Novel synthetic strategy of carbolines via palladium-catalyzed amination and arylation reaction

Article abstract of DOI:10.1039/a901088b

Four parent carbolines and the corresponding 5- or 9-methylsulfonyl derivatives were synthesized by the palladium-catalyzed intramolecular arylation reaction of ortho-bromo-substituted anilinopyridines which were prepared by the palladium-catalyzed amination reaction of iodobenzenes with aminopyridines. Carbazole and its 9-methylsulfonyl derivative were also synthesized by the same method.

Full text of DOI:10.1039/a901088b

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Novel synthetic strategy of carbolines via palladium-catalyzed
amination and arylation reaction
Takehiko Iwaki, Akito Yasuhara and Takao Sakamoto*
Faculty of Pharmaceutical Sciences, Tohoku University Aoba-ku, Sendai 980-8578, Japan
Received (in Cambridge) 9th February 1999, Accepted 7th April 1999
Four parent carbolines and the corresponding 5- or 9-methylsulfonyl derivatives were synthesized by the palladium-
catalyzed intramolecular arylation reaction of ortho-bromo-substituted anilinopyridines which were prepared by the
palladium-catalyzed amination reaction of iodobenzenes with aminopyridines. Carbazole and its 9-methylsulfonyl
derivative were also synthesized by the same method.
reaction of 1-pyridinylbenzotriazoles2a–c or phenylpyridotri-
Introduction
azoles,2d and the radical cyclization reaction of the aryl radicals
Carbolines (pyrido[x,y-b]indoles) are known as the skeletons of
generated from the o-diazonium derivatives,2e,f but these
naturally occurring compounds, and, particularly, β-carboline
(9H-pyrido[3,4-b]indole) is known as the skeleton of numerous
methods have no generality for the synthesis of all carboline
skeletons and sometimes gave a mixture of isomers. The
alkaloids. Although many synthetic methods for producing
Type 2 synthetic methods involve the thermolysis reaction of
carboline ring systems have been studied,1 most of them are
o-pyridinylphenyl azides3a or o-phenylpyridinyl azides3b and
applications of the Fischer indole cyclization reaction to
the insertion reaction of the arylnitrenes generated from the
cyclohexanone pyridinylhydrazones or piperidinone phenyl-
corresponding nitroso3c or nitro derivatives.3d,e These methods
hydrazones and isoquinoline cyclization reactions (e.g.,
also have no generality for the synthesis of the four carbolines
Bischler–Napieralsky or Pictet–Spengler reaction) to indole
and sometimes gave the products in low yields. Recently, a
derivatives. These methods are suitable for partially hydrogen-
general Type 2 method giving high yields was developed by
ated carbolines, but not very effective for fully aromatic deriv-
Quéguiner et al.4a–d who applied their method to the synthesis
atives. In addition, the Fischer cyclization reaction sometimes
affords isomers and the synthesis of α- and δ-carbolines is not
possible using isoquinoline cyclization reactions. Simple,
general, and efficient synthetic methods for the four parent
carbolines are scarcely known (to our knowledge) except for
Quéguiner’s method to be discussed later.
of natural products. Their method consists of the combination
of the palladium-catalyzed cross-coupling reaction of iodo-
fluoropyridines with aminophenylboronic acid derivatives
and the intramolecular nucleophilic substitution reaction of
the amino group on the benzene ring to the fluoro group of the
pyridine ring.
One of the simple and general synthetic methods for fully
On the basis of the background described above, we designed
aromatic carbolines is considered to be the pyrrole-ring con-
a new strategy for the Type 1 synthesis of the four parent
struction from benzene and pyridine building blocks. One of
carbolines. This strategy consists of the combination of two
the two routes known up to now is the Type 1 route shown in
palladium-catalyzed reactions, namely the amination reaction
Scheme 1, which is the cyclization reaction of anilinopyridine
equivalent derivatives or the ring-transformation reaction of
benzo- or pyridotriazoles, and the other one (Type 2 route) is
the cyclization reaction of phenylpyridine derivatives which
have a nitrogen substituent at an ortho-position.
Examples of the Type 1 synthesis are the thermolysis
of iodobenzenes with aminopyridines and the intramolecular
arylation reaction of ortho-bromo-substituted anilinopyridines.
There are two possible strategies to synthesize ortho-bromo-
substituted anilinopyridines using the method reported by
Buchwald et al.5 (Step 1). These are the palladium-catalyzed
reactions of halogenopyridines with aniline derivatives, and
of halogenobenzenes with aminopyridines. We chose the
latter route, because of the easy availability of the starting
compounds and the selectivity of the palladium-catalyzed
N
X
N
N
X
reaction. As the cyclization reaction to carbolines (Step 2),
the palladium-catalyzed intramolecular arylation reactions6,7
of ortho-monohalogenoanilinopyridines and of ortho,orthoЈ-
dihalogenoanilinopyridines were selected.
N
Step 1
N
N
Type 1 Step 2
Results and discussion
N
The palladium-catalyzed cross-coupling reaction of 2-bromo-
iodobenzene 1a with 2-aminopyridine 2a under the reported
conditions5a gave 2-(2-bromoanilino)pyridine 4a in 95%
yield. Analogously, 4- 4b and 3-(2-bromoanilino)pyridine 4c
were also obtained from the reaction of 1a with 2b,c in
96 and 90% yield, respectively. Although the cyclization by
the intramolecular palladium-catalyzed arylation reaction of
4b,c in the presence of palladium diacetate and sodium carb-
onate in DMF under reflux conditions gave the corresponding
γ-(5H-pyrido[4,3-b]indole) 8c and δ-carboline (5H-pyrido-
N
Type 2
N
N
Scheme 1
J. Chem. Soc., Perkin Trans. 1, 1999, 1505–1510
1505

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d
c
b
c
Br
b
c
X=Br
Y=H
N
N
b
N
H2N
a
a
N
R
N
H
2a-c
a
8a-d: R=H (31-70%)
9a-d: R=Ms (64-91%)
ii
4a-c (90-96%)
d
Y
X
I
Br
c
i
X=H
N
+
N
iv
b
Y=Br
H2N
N
H
a
1a: X=Br
1b: X=H
3a-d: Y=Br
5a-d (53-90%)
Br
Br
d
Br
Br
d
c
c
X=Br
Y=Br
iii
N
N
N
b
b
N
N
a
a
H
N
Ms
7a-d (78-95%)
6a-d (71-95%)
10 (59%)
Scheme 2 Reagents and conditions: i, Pd2(dba)3, DPPF, t-BuONa, toluene, 100 ЊC; ii, Pd(OAc)2, Na2CO3, DMF, reflux; iii, NaH, MsCl, THF, rt;
iv, PdCl2(PPh3)2, (SnBu3)2, Li2CO3, Et4NI, toluene (DMF), reflux. a N replaces CH at a; b N replaces CH at b; c N replaces CH at c; d N replaces
CH at d.
[3,2-b]indole) 8d in 70 and 51% yield, respectively, the
cyclization reaction of 4a gave no α-carboline (9H-pyrido[2,3-b]-
indole) 8a but, gave instead, the pyrido[1,2-a]benzimidazole 10
in 59% yield, which resulted from the cyclization reaction at the
pyridine ring nitrogen of 4a (Scheme 2). Although the yields of
4a–c were satisfactory, this route has some weak points, such as
the fact that the starting (2-bromoanilino)pyridines necessary
to synthesize all four carbolines were not available, the
palladium-catalyzed cyclization reaction of 4a gave no α-carbol-
ine, and the yield of δ-carboline was unsatisfactory.
In order to overcome these weak points, we next examined
an alternative route which consists of the cross-coupling
reaction of iodobenzene 1b with o-aminobromopyridines 3a–d.
This route is suitable for the synthesis of the starting materials
for all carbolines and cannot yield the unexpected pyrido-
[1,2-a]benzimidazole 10. Moreover, the palladium-catalyzed
cyclization reaction of the relatively π-deficient bromopyridine
moieties with the relatively π-excessive aniline moiety is
expected to proceed smoothly, because the palladium-catalyzed
cross-coupling reactions of π-deficient heteroaryl halides with
π-excessive heterocycles have been reported.8
o-Aminobromopyridines 3a–c, but not 3-amino-2-bromo-
pyridine 3d, were synthesized by the alkaline hydrolysis reac-
tion of o-bromo-(2,2-dimethylpropanoylamino)pyridines which
were prepared by the ortho-directed lithiation reaction of (2,2-
dimethylpropanoylamino)pyridines9 and subsequent bromin-
ation with 1,2-dibromoethane. The palladium-catalyzed
cross-coupling reaction of iodobenzene 1b with 2-amino-3-
bromopyridine 3a under the above mentioned reaction condi-
tions gave 2-anilino-3-bromopyridine 5a in 90% yield. The
analogous cross-coupling reaction of 1b with 3-amino-2-
bromo- 3b, 4-amino-3-bromo- 3c, and 3-amino-2-bromo-
pyridine 3d gave the corresponding anilinobromopyridines
5b–d in 53–88% yield, respectively. The four o-anilinobromo-
pyridines 5a–d were subjected to the same conditions as the
cyclization reaction of isomers 4a–c to give the corresponding
carbolines 8a–d in yields of 31–61%.
As a result, this general route can synthesize all parent
carbolines, but the yields of the cyclization reactions were un-
satisfactory. In order to improve the yields of the cyclization
step, we examined the aforementioned third method. The
palladium-catalyzed cross-coupling reaction of 2-bromoiodo-
benzene 1a with o-aminobromopyridines 3a–d gave o,oЈ-di-
bromoanilinopyridines 6a–d in 71–93% yield. The cyclization
reaction to carbolines 9a–d via the intermediary tributylstannyl
derivatives by reaction with hexabutyldistannane in the
presence of dichlorobis(triphenylphosphine)palladium, lithium
carbonate, and tetraethylammonium iodide in toluene under
reflux conditions6 did not proceed. Then 6a–d were converted
to the corresponding N-methylsulfonyl derivatives 7a–d under
conventional conditions in yields of 78–95%, and 7a–d were
cyclized under the conditions mentioned above to give N-
methylsulfonyl-α- 9a and -δ-carboline 9d in 91 and 84% yield,
respectively. However, the β- 9b and γ-carboline 9c were hardly
formed under these conditions, because of the low solubilities
of 7b,c in toluene. Improvements in the yields were achieved
using toluene–DMF (10:1) as the solvent, and 9b,c were
obtained in 64 and 74% yield, respectively.
Finally, we applied the successful carboline synthesis method
to carbazole synthesis. Namely, the palladium-catalyzed re-
action of 1a,b with 2-bromoaniline 11b gave 2-bromo- 12a
and 2,2Ј-dibromodiphenylamine 12b in 46 and 96% yield,
respectively (Scheme 3). Although the yields (41–47%) of the
cyclization reaction were unsatisfactory, carbazole 14a and
9-(methylsulfonyl)carbazole 14b were obtained.
Conclusions
A simple and general method for the synthesis of four parent
carbolines and carbazoles was achieved by the combination of
two palladium-catalyzed reactions, which are the amination
reaction of iodobenzenes with aminopyridines or anilines and
the intramolecular biaryl coupling reaction of ortho-bromo-
and ortho,orthoЈ-dibromo-substituted anilinoarenes.
Experimental
General comments
THF and Et2O were distilled from sodium/benzophenone ketyl
before use. n-BuLi was titrated using 2,5-dimethoxybenzyl
alcohol before use. All mps (recorded on a YAZAWA micro
melting point BY-2 apparatus) and bps are uncorrected. IR
spectra were taken on a JASCO IR-810 spectrophotometer. 1H
NMR spectra were recorded on Varian Gemini 2000 (300
MHz) and Hitachi R-300 (300 MHz) spectrometers. Chemical
shifts are expressed in δ (ppm) values with tetramethylsilane
(TMS) as internal reference, and coupling constants (J) are
expressed in Hz. The following abbreviations are used: s = sin-
glet, d = doublet, t = triplet, m = multiplet, dd = double doub-
let, dt = double triplet, br = broad, and br s = broad singlet.
Mass spectra (MS) and high-resolution mass spectra (HRMS)
were recorded on JMS-DX303 and JMS-AX500 instruments.
3-Amino-2-bromopyridine 3d was prepared according to the
literature method.10
1506
J. Chem. Soc., Perkin Trans. 1, 1999, 1505–1510

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Y
3-Bromo-4-(2,2-dimethylpropanoylamino)pyridine. According
Br
I
+
to the typical procedure, 3-bromo-4-(2,2-dimethylpropan-
oylamino)pyridine was obtained from the reaction using
4-(2,2-dimethylpropanoylamino)pyridine (1.38 g, 7.75 mmol).
Recrystallization from i-Pr2O–n-hexane gave prisms (1.64 g,
83%), mp 70–72 ЊC (Found: C, 46.51; H, 5.15; Br, 30.99; N,
10.70. C10H13BrN2O requires C, 46.71; H, 5.10; Br, 31.08; N,
10.89%); νmax(KBr)/cmϪ1 3275 and 1660; δH 1.36 (9 H, s), 8.17 (1
H, br s), 8.42 (1 H, d, J 0.82), 8.64 (1 H, s); m/z 256 (Mϩ)
(Found: Mϩ, 256.0246. Calc. for C11H979BrN2O: M, 256.0211).
H2N
1a: X=Br
11a: Y=H
11b: Y=Br
i
Br
Y
2-Amino-3-bromopyridine 3a; typical procedure for alkaline
hydrolysis reaction of o-bromo-(2,2-dimethylpropanoyl-
amino)pyridine
N
H
12a: Y=H (46%)
12b: Y=Br (96%)
A
mixture of 3-bromo-2-(2,2-dimethylpropanoylamino)-
pyridine (8.35 g, 32.7 mmol) and 3 M KOH (15 ml) in MeOH
(35 ml) was refluxed for 4 h. After removal of the solvent, the
residue was diluted with Et2O and the Et2O phase was washed
with brine, dried over MgSO4, and evaporated. The residue was
purified by silica gel column chromatography using n-hexane–
AcOEt (1:1) as eluent. The product was recrystallized from
Et2O–n-hexane to give needles (2.78 mg, 95%), mp 64–65 ЊC
(Found: C, 34.78; H, 3.11; Br, 45.90; N, 16.34. C5H5BrN2
requires C, 34.71; H, 2.91; Br, 46.18; N, 16.19%); νmax(KBr)/
cmϪ1 3425; δH 4.92 (2 H, br s), 6.53–6.58 (1 H, m), 7.66 (1 H, dd,
J 1.37, 6.59), 8.02 (1 H, dd, J 1.37, 4.95); m/z 172 (Mϩ) (Found:
Mϩ, 171.9623. Calc. for C5H579BrN2: M, 171.9636).
ii
iii
Br
Br
N
R
N
Ms
13 (83%)
14a: R=H (41%)
14b: R=Ms (47%)
3-Amino-4-bromopyridine 3b. According to the typical pro-
cedure, 3b was obtained from the reaction using 4-bromo-3-
(2,2-dimethylpropanoylamino)pyridine (1.66 g, 6.5 mmol), as
an oil (848.6 mg, 76%); bp 46–49 ЊC/3 mmHg; νmax(neat)/cmϪ1
3448; δH 4.14 (2 H, br s), 7.35 (1 H, dd, J 1.37, 4.95), 7.81 (1 H,
d, J 4.67), 8.12 (1 H, s); m/z 172 (Mϩ) (Found: Mϩ, 171.9628).
iv
Scheme 3 Reagents and conditions: i, Pd2(dba)3, DPPF, t-BuONa,
toluene, 100 ЊC; ii, Pd(OAc)2, Na2CO3, DMF, reflux; iii, NaH, MsCl,
THF, rt; iv, PdCl2(PPh3)2, (SnBu3)2, Li2CO3, Et4NI, toluene (DMF),
reflux.
4-Amino-3-bromopyridine 3c. According to the typical pro-
cedure, 3c was obtained from the reaction 3-bromo-4-(2,2-
dimethylpropanoylamino)pyridine (1.85 g, 7.25 mmol). Re-
crystallization from Et2O–n-hexane gave needles (1.21 g, 97%),
mp 70–71 ЊC (Found: C, 34.78; H, 3.14; Br, 45.98; N, 16.41%);
νmax(KBr)/cmϪ1 3365; δH 4.65 (1 H, br s,), 6.61 (2 H, d, J 5.49),
8.12 (1 H, d, J 5.49), 8.41 (1 H, s); m/z 172 (Mϩ) (Found:
Mϩ, 171.9641).
3-Bromo-2-(2,2-dimethylpropanoylamino)pyridine; typical
procedure for ortho-directed lithiation-bromination reaction
of (2,2-dimethylpropanoylamino)pyridine
n-BuLi (1.94 ml, 2.62 mmol) was slowly added to a solution
of 2-(2,2-dimethylpropanoylamino)pyridine (186.2 mg, 1.04
mmol) and TMEDA (0.39 ml, 2.62 mmol) in THF (5 ml) at
Ϫ70 ЊC. The resulting solution was stirred at Ϫ70 ЊC for 15 min
and at Ϫ10 ЊC for 2 h. Then the mixture was cooled to Ϫ70 ЊC,
and 1,2-dibromoethane (0.23 ml, 2.62 mmol) was added. The
resulting solution was stirred at Ϫ70 ЊC for 15 min and at
Ϫ10 ЊC for 2 h. After evaporation of the THF, the residue
was taken up into Et2O, and the Et2O phase was washed succes-
sively with water and brine, dried over MgSO4, and evaporated.
The residue was purified by silica gel column chromatography
using n-hexane–AcOEt (1:1) as eluent. The product was re-
crystallized from Et2O–n-hexane to give 3-bromo-2-(2,2-
dimethylpropanoylamino)pyridine as needles (132.6 mg, 50%),
mp 140–141 ЊC (Found: C, 46.73; H, 5.04; Br, 31.18; N, 11.14.
C10H13BrN2O requires C, 46.71; H, 5.10; Br, 31.08; N, 10.89%);
νmax(KBr)/cmϪ1 3290 and 1650; δH 1.37 (9 H, s), 6.99 (1 H, dd,
J 4.67, 7.97), 7.89 (1 H, dd, J 1.64, 7.97), 8.05 (1 H, br s), 8.46
(1 H, dd, J 1.37, 4.67); m/z 256 (Mϩ) (Found: Mϩ, 256.0209.
Calc. for C10H1379BrN2O: M, 256.0211).
2-(2-Bromoanilino)pyridine 4a; typical procedure for the
palladium-catalyzed reaction of iodobenzenes with arylamines
A mixture of 2-aminopyridine 2a (343.6 mg, 3.65 mmol), 2-
bromoiodobenzene 1a (0.56 ml, 4.38 mmol), t-BuONa (475.7
mg, 5.11 mmol), Pd2(dba)3 † (174.2 mg, 0.19 mmol), and
DPPF‡ (204.9 mg, 0.37 mmol) in toluene (18 ml) was stirred at
100 ЊC for 14 h. After cooling, the mixture was diluted with
Et2O and filtered through a Celite pad. The filtrate was evap-
orated, and purified by silica gel column chromatography using
n-hexane–AcOEt (7:3) as eluent to give a pale yellow oil (853.9
mg, 94%); bp 140–143 ЊC/3 mmHg; νmax(neat)/cmϪ1 3410; δH 6.09
(1 H, br s), 6.98–6.84 (1 H, m), 7.16–7.27 (3 H, m), 7.45–7.49
(1 H, m), 7.55 (1 H, dd, J 1.10, 7.97), 8.27 (1 H, dd, J 1.10, 4.67),
8.47 (1 H, d, J 2.47); m/z 248 (Mϩ) (Found: Mϩ, 247.9940. Calc.
for C11H979BrN2: M, 247.9949).
4-(2-Bromoanilino)pyridine 4b. According to the typical pro-
cedure, 4b was obtained from the reaction using 4-amino-
pyridine 2b (222.1 mg, 2.36 mmol). Recrystallization from
i-Pr2O–n-hexane gave needles (555.9 mg, 96%), mp 94–95 ЊC
(Found: C, 53.06; H, 3.62; Br, 32.07; N, 11.14. C11H9BrN2
requires C, 53.04; H, 3.64; Br, 32.08; N, 11.25%); νmax(KBr)/
cmϪ1 3207; δH 6.23 (1 H, br s), 6.89 (2 H, d, J 6.32), 6.98 (1 H,
4-Bromo-3-(2,2-dimethylpropanoylamino)pyridine. According
to the typical procedure, 4-bromo-3-(2,2-dimethylpropanoyl-
amino)pyridine was obtained from the reaction using 3-(2,2-
dimethylpropanoylamino)pyridine (340.1 mg, 1.91 mmol). Re-
crystallization from i-Pr2O–n-hexane gave needles (204.2 mg,
45%), mp 98–99 ЊC (Found: C, 46.82; H, 5.09; Br, 30.84; N,
10.95%); νmax(KBr)/cmϪ1 3410 and 1705; δH 1.37 (9 H, s), 7.50
(1 H, d, J 5.22), 7.84 (1 H, br s), 8.18 (1 H, d, J 5.22), 9.54 (1 H,
s); m/z 256 (Mϩ) (Found: Mϩ, 256.0250).
† dba = dibenzylideneacetone.
‡ DPPF = 1,1Ј-bis(diphenylphosphino)ferrocine.
J. Chem. Soc., Perkin Trans. 1, 1999, 1505–1510
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dt, J 1.37, 7.97), 7.31 (1 H, dt, J 1.37, 7.97), 7.46 (1 H, dd,
J 1.37, 7.97), 7.62 (1 H, dd, J 1.37, 7.97), 8.36 (2 H, d, J 6.32);
m/z 248 (Mϩ) (Found: Mϩ, 247.9935).
lization from n-hexane gave needles (1.49 g, 86%), mp 89–91 ЊC
(Found: C, 40.51; H, 2.59; Br, 48.69; N, 8.52%); νmax(KBr)/cmϪ1
3380; δH 6.30 (1 H, br s), 6.89–6.94 (1 H, m), 7.23–7.33 (2 H, m),
7.52 (1 H, d, J 5.22), 7.62 (1 H, dd, J 1.10, 7.96), 8.02 (1 H, d,
J 5.22), 8.54 (1 H, s); m/z 326 (Mϩ) (Found: Mϩ, 325.9009).
3-(2-Bromoanilino)pyridine 4c. According to the typical pro-
cedure, 4c was obtained from the reaction using 3-amino-
pyridine 2c (95.8 mg, 1.02 mmol), as a pale yellow oil (222.4 mg,
90%), bp 150–153 ЊC/3 mmHg; νmax(neat)/cmϪ1 3380; δH 6.07
(1 H, br s), 6.98–6.84 (1 H, m), 7.16–7.27 (3 H, m), 7.45–7.49
(1 H, m), 7.55 (1 H, dd, J 1.10, 7.97), 8.27 (1 H, dd, J 1.10, 4.67),
8.47 (1 H, d, J 2.75); m/z 248 (Mϩ) (Found: Mϩ, 247.9941).
3-Bromo-4-(2-bromoanilino)pyridine 6c. According to the
typical procedure, 6c was obtained from the reaction for 18 h
using 4-amino-3-bromopyridine 3c (946.8 mg, 5.50 mmol)
and 2-bromoiodobenzene 1a (0.85 ml, 6.61 mmol). Recrystal-
lization from CHCl3–n-hexane gave needles (1.67 g, 90%), mp
125–127 ЊC (Found: C, 40.38; H, 2.54; Br, 48.81; N, 8.47%);
νmax(KBr)/cmϪ1 3380; δH 6.74 (1 H, br s), 6.93 (1 H, d, J 5.77),
7.08 (1 H, dt, J 1.65, 7.69), 7.36 (1 H, dt, J 1.37, 8.24), 7.45 (1 H,
dd, J 1.65, 8.24), 7.68 (1 H, dd, J 1.37, 8.24), 8.19 (1 H, d,
J 5.77), 8.55 (1 H, s); m/z 326 (Mϩ) (Found: Mϩ, 325.9034).
2-Anilino-3-bromopyridine 5a. According to the typical pro-
cedure, 5a was obtained from the reaction for 17 h using
2-amino-3-bromopyridine 3a (638.0 mg, 3.68 mmol) and
iodobenzene (0.90 ml, 4.43 mmol), as a pale yellow oil (817.4
mg, 90%), bp 153–156 ЊC/3 mmHg (Found: C, 52.98; H, 3.86;
Br, 31.77; N, 11.13%); νmax(neat)/cmϪ1 3400; δH 6.63 (1 H, dd,
J 4.95, 7.69), 7.01 (1 H, br s), 7.03–7.13 (1 H, m), 7.32–7.37
(2 H, m), 7.62 (2 H, d, J 7.69), 7.73 (1 H, dd, J 1.65, 7.69), 8.15
(1 H, dd, J 1.65, 4.67); m/z 248 (Mϩ) (Found: Mϩ, 247.9949).
2-Bromo-3-(2-bromoanilino)pyridine 6d. According to the
typical procedure, 6d was obtained from the reaction for 18 h
using 3-amino-2-bromopyridine 3d (554.8 mg, 3.23 mmol)
and 2-bromoiodobenzene 1a (0.50 ml, 3.87 mmol). Recrystal-
lization from n-hexane gave needles (751.7 mg, 71%), mp
49–51 ЊC (Found: C, 40.45; H, 2.64; Br, 48.67; N, 8.52%);
νmax(KBr)/cmϪ1 3375; δH 6.49 (1 H, br s), 6.92–6.98 (1 H, m),
7.15 (1 H, dd, J 4.67, 8.24), 7.27–7.32 (2 H, m), 7.47 (1 H, dd,
J 1.65, 7.96), 7.63 (1 H, d, J 8.79), 7.94 (1 H, dd, J 1.37, 4.67);
m/z 326 (Mϩ) (Found: Mϩ, 325.9019).
3-Anilino-4-bromopyridine 5b. According to the typical
procedure, 5b was obtained from the reaction for 17 h using
3-amino-4-bromopyridine 3b (824.3 mg, 4.79 mmol) and iodo-
benzene (0.64 ml, 5.75 mmol). Recrystallization from i-Pr2O–n-
hexane gave needles (628.3 mg, 53%), mp 109–110 ЊC (Found:
C, 53.04; H, 3.69; Br, 32.08; N, 11.18%); νmax(KBr)/cmϪ1 3220;
δH 5.96 (1 H, br s), 7.11 (1 H, t, J 7.42), 7.19 (1 H, d, J 7.69),
7.36 (1 H, dt, J 1.92, 7.42), 7.46 (1 H, d, J 5.22), 7.93 (1 H, d,
J 4.95), 8.51 (1 H, s); m/z 248 (Mϩ) (Found: Mϩ, 247.9928).
2-Bromodiphenylamine 12a. According to the typical pro-
cedure, 12a was obtained from the reaction for 12 h using
aniline 11a (94.9 mg, 1.02 mmol) and 1a (0.16 ml, 1.22 mmol),
as a pale yellow oil (116.2 mg, 46%), bp 138–141 ЊC/3 mmHg;
νmax(neat)/cmϪ1 3390; δH 6.08 (1 H, br s), 6.73 (1 H, dt, J 1.65,
7.96), 7.01–7.07 (1 H, m), 7.13–7.19 (3 H, m), 7.25 (1 H, dd,
J 1.37, 5.77), 7.29–7.35 (2 H, m), 7.52 (1 H, dd, J 1.65, 7.96);
m/z 247 (Mϩ) (Found: Mϩ, 246.9984. Calc. for C12H1079BrN:
M, 246.9996).
4-Anilino-3-bromopyridine 5c. According to the typical
procedure, 5c was obtained from the reaction for 17 h using
4-amino-3-bromopyridine 3c (342.7 mg, 1.99 mmol) and iodo-
benzene (0.27 ml, 2.39 mmol). Recrystallization from i-Pr2O–n-
hexane gave plates (436.4 mg, 88%), mp 66–68 ЊC (Found: C,
53.09; H, 3.66; Br, 31.99; N, 11.08%); νmax(KBr)/cmϪ1 3380;
δH 6.50 (1 H, br s), 6.92 (1 H, d, J 5.77), 7.20–7.27 (3 H, m),
7.39–7.44 (2 H, m), 8.14 (1 H, d, J 5.49), 8.49 (1 H, s); m/z 248
(Mϩ) (Found: Mϩ, 247.9919).
2,2Ј-Dibromodiphenylamine 12b. According to the typical
procedure, 12b was obtained from the reaction for 12 h using
2-bromoaniline 11b (821.9 mg, 4.78 mmol) and 1a (0.74 ml,
5.73 mmol), as an oil (1.50 g, 96%), bp 154–158 ЊC/3 mmHg;
νmax(KBr)/cmϪ1 3370; δH 6.44 (1 H, br s), 6.84 (2 H, dt, J 1.65,
7.96), 7.22 (2 H, dd, J 1.37, 8.24), 7.29 (2 H, dt, J 1.65, 8.24), 7.58
(2 H, dd, J 1.37, 7.96); m/z 325 (Mϩ) (Found: Mϩ, 324.9092.
Calc. for C12H979Br2N: M, 324.9102).
3-Anilino-2-bromopyridine 5d. According to the typical pro-
cedure, 5d was obtained from the reaction for 17 h using
3-amino-2-bromopyridine 3d (142.9 mg, 0.90 mmol) and iodo-
benzene (0.12 ml, 1.08 mmol). Recrystallization from i-Pr2O–
n-hexane gave needles (142.5 mg, 64%), mp 85–86 ЊC (Found:
C, 53.03; H, 3.83; Br, 32.13; N, 11.44. C11H9BrN2 requires C,
53.04; H, 3.64; Br, 32.08; N, 11.25%); νmax(KBr)/cmϪ1 3400;
δH 6.16 (1 H, br s), 7.06–7.18 (4 H, m), 7.30–7.40 (2 H, m), 7.43
(1 H, dd, J 1.65, 7.97), 7.85 (1 H, dd, J 1.65, 4.67); m/z 248 (Mϩ)
(Found: Mϩ, 247.9949).
9H-Pyrido[2,3-b]indole or á-carboline 8a; typical procedure for
the palladium-catalyzed reaction of ortho-anilinobromoarenes
A mixture of 5a (204.5 mg, 0.82 mmol), Pd(OAc)2 (18.5 mg,
0.08 mmol), and Na2CO3 (143.1 mg, 1.15 mmol) in DMF (7 ml)
was refluxed for 67 h. After cooling, the mixture was diluted
with AcOEt and filtered through a Celite pad. The filtrate was
washed successively with water and brine, dried over MgSO4,
and evaporated. The residue was purified by silica gel column
chromatography using n-hexane–AcOEt (1:1) as eluent. The
product was recrystallized from toluene to give needles (43.3
mg, 31%), mp 210–211 ЊC (lit.,4a 212 ЊC); νmax(KBr)/cmϪ1 3400;
δH(CDCl3–d6-DMSO) 7.19 (1 H, dd, J 4.95, 7.49), 7.25–7.30
(1 H, m), 7.45–7.55 (2 H, m), 8.07 (1 H, d, J 7.69), 8.34 (1 H, dd,
J 1.65, 7.69), 8.47 (1 H, d, J 7.69).
3-Bromo-2-(2-bromoanilino)pyridine 6a. According to the
typical procedure, 6a was obtained from the reaction for 18 h
using 2-amino-3-bromopyridine 3a (188.7 mg, 1.10 mmol)
and 2-bromoiodobenzene 1a (0.17 ml, 1.32 mmol). Recrystal-
lization from n-hexane gave prisms (333.8 mg, 93%), mp 73–
74 ЊC (Found: C, 40.12; H, 2.49; Br, 48.70; N, 8.48. C11H8Br2N2
requires C, 40.28; H, 2.46; Br, 48.72; N, 8.54%); νmax(KBr)/cmϪ1
3355; δH 6.71 (1 H, dd, J 4.95, 7.69), 6.90 (1 H, dt, J 1.37, 7.69),
7.33 (1 H, dt, J 1.37, 8.24), 7.57 (1 H, dd, J 1.37, 7.96), 7.73
(1 H, br s), 7.80 (1 H, dd, J 1.65, 7.96), 8.19 (1 H, dd, J 1.65,
4.65), 8.59 (1 H, dd, J 1.65, 8.24); m/z 326 (Mϩ) (Found:
Mϩ, 325.9032. Calc. for C11H879Br2N2: M, 325.9055).
9H-Pyrido[3,4-b]indole or â-carboline 8b. According to the
typical procedure, 8b was obtained from the reaction using 5b
(132.5 mg, 0.53 mmol). Recrystallization from toluene gave
needles (54.1 mg, 61%), mp 199–200 ЊC (lit.,4a mp 198–200 ЊC);
νmax(KBr)/cmϪ1 3400; δH(CDCl3–d6-DMSO) 7.19 (1 H, dd,
J 2.74, 5.22), 7.42–7.47 (2 H, m), 7.88 (1 H, d, J 5.22), 8.05 (1 H,
d, J 7.69), 8.34 (1 H, dd, J 5.22), 8.84 (1 H, s), 10.14 (1 H, br s).
4-Bromo-3-(2-bromoanilino)pyridine 6b. According to the
typical procedure, 6b was obtained from the reaction for 18 h
using 3-amino-4-bromopyridine 3b (909.2 mg, 5.29 mmol)
and 2-bromoiodobenzene 1a (0.81 ml, 6.34 mmol). Recrystal-
1508
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5H-Pyrido[4,3-b]indole or ã-carboline 8c. According to the
typical procedure, 8c was obtained from the reaction using
5c (151.2 mg, 0.61 mmol). Yield 48 mg (47%).
(1 H, d, J 5.22), 9.14 (1 H, s); m/z 404 (Mϩ) (Found: Mϩ,
403.8832).
According to the typical procedure, 8c was obtained from the
reaction after 10 h using 4b (257.1 mg, 1.04 mmol). Yield 123.0
mg (70%). Recrystallization from toluene gave needles, mp
216–218 ЊC (lit.,4a 218 ЊC); νmax(KBr)/cmϪ1 3400; δH(CDCl3–
d6-DMSO) 6.98 (1 H, dt, J 1.37, 7.69), 7.08–7.24 (3 H, m), 7.82
(1 H, d, J 7.69), 8.16 (1 H, d, J 8.24), 8.99 (1 H, s), 10.54 (1 H,
br s).
3-Bromo-4-[2-bromo-N-(methylsulfonyl)anilino]pyridine 7c.
According to the typical procedure, 7c was obtained from the
reaction using 6c (570.4 mg, 1.75 mmol). Recrystallization from
MeOH gave needles (579.7 mg, 82%), mp 199–201 ЊC (Found:
C, 35.51; H, 2.54; Br, 39.60; N, 6.88; S, 7.92%); νmax(KBr)/cmϪ1
1350 and 1120; δH 3.32 (3 H, s), 7.29 (1 H, dt, J 1.65, 7.69), 7.45
(1 H, dt, J 1.65, 7.96), 7.64–7.69 (2 H, m), 8.06 (1 H, dd, J 1.65,
8.24), 8.53 (1 H, d, J 5.94), 8.79 (1 H, s); m/z 404 (Mϩ) (Found:
Mϩ, 403.8826).
5H-Pyrido[3,2-b]indole or ä-carboline 8d. According to the
typical procedure, 8d was obtained from the reaction using
5d (142.5 mg, 0.57 mmol). Yield 49.0 mg (51%).
According to the typical procedure, 8c was obtained from
the reaction after 14 h using 4b (117.2 mg, 0.47 mmol). Yield
40.1 mg (51%). Recrystallization from toluene gave needles, mp
205–207 ЊC (lit.,4a 206 ЊC); νmax(KBr)/cmϪ1 3400; δH(CDCl3–d6-
DMSO) 6.97–7.07 (2 H, m), 7.19–7.25 (2 H, m), 7.52 (1 H, dd,
J 1.37, 8.24), 8.05 (1 H, d, J 7.69), 8.24 (1 H, d, J 4.67), 10.29
(1 H, br s).
2-Bromo-3-[2-bromo-N-(methylsulfonyl)anilino]pyridine 7d.
According to the typical procedure, 7d was obtained from
the reaction using 6d (275.4 mg, 0.85 mmol). Recrystallization
from acetone–n-hexane gave needles (327.5 mg, 95%), mp 142–
143 ЊC (Found: C, 35.57; H, 2.49; Br, 39.46; N, 6.91; S, 7.86%);
νmax(KBr)/cmϪ1 1350 and 1120; δH 3.31 (3 H, s), 7.23–7.28 (1 H,
m), 7.36–7.46 (2 H, m), 7.65 (1 H, dd, J 1.65, 7.96), 8.09 (1 H,
dd, J 1.37, 8.24), 8.35 (1 H, dd, J 1.65, 4.77), 8.42 (1 H, dd,
J 1.37, 7.96); m/z 404 (Mϩ) (Found: Mϩ, 403.8839).
Pyrido[1,2-a]benzimidazole 10. According to the typical pro-
cedure, 10 was obtained from the reaction using 4a (672.1 mg,
2.71 mmol). Recrystallization from acetone–n-hexane gave
needles (269.8 mg, 59%), mp 179–182 ЊC (lit.,11 180 ЊC); δH 6.87
(1 H, t, J 6.87), 7.36–7.47 (2 H, m), 7.55 (1 H, dt, J 1.10, 8.24),
7.71 (1 H, d, J 9.34), 7.91 (1 H, d, J 8.24), 7.95 (1 H, d, J 8.24),
8.47 (1 H, d, J 6.87); m/z 168 (Mϩ) (Found: Mϩ, 168.0683. Calc.
for C11H8N2: M, 168.0687).
2,2Ј-Dibromo-N-(methylsulfonyl)diphenylamine 13. Accord-
ing to the typical procedure, 13 was obtained from the re-
action using 12b (670.1 mg, 2.05 mmol). Recrystallization from
acetone–n-hexane gave needles (692.7 mg, 83%), mp 163–
165 ЊC (Found: C, 38.49; H, 2.81; Br, 39.66; N, 3.52; S, 7.87.
C13H11Br2NO2S requires C, 38.54; H, 2.74; Br, 39.45; N, 3.46; S,
7.91%); νmax(KBr)/cmϪ1 3220; δH 3.30 (3 H, s), 7.21 (2 H, dt,
J 1.65, 7.96), 7.38 (2 H, dt, J 1.65, 7.96), 7.65 (2 H, dd, J 1.65,
7.96), 8.08 (2 H, dd, J 1.37, 7.96); m/z 403 (Mϩ) (Found: Mϩ,
402.8901. Calc. for C13H1179Br2NO2S: M, 402.8878).
Carbazole 14a. According to the typical procedure, 14 was
obtained from the reaction for 15 h using 12a (219.1 mg, 0.89
mmol). Recrystallization from acetone–n-hexane gave needles
(60.5 mg, 41%), mp 242–247 ЊC (lit.,12 246 ЊC); νmax(KBr)/Ϫ1
3415; δH(CDCl3–d6-DMSO) 7.22 (2 H, dt, J 1.37, 7.69), 7.38–
7.44 (4 H, m), 8.08 (2 H, d, J 7.69), 9.03 (1 H, br s).
9-Methylsulfonyl-á-carboline 9a; typical procedure for the
palladium-catalyzed cyclization reaction of ortho,orthoЈ-di-
bromoarylamines 7a–d, 13
A mixture of 7a (131.9 mg, 0.32 mmol), (Bu3Sn)2 (0.19 ml, 0.38
mmol), Et4NI (115.2 mg, 0.45 mmol), Li2CO3 (33.1 mg, 0.45
mmol), Pd(PPh3)2Cl2 (22.8 mg, 0.03 mol), and toluene (5 ml)
was refluxed for 6 h. After cooling, the mixture was diluted
with Et2O and filtered through a Celite pad. The filtrate was
evaporated, and the residue was purified by silica gel column
chromatography using n-hexane–AcOEt (7:3) as eluent. The
product was recrystallized from acetone–n-hexane to give
needles (71.4 mg, 91%), mp 109–110 ЊC (Found: C, 58.49; H,
4.10; N, 11.40; S, 13.01. C12H10N2O2S requires C, 58.52; H, 4.09;
N, 11.37; S, 13.02%); νmax(KBr)/cmϪ1 1355 and 1120; δH 3.61
(3 H, s), 7.38 (1 H, dd, J 4.95, 7.69), 7.43 (1 H, dt, J 1.10, 7.42),
7.55 (1 H, dt, J 1.37, 7.42), 8.01 (1 H, d, J 7.69), 8.32 (1 H, dd,
J 1.65, 7.69), 8.33 (1 H, d, J 8.52), 8.61 (1 H, dd, J 1.65, 4.94);
m/z 246 (Mϩ) (Found: Mϩ, 246.0436. Calc. for C12H10N2O2S:
M, 246.0462).
3-Bromo-2-[2-bromo-N-(methylsulfonyl)anilino]pyridine 7a;
typical procedure for the preparation of 2,2Ј-dibromo-N-(methyl-
sulfonyl)diarylamines
A THF (5 ml) solution of 6a (353.4 mg, 1.08 mmol) was added
dropwise to a THF (5 ml) suspension of 60% NaH (130.1 mg,
3.25 mmol), and the mixture was stirred at room temperature
(rt) for 1 h. To this mixture was added methanesulfonyl chloride
(0.17 ml, 2.16 mmol), and the whole mixture was stirred at rt
for 4 h. After evaporation of the THF, the residue was taken up
into AcOEt. The AcOEt phase was washed successively with
water and brine, dried over MgSO4, and evaporated. The
residue was purified by silica gel column chromatography with
n-hexane–AcOEt (4:1) as eluent. The product was recrystal-
lized from acetone–n-hexane to give needles (340.6 mg, 78%),
mp 120–122 ЊC (Found: C, 35.55; H, 2.50; Br, 39.54; N, 6.83;
S, 7.87. C12H10Br2N2O2S requires C, 35.49; H, 2.48; Br, 39.35;
N, 6.90; S, 7.89%); νmax(KBr)/cmϪ1 1350 and 1150; δH 3.55 (3 H,
s), 7.09 (1 H, dd, J 4.95, 7.69), 7.24 (1 H, dt, J 1.37, 7.69), 7.40
(1 H, dt, J 1.37, 8.29), 7.58 (1 H, dd, J 1.37, 7.96), 7.88 (1 H,
dd, J 1.65, 7.96), 7.93 (1 H, dd, J 1.65, 8.24), 8.47 (1 H, dd,
J 1.65, 4.65); m/z 404 (Mϩ) (Found: Mϩ, 403.8830. Calc. for
C12H1079Br2N2O2S: M, 403.8830).
9-Methylsulfonyl-â-carboline 9b. According to the typical
procedure, 9b was obtained from the reaction using 7b (131.9
mg, 0.33 mmol) and toluene–DMF (10:1; 5 ml) as solvent. Re-
crystallization from acetone–n-hexane gave needles (51.5 mg,
64%), mp 163–165 ЊC (Found: C, 58.48; H, 3.82; N, 11.35; S,
13.04%); νmax(KBr)/cmϪ1 1355 and 1115; δH 3.08 (3 H, s), 7.51
(1 H, dt, J 1.10, 9.96), 7.68 (1 H, dt, J 1.37, 8.24), 7.93 (1 H, d,
J 5.22), 8.11 (1 H, d, J 7.96), 8.21 (1 H, d, J 8.24), 8.69 (1 H,
d, J 5.22), 9.50 (1 H, s); m/z 246 (Mϩ) (Found: Mϩ, 246.0450).
4-Bromo-3-[2-bromo-N-(methylsulfonyl)anilino]pyridine 7b.
According to the typical procedure, 7b was obtained from the
reaction using 6b (408.3 mg, 1.25 mmol). Recrystallization from
acetone–n-hexane gave needles (420.8 mg, 83%), mp 159–
160 ЊC (Found: C, 35.58; H, 2.52; Br, 39.44; N, 6.80; S, 7.82%);
νmax(KBr)/cmϪ1 1350 and 1130; δH 3.31 (3 H, s), 7.27 (1 H, dt,
J 1.65, 8.24), 7.43 (1 H, dt, J 1.65, 8.24), 7.59 (1 H, d, J 5.22),
7.65 (1 H, dd, J 1.65, 7.96), 8.16 (1 H, dd, J 1.65, 8.24), 8.32
5-Methylsulfonyl-ã-carboline 9c. According to the typical
procedure, 9c was obtained from the reaction using 7c (464.6
mg, 1.15 mmol) and toluene–DMF (10:1; 5 ml) as solvent.
Recrystallization from CHCl3–n-hexane gave needles (210.3
mg, 74%), mp 165–166 ЊC (Found: C, 58.19; H, 3.94; N, 11.29;
J. Chem. Soc., Perkin Trans. 1, 1999, 1505–1510
1509

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O. Bremer, Justus Liebigs Ann. Chem., 1934, 514, 279; (e) R. A.
S, 13.11%); νmax(KBr)/cmϪ1 1350 and 1125; δH 3.12 (3 H, s),
7.64–7.71 (2 H, m), 8.06 (1 H, d, J 6.04), 8.12 (1 H, d, J 7.42),
8.17 (1 H, d, J 8.24), 8.68 (1 H, d, J 6.04), 9.33 (1 H, s); m/z 246
(Mϩ). (Found: Mϩ, 246.0442).
Abramovitch, D. H. Hey and R. D. Mulley, J. Chem. Soc., 1954,
4263; ( f ) R. A. Abramovitch, Can. J. Chem., 1960, 38, 2273.
3 (a) P. A. S. Smith and J. H. Boyer, J. Am. Chem. Soc., 1951, 73, 2626;
(b) R. A. Abramovitch, K. A. H. Adams and A. D. Notation,
Can. J. Chem., 1960, 38, 2152; (c) P. J. Bunyan and J. I. G. Cadogan,
J. Chem. Soc., 1963, 42; (d) R. A. Abramovitch, J. Chem. Soc., 1964,
2175; (e) T. Kametani, K. Ogasawara and T. Yamanaka, J. Chem.
Soc. C, 1968, 1006.
5-Methylsulfonyl-ä-carboline 9d. According to the typical
procedure, 9d was obtained from the reaction using 7d (237.9
mg, 0.58 mmol). Recrystallization from acetone–n-hexane gave
needles (119.3 mg, 84%), mp 153–154 ЊC; νmax(KBr)/cmϪ1 1358
and 1115 (Found: C, 58.55; H, 4.12; N, 11.29; S, 13.21%);
δH 3.03 (3 H, s), 7.43 (1 H, dd, J 4.67, 8.52), 7.51–7.56 (1 H, m),
7.64 (1 H, dt, J 1.37, 8.24), 8.19 (1 H, d, J 8.52), 8.35 (1 H, d,
J 7.69), 8.45 (1 H, dd, J 1.37, 8.52), 8.71 (1 H, dd, J 1.37, 4.95);
m/z 246 (Found: Mϩ, 246.0465).
4 P. Rocca, F. Marsais, A. Godard and G. Quéguiner, Tetrahedron,
1993, 49, (a) 49; (b) 3325; (c) Tetrahedron Lett., 1993, 34, 7917;
(d) J. Heterocycl. Chem., 1995, 32, 1171.
5 (a) A. S. Guram, R. A. Rennels and S. L. Buchwald, Angew. Chem.,
Int. Ed. Engl., 1995, 34, 1348; (b) J. F. Louie and J. F. Hartwig,
Tetrahedron Lett., 1995, 36, 3609.
6 D. E. Ames and D. Bull, Tetrahedron, 1982, 38, 383.
7 (a) T. R. Kelly, Q. Li and V. Bhushan, Tetrahedron Lett., 1990,
31, 161; (b) J. K. Stille, Angew. Chem., Int. Ed. Engl., 1986, 25, 508;
(c) T. R. Bailey, Tetrahedron Lett., 1986, 27, 4407; (d) A. M.
Echavarren and J. K. Stille, J. Am. Chem. Soc., 1987, 109, 5486.
8 (a) Y. Akita, A. Inoue, K. Yamamoto, A. Ohta, T. Kurihara and
M. Shimizu, Heterocycles, 1985, 23, 2327; (b) Y. Akita, Y. Itagaki,
S. Takizawa and A. Ohta, Chem. Pharm. Bull., 1989, 37, 1477;
(c) A. Aoyagi, A. Inoue, K. Koizumi, R. Hashimoto, K. Tokunaga,
K. Gohma, J. Komatsu, K. Sekine, A. Miyafuji, J. Kunoh, R.
Honma, Y. Akita and A. Ohta, Heterocycles, 1992, 33, 257;
(d) A. Ohta, Y. Akita, T. Ohkuwa, M. Chiba, R. Fukunaga,
A. Miyafuji, T. Nakata and N. Tani, Heterocycles, 1990, 31, 1951.
9 L. Estel, F. Linard, F. Marsais, A. Godard and G. Quéguiner,
J. Heterocycl. Chem., 1989, 26, 105.
9-(Methylsulfonyl)carbazole 14b. According to the typical
procedure, 14b was obtained from the reaction using 13 (137.2
mg, 0.34 mmol). Recrystallization from n-hexane gave needles
(39.2 mg, 47%), mp 108–109 ЊC (Found: C, 63.70; H, 4.49;
N, 5.74; S, 13.10. C13H11NO2S requires C, 63.66; H, 4.52; N,
5.71; S, 13.07%); νmax(KBr)/cmϪ1 1350 and 1120; δH 2.99 (3 H,
s), 7.41–7.54 (4 H, m), 8.03 (2 H, d, J 7.69), 8.18 (2 H, d, J 8.24);
m/z 245 (Mϩ) (Found: Mϩ, 245.0506. Calc. for C13H11NO2S: M,
245.0510).
References
10 G. J. Fox, J. D. Hepworth and G. Halias, J. Chem. Soc., Perkin
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1 (a) J. V. Greenhill, in Comprehensive Heterocyclic Chemistry, eds.
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Heterocycl. Chem., 1964, 3, 79.
2 (a) B. Witkop, J. Am. Chem. Soc., 1953, 75, 3361; (b) A. Molina,
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Rodrigo and M. Ballesteros, J. Org. Chem., 1996, 61, 5587; (d)
11 C. Combet-Farnoux and M. Miocque, J. Heterocycl. Chem., 1985,
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12 The Aldrich Library of 13C and 1H FT NMR Spectra, eds. C. J.
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Paper 9/01088B
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J. Chem. Soc., Perkin Trans. 1, 1999, 1505–1510