A novel reductive amino-cyclization method and its application for the total syntheses of (±)-aurantio-clavine and (±)-lophocerine

Article abstract of DOI:10.3987/com-07-s(w)14

A novel reductive amino-cyclization method for the synthesis of azacycloalkanes is developed. Its versatility is proved by the total syntheses of (±)-aurantioclavine (1), an ergot alkaloid, and (±)-lophocerine (2), a cactus alkaloid, as examples of azepan

Full text of DOI:10.3987/com-07-s(w)14

HETEROCYCLES, Vol. 74, 2007
943
HETEROCYCLES, Vol. 74, 2007, pp. 943 - 950. © The Japan Institute of Heterocyclic Chemistry
Received, 9th July, 2007, Accepted, 27th August, 2007, Published online, 28th August, 2007. COM-07-S(W)14
A NOVEL REDUCTIVE AMINO-CYCLIZATION METHOD AND ITS
APPLICATION FOR THE TOTAL SYNTHESES OF (±)-AURANTIO-
CLAVINE AND (±)-LOPHOCERINE1a#
Masanori Somei*,1b and Fumio Yamada
Division of Pharmaceutical Sciences, Graduate School of Natural Science and
Technology, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
Corresponding author: e-mail address: syamoji_usa@r9.dion.ne.jp
Abstract – A novel reductive amino-cyclization method for the synthesis of
azacycloalkanes is developed. Its versatility is proved by the total syntheses of
(±)-aurantioclavine (1), an ergot alkaloid, and (±)-lophocerine (2), a cactus
alkaloid, as examples of azepane and piperidine skeletons, respectively.
In our project for developing biologically active compounds,2 we needed a novel simple method for
constructing azacycloalkanes under acidic conditions. Generally speaking, however, the formation of a
C—N bond between nitrogen atom of amines and carbocation generated in situ by the action of an acid is
impossible, because the basic nitrogen is protonated completely and eventually loses the nucleophilic
ability.
To overcome the problem we have conceived the following idea as shown in general formula in Scheme 1.
If the type A compound, having both nitro and unsaturated groups in a molecule, is subjected to an acidic
reduction (in this case, E+ = H+), the nitrogen atoms of both the resulting intermediates, hydroxylamine
(B) or oxime (C), would not be protonated completely due to the attached electron-attracting oxygen
atom. So, in cases where a carbocation is generated in the neighborhood of the nitrogen atom, both carbon
and nitrogen atoms can connect together resulting in the formation of a cyclic hydroxylamine or a cyclic
nitrone (D). Simultaneous acidic reduction can provide the desired type E azacycloalkanes.
On the basis of the above idea, we have succeeded in creating a novel reductive amino-cyclization
method.3 We wish to report its application for the total syntheses of (±)-aurantioclavine4 (1), a member of
ergot alkaloid and (±)-lophocerine (2), a cactus alkaloid, as examples of azepane and a piperidine forma-
tions, respectively (Scheme 2). Part of these works is reported as preliminary communications.3,6
# Dedicated to the 75th birthday of Prof. Dr. Ekkelhard Winterfeldt.

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HETEROCYCLES, Vol. 74, 2007
As for an example of pyrrolidine formation, we had already applied the method for the synthesis of
6,6a,7,8,9,9a-hexahydro-2H-isoindolo[4,5,6-cd]indole3,6 (3), a synthetic intermediate for α-cyclopiazonic
acid (4). We had demonstrated as well that the process, C → D in Scheme 1, actually worked.7 Thus, the
compound (5) was successfully converted to a nitrone (6, in this case, E+ = Br+), an important
intermediate for the synthesis of gibberellin A15 (7).7
S1—S3: an appropriate substituent. E+: an electrophile.
Scheme 1.
e-
–
S2
E
O
N
S2
E
OH
NH
S1
S3
S1
S3
S1
S3
S2
S1
S3
S2
S1
S3
S2
+
+
E+
e-
NH
NOH
NO2
E+
e-
(CH2)n
(CH2)n
(CH2)n-1
(CH2)n-1
(CH2)n
E
B
E
C
D
A
An Efficient Total Synthesis of (±)-Aurantioclavine (1)
According to our synthetic procedures,6,8 we first prepared (E)-2-methyl-4-[3-(2-nitroethyl)indol-
4-yl]-3-buten-2-ol (9, Scheme 2), our common synthetic intermediate for the ergot alkaloids,2 in 46%
overall yield from indole-3-carbaldehyde (8) in four steps.8 Since the compound (9) contains the type A
structure, the desired allyl cation being a benzyl cation as well, can be generated on the side chain at the
4-position of 9 by an acid treatment. The carbocation is so stable that it would survive during the time
when the acidic reduction of the nitro group on the side chain at the 3-position of 9 proceeds, and it would
eventually have a chance to form a bond to the hydroxylamine nitrogen.
Scheme 2
O
H
HON
MeO
HO
NH
H
N
H
N
H
H
O
OH
Me
N
Me
H
H
OH
H
N
NH
NH
H
2: lophocerine
4
1: aurantioclavine
3
5
Zn (Hg), MeOH-HCl
Ac2O
Py
OH
Ac
N
NO2
H
–
O
CHO
4 steps
Ref. 8
4
3
O
N
+
OH
N
H
H
Br
H
Ref. 7
N
1
O
N
H
CO2H
H
10
9
8
6
7

HETEROCYCLES, Vol. 74, 2007
945
In fact, however, treatment of 9 with such reagent systems as SnCl2/HCl/MeOH, TiCl3/MeOH, Fe/AcOH,
and Zn/AcOH ended in failure under various examined reaction conditions. Finally, we tried
amalgamated zinc (Zn (Hg)) and found it a reagent of choice. Thus, treatment of 9 with Zn (Hg) in
refluxing methanolic HCl gave (±)-aurantioclavine (1) in 72% yield. Further treatment of 1 with Ac2O
and pyridine afforded (±)-N-acetylaurantioclavine (10) in 93% yield. Spectral data of 1 were identical
with those of aurantioclavine, reported in the literature.4
Thus, we accomplished the first total synthesis of (±)-aurantioclavine (1) in the simplest five steps with a
33% overall yield from 8 without using any protective groups. Hegedus’ group9 achieved the total
syntheses of (±)-1 afterwards, too.10
Total Synthesis of (±)-Lophocerine (2)
In order to examine whether our amino-cyclization method works for the piperidine formation, we
selected (±)-lophocerine (2)5 as a target molecule, which is known to exist as a racemate.5
For the synthesis of intermediates having 1-substituted isoquinoline skeletons (12a,b, Scheme 3), we
chose 4-[4,5-dimethoxy- (11a) and 4-[5-benzyloxy-4-methoxy-2-(2-nitroethyl)phenyl]-2-methyl-3-
buten-2-ol11 (11b) as suitable substrates because they have the type A structure (Scheme 1) in the
molecules.
Scheme 3
a) R = Me; b) R = CH2Ph
MeO
RO
MeO
RO
MeO
RO
MeO
RO
NO2
OH
CHO
NO2
OH
MeO
RO
NaBH4
MeOH
CHO
Br
Zn
NH
MeOH
HCl
OH
13
14
15
11
12
ClCO2Me
Et3N, CH2Cl2
MeO
PhCH2O
MeO
HO
MeO
PhCH2O
H2, Pd/C
MeOH
LiAlH4
THF
2
+
NMe
NMe
NCO2Me
18
17
16
Employing the reduction with NaBH4 in MeOH, compounds (11a,b11) were easily prepared in 74 and
81% yields, respectively, from 13a and 13b.11 They were prepared according to our procedures11 from
6-bromoveratraldehyde (14a) and 6-bromo-4-benzyloxy-3-methoxybenzaldehyde (14b) in two steps
through 15a and 15b.
The reductive amino-cyclization method, using zinc instead of Zn (Hg), was successfully applied for 11a
and 11b. Thus, treatment of 11a and 11b with zinc in refluxing methanolic HCl provided 6,7-dimethoxy-

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HETEROCYCLES, Vol. 74, 2007
(12a) and 7-benzyloxy1-6-methoxy-1-(2-methyl-1-propen-1-yl)-1,2,3,4-tetrahydroisoquinoline (12b) in
67 and 77% yields, respectively.
Further treatment of 12b with ClCO2Me and Et3N afforded 7-benzyloxy-6-methoxy-2-methoxy-
carbonyl-1-(2-methyl-1-propen-1-yl)-1,2,3,4-tetrahydroisoquinoline (16) in 99% yield. Subsequent
reduction of 16 with LiAlH4 in dry THF gave 7-benzyloxy-1-(2-methyl-1-propen-1-yl)-6-meth-
oxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (17) in 86% yield together with an 11% yield of the
debenzylated compound 18. Catalytic hydrogenation of the double bond and debenzylation of 17 over
10% Pd/C in MeOH produced (±)-lophocerine (2) in 39% yield. Our synthesized 2 and its picrate were
identical with the samples prepared according to the procedure described in the literature.5
In conclusion, we have established a novel reductive amino-cyclization method for the synthesis of
azacycloalkanes based on our idea shown in Scheme 1. Its versatility was proved by the total syntheses of
(±)-aurantioclavine (1) and (±)-lophocerine (2) as examples of the azepane and piperidine skeletons,
respectively.
EXPERIMENTAL
Melting points were determined on a Yanagimoto micro melting point apparatus and are uncorrected. IR
1
spectra were determined with a Shimadzu IR-420 spectrophotometer, and H-NMR spectra with a JEOL
JNM-PMX 60 or a JEOL FX-100 spectrometer, with tetramethylsilane as an internal standard. MS were
recorded on a Hitachi M-80 spectrometer. Preparative thin-layer chromatography (p-TLC) was performed
on Merck Kiesel-gel GF245 (Type 60) (SiO2). Column chromatography was performed on silica gel (SiO2,
100—200 mesh, from Kanto Chemical Co., Inc.) throughout the present study.
(±)-Aurantioclavine (1) from (E)-2-Methyl-4-[3-(2-nitroethyl)indol-4-yl]-3-buten-2-ol (9) — A
solution of 9 (113.2 mg, 0.41 mmol) in MeOH (24 mL) and 3% HCl (8 mL) was added to Zn (Hg),
prepared from Zn powder (1.386 g, 21.2 mmol) and HgCl2 (229.0 mg, 0.84 mmol) in 3% HCl (8 mL),
and the mixture was refluxed for 3.5 h with stirring. Unreacted Zn (Hg) was filtered off and the filtrate
was evaporated under reduced pressure. The residue was made basic by adding 8% NaOH and the whole
was extracted with CH2Cl2–MeOH (95:5, v/v). The organic layer was washed with brine, dried over
Na2SO4, and evaporated under reduced pressure to leave an oil, which was subjected to p-TLC on SiO2
with CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v) as a developing solvent. Extraction of the band having
an Rf value of 0.29—0.58 with CHCl3–MeOH-28% aq. NH3 (46:5:0.5, v/v) gave 1 (66.9 mg, 72%). 1: mp
194—196 °C (colorless leaves, recrystallized from CH2Cl2–hexane). IR (KBr): 3290, 2915 cm-1.
1H-NMR (CDCl3) δ: 1.71 (1H, br s, disappeared on addition of D2O), 1.84 (6H, s), 2.83—3.24 (3H, m),
3.33—3.71 (1H, m), 4.86 (1H, d, J=9.0 Hz), 5.44 (1H, br d, J=9.0 Hz), 6.80 (1H, br d, J=6.8 Hz),
6.89—7.27 (2H, m), 6.94 (1H, br s), 8.17 (1H, br s, disappeared on addition of D2O). MS m/z: 226 (M+).

HETEROCYCLES, Vol. 74, 2007
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Anal. Calcd for C15H18N2: C, 79.60; H, 8.02; N, 12.38. Found: C, 79.52; H, 8.10; N, 12.53.
(±)-N-Acetylaurantioclavine (10) from 1 — Ac2O (1 mL) was added to a solution of 1 (53.1 mg, 0.24
mmol) in pyridine (2 mL) and the mixture was stirred at rt for 13 h. After evaporation of the solvent,
saturated aqueous NaHCO3 was added and the whole was extracted with CH2Cl2–MeOH (95:5, v/v). The
organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave
a solid, which was recrystallized from MeOH to give 10 (58.5 mg, 93%) as colorless needles. 10: mp
1
235—236 °C. IR (KBr): 3200, 1664, 1593 cm-1. H-NMR (10% CD3OD in CDCl3) δ: 1.70 (3H, s), 1.80
(3H, s), 2.18 (3H, s), 2.64—4.54 (4H, m), 5.72 (1H, br d, J=7.5 Hz), 5.80 (1H, br d, J=7.5 Hz),
6.57—7.28 (4H, m). MS m/z: 268 (M+). Anal. Calcd for C17H20N2O: C, 76.08; H, 7.51; N, 10.44. Found:
C, 75.90; H, 7.59; N, 10.22.
(E)-4-[4,5-Dimethoxy-2-(2-nitroethyl)phenyl]-2-methyl-3-buten-2-ol (11a) from (E,E)-4-[4,5-
Dimethoxy-2-(2-nitrovinyl)phenyl]-2-methyl-3-buten-2-ol (13a) — NaBH4 (1.045g, 27.5 mmol) was
added to a solution of 13a (2.009g, 6.86 mmol) in MeOH (120 mL) and the mixture was stirred at rt for
30 min. Brine was added and the mixture was adjusted to pH 8 by adding 6% HCl. The whole was
extracted with CH2Cl2–MeOH (95:5, v/v). The organic layer was washed with brine, dried over Na2SO4,
and evaporated under reduced pressure to leave an oil, which was column-chromatographed on SiO2 with
Et2O–hexane (3:1, v/v) to give 11a (1.245 g, 62%). 11a: mp 99—100 °C (colorless prisms, recrystallized
1
from CH2Cl2–hexane). IR (KBr): 3460, 1602, 1538, 1503, 1343, 1261 cm-1. H-NMR (CDCl3) δ: 1.42
(6H, s), 1.83 (1H, br s, disappeared on addition of D2O), 3.27 (2H, t, J=7.2 Hz), 3.78 (3H, s), 3.81 (3H, s),
4.43 (2H, t, J=7.2 Hz), 6.03 (1H, d, J=15.6 Hz), 6.52 (1H, s), 6.64 (1H, d, J=15.6 Hz), 6.82 (1H, s). MS
m/z: 295 (M+). Anal. Calcd for C15H21NO5·1/10H2O: C, 60.63; H, 7.19; N, 4.71. Found: C, 60.61; H, 7.27;
N, 4.79.
6,7-Dimethoxy-1-(2-methyl-1-propen-1-yl)-1,2,3,4-tetrahydroisoquinoline (12a) from 11a — A
solution of 11a (50.9 mg, 0.17 mmol) in MeOH (6 mL) was added to a mixture of Zn powder in 6% HCl
(2 mL), and the mixture was refluxed for 3 h with stirring. Unreacted Zn was filtered off and the filtrate
was evaporated under reduced pressure. The residue was made basic by adding 8% NaOH and the whole
was extracted with CH2Cl2–MeOH (95:5, v/v). The organic layer was washed with brine, dried over
Na2SO4, and evaporated under reduced pressure to leave an oil, which was column-chromatographed on
SiO2 with CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v) to give 12a (28.7 mg, 67%). 12a: mp 57—58 °C
(colorless needles, recrystallized from petroleum ether). IR (KBr): 3400, 2910, 2760, 1605, 1509, 1259
cm-1. 1H-NMR (CDCl3) δ: 1.80 (3H, d, J=1.2 Hz), 1.84 (3H, d, J=1.2 Hz), 2.04 (1H, br s, disappeared on
addition of D2O), 2.44—3.40 (4H, m), 3.80 (3H, s), 3.84 (3H, s), 4.65 (1H, d, J=9.3 Hz), 5.28 (1H, br d,
J=9.3 Hz), 6.51 (1H, s), 6.57 (1H, s). MS m/z: 247 (M+). Anal. Calcd for C15H21NO2: C, 72.84; H, 8.56; N,
5.66. Found: C, 72.62; H, 8.66; N, 5.59.

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7-Benzyloxy-6-methoxy-1-(2-methyl-1-propen-1-yl)-1,2,3,4-tetrahydroisoquinoline (12b) from 11b
— A solution of 11b (36.2 mg, 0.09 mmol) in MeOH (6 mL) was added to a mixture of Zn powder
(332.1 mg, 5.08 mmol) in 6% HCl (2 mL) and the mixture was refluxed for 4 h with stirring. Unreacted
Zn was filtered off and the filtrate was evaporated under reduced pressure. The residue was made basic by
adding 20% NaOH and the whole was extracted with CH2Cl2–MeOH (95:5, v/v). The organic layer was
washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave an oil, which was
subjected to p-TLC on SiO2 with CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v) as a developing solvent.
Extraction of the band having an Rf value of 0.49—0.72 with CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v)
gave 12b (24.2 mg, 77%). 12b: mp 114—116 °C (colorless prisms, recrystallized from MeOH–H2O). IR
(KBr): 3230, 2900, 1604, 1502, 1359, 1258, 1245, 1215 cm-1. 1H-NMR (CDCl3) δ: 1.71 (6H, d, J=2 Hz),
1.89 (1H, br s, disappeared on addition of D2O), 2.46—2.89 (2H, m), 2.89—3.33 (2H, m), 3.77 (3H, s),
4.46 (1H, d, J=9 Hz), 4.97 (2H, s), 5.07 (1H, br d, J=9 Hz), 6.36 (1H, s), 6.44 (1H, s), 7.02—7.45 (5H, m).
MS m/z: 323 (M+). Anal. Calcd for C21H25NO2: C, 77.98; H, 7.79; N, 4.33. Found: C, 77.69; H, 7.83; N,
4.20.
7-Benzyloxy-6-methoxy-2-methoxycarbonyl-1-(2-methyl-1-propen-1-yl)-1,2,3,4-tetrahydroisoquino-
line (16) from 12b — A solution of ClCO2Me (45.4 mg, 0.48 mmol) in CH2Cl2 (1 mL) and Et3N (0.2
mL) were added to a solution of 12b (82.4 mg, 0.26 mmol) in CH2Cl2 (4 mL) and the mixture was stirred
at rt for 3 h. Saturated aqueous NaHCO3 was added and the whole was extracted with CH2Cl2–MeOH
(95:5, v/v). The organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced
pressure to leave an oil, which was subjected to p-TLC on SiO2 with CH2Cl2–MeOH (99:1, v/v) as a
developing solvent. Extraction of the band having an Rf value of 0.34—0.68 with CH2Cl2–MeOH (95:5,
v/v) gave 16 (96.6 mg, 99%). 16: Colorless oil. IR (film): 1697, 1608 cm-1. 1H-NMR (CDCl3) δ: 1.67 (3H,
d, J=1.2 Hz), 1.83 (3H, d, J=1.2 Hz), 2.21—4.37 (4H, m), 3.61 (3H, s), 3.73 (3H, s), 4.91 (2H, s), 5.08
(1H, br d, J=9.5 Hz), 5.49 (1H, d, J=9.5 Hz), 6.31 (1H, s), 6.39 (1H, s), 7.01—7.42 (5H, m).
High-resolution MS m/z: Calcd for C23H27NO4: 381.1938. Found: 381.1956.
7-Benzyloxy-
(17)
and
7-Hydroxy-6-Methoxy-2-methyl-1-(2-methyl-1-propen-1-yl)-1,2,3,4-
tetrahydroisoquinoline (18) from 16 — LiAlH4 (109.2 mg, 0.29 mmol) was added to a solution of 16
(96.6 mg, 0.25 mmol) in anhydrous THF (6 mL) and the mixture was refluxed for 24 h. After the addition
of MeOH and saturated aqueous Rochelle salt under ice cooling, the whole was extracted with
CH2Cl2–MeOH (95:5, v/v). The organic layer was washed with brine, dried over Na2SO4, and evaporated
under reduced pressure to leave an oil, which was subjected to p-TLC on SiO2 with CHCl3–MeOH–28%
aq. NH3 (46:5:0.5, v/v) as a developing solvent. Extraction of the band having an Rf value of 0.37—0.69
with CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v) gave 17 (73.8 mg, 86%). 17: Colorless oil. IR (film):
2930, 2780, 1610, 1507, 1252 cm-1. 1H-NMR (CDCl3) δ: 1.67 (3H, d, J=1.2 Hz), 1.85 (3H, d, J=1.5 Hz),

HETEROCYCLES, Vol. 74, 2007
949
2.15—3.28 (4H, m), 2.28 (3H, s), 3.72 (1H, d, J=9.5 Hz), 3.77 (3H, s), 4.93 (1H, d, J=9.5 Hz), 4.98 (2H,
s), 6.35 (1H, s), 6.46 (1H, s), 7.02—7.38 (5H, m). High-resolution MS m/z: Calcd for C22H27NO2:
337.2040. Found: 337.2038. Extraction of the band having an Rf value of 0.20—0.29 with
CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v) gave 18 (6.7 mg, 11%). 18: mp 159—160 °C (colorless
1
prisms, recrystallized from MeOH–H2O). IR (KBr): 2900, 1589, 1501, 1268 cm-1. H-NMR (CDCl3) δ:
1.77 (6H, d, J=1.2 Hz), 2.17—3.17 (4H, m), 2.32 (3H, s), 3.74 (3H, s), 3.83 (1H, d, J=9.6 Hz), 4.77 (1H,
br s, disappeared on addition of D2O), 5.05 (1H, br d, J=9.6 Hz), 6.42 (2H, s). MS m/z: 247 (M+).
High-resolution MS m/z: Calcd for C15H21NO2: 247.1573. Found: 247.1569.
(±)-Lophocerine (2) from 17 — A solution of 17 (30.9 mg, 0.09 mmol) in MeOH (7 mL) was
hydrogenated in the presence of 10% Pd/C (33.7 mg) at rt and 1 atm for 7 h. Catalyst was filtered off and
the filtrate was evaporated under reduced pressure to leave an oil, which was purified by p-TLC with
CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v) as a developing solvent. Extraction of the band having an Rf
value of 0.37—0.50 with CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v) gave 2 (8.8 mg, 39%). 2: Colorless
1
oil. IR (film): 2940, 1592, 1505, 1461, 1360, 1266, 1210, 1130, 1102, 1021, 869, 775 cm-1. H-NMR
(CDCl3) δ: 0.90 (3H, d, J=6 Hz), 0.95 (3H, d, J=6 Hz), 1.22—2.02 (3H, m), 2.17—3.57 (5H, m), 2.40
(3H, s), 3.80 (3H, s), 4.33 (1H, br s, disappeared on addition of D2O), 6.43 (1H, s), 6.50 (1H, s). MS m/z:
249 (M+). 2·picrate: mp 194—196 °C (lit.,5 mp 191.5—193 °C, yellow prisms, recrystallized from
benzene). IR (KBr): 3370, 2950, 1609, 1507, 1309, 1269 cm-1.
REFERENCES AND NOTES
1. a) This report is part 132 of a series entitled “The Chemistry of Indoles”. Part 131: M. Somei, S.
Sayama, K. Naka, K. Shinmoto, and F. Yamada, Heterocycles, submitted. COM-07-S(U)31. b)
Professor Emeritus of Kanazawa University. Present address: 2-40-3 Sodani, Hakusan-shi, Ishikawa,
Japan 920-2101.
2. M. Somei, Y. Yokoyama, Y. Murakami, I. Ninomiya, T. Kiguchi, and T. Naito, The Alkaloids, Vol.
54, ed. by G. A. Cordell, Academic Press, 2000, pp. 191—257, references cited therein; M. Somei, K.
Yamada, M. Hasegawa, M. Tabata, Y. Nagahama, H. Morikawa, and F. Yamada, Heterocycles, 1996,
43, 1855; Somei, H. Hayashi, T. Izumi, and S. Ohmoto, ibid., 1995, 41, 2161; M. Somei, Y. Fukui,
and M. Hasegawa, ibid., 1995, 41, 2157; K. Nakagawa and M. Somei, ibid., 1991, 32, 873.
3. F. Yamada, T. Hasegawa, M. Wakita, M. Sugiyama, and M. Somei, Heterocycles, 1986, 24, 1223.
4. V. G. Sakharovskii, A. V. Aripovskii, M. B. Baru, and A. G. Kozlovskii, Khim. Prir. Soedin., 1983,
656; A. G. Kozlovskii, T. F. Solovera, V. G. Sakharovskii, and V. M. Adanin, Dolk. Akad. Nauk.
SSSR, 1981, 260, 230.
5. J. M. Bobbitt and T.-T. Chou, J. Org. Chem., 1959, 24, 1106; C. Djerassi, T. Nakano, and J. M.

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Bobbitt, Tetrahedron, 1958, 2, 58.
6. F. Yamada, Y. Makita, T. Suzuki, and M. Somei, Chem. Pharm. Bull., 1985, 33, 2162.
7. M. Somei and T. Okamoto, Yakugaku Zasshi, 1972, 92, 397; M. Somei and T. Okamoto, Chem.
Pharm. Bull., 1970, 18, 2135.
8. F. Yamada, Y. Makita, and M. Somei, Heterocycles, 2007, 72, 599.
9. L. S. Hegedus, J. L. Toro, W. H. Miles, and P. J. Harrington, J. Org. Chem., 1987, 52, 3319.
10. M. Iwao and O. Motoi, Tetrahedron Lett., 1995, 36, 5929.
11. M. Somei, F. Yamada, Y. Yamazaki, and A. Shinkura, Chem. Pharm. Bull., 1996, 44, 21.