A convenient synthesis of benzo[g]pyrrolo[3,2-c]quinoline-6,11-diones

Article abstract of DOI:10.1055/s-2005-861802

The synthesis of a new class of angular tetracyclic quinones is described. Our strategy involves Diels-Alder reaction of pyrroloquinolinequinone 9, generated in situ from pyrroloquinoline 8, and dienes. The required pyrroloquinoline 8 was prepared in four

Full text of DOI:10.1055/s-2005-861802

PAPER
903
A Convenient Synthesis of Benzo[g]pyrrolo[3,2-c]quinoline-6,11-diones
A
C
onvenient
Sy
i
nthesis
c
of Benzop
a
r
line
s
do A. Tapia,*a Claudio López,a Antonio Morello,b Juan Diego Maya,b Jaime A. Valderramaa
a
Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago-22, Chile
Fax +56(2)6864744; E-mail: rtapia@puc.cl
Facultad de Medicina, ICBM, Universidad de Chile, Casilla 70086, Santiago-7, Chile
b
Received 25 October 2004; revised 3 December 2004
ed intense synthetic studies,5 however, the search for sim-
ple and suitable methods that incorporate the quinone
moiety is always necessary. We describe here our ap-
proach to obtain benzo[g]pyrrolo[3,2-c]quinolines from
Abstract: The synthesis of a new class of angular tetracyclic quino-
nes is described. Our strategy involves Diels–Alder reaction of pyr-
roloquinolinequinone 9, generated in situ from pyrroloquinoline 8,
and dienes. The required pyrroloquinoline 8 was prepared in four
steps from commercially available compounds. All compounds readily available compounds. Retrosynthetic consider-
were tested for trypanocidal activity in vitro against Trypanosoma
cruzi epimastigotes.
ations suggested that a useful precursor for our purpose
was dichloroquinoline 6, which could be obtained from
2,5-dimethoxyaniline (4) (Scheme 1). The reaction of
anilines with 2-acetylbutyrolactone, described first by
Ozawa et al.,6 is emerging as a helpful method for the syn-
thesis of pyrroloquinolines.7
Key words: benzo[g]pyrrolo[3,2-c]quinoline, heterocyclic quino-
nes, pyrroloquinoline, Diels–Alder reaction, heterocycles
Phenanthroviridin (1) and its aglycon 2 are the only exam-
ples of naturally occurring benzo[b]phenanthridines
(Figure 1). These compounds were isolated from Strepto-
myces viridiochromogenes DSM3972, and both are active
against lung carcinoma in mice.1 The unique structural
pattern and the potential pharmacological interest of
phenanthroviridins 1 and 2, have stimulated the total syn-
thesis of these compounds.2 However, analogues of these
molecules with heterocyclic rings replacing the phenyl
moieties have not been reported.
O
O
MeO
MeO
OMe
O
O
MeO
MeO
Cl
N
Cl
O
c
a
b
NH2
N
H
Me
Me
OMe
4
6
5
R
Ph
Ph
MeO
MeO
MeO
MeO
O
O
N
N
N
N
N
e
d
OH
Me
MeHN
Me
N
Me
Me
O
N
7a R = H
7b R = Ph
9
R2
8
HO
Me
O
Me
O
O
N
O
O
O
Scheme 1 Reagents and conditions: (a) 2-acetylbutyrolactone, to-
luene, reflux, 24 h, 83%; (b) POCl3, reflux, 4 h, 63%; (c) aniline,
EtOH, reflux, 2 h, 70%; (d) Pd/C, mesitylene, reflux, 24 h, 57%; (e)
AgO, HNO3, THF, 5 min.
N
N
R1
OH
O
OH
3
2
1
Reaction of aniline 4 with acetylbutyrolactone in toluene
at 110 °C gave furanone 5 in good yield, which underwent
cyclization upon treatment with phosphorus oxychloride
at 80–90 °C to give dichloroquinoline 6. Attempt to ob-
tain N-unsubstituted pyrrolo[3,2-c]quinoline 7a by reac-
tion of 6 with sodium azide and triphenylphosphine failed;
nevertheless N-phenylpyrrolo[3,2-c]quinoline 7b was ob-
tained in 70% yield by treatment of compound 6 with
aniline in ethanol at reflux. The next step was the aroma-
tization of the five-membered ring using 10% Pd/C in
boiling mesitylene, to afford compound 8. The shielding
effect of the N-phenyl ring accounts for the unusual chem-
ical shift of the methoxy group at C-6 in compounds 7b
and 8 (d = 2.64 and 3.00, respectively). Then the oxidative
demethylation of hydroquinone dimethyl ether 8 was
studied. Initially, we attempted oxidation with ceric am-
monium nitrate (CAN),8 but after 6 hours at room temper-
Figure 1 Phenanthroviridin (1), its aglycon 2 and the hetero ana-
logue 3
In our continuing search for new heterocyclic quinones
with useful biological activity,3 we wished to develop a
method for the synthesis of hetero analogs of phenan-
throviridin such as 3 (Figure 1). We assumed that these
compounds would be accessible through pyrroloquinoline
7 as key intermediate. It is interesting to note that com-
pound 7 has an angular tricyclic ring system which is the
core structure unit of some natural alkaloids with unique
biological activity.4 Their unusual structure have stimulat-
SYNTHESIS 2005, No. 6, pp 0903–0906
x
x
.
x
x
.2
0
0
5
Advanced online publication: 21.02.2005
DOI: 10.1055/s-2005-861802; Art ID: M08504SS
© Georg Thieme Verlag Stuttgart · New York

904
R. A. Tapia et al.
PAPER
Table 1 Effect of Compounds upon Culture Growth of T. cruzi
Epimastigotes
ature the starting material was recovered. However, using
silver(II) oxide and nitric acid9 quinone 9 could be ob-
served by TLC, but decomposed during chromatographic
purification. To overcome this problem, quinone 9 gener-
ated in situ, was trapped with 2,3-dimethylbuta-1,3-diene
followed by the addition of DBU to give tetracyclic
quinone 10 in 81% yield.
Compound
ICkc50 (mM)
>100
5
6
6.0 0.2
21.2 2.8
19.1 1.2
13.2 2.7
10.4 0.1
17.1 0.4
11.4 1.5
7b
Similarly, quinone 9 was reacted with penta-1,3-diene to
afford a mixture of regioisomers 11 and 12 in a 1:2.4 ratio
(Scheme 2). Although in this case the regioselectivity was
not high, it is interesting to note that the reaction of quin-
oline-5,8-dione with penta-1,3-diene gave almost a 1:1
mixture of regioisomers.10
8
10
11
12
Ph
Ph
benznidazole
O
O
N
N
N
Me
Me
a
Me
N
Me
O
O
Melting points were determined with a Meltemp apparatus and are
not corrected. IR spectra were obtained on a Bruker Model Vector
22 spectrophotometer. NMR spectra (1H and 13C) were recorded on
a Bruker AM-200 spectrometer 200 (200 MHz and 50 MHz), using
TMS as internal reference. Column chromatography was performed
on silica gel Merck 60 (70–230 mesh). Elemental analyses were
performed on a Fison EA 1108 CHNS-O analyzer. Accurate MS
measurements were determined at the SERC Mass Spectrometry
Centre, Leicester University.
9
10
b
Ph
Ph
O
O
Me
O
N
N
N
+
N
Me
Me
Me
O
3-[1-(2,5-Dimethoxyphenylamino)ethylidene]dihydrofuran-
2(3H)-one (5)
12
11
A solution of 2,5-dimethoxyaniline 4 (7.66 g, 50 mmol) and 2-
acetylbutyrolactone (6.41 g, 50 mmol) in toluene (25 mL) was re-
fluxed for 24 h. Evaporation of the solvent gave a solid, which was
washed with cold Et2O and recrystallized from EtOH to afford fura-
none 5 (10.9 g, 83%); mp 108.5–110 °C.
Scheme 2 Reagents and conditions: (a) i. 2,3-dimethylbuta-1,3-die-
ne, CHCl3, 120 °C, 18 h, ii. DBU, r.t., 24 h, 81%; (b) i. penta-1,3-die-
ne, CHCl3, 120 °C, 18 h, ii. DBU, r.t., 24 h, 64%.
The structural assignment was made by 2D 1H-13C HMBC
correlations performed on the major regioisomer 12. In-
terestingly, the chemical shift of the methyl protons at C-
10 in compound 11 (d = 2.31) is shielded compared to that
of the methyl protons at C-7 in 12 (d = 2.87), probably due
to the anisotropic shielding effect of the N-aromatic ring.
IR (KBr): 3280, 3205, 1690, 1640, 1610, 1255, 1220 cm–1.
1H NMR (200 MHz, CDCl3): d = 2.03 (s, 3 H, CH3), 2.90 (t, 2 H,
CH2C=, J = 7.9 Hz), 3.75 (s, 3 H, OCH3), 3.80 (s, 3 H, OCH3), 4.34
(t, 2 H, CH2O, J = 7.9 Hz), 6.60 (m, 2 H), 6.82 (d, 1 H, J = 8.6 Hz),
9.91 (s, 1 H, NH).
13C NMR (50 MHz, CDCl3): d = 17.8 (q), 26.6 (t), 55.8 (q), 56.38
(q), 65.3 (t), 89.8 (s), 109.0 (d), 111.2 (d), 111.3 (s), 112.0 (d), 129.3
(s), 147.0 (s), 153.4 (s), 173.8 (s).
Encouraged by the interesting antiprotozoal activity ex-
hibited by many heterocyclic quinones,3,11 we next exam-
ined the in vitro trypanocidal activity of the synthesized
compounds against Tulahuén strain at 50, 20, 10 and 5 mM
concentrations as described earlier.12 The ICKC50 at 5 mM
concentration for all compounds was then determined in
order to establish their relative efficacy in vitro, compared
to the standard drug benznidazole. Compounds 6 and 11
are more active than the standard drug benznidazole. The
most active compound is the one not possessing the
quinone moiety 6, probably because it is a better electro-
phile than quinone 11 (Table 1).
Anal. Calcd for C14H17NO4 (263.30): C, 63.87; H, 6.51; N, 5.32.
Found: C, 63.90; H, 6.64; N, 5.34.
4-Chloro-3-(2-chloroethyl)-5,8-dimethoxy-2-methylquinoline
(6)
A solution of furanone 5 (2.63 g, 10.0 mmol) in POCl3 (15 mL) was
refluxed for 4 h, and then the excess POCl3 was removed in vacuo.
The residue was poured onto iced water, neutralized with Na2CO3
and stirred overnight. The solid was filtered, dried and recrystal-
lized from EtOH to give quinoline 6 (1.90 g, 63%); mp 156–158 °C
IR (KBr): 1612, 1475, 1315, 1270 cm–1.
1H NMR (200 MHz, CDCl3): d = 2.85 (s, 3 H, CH3), 3.49 (m, 2 H,
CH2CH2Cl), 3.75 (m, 2 H, CH2CH2Cl), 3.91 (s, 3 H, OCH3), 4.02
(s, 3 H, OCH3), 6.85 (d, 1 H, ArH, J = 8.9 Hz), 6.95 (d, 1 H, ArH,
J = 8.9 Hz).
13C NMR (50 MHz, CDCl3): d = 25.0 (q), 33.7 (t), 41.3 (t), 56.2 (q),
56.8 (q), 107.6 (2 d), 118.5 (s), 129.5 (s), 140.4 (s), 140.6 (s), 149.1
(s), 149.2 (s), 157.5 (s).
In summary, the synthesis of the phenanthroviridin hetero
analogues of 3 has been successfully accomplished
through a simple method. This strategy should enable ac-
cess to other hetero analogues of phenanthroviridin.
Synthesis 2005, No. 6, 903–906 © Thieme Stuttgart · New York

PAPER
A Convenient Synthesis of Benzopyrroloquinolines
905
Anal. Calcd for C14H15Cl2NO2 (300.19): C, 56.02; H, 5.04; N, 4.67.
Found: C, 56.20; H, 5.10; N, 4.65.
13C NMR (50 MHz, CDCl3): d = 20.1 (2 q), 22.7 (q), 103.7 (d),
118.1 (s), 124.6 (2 d), 127.4 (d), 127.6 (d), 128.2 (d), 128.9 (2 d),
129.8 (s), 130.6 (s), 131.7 (s), 135.3 (s), 136.5 (d), 142.1 (s), 143.5
(s), 143.7 (s), 144.0 (s), 158.0(s), 182.6 (s), 182.9 (s).
HRMS: m/z calcd for C24H19N2O2: 367.14464 (MH+); found
367.14466.
2,3-Dihydro-6,9-dimethoxy-4-methyl-1-phenyl-1H-pyrrolo[3,2-
c]quinoline (7b)
A solution of 6 (300 mg, 1.0 mmol) and aniline (190 mg, 2.0 mmol)
in EtOH (30 mL) was refluxed for 2 h, and the solvent was removed
in vacuo. The residue was taken up in aq NaHCO3, and the crude
product was extracted with CHCl3. The organic solution was
washed with H2O, dried, and evaporated. Recrystallization from
EtOH gave 7b (225 mg, 70%); mp 188–190 °C.
4,8,9-Trimethyl-1-phenyl-1H-benzo[g]pyrrolo[3,2-c]quinoline-
6,11-dione (11) and 4,8,9-Trimethyl-1-phenyl-1H-benzo[g]pyr-
rolo[3,2-c]quinoline-6,11-dione (12)
To a solution of quinone 9 obtained from pyrroloquinoline 8 (70
mg, 0.20 mmol) as above, was added penta-1,3-diene (25 mL, 0.25
mmol) and the mixture was heated at 120 °C in a sealed tube for 18
h. After cooling to r.t., the cycloadduct was aromatized by stirring
24 h in the presence of DBU (100 mL). Column chromatography of
the residue, obtained after evaporation of the solvent, on silica gel
(CH2Cl2) gave the aromatized adducts 11 and 12 (50 mg, 64%).
IR (KBr): 1262, 1065, 1090 cm–1.
1H NMR (200 MHz, CDCl3): d = 2.64 (s, 3 H, OCH3), 3.06 (s, 3 H,
CH3), 3.20 (t, J = 9.0 Hz, 2 H, NCH2CH2), 4.00 (s, 3 H, OCH3), 4.23
(t, J = 9.0 Hz, 2 H, NCH2CH2), 6.41 (d, J = 8.7 Hz, 1 H, 7-H or 8-
H), 6.80 (d, J = 8.7 Hz, 1 H, 8-H or 7-H), 6.95 (m, 3 H), 7.20 (m, 2
H).
13C NMR (50 MHz, CDCl3): d = 23.1 (q), 27.0 (t), 54.4 (q), 56.0 (q),
57.7 (t), 102.6 (d), 106.1 (d), 111.4 (s), 120.0 (2 d), 123.0 (d), 123.6
(s), 128.6 (2 d), 142.0 (s), 147.9 (s), 149.2 (s), 150.5 (s), 150.8 (s),
154.4 (s).
HRMS: m/z calcd for C23H17N2O2: 353.12899 (MH+); found:
353.12907.
The mixture of aromatized adducts 11 and 12 was purified by two
consecutive flash chromatography on silica gel (CH2Cl2) to afford
11 and 12.
Anal. Calcd for C20H20N2O2 (320.40): C, 74.98; H, 6.29; N, 8.74.
Found: C, 75.10; H, 6.32; N, 9.04.
11
Yield: 9.0 mg (11%); mp 220–222 °C.
IR (KBr): 1675 cm–1 (C=O).
6,9-Dimethoxy-4-methyl-1-phenyl-1H-pyrrolo[3,2-c]quinoline
(8)
A mixture of 7b (150 mg, 0.47 mmol), 10% Pd/C (30 mg) and mes-
itylene (25 mL) was heated at 200 °C in an autoclave for 24 h. After
removal of the catalyst on Celite, the solvent was evaporated under
reduced pressure. The residue was purified by column chromatog-
raphy using EtOAc–CH2Cl2 (1:1) as eluent to afford pyrroloquino-
line 8 (85 mg, 57%); mp 155–157 °C.
1H NMR (200 MHz, CDCl3): d = 2.31 (s, 3 H, CH3), 3.00 (s, 3 H,
CH3), 6.93 (d, J = 3.3 Hz, 1 H, 3-H), 7.32 (m, 2 H, ArH), 7.52 (m,
5 H, ArH), 7.54 (d, J = 3.3 Hz, 1 H, 2-H), 8.21 (d, J = 7.3 Hz,1 H,
7-H).
13C NMR (50 MHz, CDCl3): d = 21.6 (q), 23.1 (q), 103.9 (d), 120.6
(s), 125.0 (2 d), 126.3 (d), 128.1 (d), 129.6 (2 d), 130.0 (s), 132.8 (s),
132.9 (d), 134.5 (s), 135.4 (s), 136.1 (d), 137.6 (d), 139.9 (s), 141.8
(s), 143.0 (s), 158.2 (s), 183.5 (s), 185.8 (s).
IR (KBr): 1615, 1510, 1493, 1260 cm–1.
1H NMR (200 MHz, CDCl3): d = 3.00 (s, 3 H, OCH3), 3.01 (s, 3 H,
CH3), 4.06 (s, 3 H, OCH3), 6.58 (d, J = 8.6 Hz, 1 H, 7-H or 8-H),
6.88 (d, J = 8.6 Hz, 1 H, 8-H or 7-H), 6.89 (d, J = 3.3 Hz, 1 H, 6-H
or 7-H), 7.28 (m, 2 H, ArH), 7.40 (m, 3 H, ArH).
12
Yield: 21 mg (26%); mp 228–230 °C.
13C NMR (50 MHz, CDCl3): d = 23.1 (q), 54.0 (q), 56.2 (q), 103.2
(d), 103.5 (d), 105.0 (d), 110.6 (s), 123.9 (s), 124.4 (2 d), 126.5 (d),
128.7 (2 d), 131.7 (d), 134.2 (s), 137.0 (s), 144.9 (s), 147.0 (s), 149.5
(s), 153.9 (s).
IR (KBr): 1670 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): d = 2.87 (s, 3 H, CH3), 3.00 (s, 3 H,
CH3), 6.91 (d, J = 3.3 Hz, 1 H, 3-H), 7.24 (m, 2 H, ArH), 7.48 (m,
5 H, ArH), 7.51 (d, J = 3.3 Hz, 1 H, 2-H), 7.75 (m, 1 H, 7-H).
Anal. Calcd for C20H18N2O2 (318.38): C, 75.45; H, 5.70; N, 8.80.
Found: C, 75.15; H, 5.95; N, 8.60.
13C NMR (50 MHz, CDCl3): d = 23.2 (q), 23.8 (q), 104.2 (d), 117.5
(s), 125.1 (2 d), 125.4 (d), 128.1 (d), 129.3 (2 d), 129.8 (s), 131.0 (s),
133.2 (d), 135.3 (s), 135.8 (s), 136.5 (d), 137.9 (d), 142.2 (s), 142.3
(s), 144.9 (s), 158.7 (s), 183.5 (s), 184.6 (s).
4,8,9-Trimethyl-1-phenyl-1H-benzo[g]pyrrolo[3,2-c]quinoline-
6,11-dione (10)
To a solution of pyrroloquinoline 8 (70 mg, 0.22 mmol) in MeCN
(5 mL), were added AgO (150 mg, 1.2 mmol) and 6 N HNO3 (0.4
mL). The suspension was stirred for 5 min at r.t., and H2O (10 mL)
was added. The mixture was extracted with CHCl3 (2 × 15 mL), the
combined organic extracts were dried (MgSO4) and filtered. To the
solution was added 2,3-dimethylbuta-1,3-diene (25 mL, 0.22 mmol)
and the mixture was heated at 120 °C in a sealed tube for 18 h. After
cooling to r.t., the cycloadduct was aromatized by stirring 24 h in
the presence of DBU (100 mL). The residue obtained after evapora-
tion of the solvent was purified by flash column chromatography on
silica gel (CH2Cl2) to give compound 10 (65 mg, 81%); mp 233–
235 °C.
Acknowledgment
We are grateful to FONDECYT (Research Grants 2010084 and
1020874) for financial support.
References
(1) Fendrich, G.; Zimmermann, W.; Gruner, J.; Auden, J. A. L.
Eur. Pat. Appl. EP 304400, 1989; Chem. Abstr. 1990, 112,
75295.
(2) (a) Gore, M. P.; Gould, S. J.; Weller, D. D. J. Org. Chem.
1991, 56, 2289. (b) Gore, M. P.; Gould, S. J.; Weller, D. D.
J. Org. Chem. 1992, 57, 2774. (c) Mohri, S.; Stefinovic, M.;
Snieckus, V. J. Org. Chem. 1997, 62, 7072.
(3) (a) Tapia, R. A.; Salas, C.; Morello, A.; Maya, J. D.; Toro-
Labbé, A. Bioorg. Med. Chem. 2004, 12, 2451. (b) Tapia,
R. A.; Prieto, Y.; Pautet, F.; Walchshofer, N.; Fillion, H.;
IR (KBr): 1670 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): d = 2.34 (s, 3 H, CH3), 2.40 (s, 3 H,
CH3), 3.02 (s, 3 H, CH3), 6.92 (d, J = 3.3 Hz, 1 H), 7.28 (m, 2 H,
ArH), 7.50 (m, 3 H, ArH), 7.52 (d, J = 3.3 Hz, 1 H), 7.63 (s, 1 H,
ArH), 8.08 (m, 1 H, ArH).
Synthesis 2005, No. 6, 903–906 © Thieme Stuttgart · New York

906
R. A. Tapia et al.
PAPER
Fenet, B.; Sarciron, M.-E. Bioorg. Med. Chem. 2003, 11,
3407. (c) Tapia, R. A.; Alegria, L.; Pessoa, C. D.; Salas, C.;
Cortés, M. J.; Valderrama, J. A.; Sarciron, M.-E.; Pautet, F.
N.; Walchshofer, N.; Fillion, H. Bioorg. Med. Chem. 2003,
11, 2175. (d) Cuellar, M. A.; Alegría, L. K.; Prieto, Y.;
Cortés, M. J.; Tapia, R. A.; Preite, M. D. Tetrahedron Lett.
2002, 43, 2127.
(7) (a) Badawey, E.-S.; Kappe, T. Eur. J. Med. Chem. 1997, 32,
815. (b) Brown, T. H.; Ife, R. J.; Keeling, D. J.; Laing, S. M.;
Leach, C. A.; Parsons, M. E.; Price, C. A.; Reavill, D. R.;
Wiggall, K. J. J. Med. Chem. 1990, 33, 52.
(8) Jacob, P. III; Callery, P. S.; Shulgin, A. T.; Castagnoli, N. Jr.
J. Org. Chem. 1976, 41, 3627.
(9) (a) Luly, J. R.; Rapoport, H. J. Org. Chem. 1981, 46, 2745.
(b) Snyder, C. D.; Rapoport, H. J. Am. Chem. Soc. 1972, 94,
227.
(10) Ohgaki, E.; Motoyoshiya, J.; Narita, S.; Nakurai, T.;
Hayashi, S.; Hirakawa, K. J. Chem. Soc., Perkin Trans. 1
1990, 3109.
(11) (a) Zani, C. L.; Fairlamb, A. H. Mem. Inst. Oswaldo Cruz.
2003, 98, 565. (b) Zani, C. L.; Chiari, E.; Krettli, A. U.;
Murta, S. M. F.; Cunningham, M. L.; Fairlamb, A. H.;
Romanha, A. J. Bioorg. Med. Chem. 1997, 5, 2185.
(c) Ribeiro-Rodrigues, R.; Dos Santos, W. G.; Zani, C. L.;
Oliveira, A. B.; Romanha, A. J. Bioorg. Med. Chem. Lett.
1995, 5, 1509.
(12) Maya, J. D.; Bollo, S.; Nuñez-Vergara, L. J.; Squella, J. A.;
Repetto, Y.; Morello, A.; Périé, J.; Chauvière, G. Biochem.
Pharm. 2003, 65, 999.
(4) (a) Witherup, K.; Ranson, R. W.; Graham, A. C.; Bernard,
A. M.; Salvatore, M. J.; Limma, W. C.; Anderson, P. S.;
Pitzenberger, S. M.; Varga, S. L. J. Am. Chem. Soc. 1995,
117, 6682. (b) Leach, C. A.; Brown, T. H.; Ife, R. J.;
Keeling, D. J.; Laing, S. M.; Parsons, M. E.; Price, C. A.;
Wiggall, K. J. J. Med. Chem. 1992, 35, 1845.
(5) (a) Powell, D. A.; Batey, R. A. Org. Lett. 2002, 4, 2913.
(b) Snider, B. B.; Ahn, Y.; Ohare, S. M. Org. Lett. 2001, 3,
4217. (c) Ma, D.; Xia, C.; Jiang, J.; Zhang, J. Org. Lett.
2001, 3, 2189; and references cited therein.
(6) (a) Ozawa, T.; Nagaoka, S. J. Pharm. Soc. Jpn. 1955, 75,
1405; Chem. Abstr. 1956, 50, 10002a. (b) Ozawa, T.;
Nagaoka, S. Yakugaku Zasshi 1959, 79, 226; Chem. Abstr.
1959, 53, 13146h.
Synthesis 2005, No. 6, 903–906 © Thieme Stuttgart · New York