The radical reactions of imine radicals produced from the metal salts oxidation of 2-amino-1,4-benzoquinones

Article abstract of DOI:10.1016/j.tet.2009.07.025

The metal salts mediated oxidative free radical reaction of 2-amino-1,4-benzoquinones is described. Imine radicals can be generated by the oxidation of 2-amino-1,4-benzoquinones with Mn(III) and Ag(II). The dimeric products 4 and 14 were formed via the in

Full text of DOI:10.1016/j.tet.2009.07.025

Tetrahedron 65 (2009) 7415–7421
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The radical reactions of imine radicals produced from the metal salts
oxidation of 2-amino-1,4-benzoquinones
*
Po-Yuan Lu, Kuang-Po Chen, Che-Ping Chuang
Department of Chemistry, National Cheng Kung University, Tainan, Taiwan 70101, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
The metal salts mediated oxidative free radical reaction of 2-amino-1,4-benzoquinones is described.
Imine radicals can be generated by the oxidation of 2-amino-1,4-benzoquinones with Mn(III) and Ag(II).
The dimeric products 4 and 14 were formed via the intermolecular radical coupling reaction of the
corresponding radical intermediates 5 and 15. In the presence of styrene, twistane 17 was afforded from
2-phenylamino-1,4-benzoquinone 1 via a radical annulation reaction of imine radical 5.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 14 April 2009
Received in revised form 30 June 2009
Accepted 7 July 2009
Available online 10 July 2009
Keywords:
Manganese(III) acetate
Silver(I) nitrate–potassium persulfate
2-Amino-1,4-benzoquinones
Imine radical
1. Introduction
formation of this dimeric product 4b is interesting. Although it has
been known that imine radical 8 can be generated by the oxidation
Carbon–carbon bond forming reactions mediated by radical
have received considerable attention in organic synthesis during
the last two decades.1 The oxidative free radical reaction mediated
by metal salts has been developed into a versatile protocol for the
formation of highly functionalized products from simple pre-
cursors.2–5 Among these, manganese(III) acetate, cerium(IV) am-
monium nitrate, and silver(I) carbonate have been used most
efficiently. Previously, we found that oxidative free radical reactions
of enamine 6 with metal salts (Eq. 2) and it undergoes efficient
addition to the C–C double bond.8 The generation of imine radial 5
has not yet been reported. In this report, we wish to describe our
results on the free radical reaction of imine radical produced from
the metal salts oxidation of 2-amino-1,4-benzoquinones.
O
O
O
H
N
OEt
2
of 2-phenylamino-1,4-naphthoquinones with
b-dicarbonyl com-
Mn(OAc)3
HCO2H
pounds produced benzo[f]indole-4,9-diones and benzo[b]acridine-
6,11-diones effectively.3f,j,k The solvent effects play an important
role in this free radical reaction.3k We have continued to study this
manganese(III) mediated reaction with 2-phenylamino-1,4-ben-
zoquinone 1. When 2,3-dimethyl-5-(4-methylphenylamino)-1,4-
benzoquinone (1b) was treated with ethyl acetoacetate (2) and
manganese(III) acetate in formic acid, dimer 4b was obtained ex-
clusively in 46% yield and no trace of the expected indole-4,9-dione
3b could be isolated (Eq. 1).6 Dimer 4b was formed presumably via
the intermolecular coupling reaction of imine radical 5b produced
by the manganese(III) oxidation of 1b (Scheme 1).7 This different
behavior of 1b can be explained by the higher the electron density
of 1b, owing to electron donating of the two methyl groups,
therefore it was oxidized in a much faster rate than that of the
corresponding 2-phenylamino-1,4-naphthoquinone derivative. The
1b
O
O
O
N
Tol
N
(1)
O
+
O
CO2Et
3b (0%)
O
N
4b (46%)
O
2. Results and discussion
We began our studies of the manganese(III) mediated
dimerization reaction with 2-phenylamino substituted 1,4-benzo-
quinones 1 (Eq. 3). When 2,3-dimethyl-5-(3,5-dimethylphenyl-
amino)-1,4-benzoquinone (1a) was treated with manganese(III)
* Corresponding author. Fax: þ886 6 2740552.
E-mail address: cpchuang@mail.ncku.edu.tw (C.-P. Chuang).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.07.025

7416
P.-Y. Lu et al. / Tetrahedron 65 (2009) 7415–7421
R3
R6
O
H
NHR O
Mn(III) or Ce(IV)
R1
R2
N
R4
R5
Mn(OAc)3
HCO2H
R1
R1
R2
R2
3
6
NR
O
NR
O
1 O
(2)
O
R3
R1
R2
7
8
R1
N
R4
R2
R5
R5
R2
O
R6
R6
(3)
O
O
H
N
O
O
N
Mn(III)
Mn(III)
R4
N
R1
O
1a
O
R3
4 O
5a
N
H
9a
O
O
H
N
O
O
O
O
N
N
N
N
Et
O
O
O
Mn(III)
O
O
13a
O
N
H
N
H
11a
10a
O
12a
O
O
4a
C3
C19
C4
Scheme 1.
O3
O1
C2
C6
C18
C1
acetate in formic acid at 0 ꢀC, 4a was obtained in 56% yield (Table 1,
entry 1). The structure of 4a was revealed by 1H NMR and 13C NMR
analyses. In addition, the NMR-based structure was confirmed by
single crystal X-ray crystallographic analysis (Figure 1).9 By using
acetic acid as solvent, this reaction only resulted in the deterioration
of 1a and no desired product 4a can be found after stirred at room
temperature for 16 h (entry 2). Although the mechanistic details of
this reaction are unclear, dimer 4a may be formed by the reaction
mechanism presented in Scheme 1. Initiation occurs with the man-
ganese(III) oxidation of 1a to produce imine radical 5a. In-
termolecular coupling7 of 5a generates 9a, which is then oxidized by
manganese(III) to produce imine radical 10a. Six-membered-ring
radical cyclization of 10a gives 11a after aromatization. Oxidation of
11a by manganese(III) produces imine radical 12a and then it un-
dergoes another six-membered-ring radical cyclization and sub-
sequent aromatization to give dimer 4a. The generalities of this
reaction were examined with other 2-phenylamino-1,4-benzoqui-
nones 1 and the results are summarized in Table 1. This reaction
worked well and dimers 4 were formed in 21–60% yields. It shows
that the reaction yields for this reaction are highly dependent on the
effect of substituent on the benzene ring. The reactions of 1d and 1e
bearing an ortho-methyl group gave the corresponding dimers 4d
C5
O2
C17
C16
C20
C21
O4
C22
C23
C32
C7
N1
C15
C31
N2
C24
C25
C29
C26
C8
C9
C30
C14
C13
C28
C12
C11
C10
C27
Figure 1. The molecular structure of 4a.
and 4e in lower yields (entries 5 and 6). This can be attributed to the
steric effect of the ortho substituent, which retards the free radical
cyclization of 10 and 12 onto the benzene ring. When the electron-
withdrawing halogeno groups weresubstituted on the benzene ring,
the yields of 4f and 4g are reduced substantially (entries 7 and 8).
These results can be rationalized by consideration that the electron
deficiency of radical intermediates 10 and 12 makes the rate of free
radical cyclization to the halogeno group substituted benzene ring
much slower. To test the regioselectivity of this reaction, the oxida-
tive radical reaction of 2-methyl-5-phenylamino-1,4-benzoqui-
nones 1h and 1i was next studied. Treatment of 1h with
manganese(III)acetate under thesameconditions affordeddimer4h
exclusively in 51% yield (entry 9). No product derived from the ad-
dition of radical 5h to the C3 of another 1h can be found. It indicates
that the intermolecular radical coupling reaction of 5h proceeds in
a much faster reaction rate than that of the intermolecular addition
of it to C3 of another 1h. Reaction of 1i with manganese(III) acetate
gave result similar to 1h, with the corresponding dimer 4i as the sole
product in 37% yield (entry 10). Thisreactionwas also examined with
2-alkylamino substituted 1,4-benzoquinone. In contrast to the
results shown above, the reaction of 5-ethylamino-2,3-dimethyl-
1,4-benzoquinone (13a) with manganese(III) acetate gave no
distinguishable product (entry 11).
Table 1
Oxidative dimerization mediated by manganese(III) acetate
Entry
1,4-Benzoquinone
Product (yield (%))
R1
R2
R3
H
R4
R5
H
R6
1
2
3
4
5
6
7
8
1a
1a
1b
1c
1d
1e
1f
1g
1h
1i
Me
Me
Me
Me
4a (56)a
4a (0)b
4b (60)a
4c (49)a
4d (31)a
4e (46)a
4f (24)a
4g (21)a
4h (51)a
4i (37)a
d
Me
Me
Me
Me
Me
Me
H
Me
Me
Me
Me
Me
Me
Me
Me
H
H
H
H
H
H
H
H
H
H
Me
H
H
Me
Br
Cl
Me
H
H
H
H
H
H
H
H
H
Me
Me
H
H
H
H
9
10
11
H
13a
a
These reactions were carried with
1
(0.71 mmol), manganese(III) acetate
(2.94 mmol) in formic acid (10 mL) at 0 ꢀC for 30 min.
b
The reaction mixture was stirred at rt in HOAc for 16 h.

P.-Y. Lu et al. / Tetrahedron 65 (2009) 7415–7421
7417
Carbon radical is produced by the Ag(I)/S2Oꢁ8 2 redox system and
it undergoes efficient addition to the C–C double bond.10 In this
reaction, Ag(II) was generated in situ from Ag(I) by the action of
S2Oꢁ8 2 and catalytical amount of silver(I) was used. Today’s envi-
ronmental concerns encourage the development of greener re-
action conditions. We have continued to study the radical
found. Again, it can be concluded that radical 15c is preferred to
undergo intermolecular coupling reaction. Analogous results were
obtained with 13d–f and are also listed in Table 2 (entries 12–14).
We also studied this silver(II) mediated reaction with 2-phenyl-
amino substituted 1,4-benzoquinone 1. Under Ag(I)/S2Oꢁ8 2 condi-
tions, 1c was converted to the corresponding dimeric product 9c in
48% yield (entry 15). Contrary to the results shown in Table 1, 9c is
the only product and no trace of 4c can be found. This can be as-
cribed to the poor solubility of 9c in acetonitrile–H2O. It pre-
cipitated as the reaction proceeded and could not undergo further
oxidation reaction (9c/4c).
O
R
NH
O
H
N
R1
R2
R1
R2
AgNO3
K2S2O8
R
2
13
O
14 O
R3
(4)
O
O
O
Ph
NH
H
N
R1
R2
R4
R5
R1
R2
N
Ph
R
+
16
R6
2
1 O
15 O
9c O
H
Ph
O
dimerization reaction of 2-alkylamino substituted 1,4-benzoqui-
nones under Ag(I)/S2Oꢁ8 2 conditions (Eq. 4). When 5-ethylamino-
2,3-dimethyl-1,4-benzoquinone (13a) was treated with silver(I)
nitrate and potassium persulfate in acetonitrile–H2O at 70 ꢀC, 14a
was obtained in 66% yield (Table 1, entry 1). Similar result was
obtained when ammonium persulfate was employed in place of
potassium persulfate (entry 2). In the absence of silver(I) nitrate,
the yield of 14a decreased to 37% (entry 3). The formation of 14a
occurs from the intermolecular coupling reaction of imine radical
15a, which was produced by the manganese(III) oxidation of 13a. To
find the optimum reaction conditions, a solvent-screening for this
dimerization reaction of 13a was then undertaken. The change of
solvent to DMA, acetone, and dioxane gave 14a in much poor yields
(entries 6–8). In ethanol, 14a was afforded in 69% yield (entry 4).
Encouraged by these initial results, by choosing acetonitrile
and ethanol as solvent, we applied these reaction conditions to
other 5-ethylamino-1,4-benzoquinones 13b–f. The reaction of 13b
worked well and 14b was produced in good yield (entry 9 and 10).
Reaction of 13c under these reaction conditions afforded dimer 14c
in 63% yield (entry 11). Similar to the results shown in Table 1, di-
mer 14c was formed in high regioselectivity, no product derived
from the addition of radical 15c to the C3 of another 13c can be
NH R3
Mn(OAc)3
O
R4
H
(5)
Ph
17
R6
R5
Ph
O
NH
O
Ph
22a
Radical annulationdthe combination of addition and cycliza-
tion reaction mediated by manganese(III) acetate has been used
for the synthesis of cyclic systems.11 Since imine radical 5 can be
generated effectively from the manganese(III) acetate oxidation
of 2-phenylamino-1,4-benzoquinone 1, we next investigated the
manganese(III) mediated radical annulation reaction between 1
and styrene (16) (Eq. 5). Treatment of 2,3-dimethyl-5-(3,5-
dimethylphenylamino)-1,4-benzoquinone (1a), styrene (16) with
manganese(III) acetate in acetonitrile at 70 ꢀC led to the forma-
tion of 17a in 24% yield (Table 3, entry 1). The structure of 17a
was characterized by 1H NMR and 13C NMR spectra. Furthermore,
the exact configuration of 17a was determined by X-ray crystal-
lographic analysis.12 Twistane 17a may be formed by the reaction
Table 2
Oxidative dimerization mediated by silver(I) nitrate and potassium persulfate
Entry
1,4-Benzoquinone
R1
Solvent
Product (yield (%))
R2
R
Table 3
1
2
3
4
5
6
7
8
13a
13a
13a
13a
13a
13a
13a
13a
13b
13b
13c
13d
13e
13f
1c
Me
Me
Et
CH3CN–H2O
CH3CN–H2O
CH3CN–H2O
EtOH–H2O
EtOH–H2O
DMA–H2O
Acetone–H2O
Dioxane–H2O
CH3CN–H2O
EtOH–H2O
EtOH–H2O
EtOH–H2O
EtOH–H2O
CH3CN–H2O
CH3CN–H2O
14a (66)a
14a (64)b
14a (37)c
14a (69)a
14a (69)b
14a (51)a
14a (35)a
14a (37)a
14b (62)a
14b (67)d
14c (63)a
14d (58)a
14e (70)a
14f (63)e
9c (48)f
Radical annulation reaction mediated by manganese(III) acetate
Entry
1,4-Benzoquinone
Product (yield (%))
R1
H
R2
R3
H
R4
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1b
1b
1c
1d
1e
1f
Me
Me
d
17a (24)
17a (38)a
17a (25)b
17a (33)c
17a (30)c
17b (30)a
17b (25)a
17c (33)a
17d (20)a
17e (21)a
17f (31)a
17g (30)a
17j (30)a
i-PrOH
i-PrOH
Et3SiH
Ph3SiH
i-PrOH
Et3SiH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
9
Me
Me
Bn
10
11
12
13
14
15
H
H
t-Bu
t-Bu
Me
Me
H
Et
H
H
Me
H
Bn
Me
Bn
H
H
H
H
H
H
H
Me
Br
Cl
H
H
H
H
H
H
H
H
9
Me
Me
H
10
11
12
13
a
These reactions were carried with 13 (0.84 mmol), potassium persulfate
1g
1j
H
H
H
OMe
(1.67 mmol), and silver(I) nitrate (0.25 mmol) at 70 ꢀC for 1 h.
b
The reaction was performed with silver(I) nitrate and ammonium persulfate
a
under similar reaction conditions.
These reactions were carried with 1 (0.59 mmol), styrene (12.4 mmol), iso-
propanol (2 mL), and manganese(III) acetate (2.98 mmol) in acetonitrile (8 mL) at
70 ꢀC for 7 h.
c
The reaction was performed with ammonium persulfate under similar reaction
conditions.
d
b
The reaction yield was based on 89% conversion of 13b.
The reaction yield was based on 93% conversion of 13f.
The reaction was carried with 1c, potassium persulfate, and silver(I) nitrate
The reaction was performed in i-PrOH.
These reactions were carried with 1 (0.59 mmol), styrene (12.4 mmol), silane
e
c
f
(1.18 mmol), and manganese(III) acetate (2.94 mmol) in acetonitrile (10 mL) at 70 ꢀ
for 7 h.
C
under similar reaction conditions.

7418
P.-Y. Lu et al. / Tetrahedron 65 (2009) 7415–7421
Ph
Ph
O
O
H
Ph
N
O
O
Ar
Mn(III)
Ph
16
1a
N
N
Ar
O
Ar
O
H
Ar = 3,5-(CH3)2C6H3
18a
19a
5a
H
Ph
Ph
O
O
16
17a
N
N
Ar
O
Ar
O
20a
21a
Ph
H
Ph
Scheme 2.
mechanism presented in Scheme 2. Manganese(III) oxidation of
1a produces imine radical 5a. Intermolecular addition of 5a to the
C–C double bond of styrene generates radical 18a, which un-
dergoes 6-exo radical cyclization to produce radical 19a. This
radical intermediate 19a undergoes intermolecular addition to
another styrene to generate 20a. Free radical cyclization of 20a to
the imine group followed by hydrogen atom abstraction from the
reaction mixture gives 17a. There is no trace of another expected
product 22a, derived from the 5-exo radical cyclization of 18a, can
be found. To improve the reaction yield of 17a, we next con-
ducted this annulation reaction of 1a with isopropanol, tri-
ethylsilane, and triphenylsilane as hydrogen atom sources
(entries 2–5). As shown in Table 3, in the presence of isopropanol,
17a was produced in best reaction yield (entry 4). Other examples
with isopropanol as hydrogen atom source are also listed in Table
3 (entries 7–13). In all cases, 1 was converted to 17 effectively in
fair yield. Due to the steric effect of the ortho-methyl group, 1d
and 1e gave the corresponding 17d and 17e in lower yields
(entries 9 and 10) (Fig. 2).
of styrene, twistane 17 was afforded from 2-phenylamino-1,4-
benzoquinone
1 via a radical annulation reaction of imine
radical 5.
3. Experimental
3.1. General
Melting points are uncorrected. Infrared spectra were taken
with a Hitachi 260–30 spectrometer. 1H and 13C NMR spectra were
recorded on a Bruker AMX-400, AVANCE 500 or AVANCE 300
spectrometer. Chemical shifts are reported in parts per million
relative to TMS as internal reference. Elemental analyses were
performed with Heraeus CHN-Rapid Analyzer. Mass spectra were
recorded with Finnigan MAT-95XL mass spectrometer. Analytical
thin-layer chromatography was performed with precoated silica gel
60 F254 plates (0.25 mm thick) from EM Laboratories and visualized
by UV. The reaction mixture was purified by column chromatog-
raphy over EM Laboratories silica gel (70–230 mesh). The starting
2-amino-1,4-benzoquinones 1 and 13 were synthesized according
to literature procedure.13
C26
C27
3.2. Typical experimental procedure for the manganese(III)
mediated dimerization reaction
C25
C28
C24
A mixture of 2,3-dimethyl-5-(3,5-dimethylphenylamino)-1,4-
benzoquinone (1a, 182 mg, 0.71 mmol) and manganese(III) acetate
(788 mg, 2.94 mmol) in formic acid (10 mL) was stirred at 0 ꢀC for
30 min. The reaction mixture was diluted with ethyl acetate
(100 mL), washed with saturated aqueous sodium bisulfite (50 mL),
water (2ꢂ50 mL), saturated aqueous sodium bicarbonate (50 mL),
and dried (Na2SO4). The solvent was evaporated under reduced
pressure and the crude product was purified by column chroma-
tography over silica gel (20 g) using dichloromethane–ethyl acetate
(30:1) as eluent, followed by crystallization (chloroform–hexane)
to give 4a (100 mg, 56%).
C29
C22
C23
C30
C21
C18
O1
C31
C32
C19
C20
C9
O2
N1
C1
3.2.1. Dimer 4a
C8
C10
C16
C17
Yellow powders; mp 271–272 ꢀC (dec); IR (KBr) 1680, 1600,
C6
C2
1255, 1065, 735 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.97 (s, 6H,
C11
C12
C3
2ꢂCH3), 2.12 (s, 6H, 2ꢂCH3), 2.19 (s, 6H, 2ꢂCH3), 2.25 (s, 6H,
C7
C15
2ꢂCH3), 6.74 (s, 2H, 2ꢂArH), 7.31 (s, 2H, 2ꢂArH); 13C NMR
C5
(125.8 MHz, CDCl3)
d 13.4, 14.7, 20.4, 23.0, 56.2, 116.4, 129.6, 135.6,
C14
136.2, 139.9, 144.4, 147.5, 147.8, 157.2, 181.5, 191.7; HRMS calcd for
C32H28N2O4: m/z 504.2051, found m/z 504.2050.
C4
C13
Figure 2. The molecular structure of 17a.
3.2.2. Dimer 4b
Yellow crystals; mp 253–254 ꢀC (dec); IR (KBr) 1680, 1665,
In conclusion, imine radicals 5 and 15 can be generated from
the manganese(III), silver(II) oxidation of 2-amino-1,4-benzoqui-
nones. These free radical reactions provide efficient methods for
the generation of the dimeric products 4 and 14. In the presence
1615, 1375, 1260 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.97 (s, 6H,
2ꢂCH3), 2.21 (s, 6H, 2ꢂCH3), 2.34 (s, 6H, 2ꢂCH3), 6.68 (s, 2H, ArH),
7.11 (d, J¼7.9 Hz, 2H, ArH), 7.53 (d, J¼7.9 Hz, 2H, ArH); 13C NMR
(125.8 MHz, CDCl3)
d 13.7, 14.5, 21.6, 54.9, 122.6, 126.9, 131.0, 131.2,

P.-Y. Lu et al. / Tetrahedron 65 (2009) 7415–7421
7419
140.0, 141.3, 146.2, 148.4, 155.8, 181.6, 191.4. Anal. Calcd for
(75.4 MHz, CDCl3)
d
17.4, 55.1, 121.7, 126.6, 130.88, 130.91, 131.4,
C30H24N2O4: C, 75.61; H, 5.08; N, 5.88. Found: C, 75.63; H, 5.05; N,
5.88.
139.7, 141.4, 150.9, 156.5, 181.2, 191.5; HRMS calcd for C26H16N2O4:
m/z 420.1100, found m/z 420.1105.
3.2.3. Dimer 4c
3.3. Typical experimental procedure for the silver(II)
mediated dimerization reaction
Yellow powders; mp 275–276 ꢀC (dec); IR (KBr) 1665, 1610,
1375, 1260, 775 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.98 (s, 6H,
2ꢂCH3), 2.34 (s, 6H, 2ꢂCH3), 6.93 (d, J¼7.6 Hz, 2H, ArH), 7.18 (t,
A solution of 5-ethylamino-2,3-dimethyl-1,4-benzoquinone
J¼7.6 Hz, 2H, ArH), 7.32 (t, J¼7.6 Hz, 2H, ArH), 7.64 (d, J¼7.6 Hz, 2H,
(13a, 150 mg, 0.84 mmol), potassium persulfate (452 mg,
1.67 mmol), and silver(I) nitrate (43 mg, 0.25 mmol) in ethanol–
water (8 mL, 1:3) was heated at 70 ꢀC for 1 h. The reaction mixture
was diluted with ethyl acetate (100 mL), washed with water
(3ꢂ50 mL), and dried (Na2SO4). The solvent was evaporated under
reduced pressure and the crude product was purified by column
chromatography over silica gel (20 g) using dichloromethane as
eluent, followed by crystallization (chloroform–hexane) to give 14a
(104 mg, 69%).
ArH); 13C NMR (125.8 MHz, CDCl3)
d 13.8, 14.5, 54.9, 122.6, 126.4,
130.6, 131.1, 142.0, 146.3, 148.6, 156.6, 181.4, 191.2; HRMS calcd for
C28H20N2O4: m/z 448.1431, found m/z 448.1427.
3.2.4. Dimer 4d
Yellow powders; mp 348–349 ꢀC (dec); IR (KBr) 1665, 1610,
1370, 1260, 1075 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.96 (s, 6H,
2ꢂCH3), 2.32 (s, 6H, 2ꢂCH3), 2.50 (s, 6H, 2ꢂCH3), 6.75 (d,
J¼7.6 Hz, 2H, ArH), 7.04 (t, J¼7.6 Hz, 2H, ArH), 7.14 (d, J¼7.6 Hz,
2H, ArH); 13C NMR (100.6 MHz, CDCl3)
d
13.7, 14.4, 17.7, 54.7,
3.3.1. 2,20-Bi(3-ethylamino-5,6-dimethyl-1,4-benzoquinone) 14a
122.6, 124.1, 129.9, 132.2, 139.8, 140.4, 146.1, 148.4, 155.4, 181.4,
191.6; HRMS calcd for C30H24N2O4: m/z 476.1752, found m/z
476.1744.
Dark violet crystals; mp 174–175 ꢀC; IR (KBr) 3305, 3265, 1660,
1575, 1300 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.13 (t, J¼7.0 Hz, 6H,
2ꢂCH3), 2.01 (s, 6H, 2ꢂCH3), 2.04 (s, 6H, 2ꢂCH3), 3.13 (dq, J¼11.0,
7.0 Hz, 2H, CH2), 3.25 (dq, J¼11.0, 7.0 Hz, 2H, CH2), 5.61 (br s, 2H,
3.2.5. Dimer 4e
2ꢂNH); 13C NMR (75.4 MHz, CDCl3)
d 11.9, 13.1, 15.2, 37.7, 104.7,
136.1, 143.8, 144.4, 184.06, 184.11. Anal. Calcd for C20H24N2O4: C,
67.40; H, 6.79; N, 7.86. Found: C, 67.32; H, 6.82; N, 7.85.
Yellow powders; mp 327–328 ꢀC (dec); IR (KBr) 2920, 1665,
1610, 1260, 740 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.95 (s, 6H,
2ꢂCH3), 2.17 (s, 6H, 2ꢂCH3), 2.31 (s, 6H, 2ꢂCH3), 2.47 (s, 6H,
2ꢂCH3), 6.51 (s, 2H, ArH), 6.94 (s, 2H, ArH); 13C NMR (125.8 MHz,
3.3.2. 2,20-Bi(3-benzylamino-5,6-dimethyl-1,4-benzoquinone) 14b
CDCl3)
d
13.7, 14.5, 17.6, 21.5, 54.7, 122.7, 124.7, 133.0, 138.5, 139.6,
Pink crystals; mp 197–198 ꢀC; IR (KBr) 3330, 1650, 1580, 1500,
140.4, 146.1, 148.2, 154.5, 181.7, 191.8; HRMS calcd for C32H28N2O4:
m/z 504.2043, found m/z 504.2046.
1300 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.95 (s, 6H, 2ꢂCH3), 1.97 (s,
6H, 2ꢂCH3), 4.29 (dd, J¼13.6, 5.2 Hz, 2H, CH2), 4.33 (dd, J¼13.6,
5.2 Hz, 2H, CH2), 5.99 (t, J¼5.2 Hz, 2H, 2ꢂNH), 7.06–7.12 (m, 4H,
3.2.6. Dimer 4f
ArH), 7.21–7.31 (m, 6H, ArH); 13C NMR (75.4 MHz, CDCl3)
d 12.0,
Yellow crystals; mp 314–315 ꢀC (dec); IR (KBr) 1675, 1610, 1370,
13.2, 47.2, 105.5, 127.1, 127.5, 128.7, 136.4, 137.9, 144.0, 144.3, 183.9,
184.2. Anal. Calcd for C30H28N2O4: C, 74.98; H, 5.87; N, 5.83. Found:
C, 74.98; H, 5.92; N, 5.84.
1260, 740 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
2.01 (s, 6H, 2ꢂCH3),
2.36 (s, 6H, 2ꢂCH3), 7.00 (d, J¼1.8 Hz, 2H, ArH), 7.48 (dd, J¼8.4,
1.8 Hz, 2H, ArH), 7.55 (d, J¼8.4 Hz, 2H, ArH); 13C NMR (125.8 MHz,
CDCl3)
d
13.9, 14.6, 54.5, 124.1, 124.6, 129.2, 132.4, 134.1, 140.8, 146.2,
3.3.3. 2,20-Bi(3-ethylamino-6-methyl-1,4-benzoquinone) 14c
149.1, 156.0, 180.7, 190.5; HRMS calcd for C28H18 Br2N2O4: m/z
603.9641, found m/z 603.9637.
Dark violet crystals; mp 164–165 ꢀC (dec); IR (KBr) 3330, 1670,
1560,1515,1290 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.14 (t, J¼7.2 Hz,
6H, 2ꢂCH3), 2.08 (d, J¼1.5 Hz, 6H, 2ꢂCH3), 3.05–3.35 (m, 4H,
3.2.7. Dimer 4g
2ꢂCH), 5.59 (br s, 2H, 2ꢂNH), 6.52 (q, J¼1.5 Hz, 2H, 2ꢂCH); 13C
Yellow crystals; mp 315–316 ꢀC; IR (KBr) 2920, 1675, 1550, 1330,
NMR (75.4 MHz, CDCl3) d 15.3, 16.9, 37.8, 105.1, 129.1, 144.2, 150.3,
1260 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
2.01 (s, 6H, 2ꢂCH3), 2.36 (s,
183.7, 184.3. Anal. Calcd for C18H20N2O4: C, 65.84; H, 6.14; N, 8.53.
Found: C, 65.77; H, 6.18; N, 8.50.
6H, 2ꢂCH3), 6.86 (d, J¼2.0 Hz, 2H, ArH), 7.32 (dd, J¼8.5, 2.0 Hz, 2H,
ArH), 7.62 (d, J¼8.5 Hz, 2H, ArH); 13C NMR (75.4 MHz, CDCl3)
d 13.8,
14.5, 54.5, 123.9, 126.4, 131.0, 132.2, 136.3, 140.4, 146.2, 149.1, 156.0,
180.7, 190.5; HRMS calcd for C28H18Cl2N2O4: m/z 516.0649, found:
m/z 516.0646.
3.3.4. 2,20-Bi(3-benzylamino-6-methyl-1,4-benzoquinone) 14d
Dark violet crystals; mp 174–175 ꢀC; IR (KBr) 3315, 3290, 1670,
1565, 1335 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.98 (d, J¼1.3 Hz, 6H,
2ꢂCH3), 4.31 (d, J¼6.1 Hz, 4H, 2ꢂCH2), 5.97 (t, J¼6.1 Hz, 2H, 2ꢂNH),
6.48 (q, J¼1.3 Hz, 2H, 2ꢂCH), 7.06–7.11 (m, 4H, ArH), 7.22–7.32 (m,
3.2.8. Dimer 4h
Yellow powders; mp 209–210 ꢀC (dec); IR (KBr) 1685, 1615,
6H, ArH); 13C NMR (75.4 MHz, CDCl3)
d 16.8, 47.0, 105.7, 127.1, 127.7,
1565, 1310, 1210 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
2.02 (d,
128.8, 129.2, 137.6, 144.2, 150.1, 183.5, 184.2. Anal. Calcd for
C28H24N2O4: C, 74.32;H, 5.35; N, 6.19. Found:C, 74.17; H, 5.33; N, 6.16.
J¼1.4 Hz, 6H, 2ꢂCH3), 2.24 (s, 6H, 2ꢂCH3), 6.79 (d, J¼0.8 Hz, 2H,
ArH), 7.14 (dd, J¼7.9, 0.8 Hz, 2H, ArH), 7.27 (q, J¼1.4 Hz, 2H, 2ꢂCH),
7.55 (d, J¼7.9 Hz, 2H, ArH); 13C NMR (125.8 MHz, CDCl3)
d
17.4, 21.6,
3.3.5. 2,20-Bi(5-tert-butyl-3-methylamino-1,4-benzoquinone) 14e
55.1, 121.8, 127.2, 131.3, 131.5, 139.5, 139.7, 141.8, 150.9, 155.8, 181.4,
191.8; HRMS calcd for C28H20N2O4: m/z 448.1417, found m/z
448.1420.
Dark red crystals; mp 194–195 ꢀC; IR (KBr) 3310,1670,1580,1510,
1335 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.27 (s,18H, 6ꢂCH3), 2.89 (s,
6H, 2ꢂCH3), 6.56 (s, 2H, 2ꢂCH); 13C NMR (75.4 MHz, CDCl3)
d 28.9,
30.3, 34.7, 103.5, 135.3, 146.3, 150.9, 183.5, 184.7. Anal. Calcd for
C22H28N2O4:C, 68.73;H, 7.34;N,7.29. Found:C, 68.83;H, 7.36;N, 7.23.
3.2.9. Dimer 4i
Yellow powders; mp 235–236 ꢀC (dec); IR (KBr) 1680, 1625,
1565, 1310, 1210 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
2.02 (d,
3.3.6. 2,20-Bi(3-benzylamino-5-tert-butyl-1,4-benzoquinone) 14f
J¼1.3 Hz, 6H, 2ꢂCH3), 7.05 (dd, J¼7.8, 1.1 Hz, 2H, ArH), 7.23 (td,
J¼7.8, 1.1 Hz, 2H, ArH), 7.29 (q, J¼1.3 Hz, 2H, 2ꢂCH), 7.36 (td, J¼7.8,
1.1 Hz, 2H, ArH), 7.67 (dd, J¼7.8, 1.1 Hz, 2H, ArH); 13C NMR
Dark redcrystals; mp 164–165 ꢀC (dec); IR (KBr) 3280,1665,1575,
1505, 1330 cmꢁ1; 1H NMR (400 MHz, CDCl3)
4.29 (d, J¼5.9 Hz, 4H, 2ꢂCH2), 6.04 (t, J¼5.9 Hz, 2H, 2ꢂNH), 6.49 (s,
d
1.27 (s, 18H, 6ꢂCH3),

7420
P.-Y. Lu et al. / Tetrahedron 65 (2009) 7415–7421
2H, 2ꢂCH), 7.07–7.13 (m, 4H, ArH), 7.23–7.32 (m, 6H, ArH); 13C NMR
1.21 (s, 3H, CH3), 1.90 (dd, J¼13.5, 11.1 Hz, 1H, CH), 1.99 (dd, J¼13.5,
9.1 Hz, 1H, CH), 2.10–2.25 (m, 2H, 2ꢂCH), 3.09 (dd, J¼11.6, 8.6 Hz,
1H, CH), 3.72 (dd, J¼4.5, 1.6 Hz, 1H, CH), 3.98 (dd, J¼11.1, 9.1 Hz, 1H,
CH), 4.89 (br s, 1H, NH), 6.61 (dd, J¼7.7, 1.2 Hz, 2H, ArH), 6.68 (t,
J¼7.7 Hz, 1H, ArH), 6.81 (dd, J¼7.7, 1.2 Hz, 2H, ArH), 6.98–7.11 (m,
7H, ArH), 7.27–7.34 (m, 3H, ArH); 13C NMR (75.4 MHz, CDCl3)
(75.4 MHz, CDCl3) d 29.0, 34.8, 47.3, 104.0, 127.2, 127.8, 128.9, 135.3,
137.8, 145.3, 151.1, 183.3, 184.9. Anal. Calcd for C34H36N2O4: C, 76.09;
H, 6.76; N, 5.22. Found: C, 75.76; H, 6.75; N, 5.11.
3.3.7. 2,20-Bi(5,6-dimethyl-3-phenylamino-1,4-benzoquinone) 9c
Dark red powder; mp 235–236 ꢀC; IR (KBr) 3360, 3305, 1635,
d 11.6, 12.7, 31.0, 37.6, 46.8, 48.1, 51.9, 53.8, 57.2, 70.1, 115.2, 118.2,
1580, 1310 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
1.82 (s, 6H, 2ꢂCH3),
127.1, 127.7, 127.8, 128.3, 128.72, 128.74, 128.9, 138.4, 139.0, 144.2,
214.6, 216.1. Anal. Calcd for C30H29NO2: C, 82.73; H, 6.71; N, 3.22.
Found: C, 82.81; H, 6.82; N, 3.15.
2.01 (s, 6H, 2ꢂCH3), 6.84 (d, J¼7.5 Hz, 4H, ArH), 6.96 (t, J¼7.5 Hz, 2H,
ArH), 7.01 (br s, 2H, 2ꢂNH), 7.05 (t, J¼7.5 Hz, 4H, ArH); 13C NMR
(75.4 MHz, CDCl3) d 11.6, 12.9, 108.4, 123.9, 124.9, 127.8, 135.9, 137.8,
139.2, 144.0, 183.2, 184.1. Anal. Calcd for C28H24N2O4: C, 74.32; H,
5.35; N, 6.19. Found: C, 74.12; H, 5.33; N, 6.17.
3.4.4. rel-(1R,3S,4S,6S,10R)-1,6-Dimethyl-3-(2-methylphenyl-
amino)-4,10-diphenyl-tricyclo[4,4,0,03,8]decane-2,7-dione 17d
White crystals; mp 249–250 ꢀC; IR (KBr) 3400, 2945, 1725, 1605,
3.4. Typical experimental procedure for the radical
annulation reaction
1455 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 0.83 (s, 3H, CH3), 1.22 (s,
3H, CH3), 1.78 (s, 3H, CH3), 1.91 (dd, J¼13.5, 11.1 Hz, 1H, CH), 2.00
(dd, J¼13.5, 9.2 Hz, 1H, CH), 2.13–2.28 (m, 2H, 2ꢂCH), 3.11 (dd,
J¼11.5, 8.7 Hz, 1H, CH), 3.78 (dd, J¼4.3, 1.4 Hz, 1H, CH), 4.02 (dd,
J¼11.1, 9.2 Hz,1H, CH), 4.87 (br s,1H, NH), 6.63 (t, J¼7.5 Hz,1H, ArH),
6.73 (d, J¼7.5 Hz, 2H, ArH), 6.84 (d, J¼7.5 Hz, 1H, ArH), 6.94 (d,
J¼8.0 Hz, 1H, ArH), 6.97–7.03 (m, 2H, ArH), 7.03–7.11 (m, 4H, ArH),
A mixture of 2,3-dimethyl-5-(3,5-dimethylphenylamino)-1,4-
benzoquinone (1a, 151 mg, 0.59 mmol), styrene (1.29 g,
12.4 mmol), isopropanol (2 mL), and manganese(III) acetate
(395 mg, 1.47 mmol) in acetonitrile (8 mL) was heated at 70 ꢀC.
After heated for 3 h, the color of manganese(III) acetate dis-
appeared, another manganese(III) acetate (405 mg, 1.51 mmol)
was added. The reaction mixture was heated for another 4 h and
then diluted with ethyl acetate (100 mL), washed with saturated
aqueous sodium bisulfite (50 mL), water (2ꢂ50 mL), and dried
(Na2SO4). The solvent was evaporated under reduced pressure and
the crude product was purified by column chromatography over
silica gel (20 g) using ethyl acetate–hexane (1:20) as eluent, fol-
lowed by crystallization (ethyl acetate–hexane) to give 17a
(105 mg, 38%).
7.27–7.37 (m, 3H, ArH); 13C NMR (75.4 MHz, CDCl3)
d 11.6, 12.7, 17.2,
31.0, 37.6, 46.3, 48.1, 52.5, 53.8, 57.1, 70.4, 113.0, 118.1, 124.3, 126.3,
127.0, 127.6, 127.7, 128.3, 128.68, 128.71, 130.4, 138.2, 139.0, 142.5,
215.0, 216.3. Anal. Calcd for C31H31NO2: C, 82.82; H, 6.95; N, 3.12.
Found: C, 83.05; H, 7.10; N, 3.07.
3.4.5. rel-(1R,3S,4S,6S,10R)-1,6-Dimethyl-3-(2,4-dimethylphenyl-
amino)-4,10-diphenyl-tricyclo[4,4,0,03,8]decane-2,7-dione 17e
White crystals; mp 257–258 ꢀC; IR (KBr) 3390, 2925, 1730, 1515,
1455 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 0.82 (s, 3H, CH3), 1.21 (s,
3H, CH3), 1.74 (s, 3H, CH3), 1.90 (dd, J¼13.5,11.1 Hz,1H, CH), 1.99 (dd,
J¼13.5, 9.2 Hz, 1H, CH), 2.12–2.25 (m, 2H, 2ꢂCH), 2.19 (s, 3H, CH3),
3.09 (dd, J¼11.4, 8.8 Hz,1H, CH), 3.75 (dd, J¼4.2,1.9 Hz,1H, CH), 3.99
(dd, J¼11.1, 9.2 Hz, 1H, CH), 4.72 (s, 1H, NH), 6.67 (s, 1H, ArH), 6.73
(d, J¼7.2 Hz, 2H, ArH), 6.80–6.88 (m, 2H, ArH), 6.97–7.10 (m, 5H,
3.4.1. rel-(1R,3S,4S,6S,8S,10R)-1,6-Dimethyl-3-(3,5-dimethylphenyl-
amino)-4,10-diphenyl-tricyclo[4,4,0,03,8]decane-2,7-dione 17a
White crystals; mp 222–223 ꢀC; IR (KBr) 3375, 2950, 1725, 1605,
1455 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 0.80 (s, 3H, CH3), 1.21 (s,
3H, CH3), 1.89 (dd, J¼13.5, 11.1 Hz, 1H, CH), 1.98 (dd, J¼13.5, 9.2 Hz,
1H, CH), 2.08–2.23 (m, 2H, 2ꢂCH), 2.17 (s, 6H, 2ꢂCH3), 3.08 (dd,
J¼11.7, 8.5 Hz, 1H, CH), 3.72 (dd, J¼4.4, 1.2 Hz, 1H, CH), 3.95 (dd,
J¼11.1, 9.2 Hz, 1H, CH), 4.77 (s, 1H, NH), 6.23 (s, 2H, ArH), 6.34 (s, 1H,
ArH), 6.82 (dd, J¼7.6, 1.7 Hz, 2H, ArH), 7.00–7.13 (m, 5H, ArH), 7.27–
ArH), 7.25–7.35 (m, 3H, ArH); 13C NMR (75.4 MHz, CDCl3)
d 11.6,
12.7,17.2, 20.3, 31.0, 37.6, 46.5, 48.1, 52.5, 53.8, 57.1, 70.5,113.1,124.4,
126.5, 127.0, 127.2, 127.6, 127.7, 128.3, 128.7, 131.2, 138.3, 139.1, 139.9,
215.1, 216.4. Anal. Calcd for C32H33NO2: C, 82.90; H, 7.17; N, 3.02.
Found: C, 82.73; H, 7.18; N, 2.95.
7.34 (m, 3H, ArH); 13C NMR (75.4 MHz, CDCl3)
d 11.6, 12.7, 21.4, 31.1,
37.6, 47.1, 48.1, 51.8, 53.8, 57.2, 70.2, 113.5, 120.3, 127.0, 127.7, 127.8,
128.3, 128.7, 138.5, 138.6, 139.0, 144.1, 214.6, 216.4. Anal. Calcd for
C32H33NO2: C, 82.90; H, 7.17; N, 3.02. Found: C, 82.81; H, 7.21; N,
3.00.
3.4.6. rel-(1R,3S,4S,6S,10R)-3-(4-Bromophenylamino)-1,6-
dimethyl-4,10-diphenyl-tricyclo[4,4,0,03,8]decane-2,7-dione 17f
White crystals; mp 251–252 ꢀC; IR (KBr) 3385, 2970, 1730, 1595,
1455 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 0.81 (s, 3H, CH3), 1.21 (s,
3H, CH3), 1.89 (dd, J¼13.4, 11.2 Hz, 1H, CH), 1.98 (dd, J¼13.4, 9.2 Hz,
1H, CH), 2.06–2.24 (m, 2H, 2ꢂCH), 3.09 (dd, J¼11.7, 8.4 Hz, 1H, CH),
3.63 (d, J¼3.8 Hz, 1H, CH), 3.92 (dd, J¼11.2, 9.2 Hz, 1H, CH), 4.94 (br
s, 1H, NH), 6.48 (d, J¼7.9 Hz, 2H, ArH), 6.80 (d, J¼7.9 Hz, 2H, ArH),
6.99–7.16 (m, 7H, ArH), 7.23–7.34 (m, 3H, ArH); 13C NMR (75.4 MHz,
3.4.2. rel-(1R,3S,4S,6S,10R)-1,6-Dimethyl-3-(4-methylphenyl-
amino)-4,10-diphenyl-tricyclo[4,4,0,03,8]decane-2,7-dione 17b
White powder; mp 201–202 ꢀC; IR (KBr) 3390, 2935, 1730, 1615,
1455 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 0.80 (s, 3H, CH3), 1.21 (s,
3H, CH3), 1.89 (dd, J¼13.5, 11.1 Hz, 1H, CH), 1.98 (dd, J¼13.5, 9.1 Hz,
1H, CH), 2.09–2.24 (m, 2H, 2ꢂCH), 2.20 (s, 3H, CH3), 3.08 (dd, J¼11.6,
8.6 Hz, 1H, CH), 3.70 (dd, J¼4.5, 1.6 Hz, 1H, CH), 3.94 (dd, J¼11.1,
9.1 Hz, 1H, CH), 6.52 (d, J¼8.4 Hz, 2H, ArH), 6.82 (dd, J¼7.8, 1.4 Hz,
2H, ArH), 6.86 (d, J¼8.4 Hz, 2H, ArH), 6.99–7.12 (m, 5H, ArH), 7.24–
CDCl3) d 11.6, 12.7, 30.9, 37.6, 46.8, 48.0, 51.7, 53.7, 57.2, 69.9, 110.1,
116.7,127.3,127.8,128.0,128.3,128.6,128.7,131.7,138.2, 138.8, 143.3,
214.3, 215.7. Anal. Calcd for C30H28BrNO2: C, 70.04; H, 5.49; N, 2.72.
Found: C, 69.89; H, 5.42; N, 2.63.
7.34 (m, 3H, ArH); 13C NMR (75.4 MHz, CDCl3)
d
11.5, 12.7, 20.3, 30.9,
3.4.7. rel-(1R,3S,4S,6S,10R)-3-(4-Chlorophenylamino)-1,6-
dimethyl-4,10-diphenyl-tricyclo[4,4,0,03,8]decane-2,7-dione 17g
White crystals; mp 241–242 ꢀC; IR (KBr) 3395, 2975, 1730, 1600,
37.6, 46.9, 48.0, 51.8, 53.7, 57.2, 70.2, 115.4, 127.0, 127.4, 127.6, 127.8,
128.2, 128.7, 129.4, 138.5, 139.0, 141.6, 214.6, 216.2. Anal. Calcd for
C31H31NO2: C, 82.82; H, 6.95; N, 3.12. Found: C, 82.80; H, 6.98; N,
3.06.
1500 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 0.81 (s, 3H, CH3), 1.21 (s,
3H, CH3), 1.88 (dd, J¼13.5, 11.2 Hz, 1H, CH), 1.99 (dd, J¼13.5, 9.1 Hz,
1H, CH), 2.03–2.26 (m, 2H, 2ꢂCH), 3.09 (dd, J¼11.7, 8.4 Hz, 1H, CH),
3.63 (dd, J¼4.0,1.2 Hz,1H, CH), 3.91 (dd, J¼11.2, 9.1 Hz,1H, CH), 4.93
(br s, 1H, NH), 6.52 (d, J¼8.8 Hz, 2H, ArH), 6.79 (dd, J¼7.7, 1.4 Hz, 2H,
ArH), 6.97–7.15 (m, 7H, ArH), 7.28–7.36 (m, 3H, ArH); 13C NMR
3.4.3. rel-(1R,3S,4S,6S,10R)-1,6-Dimethyl-3-phenylamino-4,10-
diphenyl-tricyclo[4,4,0,03,8]decane-2,7-dione 17c
White crystals; mp 204–205 ꢀC; IR (KBr) 3380, 2970, 1730,
1600, 1455 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
0.81 (s, 3H, CH3),
(75.4 MHz, CDCl3) d 11.6, 12.7, 30.9, 37.6, 46.8, 48.0, 51.8, 53.7, 57.2,

P.-Y. Lu et al. / Tetrahedron 65 (2009) 7415–7421
7421
4. (a) Liao, Y.-J.; Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2003, 59, 3511; (b) Tsai, A.-I.;
Lin, C.-H.; Chuang, C.-P. Heterocycles 2005, 977.
70.0, 116.2, 123.0, 127.2, 127.7, 127.9, 128.3, 128.6, 128.7, 128.8, 138.2,
138.8, 142.9, 214.3, 215.8. Anal. Calcd for C30H28ClNO2: C, 76.66; H,
6.00; N, 2.98. Found: C, 76.64; H, 6.03; N, 2.92.
5. (a) Jacobsen, N.; Torsell, K. Acta Chem. Scand. 1973, 27, 3211; (b) Brown, P. M.;
Thomson, R. H. J. Chem. Soc., Perkin Trans. 11976, 997; (c) Citterio, A.; Arnoldi, A.;
Minisci, F. J. Org. Chem. 1979, 44, 2674; (d) Citterio, A.; Vismara, E.; Bernardi, R.
J. Chem. Res., Synop. 1983, 88; (e) Citterio, A.; Vismara, E.; Bernardi, R. J. Chem.
Res., Miniprint 1983, 876; (f) Williams, D. R.; Clark, M. P. Tetrahedron Lett.1998, 39,
7629.
3.4.8. rel-(1R,3S,4S,6S,10R)-1,6-Dimethyl-3-(3-methoxyphenyl-
amino)-4,10-diphenyl-tricyclo[4,4,0,03,8]decane-2,7-dione 17j
White crystals; mp 197–198 ꢀC; IR (KBr) 3390, 2935, 1730, 1600,
6. Reaction of 2-phenylamino-1,4-naphthoquinones with
b-dicarbonyl com-
1455 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 0.81 (s, 3H, CH3), 1.21 (s,
pounds and manganese(III) acetate in formic acid produced corresponding
benzo[f]indole-4,7-diones exclusively. See: Ref. 3k.
3H, CH3), 1.90 (dd, J¼13.5, 11.1 Hz, 1H, CH), 1.99 (dd, J¼13.5, 9.2 Hz,
1H, CH), 2.08–2.25 (m, 2H, CH), 3.09 (dd, J¼12.5, 8.5 Hz, 1H, CH),
3.71 (s, 3H, OCH3), 3.71–3.76 (m, 1H, CH), 3.98 (dd, J¼11.1, 9.2 Hz,
1H, CH), 6.13 (t, J¼2.2 Hz, 1H, ArH), 6.26 (d, J¼7.9 Hz, 2H, ArH), 6.84
(dd, J¼7.9, 2.2 Hz, 2H, ArH), 6.98 (t, J¼7.9 Hz, 1H, ArH), 7.00–7.13 (m,
7. Metal salts mediated radical coupling reactions have been reported. See: (a)
Cho, L. Y.; Romero, J. R. Tetrahedron Lett. 1995, 36, 8757; (b) Ye, J.-H.; Xue, J.; Ling,
K.-Q. Tetrahedron Lett. 1999, 40, 1365; (c) Hong, B.-C.; Shen, I.-C.; Liao, J.-H.
Tetrahedron Lett. 2001, 42, 935; (d) Nicolaou, K. C.; Gary, D. L. F. J. Am. Chem. Soc.
2004, 126, 607; (e) Chuang, C.-P.; Wu, Y.-L. Tetrahedron 2004, 60, 1841; (f) Tsai,
A.-I.; Chuang, C.-P. Tetrahedron 2006, 62, 2235.
8. (a) Cossy, J.; Bouzide, A. J. Chem. Soc., Chem. Commun. 1993, 1218; (b) Cossy, J.;
Bouzide, A.; Leblanc, C. Synlett 1993, 202; (c) Cossy, J.; Bouzide, A. Tetrahedron
Lett. 1993, 34, 5583; (d) Cossy, J.; Bouzide, A. Tetrahedron 1999, 55, 6483; (e)
Cossy, J.; Bouzide, A.; Leblanc, C. J. Org. Chem. 2000, 65, 7257; (f) Zhang, Y.;
Raines, A. J.; Flowers, R. A., II. J. Org. Chem. 2004, 69, 6267; Also see: Refs. 3i,7e,f.
5H, ArH), 7.27–7.32 (m, 3H, ArH); 13C NMR (75.4 MHz, CDCl3)
d 11.6,
12.7, 31.0, 37.6, 46.8, 48.0, 51.7, 53.7, 55.0, 57.2, 70.1, 101.6, 103.5,
108.1, 127.1, 127.7, 127.8, 128.3, 128.7, 129.6, 138.4, 138.9, 145.4, 160.4,
214.5, 215.9. Anal. Calcd for C31H31NO3: C, 79.97; H, 6.71; N, 3.01.
Found: C, 79.98; H, 6.79; N, 2.93.
9. Crystal data for 4a: C32H28N2O3, M¼504.21, T¼296(2) K, ¼0.71073 Å, Mono-
l
clinic, space group P21/c, a¼12.9982(7) Å, b¼13.4719(8) Å, c¼18.1372(9) Å,
a
¼90ꢀ,
b
¼108.346(2)ꢀ,
g
¼90ꢀ, V¼3014.6(3) Å3, Z¼4, Dc¼1.240 mg/m3,
m
¼0.
083 mmꢁ1
,
F(000)¼1192, crystal size 0.65ꢂ0.40ꢂ0.14 mm3, reflections col-
Acknowledgements
lected 24,647, independent reflections 5241 [R(int)¼0.0489], refinement
method, full-matrix least-squares on F2, goodness-of-fit on F2 1.059, final R
indices [I>2
s
(I)] R1¼0.0854, wR2¼0.2568,
R
indices (all data) R1¼0.1158,
We are grateful to the National Science Council of the ROC for
financial support (Grant No. NSC-95-2113-M-006-010-MY3).
wR2¼0.2850, largest diff. peak and hole 1.002 and ꢁ0.567 e Åꢁ3. Crystallo-
graphic data for the structure in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication no.
CCDC 658188. Copies of the data can be obtained, free of charge, on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: þ44 (0)1223 336033 or
e-mail: deposit@ccdc.cam.ac.uk).
References and notes
10. Minisci, F.; Citterio, A. Acc. Chem. Res. 1983, 16, 27.
1. (a) Hart, D. J. Science 1984, 223, 883; (b) Neumann, W. P. Synthesis 1987, 665;
(c) Curran, D. P. Synthesis 1988, 417 and 489; (d) Melikyan, G. G. Synthesis
1993, 833; (e) Iqbal, J.; Bhatia, B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519; (f)
Snider, B. B. Chem. Rev. 1996, 96, 339.
11. (a) Citterio, A.; Sebastiano, R.; Marion, A. J. Org. Chem. 1991, 56, 5328; (b) Citterio,
A.; Sebastiano, R.; Carvayal, M. C. J. Org. Chem. 1991, 56, 5335; (c) Mellor, J. M.;
Mohammed, S. Tetrahedron 1993, 49, 7567.
12. Crystal data for 17a: C32H33NO2, M¼463.59, T¼200(2) K,
l
¼0.71073 Å, Or-
2. (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, 5328; (c) Citterio, A.; Sebastiano, R.; Nicolini, M.
Tetrahedron 1993, 49, 7743.
thorhombic, space group Pcab, a¼12.1928(4) Å, b¼15.2127(5) Å, c¼27.
2743(9) Å,
a
¼90ꢀ,
b
¼90ꢀ,
g
¼90ꢀ, V¼5059.0(3) Å3, Z¼8, Dc¼1.217 mg/m3,
¼0.
m
075 mmꢁ1, F(000)¼1984, crystal size 0.42ꢂ0.28ꢂ3 mm3, reflections collected
30,151, independent reflections 4627 [R(int)¼0.1528], refinement method,
full-matrix least-squares on F2, goodness-of-fit on F2 1.133, final R indices
3. (a) Chuang, C.-P.; Wang, S.-F. Tetrahedron Lett. 1994, 35, 4365; (b) Chuang, C.-P.;
Wang, S.-F. J. Chin. Chem. Soc. 1997, 44, 271; (c) Chuang, C.-P.; Wang, S.-F. Tet-
rahedron 1998, 54, 10043; (d) Chuang, C.-P.; Wang, S.-F. Heterocycles 1999, 50,
489; (e) Chuang, C.-P.; Wu, Y.-L.; Jiang, M.-C. Tetrahedron 1999, 55, 11229;
(f) Jiang, M.-C.; Chuang, C.-P. J. Org. Chem. 2000, 65, 5409; (g) Wu, Y.-L.; Chuang,
C.-P.; Lin, P.-Y. Tetrahedron 2001, 57, 5543; (h) Tsai, A.-I.; Wu, Y.-L.; Chuang, C.-P.
Tetrahedron 2001, 57, 7829; (i) Chuang, C.-P.; Wu, Y.-L. Tetrahedron Lett. 2001, 42,
1719; (j) Tseng, C.-C.; Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2002, 58, 7625;
(k) Tseng, C.-M.; Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2004, 60, 12249; (l) Chen,
H.-L.; Lin, C.-Y.; Cheng, Y.-C.; Tsai, A.-I.; Chuang, C.-P. Synthesis 2005, 977; (m)
Lin, C.-Y.; Cheng, Y.-C.; Tsai, A.-I.; Chuang, C.-P. Org. Biomol. Chem. 2006, 1097;
(n) Chuang, C.-P.; Tsai, A.-I. Tetrahedron 2007, 63, 11911; (o) Tsai, A.-I.; Chuang,
C.-P. Tetrahedron 2008, 64, 5098.
[I>2
s
(I)] R1¼0.0982, wR2¼0.2173, R indices (all data) R1¼0.1764, wR2¼0.2563,
largest diff. peak and hole 0.420 and ꢁ0.440 e Åꢁ3. Crystallographic data for
the structure in this paper have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication no. CCDC 727230.
Copies of the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK, (fax: þ44 (0)1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk).
13. (a) Yogo, M.; Ito, C.; Furukawa, H. Chem. Pharm. Bull. 1991, 39, 328; (b) Kno¨lker,
H.-J.; Reddy, K. R. Heterocycles 2003, 60, 1049; (c) Kallmayer, H.-J.; Tappe, C. Arch.
Pharmacol.1986, 319, 29; (d) Kallmayer, H.-J.; Tappe, C. Arch. Pharmacol.1986, 319,
421; (e) Mure, M.; Wang, S. X.; Klinman, J. P. J. Am. Chem. Soc. 2003, 125, 6113.