Studies of palladium-catalyzed coupling reactions for preparation of hindered 3-arylpyrroles relevant to (-)-rhazinilam and its analogues

Article abstract of DOI:10.1139/v01-156

Suzuki cross-coupling reactions of 3-pyrroleboronic acid derivatives with haloaromatics and the reverse process i.e., the coupling of 3-iodo(bromo)pyrroles with arylboronic acids have been investigated as a potential key step in the synthesis of (-)-rhazinilam and analogues. It was found that 3-iodo-2-formyl-1-tosylpyrroles efficiently coupled with a variety of arylboronic acids in the presence of PdCl₂(dppf) as catalyst. This catalytic system is compatible with a broad spectrum of arylboronic acids - electron-rich, electron-poor, hindered, heterocyclic - which easily coupled with the pyrrole substrate.

Full text of DOI:10.1139/v01-156

1827
Studies of palladium-catalyzed coupling reactions
for preparation of hindered 3-arylpyrroles relevant
to (–)-rhazinilam and its analogues
Léon Ghosez, Cécile Franc, Frédéric Denonne, Claire Cuisinier, and
Roland Touillaux
Abstract: Suzuki cross-coupling reactions of 3-pyrroleboronic acid derivatives with haloaromatics and the reverse pro-
cess i.e., the coupling of 3-iodo(bromo)pyrroles with arylboronic acids have been investigated as a potential key step in
the synthesis of (–)-rhazinilam and analogues. It was found that 3-iodo-2-formyl-1-tosylpyrroles efficiently coupled
with a variety of arylboronic acids in the presence of PdCl2(dppf) as catalyst. This catalytic system is compatible with
a broad spectrum of arylboronic acids — electron-rich, electron-poor, hindered, heterocyclic — which easily coupled
with the pyrrole substrate.
Key words: 2-substituted-3-arylpyrroles, biaryls, coupling reactions, arylboronic acids, palladium coupling, catalysis.
Résumé : Nous avons étudié les réactions de couplage de Suzuki entre les acides 3-pyrroleboroniques et divers aroma-
tiques halogénés ainsi que les réactions inverses de couplage entre les 3-iodo(bromo)- pyrroles avec des acides boroni-
ques aromatiques. Cette réaction de couplage pourrait être une étape clé dans la synthèse du (–)-rhazinilame. Nous
avons découvert que les 3-bromo- et 3-iodo-2-formyl-1-tosylpyrroles pouvaient être couplés efficacement avec un grand
nombre d’acides boroniques en utilisant PdCl2(dppf) comme catalyseur. Ce catalyseur permet d’introduire facilement
une grande diversité d’acides arylboroniques (riches ou pauvres en électrons, encombrés ou hétérocycliques) en position
3 du pyrrole.
Mots clés : pyrroles 2-substitutés-3-halogénés, biaryles, réactions de couplage, acides arylboroniques, couplage au palla-
dium, catalyse.
Ghosez et al. 1839
Introduction
the presence of Pd0 or Ni0 catalysts are nowadays part of the
armamentarium of synthetic chemists (for a recent review
see ref. 6). The palladium-catalyzed cross-coupling of aryl-
boronic acids with aryl bromides or iodides was first de-
scribed by Suzuki and co-workers (for recent reviews, see
ref. 7). It has been shown to be applicable to the coupling of
pyrrole derivatives with other aromatic compounds (8, 9).
We selected a Suzuki coupling reaction of 3 with 4 as an at-
tractive approach towards 2 since: (i) it is highly convergent;
(ii) aryl- and heteroaryl halides as well as boron derivatives
are easily available and readily undergo the cross-coupling
reaction (see for example refs. 10, 11); (iii) the presence of a
carbonyl or a carboxyl group at C-2 of the pyrrole should al-
low numerous transformations; (iv) a tosyl group on nitro-
gen should be a good model for a polymer-bound
arylsulfonic group. An account of our first results was pub-
lished in 1999 (12). Two more recent papers also report the
The pyrrole ring is common to many compounds which
have found applications in the pharmaceutical field (1) and
also in material sciences (see for example ref. 2). Not sur-
prisingly, they have represented a continuous challenge for
synthetic chemists (1, 3). In the context of a total synthesis
of the alkaloid (–)-rhazinilam 1, an inhibitor of microtubules
disassembly (4) (Scheme 1), we became interested in the
development of a convenient synthetic route towards 1,2-
disubstituted-3-aryl pyrroles. Our goal was to develop a
method applicable to the synthesis of the natural product and
a large variety of simpler analogues 2.
A literature survey indicated that efficient methods of syn-
thesis of 1,2,3-trisubstituted pyrroles are not numerous (5).
Most of them give rather low yields or lack generality. On
the other hand, coupling reactions of aromatic compounds in
Received April 20, 2001. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on November 22, 2001.
This paper is dedicated to Professor Victor Snieckus in recognition of his important contribution to the development of organic
synthesis.
L. Ghosez,1,2 C. Franc, F. Denonne,1 C. Cuisinier, and R. Touillaux. Département de chimie, Université Catholique de Louvain,
place Louis Pasteur, 1, B-1348 Louvain-la-Neuve, Belgique.
1Institut Européen de Chimie et Biologie, ENSCPB, 16, Avenue Pey Berland, 33607 Pessac CEDEX, France.
2Corresponding author (fax: 32 10 47 27 88; e-mail: ghosez@chim.ucl.ac.be or l.ghosez@iecb-polytechnique.u-bordeaux.fr).
Can. J. Chem. 79: 1827–1839 (2001)
© 2001 NRC Canada
DOI: 10.1139/cjc-79-11-1827

1828
Can. J. Chem. Vol. 79, 2001
Scheme 1.
Scheme 3. Reagents and conditions: (i) t-BuLi in hexane, THF,
–78°C then B(OMe)3, –78°C then H2O–MeOH, work-up;
(ii) compound 9 (1.5 equiv), ArX (1 equiv), benzene–water–
methanol (5:1.5:1), Ba(OH)2 (1.5 equiv), Pd(PPh3)4 (5%), reflux.
N
Et
Ar
Y
H
N
+
Ar
X
R2
Z
B(OH)2
Br
Ar
N
N
R1
Ts
i
ii
O
Ph
Ph
Ph
N
N
N
2
3
4
1
Ts
Ts
Ts
X, Y = Br, I, B(OR')2
Z = COR2, CO2R3
6a
9
10
a, Ar = Ph, 56%
b, Ar = p-MeOPh, 53%
c, Ar = p-NO2Ph, 36%
d, Ar = o-NO2Ph, 35%
Scheme 2. Reagents and conditions: (i) TsNH2, BF3·OEt2, tolu-
ene, ª; (ii) HCCCH(OEt)2, n-BuLi, ether, –78°C then ZnCl2 in
ether, –78°C; (iii) 8.8 M HBr(aq) (9.5 equiv), 15 min, 80°C or
57% HI(aq) (7 equiv), 1 h, –10°C; (iv) KMnO4 (3 equiv), H2O–
dioxane, 1 h, rt; (v) same as (iv) but at 90°C, yield from 5.
much faster. At room temperature, the products were the ex-
pected aldehydes 7a, 7b. At 90°C, hydrolytic cleavage of the
tosyl group simultaneously occurred to yield 8a, 8b.
Coupling reactions with 1-tosyl-2-styrylpyr-
role boronic acid (9)
We first studied the synthesis of pyrroleboronic acid 9 and
its coupling reaction with aryl iodides. Compound 9 was ob-
tained from 6a by a metal-bromide exchange with t-BuLi
followed by treatment with trimethylborate and hydrolysis
(Scheme 3).
Compound 9 was used without purification. The coupling
reactions were performed under the conditions described by
Muchowski (8a) for related cases. Yields were moderate
with phenyl iodide and o-iodoanisole. However the presence
of an electron-withdrawing nitro group in para or ortho po-
sition of the iodide considerably lowered the yields. The
coupling of 9 with o-iodonitrobenzene was of special inter-
est in the context of the rhazinilam problem. Next to the ex-
pected coupling product 10d, we found a reduction product
11 (30%) and, more surprisingly, a compound 12 (25%) result-
ing from a coupling at position 5 of pyrrole 9 (Scheme 4).
We were able to show that the reduction product was
formed as a result of the incomplete conversion of the
organolithium intermediate into the corresponding boronic
acid. Product 12 could be the result of an isomerization of
the 3-lithio compound to the thermodynamically more stable
5-lithio isomer. There was little hope to improve the yields
of 10d by bringing the temperature further down; this would
probably slow down the isomerization of the organolithium
compound but also increase the amount of reduction prod-
uct. We thus decided to study the Suzuki coupling reactions
between 3-bromo- or 3-iodo-pyrrole derivatives 6a, 6b and
7a, 7b with various arylboronic acids.
use of a cross-coupling reaction involving substituted 3-
iodopyrroles for the synthesis of analogues of (–)-rhazinilam
(13). We now report the full details of our studies.
Synthesis of 1,2-disubstituted 3-halopyrroles
Our strategy required an easy access to 3-halopyrroles 3
(Y = Br, I) and the corresponding boronic acid (Y = B(OH)2).
We selected the efficient method described by Masquelin
and Obrecht (3) using aldimines and acetylenic acetals or
ketones as starting materials. Compound 5 was obtained in
excellent yields as described (Scheme 2).
However, very low yields (<3%) of 6a were obtained from
the treatment of 5 with 2.4 M aq HBr as described by the
authors. The use of a more concentrated HBr solution at
80°C for 15 min gave 6a in 78% yield. Similarly, treatment
of 5 with 57% aq HI gave a 71% yield of 6b if the tempera-
ture was kept at –10°C to avoid degradation of the product
under these strongly acidic conditions. This practical se-
quence has been applied to the preparation of up to 23 g of
6a and 43 g of 6b.
Pyrroles are extremely sensitive to oxidizing agents (1). How-
ever, the selective oxidation of the olefinic double bond of a
3-vinylpyrrole bearing an electron-withdrawing benzenesulfonyl
group on nitrogen has been successfully performed with
NaIO4–OsO4 cat (14). However, under these conditions, the
oxidation of the styryl double bond of 6a, 6b took approxi-
mately 5 days. The oxidative cleavage with aq KMnO4 was
Study of the coupling conditions of 1,2-
disubstituted-3-halopyrroles with arylboronic
acids
We first examined the reaction of 6b with the commer-
cially available phenylboronic acid 13a. We used Ba(OH)2
(15) as base (Scheme 5, Table 1). In the presence of Pd(PPh3)4
as catalyst, no coupling product 10a was obtained in solvent
mixtures (entries 1 and 2) which had been successfully used
in similar coupling reactions (6, 7).
© 2001 NRC Canada

Ghosez et al.
1829
Scheme 4.
H
H2O – MeOH
Ph
N
Ts
(30%)
11
O2N
Br
Li
1. BOMe)3
2. H2O – MeOH
t-BuLi
Ph
N
Ph
N
-78°C
3. coupling
Ph
N
Ts
Ts
Ts
10d (35%)
6a
NO2
1. BOMe)3
2. H2O – MeOH
Ph
N
Ph
Li
N
3. coupling
Ts
Ts
12 (25%)
Scheme 5.
X
X
I
Ba(OH)2
catalyst
solvent
H
B(OH)2
+
+
Ph
N
Ph
Ph
N
N
reflux
Ts
Ts
Ts
16 a: X = H
b: X = NO2
10 a,b
6b
11
Table 1. Conditions for the cross-coupling of 6b with phenyl- and o-nitrophenylboronic acids.
Yield of Yield of
Entry
X
Catalyst
Solvent
T (°C)
10 (%)
11 (%)
1
2
3
4
5
6
7
8
H
H
H
NO2
NO2
NO2
NO2
NO2
5% Pd(PPh3)4
5% Pd(PPh3)4
5% Pd(PPh3)4
10% Pd(PPh3)4
10% PdCl2(PPh3)2
10% PdCl2dppe
10% PdCl2dppf
10% PdCl2dppf
MeOH–C6H6–H2O (1:3:2)
DME–H2O (2:1)
DMF–H2O (4:1)
DMF–H2O (4:1)
DMF–H2O (4:1)
DMF–H2O (4:1)
DMF–H2O (4:1)
DMF–H2O (4:1)
80
80
80
120
120
120
120
120
0
0
—
—
—
64b
50b
58b
—
86a
36b
50b
42b
80a
73a
—
aIsolated pure coupling products.
bNMR yields.
Table 2. Hydrodeiodination of 6b.
Scheme 6.
D
I
H
Entry
Base
Solvent
Product
10% Pd(PPh3)4
120°C
1
2
3
4
5
None
DMF–H2O (1:1)
MeCONMe2–H2O (1:1)
DMF–D2O (1:1)
DCONMe2–H2O (1:1)
DCON(CD3)2–H2O (1:1)
6b
6b
11
11
d-1
+
Sty
Sty
N
N
Sty
Ba(OH)2
Ba(OH)2
Ba(OH)2
Ba(OH)2
N
Ts
Ts
Ts
11
Sty =
Ph
6b
d - 11
Running the coupling reaction in a more polar solvent
(entry 3) led to a high yield of 10a. The accelerating effect
of a polar solvent such as DMF had been used before to ef-
fect Suzuki coupling reactions (15b, 15e) of bromo- and
iodo-pyrroles (9a). However, when we applied these condi-
tions to the coupling of 6b with the electron-deficient and
hindered o-nitrophenylboronic acid, we observed a dramatic
decrease of the yield of coupling product 10b, even at higher
temperatures (entry 4). The presence of chloride ion (16) or
the use of a bidentate phosphine (17) such as dppe (18) (en-
tries 5 and 6) did not much improve the yield of coupling
product 10b. The major product 11 of the reaction resulted
© 2001 NRC Canada

1830
Can. J. Chem. Vol. 79, 2001
Scheme 7.
I
I
I
L
Ar Pd
L
L
Ar Pd
L
L
Pd
O
H
O
N
N
Ar
I
OH
H
Ph
N
L
Ts
HCO2H
I
OH
6b
H
L
L
Pd
L
Pd
L
Ar
H
Ar
N
Ph
N
Ts
11
H
N
Scheme 8.
Scheme 9.
O2N
I
Ar
X
ArB(OH)2, 10% PdCl2(dppf)
Table 1, entry 7
Ba(OH)2, DMF: H2O (4:1)
80°C
CHO
CHO
N
N
CHO
7a,b
CHO
N
N
Ts
Ts
Ts
Ts
7b
13
13a
X = I: 98%
X = Br: 75%
86% KOH (8 equiv)
(D3C)2NC(O)D (entry 5). These observations were rational-
ized by the mechanism outlined in Scheme 7.
I
Table 1, entry 7
We have successfully applied the conditions of Table 1,
entry 7 to the coupling of 2-formyl-3-halo-1-tosylpyrroles
7a, 7b with o-nitrophenylboronic acid (Scheme 8). Under
these conditions, Ba(OH)2 did not add to the aldehyde func-
tion of 7a, 7b (NMR control) and was thus available for the
coupling reaction.
No coupling product
CHO
N
H
8b
100% MeI – NaH
I
O2N
As expected, the reaction of iodopyrrole was much faster
than that of the corresponding bromide and gave a higher
yield of 13a. The coupling reaction could also be effected in
very high yield on the N-methylated pyrrole but did not oc-
cur when nitrogen was unsubstituted.
Table 1, entry 7
CHO
N
CHO
N
Me
Me
98%
from the reductive cleavage of the carbon—iodine bond. We
also observed variable amounts of nitrobenzene resulting from
a base-catalyzed hydrolysis of o-nitrophenylboronic acid (19).
The use of 1,1>-bis(diphenylphosphino)ferrocene (dppf)
bidentate ligand (20a, 20b; for a more recent example see
ref. 20c) on palladium led to a significant increase of rate
and yield (entries 7 and 8); the reaction was over in a few
minutes even at 80°C and yields of coupling product 10b
were up to 80%. After completion of our work, Buchwald,
Hermann, Fu and co-workers (21) reported new efficient cata-
lysts for Suzuki cross-coupling reactions. However, no cross-
coupling reactions involving a pyrrole derivative was de-
scribed and we have not examined these new catalysts.
The palladium-catalyzed dehalogenation of aromatic com-
pounds has been abundantly documented (review see ref. 22).
Hydrodehalogenation products have sometimes been observed
as by-products of Pd-catalyzed cross-coupling reactions (23).
In these cases, water or tertiary amines have been assigned
the role of hydride donors. In Table 2, we describe a study
of the hydrodeiodination reaction of 6b (Scheme 6).
Generalization of the coupling reaction
With these optimized conditions in hand, we carried out
the cross-coupling reaction of 7b with a wide variety of aryl
and heteroarylboronic acids (Scheme 9, Table 3).
High yields of cross-coupled 1,2-disubstituted-3-arylpyrroles
have been obtained. The reaction tolerates both electron-rich
and electron-poor arylboronic acids. It could also be applied
successfully to the coupling of 7b with the sterically hin-
dered mesitylboronic acid.
The electron-poor 2-nitro-6-(trifluoromethyl)phenylboronic
acid 14 was prepared by nitration of 2-(trifluoromethyl)-
phenylboronic acid (Scheme 10). The conditions described
for the nitration of boric acid (28), gave no reaction and sul-
furic acid had to be used to obtain 14 in a 42% yield, to-
gether with its isomer 15 (12%). However, 2-nitro-6-
(trifluoromethyl)phenylboronic acid 14 gave no coupling
product. Interestingly, the corresponding aniline 16 gave 3-
tosyl-9-(trifluoromethyl)-3H-pyrrolo[2,3-c]-quinoline 17 in
26% yield (Scheme 10).
This illustrates a further application of this coupling reaction
for the synthesis of pyrroles fused to other heterocycles.
However, at this stage, we did not try to optimize the reaction.
In conclusion, we have fulfilled our goal and developed a
practical synthetic route towards 1,2-disubstituted-3-aryl-
(heteroaryl)pyrroles. The method should offer the possibility of
It shows that: (i) no hydrodeiodination was observed in
the absence of base or when DMF was replaced by N,N-
dimethylacetamide (entries 1 and 2); (ii) no incorporation of
deuterium was observed in the presence of D2O or
Me2NC(O)D (entries 3 and 4); (iii) incorporation of deute-
rium at C-3 of 11 occurred when the reaction was run in
© 2001 NRC Canada

Ghosez et al.
1831
Table 3. Cross-coupling reactions of iodopyrrole 7b with aryl- and
heteroarylboronic acids.
ArB(OH)2
Ref.
Yielda
ArB(OH)2
Ref.
Yielda
Me
NO2
B(OH)2
Me
B(OH)2
(24)
98
(25)
61
Me
b
NO2
B(OH)2
B(OH)2
CF3
-
92
B(OH)2
B(OH)2
b
66
85
b
88
84
N
NO2
B(OH)2
(24)
(26)
B(OH)2
S
NO2
OMe
B(OH)2
b
88
B(OH)2
N
(27)
77
BOC
aYield of isolated pure products.
bCommercially available.
Scheme 10.
No coupling
CF3
CF3
O2N
+
CF3
B(OH)2
HNO3 - H2SO4
Ac2O, t < 6°C
B(OH)2
B(OH)2
NO2
14
15
F3C
N
F3C
I
CF3
10% PdCl2(dppf)
NH2
+
N
CHO
N
Ts
Ba(OH)2
DMF: H2O (4:1)
80°C
B(OH)2
CHO
N
Ts
NH2
7b
16
Ts
17
building libraries of a wide variety of 2-substituted-3-
arylpyrroles or polycyclic heteroaromatics derived therefrom
using a polystyrene-bound 2-formyl-3-iodo-1-sulfonylpyrrole.
Further applications of these findings to the total synthesis
of (–)-rhazinilam and analogues will be reported in due course.
Experimental
General
Melting points were taken on Buchi Melting Point B-545
or on a Microthermal 8103 apparatus. NMR experiments
© 2001 NRC Canada

1832
Can. J. Chem. Vol. 79, 2001
were performed on GEMINI-200, GEMINI-300, and Brucker
AM-500 spectrometers. Internal standards were TMS
(1H NMR) and CDCl3 (77.23 ppm, 13C NMR). IR spectra
were recorded on PerkinElmer 681 and Bio-Rad FTS 135
spectrometers (polystyrene ref. 1601 cm–1). Mass spectra
were recorded on Varian MAT-44 or FINNIGAN-MAT
TSQ-70 spectrometers (electronic impact 70 eV or chemical
ionization 100 eV with 2 bar isobutane as the ionizing gas).
Tetrakis(triphenylphosphine)palladium (29) and dichloro-
(diphenylphosphinoferrocene)palladium (30), o-nitrophenyl-
boronic and p-nitrophenylboronic acids were prepared as
described in the literature (28). Unless otherwise noted, the
other boronic acids used were purchased from commercial
sources. THF and toluene were distilled from sodium-benzo-
phenone. Organic phases were dried over magnesium sul-
phate. Solvents were degassed by bubbling argon for at least
15 min. Chromatographic separations were performed with
silica gel purchased from Merck (thickness 40–63 m)
aqueous phase was extracted with ether, the combined or-
ganic layers washed with brine, dried and concentrated in
vacuo. Purification by flash chromatography on silica gel
(10% diethyl ether in petroleum ether) Yield of 4: 19 g,
71%, pale solid (mp 119°C). Rf = 0.7 (30% diethyl ether in
C+
petroleum ether). MS (EI) m/z: 449 (100, M ), 335 (18),
279 (18), 167 (33). HRMS calcd. for C19H16INO2S:
1
448.9946; found: 448.9950. IR: 1369, 1175, 670. H NMR
(CDCl3, 500 MHz) d: 7.65 (d, 3J
NSO2C(CHCH)2CCH3), 7.49 (d, 3J
=
=
8.5 Hz, 2H,
8.3 Hz, 2H,
8.3 Hz, 2H,
CHC(CHCH)2CH), 7.39 (t, 3J
=
3
CHC(CHCH)2CH), 7.34 (d, J = 3.4 Hz, 1H, NCHCH), 7.31
(m, 1H, CHC(CHCH)2CH), 7.29 (d, 3J = 16.5 Hz, 1H,
3
CHCHC(CHCH)2CH), 7.21 (d, J = 8.5 Hz, 2H, NSO2C-
(CHCH)2CCH3), 7.12 (d, 3J = 16.5 Hz, 1H, CHCHC-
3
(CHCH)2CH), 6.43 (d, J = 3.4 Hz, 1H, NCHCH), 2.37 (s,
3H, CH3). 13C NMR (CDCl3, 500 MHz) d: 145.30 (NSO2C-
(CHCH)2CCH3), 136.53 (CHC(CHCH)2CH), 135.21
(NSO2C(CHCH)2CCH3), 134.74 (CHC(CHCH)2CH), 132.11
(NCC), 129.80 (NSO2C(CHCH)2CCH3), 128.67 (CHCHC-
(CHCH)2CH), 128.15 (CHCHC(CHCH)2CH), 127.21 (NSO2C-
(CHCH)2CCH3), 126.50 (CHCHC(CHCH)2CH), 123.71
(NCHCH), 120.64 (NCHCH), 116.24 (CHCHC(CHCH)2CH),
69.16 (NCC), 21.51 (CH3).
3-Bromo-2-styryl-1-tosylpyrrole (6a) (RN: 168030-84-0)
To a solution of (E)-N-(4,4>-diethoxy-1-styrylbut-2-ynyl)-
4-toluenesulfonamide (3) (18 g, 45 mmol) in toluene (100 mL)
was added bromohydric acid (48% aqueous, 48 mL, 425 mmol).
The reaction mixture was stirred for 10 min at 80°C and
then allowed to cool to room temperature. It was poured into
ice and ether, sodium hydroxide (14.4 g, 360 mmol) was
then added, and the pH adjusted to 7 with 1 N aqueous so-
dium hydroxide. The aqueous phase was extracted with
ether, the organic layers were washed with brine, dried and
concentrated in vacuo. Purification by flash chromatography
on silica gel (10% diethyl ether in petroleum ether) Yield of
4: 14.1 g, 78%, pale yellow solid (mp 97°C). Rf = 0.38 (30%
diethyl ether in petroleum ether). MS (EI) m/z (IE, 70 eV):
2-Formyl-3-bromo-1-tosylpyrrole (7a)
To a solution of 6a (0.1 g, 0.25 mmol) in dioxane (3 mL)
was added potassium permanganate (0.2 g, 0.75 mmol) and
water (1 mL). The mixture was stirred at room temperature
for 1 h then treated with saturated aqueous sodium thiosulfate
(1 mL), then with 1 N HCl until the mixture was discol-
oured. The aqueous phase was extracted with ethyl acetate,
the combined organic layers were washed with brine, dried
and concentrated in vacuo. Purification by flash chromatog-
raphy on silica gel (20% diethyl ether in petroleum ether).
Yield of 7a: 52 mg, 58%, pale yellow solid (mp 70°C). Rf =
0.54 (40% diethyl ether in petroleum ether). MS (EI) m/z:
C+
C+
403 (100, [M + 2] ), 401 (80, M ), 249 (18, [M + 2-Tos +
C+
C+
H] ), 247 (20, [M-Tos + H] ), 168 (48), 167 (97, (249 and
C+
247 -Br) ), 166 (14), 139 (14). IR: 3149–3025, 1596, 1469,
1371, 1145–1089, 1028, 965. 1H NMR (CDCl3, 500 MHz) d:
C+
C+
329 (15, [M + 2] ), 327 (16, M ), 265 (26, [M + 2-SO2]+),
263 (26, [M – SO2]+), 174 (24, [M + 2-C7H7SO2]+), 172 (23,
[M – C7H7SO2]+), 155 (84, [C7H7SO2]+), 91 (100, [C7H7]+).
3
7.67 (d, J = 8.5 Hz, 2H, NSO2C(CHCH)2CCH3), 7.49 (d,
3J = 8.3 Hz, 2H, CHC(CHCH)2CH), 7.38 (t, J = 8.3 Hz,
3
2H, CHC(CHCH)2CH), 7.36 (d, 3J = 16.5 Hz, 1H,
1
3
IR: 1677, 1373, 1175. H NMR (CDCl3, 300 MHz) d: 9.84
CHCHC(CHCH)2CH), 7.33 (d, J = 3.4 Hz, 1H, NCHCH),
(s, 1H, CHO), 7.87 (d, 3J = 8.4 Hz, 2H, NSO2C(CHCH)2CCH3),
7.70 (d, 3J = 3.3 Hz, 1H, NCHCH), 7.33 (d, 3J = 8.4 Hz, 2H,
3
7.35–7.22 (m, 1H, CHC(CHCH)2CH), 7.23 (d, J = 8.5 Hz,
2H, NSO2C(CHCH)2CCH3), 7.20 (d, 3J = 16.5 Hz, 1H,
3
3
NSO2C(CHCH)2CCH3), 6.48 (d, J = 3.3 Hz, 1H, NCHCH),
CHCHC(CHCH)2CH), 6.35 (d, J = 3.4 Hz, 1H, NCHCH),
2.43 (s, 3H, CH3). 13C NMR (CDCl3, 75 MHz) d:
176.89 (CHO), 145.46 (NSO2C(CHCH)2CCH3), 133.79
(NSO2C(CHCH)2CCH3), 129.24 (NSO2C(CHCH)2CCH3),
128.52 (NCH), 127.53 (NSO2C(CHCH)2CCH3), 127.33
(NCCHO), 115.11 (CBr), 114.84 (NCHCH), 20.97 (CH3).
Anal. calcd. for C12H10BrNO3S: C 43.92, H 3.07, N 4.27;
found: C 43.80, H 2.78, N 4.15.
2.36 (s, 3H, CH3). 13C NMR (CDCl3, 125 MHz) d: 145.33
(NSO2C(CHCH)2CCH3), 136.81 (CHC(CHCH)2CH), 135.27
(NSO2C(CHCH)2CCH3),
133.81
(CHC(CHCH)2CH),
129.19 (NCC), 129.85 (NSO2C(CHCH)2CCH3), 128.65
(CHCHC(CHCH)2CH), 128.05 (CHCHC(CHCH)2CH), 127.13
(NSO2C(CHCH)2CCH3), 126.47 (CHCHC(CHCH)2CH), 122.32
(NCHCH), 116.15 (NCHCH), 115.18 (CHCHC(CHCH)2CH),
102.13 (NCC), 21.48 (CH3).
2-Formyl-3-iodo-1-tosylpyrrole (7b) (RN: 233770-15-5)
To a solution of 6b (17 g, 37.8 mmol) in dioxane (300 mL)
was added potassium permanganate (17.9 g, 113.4 mmol)
and water (150 mL). The mixture was stirred at room tem-
perature for 1 h, then treated with a saturated aqueous so-
dium thiosulfate (100 mL) and with 1 N HCl until the
mixture was discoloured. The mixture was stirred overnight.
The pale yellow precipitate was filtered, dissolved in ethyl
acetate, washed with brine, dried and concentrated in vacuo.
3-Iodo-2-styryl-1-tosylpyrrole (6b) (RN: 233770-17-7)
To a solution of (E)-N-(4,4>-diethoxy-1-styrylbut-2-ynyl)-
4-toluenesulfonamide 5 (3) (25 g, 61 mmol) in toluene
(200 mL) at –10°C was added iodohydric acid (57% aque-
ous, 57 mL, 424 mmol). The mixture was stirred for 1 h at
room temperature then poured into ice and ether. Sodium
hydroxide (13.3 g, 333 mmol) was then added and the pH
adjusted to 7 with 1 N aqueous sodium hydroxide. The
© 2001 NRC Canada

Ghosez et al.
1833
Purification by recrystallization from cyclohexane and ether.
Yield of 7b: 8.3 g, 58%, pale yellow solid (mp 104°C). Rf =
0.50 (30% diethyl ether in petroleum ether). MS (EI) m/z
(70eV): 375 (46, M+), 311 (44), 220 (34), 155 (72), 91
(100). IR: 3140, 1682, 1429, 1317, 1175, 668. 1H NMR
(CDCl3, 300 MHz) d: 9.79 (s, 1H, CHO), 7.84 (d, 3J =
8.3 Hz, 2H, NSO2C(CHCH)2CCH3), 7.66 (d, 3J = 3.3 Hz, 1H,
reaction was quenched by adding 0.5 mL of methanol and
0.5 mL of water. The solution was poured into water (20 mL),
the aqueous phase extracted with diethyl ether. The com-
bined organic phases were washed with brine, dried and
concentrated in vacuo. The crude product was used in the
coupling reaction without further purification.
3
NCHCH), 7.33 (d, J = 8.3 Hz, 2H, NSO2C(CHCH)2CCH3),
Coupling reactions
6.60 (d, 3J = 3.3 Hz, 1H, NCHCH), 2.42 (s, 3H, CH3).
13C NMR (CDCl3, 75 MHz) d: 178.7 (CHO), 145.89
(NSO2C(CHCH)2CCH3), 134.45 (NSO2C(CHCH)2CCH3),
130.00 (NCH), 129.76 (NSO2C(CHCH)2CCH3), 129.38
(NCCHO), 127.84 (NSO2C(CHCH)2CCH3), 120.58 (NCHCH),
82.17 (CI), 21.51 (CH3). Anal. calcd. for C12H10INO3S:
C 38.42, H 2.69, N 3.73; found: C 38.32, H 2.49, N 3.62.
Method A refers to the coupling reaction of 2-styryl-1-
tosylpyrrole boronic acid 9 with iodoaryls: A mixture of
aryliodide (1 equiv), crude boronic acid 9 (1.5 equiv,
0.16 M), barium hydroxide octahydrate (1.5 equiv), and
tetrakis(triphenylphosphine)palladium (0.05 equiv) in a de-
gassed mixture of water, methanol, and benzene (3:2:10)
was refluxed for 16 h. It was then concentrated and the
crude material was dissolved in ethyl acetate and filtered on
a Celite® pad to remove metallic palladium. The filtrate was
then dried and concentrated in vacuo. The crude product was
purified by flash chromatography on silica gel.
Method B refers to the coupling reaction of 3-iodo-2-
styryl-1-tosylpyrrole 6b with an arylboronic acid: A mixture
of 3-iodo-2-styryl-1-tosylpyrrole 6b (1 equiv, 0.044 M), boronic
acid (1.5 equiv), barium hydroxide octahydrate (1.5 equiv),
and catalyst (0.05 or 0.1 equiv) in a degassed mixture of
DMF and water (4:1) was placed in a bath which had been
preheated to 120°C. After 20 min, it was cooled to room
temperature and diluted with ethyl acetate and water. After
filtration on a Celite® pad, the solution was washed with wa-
ter, brine, dried and concentrated in vacuo. The crude prod-
uct was purified by flash chromatography on silica gel.
Method C refers to the coupling reaction of 2-formyl-3-
iodo-1-tosylpyrrole 7b with an arylboronic acid: A mix-
ture of 2-formyl-3-iodopyrrole (1 equiv, 0.044 M), aryl
boronic acid (1.5 equiv), barium hydroxide octahydrate
(1.5 equiv) and dichloro(diphenylphosphinoferrocene)palla-
dium(II) (0.1 equiv) in a degassed mixture of DMF and wa-
ter (4:1) was placed in a bath which had been preheated to
80°C. After 5 min, it was cooled to room temperature and
diluted with ethyl acetate and water. After filtration on a
Celite® pad, the solution was washed with water, brine, dried
and concentrated in vacuo. The crude product was purified
by flash chromatography on silica gel.
3-Bromo-2-formylpyrrole (8a)
To a solution of 6a (0.50 g, 1.24 mmol) in dioxane (10 mL)
was added potassium permanganate (0.59 g, 3.73 mmol) and
water (3 mL). The mixture was refluxed overnight then al-
lowed to cool to room temperature and filtered on a Celite®
pad. The organic layer was washed with sodium thiosulfate,
brine, dried and concentrated in vacuo. Purification by flash
chromatography on silica gel (30% diethyl ether in petro-
leum ether). Yield of 8a: 134 mg, 62%, white solid (mp
118°C). Rf = 0.40 (40% diethyl ether in petroleum ether).
C+
C+
MS (EI) m/z (70 eV): 175 (94, [M + 2] ), 173 (100, M ),
146 (20, [M + 2-COH]+), 144 (20, [M – COH]+). IR: 3238,
1635. H NMR (CDCl3, 500 MHz) d: 9.82 (br s, 1H, NH),
9.59 (s, 1H, CHO), 7.07 (ddd, J = 3.2 Hz, J = 2.6 Hz, J =
1.1 Hz, 1H, NCHCH), 6.39 (dd, J = 2.6 Hz, J = 2.4 Hz,
1H, NCHCH). 13C NMR (CDCl3, 125 MHz) d: 178.47
(CHO), 129.0 (NCCHO), 125.77 (NCH), 114.24 (NCHCH),
109.34 (CBr). Anal. calcd. for C5H4BrNO: C 34.51, H 2.32,
N 8.05; found: C 34.79, H 2.04, N 7.78.
1
3
3
5
3
4
3-Iodo-2-formylpyrrole (8b) (RN: 40566-07-2)
To a solution of 6a (0.1g, 0.22 mmol) in dioxane (2 mL)
was added potassium permanganate (0.1g, 0.66 mmol) and
water (0.6 mL). The mixture was refluxed overnight then
allowed to cool to room temperature and filtered on a
Celite® pad. The organic layer was then washed with sodium
thiosulfate, brine, dried and concentrated in vacuo. Purifica-
tion by flash chromatography on silica gel (30% diethyl
ether in petroleum ether). Yield of 8b: 20 mg, 40%, white
solid (decomposed at 128°C). Rf = 0.57 (50% diethyl ether
3-Phenyl-2-styryl-1-tosylpyrrole (10a)
Method A: 1.36 g (3.71 mmol) of the crude boronic acid 9,
0.5 g (2.47 mmol) of iodobenzene, 1.17 g (3.71 mmol) of
barium hydroxide octahydrate, 57 mg (0.05 mmol) of
tetrakis(triphenylphosphine)palladium. Eluent: 10% of diethyl
ether in petroleum ether. Yield of 10a: (560 mg, 56%).
C+
in petroleum ether). MS (EI) m/z (70 eV): 221 (100, M ),
220 (100, [M – H]+), 192 (16, [M – COH]+). IR: 3255, 1635,
1
1340, 758, 737. H NMR (CDCl3, 200 MHz) d: 9.90 (br s,
1H, NH), 9.45 (s, 1H, CHO), 7.12–7.05 (m, 1H, NCHCH),
3
4
6.53 (t, J = J = 2.55 Hz, 1H, NCHCH). 13C NMR (CDCl3,
50 MHz) d: 180.00 (CHO), 130.78 (CCHO), 126.98 (NCH),
119.21 (NCHCH), 77.23 (CI).
Method B: 0.3 mg (0.7 mmol) of the 3-iodo-2-styryl-1-
tosylpyrrole 6b, 0.5 mg (1 mmol) of phenylboronic acid,
0.17 mg (1 mmol) of barium hydroxide octahydrate, and
38 mg (0.03 mmol) of tetrakis(triphenylphosphine)palladium.
Eluent: 10% diethyl ether in petroleum ether. Yield of 10a:
240 mg, 90%, white solid (mp 140°C). Rf = 0.74 (30% diethyl
ether in petroleum ether). MS (CI) m/z: 400 (100, [M + 1]+),
2-Styryl-1-tosylpyrrole boronic acid (9)
To a solution of 3-bromo-2-styryl-1-tosylpyrrole 6a in dry
THF (12 mL) at –78°C was added t-BuLi (1.7 M in pentane,
3.3 mL, 5.3 mmol). The mixture was stirred for 25 min and
turned brown. A solution of trimethyl borate (2.8 mL,
25 mmol) in THF (50 mL) at –78°C was then added via can-
nula. The reaction mixture turned orange. After 45 min, the
C+
247 (46, [400 – SO2C6H4CH3] ), 157 (16, [SO2C6H5CH3 +
2H]+). HRMS calcd. for C25H22NO2S: 400.1371; found:
400.1351. IR: 3148–2869, 1369, 1175, 1136. 1H NMR
(CDCl3, 500 MHz) d: 7.68 (d, 3J = 8.4 Hz, 2H,
© 2001 NRC Canada

1834
Can. J. Chem. Vol. 79, 2001
3
NSO2C(CHCH)2CCH3), 7.41 (d, J = 3.4 Hz, 1H, NCHCH),
7.41–7.38 (m, 2H), 7.38 (d, 3J
16.5 Hz, 1H,
7.34–7.22 (m, 7H, CHC(CHCH)2CH and NSO2C-
3
=
(CHCH)2CCH3), 6.40 (d, J = 3.4 Hz, 1H, NCHCH), 6.30
3
CHCHC(CHCH)2CH), 7.32–7.28 (m, 4H), 7.25–7.19 (m,
4H), 7.20 (d, J = 8.4 Hz, 2H, NSO2C(CHCH)2CCH3), 6.38
(d, J = 16.5 Hz, 1H, CHCHC(CHCH)2CH), 2.36 (s, 3H,
3
CH3). 13C NMR (CDCl3, 125 MHz) d: 146.02 (CNO2),
144.96 (NSO2C(CHCH)2C), 142.12 (NO2CCHCHC), 135.98
(NSO2C), 135.73 (CHCHC(CHCH)2CH), 135.23 (CHCHC-
(CHCH)2C), 129.47 (NO2C(CHCH)2C), 128.77 (NSO2C-
(CHCH)2C), 128.41 (CHCHC(CHCH)2CH), 128.40 (NO2C-
(CHCH)2C), 128.05 (CHCHC(CHCH)2CH), 127.97 (NCC),
127.07 (NSO2C(CHCH)2C), 126.00 (CHCHC-(CHCH)2CH),
125.99 (NO2C(CHCH)2C), 125.31 (NCC), 123.45 (NCHCH),
115.46 (CHCHC(CHCH)2CH), 113.04 (NCHCH). Anal.
calcd. for C25H20N2O4S: C 67.55, H 4.54, N 6.30; found:
C 67.82, H 4.40, N 6.09.
3
3
(d, J = 16.5 Hz, 1H, CHCHC(CHCH)2CH), 6.36 (d, J =
3.4 Hz, 1H, NCHCH), 2.35 (s, 3H, CH3). 13C NMR (CDCl3,
125 MHz) d: 144.86 (NSO2C(CHCH)2CCH3), 137.03
(CHC(CHCH)2CH), 135.88 (NSO2C(CHCH)2CCH3), 135.35
(CC(CHCH)2CH), 133.99 (CHC(CHCH)2CH), 129.68
(NSO2C(CHCH)2CCH3), 128.58 (CC(CHCH)2CH), 128.54
(CHC(CHCH)2CH), 128.47 (NCC), 128.41 (CC(CHCH)2CH),
127.68 (CHC(CHCH)2CH), 127.20 (NSO2C(CHCH)2CCH3),
127.17
(CHCHC(CHCH)2CH),
(NCC),
126.76
(CC(CHCH)2CH),
(NCHCH),
126.18
116.35
122.57
(CHCHC(CHCH)2CH), 113.45 (NCHCH), 21.48 (CH3).
Reaction of 2-styryl-1-tosylpyrrole boronic acid and o-
iodonitrobenzene (method A)
3-(o-Methoxyphenyl)-2-styryl-1-tosylpyrrole (10b)
1.36 g (3.71 mmol) of crude boronic acid 9, 0.62 g
(2.47 mmol) of o-iodonitrobenzene, 1.17 g (3.71 mmol) of
barium hydroxide octahydrate, 57 mg (0.05 mmol) of
tetrakis(triphenylphosphine)palladium. Eluent: 10–30% diethyl
ether in petroleum ether. Yield of 11 : 359 mg, 30%; 10d:
385 mg, 35%; and 12: 275 mg, 25%. Rf = 0.26 (30% diethyl
ether in petroleum ether). MS (EI) m/z: 444 (100, M+), 240
(48), 230 (42). HRMS calcd. for C25H20N2O4S: 444.1143;
found: 444.1149. IR: 3160–2853, 1528, 1370–1348, 1172.
Method A: 1.36 g (3.71 mmol) of the crude boronic acid 9,
0.58 g (2.47 mmol) of o-iodomethoxybenzene, 1.17 g
(3.71 mmol) of barium hydroxide octahydrate, 57 mg
(0.05 mmol) of tetrakis(triphenylphosphine)palladium. Eluent:
10% diethyl ether in petroleum ether. Yield of 10c: 0.56 g,
53%, yellow solid (mp 147°C). Rf = 0.56 (30% diethyl ether
in petroleum ether). MS (CI) m/z: 430 (57, [M + 1]+), 275
C+
(100, [M + 1-C7H7SO2] ). HRMS calcd. for C26H24NO3S:
430.1476; found: 430.1459. IR: 1594, 1496, 1369, 1178,
3
4
1H NMR (CDCl3, 500 MHz) d: 8.09 (dd, J = 7.9 Hz, J =
1
3
1137, 671. H NMR (CDCl3, 500 MHz) d: 7.71 (d, J =
3
1.4 Hz, 1H, NO2CCHCHCH), 7.67 (d, 2H, J = 7.2 Hz,
3
8.2 Hz, 2H, NSO2C(CHCH)2CCH3), 7.47 (d, J = 16.5 Hz,
3
4
CHC(CHCH)2CH), 7.60 (dt, J = 7.9 Hz, J = 1.4 Hz, 1H,
1H, CHCHC(CHCH)2CH), 7.41 (d, 3J = 3.4 Hz, 1H,
NCHCH), 7.30–7.20 (m, 7H, CHC(CHCH)2CH and
3
4
NO2CCHCHCH), 7.55 (dt, J = 7.7 Hz, J = 1.4 Hz, 1H,
NO2CCHCHCH), 7.50 (d, 3J
=
16.5 Hz, 1H,
3
4
NSO2C(CHCH)2CCH3), 6.91 (dt, J = 8.2 Hz, J = 1.2 Hz,
3
CHCHC(CHCH)2CH), 7.39 (d, J = 8.0 Hz, 2H, NSO2C-
(CHCH)2CCH3), 7.42–7.37 (m, 2H, CHC(CHCH)2CH), 7.35
1H, CH3OCCCHCH), 6.90 (d, 3J = 8.2 Hz, 1H, CH3OCCH),
3
6.85 (m, 2H, CH3OCCHCHCH), 6.37 (d, J = 3.4 Hz, 1H,
3
4
(dd, J = 7.7 Hz, J = 1.4 Hz, 1H, NO2CCCH), 7.30–7.26
3
NCHCH), 6.25 (d, J = 16.5 Hz, 1H, CHCHC(CHCH)2CH),
(m, 1H, CHC(CHCH)2CH), 7.14 (d, 3J = 8.0 Hz, 2H,
3.02 (s, 3H, CH3), 2.35 (s, 3H, CH3). 13C NMR (CDCl3,
125 MHz) d: 156.60 (CH3OC), 144.69 (NSO2C(CHCH)2C),
137.37 (CHCHC(CHCH)2C), 136.05 (NSO2C), 131.97
(CHCHC(CHCH)2CH), 131.29 (CH3OCCCH), 129.65
(NSO2C(CHCH)2C), 129.33 (NCC), 128.57 (CHCHC-
3
NSO2C(CHCH)2CCH3), 6.57 (d, J = 3.4 Hz, 1H, NCCH),
6.52 (d, J = 16.5 Hz, 1H, CHCHC(CHCH)2CH), 6.24 (d,
3
3J = 3.4 Hz, 1H, NC(CHCHPh)CH), 2.33 (s, 3H, CH3). 13C
NMR (CDCl3, 125 MHz) d: 149.06 (CNO2), 144.86
(NSO2C(CHCH)2CCH3), 137.47 (CHC(CHCH)2CH), 136.94
(NCCCNO2), 135.83 (NSO2C(CHCH)2CCH3), 133.22
(CHCCNO2), 132.58 (NCCHCHPh), 131.79 (CHCHCCNO2),
130.42 (CHC(CHCH)2CH), 129.51 (CCNO2), 129.42
(NSO2C(CHCH)2CCH3), 129.08 (NO2CCHCH), 128.67
(CHCHC(CHCH)2CH), 127.82 (CHCHC(CHCH)2CH),
126.94 (NSO2C(CHCH)2CCH3), 126.55 (CHCHC(CHCH)2CH),
124.16 (NO2CCH), 118.49 (CHCHC(CHCH)2CH), 116.64
(NC(CHCHPh)CH), 111.99 (NCCH), 21.60 (CH3).
(CHCH)2CH),
128.42
(CHCHC(CHCH)2CH),
127.35
(CH3OCCHCH), 127.06 (NSO2C(CHCH)2C), 126.05
(CHCHC(CHCH)2CH), 124.67 (NCC), 124.30 (CH3OCC),
122.04 (NCHCH), 120.54 (CH3OCCCHCH), 116.92
(CHCHC(CHCH)2CH), 115.40 (NCHCH), 111.17 (CH3OCCH),
55.38 (CH3O), 21.45 (CH3).
3-(p-Nitrophenyl)-2-styryl-1-tosylpyrrole (10c)
Method A: 1.36 g (3.71 mmol) of crude boronic acid 9,
0.62 g (2.47 mmol) of p-iodonitrobenzene, 1.17 g (3.71 mmol)
of barium hydroxide octahydrate, 57 mg (0.05 mmol) of
tetrakis(triphenylphosphine)palladium. Eluent: 20% diethyl
ether in petroleum ether. Yield of 10c: 400 mg, 36%, yellow
solid (mp 141°C). Rf = 0.36 (30% diethyl ether in petroleum
3-(o-Nitrophenyl)-2-styryl-1-tosylpyrrole (10d)
Method B: 90 mg (0.2 mmol) of the 3-iodo-2-styryl-1-
tosylpyrrole 6b, 50 mg (0.3 mmol) of o-nitrophenylboronic
acid, 95 mg (0.3 mmol) of barium hydroxide octahydrate, and
15 mg (0.02 mmol) of dichloro(diphenylphosphinoferrocene)pal-
ladium(II). Eluent: 20% diethyl ether in petroleum ether.
Yield of 10d: 71 mg, 80%, yellow solid (mp 104°C). Rf =
0.33 (30% diethyl ether in petroleum ether). MS (EI) m/z:
C+
ether). MS (EI) m/z: 444 (100, M ), 289 (69, [M –
C+
C7H7SO2]+), 243 (85, [289 – NO2] ), 241 (62). IR: 3052–
1
2850, 1598, 1516, 1374, 1342, 1178, 1139, 670. H NMR
(CDCl3, 300 MHz) d: 8.14 (d, 3J = 9.0 Hz, 2H, NO2CCHCHC),
3
C+
7.65 (d, J = 8.5 Hz, 2H, NSO2C(CHCH)2CCH3), 7.58 (d,
444 (100, M+), 289 (16, [M – C7H7SO2] ), 255 (18), 242
3
3J = 8.9 Hz, 2H, NO2CCHCHC), 7.46 (d, J = 3.4 Hz, 1H,
(19). HRMS calcd. for C25H20N2O4S: 444.1143; found:
3
NCHCH), 7.39 (d, J = 16.5 Hz, 1H, CHCHC(CHCH)2CH),
444.1131. IR: 3162–2859, 1526, 1370, 1190–1089. 1H NMR
© 2001 NRC Canada

Ghosez et al.
1835
(CDCl3, 500 MHz) d: 7.87 (dd, 3J = 8.0 Hz, 4J = 1.3 Hz, 1H,
CHCHC(CHCH)2CH), 7.45 (d, 3J
=
8.3 Hz, 2H,
NO2CCHCHCH), 7.63 (d, 3J
=
8.0 Hz, 2H,
CHC(CHCH)2CH), 7.35 (t, 3J = 8.3 Hz, 2H, CHC(CHCH)2CH),
7.33 (d, 3J = 3.4 Hz, 1H, NCHCH), 7.27–7.25 (m, 1H,
CHC(CHCH)2CH), 7.23 (d, 3J = 8.5 Hz, 2H, NSO2C-
(CHCH)2CCH3), 6.78 (d, 3J = 15.5 Hz, 1H, CHCHC-
3
4
NSO2C(CHCH)2CCH3), 7.50 (dt, J = 7.7 Hz, J = 1.4 Hz,
1H, NO2CHCHCH), 7.41 (dt, J = 7.7 Hz, J = 1.4 Hz, 1H,
NO2CHCHCH), 7.41 (d, J = 3.4 Hz, 1H, NCHCH), 7.37
(dd, J = 7.9 Hz, J = 1.3 Hz, 1H, NO2CCCH), 7.30 (d, J =
16.5 Hz, 1H, CHCHC(CHCH)2CH), 7.28–7.20 (m, 3H,
CHC(CHCH)2CH), 7.22 (d, 3J = 8.0 Hz, 2H, NSO2C-
(CHCH)2CCH3), 7.16–7.14 (m, 2H, CHC(CHCH)2CH), 6.24
3
4
3
3
4
3
3
(CHCH)2CH), 6.27 (d, J = 3.4 Hz, 1H, NCHCH), 2.35 (s,
3H, CH3). 13C NMR (CDCl3, 125 MHz) d: 144.85
(NSO2C(CHCH)2CCH3), 136.94 (CHC(CHCH)2CH), 135.93
(NSO2C(CHCH)2CCH3), 133.84 (NCCH), 127.63 (CHCHC-
(CHCH)2CH), 129.80 (NSO2C(CHCH)2CCH3), 129.56
(CHC(CHCH)2CH), 128.60 (CHCHC(CHCH)2CH), 126.77
(NSO2C(CHCH)2CCH3), 126.33 (CHCHC(CHCH)2CH), 123.23
(NCHCH), 116.79 (CHCHC(CHCH)2CH), 112.38 (NCHCH),
111.34 (t, NCCD), 21.47 (CH3).
3
3
(d, J = 3.4 Hz, 1H, NCHCH), 6.02 (d, J = 16.5 Hz, 1H,
CHCHC(CHCH)2CH), 2.35 (s, 3H, CH3). 13C NMR (CDCl3,
125 MHz) d: 149.48 (CNO2), 145.07 (NSO2C(CHCH)2CCH3),
136.62 (CHC(CHCH)2CH), 135.77 (NSO2C(CHCH)2CCH3),
134.00 (CHC(CHCH)2CH), 132.64 (CHCCNO2), 132.60
(CHCHCHCCNO2), 130.36 (CCNO2), 129.80 (NSO2C-
(CHCH)2CCH3), 129.75 (NCC), 128.47 (CHCHC(CHCH)2-
CH), 128.17 (NO2CCHCH), 127.90 (CHCHC(CHCH)2CH),
126.87 (NSO2C(CHCH)2CCH3), 126.23 (CHCHC(CHCH)2CH),
124.2 (NO2CCCH), 123.30 (NCC), 122.93 (NCHCH),
115.85 (CHCHC(CHCH)2CH), 113.82 (NCHCH), 21.60
(CH3).
2-Formyl-3-(o-nitrophenyl)-1-tosylpyrrole (13a) (RN:
233770-18-8)
Method C: 120 mg (0.32 mmol) of the 3-iodo-2-formyl-1-
tosylpyrrole 7b, 80 mg (0.48 mmol) of o-nitrophenylboronic
acid, 150 mg (0.48 mmol) of barium hydroxide octahydrate,
23 mg (0.032 mmol) of dichloro(diphenylphosphinoferrocene)pal-
ladium(II). Eluent: 30% diethyl ether in petroleum ether.
Yield of 13a: 120 mg, 98%, pale yellow solid (mp 143°C).
Rf = 0.29 (40% diethyl ether in petroleum ether). MS (EI)
m/z: 369 (8, M+), 341 (42, [M – CO]+), 324 (38, [M –
NO2]+), 215 (100, [M – C7H7SO2]+), 187 (50, [215 – CO]+),
155 (47, [C7H7SO2]+), 91 (88, [C7H7]+). IR: 3074, 1678,
1536, 1269, 740. 1H NMR (CDCl3, 500 MHz) d: 9.88 (s, 1H,
2-Styryl-1-tosylpyrrole (11) and 3-[2H]-2-styryl-1-tosylpyrrole
(d-11)
To 3-iodo-2-styryl-1-tosylpyrrole 6b (100 mg, 0.22 mmol),
barium hydroxide octahydrate (1.5 equiv), and catalyst (0.05
or 0.1 equiv), a degassed mixture of DMF (8 mL) and water
(2 mL) was added. The mixture was then placed in a bath
preheated to 120°C. After 20 min, it was cooled to room
temperature and diluted with ethyl acetate and water. After
filtration on a Celite® pad (washed with ethyl acetate), the
solution was washed with water, brine, and dried. Purifica-
tion by flash chromatography on silica gel (20% diethyl
ether in petroleum ether). Yield of 11: 57 mg, 79%, colour-
less oil. Rf = 0.38 (30% diethyl ether in petroleum ether).
MS (EI) m/z: 323 (100, M+), 168 (54, [M – C7H7SO2]+).
HRMS calcd. for C19H17NO2S: 323.0980; found: 323.0979.
3
4
CHO), 8.04 (dd, J = 8.1 Hz, J = 1.5 Hz, 1H, CHCNO2),
3
7.79 (d, J = 8.1 Hz, 2H, NSO2C(CHCH)2CCH3), 7.67 (d,
3J = 3.3 Hz, 1H, NCHCH), 7.59 (td, J = 7.7 Hz, J =
3
4
3
4
1.4 Hz, 1H, NO2CCHCHCH), 7.52 (td, J = 7.7 Hz, J =
1.4 Hz, 1H, NO2CCHCH), 7.35 (d, 3J = 8.1 Hz, 2H,
3
4
NSO2C(CHCH)2CCH3), 7.33 (dd, J = 7.7 Hz, J = 1.4 Hz,
3
1H, NO2CCCH), 6.39 (d, J = 3.3 Hz, 1H, NCHCH), 2.43
(s, 3H, CH3). 13C NMR (CDCl3, 125 MHz) d: 178.9 (CHO),
148.98 (CNO2), 145.98 (NSO2C(CHCH)2CCH3), 135.42
3
1H NMR (CDCl3, 500 MHz) d: 7.68 (d, J = 8.5 Hz, 2H,
(NSO2C(CHCH)2CCH3), 135.26 (NCCHO),
132.44
(NSO2C(CHCH)2CCH3), 7.55 (d, 3J = 15.5 Hz, 1H,
CHCHC(CHCH)2CH), 7.45 (d, 3J = 8.3 Hz, 2H, CHC-
(CHCH)2CH), 7.35 (dd (t), 3J = 8.3 Hz, 2H, CHC-
(CHCH)2CH), 7.33 (dd, 3J = 3.4 Hz, 4J = 1.6 Hz, 1H,
NCHCH), 7.30–7.26 (m, 1H, CHC(CHCH)2CH), 7.23 (d,
3J = 8.5 Hz, 2H, NSO2C(CHCH)2CCH3), 6.78 (d, 3J =
(NO2CCHCHCH), 132.25 (NO2CCCH), 130.15 (NSO2C-
(CHCH)2CCH3), 129.2 (NO2CCHCH), 128.48 (NO2CC),
128.34 (NCC), 128.34 (NCH), 127.24 (NSO2C-
(CHCH)2CCH3), 124.39 (CHCNO2), 113.85 (NCHCH), 21.59
(CH3). Anal. calcd. for C18H14N2O5S: C 58.37, H 3.81,
N 7.56; found: C 58.23, H 3.56, N 7.37.
3
15.5 Hz, 1H, CHCHC(CHCH)2CH), 6.52 (dd, J = 3.4 Hz,
4J = 1.6 Hz, 1H, NCCH), 6.27 (t, 3J = 3.4 Hz, 1H, NCHCH),
2.35 (s, 3H, CH3). 13C NMR (CDCl3, 125 MHz) d: 144.85
(NSO2C(CHCH)2CCH3), 136.94 (CHC(CHCH)2CH), 135.93
(NSO2C(CHCH)2CCH3), 129.80 (NSO2C(CHCH)2CCH3),
129.56 (CHC(CHCH)2CH), 128.60 (CHCHC(CHCH)2CH),
128.20 (NCCH), 127.63 (CHCHC(CHCH)2CH), 126.77
(NSO2C(CHCH)2CCH3), 126.33 (CHCHC(CHCH)2CH),
123.23 (NCHCH), 116.79 (CHCHC(CHCH)2CH), 112.46
(NCHCH), 111.56 (NCCH), 21.47 (CH3).
2-Formyl-3-phenyl-1-tosylpyrrole (13b)
Method C: 150 mg (0.4 mmol) of the 3-iodo-2-formyl-1-
tosylpyrrole 7b, 73 mg (0.6 mmol) of phenylboronic acid,
189 mg (0.6 mmol) of barium hydroxide octahydrate, 30 mg
(0.04 mmol) of dichloro(diphenylphosphinoferrocene)palla-
dium(II). Eluent: 30% diethyl ether in petroleum ether. Yield
of 13b: 120 mg, 92%, white solid (mp 175°C). Rf = 0.37
(40% diethyl ether in petroleum ether). MS (EI) m/z: 325
C+
When using deuterated DMF-d7, d-11 was obtained. Rf =
0.38 (30% diethyl ether in petroleum ether). MS (EI) m/z:
(78, M ), 260 (45, [M – SO2]+), 170 (100, [M –
C7H7SO2]+), 169 (75), 155 (38, [C7H7SO2]+), 115 (41), 91
(53, [C7H7]+). HRMS calcd. for C18H151NO3S: 325.0772;
found: 325.0765. IR: 1675, 1374, 1174. H NMR (CDCl3,
C+
324 (38, M+), 169 (100, [M – C7H7SO2] ), 168 (58, [M-D +
H-C7H7SO2]+), 91 (24, [C7H7]+), 44 (64). HRMS calcd. for
C19H16DNO2S: 324.1042; found: 324.1048. 1H NMR
(CDCl3, 500 MHz) d: 7.68 (d, 3J = 8.5 Hz, 2H,
(NSO2C(CHCH)2CCH3), 7.55 (d, 3J = 15.5 Hz, 1H,
3
500 MHz) d: 9.62 (s, 1H, COH), 7.94 (d, J = 8.8 Hz, 2H,
(NSO2C(CHCH)2CCH3), 7.84 (d, 3J = 3.4 Hz, 1H, NCHCH),
3
7.40 (s, 5H), 7.34 (d, J = 8.8 Hz, 2H, NSO2C(CHCH)2CCH3),
© 2001 NRC Canada

1836
Can. J. Chem. Vol. 79, 2001
3
6.49 (d, J = 3.4 Hz, 1H, NCHCH), 2.43 (s, 3H, CH3). 13C
NMR (CDCl3, 125 MHz) d: 178.22 (CHO), 145.36 (NSO2C-
(CHCH)2CCH3), 143.46 (NCCHO), 135.11 (NSO2C-
(CHCH)2CCH3), 132.27 (NCCC(CHCH)2CH), 129.54
(NSO2C(CHCH)2CCH3), 129.54 (NCHCH), 129.47 (NCCC-
(CHCH)2C), 128.63 (NCCC(CHCH)2CH), 128.44 (NCCC-
(CHCH)2CH), 128.34 (NSO2C(CHCH)2CCH3), 127.98
(NCCC(CHCH)2CH), 112.80 (NCHCH), 21.61 (CH3).
(CHCH)2CCH3), 130.29 (NO2CCHCH), 129.96 (NSO2C-
(CHCH)2CCH3), 129.14 (NCH), 128.08 (NCC), 128.01
(NSO2C(CHCH)2CCH3), 123.46 (NO2CCH), 113.14
(NCHCH), 21.65 (CH3). Anal. calcd. for C18H14N2O5S:
C 58.37, H 3.81, N 7.56; found: C 58.30, H 3.66, N 7.48.
2-Formyl-3-(o-methoxyphenyl)-1-tosylpyrrole (13e) (RN:
233770-28-0)
2-Formyl-3-(m-nitrophenyl)-1-tosylpyrrole (13c) (RN:
233770-24-6)
Method C: 250 mg (0.7 mmol) of the 3-iodo-2-formyl-1-
tosylpyrrole 7b, 151 mg (1 mmol) of o-methoxyphenylboronic
acid, 315 mg (1 mmol) of barium hydroxide octahydrate,
48 mg (0.07 mmol) of dichloro(diphenylphosphinoferrocene)pal-
ladium(II). Eluent: 30% diethyl ether in petroleum ether.
Yield of 13e: 210 mg, 89%, white solid (mp 131°C). Rf =
0.31 (40% diethyl ether in petroleum ether). MS (EI) m/z:
Method C: 150 mg (0.4 mmol) of the 3-iodo-2-formyl-1-
tosylpyrrole 7b, 102 mg (0.6 mmol) of m-nitrophenylboronic
acid, 189 mg (0.6 mmol) of octahydrate barium hydroxide,
30 mg (0.04 mmol) of dichloro(diphenylphosphinoferrocene)pal-
ladium(II). Eluent: 30% diethyl ether in petroleum ether.
Yield of 13c:130 mg, 88%, pale yellow solid (mp 142°C).
Rf = 036 (40% diethyl ether in petroleum ether). MS (EI)
C+
355 (30, M ), 324 (100, [355 – OMe-H]+), 201 (44, [M –
C7H7SO2]+), 185 (45), 170 (57, [201 – OMe]+), 152 (49),
C+
C+
1
m/z: 370 (51, M ), 306 (67, [215 + 91] ), 215 (63, [M –
134 (30), 91 (45, [C7H7]+). IR: 1676, 1174, 672. H NMR
C7H7SO2]+), 214 (61, [215 – H] ), 155 (100, [C7H7SO2]+),
(CDCl3, 500 MHz) d: 9.48 (s, 1H, CHO), 7.96 (d, 3J =
C+
91 (92, [C7H7]+). IR: 1676, 1526, 1348, 1175, 669. H NMR
8.8 Hz, 2H, NSO2C(CHCH)2CCH3), 7.82 (d, J = 3.3 Hz,
1
3
4
(CDCl3, 500 MHz) d: 9.87 (s, 1H, CHO), 8.25 (dd, J =
1H, NCH), 7.36–7.33 (m, 3H, CH3OCCHCH and NSO2C-
4
3
3
2.3 Hz, J = 1.7 Hz, 1H, CCHCNO2), 8.20 (dd, J = 8.3 Hz,
(CHCH)2CCH3), 7.21 (d, J = 8.2 Hz, 1H, CH3OCCCH),
4J = 2.3 Hz, 1H, CCHCNO2CH), 7.87 (d, J = 8.8 Hz, 2H,
3
3
6.97–6.95 (m, 2H,CH3OCCHCHCH), 6.49 (d, J = 3.3 Hz,
3
1H, NCHCH), 3.23 (s, 3H, OCH3), 2.41 (s, 3H, CH3). 13C
NMR (CDCl3, 125 MHz) d: 178.32 (CHO), 156.62
(CH3OC), 145.08 (NSO2C(CHCH)2CCH3), 139.37 (NCCHO),
NSO2C(CHCH)2CCH3), 7.77 (d, J = 3.4 Hz, 1H, NCHCH),
7.74 (ddd, 3J = 7.7 Hz, 4J = 1.7 Hz, 4J = 1.1 Hz, 1H,
3
CHCCHCNO2), 7.55 (t, J = 7.7 Hz, 2H, CHCHCCHCNO2),
3
7.34 (d, J = 8.8 Hz, 2H, NSO2C(CHCH)2CCH3), 6.50 (d,
136.02
(NSO2C),
131.75
(CH3OCCCH),
130.08
3J = 3.3 Hz, 1H, NCHCH), 2.42 (s, 3H, CH3). 13C NMR
(CDCl3, 125 MHz) d: 178.33 (CHO), 147.98 (CNO2), 146.01
(CH3OCCHCH), 129.37 (NSO2C(CHCH)2CCH3), 128.98
(NCH), 128.43 (NCC), 128.28 (NSO2C(CHCH)2CCH3), 120.32
(CH3OCCCHCH), 113.89 (NCHCH), 110.93 (CH3OCCH),
55.36 (CH3O), 21.50 (CH3). Anal. calcd. for C19H17NO4S:
C 64.21, H 4.82, N 3.94; found: C 63.91, H 4.69, N 3.97.
(NSO2C(CHCH)2CCH3),
138.42
(NCCHO),
135.33
(CHCCHCNO2), 135.01 (CCHNO2), 134.76 (NSO2C-
(CHCH)2CCH3), 129.97 (NSO2C(CHCH)2CCH3), 129.15
(NCH), 129.05 (CHCHCCHNO2), 127.97 (NCC), 127.83
(NSO2C(CHCH)2CCH3), 124.16 (CCHNO2), 123.17
(CCHCNO2CH), 113.24 (NCHCH), 21.58 (CH3). Anal.
calcd. for C18H14N2O5S: C 58.37, H 3.81, N 7.56; found:
C 58.46, H 3.72, N 7.33.
2-Formyl-3-mesityl-1-tosylpyrrole (13f) (RN: 233770-32-6)
Method C: 150 mg (0.4 mmol) of the 3-iodo-2-formyl-1-
tosylpyrrole 7b, 98 mg (0.6 mmol) of mesitylboronic acid
(26), 189 mg (0.6 mmol) of barium hydroxide octahydrate,
30 mg (0.04 mmol) of dichloro(diphenylphosphinoferrocene)pal-
ladium(II). Eluent: 20% diethyl ether in petroleum ether.
Yield of 13f: 90 mg, 61%, white solid (mp 141°C). Rf = 0.57
(40% diethyl ether in petroleum ether). MS (EI) m/z: 367
(83, M+), 212 (43, [M – C7H7SO2]+), 184 (100 [212 –
CO]+), 168 (32, [184 – CH3-H]+), 155 (32, [C7H7SO2]+), 91
(33, [C7H7]+). IR: 1679, 1370, 1175. 1H NMR (CDCl3,
2-Formyl-3-(p-nitrophenyl)-1-tosylpyrrole (13d) (RN:
233770-26-8)
Method C: 150 mg (0.4 mmol) of the 3-iodo-2-formyl-1-
tosylpyrrole 7b, 102 mg (0.6 mmol) of p-nitrophenylboronic
acid, 189 mg (0.6 mmol) of barium hydroxide octahydrate,
30 mg (0.04 mmol) of dichloro(diphenylphosphinoferrocene)pal-
ladium(II). Eluent: 30% diethyl ether in petroleum ether.
Yield of 13d: 124 mg, 84%, pale yellow solid (mp 167°C).
Rf = 0.38 (40% diethyl ether in petroleum ether). MS (EI)
3
500 MHz) d: 9.32 (s, 1H, CHO), 7.87 (d, J = 8.8 Hz, 2H,
3
NSO2C(CHCH)2CCH3), 7.85 (d, J = 3.3 Hz, 1H, NCH),
3
C+
C+
7.33 (d, J = 8.8 Hz, 2H, NSO2C(CHCH)2CCH3), 6.89 (s,
m/z: 370 (56, M ), 306 (67, [215 + 91] ), 294 (49), 226
2H, CH3C(CHCCH3)2C), 6.26 (d, 3J = 3.3 Hz, 1H,
NCHCH), 2.43 (s, 3H, CH3), 1.94 (s, 9H, CH3). 13C NMR
(CDCl3, 125 MHz) d: 177.87 (CHO), 145.34 (NSO2C-
(CHCH)2CCH3), 142.1 (NCCHO), 137.84 (CH3C-
(CHCCH3)2C), 136.41 (CH3C(CHCCH3)2C), 135.19
(NSO2C(CHCH)2CCH3), 129.97 (NCH), 129.57 (NSO2C-
(CHCH)2CCH3), 128.74 (CH3C(CHCCH3)2C), 128.40
(57), 215 (49, [M – C7H7SO2]+), 214 (43, [215 – H] ), 155
C+
(88, [C7H7SO2]+), 91 (86, [C7H7]+), 44 (100). IR: 1677,
1
1517, 1345, 1137, 669. H NMR (CDCl3, 500 MHz) d: 9.88
3
(s, 1H, CHO), 8.25 (d, J = 8.8 Hz, 2H, NO2CCH), 7.90 (d,
3J = 8.8 Hz, 2H, NSO2C(CHCH)2CCH3), 7.80 (d, 3J =
3.3 Hz, 1H, NCHCH), 7.59 (d, 3J = 8.8 Hz, 2H,
NO2CCHCH), 7.37 (d, 3J
= 8.8 Hz, 2H, NSO2C-
3
(CHCH)2CCH3), 6.51 (d, J = 3.3 Hz, 1H,NCHCH), 2.45 (s,
3H, CH3). 13C NMR (CDCl3, 125 MHz) d: 178.36 (CHO),
147.67 (CNO2), 146.07 (NSO2C(CHCH)2CCH3), 139.16
(NCCHO), 138.69 (NO2CCHCHC), 134.81 (NSO2C-
(NCC), 128.03 (CH3C(CHCCH3)2C), 127.80 (NSO2C-
(CHCH)2CCH3), 113.81 (NCHCH), 21.58 (CH3), 20.38 (CH3).
Anal. calcd. for C21H21NO3S: C 68.64, H 5.76, N 3.81;
found: C 68.52, H 5.79, N 3.76.
© 2001 NRC Canada

Ghosez et al.
1837
leum ether). MS (EI) m/z: 414 (71, M+), 314 (100), 159 (96).
HRMS calcd. for C21H22N2O5S: 414.1249; found: 414.1241.
IR: 1700, 1700, 1371, 1316, 1174. 1H NMR (CDCl3,
2-Formyl-3-(3-pyridyl)-1-tosylpyrrole (13g)
Method C: 150 mg (0.4 mmol) of the 3-iodo-2-formyl-1-
tosylpyrrole 7b, crude 3-pyridylboronic acid (28) from
3
300 MHz) d: 9.64 (s, 1H, COH), 7.91 (d, J = 8.4 Hz, 2H,
diethyl-3-pyridylborane (588 mg,
4
mmol), 189 mg
3
NSO2C(CHCH)2CCH3), 7.71 (d, J = 3.4 Hz, 1H, NCHCH),
(0.6 mmol) of barium hydroxide octahydrate, 30 mg
(0.04 mmol) of dichloro(diphenylphosphinoferrocene)palla-
dium(II). Eluent: 30% ethyl acetate in dichloromethane.
Yield of 13g: 128 mg, 77%, pale yellow oil. Rf = 0.49 (50%
ethyl acetate in dichloromethane). MS (EI) m/z: 326 (100,
3
4
7.38 (dd, J = 3.3 Hz, J = 1.8 Hz, 1H, NCHCHCH), 7.33
3
3
(d, J = 8.4 Hz, 2H, NSO2C(CHCH)2CCH3), 6.40 (d, J =
3.4 Hz, 1H, NCHCH), 6.22–6.18 (m, 2H, NCCH and
NCHCH), 2.42 (s, 3H, CH3), 1.37 (s, 9H, CH3). 13C NMR
(CDCl3, 75 MHz) d: 178.13 (CHO), 148.55 (OCON), 145.41
(NSO2C(CHCH)2CCH3), 135.14 (NSO2C(CHCH)2CCH3),
134.18 (NCCHO), 129.58 (NSO2C(CHCH)2CCH3), 129.35
C+
M ), 262 (27), 261 (28), 171 (35, [M – SO2C7H7)+], 170
(29), 155 (44, [SO2C7H7]+), 91 (66, C7H7). HRMS calcd. for
C17H14N2O3S: 326.0725; found: 326.0711. IR: 1675, 1377,
(NCCH),
128.17
(NSO2C(CHCH)2CCH3),
128.08
1
1175. H NMR (CDCl3, 300 MHz) d: 9.82 (s, 1H, COH),
(NCHCH), 124.11 (NCC), 123.53 (CHNC), 117.68
(NCCH), 114.25 (NCHCH), 110.55 (NCHCHCH), 84
(C(CH3)3), 27.49 (C(CH3)3), 21.57 (CH3).
3
8.66 (s, 1H, CCHN), 8.62 (d, J = 4.8 Hz, 1H, (NCHCHCH),
3
7.91 (d, J = 8.2 Hz, 2H, (NSO2C(CHCH)2CCH3), 7.82 (d,
3J = 3.1 Hz, 1H, NCHCH), 7.79 (d, 3J = 3.1 Hz, 1H,
(NCHCHCH), 7.39–7.26 (m, 3H, NCHCHCH and
2-Nitro-6-trifluoromethylboronic acid (14) and 4-nitro-6-
trifluoromethylboronic acid (15)
3
NSO2C(CHCH)2CCH3), 6.51 (d, J = 3.2 Hz, 1H, NCHCH),
2.44 (s, 3H, CH3). 13C NMR (CDCl3, 50 MHz) d: 177.80
(CHO), 149.30 (CCHN), 149.1 (NCHCHCH), 145.48
(NSO2C(CHCH)2CCH3), 137.57 (NSO2C(CHCH)2CCH3),
136.37 (CHCCHN), 134.59 (NCCHO), 129.51 (NSO2C-
(CHCH)2CCH3), 128.92 (NCHCH), 128.21 (CCHN), 127.87
(NCC), 127.64 (NSO2C(CHCH)2CCH3), 122.64 (CHCHN),
112.75 (NCHCH), 21.26 (CH3).
To a solution of nitric acid (90% aqueous, 2.25 mL, 48 mmol)
and sulfuric acid (6.8 mL, 128 mmol) and a few urea crys-
tals at 0°C, a solution of 2-(trifluoromethyl)phenylboronic
acid (3.2 g, 16 mmol) in acetic anhydride (42 mL) was
slowly added through an addition funnel. During the addi-
tion, the temperature was kept under 5°C. After the addition,
the mixture was stirred for 4 h at 0°C and overnight at room
temperature. It was then poured onto ice (500 mL) and so-
dium hydroxide was added until the pH reached a value be-
tween 3 and 5. The aqueous phase was then extracted with
diethyl ether. The organic layer was washed with brine,
dried and concentrated in vacuo. The purification by reverse-
phase MPLC yielded 2-nitro-6-trifluoromethylboronic acid
(14) (1.6 g, 42%) as a white solid (mp 154°C) and 4-nitro-2-
trifluoromethylboronic acid (15) (0.46 g, 12%) as a white
solid (mp 141°C).
2-Formyl-3-thiophenyl-1-tosylpyrrole (13h) (RN: 233770-
30-4)
Method C: 150 mg (0.4 mmol) of the 3-iodo-2-formyl-1-
tosylpyrrole 7b, 77 mg (0.6 mmol) of 2-thiophenylboronic
acid, 189 mg (0.6 mmol) of octahydrate barium hydroxide,
30 mg (0.04 mmol) of dichloro(diphenylphosphinoferrocene)pal-
ladium(II). Eluent: 30% diethyl ether in petroleum ether.
Yield of 13h: 113 mg, 85%, white solid (mp 146°C). Rf =
0.34 (40% diethyl ether in petroleum ether). MS (EI) m/z:
331 (72, M+), 176 (100, [M – C7H7SO2]+). IR: 1670, 1374,
(14): r.t. = 11.9 min (col. MATREX 4 RP 18 15 ; eluent:
CH3CN–H2O, 35:65; flow 0.5 mL min–1; UV detector
1
1174. H NMR (CDCl3, 500 MHz) d: 9.99 (s, 1H, COH),
C+
3
254 nm, 25°C). MS (EI) m/z: 235 (3, M ), 191 (100, [M –
7.87 (d, J = 8.8 Hz, 2H, NSO2C(CHCH)2CCH3), 7.75 (d,
C+
B(OH)2 + H] ), 171 (88, [M – NO2-F]+). HRMS calcd. for
3
4
3J = 3.4 Hz, 1H, NCHCH), 7.44 (dd, J = 3.6 Hz, J =
3
4
C7H5BF3NO4: 235.0263; found: 235.0266. IR: 3591 and
1.1 Hz, 1H, SCCH), 7.39 (dd, J = 5.1 Hz, J = 1.1 Hz, 1H,
1
3
3385, 1543, 1387–1292 (B—OH), 1134. H NMR (DMSO-
SCHCH), 7.33 (d, J = 8.8 Hz, 2H, NSO2C(CHCH)2CCH3),
3
3
4
d6, 500 MHz) d: 8.46 (d, J = 7.6 Hz, 1H, CHCNO2), 8.28
7.08 (dd, J = 5.1 Hz, J = 3.6 Hz, 1H, SCHCH), 6.58 (d,
3J = 3.4 Hz, 1H, NCHCH), 2.42 (s, 3H, CH3). 13C NMR
(CDCl3, 125 MHz) d: 178.37 (CHO), 145.61 (NSO2C(CHCH)2-
CCH3), 135.01(NSO2C(CHCH)2CCH3), 134.42 (NCCHO), 133.61
(SCCH), 129.77 (NSO2C(CHCH)2CCH3), 129.38 (NCHCH),
129.04 (SCCH), 127.94 (NSO2C(CHCH)2CCH3), 127.67
(SCHCH), 127.48 (NCC), 112.92 (NCHCH), 21.61 (CH3).
Anal. calcd. for C16H13NO3S2: C, 57.98, H 3.95, N 4.23;
found: C 58.09, H 4.07, N 4.13.
3
(s, 2H, B(OH)2), 8.14 (d, J = 7.6 Hz, 1H, CHCF3), 7.81 (t,
3J = 7.6 Hz, 1H, CHCHCH). 13C NMR (DMSO-d6,
75 MHz) d: 150.47 (CNO2), 133.5–132 (m, C-B), 131.77
(CHCHCH), 130.02 (CHCCF3), 125.32 (CCF3), 126.56
(CHCNO2), 120.92 (CF3).
(15): r.t. = 19.2 min (col. MATREX 4 RP 18 15 ; eluent:
CH3CN–H2O 35:65; flow 0.5 mL min–1; UV detector
C+
254 nm, 25°C). MS (EI) m/z: 235 (100, M ), 189 (24, [M –
NO2]+), 171 (55, [189 – F]+), 125 (39, [189 – B(OH)2-F]+),
2-Formyl-3-(1-tert-butoxycarbonyl)-pyrrole-1-tosylpyrrole
(13i)
C+
75 (25, [M – CF3-NO2-B(OH)2] ). HRMS calcd. for
C7H5BF3NO4: 235.0263; found: 235.0257. IR: 3470–3359,
1
Method C: 150 mg (0.4 mmol) of the 3-iodo-2-formyl-1-
tosylpyrrole 7b, 127 mg (0.6 mmol) of 1-tert-butoxy-
carbonylpyrrol-2-ylboronic acid (31), 189 mg (0.6 mmol) of bar-
ium hydroxide octahydrate, 30 mg (0.04 mmol) of
dichloro(diphenylphosphinoferrocene)palladium(II). Eluent:
20% diethyl ether in petroleum ether. Yield of 13i: 128 mg,
77%, pale yellow oil. Rf = 0.59 (40% diethyl ether in petro-
1530, 1409–1321 (B—OH), 1287, 1128. H NMR (DMSO-
3
d6, 75 MHz) d: 8.71 (s, 2H, B(OH)2), 8.42 (d, J = 9.2 Hz,
1H, CHCNO2), 8.14 (s, 1H, NO2CHCF3), 7.83 (d, 3J =
9.2 Hz, 1H, CHCB(OH)2). 13C NMR (DMSO-d6, 50 MHz)
d: 146.80 (NO2C), 134.11 (NO2CCHCH), 132.5–130.85 (m,
C-B), 126.28 (CCF3), 125.94 (NO2CCHCH), 121.35 (CF3),
119.85 (NO2CCHCF3).
© 2001 NRC Canada

1838
Can. J. Chem. Vol. 79, 2001
Sévenet, O. Thoison, K. Awong, M. Païs, M. Wright, and D.
Guénard. Bioorg. Med. Chem. Lett. 7, 2155 (1997); (f) C.
Pascal, J. Dubois, D. Guénard, L. Tchertanov, S. Thoret, and
F. Guéritte. Tetrahedron, 54, 14737 (1998).
2-Amino-6-trifluoromethylboronic acid (16)
Palladium (10% on activated carbon, 38 mg) was added to
a solution of o-nitro-o>-trifluoromethylboronic acid (14) in
ethanol (10 mL). The resulting suspension was then stirred
under hydrogen (2 bar) overnight, filtered on a Celite® pad
and concentrated in vacuo. Owing to its unstability, the
product was used in the coupling reaction without further
purification.
5. (a) K. Tanaka, K. Karigone, and S. Umio. Chem. Pharm. Bull.
17, 611 (1969); (b) G.C. Spence, E.C. Taylor, and O. Büchardt.
Chem. Rev. 70, 231 (1970); (c) A.H. Ratcliffe, G.F. Smith, and
G.N. Smith. Tetrahedron Lett. 52, 5179 (1973); (d) F. Bellamy,
P. Martz, and J. Streith. Heterocycles, 3, 395 (1975); (e) H.
Horikawa, T. Iwasaki, K. Matsumoto, and M. Miyoshi. J. Org.
Chem. 43, 335 (1978); (f) D.J. Arnold, L. Burgess-Dean, J.Hub-
bard, and M.A. Rahman. Aust. J. Chem. 47, 969 (1994); (g)
J.T. Gupton, S.A. Petrich, L.L. Smith, M.A. Bruce, P. Vu, K.X.
Du, and E.E. Dueno. Tetrahedron, 52, 6879 (1996).
3-Tosyl-9-(trifluoromethyl)-3H-pyrrolo[2,3-c]-quinoline (17)
Method C: 150 mg (0.4 mmol) of the 3-iodo-2-formyl-1-
tosylpyrrole 7b, 120 mg (0.6 mmol) of the crude o-amino-o>-
trifluoromethylboronic acid (16), 189 mg (0.6 mmol) of
barium hydroxide octahydrate, 30 mg (0.04 mmol) of
dichloro(diphenylphosphinoferrocene)palladium(II). Eluent:
30% ethyl acetate in petroleum ether. Yield of 17: 40 mg,
26%, pale yellow solid (mp 163°C). Rf = 0.5 (70% diethyl
6. S.P. Stanforth. Tetrahedron, 54, 263 (1998).
7. N. Miyaura and A. Suzuki. Chem. Rev. 95, 2457 (1995); A.
Suzuki. J. Organomet. Chem. 576, 147 (1999).
8. (a) J.M. Muchowski. J. Org. Chem. 57, 1653 (1992); (b) G.G
Grieb and D.M. Ketcha. Synth. Commun. 25, 2195 (1995); (c)
R. D’Alessio and A. Rossi. Synlett, 513 (1996); (d) D. Bolton,
I. Boyfield, M.C. Coldwell, M.S. Hadley, A. Johns, C.N. John-
son, R.E. Markwell, D.J. Nash, G.I. Riley, E.E. Scott, S.A.
Smith, G. Stemp, H.J. Wadsworth, and E.A. Watts. Bioorg.
Med. Chem. Lett. 7, 327 (1997); (e) C.N. Johnson, G. Stemp,
N. Arnaud, S.C. Stephen, and T. Gallagher. Synlett, 1025 (1998);
(f) T. Murashima, D. Shiya, K. Nishi, H. Uno, and N. Quo.
J. Chem. Soc. Perkin Trans. 1, 16, 2671 (2000).
9. (a) C.K. Chang, and N. Bag. J. Org. Chem. 60, 7030 (1995);
(b) J. Cossy and D. Belotti. J. Org. Chem. 62, 7900 (1997); (c)
M.G. Banwell, B.L. Flynn, E. Harmel, and D.C.R. Hockless. J.
Chem. Soc. Chem. Commun. 207 (1997); (d) H.W. Chan, P.C.
Chan, J.H. Lin, and H.N.C. Wong. J. Chem. Soc. Chem. Commun.
1515 (1997); (e) A. Fürstner, J. Grabowski, and C.W. Lehmann.
J. Org. Chem. 64, 8275 (1999); (f) T. Murashima, D. Shiya, K.
Nishi, H. Uno, and N. Ono. J. Chem. Soc. Perkin Trans. 1, 16,
2671 (2000); (g) J.H. Liu, Q.-C. Yang, T.C.W. Mak, and H.N.C.
Wong. J. Org. Chem. 65, 3587 (2000).
C+
ether in petroleum ether). MS (EI) m/z: 390 (100, M ), 235
(15, [M – C7H7SO2]+), 155 (29, [C7H7SO2]+), 91 (21,
[C7H7]+) HRMS calcd. for C19H13F3N2O2S: 390.0649; found:
390.0654. IR: no carbonyl signal. 1H NMR (CDCl3,
3
500 MHz) d: 9.70 (s, 1H, CHN), 8.40 (d, J = 8.0 Hz, 1H,
3
CHCCCF3), 8.02 (d, J = 8.0 Hz, 1H, CHCCF3), 7.86 (d,
3J = 3.7 Hz, 1H, NCHCH), 7.85 (d, 3J = 8.5 Hz, 1H,
NSO2C(CHCH)2CCH3), 7.69 (t, 3J
= 8.0 Hz, 1H,
3
CHCHCCF3), 7.45–7.43 (m, 1H, NCHCH), 7.26 (d, J =
8.6 Hz, 2H, NSO2C(CHCH)2CCH3), 2.34 (s, 3H, CH3). 13C
NMR (CDCl3, 125 MHz) d: 145.94 (NSO2C(CHCH)2CCH3),
144.74 (CNCH), 138.73 (CNCH), 135.26 (CHCNCCCF3),
134.72 (NSO2C(CHCH)2CCH3), 130.22 (NSO2C(CHCH)2-
CCH3), 128.90 (NCC), 128.03 (NCH), 126.96 (NSO2C-
(CHCH)2CCH3),
126.03
(CHCCF3),
125.83
(NCCHCHCHCCF3), 21.51 (CH3).
Acknowledgements
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This work was supported by fellowships from the Euro-
pean Community (C.F.), the Fonds National de la Recherche
Scientifique, and the European Institute for Chemistry and
Biology (F.D.). We thank the Ministère de l’Education et de
la Recherche Scientifique de la Communauté Française de
Belgique (Action concertée 96/01–197) for a generous grant.
We also thank L. Delhaye and V. Gevears for technical help.
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© 2001 NRC Canada