (entry 7). The
different behavior between 22a and 22f suggests that
the strong electron donating ethoxy group enhances the
dehydrogenation rate of 22a. Since the separation of 22f and
23f was problematic, the reaction mixture of 22f and 23f
was heated further for another 99 h with another 2 equiv of
manganese (III) acetate and 23f was afforded in 66% yield
(entry 8). The reaction yield of 23f can be improved
significantly to 79% by heating the crude product mixture of
(3)
2
3
2f and 23f directly with DDQ for 1 h (entry 9). Other
-substituted cyclohexenones (21e, 21f) behaved similarly,
giving the corresponding product mixture of 22 and 23, and
again this crude product mixture could be converted to 23
effectively by heating further with DDQ (entries 10 and 11).
With 3-unsubstituted 2-cyclohexenone 21, carbazole 23 was
formed in poor yield and no 22 could be detected (entries
1
2–15). When cyclohexenones 24 and 26, bearing geminal
dimethyl group, were allowed to react with 1, dihydro-
carbazoles 25 and 27 were obtained (entries 16 and 17).
We also investigated this manganese (III) mediated radical
reaction with 2-cyclohexenone 21 (Eq. 4). Reaction of 2-
(
methylamino)-1,4-naphthoquinone (1a) with 3-ethoxy-2-
cyclohexenone (21a) and manganese (III) acetate in
acetonitrile at 80 8C for 36 h provides 23a in 66% yield
(
Table 4, entry 1). Carbazole 23a was produced presumably
1
2
3
from the dehydrogenation of 22a (R ZH, R ZOEt, R Z
H), which was formed via a similar reaction route outlined
in Scheme 1 (path a). With other 3-ethoxy-2-cyclohexenone
(
4)
Table 4. Free radical reactions of 2-(alkylamino)-1,4-naphthoquinone 1 and 2-cyclohexenones
Entry
Quinone
2-Cyclohexenone
Solvent
Reaction time (h)
Product (yield(%))
1
2
3
1
2
3
4
5
6
7
8
9
1a: RZMe
1b: RZEt
1a: RZMe
1b: RZEt
1a: RZMe
1a: RZMe
1b: RZEt
1b: RZEt
1b: RZEt
1a: RZMe
1a: RZMe
1a: RZMe
1b: RZEt
1a: RZMe
1a: RZMe
1a: RZMe
1b: RZEt
21a: R ZH, R ZOEt, R ZH
CH
3
CN
36
26
43
24
49
39
16
16
16
19
72
53
39
68
34
23
17
23a (66)
1
2
3
21a: R ZH, R ZOEt, R ZH
C
CH
6
H
6
23b (87)
23c (47)
23d (62)
23e (66)
23e (72)
22f (45)
1
2
3
21b: R ZH, R ZOEt, R ZMe
3
CN
1
2
3
21b: R ZH, R ZOEt, R ZMe
C
CH
6
H
6
1
2
3
21c: R ZH, R ZOEt, R ZPh
3
CN
1
2
3
21c: R ZH, R ZOEt, R ZPh
C
C
C
C
C
C
6
H
6
H
6
H
6
H
6
H
6
H
6
6
6
6
6
1
2
3
21d: R ZH, R ZMe, R ZH
23f (43)
1
2
3
a
21d: R ZH, R ZMe, R ZH
23f (66)
23f (79)
1
2
3
b
21d: R ZH, R ZMe, R ZH
1
2
3
b
b
10
11
12
13
14
15
16
17
21e: R ZH, R ZMe, R ZMe
23g (70)
1
2
3
21f: R ZCl, R ZMe, R ZH
6
23h (56)
23i (19)
23j (0)
1
2
3
21g: R ZH, R ZH, R ZH
CH
3
CN
1
2
3
21g: R ZH, R ZH, R ZH
C
CH
6
H
6
1
2
3
21h: R ZCl, R ZH, R ZH
3
CN
23k (20)
23k (23)
25 (76)
27 (57)
1
2
3
21h: R ZCl, R ZH, R ZH
24
26
C
C
C
6
H
6
H
6
H
6
6
6
a
The reaction mixture was reacted further with another 2 equiv of Mn(OAc)
The crude product was heated further with 1 equiv of DDQ for 1 h.
3
for 99 h.
b

C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
12253
Table 5. Free radical reactions between 2-(anilino)-1,4-naphthoquinone
28) and b-dicarbonyl compounds
(
Entry b-Dicarbonyl
compound
Solvent
Reaction Product
time
(yield(%))
1
2
1
2
3
4
5
6
7
8
9
1
1
1
2a: R Zn-Pr, R ZOEt HCO
2
2
2
2
2
2
2
2
2
H
H
H
H
H
H
H
H
H
30 min
3.5 h
30 min
30 min
30 min
5 h
30 min
1 h
3.5 h
29a (66)
29b (15)
29c (71)
29d (76)
29e (77)
29f (0)
29g (68)
29h (50)
29i (17)
30a (64)
30a (46)
30a (48)
30a (46)
30a (66)
30b (69)
30c (56)
30d (57)
1
2
2b: R Zi-Pr, R ZOme HCO
1
2
2f: R ZMe, R ZOEt
HCO
HCO
HCO
HCO
HCO
HCO
HCO
1
2
2g: R ZMe, R ZMe
1
2
2h: R ZEt, R ZEt
1
2
2i: R Zi-Pr, R Zi-Pr
1
2
2j: R ZMe, R ZPh
1
2
2k: R ZMe, R Zi-Bu
1
2
2l: R ZMe, R Zt-Bu
1
2
0
1
2
2a: R Zn-Pr, R ZOEt CF
3
CH
CN
2
OH 48 h
1
2
2a: R Zn-Pr, R ZOEt CH
3
42 h
47 h
42 h
2
1
.2. The oxidative free radical reactions of 2-(anilino)-
,4-naphthoquinones
1
2
2a: R Zn-Pr, R ZOEt
C
6
H
6
1
2
13
2a: R Zn-Pr, R ZOEt CHCl
3
1
2
14
15
16
17
2f: R ZMe, R ZOEt
CF
3
CF
3
CF
3
CF
3
CH
2
2
2
2
OH 39 h
OH 23 h
OH 23 h
OH 23 h
1
2
2g: R ZMe, R ZMe
CH
CH
CH
Manganese (III) mediated free radical reaction between
2-(anilino)-1,4-naphthoquinone (28) and b-dicarbonyl
compound 2 in acetic acid produced 29 and 30 (Eq. 5).
1
2
2h: R ZEt, R ZEt
1
2
2i: R Zi-Pr, R Zi-Pr
6
h
In all cases, acridine 30 is the major product. A possible
mechanism for this reaction is shown in Scheme 2.
Oxidation of the b-dicarbonyl compound 2 by manganese
also summarized in Table 5 (entries 14–17). It shows the
same selectivity, in all cases, acridine 30 was obtained as the
only product.
(
III) acetate oxidation produces radical 5. This radical
intermediate 5 undergoes intermolecular addition to the
quinone ring followed by oxidation to give 31, which
undergoes either condensation to produce 29 (path a) or
oxidation to generate radical 32 (path b). This radical 32
undergoes further intramolecular cyclization followed by
aromatization to give 33. Quinone 33 undergoes retro
Claisen condensation followed by aromatization to produce
3
0. On the contrary, in the reaction between 28 and 2
mediated by cerium (IV) sulfate, indole 29 was obtained as
(5)
6
j
the only product. This is presumably due to the Lewis
acidity of cerium salt, which enhances the condensation rate
of 31 (path a). Based on these results, we expected that the
chemoselectivity of this reaction would be affected by the
acidity of the solvent. In agreement with this expectation,
when 2-(anilino)-1,4-naphthoquinone (28) was reacted with
ethyl butyrylacetate (2a) and manganese (III) acetate in
In conclusion, carbon radical can be generated from the
manganese (III) acetate oxidation of carbonyl compounds
and it undergoes efficient addition to the C–C double bond
of 2-amino-1,4-naphthoquinones. This free radical reaction
provides a novel method for the synthesis of benzo[f]indole-
8
0% aqueous formic acid at 0 8C, 29a was obtained as the
only product in 66% yield and no trace of 30a could be
isolated (Table 5, entry 1). This can be ascribed to the higher
acidity of formic acid, which promotes the condensation of
4
,9-diones, benzo[f]indole-2,4,9-triones, benzo[b]carba-
zole-6,11-diones and benzo[b]acridine-6,11-diones. With
b-dicarbonyl compounds, by changing the solvent, these
products can be generated in high chemoselectivities. With
simple ketones and a,b-unsaturated ketones, these reactions
gave better results in neutral solvents.
3
1. These reaction conditions were then applied to other
b-dicarbonyl compounds and the corresponding 29 was
isolated as the only product. Steric hindrance plays an
important role in the final outcome of this reaction. In most
cases, the reaction yield decreases as the size of R and R
increases (entries 1–6) and the condensation reaction occurs
only on the less hindered carbonyl group of the 1,3-diones
1
2
(
entries 7–9). We next studied this reaction in less acidic or
neutral solvents. Treatment of 28 with 2a and manganese
III) acetate in CF CH OH at 80 8C resulted in the
3. Experimental
(
3
2
formation of 30a (64%) and no trace of 29a could be
found (entry 10). This again is presumably due to the rate of
condensation (path a) decreases as the acidity of reaction
medium decreases and the oxidation of 31 (/32) occurred
Melting points are uncorrected. Infrared spectra were taken
1
13
with a Hitachi 260-30 spectrometer. H and C NMR
spectra were recorded on a Bruker AMX-400 or AVANCE
300 spectrometer. Chemical shifts are reported in ppm
relative to TMS as internal reference. Elemental analyses
were performed with Heraeus CHN-Rapid Analyzer.
Analytical thin-layer chromatography was performed 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 chromatography over EM
(
path b). In attempt to investigate the range of solvents
compatible with this reaction, this manganese (III) mediated
reaction between 28 and 2a was performed in various
solvents. As shown in Table 5 (entry 10–13), it gave best
results in CF CH OH. This investigation was extended to a
3
2
number of other b-dicarbonyl compounds and the results are

12254
C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
Scheme 2.
K1
1
Laboratories silica gel (70–230 mesh). The starting
2
1275 cm ; H NMR (400 MHz, CDCl ) d 1.26 (t, JZ
3
1
1
4c
-amino-1,4-naphthoquinone 1, 28, enones 21b,
12a
7.6 Hz, 3H, CH ), 2.89 (q, JZ7.6 Hz, 2H, CH ), 3.96 (s, 3H,
3
2
1
2a
12b
12b
2
1c,
21f
and 21h
were synthesized according to
OCH ), 4.07 (s, 3H, NCH ), 7.63–7.70 (m, 2H, ArH), 8.08–
3 3
13
6
j
6j
6h
literature procedure. The spectra data of 3a, 3b6,j 3d,
3
2
8.17 (m, 2H, ArH); C NMR (100.6 MHz, CDCl ) d 13.3
3
6j
6h
6h
6i
6i
6i
6j
6j
e, 4a, 4d,6h 11b–f, 12a, 12b, 29a, 29c, 29d,
9g and 30a have been reported.
(q), 18.2 (t), 32.8 (q), 52.1 (q), 112.8 (s), 125.6 (s), 126.1 (d),
126.7 (d), 130.5 (s), 132.9 (d), 133.1 (s), 133.3 (d), 133.8 (s),
6
j
1
47.5 (s), 165.0 (s), 176.4 (s), 179.5 (s). Anal. Calcd for
: C, 68.68; H, 5.09; N, 4.71. Found: C, 68.64; H,
5.15; N, 4.71.
3.1. Typical experimental procedure for the reaction
between 2-(methylamino)-1,4-naphthoquinone (1a) and
b-keto esters in formic acid
C H15NO
17 4
3.2.2. 2,3,4,9-Tetrahydro-3-isopropyl-3-(methoxycarbo-
nyl)-1-methyl-2,4,9-trioxo-1H-benzo[f]indole 4b. Orange
A mixture of 152 mg (0.81 mmol) of 2-(methylamino)-1,4-
naphthoquinone (1a), 508 mg (3.22 mmol) of ethyl butyr-
ylacetate (2a) and 1.29 g (4.81 mmol) of Mn(OAc) in
3
crystals; mp 153–154 8C; IR (CHCl ) 2975, 1760, 1675,
3
K1
1595, 1275, 1240 cm ; H NMR (400 MHz, CDCl ) d
1
3
1
0 mL of formic acid was stirred at 0 8C for 30 min. The
1.02 (d, JZ6.9 Hz, 3H, CH ), 1.03 (d, JZ6.9 Hz, 3H, CH ),
3
3
reaction mixture was diluted with 100 mL of ethyl acetate,
washed with 50 mL of saturated aqueous sodium bisulfite,
three 50 mL portions of water, 50 mL of saturated aqueous
sodium bicarbonate, dried (Na SO ), The solvent was
3.06 (septet, JZ6.9 Hz, 1H, CH), 3.55 (s, 3H, NCH ), 3.71
3
(s, 3H, OCH ), 7.73 (td, JZ7.3, 1.4 Hz, 1H, ArH), 7.78 (td,
3
JZ7.3, 1.4 Hz, 1H, ArH), 8.09 (dd, JZ7.3, 1.4 Hz, 1H,
13
ArH), 8.11 (dd, JZ7.3, 1.4 Hz, 1H, ArH); C NMR
2
4
evaporated under reduced pressure and the crude product
was purified by column chromatography on silica (20 g)
using dichloromethane–hexane (2:1) as eluent, followed by
crystallization (ethyl acetate–hexane) to give 224 mg (85%)
of 3a.
(100.6 MHz, CDCl ) d 17.0 (q), 18.8 (q), 28.9 (q), 33.6 (d),
3
53.1 (q), 64.9 (s), 125.2 (s), 126.3 (d), 126.5 (d), 131.5 (s),
132.3 (s), 133.1 (d), 134.6 (d), 147.6 (s), 166.4 (s), 174.4 (s),
178.3 (s), 178.5 (s). Anal. Calcd for C H NO : C, 66.05;
1
8
17
5
H, 5.23; N, 4.28. Found: C, 65.99; H, 5.26; N, 4.29.
3.2. Typical experimental procedure for the reaction
between 2-(methylamino)-1,4-naphthoquinone (1a) and
3.2.3. 3-Ethyl-2,3,4,9-tetrahydro-3-(methoxycarbonyl)-
1-methyl-2,4,9-trioxo-1H-benzo[f]indole 4c. Yellow crys-
b-keto esters in less acidic or neutral solvent
tals; mp 155–156 8C; IR (CHCl ) 1760, 1675, 1600, 1240,
3
K1
1
1
390 cm ; H NMR (400 MHz, CDCl ) d 0.74 (t, JZ
3
A mixture of 150 mg (0.80 mmol) of 2-(methylamino)-1,4-
naphthoquinone (1a), 520 mg (3.29 mmol) of ethyl butyryl-
7.5 Hz, 3H, CH ), 2.40–2.58 (m, 2H, CH ), 3.56 (s, 3H,
3 2
NCH ), 3.71 (s, 3H, OCH ), 7.74 (td, JZ7.4, 1.6 Hz, 1H,
3 3
acetate (2a) and 1.29 g (4.81 mmol) of Mn(OAc) in 10 mL
3
ArH), 7.79 (td, JZ7.4, 1.6 Hz, 1H, ArH), 8.09 (dd, JZ7.4,
13
of CF CH OH was heated at 80 8C for 16 h. The reaction
3
1.6 Hz, 1H, ArH), 8.13 (dd, JZ7.4, 1.6 Hz, 1H, ArH);
C
NMR (100.6 MHz, CDCl ) d 8.3 (q), 26.3 (t), 29.0 (q), 53.3
2
mixture was diluted with 100 mL of ethyl acetate, washed
with 50 mL of saturated aqueous sodium bisulfite, three
3
(q), 61.0 (s), 125.6 (s), 126.3 (d), 126.5 (d), 131.7 (s), 132.1
(s), 133.2 (d), 134.6 (d), 147.4 (s), 166.7 (s), 174.8 (s), 178.3
(s), 178.4 (s). Anal. Calcd for C H NO : C, 65.17; H,
5
0 mL portions of water, dried (Na SO ), and concentrated
2 4
in vacuo. The residue was chromatographed over 20 g of
silica gel (eluted with 1:15 ethyl acetate–hexane and then
1
7
15
5
4.83; N, 4.47. Found: C, 65.10; H, 4.85; N, 4.42.
1
(
:12 ethyl acetate–hexane) followed by crystallization
ethyl acetate–hexane) to give 174 mg (63%) of 4a and
3.2.4. 2,3,4,9-Tetrahydro-3-(methoxycarbonyl)-3-(meth-
oxymethyl)-1-methyl-2,4,9-trioxo-1H-benzo[f]indole 4e.
3
2 mg (12%) of 3a.
Yellow crystals; mp 207–208 8C; IR (CHCl ) 3015, 1760,
3
K1
1730, 1650, 1240 cm ; H NMR (300 MHz, CDCl ) d
1
3.2.1. 2-Ethyl-4,9-dihydro-3-(methoxycarbonyl)-1-
methyl-4,9-dioxo-1H-benzo[f]indole 3c. Yellow needles;
3
3.25 (s, 3H, OCH ), 3.55 (s, 3H, NCH ), 3.72 (s, 3H, OCH ),
3
3
3
mp 119–120 8C; IR (CHCl ) 1715, 1660, 1600, 1505,
3
4.21 (d, JZ8.6 Hz, 1H, OCH), 4.33 (d, JZ8.6 Hz, 1H,

C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
12255
OCH), 7.70–7.82 (m, 2H, ArH), 8.05–8.15 (m, 2H, ArH);
C NMR (75.5 MHz, CDCl ) d 29.2 (q), 53.4 (q), 59.4 (q),
ethyl acetate, washed with 50 mL of saturated aqueous
sodium bisulfite, three 50 mL portions of water, dried
(Na SO ). The solvent was evaporated under reduced
pressure and the crude product mixture of 22f and 23f was
then heated at 80 8C with DDQ (136 mg, 0.60 mmol) in
10 mL of benzene for another 1 h. The reaction mixture was
diluted with 100 mL of ethyl acetate, washed with three
1
3
3
6
1
1
0.8 (s), 72.3 (t), 124.5 (s), 126.1 (d), 126.5 (d), 131.8 (s),
32.2 (s), 133.2 (d), 134.5 (d), 147.9 (s), 164.8 (s), 173.8 (s),
78.4 (s), 178.6 (s). Anal. Calcd for C H NO : C, 62.00;
2
4
1
7
15
6
H, 4.59; N, 4.25. Found: C, 62.29; H, 4.63; N, 4.20.
3
.3. Typical experimental procedure for the reaction
50 mL portions of water and dried (Na SO ). The solvent
2 4
between 2-(methylamino)-1,4-naphthoquinone (1a) and
simple ketones
was evaporated under reduced pressure and the crude
product was purified by column chromatography on silica
(20 g) using dichloromethane–hexane (2:1) as eluent,
followed by crystallization (ethyl acetate–hexane) to give
23f (135 mg, 79%).
A mixture of 118 mg (0.63 mmol) of 2-(methylamino)-1,4-
naphthoquinone (1a), 375 mg (6.47 mmol) of acetone (10a)
and 1.03 g (3.84 mmol) of Mn(OAc) in 10 mL of CH CN
3
3
was heated at 80 8C for 16 h, followed by the addition of
.04 g (3.88 mmol) of Mn(OAc) . The reaction mixture
heated for another 23 h 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
3.5.1. 4,9-Dihydro-1-methyl-(E)-4,9-dioxo-2-styryl-1H-
benzo[f]indole 16a. Red needles; mp 205–206 8C; IR
(CHCl ) 3010, 2955, 1645, 1595, 1470 cm ; H NMR
1
3
K1
1
3
(400 MHz, CDCl ) d 4.11 (s, 3H, NCH ), 6.90 (d, JZ
3
3
16.1 Hz, 1H, ]CH), 6.97 (s, 1H, ArH), 7.14 (d, JZ16.1 Hz,
1H, ]CH), 7.28–7.35 (m, 1H, ArH), 7.35–7.42 (m, 2H,
ArH), 7.45–7.54 (m, 2H, ArH), 7.54–7.68 (m, 2H, ArH),
(
Na SO ), The solvent was evaporated under reduced
2 4
pressure and the crude product was purified by column
chromatography on silica (20 g) using dichloromethane–
hexane (1:1) as eluent, followed by crystallization (ethyl
acetate–hexane) to give 121 mg (85%) of 11a.
1
3
8.06–8.17(m, 2H, ArH); C NMR (75.4 MHz, CDCl ) d
3
32.7 (q), 105.4 (d), 114.1 (d), 126.3 (2!d), 126.8 (2!d),
128.6 (s), 128.7 (d), 128.9 (2!d), 130.8 (s), 132.7 (d), 133.1
(d), 133.4 (s), 134.1 (d), 134.5 (s), 136.1 (s), 141.1 (s), 175.5
(s), 180.8 (s). Anal. Calcd for C21 : C, 80.49; H,
4.82; N, 4.47. Found: C, 80.28; H, 4.83; N, 4.49.
3.3.1. 4,9-Dihydro-1,2-dimethyl-4,9-dioxo-1H-benzo[-
f]indole 11a. Yellow crystals; mp 236–237 8C; IR
H15NO
2
K1
CHCl ) 1650, 1600, 1500, 1485, 1250 cm ; H NMR
1
(
3
(
NCH ), 6.52 (s, 1H, ArH), 7.60–7.70 (m, 2H, ArH), 8.09–
400 MHz, CDCl ) d 2.32 (s, 3H, ArCH ), 4.00 (s, 3H,
3.5.2. (E)-2-[2-(4-Chlorophenyl)vinyl]-4,9-dihydro-1-
methyl-4,9-dioxo-1H-benzo[f]indole 16b. Red crystals;
mp 264–265 8C; IR (CHCl ) 2930, 1730, 1650, 1595,
3
3
3
13
8
.17 (m, 2H, ArH); C NMR (100.6 MHz, CDCl ) d 12.2
3
3
K1
1
(
q), 32.6 (q), 107.2 (d), 126.28 (d), 126.32 (d), 128.2 (s),
1495 cm ; H NMR (400 MHz, CDCl ) d 4.19 (s, 3H,
3
1
1
30.6 (s), 132.7 (d), 132.9 (d), 133.5 (s), 134.2 (s), 139.9 (s),
75.6 (s), 181.1 (s). Anal. Calcd for C H NO : C, 74.65;
NCH ), 6.96 (d, JZ16.1 Hz, 1H, ]CH), 7.05 (s, 1H, ArH),
3
7.16 (d, JZ16.1 Hz, 1H, ]CH), 7.36 (d, JZ8.5 Hz, 2H,
ArH), 7.45 (d, JZ8.5 Hz, 2H, ArH), 7.63–7.72 (m, 2H,
ArH), 8.12–8.20 (m, 2H, ArH); C NMR (75.4 MHz,
1
4
11
2
H, 4.92; N, 6.22. Found: C, 74.64; H, 4.94; N, 6.25.
1
3
3.4. Typical experimental procedure for the reaction
between 2-(methylamino)-1,4-naphthoquinone (1a) and
a,b-unsaturated ketones
CDCl ) d 32.8 (q), 105.6 (d), 114.8 (d), 126.5 (2!d), 127.9
3
(2!d), 128.7 (s), 129.1 (2!d), 131.0 (s), 132.8 (d), 132.9
(d), 133.2 (d), 133.5 (s), 134.47 (s), 134.54 (s), 134.6 (s),
1
C
40.8 (s), 175.7 (s), 181.0 (s). Anal. Calcd for
14ClNO : C, 72.52; H, 4.06; N, 4.03. Found: C,
72.30; H, 4.14; N, 3.98.
A mixture of 101 mg (0.54 mmol) of 2-(methylamino)-1,4-
naphthoquinone (1a), 782 mg (5.35 mmol) of trans-4-
phenyl-3-buten-2-one (15a) and 717 mg (2.67 mmol) of
Mn(OAc) in 10 mL of CH CN was heated at 80 8C for
21
H
2
3.5.3. 4,9-Dihydro-(E)-2-[2-(4-methoxycarbonylphenyl)-
vinyl]-1-methyl-4,9-dioxo-1H-benzo[f]indole 16c. Orange
needles; mp 208–209 8C; IR (CHCl ) 1720, 1670, 1645,
3
3
24 h, followed by the addition of 287 mg (1.07 mmol) of
Mn(OAc) . The reaction mixture heated for another 17 h
and then diluted with 100 mL of ethyl acetate, washed with
3
3
K1
1
1410, 1285 cm ; H NMR (400 MHz, CDCl ) d 3.94 (s,
3
5
portions of water, dried (Na SO ), and concentrated in
vacuo. The residue was chromatographed over 20 g of silica
gel (eluted with 2:1 dichloromethane–hexane) followed by
crystallization (ethyl acetate–hexane) to give 97 mg (58%)
of 16a.
0 mL of saturated aqueous sodium bisulfite, three 50 mL
3H, OCH ), 4.20 (s, 3H, NCH ), 7.089 (d, JZ16.1 Hz, 1H,
3
3
]CH), 7.093 (s, 1H, ArH), 7.23 (d, JZ16.1 Hz, 1H, ]CH),
7.57 (d, JZ8.3 Hz, 2H, ArH), 7.62–7.73 (m, 2H, ArH), 8.05
2
4
1
3
(d, JZ8.3 Hz, 2H, ArH), 8.14–8.20 (m, 2H, ArH);
C
NMR (75.4 MHz, CDCl ) d 32.8 (q), 52.2 (q), 106.0 (d),
3
116.6 (d), 126.5 (2!d), 126.6 (2!d), 128.7 (s), 129.9 (s),
1
30.1(s), 130.17 (2!d), 131.2 (s), 132.7 (d), 133.0 (d),
133.2 (d), 133.4 (s), 134.5 (s), 140.4 (s), 166.6 (s), 175.8 (s),
180.9 (s). Anal. Calcd for C23 : C, 74.38; H, 4.61; N,
3.5. Typical experimental procedure for the reaction
between 2-(methylamino)-1,4-naphthoquinone (1a) and
a,b-unsaturated ketones followed by DDQ oxidation
H17NO
4
3.77. Found: C, 74.18; H, 4.64; N, 3.70.
A mixture of 120 mg (0.60 mmol) of 2-(ethylamino)-1,4-
naphthoquinone (1b), 658 mg (5.98 mmol) of 3-methyl-2-
cyclohexenone (21d) and 801 mg (2.99 mmol) of manga-
nese (III) acetate in 10 mL of benzene was heated at 80 8C
for 16 h. The reaction mixture was diluted with 100 mL of
3.5.4. 4,9-Dihydro-(E)-2-[2-(4-methoxyphenyl)vinyl]-1-
methyl-4,9-dioxo-1H-benzo[f]indole 16d. Red needles;
mp 207–208 8C; IR (CHCl ) 3010, 2960, 1645, 1510,
3
K1
1
1465 cm ; H NMR (400 MHz, CDCl ) d 3.85 (s, 3H,
3
OCH ), 4.16 (s, 3H, NCH ), 6.83 (d, JZ16.0 Hz, 1H,
3
3

12256
C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
]
7
CH), 6.92 (d, JZ8.7 Hz, 2H, ArH), 7.00 (s, 1H, ArH),
.16 (d, JZ16.0 Hz, 1H, ]CH), 7.46 (d, JZ8.7 Hz, 2H,
ArH), 7.61–7.70 (m, 2H, ArH), 8.12–8.16 (m, 2H, ArH);
126.64 (d),126.66 (d), 128.3 (s), 130.0 (d), 132.4 (s), 133.32
(d), 133.36 (d), 133.40 (s), 134.3 (s), 137.4 (s), 166.6 (s),
176.3 (s), 180.5 (s). Anal. Calcd for C H NO : C, 69.15;
1
7
13
4
1
3
C NMR (75.4 MHz, CDCl ) d 32.7 (q), 55.4 (q), 105.0 (d),
3
H, 4.44; N, 4.74. Found: C, 69.01; H, 4.51; N, 4.72.
1
12.0 (d), 114.3 (2!d), 126.4 (2!d), 128.2 (2!d), 128.8
(
(
s), 128.9 (s), 130.6 (s), 132.7 (d), 133.1 (d), 133.5 (s), 133.9
d), 134.6 (s), 141.7 (s), 160.2 (s), 175.4 (s), 181.1 (s). Anal.
3.5.9. 4,9-Dihydro-1-methyl-2-(2-methyl-1-propenyl)-
4,9-dioxo-1H-benzo[f]indole 16i. Orange needles; mp
Calcd for C H NO : C, 76.95; H, 4.99; N, 4.08. Found: C,
2
159–160 8C; IR (CHCl ) 3010, 2925, 1650, 1595,
3
2
17
3
K1 1
1470 cm ; H NMR (400 MHz, CDCl ) d 1.94 (s, 3H,
7
6.67; H, 5.04; N, 4.02.
3
CH ), 2.00 (s, 3H, CH ), 3.99 (s, 3H, NCH ), 6.01 (s, 1H,
3
3
3
3.5.5. 4,9-Dihydro-1-methyl-4,9-dioxo-(E)-2-(2-thieylvi-
nyl)-1H-benzo[f]indole 16e. Red needles; mp 215–
]CH), 6.66 (s, 1H, ArH), 7.60–7.68 (m, 2H, ArH), 8.09–
8.15 (m, 2H, ArH); C NMR (75.4 MHz, CDCl ) d 20.4
13
3
K1
2
16 8C; IR (CHCl ) 3015, 2955, 1645, 1595, 1410 cm
;
H NMR (400 MHz, CDCl ) d 4.14 (s, 3H, NCH ), 6.74 (d,
(q), 27.1 (q), 32.8 (q), 108.0 (d), 112.4 (d), 126.2 (2!d),
128.1 (s), 129.7 (s), 132.6 (d), 132.9 (d), 133.5 (s), 134.4 (s),
140.3 (s), 143.2 (s), 175.6 (s), 181.1 (s). Anal. Calcd for
C H NO : C, 76.96; H, 5.70; N, 5.28. Found: C, 76.93; H,
3
1
3
3
JZ15.9 Hz, 1H, ]CH), 6.98 (s, 1H, ArH), 7.04 (dd, JZ4.6,
.6 Hz, 1H, ArH), 7.14 (d, JZ3.6 Hz, 1H, ArH), 7.28 (d,
JZ4.6 Hz, 1H, ArH), 7.30 (d, JZ15.9 Hz, 1H, ]CH),
3
1
7
15
2
5.80; N, 5.28.
1
3
7
(
(
(
(
.60–7.69 (m, 2H, ArH), 8.10–8.16 (m, 2H, ArH); C NMR
75.4 MHz, CDCl ) d 32.7 (q), 105.3 (d), 113.5 (d), 125.9
3
3.5.10. 4,9-Dihydro-1-methyl-(E)-2-(1-methyl-1-prope-
nyl)-4,9-dioxo-1H-benzo[f]indole 16j. Orange needles;
mp 101–102 8C; IR (CHCl ) 3010, 1655, 1595, 1475,
d), 126.4 (2!d), 127.0 (d), 128.0 (2!d), 128.7 (s), 130.8
s), 132.8 (d), 133.1 (d), 133.4 (s), 134.6 (s), 140.8 (s), 141.6
s), 175.5 (s), 180.9 (s). Anal. Calcd for C H NO S: C,
3
K1
1
1
9
13
2
1445 cm ; H NMR (400 MHz, CDCl ) d 1.85 (d, JZ
3
7
1.45; H, 4.10; N, 4.39. Found: C, 71.41; H, 4.11; N, 4.44.
6.5 Hz, 3H, CH ), 1.98 (d, JZ1.3 Hz, 3H, CH ), 3.99 (s, 3H,
3
3
NCH ), 5.78 (qq, JZ6.5, 1.3 Hz, 1H, ]CH), 6.58 (s, 1H,
3
3
1
.5.6. 4,9-Dihydro-1,3-dimethyl-4,9-dioxo-(E)-2-styryl-
H-benzo[f]indole 16f. Red crystals; mp 218–219 8C; IR
ArH), 7.61–7.70 (m, 2H, ArH), 8.10–8.18 (m, 2H, ArH);
C NMR (75.4 MHz, CDCl ) d 14.2 (q), 16.9 (q), 34.5 (q),
1
3
3
K1
1
(CHCl ) 3015, 2950, 1645, 1595, 1495, 1465 cm ; H
NMR (400 MHz, CDCl ) d 2.60 (s, 3H, ArCH ), 4.14 (s, 3H,
NCH ), 6.93 (d, JZ16.5 Hz, 1H, ]CH), 6.99 (d, JZ
106.7 (d), 126.0 (s), 126.30 (d), 126.34 (d), 128.2 (s), 130.1
(d), 130.7 (s), 132.7 (d), 133.0 (d), 133.6 (s), 134.4 (s), 147.2
(s), 175.9 (s), 181.2 (s). Anal. Calcd for C H NO : C,
3
3
3
3
17 15
2
1
6.5 Hz, 1H, ]CH), 7.30–7.37 (m, 1H, ArH), 7.37–7.44
m, 2H, ArH), 7.49–7.53 (m, 2H, ArH), 7.60–7.68 (m, 2H,
76.96; H, 5.70; N, 5.28. Found: C, 76.94; H, 5.77; N, 5.30.
(
ArH), 8.10–8.17 (m, 2H, ArH); C NMR (75.4 MHz,
CDCl ) d 11.7 (q), 33.5 (q), 115.1 (d), 121.4 (s), 125.7 (s),
3
1
3
3.5.11. 2-(1-Cyclohexenyl)-4,9-dihydro-1-methyl-4,9-
dioxo-1H-benzo[f]indole 16k. Yellow needles; mp 155–
K1
126.1 (d), 126.2 (d), 126.6 (2!d), 128.7 (d), 128.9 (2!d),
130.0 (s), 132.76 (d), 132.82 (d), 134.0 (s), 134.3 (s), 135.7
156 8C; IR (CHCl ) 3010, 2940, 1650, 1455, 1340 cm
3
;
1
H NMR (400 MHz, CDCl ) d 1.67–1.74 (m, 2H, CH ),
3 2
(
C H NO : C, 80.71; H, 5.23; N, 4.28. Found: C, 80.68; H,
d), 136.5 (s), 138.1 (s), 175.7 (s), 182.2 (s). Anal. Calcd for
1.74–1.83 (m, 2H, CH ), 2.22–2.31 (m, 4H, CH ), 4.00 (s,
2 2
2
2
17
2
3H, NCH ), 5.96 (s, 1H, ]CH), 6.58 (s, 1H, ArH), 7.61–
3
13
5
.24; N, 4.29.
7.67 (m, 2H, ArH), 8.09–8.15 (m, 2H, ArH); C NMR
75.4 MHz, CDCl ) d 21.6 (t), 22.5 (t), 25.5 (t), 29.0 (t), 34.5
(q), 106.5 (d), 126.2 (2!d), 128.06 (s), 128.09 (s), 130.7 (s),
(
3
3.5.7. 4,9-Dihydro-3-isopropyl-1-methyl-4,9-dioxo-(E)-2-
styryl-1H-benzo[f]indole 16g. Red needles; mp 165–
131.9 (d), 132.6 (d), 132.9 (d), 133.5 (s), 134.3 (s), 145.8 (s),
175.7 (s), 181.1 (s). Anal. Calcd for C19H17NO : C, 78.33;
2
H, 5.88; N, 4.81. Found: C, 78.29; H, 5.90; N, 4.82.
K1
1
66 8C; IR (CHCl ) 3010, 1590, 1460, 1410, 1360 cm
3
;
1
H NMR (400 MHz, CDCl ) d1.43 (d, JZ7.1 Hz, 6H, 2!
3
CH ), 3.54 (septet, JZ7.1 Hz, 1H, CH), 4.11 (s, 3H, NCH ),
3
3
6
]
7
8
.82 (d, JZ17.7 Hz, 1H, ]CH), 6.96 (d, JZ17.7 Hz, 1H,
CH), 7.32–7.38 (m, 1H, ArH), 7.39–7.45 (m, 2H, ArH),
.52–7.56 (m, 2H, ArH), 7.64–7.68 (m, 2H, ArH), 8.12–
3.5.12. 4,9-Dihydro-1-methyl-4,9-dioxo-2-(phenylethy-
nyl)-1H-benzo[f]indole 20a. Orange needles; mp 193–
K1
194 8C; IR (CHCl ) 3010, 1660, 1595, 1480, 1465 cm
3
;
1
3
1
.20 (m, 2H, ArH); C NMR (75.4 MHz, CDCl ) d 21.1
3
H NMR (400 MHz, CDCl ) d 4.15 (s, 3H, NCH ), 6.97 (s,
3 3
(
2!q), 25.9 (d), 34.3 (q), 115.9 (d), 125.1 (s), 125.9 (d),
1H, ArH), 7.36–7.41 (m, 3H, ArH), 7.52–7.57 (m, 2H,
ArH), 7.63–7.68 (m, 2H, ArH), 8.09–8.18 (m, 2H, ArH);
C NMR (75.4 MHz, CDCl ) d 34.3 (q), 78.5 (s), 97.9 (s),
1
1
1
26.6 (d), 126.7 (2!d), 128.8 (d), 128.9 (2!d), 131.4 (s),
32.3 (s), 132.7 (d), 132.9 (d), 133.8 (s), 134.3 (s), 136.1 (s),
37.3 (d), 137.6 (s), 176.2 (s), 181.1 (s). Anal. Calcd for
1
3
3
112.8 (d), 121.6 (s), 125.2 (s), 126.4 (d), 126.6 (d), 127.8 (s),
128.5 (2!d), 129.3 (d), 131.0 (s), 131.6 (2!d), 133.1 (2!
d), 133.5 (s), 134.0 (s), 175.6 (s), 180.3 (s). Anal. Calcd for
C H NO : C, 81.01; H, 4.21; N, 4.50. Found: C, 80.94; H,
C H NO : C, 81.10; H, 5.96; N, 3.94. Found: C, 81.14; H,
2
6
4
21
2
.00; N, 3.91.
2
1
13
2
3.5.8. 4,9-Dihydro-(E)-2-[2-(methoxycarbonyl)vinyl]-1-
methyl-4,9-dioxo-1H-benzo[f]indole 16h. Yellow crystals;
4.27; N, 4.50.
mp 248–249 8C; IR (CHCl ) 3015, 2955, 1730, 1655,
3
3.5.13. 2-(Butyn-1-yl)-4,9-dihydro-1-methyl-4,9-dioxo-
1H-benzo[f]indole 20b. Yellow needles; mp 192–193 8C;
K1
440 cm ; H NMR (400 MHz, CDCl ) d 3.84 (s, 3H,
1
1
3
K1
IR (CHCl ) 3010, 2990, 1660, 1595, 1465 cm ; H NMR
1
OCH ), 4.19 (s, 3H, NCH ), 6.51 (d, JZ15.8 Hz, 1H,
3
3
3
]
7
CH), 7.16 (s, 1H, ArH), 7.65 (d, JZ15.8 Hz, 1H, ]CH),
.68–7.73 (m, 2H, ArH), 8.12–8.20 (m, 2H, ArH); C NMR
(400 MHz, CDCl ) d 1.28 (t, JZ7.5 Hz, 3H, CH ), 2.51
3
3
1
3
(q, JZ7.5 Hz, 2H, CH ), 4.05 (d, JZ1.9 Hz, 3H, NCH ),
2
3
(
75.4 MHz, CDCl ) d 32.9 (q), 52.0 (q), 108.5 (d), 121.4 (d),
3
6.80 (d, JZ1.9 Hz,1H, ArH), 7.61–7.68 (m, 2H, ArH),

C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
12257
1
.07–8.16 (m, 2H, ArH); C NMR (75.4 MHz, CDCl ) d
3.3 (t), 13.5 (q), 34.1 (q), 69.5 (s), 101.1 (s), 111.9 (d),
26.0 (s), 126.4 (d), 126.5 (d), 127.6 (s), 130.4 (s), 132.95
3
8
1
1
C, 75.22; H, 5.37; N, 4.39. Found: C, 75.07; H, 5.39; N,
4.40.
3
(d), 133.02 (d), 133.6 (s), 134.0 (s), 175.5 (s), 180.4 (s).
Anal. Calcd for C H NO : C, 77.55; H, 4.98; N, 5.32.
Found: C, 77.22; H, 5.09; N, 5.30.
3.5.18. 3-Ethoxy-5-ethyl-6,11-dihydro-1-methyl-6,11-
dioxo-5H-benzo[b]carbazole 23d. Red crystals; mp 168–
1
7
13
2
169 8C; IR (CHCl ) 2985, 2930, 1655, 1615, 1595,
3
K1
1
1
495 cm ; H NMR (400 MHz, CDCl ) d 1.45 (t, JZ
3
3
5
.5.14. 5-Ethyl-1,2,6,11-tetrahydro-3-methyl-6,11-dioxo-
H-benzo[b]carbazole 22f. Red crystals; mp 195–196 8C;
7.2 Hz, 3H, CH ), 1.47 (t, JZ7.0 Hz, 3H, CH ), 2.95 (s, 3H,
ArCH ), 4.09 (q, JZ7.0 Hz, 2H, OCH ), 4.70 (q, JZ7.2 Hz,
3 2
3
3
K1
1
IR(CHCl ) 2985, 2930, 1635, 1595, 1575, 1475 cm ; H
3
2H, NCH ), 6.58 (d, JZ2.0 Hz, 1H, ArH), 6.74–6.80 (m,
2
NMR(400 MHz, CDCl ) d 1.40 (t, JZ7.2 Hz, 3H, CH ),
1H, ArH), 7.63 (td, JZ7.3, 1.6 Hz, 1H, ArH), 7.67 (td, JZ
7.3, 1.6 Hz, 1H, ArH), 8.09 (dd, JZ7.3, 1.6 Hz, 1H, ArH),
8.15 (dd, JZ7.3, 1.6 Hz, 1H, ArH); C NMR (75.4 MHz,
3
3
1
8
1
.97 (s, 3H, CH ), 2.39 (t, JZ8.7 Hz, 2H, CH ), 3.08 (t, JZ
3
2
1
3
.7 Hz, 2H, CH ), 4.46 (q, JZ7.2 Hz, 2H, NCH ), 6.15 (s,
2
2
H, ]CH), 7.56–7.66 (m, 2H, ArH), 8.06–8.13 (m, 2H,
CDCl ) d 14.7 (q), 14.8 (q), 23.7 (q), 40.2 (t), 63.7 (t), 90.3
3
1
3
ArH); C NMR (75.4 MHz, CDCl ) d 15.9 (q), 20.1 (t),
3
(d), 117.0 (d), 118.3 (s), 120.9 (s), 125.7 (d), 126.5 (d),
132.4 (d), 133.0 (s), 133.4 (d), 134.36 (s), 134.38 (s), 136.9
(s), 141.2 (s), 159.2 (s), 178.3 (s), 180.2 (s). Anal. Calcd for
C H NO : C, 75.66; H, 5.74; N, 4.20. Found: C, 75.45; H,
2
1
4.3 (q), 29.5 (t), 40.2 (t), 110.2 (d), 118.7 (s), 124.6 (s),
25.9 (2!d), 128.1 (s), 132.1 (d), 132.8 (d), 133.9 (s), 134.9
(
s), 138.5 (s), 143.7 (s), 174.0 (s), 182.4 (s). Anal. Calcd for
C H NO : C, 78.33; H, 5.88; N, 4.81. Found: C, 78.32; H,
2
1
19
3
5.77; N, 4.15.
1
9
17
2
5
.89; N, 4.84.
3.5.19. 3-Ethoxy-6,11-dihydro-5-methyl-6,11-dioxo-1-
phenyl-5H-benzo[b]carbazole 23e. Red crystals; mp
3.5.15. 3-Ethoxy-6,11-dihydro-5-methyl-6,11-dioxo-5H-
benzo[b]carbazole 23a. Orange needles; mp 233–234 8C;
246–247 8C; IR (CHCl ) 3010, 1655, 1615, 1495,
3
K1
IR (CHCl ) 2990, 1655, 1625, 1595, 1480 cm ; H NMR
1
K1
1
1480 cm ; H NMR (400 MHz, CDCl ) d 1.46 (t, JZ
3
3
(
400 MHz, CDCl ) d 1.48 (t, JZ7.0 Hz, 3H, CH ), 4.11 (q,
7.0 Hz, 3H, CH ), 4.12 (q, JZ7.0 Hz, 2H, OCH ), 4.24 (s,
3
3
3
2
JZ7.0 Hz, 2H, OCH ), 4.18 (s, 3H, NCH ), 6.75 (d, JZ
3H, NCH ), 6.77 (d, JZ2.0 Hz, 1H, ArH), 6.93 (d, JZ
2
3
3
2
7
8
3
1
.1 Hz, 1H, ArH), 7.01 (dd, JZ8.9, 2.1 Hz, 1H, ArH), 7.62–
.72 (m, 2H, ArH), 8.10–8.20 (m, 2H, ArH), 8.27 (d, JZ
2.0 Hz, 1H, ArH), 7.35–7.40 (m, 2H, ArH), 7.43–7.48 (m,
3H, ArH), 7.57–7.62 (m, 2H, ArH), 7.95–7.99 (m, 1H,
1
.9 Hz, 1H, ArH); C NMR (75.4 MHz, CDCl ) d 14.8 (q),
3
13
ArH), 8.06–8.11 (m, 1H, ArH); C NMR (75.4 MHz,
3
1.9 (q), 63.9 (t), 93.2 (d), 116.0 (d), 118.0 (s), 119.3 (s),
24.6 (d), 126.1 (d), 126.3 (d), 132.7 (d), 133.4 (d), 133.7
CDCl ) d 14.8 (q), 32.2 (q), 64.0 (t), 92.3 (d), 116.2 (s),
3
117.6 (d), 120.2 (s), 125.7 (d), 126.7 (d), 127.2 (d), 127.4
(2!d), 128.8 (2!d), 132.2 (d), 132.9 (s), 133.4 (d), 134.5
(s), 135.5 (s), 140.3 (s), 142.1 (s), 142.4 (s), 158.8 (s), 178.8
(s), 178.9 (s). Anal. Calcd for C H NO : C, 78.72; H,
(
(
s), 134.0 (s), 134.5(s), 141.5 (s), 159.6 (s), 178.4 (s), 181.3
s). Anal. Calcd for C H NO : C, 74.74; H, 4.95; N, 4.59.
1
9
15
3
Found: C, 74.77; H, 4.91; N, 4.57.
2
5
19
3
5.02; N, 3.67. Found: C, 78.71; H, 5.11; N, 3.60.
3.5.16. 3-Ethoxy-5-ethyl-6,11-dihydro-6,11-dioxo-5H-
benzo[b]carbazole 23b. Orange needles; mp 190–191 8C;
3.5.20. 5-Ethyl-6,11-dihydro-3-methyl-6,11-dioxo-5H-
benzo[b]carbazole 23f. Orange crystals; mp 223–224 8C;
IR (CHCl ) 2930, 1655, 1625, 1595, 1475 cm ; H NMR
K1 1
IR (CHCl ) 2990, 1655, 1625, 1505, 1475 cm ; H NMR
3
K1
1
(
400 MHz, CDCl ) d 1.43 (t, JZ7.2 Hz, 3H, CH ), 1.44 (t,
3
3
3
JZ7.0 Hz, 3H, CH ), 4.03 (q, JZ7.0 Hz, 2H, OCH ), 4.60
(400 MHz, CDCl ) d 1.48 (t, JZ7.1 Hz, 3H, CH ), 2.50 (s,
3
2
3
3
(
q, JZ7.2 Hz, 2H, NCH ), 6.66 (d, JZ2.1 Hz, 1H, ArH),
3H, ArCH ), 4.72 (q, JZ7.1 Hz, 2H, NCH ), 7.20 (d, JZ
2
3
2
6
1
7
8
.92 (dd, JZ8.8, 2.1 Hz, 1H, ArH), 7.60 (td, JZ7.2, 1.7 Hz,
H, ArH), 7.64 (td, JZ7.2, 1.7 Hz, 1H, ArH), 8.05 (dd, JZ
.2, 1.7 Hz, 1H, ArH), 8.10 (dd, JZ7.2, 1.7 Hz, 1H, ArH),
8.1 Hz, 1H, ArH), 7.21 (s, 1H, ArH), 7.63–7.72 (m, 2H,
ArH), 8.13 (d, JZ7.2 Hz, 1H, ArH), 8.18 (d, JZ7.2 Hz, 1H,
ArH), 8.29 (d, JZ8.1 Hz, 1H, ArH); C NMR (75.4 MHz,
1
3
1
3
.19 (d, JZ8.8 Hz, 1H, ArH); C NMR (75.4 MHz,
CDCl ) d 15.2 (q), 22.3 (q), 40.1 (t), 110.4 (d), 119.1(s),
3
CDCl ) d 14.7 (q), 14.9 (q), 40.1 (t), 63.7 (t), 93.1 (d),
1
(
(
122.0 (s), 123.5 (d), 126.2 (d), 126.3 (d), 126.6 (d), 132.7
(d), 133.6 (d), 133.7 (s), 134.12 (s), 134.13 (s), 137.8 (s),
139.5 (s), 178.7 (s), 181.2 (s). Anal. Calcd for C H NO :
C, 78.87; H, 5.23; N, 4.84. Found: C, 78.86; H, 5.25; N,
4.84.
3
15.6 (d), 118.0 (s), 119.2 (s), 124.5 (d), 125.9 (d), 126.1
d), 132.6 (d), 133.2 (d), 133.6 (s), 133.7 (s), 133.8 (s), 140.3
s), 159.3 (s), 177.8 (s), 181.2 (s). Anal. Calcd for
1
9
15
2
C H NO : C, 75.22; H, 5.37; N, 4.39. Found: C, 75.19;
2
0
17
3
H, 5.42; N, 4.37.
3.5.21. 6,11-Dihydro-1,3,5-trimethyl-6,11-dioxo-5H-ben-
zo[b]carbazole 23g. Orange needles; mp 247–248 8C; IR
3
5
.5.17. 3-Ethoxy-6,11-dihydro-1,5-dimethyl-6,11-dioxo-
H-benzo[b]carbazole 23c. Red needles; mp 227–228 8C;
K1 1
(CHCl ) 3010, 1655, 1620, 1595, 1495, 1480 cm ; H
3
K1
1
IR (CHCl ) 2925, 1655, 1615, 1595, 1495 cm ; H NMR
3
NMR (400 MHz, CDCl ) d 2.43 (s, 3H, ArCH ), 2.96 (s, 3H,
3
3
(
400 MHz, CDCl ) d 1.47 (t, JZ6.9 Hz, 3H, CH ), 2.94 (s,
ArCH ), 4.18 (s, 3H, NCH ), 6.94 (s, 1H, ArH), 7.00 (s, 1H,
3 3
3
3
3
NCH ), 6.53 (s, 1H, ArH), 6.75 (s, 1H, ArH), 7.59–7.69 (m,
H, ArCH ), 4.08 (q, JZ6.9 Hz, 2H, OCH ), 4.16 (s, 3H,
ArH), 7.60–7.73 (m, 2H, ArH), 8.10 (d, JZ7.3 Hz, 1H,
ArH), 8.17 (d, JZ7.3 Hz, 1H, ArH); C NMR (75.4 MHz,
3
2
13
3
1
H, ArH), 8.04–8.17 (m, 2H, ArH); C NMR (75.4 MHz,
3
2
CDCl ) d 14.8 (q), 23.7 (q), 32.1 (q), 63.7 (t), 90.3 (d), 117.2
CDCl ) d 21.9 (q), 23.5 (q), 32.1 (q), 107.8 (d), 120.3 (s),
3
121.6 (s), 125.7 (d), 126.6 (d), 128.2 (d), 132.4 (d), 133.0
(s), 133.6 (d), 134.5 (s), 135.1 (s), 135.3 (s), 137.8 (s), 141.3
(s), 179.3 (s), 180.0 (s). Anal. Calcd for C H NO : C,
3
(
d), 118.0 (s), 120.7 (s), 125.7 (d), 126.5 (d), 132.4 (d),
1
1
33.0 (s), 133.4 (d), 134.4 (s), 134.9 (s), 136.8 (s), 142.3 (s),
59.2 (s), 178.7 (s), 180.1 (s). Anal. Calcd for C H NO :
1
9
15
2
78.87; H, 5.23; N, 4.84. Found: C, 78.92; H, 5.28; N, 4.87.
2
0
17
3

12258
C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
3
5
2
1
.5.22. 4-Chloro-6,11-dihydro-3,5-dimethyl-6,11-dioxo-
H-benzo[b]carbazole 23h. Orange needles; mp 269–
132.4 (d), 132.9 (d), 133.8 (s), 134.8 (s), 136.5 (s), 144.0 (d),
174.6 (s), 182.4 (s). Anal. Calcd for C H NO : C, 78.66;
H, 6.27; N, 4.59. Found: C, 78.25; H, 6.28; N, 4.55.
2
0
19
2
70 8C; IR (CHCl ) 3065, 2915, 1660, 1520, 1465,
3
K1
250 cm ; H NMR (400 MHz, CDCl ) d 2.52 (s, 3H,
1
3
ArCH ), 4.70 (s, 3H, NCH ), 7.25 (d, JZ8.2 Hz, 1H, ArH),
3.6. Typical experimental procedure for the reaction
between 2-(anilino)-1,4-naphthoquinone (28) and
b-dicarbonyl compounds in formic acid
3
3
7
.65–7.79 (m, 2H, ArH), 8.12–8.25 (m, 2H, ArH), 8.31 (d,
1
3
JZ8.2 Hz, 1H, ArH); C NMR (75.4 MHz, CDCl ) d 20.7
3
(
(
q), 35.5 (q), 118.2 (s), 118.9 (s), 121.7 (d), 125.1 (s), 126.1
d), 126.7 (d), 127.8 (d), 131.7 (s), 133.0 (d), 133.7 (dCs),
A mixture of 151 mg (0.61 mmol) of 2-(anilino)-1,4-
naphthoquinone (28), 383 mg (2.42 mmol) of ethyl butyr-
ylacetate (2a) and 646 mg (2.41 mmol) of Mn(OAc) in
3
135.5 (s), 136.1 (s), 136.5 (s), 179.0 (s), 181.1 (s). Anal.
Calcd for C H ClNO : C, 69.80; H, 3.90; N, 4.52. Found:
C, 69.67; H, 3.97; N, 4.52.
1
8
12
2
10 mL of 80% aqueous formic acid was stirred at 0 8C for
3
0 min. The reaction mixture was diluted with 100 mL of
3.5.23. 6,11-Dihydro-5-methyl-6,11-dioxo-5H-benzo[b]-
carbazole 23i. Yellow needles; mp 213–214 8C; IR
ethyl acetate, washed with 50 mL of saturated aqueous
sodium bisulfite, three 50 mL portions of water, 50 mL of
saturated aqueous sodium bicarbonate, dried (Na SO ), and
K1
CHCl ) 3015, 2925, 1660, 1595, 1480 cm ; H NMR
1
(
3
2
4
(
400 MHz, CDCl ) d 4.19 (s, 3H, NCH ), 7.30–7.45 (m, 3H,
3
concentrated in vacuo. The residue was chromatographed
over 20 g of silica gel (eluted with 2:1 dichloromethane–
hexane) followed by crystallization (ethyl acetate–hexane)
to give 155 mg (66%) of 29a.
3
ArH), 7.64 (td, JZ7.4, 1.5 Hz, 1H, ArH), 7.69 (td, JZ7.4,
.5 Hz, 1H, ArH), 8.10 (dd, JZ7.4, 1.5 Hz, 1H, ArH), 8.16
dd, JZ7.4, 1.5 Hz, 1H, ArH), 8.38 (d, JZ8.0 Hz, 1H,
1
(
1
3
ArH); C NMR (75.4 MHz, CDCl ) d 31.9 (q), 110.7 (d),
3
1
(
1
18.6 (s), 123.7 (d), 123.8 (s), 124.4 (d), 126.1 (d), 126.3
d), 127.1 (d), 132.7 (d), 133.4 (s), 133.6 (d), 134.0 (s),
35.0 (s), 139.8 (s), 179.0 (s), 180.9 (s). Anal. Calcd for
C H NO : C, 78.15; H, 4.24; N, 5.36. Found: C, 78.16; H,
3.6.1. 4,9-Dihydro-2-isopropyl-3-(methoxycarbonyl)-4,9-
dioxo-1-phenyl-1H-benzo[f]indole 29b. Yellow powders;
mp 210–211 8C; IR (CHCl ) 1730, 1665, 1595, 1290,
3
K1
1
1
7
11
2
1240 cm ; H NMR (400 MHz, CDCl ) d 1.24 (d, JZ
3
4
.25; N, 5.36.
7.1 Hz, 6H, 2!CH ), 2.81 (septet, JZ7.1 Hz, 1H, CH),
3
4
.03 (s, 3H, OCH ), 7.28–7.34 (m, 2H, ArH), 7.55–7.60 (m,
3
3.5.24. 4-Chloro-6,11-dihydro-5-methyl-6,11-dioxo-5H-
benzo[b]carbazole 23k. Yellow needles; mp 225–226 8C;
3H, ArH), 7.62 (td, JZ7.2, 1.6 Hz, 1H, ArH), 7.66 (td, JZ
7.2, 1.6 Hz, 1H, ArH), 7.94–7.99 (m, 1H, ArH), 8.13 (dd,
K1
IR (CHCl ) 3015, 2925, 1665, 1600, 1470 cm ; H NMR
1
13
JZ7.2, 1.6 Hz, 1H, ArH); C NMR (100.6 MHz, CDCl ) d
3
3
(
1
400 MHz, CDCl ) d 4.62 (s, 3H, NCH ), 7.21 (t, JZ7.8 Hz,
H, ArH), 7.34 (d, JZ7.8 Hz, 1H, ArH), 7.63–7.74 (m, 2H,
21.4 (2!q), 26.1 (d), 52.7 (q), 113.2 (s), 125.9 (s), 126.3
(d), 126.5 (d), 127.5 (2!d), 129.5 (2!d), 129.7 (d), 130.0
(s), 133.2 (2!d), 133.3 (s), 133.4 (s), 136.8 (s), 148.4 (s),
166.4 (s), 174.6 (s), 180.1 (s). Anal. Calcd for C H NO :
3
3
ArH), 8.07–8.18 (m, 2H, ArH), 8.37 (d, JZ7.8 Hz, 1H,
1
ArH); C NMR (75.4 MHz, CDCl ) d 35.1 (q), 118.5 (s),
3
3
23 19
4
1
18.7 (s), 122.5 (d), 124.8 (d), 126.1 (d), 126.6 (d), 126.8
C, 73.98; H, 5.13; N, 3.75. Found: C, 74.04; H, 5.18;
N, 3.74.
(
(
s), 129.0 (d), 132.9 (d), 133.5 (s), 133.6 (s), 133.8 (d), 135.2
s), 135.7 (s), 178.9 (s), 180.7 (s). Anal. Calcd for
C H ClNO : C, 69.05; H, 3.41; N, 4.74. Found: C,
2
3.6.2. 2-Ethyl-4,9-dihydro-4,9-dioxo-1-phenyl-3-propio-
nyl-1H-benzo[f]indole 29e. Yellow powders; mp 120–
1
7
10
6
8.82; H, 3.37; N, 4.71.
K1
1
21 8C; IR (CHCl ) 1660, 1600, 1495, 1465, 1270 cm
3
;
1
3
.5.25. 1,2,6,11-Tetrahydro-1,1,3,5-tetramethyl-6,11-
dioxo-5H-benzo[b]carbazole 25. Red needles; mp 152–
H NMR (400 MHz, CDCl ) d 1.02 (t, JZ7.5 Hz, 3H, CH ),
3
3
1.26 (t, JZ7.3 Hz, 3H, CH ), 2.56 (q, JZ7.5 Hz, 2H, CH ),
3 2
K1
1
53 8C; IR (CHCl ) 3010, 2915, 1640, 1590, 1410 cm
;
H NMR (400 MHz, CDCl ) d 1.44 (s, 6H, 2!CH ), 1.98
3.16 (q, JZ7.3 Hz, 2H, CH ), 7.25–7.35 (m, 2H, ArH),
3
2
1
7.54–7.61 (m, 3H, ArH), 7.64 (td, JZ7.6, 1.4 Hz, 1H, ArH),
7.68 (td, JZ7.6, 1.4 Hz, 1H, ArH), 7.98 (dd, JZ7.6, 1.4 Hz,
3
3
(
s, 3H, CH ), 2.28 (s, 2H, CH ), 4.03 (s, 3H, NCH ), 6.19 (s,
3 2 3
1
3
1
ArH); C NMR (75.4 MHz, CDCl ) d 24.2 (q), 27.7 (2!q),
H, ]CH), 7.59–7.64 (m, 2H, ArH), 8.07–8.13 (m, 2H,
1H, ArH), 8.16 (dd, JZ7.6, 1.4 Hz, 1H, ArH); C NMR
1
3
(100.6 MHz, CDCl ) d 8.6 (q), 14.4 (q), 18.3 (t), 37.0 (t),
3
3
3
1
1
2.5 (q), 33.1 (s), 47.5 (t), 109.4 (d), 124.7 (s), 125.6 (d),
26.4 (d), 127.6 (s), 130.0 (s), 132.4 (d), 132.6 (d), 134.1 (s),
34.2 (s), 138.7 (s), 142.6 (s), 175.1 (s), 181.3 (s). Anal.
122.2 (s), 125.2 (s), 126.2 (d), 126.7 (d), 127.3 (2!d), 129.5
(2!d), 129.6 (d), 130.8 (s), 133.2 (s), 133.3 (2!d), 133.5
(s), 136.8 (s), 147.2 (s), 174.9 (s), 181.0 (s), 202.8 (s). Anal.
Calcd for C H NO : C, 77.29; H, 5.36; N, 3.92. Found: C,
Calcd for C H NO : C, 78.66; H, 6.27; N, 4.59. Found: C,
2
0
19
2
23 19
3
7
8.70; H, 6.27; N, 4.62.
77.02; H, 5.35; N, 3.97.
3.5.26. 5-Ethyl-1,2,6,11-tetrahydro-2,2-dimethyl-6,11-
dioxo-5H-benzo[b]carbazole 27. Orange crystals; mp
3.6.3. 4,9-Dihydro-3-isovaleryl-2-methyl-4,9-dioxo-1-
phenyl-1H-benzo[f]indole 29h. Pale yellow powders; mp
1
1
2
4
42–143 8C; IR (CHCl ) 2970, 2930, 1640, 1595,
3
151–152 8C; IR (CHCl ) 2960, 1660, 1595, 1500,
3
K1 1
480 cm ; H NMR (400 MHz, CDCl ) d 1.14 (s, 6H,
K1 1
1285 cm ; H NMR (400 MHz, CDCl ) d 1.01 (d, JZ
3
3
!CH ), 1.42 (t, JZ7.2 Hz, 3H, CH ), 3.01 (s, 2H, CH ),
6.8 Hz, 6H, 2!CH ), 2.16 (s, 3H, ArCH ), 2.27 (septet, JZ
3
3
2
3
3
.52 (q, JZ7.2 Hz, 2H, NCH ), 5.94 (d, JZ10.0 Hz, 1H,
6.8 Hz, 1H, CH), 3.08 (d, JZ6.8 Hz, 2H, CH ), 7.27–7.32
2
2
]
ArH), 8.09–8.17 (m, 2H, ArH); C NMR (75.4 MHz,
CDCl ) d 16.1 (q), 28.5 (q), 28.6 (q), 33.6 (s), 34.9 (t), 40.5
3
CH), 6.32 (d, JZ10.0 Hz, 1H, ]CH), 7.60–7.70 (m, 2H,
(m, 2H, ArH), 7.55–7.60 (m, 3H, ArH), 7.64 (td, JZ7.4,
1.5 Hz, 1H, ArH), 7.69 (td, JZ7.4, 1.5 Hz, 1H, ArH), 7.99
(dd, JZ7.4, 1.5 Hz, 1H, ArH), 8.18 (dd, JZ7.4, 1.5 Hz, 1H,
1
3
1
3
(
t), 112.3 (d), 120.0 (s), 125.3 (s), 126.1 (2!d), 128.8 (s),
ArH); C NMR (100.6 MHz, CDCl ) d 11.6 (q), 22.7
3

C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
12259
(
1
1
2!q), 25.4 (d), 52.5 (t), 123.1 (s), 125.0 (s), 126.2 (d),
26.8 (d), 127.1 (2!d), 129.6 (3!d), 130.9 (s), 133.1 (s),
33.27 (d), 133.31 (d), 133.5 (s), 136.9 (s), 141.8 (s), 174.9
3.7.3. 6,11-Dihydro-12-isobutyryl-6,11-dioxo-benzo[b]-
acridine 30d. Pale yellow powders; mp 229–230 8C; IR
(CHCl ) 1690, 1600, 1335, 1255, 1105 cm ; H NMR
K1
1
3
(
s), 180.8 (s), 202.2 (s). Anal. Calcd for C H NO : C,
21
(400 MHz, C D Cl ) d 1.12 (d, JZ6.9 Hz, 3H, CH ), 1.35
2
4
3
2
2
4
3
7
7.61; H, 5.70; N, 3.77. Found: C, 77.56; H, 5.77; N, 3.73.
(d, JZ6.9 Hz, 3H, CH ), 3.00 (septet, JZ6.9 Hz, 1H, CH),
3
7
8
.71–7.88 (m, 4H, ArH), 7.96 (t, JZ7.5 Hz, 1H, ArH),
.24–8.29 (m, 1H, ArH), 8.34–8.40 (m, 1H, ArH), 8.43 (d,
3
.6.4. 4,9-Dihydro-2-methyl-4,9-dioxo-1-phenyl-3-piva-
loyl-1H-benzo[f]indole 29i. Yellow powders; mp 155–
1
3
JZ8.5 Hz, 1H, ArH); C NMR (100.6 MHz, C D Cl ) d
18.1 (q), 19.0 (q), 42.4 (d), 123.5 (s), 125.5 (s), 127.0 (d),
127.9 (d), 128.3 (d), 130.8 (d), 131.9 (d), 133.2 (s), 133.9
2
2
4
K1
1
56 8C; IR (CHCl ) 1660, 1595, 1505, 1430, 1280 cm
;
H NMR (400 MHz, CDCl ) d 1.34 (s, 9H, 3!CH ), 2.03
3
1
3
3
(d), 135.2 (d), 135.4 (d), 147.7 (s), 149.9 (s), 151.3 (s), 181.4
(
s, 3H, ArCH ), 7.29–7.33 (m, 2H, ArH), 7.54–7.60 (m, 3H,
3
(s), 182.8 (s), 209.4 (s). Anal. Calcd for C H NO : C,
21 15
ArH), 7.63 (td, JZ7.4, 2.0 Hz, 1H, ArH), 7.66 (td, JZ7.4,
3
76.58; H, 4.59; N, 4.25. Found: C, 76.49; H, 4.63; N, 4.11.
2
1
(
.0 Hz, 1H, ArH), 7.98–8.19 (m, 1H, ArH), 8.14–8.56 (m,
H, ArH); C NMR (100.6 MHz, CDCl ) d 11.6 (q), 27.1
3!q), 45.9 (s), 122.4 (s), 126.2 (s), 126.4 (d), 126.5 (d),
1
3
3
1
1
27.2 (2!d), 129.5 (3!d), 130.4 (s), 133.1 (d), 133.3 (d),
33.6 (s), 136.3 (s), 136.9 (s), 174.6 (s), 180.6 (s), 211.6 (s).
Acknowledgements
Anal. Calcd for C H NO : C, 77.61; H, 5.70; N, 3.77.
4
Found: C, 77.62; H, 5.69; N, 3.77.
We are grateful to the National Science Council of the ROC
for financial support (Grant No. NSC-92-2113-M-006-008).
2
21
3
3.7. Typical experimental procedure for the reaction
between 2-(anilino)-1,4-naphthoquinone (28) and
b-dicarbonyl compounds in less acidic or neutral solvent
References and notes
A mixture of 151 mg (0.61 mmol) of 2-(anilino)-1,4-
naphthoquinone (28), 390 mg (2.47 mmol) of ethyl butyryl-
acetate (2a) and 969 g (3.61 mmol) of Mn(OAc) in 10 mL
3
1
2
. (a) Hart, D. J. Science 1984, 223, 883. (b) Neumann, W. P.
Synthesis 1987, 665. (c) Curran, D. P. Synthesis 1988, 417 see
alsp p 489. (d) Melikyan, G. G. Synthesis 1993, 833. (e) Iqbal,
J.; Bhatia, B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519.
of CF CH OH was heated at 80 8C for 24 h, followed by the
3
2
addition of 971 mg (3.62 mmol) of Mn(OAc) . The reaction
3
(
f) Snider, B. B. Chem. Rev. 1996, 96, 339.
mixture was heated for another 24 h and then diluted with
1
. (a) The Chemistry of Functional Groups: The Chemistry of The
Quinoid Compounds; Patai, S., Rappoport, Z., Eds.; Wiley:
New York, 1988. (b) Thomson, R. H. Natural Occurring
Quinones IV: Recent Advances; Chapman & Hall: London,
00 mL of ethyl acetate, washed with 50 mL of saturated
aqueous sodium bisulfite, three 50 mL portions of water,
dried (Na SO ), and concentrated in vacuo. The residue was
2
4
chromatographed over 20 g of silica gel (eluted with
dichloromethane) followed by crystallization (chloroform–
hexane) to give 129 mg (64%) of 30a.
1
997.
. (a) Shaw, K. J.; Luly, J. R.; Rapoport, H. J. Org. Chem. 1985,
0, 4515. (b) Murphy, W. S.; O’Sullivan, P. J. Tetrahedron
3
4
5
Lett. 1992, 33, 531. (c) O’Sullivan, P. J.; Moreno, R.; Murphy,
W. S. Tetrahedron Lett. 1992, 33, 535.
3.7.1. 12-Acetyl-6,11-dihydro-6,11-dioxo-benzo[b]acri-
dine 30b. Pale yellow powders; mp 314–315 8C; IR
. (a) Yogo, M.; Ito, C.; Furukawa, H. Chem. Pharm. Bull. 1991,
39, 328. (b) Bittner, S.; Krief, P.; Massil, T. Synthesis 1991,
215. (c) Kn o¨ lker, H.-J.; O’Sullivan, N. Tetrahedron 1994, 50,
K1
1
(
CHCl ) 1690, 1600, 1335, 1310, 1255 cm ; H NMR
3
(
400 MHz, CF COOD) d 3.06 (s, 3H, CH ), 8.11–8.22 (m,
3 3
2
H, ArH), 8.30–8.41 (m, 2H, ArH), 8.53–8.64 (m, 3H,
˚
0893. (d) Akermark, B.; Oslob, J. D.; Heuschert, U.
1
1
3
ArH), 8.88 (d, JZ8.7 Hz, 1H, ArH); C NMR (100.6 MHz,
CF COOD) d 30.9 (q), 123.0 (s), 123.1 (d), 127.8 (d), 127.9
Tetrahedron Lett. 1995, 36, 1325. (e) Echavarran, A. M.;
Tamayo, N.; De Frutos, O.; Garcia, A. Tetrahedron 1997, 50,
3
(
(
s), 129.5 (d), 129.6 (d), 131.8 (s), 133.0 (s), 135.0 (d), 137.4
d), 138.8 (d), 140.4 (s), 141.4 (d), 141.6 (s), 159.9 (s), 176.2
1
6835.
5
. (a) Oumar-Mahamat, H.; Moustrou, C.; Surzur, J.-M.;
Berstrand, M. P. J. Org. Chem. 1989, 54, 5684. (b) Snider,
B. B.; Wan, B. Y. F.; Buckman, B. O.; Foxman, B. M. J. Org.
Chem. 1991, 56, 328.
(
s), 179.5 (s), 205.6 (s). Anal. Calcd for C H NO : C,
19 11 3
7
5.74; H, 3.68; N, 4.65. Found: C, 75.52; H, 3.68; N, 4.67.
3.7.2. 6,11-Dihydro-6,11-dioxo-12-propionyl-benzo[b]-
acridine 30c. Pale yellow powders; mp 218–219 8C; IR
6. (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. (j) Tseng, C.-C.; Wu, Y.-L.; Chuang, C.-P.
Tetrahedron 2002, 57, 7625.
K1
CHCl ) 1690, 1595, 1550, 1335, 1260 cm ; H NMR
1
(
3
(
400 MHz, CDCl ) d 1.49 (t, JZ7.1 Hz, 3H, CH ), 2.67–
3
3
2
.83 (m, 1H, CH ), 3.06–3.23 (m, 1H, CH ), 7.76–7.96 (m,
2 2
4
H, ArH), 7.97–8.04 (m, 1H, ArH), 8.29–8.35 (m, 1H,
ArH), 8.47–8.51 (m, 1H, ArH), 8.54 (d, JZ8.8 Hz, 1H,
1
ArH); C NMR (100.6 MHz, CDCl ) d 7.8 (q), 37.6 (t),
3
3
1
(
22.7 (s), 125.0 (s), 126.0 (d), 127.8 (d), 128.3 (d), 130.7
d), 132.1 (d), 133.2 (s), 133.5 (d), 134.0 (s), 134.9 (d),
1
2
4
35.1 (d), 147.7 (s), 150.1 (s), 151.6 (s), 181.2 (s), 182.6 (s),
06.0 (s). Anal. Calcd for C H NO : C, 76.18; H, 4.16; N,
.44. Found: C, 76.23; H, 4.12; N, 4.42.
2
0
13
3
7. (a) Williams, G. J.; Hunter, N. R. Can. J. Chem. 1976, 54,

12260
C.-M. Tseng et al. / Tetrahedron 60 (2004) 12249–12260
3
830. (b) Demir, A. S.; Jeganathan, A. Synthesis 1992, 235.
c) Snider, B. B.; Han, L.; Xie, C. J. Org. Chem. 1997, 62,
Bernardi, R. J. Chem. Res. (S) 1983, 88. (e) Citterio, A.;
Vismara, E.; Bernardi, R. J. Chem. Res. (M) 1983, 876.
(f) Williams, D. R.; Clark, M. P. Tetrahedron Lett. 1998, 39,
7629.
(
6978. (d) Tanyeli, C.; Sezen, B. Tetrahedron Lett. 2000, 41,
7973. (e) Tanyeli, C.; Ozdemirhan, D.; Sezen, B. Tetrahedron
2002, 58, 9983.
10. Similar rate enhancement by cerium salt has been reported.
See: (a) Imamoto, T.; Sugiura, Y.; Takiyama, N. Tetrahedron
Lett. 1984, 25, 4233. (b) Imamoto, T.; Takiyama, N.;
Nakamura, K. Tetrahedron Lett. 1985, 26, 4763.
11. Kobayashi, K.; Suzuki, M.; Takeuchi, H.; Konishi, A.;
Sakurai, H.; Suginome, H. J. Chem. Soc., Perkin Trans. 1
1994, 1099.
8
9
. (a) Snider, B. B.; Merritt, J. E.; Dombroski, M. A.; Buckman,
B. O. J. Org. Chem. 1991, 56, 5544. (b) Snider, B. B.;
McCarthy, B. A. J. Org. Chem. 1993, 58, 6217. (c) Ishibashi,
H.; Toyao, A.; Takeda, Y. Synlett 1999, 1468. (d) Liao, Y.-J.;
Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2003, 59, 3511. Also
see: Ref. 6d–g.
. (a) Jacobsen, N.; Torsell, K. Acta Chem. Scand. 1973, 27,
3211. (b) Brown, P. M.; Thomson, R. H. J. Chem. Soc., Perkin
12. (a) Takahashi, K.; Tanaka, T.; Suzuki, T.; Hirama, M.
Tetrahedron 1994, 50, 1327. (b) Montalban, A. G.;
Wittenberg, L.-O.; McKillop, A. Tetrahedron Lett. 1999, 40,
5893.
Trans. 1 1976, 997. (c) Citterio, A.; Arnoldi, A.; Minisci, F.
J. Org. Chem. 1979, 44, 2674. (d) Citterio, A.; Vismara, E.;