Manganese(III)-mediated direct introduction of 3-oxobutanamides into methoxynaphthalenes

Article abstract of DOI:10.1055/s-2008-1067206

The oxidation of methoxynaphthalenes with manganese(III) acetate in the presence of N-aryl-3-oxobutanamides gave the directly 3-oxobutanamide- substituted methoxynaphthalenes in moderate to good yields along with small amounts of naphtho[2,1-b] furans and

Full text of DOI:10.1055/s-2008-1067206

2686
PAPER
Manganese(III)-Mediated Direct Introduction of 3-Oxobutanamides
into Methoxynaphthalenes
Oxidation of
M
h
ethoxynapht
i
-
w
ith Mn
q
(OAc)3 i Cong, Hiroshi Nishino*
Department of Chemistry, Graduate School of Science and Technology, Kumamoto University, Kurokami 2-39-1,
Kumamoto 860-8555, Japan
Fax +81(96)3423374; E-mail: nishino@sci.kumamoto-u.ac.jp
Received 18 March 2008; revised 7 May 2008
were unexpectedly formed in fairly good yields. In gener-
al, 2-substituted 1,3-dicarbonyl compounds are versatile
intermediates in organic synthesis.7 In addition, the man-
ganese(III) acetate based oxidation showed an efficient
Abstract: The oxidation of methoxynaphthalenes with manga-
nese(III) acetate in the presence of N-aryl-3-oxobutanamides gave
the directly 3-oxobutanamide-substituted methoxynaphthalenes in
moderate to good yields along with small amounts of naphtho[2,1-
b]furans and benzo[e]indolinones. The optimized reaction condi- method for the alkylation of 1,3-dicarbonyl com-
pounds.4,5,8 In view of the potential synthetic utility of this
tions and the mechanism for the formation of the products are dis-
cussed.
approach and as a continuation of our interest in the devel-
Key words: oxidations, manganese, radicals, aromatic substitu-
tions, cyclizations
opment of efficient synthetic methodologies using man-
ganese(III) acetate, we scrutinized the direct introduction
of 3-oxobutanamides into methoxynaphthalenes.
OMe
The redox radical process is an important tool for the for-
mation of the carbon–carbon bond in organic synthesis.1
Manganese(III) acetate is well known as a mild one-elec-
tron oxidant and widely used to construct the carbon–car-
bon bond using oxidatively formed carbon radicals.2
Accordingly, the intramolecular oxidative free-radical cy-
clization or annulation2d,e and intermolecular addition2b,c,f
using manganese(III) acetate have been extensively inves-
tigated. In recent years, our research group has developed
various manganese(III) based oxidative reactions,2b,3 and
we4 and other groups5 have found that the reaction of aro-
matic substrates with active methylene species, such as
malonic acids, malonates, malonamide, a-cyanoacet-
amide, malononitrile, b-keto esters, and b-diketones gave
various interesting functionalized products. For example,
the reaction of methoxynaphthalenes with ethyl 3-oxobu-
tanoate afforded substituted products in moderate yields
together with a small amount of naphtho[2,1-b]furans
(Scheme 1).4c Dimethyl malonate also gave similar re-
sults.5a Since the naphthofuran skeleton is found in a wide
range of natural and unnatural compounds, which exhibit
important biological and pharmacological activities,6 it is
worthwhile to explore the possible manganese(III) acetate
mediated oxidation of methoxy-substituted naphthalenes
with N-aryl-3-oxobutanamides, which are expected to de-
velop an efficient method for the preparation of function-
alized naphtho[2,1-b]furans or benzo[e]indolinones.
Therefore, we initially examined the reaction using N-
phenyl-3-oxobutanamide, which gave a complex product
distribution and a poor yield of the expected cyclization
products. However, by changing the reaction conditions,
the directly 3-oxobutanamide-substituted naphthalenes
MeCOCH2CO2Et
Mn(OAc)3⋅2H2O
AcOH, reflux
CH2OAc
O
COMe
CO2Et
EtO2C
AcO
OMe
+
(49%)
(12%)
Scheme 1
Based on our previously related research experience,4b,c
2,7-dimethoxynaphthalene (1a) was selected as an aro-
matic substrate for the reaction aimed at optimizing the re-
action conditions since the obtained products could be
readily separated and characterized. The reaction of 1a
with N-phenyl-3-oxobutanamide (2a) in the presence of
manganese(III) acetate was examined in boiling acetic
acid since manganese(III) acetate is only soluble in hot
carboxylic acid (Scheme 2).4d A mixture of 1a and 2a in a
molar ratio of 1:2 was heated in glacial acetic acid, and
manganese(III) acetate (6 equiv) was added just before re-
fluxing (Method A). The reaction was complete within 1
minute similar to the previously reported result,4c,5a and
the 3-oxobutanamide-substituted naphthalene 3aa, naph-
tho[2,1-b]furan 4aa, and benzoindolinone 5aa were ob-
tained in 18, 23 and 7% yield, respectively (Table 1, entry
1). To overcome the lower conversion of the starting ma-
terial 1a, an excess amount of manganese(III) acetate was
used (Table 1, entries 2, 3). As a result, 1a was completely
consumed when 12 equivalents of the oxidant were added.
However, the total yield of the products was only slightly
improved (a 9% increase in yield).9 It seemed that the use
of a large amount of the oxidant resulted in the self-oxida-
SYNTHESIS 2008, No. 17, pp 2686–2694
x
x.
x
x
.
2
0
0
8
Advanced online publication: 24.07.2008
DOI: 10.1055/s-2008-1067206; Art ID: F06608SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Oxidation of Methoxynaphthalenes with Mn(OAc)3
2687
R2
O
O
O
CH2OAc
O
HN
1
Me
AcO
N
O
O
Mn(OAc)3⋅2H2O
H
R2
+
8
2
AcOH
Me
N
R2
H
R1
4
6
R3
R1
1a–e
2a–i
3
4
2a: R2 = H
1a: R1 = 2,7-(MeO)2
1b: R1 = 2,6-(MeO)2
1c: R1 = 2-MeO
1d: R1 = 1,7-(MeO)2
1e: R1 = 1-MeO
O
2b: R2 = 2'-Cl
2c: R2 = 4'-Cl
2d: R2 = 2'-MeO
2e: R2 = 4'-MeO
2f: R2 = 2'-O2N
2g: R2 = 2'-Me
2h: R2 = 4'-Me
2j: R2 = 4'-F
O
N
Me
HO
R2
R3
5
4aa, 5aa: R2 = H, R3 = 8-MeO
4ab, 5ab: R2 = 2'-Cl, R3 = 8-MeO
4ac, 5ac: R2 = 4'-Cl, R3 = 8-MeO
3aa: R1 = 2,7-(MeO)2, R2 = H
3ab: R1 = 2,7-(MeO)2, R2 = 2'-Cl
3ac: R1 = 2,7-(MeO)2, R2 = 4'-Cl
3ad: R1 = 2,7-(MeO)2, R2 = 2'-MeO
3ae: R1 = 2,7-(MeO)2, R2 = 4'-MeO
3af: R1 = 2,7-(MeO)2, R2 = 2'-NO2
3ag: R1 = 2,7-(MeO)2, R2 = 2'-Me
3ah: R1 = 2,7-(MeO)2, R2 = 4'-Me
3ai: R1 = 2,7-(MeO)2, R2 = 4'-F
3ba: R1 = 2,6-(MeO)2, R22 = H
3ca: R1 = 2-MeO, R2 = H
4ad, 5ad: R2 = 2'-MeO, R3 = 8-MeO
4ae, 5ae: R2 = 4'-MeO, R3 = 8-MeO
4af, 5af: R2 = 2'-NO2, R3 = 8-MeO
4ag, 5ag: R2 = 2'-Me, R3 = 8-MeO
4ah, 5ah: R2 = 4'-Me, R3 = 8-MeO
4ai, 5ai: R2 = 4'-F, R3 = 8-MeO
4ba, 5ba: R2 = H, R3 = 7-MeO
4ca, 5ca: R2 = R3 = H
4da: R2 = H, R3 = 9-MeO
3da: R1 = 4,6-(MeO)2, R2 = H
3ea: R1 = 4-MeO, R2 = H
Scheme 2
tion of 1a as well as the formation of a dimer or trimer of The mechanism for the formation of three products 3, 4,
2a.5a,10
and 5 could be explained as follows. Analogous to the pre-
viously reported oxidative radical reaction pathway,4,11
the manganese(III)-3-oxobutanamide enolate complex 2¢
is formed by the ligand-exchange reaction of manga-
nese(III) acetate with the N-aryl-3-oxobutanamides 2 dur-
ing the first stage. The electron-deficient enolate complex
2¢ would interact with the electron-rich methoxynaphtha-
lenes 1 to afford an electron donor–acceptor-like complex
A,11 followed by a one-electron transfer to give radical B,
which should be easily oxidized by manganese(III) to
yield the intermediate cation C. It was expected that the
aromatization process accompanied by deprotonation
should be fast, giving the substitution product D. Since
product D still has an active methine proton, product D
should be oxidized by an excess amount of manga-
nese(III) acetate to give 3 (Scheme 3, path a).4c On the
other hand, the intermediate cation C could be intramolec-
ularly attacked by the acetyl oxygen or amide nitrogen.
The O-cyclization followed by elimination of methanol
would give the naphthofuran F, which would then be con-
verted into acetoxymethylnaphthofuran 4 via the benzyl-
type oxidation (path b).4c On the other hand, when the
amide nitrogen would attack intramolecularly at the posi-
tive charge in cation C, a benzoindolinone H would be
produced, and the hydroxybenzoindolinone 5 would be
eventually obtained by further oxidation (path c).
In order to improve the conversion of 1a, we adopted the
high-dilution conditions of 2a toward the oxidant (Meth-
od B). To a heated solution of 1a and 2a in a molar ratio
of 1:0.3 in glacial acetic acid was added manganese(III)
acetate (6 equiv) just before refluxing, and then another
portion of 2a (1.0 equiv) dissolved in AcOH was dropwise
added through a dropping funnel. The oxidant was con-
sumed in 2 minutes and the substituted product 3aa was
preferentially produced in 63% yield along with 4aa and
5aa in 14% and 8% yields, respectively (Table 1, entry 4).
When the reaction was carried out at 70 °C, a maximum
yield of 3aa (79%) was achieved (Table 1, entry 5).
This result encouraged us to apply the process using other
N-aryl-3-oxobutanamides 2b–i because of the good selec-
tivity of 2a in the formation of the directly substituted
product 3aa. The reaction of 1a with N-(2-chlorophenyl)-
(2b), N-(4-chlorophenyl)- (2c), N-(2-methoxyphenyl)-
(2d), N-(4-methoxyphenyl)- (2e), N-(2-nitrophenyl)- (2f),
N-(2-methylphenyl)- (2g), N-(4-methylphenyl)- (2h), and
N-(4-fluorophenyl)-3-oxobutanamide (2i) gave the corre-
sponding substitution products 3ab–3ai in good yields to-
gether with a small amount of the addition products 4ab–
4ai and 5ab–5ai, respectively (Table 1, entries 6–13). Use
of 2,6-dimethoxy- (1b), 2-methoxy- (1c), 1,7-dimethoxy-
(1d), and 1-methoxynaphthalene (1e) instead of 1a also
afforded similar products (Table 1, entries 14–17).
Synthesis 2008, No. 17, 2686–2694 © Thieme Stuttgart · New York

2688
Z.-q. Cong, H. Nishino
PAPER
Table 1 Reaction of Methoxynaphthalenes 1a–e with 3-Oxobutanamides 2a–i in the Presence of Mn(OAc)3⋅2H2Oa
Entry
1
2
Molar ratiob
Temp
(°C)
Time
(min)
Recovery
(%)
Product(s) (Yield, %)c
1d
2d
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
1:2:6
reflux
reflux
reflux
reflux
70
1
1
1
2
2
2
2
2
2
2
2
2
2
3
2
2
2
30
14
–
3aa (18)
3aa (17)
3aa (22)
3aa (63)
3aa (79)
3ab (76)
3ac (70)
3ad (59)
3ae (30)
3af (69)
3ag (53)
3ah (51)
3ai (60)
3ba (35)
3ca (35)
3da (28)
3ea (67)
4aa (23)
5aa (7)
1:2:8
4aa (25)
4aa (19)
4aa (14)
4aa (5)
4ab (1)f
4ac (4)
4ad (trace)
4ae (3)
4af (trace)
4ag (19)
4ah (8)
4ai (13)
4ba (9)
4ca (15)
4da (9)
–
5aa (12)
5aa (16)
5aa (8)
5aa (5)
5ab (11)f
5ac (9)
5ad (15)
5ae (trace)
5af (12)
5ag (trace)
5ah (9)
5ai (15)
5ba (4)
5ca (12)
–
3d
1:3:12
1:1.3:6
1:1.2:6
1:1.2:6
1:1.2:6
1:1.2:6
1:1.2:6
1:1.2:6
1:1.2:6
1:1.2:6
1:1.2:6
1:1.2:6
1:1.2:6
1:1.2:6
1:1.2:6
4e
4
5e
7
6e
70
9
7e
70
10
9
8e
70
9e
70
37
5
10e
11e
12e
13e
14e
15e
16e
17e
70
2g
2h
2i
70
12
10
14
24
14
21
13
70
70
2a
2a
2a
2a
70
70
70
70
–
a The reaction was carried out in glacial AcOH.
b 1:2:Mn(OAc)3⋅2H2O.
c Isolated yield based on the amount of the added methoxynaphthalene 1.
d The reaction was conducted using Method A described in the experimental section.
e The reaction was carried out using Method B mentioned in the experimental section.
f An intractable mixture of 4ab and 5ab was obtained and the yield was estimated on the basis of the integration of the NH and OH peaks in
the 1H NMR spectrum.
Mn(OAc)2·4H2O was purchased from Wako Pure Chemical Ind.,
Ltd. Mn(OAc)3·2H2O was prepared according to the method de-
scribed in the literature.12 Methoxynaphthalenes 1a–e were pre-
pared by the methylation of the corresponding naphthols using
dimethyl sulfate in anhyd acetone in the presence of anhyd K2CO3.
In conclusion, we have developed an efficient way to di-
rectly prepare the 3-oxobutanamide-substituted naphtha-
lenes 3 by the oxidation of methoxynaphthalenes 1 with
manganese(III) acetate by controlling the proportion of
the 3-oxobutanamides 2 in the reaction mixture at 70 °C.
The reaction is very simple and the reaction times are very
short. Although it was difficult to improve the yield of 3,
this is an interesting procedure to prepare heterocyclic
compounds using the functionalized naphthalenes 3. Fur-
ther studies on the synthesis of functionalized heterocy-
clic compounds using 3 are now in progress.
Oxidation of Methoxynaphthalenes 1 with Manganese(III)
Acetate in the Presence of N-Aryl-3-oxobutanamides 2; Com-
pounds 3aa, 4aa, and 5aa; Typical Procedure (Table 1, Entry 1)
Method A: To a heated solution of 2,7-dimethoxynaphthalene (1a;
188 mg, 1 mmol) and N-phenyl-3-oxobutanamide (2a; 354 mg, 2
mmol) in glacial AcOH (25 mL) was added Mn(OAc)3·2H2O (1.608
g, 6 mmol) was added just before refluxing. The reaction was com-
plete within 1 min when the dark-brown color of the solution turned
clear red. The mixture was then cooled to r.t., and the solvent was
removed in vacuo. The residue was triturated with aq 2 M (1 M = 1
mol dm–3) HCl (30 mL) followed by extraction with CHCl3 (3 × 20
mL). The combined organic extracts were washed with sat. aq
NaHCO3 (2 × 20 mL) and H2O (2 × 20 mL), dried (MgSO4), and
concentrated to dryness. The products were separated by silica gel
TLC (Wako B-10) by eluting with CHCl3, and 3aa (76 mg, 18%;
Rf = 0.22), 4aa (89 mg, 23%; Rf = 0.43), and 5aa (24 mg, 7%;
Rf = 0.33) were obtained together with recovered 1a (56 mg, 30%;
Rf = 0.73). The products were further purified by recrystallization
The NMR spectra were recorded using a JNM AL300 FT NMR
spectrometer at 300 MHz for 1H and at 75 MHz for 13C with tetra-
methylsilane as the internal standard. The chemical shifts are given
in d values (ppm) and the coupling constants in Hz. The IR spectra
of the neat samples were measured using the KBr disc or CHCl3 so-
lution by a Shimadzu 8400 FT IR spectrometer and expressed in
cm–1. The EI MS spectra were recorded by a Shimadzu QP-5050A
gas chromatograph-mass spectrometer at an ionizing voltage of 70
eV. The elemental analyses were performed at the Instrumental
Analysis Center of Kumamoto University, Kumamoto, Japan.
Synthesis 2008, No. 17, 2686–2694 © Thieme Stuttgart · New York

PAPER
Oxidation of Methoxynaphthalenes with Mn(OAc)3
2689
O
H
O
III
Mn
III
Mn
III
Mn
III
Mn
O
H
O
O
NHAr
OMe
O
NHAr
OMe
O
Me
III
O
Me
NHAr
OMe
Mn
1
Mn(OAc)3⋅2H2O
III
Mn
O
O
Me
R
Me
NHAr
R
R
B
C
2'
electron donor–acceptor-like complex
A
– H
deprotonation
(path a)
O
O
O
O
O-cyclization
(path b)
N-cyclization
(path c)
Me
Me
NHAr
OMe
NHAr
OMe
AcO
Mn(OAc)3⋅2H2O
AcOH
R
R
D
3
O
O
O
O
O
Me
O
Me
CH2OAc
O
ArHN
ArHN
ArHN
Me
H
H
Mn(OAc)3⋅2H2O
N Ar
O
OMe
OMe
– MeOH
AcOH
R
R
R
R
F
E
G
4
– MeOH
O
O
O
N
O
Me
Me
HO
Mn(OAc)3⋅2H2O
AcOH
N
Ar
Ar
R
R
H
5
Scheme 3
from appropriate solvents. Entries 2 and 3 in Table 1 were carried
out with this method.
2-Acetoxy-2-(2,7-dimethoxy-1-naphthyl)-N-phenyl-3-oxobu-
tanamide (3aa)
Colorless needles (from MeOH); mp 161.5–162 °C.
IR (KBr): 3427, 3389, 1768, 1730, 1701 cm–1.
Method B (Table 1, Entry 4): A mixture of 2,7-dimethoxynaphtha-
lene (1a; 188 mg, 1 mmol), N-phenyl-3-oxobutanamide (2a; 35.4
mg, 0.2 mmol), and glacial AcOH (18 mL) was placed in a three-
necked flask equiped with a condenser and a dropping funnel. To
the heated solution was added Mn(OAc)3·2H2O (1.608 g, 6 mmol)
just before refluxing, and then another portion of 2a (177 mg, 1
mmol) dissolved in glacial AcOH (7 mL) was dropwise added with-
in 2 min. The mixture was cooled to r.t., and the solvent was re-
moved in vacuo. The residue was worked up by the same procedure
as described for Method A to give the products 3aa (333 mg, 79%),
4aa (21 mg, 5%), and 5aa (17 mg, 5%) along with recovered 1a (13
mg, 7%). Entries 5–17 in Table 1 were carried out by this method at
70 °C.
1H NMR (CDCl3): d = 8.43 (1 H, s, NH), 7.78 (1 H, d, J = 9.0 Hz,
H-5), 7.66–7.63 (2 H, m, H-4, H-8), 7.47 (2 H, d, J = 8.1 Hz, H-2¢,
H-6¢), 7.26 (2 H, td, J = 7.8, 1.8 Hz, H-3¢, H-5¢), 7.08–6.99 (3 H, m,
H-3, H-6, H-4¢), 3.87 (3 H, s, OCH3), 3.79 (3 H, s, OCH3), 2.35 (3
H, s, COCH3), 2.25 (3 H, s, COCH3).
13C NMR (CDCl3): d = 199.2, 168.3, 164.5, 158.1, 155.8, 137.4,
134.3, 132.2, 130.1, 128.9, 125.8, 124.5, 119.8, 116.7, 115.8, 110.9,
104.1, 89.6, 56.2, 55.0, 26.3, 21.1.
MS: m/z = 421 (M+, 12%).
Anal. Calcd for C24H23NO6: C, 68.40; H, 5.50; N, 3.32. Found: C,
68.20; H, 5.46; N, 3.25.
Synthesis 2008, No. 17, 2686–2694 © Thieme Stuttgart · New York

2690
Z.-q. Cong, H. Nishino
PAPER
2-Acetoxy-N-(2¢-chlorophenyl)-2-(2,7-dimethoxy-1-naphthyl)-
3-oxobutanamide (3ab)
Anal. Calcd for C25H25NO7: C, 66.51; H, 5.58; N, 3.10. Found: C,
66.34; H, 5.53; N, 3.09.
Colorless needles (from MeOH); mp 166–166.5 °C.
2-Acetoxy-2-(2,7-dimethoxy-1-naphthyl)-N-(2¢-nitrophenyl)-3-
oxobutanamide (3af)
Yellow microcystals (from MeOH); mp 205.5–206.5 °C.
IR (KBr): 3335, 1759, 1730, 1705 cm–1.
1H NMR (CDCl3): d = 11.25 (1 H, s, NH), 8.76 (1 H, dd, J = 1.2, 8.4
Hz, H-3¢), 8.18 (1 H, dd, J = 1.5, 8.4 Hz, H-6¢), 7.83 (1 H, d, J = 9.0
Hz, H-5), 7.68 (1 H, d, J = 9.0 Hz, H-4), 7.60 (1 H, td, J = 8.4, 1.5
Hz, H-5¢), 7.54 (1 H, s, H-8), 7.15 (1 H, td, J = 8.4, 1.5 Hz, H-4¢),
7.13 (1 H, d, J = 8.7 Hz, H-3), 7.01 (1 H, dd, J = 2.4, 9.0 Hz, H-6),
3.95 (3 H, s, OCH3), 3.80 (3 H, s, OCH3), 2.42 (3 H, s, COCH3),
2.37 (3 H, s, COCH3).
13C NMR (CDCl3): d = 197.1, 168.4, 166.0, 158.5, 155.6, 136.5,
135.9, 134.2, 133.9, 132.5, 130.4, 125.8, 125.6, 123.6, 122.1, 116.7,
114.9, 110.8, 103.7, 90.1, 56.1, 55.0, 26.5, 21.1.
IR (KBr): 3373, 3346, 1759, 1730, 1707 cm–1.
1H NMR (CDCl3): d = 9.09 (1 H, s, NH), 8.35 (1 H, dd, J = 1.5, 8.1
Hz, H-6¢), 7.82 (1 H, d, J = 8.7 Hz, H-5), 7.67 (1 H, d, J = 9.3 Hz,
H-4), 7.61 (1 H, s, H-8), 7.34 (1 H, dd, J = 1.5, 8.1 Hz, H-3¢), 7.23
(1 H, t, J = 8.1 Hz, H-5¢), 7.11 (1 H, d, J = 9.0 Hz, H-6), 7.05–6.99
(2 H, m, H-3, H-4¢), 3.92 (3 H, s, OCH3), 3.81 (3 H, s, OCH3), 2.37
(3 H, s, COCH3), 2.30 (3 H, s, COCH3).
13C NMR (CDCl3): d = 198.0, 168.1, 164.8, 158.4, 155.5, 134.3,
134.0, 132.4, 132.3, 130.3, 129.0, 127.7, 125.7, 124.8, 122.8, 116.9,
115.7,110.8, 103.8, 56.2, 55.1, 26.4, 21.1.
Anal. Calcd for C24H22ClNO6: C, 63.23; H, 4.86; N, 3.07. Found: C,
63.12; H, 4.81; N, 3.09.
2-Acetoxy-N-(4¢-chlorophenyl)-2-(2,7-dimethoxy-1-naphthyl)-
3-oxobutanamide (3ac)
Colorless microcrystals (from CHCl3–Et2O); mp 198–199 °C.
Anal. Calcd for C24H22N2O8: C, 61.80; H, 4.75; N, 6.01. Found: C,
61.65; H, 4.69; N, 6.00.
IR (KBr): 3361, 1761, 1722, 1693 cm–1.
2-Acetoxy-2-(2,7-dimethoxy-1-naphthyl)-N-(2¢-methylphenyl)-
3-oxobutanamide (3ag)
Colorless needles (from MeOH); mp 160–161 °C.
IR (KBr): 3358, 3161, 1759, 1725, 1695 cm–1.
1H NMR (CDCl3): d = 8.41 (1 H, s, NH), 7.92 (1 H, d, J = 7.5 Hz,
H-5), 7.81 (2 H, m, J = 8.7 Hz, H-8, H-4), 7.67 (1 H, d, J = 9.0 Hz,
H-6¢), 7.17–6.98 (5 Harom, m), 3.91 (3 H, s, OCH3), 3.85 (3 H, s,
OCH3), 2.35 (3 H, s, COCH3), 2.30 (3 H, s, COCH3), 2.14 (3 H, s,
CH3).
13C NMR (CDCl3): d = 199.7, 168.8, 164.2, 158.3, 155.0, 135.7,
134.2, 132.2, 130.3, 130.1, 127.8, 126.7, 125.8, 124.7, 121.6, 116.9,
116.1, 110.5, 104.6, 89.3, 56.0, 55.2, 26.2, 21.1, 17.3.
1H NMR (CDCl3): d = 8.39 (1 H, s, NH), 7.69 (1 H, d, J = 8.7 Hz,
H-5), 7.59 (1 H, s, H-8), 7.56 (1 H, d, J = 8.7 Hz, H-4), 7.32 (2 H,
dd, J = 2.1, 9.0 Hz, H-2¢, H-6¢), 7.13 (1 H, d, J = 8.7 Hz, H-3¢ or 5¢),
7.11 (1 H, d, J = 8.7 Hz, H-5¢ or 3¢ ), 6.97 (1 H, d, J = 8.7 Hz, H-6),
6.92 (1 H, dd, J = 2.7, 8.7 Hz, H-3), 3.77 (3 H, s, OCH3), 3.72 (3 H,
s, OCH3), 2.23 (3 H, s, COCH3), 2.15 (3 H, s, COCH3).
13C NMR (CDCl3): d = 199.1, 168.4, 164.6, 158.3, 155.4, 135.9,
133.9, 132.3, 130.2, 129.3, 128.8, 125.6, 121.1, 116.7, 115.5, 110.7,
104.2, 89.2, 56.2, 55.0, 26.2, 21.0.
Anal. Calcd for C24H22ClNO6: C, 63.23; H, 4.86; N, 3.07. Found: C,
63.26; H, 4.95; N, 3.07.
2-Acetoxy-2-(2,7-dimethoxy-1-naphthyl)-N-(2¢-methoxyphe-
nyl)-3-oxobutanamide (3ad)
Anal. Calcd for C25H25NO6: C, 68.95; H, 5.79; N, 3.22. Found: C,
69.03; H, 5.59; N, 3.31.
Colorless needles (from MeOH); mp 177–177.5 °C.
2-Acetoxy-2-(2,7-dimethoxy-1-naphthyl)-N-(4¢-methylphenyl)-
3-oxobutanamide (3ah)
Colorless needles (from MeOH); mp 169–170 °C.
IR (KBr): 3396, 1771, 1715, 1695 cm–1.
1H NMR (CDCl3): d = 8.32 (1 H, s, NH), 7.80 (1 H, d, J = 9.3 Hz,
H-5), 7.66 (1 H, d, J = 9.0 Hz, H-4), 7.60 (1 H, d, J = 2.4 Hz, H-8),
7.36 (2 H, d, J = 8.4 Hz, H-2¢, H-6¢), 7.09 (2 H, d, J = 8.7 Hz, H-3¢,
H-5¢), 7.08 (1 H, d, J = 9.0 Hz, H-3), 7.01 (1 H, dd, J = 2.4, 9.0 Hz,
H-6), 3.90 (3 H, s, OCH3), 3.78 (3 H, s, OCH3), 2.36 (3 H, s,
COCH3), 2.28 (3 H, s, COCH3), 2.26 (3 H, s, CH3).
13C NMR (CDCl3): d = 199.3, 168.2, 164.3, 158.3, 155.8, 134.7,
134.3, 134.1, 132.2, 130.2, 129.5, 125.8, 119.9, 116.8, 116.3, 111.0,
104.1, 90.0, 56.4, 55.1, 26.5, 21.3, 20.8.
IR (KBr): 3382, 1759, 1728, 1699 cm–1.
1H NMR (CDCl3): d = 9.11 (1 H, s, NH), 8.30 (1 H, d, J = 7.8 Hz,
H-5), 7.80 (1 H, d, J = 8.4 Hz, H-4), 7.65 (1 H, dd, J = 1.5, 9.0 Hz,
H-6¢), 7.53 (1 H, s, H-8), 7.10 (1 H, dd, J = 1.5, 9.0 Hz, H-3¢), 7.06–
6.84 (4 H, m, H-3, H-6, H-4¢, H-5¢) 3.91 (3 H, s, OCH3), 3.84 (3 H,
s, OCH3), 3.73 (3 H, s, OCH3), 2.39 (3 H, s, COCH3), 2.27 (3 H, s,
COCH3).
13C NMR (CDCl3): d = 198.0, 167.9, 164.5, 158.3, 155.8, 148.1,
133.9, 132.1, 130.2, 127.1, 125.7, 124.2, 121.1, 119.7, 116.7, 116.6,
111.1, 110.1, 103.8, 90.4, 56.3, 55.9, 54.9, 26.7, 21.2.
Anal. Calcd for C25H25NO7: C, 66.51; H, 5.58; N, 3.10. Found: C,
66.15; H, 5.51; N, 3.04.
2-Acetoxy-2-(2,7-dimethoxy-1-naphthyl)-N-(4¢-methoxyphe-
nyl)-3-oxobutanamide (3ae)
Anal. Calcd for C25H25NO6: C, 68.95; H, 5.79; N, 3.22. Found: C,
69.03; H, 5.65; N, 3.22.
Colorless microcrystals (from MeOH); mp 162–162.5 °C.
2-Acetoxy-N-(4¢-fluorophenyl)-2-(2,7-dimethoxy-1-naphthyl)-
3-oxobutanamide (3ai)
Colorless microcrystals (from MeOH); mp 127–129 °C.
IR (KBr): 3381, 3309, 1757, 1718, 1684 cm–1.
1H NMR (CDCl3): d = 8.44 (1 H, s, NH), 7.80 (1 H, d, J = 8.7 Hz,
H-5), 7.68 (1 H, s, H-8), 7.67 (1 H, d, J = 9.0 Hz, H-4), 7.44 (1 H,
d, J = 8.7 Hz, H-2¢ or H-6¢), 7.43 (1 H, d, J = 8.7 Hz, H-6¢ or H-2¢),
7.08 (1 H, d, J = 9.3 Hz, H-3), 7.02 (1 H, dd, J = 2.4, 9.0 Hz, H-6),
6.97 (1 H, d, J = 8.7 Hz, H-3¢ or H-5¢), 6.94 (1 H, d, J = 8.7 Hz, H-
5¢ or H-3¢), 3.89 (3 H, s, OCH3), 3.82 (3 H, s, OCH3), 2.34 (3 H, s,
COCH3), 2.26 (3 H, s, COCH3).
IR (KBr): 3357, 1767, 1715, 1689 cm–1.
1H NMR (CDCl3): d = 8.29 (1 H, s, NH), 7.81 (1 H, d, J = 8.7 Hz,
H-5), 7.67 (1 H, d, J = 9.0 Hz, H-4), 7.60 (1 H, s, H-8), 7.39 (2 H,
d, J = 9.0 Hz, H-2¢, H-6¢), 7.10 (1 H, d, J = 8.7 Hz, H-3), 7.01 (1 H,
dd, J = 2.7, 8.7 Hz, H-6), 6.82 (2 H, d, J = 9.0 Hz, H-3¢, H-5¢), 3.89
(3 H, s, OCH3), 3.79 (3 H, s, OCH3), 3.76 (3 H, s, OCH3), 2.36 (3
H, s, COCH3), 2.26 (3 H, s, COCH3).
13C NMR (CDCl3): d = 198.8, 168.3, 164.4, 158.3, 156.6, 155.7,
134.1, 132.2, 130.4, 130.2, 125.7, 121.6, 116.7, 116.3, 114.1, 111.0,
104.1, 89.8, 56.3, 55.4, 55.1, 26.5, 21.1.
Synthesis 2008, No. 17, 2686–2694 © Thieme Stuttgart · New York

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Oxidation of Methoxynaphthalenes with Mn(OAc)3
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13C NMR (CDCl3): d = 199.2, 168.4, 164.6, 161.0, 158.3, 157.8,
155.5, 134.0, 133.3, 132.3, 130.2, 125.7, 121.8, 121.7, 116.7, 115.7,
115.4, 110.8, 104.2, 89.3, 56.2, 55.1, 26.2, 21.1.
13C NMR (CDCl3): d = 203.5, 170.6, 164.4, 157.0, 137.2, 132.1,
128.8, 127.4, 126.8, 126.4, 125.6, 124.6, 122.6, 121.1, 120.2, 102.4,
89.9, 55.6, 26.9, 21.0.
Anal. Calcd for C24H22FNO6: C, 65.60; H, 5.05; N, 3.19. Found: C,
65.72; H, 5.06; N, 3.42.
Anal. Calcd for C23H21NO5: C, 70.58; H, 5.41; N, 3.58. Found: C,
70.51; H, 5.39; N, 3.54.
2-Acetoxy-2-(2,6-dimethoxy-1-naphthyl)-N-phenyl-3-oxobu-
tanamide (3ba)
Colorless microcrystals (from MeOH); mp 180–181 °C.
2-Acetoxymethyl-1-phenylcarbamoyl-8-methoxynaphtho[2,1-
b]furan (4aa)
Colorless needles (from EtOH); mp 177–177.5 °C.
IR (KBr): 3413, 1757, 1718 cm–1.
IR (CHCl3): 3309, 3018, 1732, 1670 cm–1.
1H NMR (CDCl3): d = 8.50 (1 H, s, NH), 8.19 (1 H, d, J = 9.6 Hz,
H-8), 7.76 (1 H, d, J = 9.0 Hz, H-4), 7.47 (2 H, d, J = 8.4 Hz, H-2¢,
H-6¢), 7.47 (2 H, t, J = 8.1 Hz, H-3¢, H-5¢), 7.20 (1 H, d, J = 9.0 Hz,
H-3), 7.47 (1 H, dd, J = 2.7, 9.6 Hz, H-7), 7.04–7.09 (2 H, m, H-5,
H-4¢), 3.83 (6 H, s, OCH3), 2.34 (3 H, s, COCH3), 2.22 (3 H, s,
COCH3).
1H NMR (CDCl3): d = 9.90 (1 H, s, NH), 8.07 (1 H, d, J = 2.7 Hz,
H-9), 7.88 (2 H, d, J = 7.8 Hz, H-2¢, H-6¢), 7.78 (1 H, d, J = 9.0 Hz,
H-6), 7.70 (1 H, d, J = 8.7 Hz, H-4 or H-5), 7.43 (1 H, d, J = 8.7 Hz,
H-5 or H-4), 7.40 (2 H, t, J = 8.1 Hz, H-3¢, H-5¢), 7.18 (1 H, td,
J = 7.5, 1.2 Hz, H-4¢), 7.12 (1 H, dd, J = 2.7, 8.7 Hz, H-7), 5.37 (2
H, s, CH2), 3.87 (3 H, s, OCH3), 2.14 (3 H, s, COCH3).
13C NMR (CDCl3): d = 198.8, 168.3, 164.6, 156.0, 153.4, 137.4,
131.7, 131.2, 128.8, 127.6, 124.5, 119.9, 119.4, 117.6, 114.3, 89.4,
56.5, 55.1, 26.3, 21.1.
13C NMR (CDCl3): d = 172.3, 162.4, 158.5, 152.9, 148.2, 138.6,
130.4, 129.1, 127.8, 125.4, 124.3, 119.7, 117.2, 109.0, 103.4, 58.9,
55.3, 20.8.
Anal. Calcd for C24H23NO6: C, 68.40; H, 5.50; N, 3.32. Found: C,
68.07; H, 5.60; N, 3.24.
MS: m/z = 389 (M+, 5%).
Anal. Calcd for C23H19NO5: C, 70.94; H, 4.92; N, 3.60. Found: C,
70.79; H, 4.87; N, 3.60.
2-Acetoxy-2-(2-methoxy-1-naphthyl)-N-phenyl-3-oxobutan-
amide (3ca)
Colorless microcrystals (from MeOH); mp 163–164.5 °C.
IR (KBr): 3352, 1770, 1715, 1699 cm–1.
2-Acetoxymethyl-1-(4¢-chlorophenylcarbamoyl)-8-methoxy-
naphtho[2,1-b]furan (4ac)
Colorless needles (from CHCl3–Et2O); mp 190–191 °C.
1H NMR (CDCl3): d = 8.46 (1 H, s, NH), 8.19 (1 H, d, J = 8.4 Hz,
H-8), 7.90 (1 H, d, J = 8.7 Hz, H-5), 7.79 (1 H, d, J = 8.1 Hz, H-4),
7.51–7.08 (8 Harom, m), 3.91 (3 H, s, OCH3), 2.35 (3 H, s, COCH3),
2.25 (3 H, s, COCH3).
13C NMR (CDCl3): d = 198.6, 168.2, 164.7, 155.2, 137.3, 132.7,
132.5, 130.4, 129.0, 128.9, 127.1, 124.9, 124.7, 124.0, 120.0, 117.4,
113.8, 89.8, 56.6, 26.4, 21.3.
IR (KBr): 3240, 1740, 1647 cm–1.
1H NMR (CDCl3): d = 10.08 (1 H, s, NH), 8.06 (1 H, d, J = 2.4 Hz,
H-9), 7.85 (2 H, d, J = 8.7 Hz, H-2¢, H-6¢), 7.79 (1 H, d, J = 9.3 Hz,
H-6), 7.72 (1 H, d, J = 8.7 Hz, H-5 or H-4), 7.44 (1 H, d, J = 8.7 Hz,
H-4 or H-5), 7.36 (2 H, d, J = 8.7 Hz, H-3¢, H-5¢), 7.13 (1 H, dd,
J = 2.7, 9.3 Hz, H-7), 5.36 (2 H, s, CH2), 3.89 (3 H, s, OCH3), 2.20
(3 H, s, COCH3).
Anal. Calcd for C23H21NO5: C, 70.58; H, 5.41; N, 3.58. Found: C,
70.66; H, 5.37; N, 3.68.
13C NMR (CDCl3): d = 172.8, 162.1, 158.5, 153.4, 148.0, 137.1,
130.2, 129.4, 129.1, 127.8, 126.0, 120.9, 119.3, 119.0, 117.0, 109.1,
104.3, 58.9, 55.3, 20.9.
2-Acetoxy-2-(4,6-dimethoxy-1-naphthyl)-N-phenyl-3-oxobu-
tanamide (3da)
Colorless microcrystals (from MeOH); mp 177–177.5 °C.
Anal. Calcd for C23H18ClNO5: C, 65.18; H, 4.28; N, 3.30. Found: C,
65.06; H, 4.38; N, 3.26.
IR (KBr): 3341, 1751, 1716, 1683 cm–1.
2-Acetoxymethyl-1-(4¢-methoxyphenylcarbamoyl)-8-methoxy-
naphtho[2,1-b]furan (4ae)
Light yellow microcrystals (from EtOH); mp 165–167 °C.
IR (KBr): 3258, 1747, 1645 cm–1.
1H NMR (CDCl3): d = 9.77 (1 H, s, NH), 8.12 (1 H, s, H-9), 7.82–
7.79 (3 H, m, H-6, H-2¢, H-6¢), 7.73 (1 H, dd, J = 2.7, 9.3 Hz, H-4
or H-5), 7.46 (1 H, dd, J = 3.0, 8.7 Hz, H-5 or H-4), 7.14 (1 H, dd,
J = 2.7, 8.7 Hz, H-7), 6.95 (1 H, dd, J = 2.7, 8.7 Hz, H-3¢ or H-5¢),
6.94 (1 H, dd, J = 3.0, 9.3 Hz, H-5¢ or H-3¢), 5.41 (2 H, s, CH2), 3.90
(3 H, s, OCH3), 3.83 (3 H, s, OCH3), 2.20 (3 H, s, COCH3).
13C NMR (CDCl3): d = 172.8, 161.7, 158.5, 156.5, 153.6, 148.0,
131.8, 130.1, 129.4, 127.7, 126.1, 121.2, 119.7, 119.3, 117.1,
114.2, 109.2, 104.3, 58.9, 55.5, 55.4, 20.9.
1H NMR (CDCl3): d = 8.79 (1 H, br s, NH), 8.52 (1 H, d, J = 9.6 Hz,
H-8), 7.61 (1 H, d, J = 2.7 Hz, H-5), 7.42 (2 H, d, J = 7.5 Hz, H-2¢,
H-6¢), 7.30–7.23 (4 H, m, H-7, H-2, H-3¢, H-5¢), 7.05 (1 H, t, J = 7.2
Hz, H-4¢), 6.73 (1 H, d, J = 8.1 Hz, H-3), 3.99 (3 H, s, OCH3), 3.92
(3 H, s, OCH3), 2.36 (3 H, s, COCH3), 2.32 (3 H, s, COCH3).
13C NMR (CDCl3): d = 203.5, 170.6, 164.4, 157.3, 155.9, 137.2,
128.8, 128.2, 127.5, 127.2, 124.5, 123.6, 121.2, 120.2, 119.5, 102.9,
101.1, 89.8, 55.5, 55.2, 26.9, 20.9.
Anal. Calcd for C24H23NO6: C, 68.40; H, 5.50; N, 3.32. Found: C,
68.01; H, 5.47; N, 3.26.
2-Acetoxy-2-(4-methoxy-1-naphthyl)-N-phenyl-3-oxobutan-
amide (3ea)
Colorless microcrystals (from MeOH); mp 176–177 °C.
IR (KBr): 3307, 1746, 1719, 1698 cm–1.
Anal. Calcd for C24H21NO6: C, 68.73; H, 5.05; N, 3.34. Found: C,
68.65; H, 5.09; N, 3.41.
2-Acetoxymethyl-8-methoxy-(2¢-methylphenylcarbam-
oyl)naphtho[2,1-b]furan (4ag)
Colorless microcrystals (from EtOH); mp 207–209 °C.
IR (KBr): 3229, 1757, 1717 cm–1.
1H NMR (CDCl3): d = 9.06 (1 H, br s, NH), 8.05 (1 H, d, J = 2.1 Hz,
H-9), 7.93 (1 H, d, J = 7.8 Hz, H-3¢), 7.83 (1 H, d, J = 8.7 Hz, H-6),
1H NMR (CDCl3): d = 8.77 (1 H, s, NH), 8.55 (1 H, d, J = 8.4 Hz,
H-5), 8.33 (1 H, dd, J = 1.2, 7.8 Hz, H-8), 7.58 (1 H, t, J = 8.4 Hz,
H-7), 7.52 (1 H, t, J = 8.1 Hz, H-6), 7.41–7.48 (3 H, m, H-2, H-2¢,
H-6¢), 7.25 (1 H, t, J = 7.8 Hz, H-3¢, H-5¢), 7.05 (1 H, t, J = 8.1 Hz,
H-4¢), 6.76 (1 H, d, J = 8.4 Hz, H-3), 4.00 (3 H, s, OCH3), 2.37 (3
H, s, COCH3), 2.33 (3 H, s, COCH3).
Synthesis 2008, No. 17, 2686–2694 © Thieme Stuttgart · New York

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Z.-q. Cong, H. Nishino
PAPER
7.75 (1 H, d, J = 9.0 Hz, H-4 or H-5), 7.49 (1 H, d, J = 9.0 Hz, H-5
or H-4), 7.34–7.20 (3 H, m, H-4¢, H-5¢, H-6¢), 7.14 (1 H, dd, J = 8.7,
2.1 Hz, H-7), 5.47 (2 H, s, CH2), 3.85 (3 H, s, OCH3), 2.39 (3 H, s,
COCH3), 2.16 (3 H, s, CH3).
13C NMR (CDCl3): d = 197.3, 174.1, 163.4, 161.6, 153.8, 140.7,
135.1, 131.3, 131.0, 130.6, 130.2, 127.6, 126.9, 125.3, 124.6, 121.5,
118.0, 110.5, 102.4, 90.0, 55.6, 22.6, 17.6.
7.60 (5 Harom, m), 7.16–7.23 (1 H, m, H-4¢), 5.37 (2 H, s, CH2), 2.18
(3 H, s, COCH3).
13C NMR (CDCl3): d = 182.8, 172.6, 164.7, 152.8, 138.2, 129.1,
128.0, 127.7, 127.0, 125.7, 125.1, 124.8, 124.6, 119.8, 111.7, 55.7,
20.9.
Anal. Calcd for C22H17NO4: C, 73.53; H, 4.77; N, 3.90. Found: C,
73.39; H, 4.67; N, 3.88.
Anal. Calcd for C24H21NO5: C, 71.45; H, 5.25; N, 3.47. Found: C,
71.21; H, 5.29; N, 3.62.
2-Acetoxymethyl-9-methoxy-1-(phenylcarbamoyl)naphtho[2,1-
b]furan (4da)
2-Acetoxymethyl-8-methoxy-1-(4¢-methylphenylcarbam-
oyl)naphtho[2,1-b]furan (4ah)
Colorless microcrystals (from EtOH); mp 197–199 °C.
IR (KBr): 3420, 3215, 1716, 1683 cm–1.
1H NMR (CDCl3): d = 8.60 (1 H, s, NH), 8.15 (1 H, d, J = 2.4 Hz,
H-9), 7.83 (1 H, d, J = 8.7 Hz, H-6), 7.72 (1 H, d, J = 9.3 Hz, H-4
or H-5), 7.61 (2 H, d, J = 8.7 Hz, H-2¢, H-6¢), 7.45 (1 H, d, J = 9.3
Hz, H-5 or H-4), 7.20 (2 H, d, J = 8.1 Hz, H-3¢, H-5¢), 7.14 (1 H, dd,
J = 2.4, 8.7 Hz, H-7), 4.96 (2 H, s, CH2), 3.82 (3 H, s, OCH3), 2.37
(3 H, s, COCH3), 2.17 (3 H, s, CH3).
13C NMR (CDCl3): d = 172.9, 162.7, 158.5, 156.7, 153.3, 148.2,
134.5, 130.5, 129.7, 128.9, 127.2, 126.1, 121.2, 119.9, 119.3, 117.1,
114.2, 109.5, 104.0, 57.3, 55.3, 31.0, 21.0.
Colorless needles (from EtOH); mp 177–177.5 °C.
IR (KBr): 3410, 1734, 1684 cm–1.
1H NMR (CDCl3): d = 8.45 (1 H, br s, NH), 7.82–7.74 (3 Harom, m),
7.62 (1 H, dd, J = 1.5, 9.0 Hz, H-6), 7.51 (1 H, d, J = 8.1 Hz, H-4 or
H-5), 7.43–7.37 (3 Harom, m), 7.15 (1 H, td, J = 1.5, 9.0 Hz, H-4¢),
6.90 (1 H, d, J = 7.8 Hz, H-8), 5.33 (2 H, s, CH2), 3.74 (3 H, s,
OCH3), 2.12 (3 H, s, COCH3).
13C NMR (CDCl3): d = 171.2, 163.3, 155.2, 152.8, 148.4, 138.7,
132.3, 129.1, 127.1, 125.2, 124.1, 121.5, 119.3, 119.1, 117.4, 112.6,
105.8, 58.0, 54.8, 20.9.
Anal. Calcd for C23H19NO5: C, 70.94; H, 4.92; N, 3.60. Found: C,
70.67; H, 4.81; N, 3.5.
Anal. Calcd for C24H21NO5: C, 71.45; H, 5.25; N, 3.47. Found: C,
71.15; H, 5.31; N, 3.56.
1-Acetyl-1-hydroxy-8-methoxy-3-phenyl-1H-benzo[e]indol-
2(3H)-one (5aa)
Colorless needles (from EtOH); mp 192–193 °C.
2-Acetoxymethyl-1-(4¢-fluorophenylcarbamoyl)-8-methoxy-
naphtho[2,1-b]furan (4ai)
Colorless microcrystals (from EtOH); mp 148–150 °C.
IR (KBr): 3283, 1736, 1695 cm–1.
1H NMR (CDCl3): d = 10.01 (1 H, s, NH), 8.10 (1 H, d, J = 2.4 Hz,
H-9), 7.90–7.68 (3 Harom, m), 7.46–7.56 (2 Harom, m), 7.18–7.08 (3
Harom, m), 5.41 (2 H, s, CH2), 3.90 (3 H, s, OCH3), 2.21 (3 H, s,
COCH3).
13C NMR (CDCl3): d = 172.3, 162.4, 158.5, 152.9, 148.2, 138.6,
130.4, 129.1, 127.8, 125.4, 124.3, 119.7, 117.2, 109.0, 103.4, 58.9,
55.3, 20.8.
IR (KBr): 3317, 2970, 1695, 1629 cm–1.
1H NMR (CDCl3): d = 8.54 (1 H, s, OH), 8.13 (1 H, d, J = 2.4 Hz,
H-9), 8.07 (1 H, d, J = 8.7 Hz, H-6), 7.75 (1 H, d, J = 9.0 Hz, H-4
or H-5), 7.58 (2 H, d, J = 8.4 Hz, H-2¢, H-6¢), 7.32 (2 H, t, J = 8.1
Hz, H-3¢, H-5¢), 7.26–7.01 (3 H, m, H-4 or H-5, H-7, H-4¢), 3.99 (3
H, s, OCH3), 1.92 (3 H, s, COCH3).
13C NMR (CDCl3): d = 197.5, 174.0, 163.4, 161.8, 161.6, 140.6,
137.0, 131.3, 130.2, 129.0, 124.8, 124.7, 119.9, 118.1, 110.5, 102.4,
89.8, 55.6, 22.6.
MS: m/z = 347 (M+, 11%).
Anal. Calcd for C21H17NO4: C, 72.61; H, 4.93; N, 4.03. Found: C,
72.47; H, 4.86; N, 3.97.
Anal. Calcd for C23H18FNO5: C, 67.81; H, 4.45; N, 3.44. Found: C,
67.72; H, 4.53; N, 3.36.
1-Acetyl-3-(4¢-chlorophenyl)-1-hydroxy-8-methoxy-1H-ben-
zo[e]indol-2(3H)-one (5ac)
Light yellow microcrystals (from EtOH); mp 244–247 °C.
IR (KBr): 3333, 1705, 1674 cm–1.
1H NMR (CDCl3): d = 8.56 (1 H, s, OH), 8.12 (1 H, d, J = 2.7 Hz,
H-9), 8.09 (1 H, d, J = 8.7 Hz, H-6), 7.76 (1 H, d, J = 9.0 Hz, H-4),
7.54 (2 H, d, J = 8.7 Hz, H-2¢, H-6¢), 7.29 (1 H, d, J = 9.0 Hz, H-5),
7.24 (2 H, d, J = 8.7 Hz, H-3¢, H-5¢), 7.13 (1 H, dd, J = 2.7, 8.7 Hz,
H-7), 3.99 (3 H, s, OCH3), 1.92 (3 H, s, COCH3).
13C NMR (CDCl3): d = 197.1, 174.0, 163.6, 161.8, 140.8, 135.6,
131.4, 130.3, 129.9, 129.1, 124.8, 121.2, 118.2, 110.5, 102.4, 89.6,
55.6, 22.7.
2-Acetoxymethyl-1-(phenylcarbamoyl)-7-methoxynaphtho[2,1-
b]furan (4ba)
Colorless needles (from EtOH); mp 186–187 °C.
IR (KBr): 3263, 3242, 1749, 1647 cm–1.
1H NMR (CDCl3): d = 9.92 (1 H, s, NH), 8.59 (1 H, d, J = 8.7 Hz,
H-9), 7.87 (2 H, d, J = 8.1 Hz, H-2¢, H-6¢), 7.71 (1 H, d, J = 8.7 Hz,
H-4 or H-5), 7.58 (1 H, d, J = 8.7 Hz, H-5 or H-4), 7.41 (2 H, t,
J = 8.1 Hz, H-3¢, H-5¢), 7.12–7.22 (3 Harom, m), 5.39 (2 H, s, CH2),
3.91 (3 H, s, OCH3), 2.19 (3 H, s, COCH3).
13C NMR (CDCl3): d = 172.3, 162.1, 156.9, 152.1, 148.3, 139.7,
138.5, 132.5, 129.1, 126.9, 125.5, 124.6, 119.9, 118.7, 112.2, 107.9,
58.9, 55.4, 21.1.
Anal. Calcd for C21H16NO4: C, 66.06; H, 4.22; N, 3.67. Found: C,
65.62; H, 4.14; N, 3.66.
Anal. Calcd for C23H19NO5: C, 70.94; H, 4.92; N, 3.60. Found: C,
70.87; H, 4.84; N, 3.46.
1-Acetyl-1-hydroxy-8-methoxy-3-(2¢-methoxyphenyl)-1H-ben-
zo[e]indol-2(3H)-one (5ad)
Colorless microcrystals (from EtOH); mp 147–148 °C.
IR (KBr): 3415, 1716, 1679 cm–1.
1H NMR (CDCl3): d = 9.11 (1 H, s, OH), 8.36 (1 H, dd, J = 1.5, 8.1
Hz, H-6¢), 8.15 (1 H, d, J = 2.7 Hz, H-9), 8.07 (1 H, d, J = 8.7 Hz,
H-6), 7.74 (1 H, d, J = 8.7 Hz, H-5), 7.25 (1 H, d, J = 9.3 Hz, H-4),
2-Acetoxymethyl-1-(phenylcarbamoyl)naphtho[2,1-b]furan
(4ca)
Colorless microcrystals (from EtOH); mp 192–194 °C.
IR (KBr): 3273, 3190, 1750, 1651 cm–1.
1H NMR (CDCl3): d = 9.90 (1 H, s, NH), 8.65 (1 H, d, J = 7.8 Hz,
H-9), 7.87–7.89 (3 Harom, m), 7.79 (1 Harom, d, J = 8.4 Hz), 7.39–
Synthesis 2008, No. 17, 2686–2694 © Thieme Stuttgart · New York

PAPER
Oxidation of Methoxynaphthalenes with Mn(OAc)3
2693
7.11 (1 H, dd, J = 2.7, 8.7 Hz, H-7), 7.04 (1 H, dt, J = 1.5, 7.8 Hz,
H-5¢ or H-4¢), 6.93 (1 H, dt, J = 1.5, 7.8 Hz, H-4¢ or H-5¢), 6.85 (1
H, dt, J = 1.2, 8.1 Hz, H-3¢), 3.97 (3 H, s, OCH3), 3.89 (3 H, s,
OCH3), 1.93 (3 H, s, COCH3).
1H NMR (CDCl3): d = 8.64 (1 H, d, J = 8.7 Hz, H-9), 8.56 (1 H, br
s, OH), 8.07 (1 H, d, J = 9.0 Hz, H-8), 7.58 (2 H, d, J = 7.5 Hz, H-
2¢, H-6¢), 7.47–7.30 (3 Harom, m), 7.21 (1 H, d, J = 2.7 Hz, H-6),
7.10–7.17 (2 Harom, m), 4.00 (3 H, s, OCH3), 2.02 (3 H, s, COCH3).
13C NMR (CDCl3): d = 196.5, 173.8, 163.3, 161.6, 148.2, 140.2,
131.4, 130.1, 126.7, 124.7, 124.3, 121.1, 119.9, 118.0, 110.7, 110.4,
109.9, 102.4, 90.3, 55.9, 55.6, 22.0.
13C NMR (CDCl3): d = 197.5, 173.3, 172.2, 163.4, 157.5, 139.7,
136.8, 131.0, 129.0, 124.8, 124.5, 121.9, 119.9, 114.1, 111.5, 107.9,
89.8, 55.4, 22.8.
Anal. Calcd for C22H19NO5: C, 70.02; H, 5.07; N, 3.71. Found: C,
69.72; H, 5.06; N, 3.61.
Anal. Calcd for C21H17NO4: C, 72.61; H, 4.93; N, 4.03. Found: C,
72.57; H, 5.09; N, 4.14.
1-Acetyl-1-hydroxy-8-methoxy-3-(2¢-nitrophenyl)-1H-ben-
zo[e]indol-2(3H)-one (5af)
Yellow microcrystals (from EtOH); mp 198–199 °C.
1-Acetyl-1-hydroxy-3-phenyl-1H-benzo[e]indol-2(3H)-one
(5ca)
Colorless microcrystals (from EtOH); mp 192–193 °C.
IR (KBr): 3314, 1722, 1686 cm–1.
IR (KBr): 3407, 1705, 1684 cm–1.
1H NMR (CDCl3): d = 11.57 (1 H, s, NH), 8.85 (1 H, d, J = 8.4 Hz,
H-3¢), 8.20 (1 H, dd, J = 1.5, 8.4 Hz, H-6¢), 8.13 (1 H, s, H-9), 8.12
(1 H, d, J = 8.7 Hz, H-6), 7.76 (1 H, d, J = 8.7 Hz, H-5), 7.65 (1 H,
dt, J = 1.5, 8.7 Hz, H-5¢), 7.37 (1 H, d, J = 8.7 Hz, H-4), 7.19 (1 H,
dt, J = 0.9, 8.4 Hz, H-4¢), 7.12 (1 H, dd, J = 2.1, 8.4 Hz, H-7), 3.96
(3 H, s, OCH3), 1.96 (3 H, s, COCH3).
1H NMR (CDCl3): d = 8.74 (1 H, d, J = 7.5 Hz, H-2¢, H-6¢), 8.59 (1
H, s, OH), 8.16 (1 H, d, J = 8.7 Hz, H-9), 7.87 (1H, d, J = 8.1 Hz,
H-6), 7.71 (1 H, t, J = 8.1 Hz, H-8 or H-7), 7.59 (1 H, d, J = 7.8 Hz,
H-5), 7.52 (1 H, t, J = 7.2 Hz, H-7 or H-8), 7.41 (1 H, dd, J = 1.8,
8.7 Hz, H-4), 7.32 (2 H, t, J = 7.5 Hz, H-3¢, H-5¢), 7.12 (1 H, t,
J = 7.8 Hz, H-4¢), 1.93 (3 H, s, COCH3).
13C NMR (CDCl3): d = 194.5, 173.7, 164.9, 161.7, 140.5, 136.4,
136.1, 133.9, 131.3, 130.2, 125.8, 125.0, 123.9, 121.9, 118.3, 110.5,
102.3, 90.5, 55.6, 21.0.
13C NMR (CDCl3): d = 197.5, 173.8, 163.3, 141.0, 136.8, 130.3,
129.6, 129.1, 129.0, 128.7, 126.0, 124.8, 123.2, 120.0, 113.7, 111.3,
89.8, 22.8.
Anal. Calcd for C23H18N2O7: C, 63.59; H, 4.18; N, 6.45. Found: C,
63.91; H, 3.97; N, 6.68.
Anal. Calcd for C20H15NO3: C, 75.70; H, 4.76; N, 4.41. Found: C,
75.57; H, 4.72; N, 4.37.
1-Acetyl-1-hydroxy-8-methoxy-3-(4¢-methylphenyl)-1H-ben-
zo[e]indol-2(3H)-one (5ah)
Acknowledgment
Colorless microcrystals (from EtOH); mp 215.5–218 °C.
IR (KBr): 3344, 1701, 1672 cm–1.
This research was supported by Grants-in-Aid for Scientific Re-
search (C), No.19550046, from Japan Society for the Promotion of
Science.
1H NMR (CDCl3): d = 8.46 (1 H, s, OH), 8.13 (1 H, d, J = 2.7 Hz,
H-9), 8.06 (1 H, d, J = 8.7 Hz, H-6), 7.73 (1 H, d, J = 9.0 Hz, H-5),
7.46 (2 H, d, J = 8.4 Hz,, H-2¢, H-6¢), 7.22 (1 H, dd, J = 1.0, 8.7 Hz,
H-7), 7.10–7.14 (3 H, m, H-4, H-3¢, H-5¢), 3.98 (3 H, s, OCH3), 2.30
(3 H, s, COCH3), 1.91 (3 H, s, CH3).
13C NMR (CDCl3): d = 197.1, 173.9, 163.3, 161.7, 140.5, 134.5,
134.3, 131.3, 130.2, 129.5, 124.7, 119.9, 118.1, 110.6, 110.5, 102.4,
89.8, 55.6, 22.6, 20.9.
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73.29; H, 5.22; N, 3.67.
1-Acetyl-3-(4¢-fluorophenyl)-1-hydroxy-8-methoxy-1H-ben-
zo[e]indol-2(3H)-one (5ai)
Colorless microcrystals (from EtOH); mp 177–177.5 °C.
IR (KBr): 3271, 1726, 1691 cm–1.
1H NMR (CDCl3): d = 8.54 (1 H, s, OH), 8.12 (1 H, d, J = 2.7 Hz,
H-9), 8.08 (1 H, d, J = 9.3 Hz, H-6), 7.75 (1 H, d, J = 9.3 Hz, H-5),
7.57–7.52 (2 H, m, H-2¢, H-6¢), 7.23 (1 H, d, J = 9.3 Hz, H-4), 7.13
(1 H, dd, J = 2.7, 9.0 Hz, H-7), 7.04–6.99 (2 H, m, H-3¢, H-5¢), 3.99
(3 H, s, OCH3), 1.92 (3 H, s, COCH3).
13C NMR (CDCl3): d = 197.2, 173.7, 167.8, 163.5, 161.8, 140.7,
132.9, 131.3, 130.8, 128.8, 124.7, 121.8, 121.7, 118.2, 115.9, 115.5,
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Colorless microcrystals (from EtOH); mp 177–177.5 °C.
IR (KBr): 3414, 3325, 1724, 1680 cm–1.
Synthesis 2008, No. 17, 2686–2694 © Thieme Stuttgart · New York

2694
Z.-q. Cong, H. Nishino
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Synthesis 2008, No. 17, 2686–2694 © Thieme Stuttgart · New York