Palladium-catalysed direct desulfitative arylation of pyrroles using benzenesulfonyl chlorides as alternative coupling partners

Article abstract of DOI:10.1002/adsc.201400736

The reactivity of pyrrole derivatives for palladium-catalysed desulfitative arylation has been investigated. 1-Methyl-, 1-phenyl- and 1-benzylpyrroles were successfully coupled with a variety of benzenesulfonyl chlorides using a phosphine-free catalyst. Highly regioselective arylations at carbon C2 of pyrroles were observed in all cases. A wide variety of substituents on the benzenesulfonyl derivative was tolerated. It should be noted that even bromo- and iodo-benzenesulfonyl chlorides were successfully coupled with pyrrole derivatives without cleavage of the C-Br or C-I bonds, allowing further transformations. Surprisingly, with indoles, mixtures of C2- and C3-arylation products were obtained.

Full text of DOI:10.1002/adsc.201400736

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DOI: 10.1002/adsc.201400736
Palladium-Catalysed Direct Desulfitative Arylation of Pyrroles
using Benzenesulfonyl Chlorides as Alternative Coupling Partners
Rongwei Jin,a Kedong Yuan,a Emmanuelle Chatelain,a Jean-FranÅois Soulꢀ,a,*
and Henri Douceta,*
a
Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Universitꢀ de Rennes 1 “Organomꢀtalliques, Matꢀriaux et
Catalyse”, Campus de Beaulieu, 35042 Rennes, France
Fax : (+33) (0)2 23 23 69 39; phone: (+33) (0)2 23 23 63 84; e-mail: jean-francois.soule@univ-rennes1.fr or
henri.doucet@univ-rennes1.fr
Received: July 28, 2014; Revised: September 1, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400736.
Abstract: The reactivity of pyrrole derivatives for
It should be noted that even bromo- and iodo-ben-
palladium-catalysed desulfitative arylation has been zenesulfonyl chlorides were successfully coupled
À
investigated. 1-Methyl-, 1-phenyl- and 1-benzylpyr- with pyrrole derivatives without cleavage of the C
roles were successfully coupled with a variety of ben- Br or C I bonds, allowing further transformations.
À
zenesulfonyl chlorides using a phosphine-free cata- Surprisingly, with indoles, mixtures of C2- and C3-ar-
lyst. Highly regioselective arylations at carbon C2 of ylation products were obtained.
pyrroles were observed in all cases. A wide variety of
À
substituents on the benzenesulfonyl derivative was Keywords: benzenesulfonyl chlorides; C H bond ac-
tolerated.
tivation; desulfitative arylation; palladium; pyrroles
Introduction
a few pyrrole derivatives with aryl halides as the cou-
[2b,3]
À
pling partners, via a C H bond activation.
For ex-
The synthesis of 2-arylated pyrroles is an important ample, they obtained a moderate yield of 25% for the
field of research in organic chemistry due to the bio- coupling of 1-methylpyrrole with a chloropyrazine
logical properties of these derivatives. For example, using 5 mol% Pd(PPh3)4 as the catalyst (Scheme 1,
Apricoxib, Isoprazone and Fendosal are nonsteroidal top). Since these exciting results, the palladium-cata-
anti-inflammatory agents, Atorvastatin is used for lysed so-called direct arylation of pyrroles has been
lowering blood cholesterol, and Leiopyrrole is an an-
ticholinergic drug (Figure 1).
Conventional methods for the synthesis of 2- or 5-
arylpyrroles include metal catalysed cross-coupling re-
actions such as Suzuki, Stille, Negishi or Kumada type
reactions.[1] They make possible either the coupling of
aryl halides with organometallic derivatives of pyr-
roles or the coupling of halopyrroles with aryl-metal
derivatives. Nevertheless, these procedures require
the preliminary preparation of an organometallic de-
rivative, and produce stoichiometric amounts of met-
allic salts as by-products. The direct regioselective
À
couplings of pyrroles via C H bond activation/func-
tionalization provide more effective and environmen-
tally attractive accesses to arylpyrroles. In 1981, Ita-
hara reported the coupling of benzene with 1-(2,6-di-
chlorobenzoyl)pyrrole using a stoichiometric amount
of Pd(OAc)2 (Scheme 1, top).[2a] Then, Ohta and co-
workers reported the Pd-catalysed 2-arylation of Figure 1. Examples of bioactive 2-arylpyrroles
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Scheme 2. Influence of the reaction conditions on the Pd-
catalysed direct arylation of 1-methylpyrrole with 4-bromo-
benzenesulfonyl chloride
In most cases, aryl halides are attractive couplings
partners in terms of cost and/or availability. On the
other hand, the use of arylboronic acids or iodonium
salts is generally less attractive. Therefore, the discov-
ery of other easily available coupling partners for the
regioselective intermolecular direct arylation of pyr-
role derivatives, especially using a simple catalyst and
base, remains an important research field in the Pd-
catalysed direct arylations.
Recently Dong et al. reported the Pd-catalysed cou-
pling of benzenesulfonyl chlorides with 2-phenylpyri-
dine to prepare sulfones.[7] In the course of their
study, in one case they observed a desulfitative direct
arylation of a quinoline derivative. Then, in 2011,
Cheng et al. extended the desulfitative[8–11] Pd-cata-
lysed direct arylation to benzoxazoles.[12] We have
also recently reported the first desulfitative Pd-cata-
Scheme 1. Reported coupling partners for the Pd-catalysed
intermolecular direct arylation of pyrroles.
demonstrated to be one of the most powerful method lysed b-arylation of thiophenes and a-arylation of
for the synthesis of 2-arylpyrroles, and several more furan derivatives.[13] To our knowledge, the copper-
effective conditions allowing the formation of 2-aryl- free, palladium-catalysed desulfitative direct arylation
pyrroles via such couplings in high yields have been of pyrroles using benzenesulfonyl chlorides as the
reported.[4,5] On the other hand, relatively little effort coupling partners has not yet been described. As the
has been expended toward the discovery of alterna- use of benzenesulfonyl chlorides as reactants instead
tive coupling partners to aryl halides for the Pd-cata- of aryl halides drastically modifies in some cases the
lysed direct arylations of pyrroles.[6] Using iodonium regioselectivity of Pd-catalysed direct arylations,[13a]
salts in the presence of 5 mol% of a palladium cata- their behaviour in the presence of pyrroles needed to
lyst, Sanford and co-workers obtained the 2-arylpyr- be investigated.
roles in moderate yields (Scheme 1, middle).[6a,b] The
Herein, we describe the regioselective access to C2-
À
catalytic coupling of benzene with a pyrrole derivative arylated pyrroles using desulfitative Pd-catalysed C
under oxidative conditions has been described by H bond functionalization of pyrroles with benzenesul-
Fagnou et al. (Scheme 1, middle).[6c] Shi and co-work- fonyl chlorides as the coupling partners (Scheme 2).
ers employed arylboronic acids as the coupling part- The functional group tolerance on the benzenesulfon-
ners for the C2-arylation of 1-methylpyrrole.[6d] Final- yl chloride and sequential arylations are also report-
ly Deng et al. employed sodium sulfinates in the pres- ed.
ence of Pd(COD)Cl2 catalyst associated to 2 equiv. of
CuCl2 as oxidant for the C2-arylation of indoles.[6e] It
should be noted that this procedure was not extended Results and Discussion
to pyrroles. Jafarpour also employed a Pd/Cu catalytic
system for arylation of 1-methylpyrrole with arenesul- Based on our previous results on the Pd-catalysed de-
fonyl chlorides.[6g]
sulfitative coupling with thiophene derivatives,[13a] we
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Table 1. Influence of the reaction conditions on the Pd-catalysed direct arylation of 1-methylpyrrole with 4-bromobenzene-
sulfonyl chloride[a]
Entry
Catalyst (mol%)
Solvent
Base
Conv. (%)
Ratio 1a:1b:1c
Yield in 1a (%)
1
2
3
4
5
6
7
8
PdCl2(CH3CN)2 (5)
Pd(OAc)2 (5)
PdCl2 (5)
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
DMA
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Na2CO3
K2CO3
Cs2CO3
KOAc
100
100
100
100
100
100
100
100
100
100
70
97:0:3
89:3:8
89:8:3
79:16:5
93:3:4
93:3:4
96:0:4
trace
80
-
-
Pd2(dba)3 (2.5)
-
PdCl2(CH3CN)2 (5)
PdCl2(CH3CN)2 (5)
PdCl2(CH3CN)2 (5)
PdCl2(CH3CN)2 (5)
PdCl2(CH3CN)2 (1)
PdCl2(CH3CN)2 (5)
PdCl2(CH3CN)2 (5)
77
76
78
-
66
-
9
10
11
Li2CO3
Li2CO3
Li2CO3
89:7:4
trace
95:4:1
ethyl-benzene
52
[a]
1-Methylpyrrole (2 equiv.), 4-bromobenzenesulfonyl chloride (1 equiv.), base (3 equiv.), 1408C, 40 h, isolated yields.
first examined the influence of several reaction condi-
Then, the coupling of 1-methylpyrrole with a variety
tions on the product formation (Scheme 2, Table 1). of diversely substituted benzenesulfonyl chlorides was
The reaction of 2 equiv. of 1-methylpyrrole and examined using 5 mol% Pd(MeCN)2Cl2 catalyst,
1 equiv. of 4-bromobenzenesulfonyl chloride in the Li2CO3 as base in dioxane at 1408C (Scheme 3,
presence of 5 mol% PdCl2(MeCN)2 catalyst and Table 2). We initially studied the influence of para
Li2CO3 as the base at 1408C during 40 h gave regiose- substituents on the benzenesulfonyl chloride deriva-
lectively the C2 arylation product 1a in 80% yield tive. Nitro, cyano, and trifluoromethyl substituents af-
À
without cleavage of the C Br bond (Table 1, entry 1). forded the C2-arylated pyrroles 2–4 in 72-82% yields
It should be noted the under these reaction conditions (Table 2, entries 1-3). A yield of 79% in 5 was also
some formation of 3-arylated product 1c was also ob- obtained from 4-chlorobenzenesulfonyl chloride
À
served by GC/MS analysis. On the other hand, no for- (Table 2, entry 4). Although C I bonds on benzene
mation of 2,5-diarylation product 1b was detected by rings are known to be very reactive in the presence of
1
GC/MS and H NMR analysis of the crude mixture. palladium catalysts, we also examined the reactivity
Then, we examined the influence of the palladium of 4-iodobenzenesulfonyl chloride. The reaction pro-
catalyst. The use of 5 mol% Pd(OAc)2, PdCl2 or ceeds nicely affording the desired coupling product 6
À
Pd2(dba)3 catalysts afforded lower yields of 1a due to in 57% yield, without cleavage of the C I bond, thus
the formation of a larger amount of 1b and 1c allowing further transformations (Table 2, entry 5).
(Table 1, entries 2-4). The influence of the nature of From 4-fluorobenzenesulfonyl chloride, benzenesul-
the base was also examined. The use of Na2CO3, fonyl chloride or 4-methylbenzenesulfonyl chloride
K2CO3 or Cs2CO3 led to slightly lower yields of 1a moderate yields of 60–69% in 7–9 were obtained due
than Li2CO3, whereas KOAc was completely ineffec- to partial conversions of these arylsulfonyl chlorides
tive (Table 1, entries 5-8). A lower yield in 1a was (Table 2, entries 6-8). In the presence of the electron-
also obtained in the presence of only 1 mol% rich 4-methoxybenzenesulfonyl chloride, which dis-
PdCl2(MeCN)2 catalyst (Table 1, entry 9). The influ- played a poor reactivity for the arylation of benzofur-
ence of two other solvents was then examined. DMA an,[13b] the desired product 10 was obtained in 68%
was completely ineffective. On the other hand, ethyl- yield. However, 4 equiv. of 1-methylpyrrole were em-
benzene afforded 1a in 52% yield due to a moderate ployed, since with only 2 equiv. of this reactant a mix-
conversion of 4-bromobenzenesulfonyl chloride ture of mono- and di-arylation products in 82:18 ratio
(Table 1, entries 10 and 11).
was obtained (Table 2, entries 9 and 10). The ortho-
substituted 2-nitrobenzenesulfonyl chloride and 2-cya-
nobenzenesulfonyl chloride were also found to be
suitable coupling partners affording 11 and 12 in good
yields of 77% and 83% (Table 2, entries 11 and 12).
A few reactions using 1-phenylpyrrole instead of 1-
methylpyrrole reveals its lower reactivity (Scheme 4).
From 4-nitro-, 4-cyano-, 4-trifluoromethyl-, 4-chloro-
or 4-iodobenzenesulfonyl chlorides, the expected cou-
pling products 13–16 were obtained in lower yields
than with 1-methylpyrrole.
Scheme 3. Influence of the benzenesulfonyl chloride sub-
stituents on the Pd-catalysed direct C2-arylation of 1-meth-
ylpyrrole
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Table 2. Influence of the benzenesulfonyl chloride substitu-
ents on the Pd-catalysed direct C2-arylation of 1-methylpyr-
role (Scheme 3)[a]
Scheme 4. Pd-catalysed direct C2-arylations of 1-phenylpyr-
role
Scheme 5. Pd-catalysed direct C2-arylations of 1-benzylpyr-
roles
group (Scheme 5). From 4-cyanobenzenesulfonyl
chloride, the arylated product 18 was synthesized in
lower yield due to some formation of the C2,C5-dia-
rylated product 26. The reaction also tolerated meta
or ortho substituents on the benzenesulfonyl chloride
partners, since 19 and 20 were obtained in 68% and
77% yield, respectively. Under these conditions,
a 2,4-disubstitued benzenesulfonyl chloride such as
2,4-dinitrobenzenesulfonyl chloride displayed a high
reactivity.
[a]
PdCl2(CH3CN)2 (0.05 equiv.), 1-methylpyrrole (2 equiv.),
benzenesulfonyl chloride derivative (1 equiv.), Li2CO3
(3 equiv.), dioxane, 1408C, 40 h, isolated yields.
1-methylpyrrole (4 equiv.).
The reaction also proceeded smoothly with 1-(4-
bromobenzyl)pyrrole, affording the desired 2-arylated
pyrroles 22 and 23 in moderate to high yields. More-
[b]
À
over, in the course of these two reactions, the C Br
bond on the benzyl moiety was not cleaved, allowing
We then turned our attention to the reactivity of 1- further transformations.
benzylpyrrole derivatives for the Pd-catalysed desulfi-
In the presence of 1 equiv. of pyrrole derivative and
tative arylations, as the deprotection of pyrroles bear- 3 equiv. of benzenesulfonyl chloride, the formation of
ing an N-benzyl is easier than the corresponding 1- the 2,5-diarylated pyrrole was also possible
methylpyrroles. We selected our previous best reac- (Scheme 6). From 4-(trifluoromethyl)- and 4-methyl-
tion conditions, i.e, 5 mol% PdCl2(MeCN)2 as catalyst benzenesulfonyl chlorides, the products 24 and 25
in the presence of 3 equiv. of Li2CO3 as base in diox- were obtained in 30% and 33% yields, respectively.
ane at 1408C. From 4-nitrobenzenesulfonyl chloride, The diarylated products 26 and 27 have been synthe-
the corresponding C2 arylated product 17 was ob- sized in higher yields from N-benzylpyrrole using only
tained in high yield without cleavage of the benzyl 2.5 equiv. of the benzenesulfonyl chlorides.
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Scheme 6. Pd-catalysed direct C2,C5-diarylations of pyrroles
Scheme 8. Competitive Pd-catalysed direct arylations using
an equimolar mixture of pyrroles
boxylate reacted with 4-bromonitrobenzene to afford
28 in 61% yield using 2 mol% PdCl(C3H5)(dppb) cat-
alyst and KOAc as base in DMA (Scheme 7, bottom).
In order to gain more insight into the influence of
pyrrole C2-substituents on their reactivity, competi-
tion reactions to probe the substituent preference of
this catalyst system for such couplings were per-
formed (Scheme 8). From an equimolar mixture of
methyl 1-methylpyrrole-2-carboxylate and 1-methyl-
pyrrole using 4-nitrobenzenesulfonyl chloride as the
coupling partner, in the presence of
5 mol%
PdCl2(MeCN)2 catalyst, the exclusive formation of 2
from coupling with 1-methylpyrrole was observed
(Scheme 8, top). This result indicates that an electron-
withdrawing substituent at C2-position of pyrrole is
strongly deactivating, but has no poisoning effect on
the palladium catalyst. In order to compare the selec-
tivity of desulfitative arylation procedure with the
direct arylation using aryl halides, a competition ex-
periment using again an equimolar mixture of 1-meth-
Scheme 7. Influence of a pyrrole C2-substituent on the Pd-
catalysed direct arylation with 4-nitrobenzenesulfonyl chlo-
ride or 4-bromonitrobenzene
The influence of an electron-withdrawing substitu- ylpyrrole and methyl 1-methylpyrrole-2-carboxylate,
ent at carbon C2 on the pyrrole substrate was also in- but in the presence of 4-nitrobromobenzene as the
vestigated (Scheme 7). No formation of desired prod- coupling partner was performed in DMA using KOAc
uct 28 was observed in the presence of methyl 1- as base and PdCl(C3H5)(dppb) as catalyst (Scheme 8,
methylpyrrole-2-carboxylate and 4-nitrobenzenesul- bottom). A mixture of the arylated pyrroles 2 and 28
fonyl chloride as the coupling partner, and the benze- in a 89:11 ratio was obtained, revealing that with aryl
nesulfonyl chloride derivative was recovered unreact- bromides as the coupling partners the direct aryla-
ed. On the other hand, methyl 1-methylpyrrole-2-car- tions are slightly less sensitive to electron-withdraw-
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Scheme 9. Consecutive Pd-catalysed direct arylations of 1-
methylpyrrole
ing substituents on pyrrole than the reactions employ-
ing benzenesulfonyl chlorides. The different behav-
iour of these two catalytic systems might allow an
easier regiocontrol for the direct arylations of some
polyheteroaromatic substrates.
Scheme 11. Regioselectivity of the Pd-catalysed direct aryla-
tions of 1-methylindole using benzenesulfonyl chlorides
The regioselectivity of the arylation of 1-methylin-
Consecutive Pd-catalysed direct arylations of 1- dole under these conditions was also investigated
methylpyrrole were also examined (Scheme 9). From (Scheme 11). In the presence of sodium sulfinates as-
1 equiv. of 1-methyl-2-(4-methoxyphenyl)pyrrole 10 sociated to 2 equiv. of CuCl2 as oxidant, a regioselec-
and 1.5 equiv. of 4-chloro, 4-cyano and 4-nitrobenze- tive Pd-catalysed C2-arylation of indoles had been ob-
nesulfonyl chlorides, using again
5
mol% served by Deng and Luo.6e Surprisingly, from 1-meth-
Pd(MeCN)2Cl2 catalyst in the presence of Li2CO3 in ylindole and 4-bromobenzenesulfonyl chloride using
dioxane, the desired C5-arylated pyrroles 29-31 were Pd(MeCN)2Cl2 catalyst, we obtained a mixture of the
obtained in 59-93% yields.
C2 and C3 arylation products 32a and 32b in a 47:53
To gain more insight into the electronic effect of ratio, and in the presence of mesitylsulfonyl chloride,
benzenesulfonyl chloride substituents, a competition the C3-arylated product 33a was obtained in 90% se-
reaction using an equimolar mixture of 4-chloroben- lectivity.
zenesulfonyl chloride and 4-nitrobenzenesulfonyl
Finally, in order to further demonstrate the poten-
chloride in the presence of 1-methyl-2-(4-methoxy- tial of benzenesulfonyl chlorides as coupling partners
phenyl)pyrrole 10 was performed (Scheme 10). A for a simpler access to pyrrole-containing poly(heter-
mixture of products 29 and 31 in a 21:79 ratio was ob- o)aromatics, the preparation of 35 using 4-bromoben-
tained, which confirms the higher reactivity of the zenesulfonyl chloride was attempted. From 10 and 4-
more electron-deficient benzenesulfonyl chloride for bromobenzenesulfonyl chloride, 34 was obtained in
such couplings.
Scheme 10. Competitive Pd-catalysed direct arylations using
an equimolar mixture of benzenesulfonyl chloride deriva-
Scheme 12. Consecutive Pd-catalysed direct arylations using
tives
4-bromobenzenesulfonyl chloride
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Palladium-Catalysed Direct Desulfitative Arylation of Pyrroles
77.0 ppm for 13C), constants were reported in Hertz.
1H NMR assignment abbreviations were the following: sin-
glet (s), doublet (d), triplet (t), quartet (q), doublet of dou-
blets (dd), doublet of triplets (dt), and multiplet (m).
13C NMR spectra were recorded at 100 MHz on the same
spectrometer and reported in ppm. All reagents were weigh-
ed and handled in air.
À
86% yield (Scheme 12). Then, a third C H bond
functionalization from 34 and 2-ethyl-4-methylthia-
zole as the coupling partner, using PdCl(C3H5)(dppb)
catalyst14 with KOAc as the base in DMA, afford the
desired tetra(hetero)aryl product 35 in 80% yield.
The reactions with 4-bromo- or 4-iodo-benzenesul-
fonyl chlorides, which afford the coupling products
À
À
without cleavage of the C Br or C I bonds, seems to
reveal that the first step of the catalytic cycle is the
oxidative addition of the benzenesulfonyl chloride to
PdII to afford an ArSO2-PdIVCl intermediate. Such
a mechanism is consistent with the results obtained by
Dong and co-workers who reported that the oxidative
addition of benzenesulfonyl chloride on PdII proceed
even at room temperature.[7b] Then, after elimination
of SO2 and coordination of pyrrole to Pd, a migration
of the aryl group at the C2-carbon of pyrrole followed
by a proton abstraction assisted by the base affords
the 2-arylpyrrole and regenerates the PdII species.
However, as the reaction also proceeds with
Pd2(dba)3 catalyst, a Pd(0)/P(II) catalytic cycle cannot
be excluded.
Preparation of the PdCl(C3H5)(dppb) catalyst:[14]
An oven-dried 40 mL Schlenk tube equipped with a magnet-
ic stirring bar under argon atmosphere, was charged with
[Pd(C3H5)Cl]2 (182 mg, 0.5 mmol) and dppb (426 mg,
1 mmol). 10 mL of anhydrous dichloromethane were added,
then, the solution was stirred at room temperature for
twenty minutes. The solvent was removed in vacuum. The
yellow powder was used without purification. 31P NMR
(81 MHz, CDCl3) d=19.3 (s).
General procedure for synthesis of arylated pyrroles:
To a 25 mL oven dried Schlenk tube, arylsulfonyl chloride
(1–1.5 mmol), pyrrole derivative (1–4 mmol), Li2CO3
(0.222 g, 3 mmol), 1,4-dioxane (2 mL) and PdCl2(CH3CN)2
(12.9 mg, 0.05 mmol) were successively added. The reaction
mixture was evacuated by vacuum-argon cycles (5 times)
and stirred at 1408C (oil bath temperature) for 16–40 h (see
Conclusions
In summary, we report here the first copper-free, pal- tables and schemes). After cooling the reaction at room
temperature and concentration, the crude mixture was puri-
fied by silica column chromatography to afford the arylated
pyrroles or indoles.
ladium-catalysed desulfitative arylations of pyrrole
derivatives. The reaction proceeds regioselectively at
carbon C2 using easily accessible, ligand-free
Pd(MeCN)2Cl2 catalyst and Li2CO3 as inexpensive
base. A chief advantage of this procedure is that it
tolerates a wide variety of substituents on the benze-
nesulfonyl chloride such as nitro, cyano, trifluoro-
methyl, fluoro, chloro, or even bromo and iodo. A
bromo substituent on a 1-benzylpyrrole was also toler-
2-(4-Bromophenyl)-1-methylpyrrole (1a):[15a] Methylpyr-
role (0.162 g, 2 mmol) and 4-bromobenzenesulfonyl chloride
(0.255 g, 1 mmol) affords 1a in 80% (0.189 g) yield as
a
white solid. 2,5-Bis(4-bromophenyl)-1-methylpyrrole
(1b)15b was also isolated in very low yield.
1a: 1H NMR (400 MHz, CDCl3): d 7.51 (d, J=6.8 Hz,
2H), 7.26 (d, J=6.4 Hz, 2H), 6.73–6.71 (m, 1H), 6.24–6.21
ated. It should be mentioned that, the successive ary- (dd, J=3.4, 1.8 Hz, 1H), 6.20 (t, J=3.4 Hz, 1H), 3.66 (s,
3H).
lations at C2 and C5 of 1-methylpyrrole with 4-me-
thoxy- and 4-bromobenzenesulfonyl chlorides, affords
1b: 1H NMR (400 MHz, CDCl3): d 7.47 (d, J=8.6 Hz,
2H), 7.25 (d, J=8.6 Hz, 2H), 6.23 (s, 2H), 3.50 (s, 3H).
1-Methyl-2-(4-nitrophenyl)pyrrole (2):[4e] 1-Methylpyrrole
(0.162 g, 2 mmol) and 4-nitrobenzenesulfonyl chloride
(0.222 g, 1 mmol) affords 2 in 82% (0.166 g) yield.
1H NMR (400 MHz, CDCl3): d 8.18 (d, J=8.6 Hz, 2H),
7.48 (d, J=8.6 Hz, 2H), 6.74 (m, 1H), 6.34 (dd, J=3.4,
1.7 Hz, 1H), 6.18 (t, J=3.4 Hz, 1H), 3.68 (s, 3H).
À
the 2,5-diarylpyrrole without cleavage of the C Br
À
bond, allowing a third Pd-catalysed C H bond func-
tionalization with another heteroarene to afford a tet-
ra(hetero)arene. As several functionalised benzene-
sulfonyl chlorides are available at a reasonable cost,
this new process should be very attractive to synthetic
chemists for access to arylated pyrroles.
1-Methyl-2-(4-cyanophenyl)pyrrole (3):[4c] 1-Methylpyrrole
(0.162 g, 2 mmol) and 4-cyanobenzenesulfonyl chloride
(0.202 g, 1 mmol) affords 3 in 81% (0.147 g) yield.
1H NMR (400 MHz, CDCl3): d 7.60 (d, J=8.6 Hz, 2H),
7.43 (d, J=8.6 Hz, 2H), 6.71 (m, 1H), 6.28 (dd, J=3.4,
1.7 Hz, 1H), 6.16 (t, J=3.4 Hz, 1H), 3.64 (s, 3H).
Experimental Section
General:
1-Methyl-2-[4-(trifluoromethyl)phenyl]pyrrole (4):[4i] 1-
Methylpyrrole (0.162 g, 2 mmol) and 4-(trifluoromethyl)ben-
zenesulfonyl chloride (0.244 g, 1 mmol) affords 4 in 72%
(0.162 g) yield.
All reactions were carried out under argon atmosphere with
standard Schlenk techniques. HPLC grade 1,4-dioxane was
used and stored under argon without further purification.
1H NMR spectra were recorded on Bruker GPX (400 MHz)
spectrometer. Chemical shifts (d) were reported in parts per
million relative to residual chloroform (7.26 ppm for 1H;
1H NMR (400 MHz, CDCl3): d 7.55 (d, J=8.6 Hz, 2H),
7.41 (d, J=8.6 Hz, 2H), 6.66 (m, 1H), 6.21 (dd, J=3.4,
1.7 Hz, 1H), 6.12 (t, J=3.4 Hz, 1H), 3.59 (s, 3H).
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1-Methyl-2-(4-chlorophenyl)pyrrole (5):[16] Methylpyrrole
(0.162 g, 2 mmol) and 4-chlorobenzenesulfonyl chloride
(0.211 g, 1 mmol) affords 5 in 79% (0.151 g) yield.
8.6 Hz, 2H), 6.95 (s, 1H), 6.56 (dd, J=3.4, 1.7 Hz, 1H), 6.34
(t, J=3.4 Hz, 1H).
1-Phenyl-2-(4-(trifluoromethyl)phenyl)-pyrrole (14): 1-
Phenylpyrrole (0.286 g, 2 mmol) and 4-(trifluoromethyl)ben-
zenesulfonyl chloride (0.244 g, 1 mmol) affords 14 in 70%
(0.201 g) yield.
1H NMR (400 MHz, CDCl3): d 7.29 (d, J=8.6 Hz, 2H),
7.25 (d, J=8.6 Hz, 2H), 6.64 (m, 1H), 6.14 (dd, J=3.4,
1.7 Hz, 1H), 6.12 (t, J=3.4 Hz, 1H), 3.57 (s, 3H).
1H NMR (400 MHz, CDCl3): d 7.45 (d, J=8.6 Hz, 2H),
7.40–7.20 (m, 3H), 7.22 (d, J=8.6 Hz, 2H), 7.17 (d, J=
8.6 Hz, 2H), 6.99 (s, 1H), 6.53 (s, 1H), 6.39 (s, 1H).
13C NMR (100 MHz, CDCl3): d 140.2, 136.4, 132.3, 129.2,
128.0 (q, J=32.5 Hz), 127.9, 127.1, 125.8, 125.6, 125.0 (q, J=
3.6 Hz), 124.9 (q, J=271.5 Hz), 112.0, 109.6.
1-Methyl-2-(4-iodophenyl)pyrrole
(6):
Methylpyrrole
(0.162 g, 2 mmol) and 4-iodobenzenesulfonyl chloride
(0.303 g, 1 mmol) affords 6 in 57% (0.161 g) yield as a white
solid.
1H NMR (400 MHz, CDCl3): d 7.64 (d, J=8.6 Hz, 2H),
7.07 (d, J=8.6 Hz, 2H), 6.65 (m, 1H), 6.15 (dd, J=3.4,
1.7 Hz, 1H), 6.12 (t, J=3.4 Hz, 1H), 3.58 (s, 3H).
13C NMR (100 MHz, CDCl3): d 137.5, 133.4, 132.8, 130.3,
124.2, 109.0, 108.0, 92.1, 35.1.
Elemental analysis: calcd (%) for C17H12F3N (287.29): C
71.07, H 4.21; found: C 71.27, H 4.28.
2-(4-Chlorophenyl)-1-phenylpyrrole (15):[18] 1-Phenylpyr-
role (0.286 g, 2 mmol) and 4-chlorobenzenesulfonyl chloride
(0.211 g, 1 mmol) affords 15 in 60% (0.152 g) yield.
1H NMR (400 MHz, CDCl3): d 7.38–7.30 (m, 3H), 7.40–
7.20 (m, 3H), 7.17 (d, J=8.6 Hz, 2H), 7.14 (d, J=8.6 Hz,
2H), 7.04 (d, J=8.6 Hz, 2H), 6.94 (s, 1H), 6.43 (s, 1H), 6.36
(s, 1H).
Elemental analysis: calcd (%) for C11H10IN (283.11): C
46.67, H 3.56; found: C 46.50, H 3.65.
1-Methyl-2-(4-fluorophenyl)pyrrole (7):[16] 1-Methylpyr-
role (0.162 g, 2 mmol) and 4-fluorobenzenesulfonyl chloride
(0.195 g, 1 mmol) affords 4 in 60% (0.105 g) yield.
1H NMR (400 MHz, CDCl3): d 7.27 (dd, J=8.6, 5.4 Hz,
2H), 7.01 (d, J=8.6 Hz, 2H), 6.63 (m, 1H), 6.14–6.10 (m,
2H), 3.55 (s, 3H).
2-(4-Iodophenyl)-1-phenylpyrrole (16): 1-Phenylpyrrole
(0.286 g, 2 mmol) and 4-iodobenzenesulfonyl chloride
(0.303 g, 1 mmol) affords 16 in 51% (0.176 g) yield as
a white solid.
1-Methyl-2-phenylpyrrole (8):[4i] 1-Methylpyrrole (0.162 g,
2 mmol) and benzenesulfonyl chloride (0.176 g, 1 mmol) af-
fords 8 in 69% (0.108 g) yield.
1H NMR (400 MHz, CDCl3): d 7.42 (d, J=8.4 Hz, 2H),
7.27–7.18 (m, 3H), 7.07 (dd, J=1.6, 8.0 Hz, 2H), 6.85 (dd,
J=1.8, 2.8 Hz, 1H), 6.77 (d, J=8.4 Hz, 2H), 6.36 (dd, J=
1.8, 3.5 Hz, 1H), 6.27 (t, J=3.1 Hz, 1H).
1H NMR (400 MHz, CDCl3): d 7.35–7.25 (m, 5H), 6.65–
6.63 (m, 1H), 6.15 (dd, J=3.4, 1.7 Hz, 1H), 6.13 (t, J=
3.4 Hz, 1H), 3.58 (s, 3H).
13C NMR (100 MHz, CDCl3): d 140.4, 137.3, 132.8, 132.6,
130.1, 129.3, 127.1, 125.9, 125.1, 111.2, 109.6, 91.9.
Elemental analysis: calcd (%) for C16H12IN (345.18): C
55.67, H 3.50; found: C 55.79, H 3.68.
1-Methyl-2-p-tolylpyrrole (9):[17] 1-Methylpyrrole (0.162 g,
2 mmol) and 4-methylbenzenesulfonyl chloride (0.190 g,
1 mmol) affords 9 in 68% (0.116 g) yield.
1H NMR (400 MHz, CDCl3): d 7.22 (d, J=8.6 Hz, 2H),
7.13 (d, J=8.6 Hz, 2H), 6.62 (m, 1H), 6.14–6.10 (m, 2H),
3.57 (s, 3H), 2.30 (s, 3H).
1-Benzyl-2-(4-nitrophenyl)pyrrole (17): 1-Benzylpyrrole
(0.314 g, 2 mmol) and 4-nitrobenzenesulfonyl chloride
(0.221 g, 1 mmol) affords 17 in 79% (0.220 g) yield as
a yellow solid.
1-Methyl-2-(4-methoxyphenyl)pyrrole (10):[4c] 1-Methyl-
pyrrole (0.324 g, 4 mmol) and 4-methoxybenzenesulfonyl
chloride (0.207 g, 1 mmol) affords 10 in 68% (0.127 g) yield.
1H NMR (400 MHz, CDCl3): d 7.24 (d, J=8.6 Hz, 2H),
6.85 (d, J=8.6 Hz, 2H), 6.61 (m, 1H), 6.10 (t, J=3.4 Hz,
1H), 6.07 (dd, J=3.4, 1.7 Hz, 1H), 3.76 (s, 3H), 3.54 (s,
3H).
1H NMR (400 MHz, CDCl3): d 8.07 (d, J=8.7 Hz, 2H),
7.36 (d, J=8.7 Hz, 2H), 7.25–7.15 (m, 3H), 6.92 (dd, J=7.4,
1.6 Hz, 2H), 6.78 (dd, J=2.7, 1.8 Hz, 1H), 6.37 (dd, J=3.6,
1.7 Hz, 1H), 6.24 (dd, J=3.7, 2.7 Hz, 1H), 5.12 (s, 2H).
13C NMR (100 MHz, CDCl3): d 145.1, 138.5, 137.0, 131.5,
127.9, 127.3, 126.7, 125.1, 124.8, 122.8, 110.6, 108.4, 50.1.
Elemental analysis: calcd (%) for C17H14N2O2 (278.31): C
73.37, H 5.07; found: C 73.59, H 5.21.
1-Methyl-2-(2-nitrophenyl)pyrrole (11):[4e] 1-Methylpyr-
role (0.162 g, 2 mmol) and 2-nitrobenzenesulfonyl chloride
(0.222 g, 1 mmol) affords 11 in 77% (0.155 g) yield.
1H NMR (400 MHz, CDCl3): d 7.85 (d, J=8.6 Hz, 1H),
7.54 (t, J=8.0 Hz, 1H), 7.42 (t, J=8.0 Hz, 1H), 7.38 (d, J=
8.6 Hz, 1H), 6.67 (m, 1H), 6.12 (t, J=3.4 Hz, 1H), 6.06 (dd,
J=3.4, 1.7 Hz, 1H), 3.36 (s, 3H).
1-Benzyl-2-(4-cyanophenyl)pyrrole (18): 1-Benzylpyrrole
(0.314 g, 2 mmol) and 4-cyanobenzenesulfonyl chloride
(0.201 g, 1 mmol) affords 18 in 54% (0.139 g) yield as
a white solid.
1H NMR (400 MHz, CDCl3): d 7.50 (d, J=8.4 Hz, 2H),
7.31 (d, J=8.4 Hz, 2H), 7.25–7.15 (m, 3H), 6.91 (dd, J=8.2,
1.6 Hz, 2H), 6.75 (dd, J=2.8, 1.8 Hz, 1H), 6.31 (dd, J=3.7,
1.8 Hz, 1H), 6.23 (dd, J=3.7, 2.8 Hz, 1H), 5.10 (s, 2H).
13C NMR (100 MHz, CDCl3): d 138.3, 137.9, 133.1, 132.4,
129.1, 128.7, 127.8, 126.4, 125.4, 119.1, 111.2, 110.2, 109.4,
51.2.
1-Methyl-2-(2-cyanophenyl)pyrrole (12):[4e] 1-Methylpyr-
role (0.162 g, 2 mmol) and 2-cyanobenzenesulfonyl chloride
(0.202 g, 1 mmol) affords 12 in 83% (0.151 g) yield.
1H NMR (400 MHz, CDCl3): d 7.65 (d, J=8.6 Hz, 1H),
7.53 (t, J=8.0 Hz, 1H), 7.35 (d, J=8.6 Hz, 1H), 7.32 (t, J=
8.0 Hz, 1H), 6.71 (m, 1H), 6.32 (dd, J=3.4, 1.7 Hz, 1H),
6.17 (t, J=3.4 Hz, 1H), 3.53 (s, 3H).
Elemental analysis: calcd (%) for C18H14N2 (258.32): C
83.69, H 5.46; found: C 83.35 H 5.77.
1-Benzyl-2-(3-(trifluoromethyl)phenyl)pyrrole (19): 1-
Benzylpyrrole (0.314 g, 2 mmol) and 3-(trifluoromethyl)ben-
zenesulfonyl chloride (0.245 g, 1 mmol) affords 19 in 68%
(0.205 g) yield as a yellow oil.
2-(4-Nitrophenyl)-1-phenylpyrrole (13):[4e] 1-Phenylpyr-
role (0.286 g, 2 mmol) and 4-nitrobenzenesulfonyl chloride
(0.222 g, 1 mmol) affords 13 in 55% (0.145 g) yield.
1H NMR (400 MHz, CDCl3): d 7.98 (d, J=8.6 Hz, 2H),
7.32–7.25 (m, 3H), 7.16 (d, J=8.6 Hz, 2H), 7.10 (d, J=
8
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Palladium-Catalysed Direct Desulfitative Arylation of Pyrroles
1H NMR (400 MHz, CDCl3): d 7.47 (s, 1H), 7.43–7.34 (m,
3H), 7.22–7.13 (m, 3H), 6.90 (d, J=7.4 Hz, 2H), 6.72 (t, J=
2.5 Hz, 1H), 6.24 (dd, J=3.5, 1.8 Hz, 1H), 6.21 (t, J=
3.2 Hz, 1H), 5.04 (s, 2H).
1-Methyl-2,5-bis(4-(trifluoromethyl)phenyl)-pyrrole (24):19
1-Methylpyrrole (0.081 g, 1 mmol) and 4-(trifluoromethyl)-
benzenesulfonyl chloride (0.732 g, 3 mmol) affords 24 in
30% (0.111 g) yield.
13C NMR (100 MHz, CDCl3): d 150.3, 138.4, 134.1, 133.3,
130.9 (q, J=32.0 Hz), 131.8, 128.9, 128.8, 127.6, 126.3, 125.5
(q, J=4.0 Hz), 124.0, 123.5 (q, J=4.0 Hz), 110.0, 108.8, 50.9.
Elemental analysis: calcd (%) for C18H14F3N (301.31): C
71.75, H 4.68; found: C 71.97 H 4.81.
1H NMR (400 MHz, CDCl3): d 7.69 (d, J=8.6 Hz, 4H),
7.59 (d, J=8.6 Hz, 4H), 6.41 (s, 2H), 3.64 (s, 3H).
1-Methyl-2,5-bis(4-methylphenyl)-pyrrole (25):[20] 1-Meth-
ylpyrrole (0.081 g, 1 mmol) and 4-methylbenzenesulfonyl
chloride (0.570 g, 3 mmol) affords 25 in 33% (0.086 g) yield.
1H NMR (400 MHz, CDCl3): d 7.30 (d, J=8.6 Hz, 4H),
7.14 (d, J=8.6 Hz, 4H), 6.20 (s, 2H), 3.52 (s, 3H), 2.33 (s,
6H).
1-Benzyl-2-(2-nitrophenyl)pyrrole (20): 1-Benzylpyrrole
(0.314 g, 2 mmol) and 2-nitrobenzenesulfonyl chloride
(0.221 g, 1 mmol) affords 20 in 77% (0.214 g) yield as
a brown oil.
1-Benzyl-2,5-bis(4-cyanophenyl)pyrrole (26): 1-Benzylpyr-
role (0.157 g, 1 mmol) and 4-cyanobenzenesulfonyl chloride
(0.505 g, 2.5 mmol) affords 26 in 71% (0.255 g) yield as
a white solid.
1H NMR (400 MHz, CDCl3): d 7.91 (dd, J=7.5, 2.0 Hz,
1H), 7.50 (d, J=7.5 Hz, 2H), 7.34–7.30 (m, 1H), 7.30–7.24
(m, 3H), 7.0 (d, J=7.4 Hz, 2H), 6.81 (dd, J=2.8, 1.8 Hz,
1H), 6.29 (dd, J=3.6, 2.8 Hz, 1H), 6.22 (dd, J=3.6, 1.7 Hz,
1H), 4.96 (s, 2H).
1H NMR (400 MHz, CDCl3): d 7.53 (d, J=8.4 Hz, 4H),
7.37 (d, J=8.4 Hz, 4H), 7.11–7.08 (m, 3H), 6.59–6.57 (m,
2H), 6.42 (s, 2H), 5.15 (s, 2H).
13C NMR (100 MHz, CDCl3): d 150.2, 137.9, 133.6, 132.0,
128.8, 128.6, 128.1, 127.8, 127.6, 127.0, 123.9, 123.1, 110.1,
108.6, 51.2.
13C NMR (100 MHz, CDCl3): d 138.3, 137.7, 136.9, 132.5,
129.2, 129.0, 127.8, 125.8, 119.0, 112.4, 110.9, 49.6.
Elemental analysis: calcd (%) for C25H17N3 (359.43): C
83.54, H 4.77; found: C 83.75 H 4.96.
Elemental analysis: calcd (%) for C17H14N2O2 (278.31): C
73.37, H 5.07; found: C 73.14, H 5.33.
1-Benzyl-2-(2,4-dinitrophenyl)pyrrole (21): 1-Benzylpyr-
role (0.314 g, 2 mmol) and 2,4-dinitrobenzenesulfonyl chlo-
ride (0.266 g, 1 mmol) affords 21 in 63% (0.204 g) yield as
a red solid.
1-Benzyl-2,5-bis(2-fluorophenyl)pyrrole (27): 1-Benzylpyr-
role (0.157 g, 1 mmol) and 2-fluorobenzenesulfonyl chloride
(0.487 g, 2.5 mmol) affords 27 in 64% (0.221 g) yield as
a white solid.
1H NMR (400 MHz, CDCl3): d 8.59 (d, J=2.3 Hz, 1H),
8.21 (dd, J=8.5, 2.3 Hz, 1H), 7.38 (d, J=8.5 Hz, 1H), 7.19–
7.14 (m, 3H), 6.84–6.81 (m, 3H), 6.23 (d, J=2.2 Hz, 2H),
4.90 (s, 2H).
1H NMR (400 MHz, CDCl3): d 7.31–7.26 (m, 4H), 7.14–
7.07 (m, 4H), 7.05–7.02 (m, 3H), 6.55 (dd, J=5.6, 4.1 Hz,
2H), 6.41 (s, 2H), 5.08 (s, 2H).
13C NMR (100 MHz, CDCl3): d 160.2 (d, J=245.0 Hz),
138.7, 132.5 (d, J=2.3 Hz), 130.2, 129.6 (d, J=8.5 Hz), 128.2,
126.9, 126.3, 124.2 (d, J=3.9 Hz), 121.7 (d, J=14.6 Hz),
115.9 (d, J=22.3 Hz), 111.1, 49.4.
13C NMR (100 MHz, CDCl3): d 149.5, 146.8, 137.4, 134.2,
133.8, 129.0, 128.1, 126.8, 126.3, 126.2, 125.9, 119.9, 112.7,
109.8, 51.7.
Elemental analysis: calcd (%) for C17H13N3O4 (323.21): C
63.16, H 4.05; found: C 63.42 H 4.31.
Elemental analysis: calcd (%) for C23H17F2N (345.39): C
79.98, H 4.96; found: C 80.21 H 5.17.
1-(4-Bromobenzyl)-2-(4-nitrophenyl)pyrrole (22): 1-(4-
Bromobenzyl)pyrrole (0.472 g, 2 mmol) and 4-nitrobenzene-
sulfonyl chloride (0.222 g, 1 mmol) affords 22 in 67%
(0.239 g) yield as a yellow solid.
Methyl 1-methyl-5-(4-nitrophenyl)-pyrrole-2-carboxylate
(28):[21] Methyl 1-methylpyrrole-2-carboxylate (0.139 g,
1 mmol), 4-bromonitrobenzene (0.303 g, 1.5 mmol), KOAc
(0.294 g, 3 mmol), DMA (2 mL) and PdCl(C3H5)(dppb)
(12.2 mg, 0.02 mmol) were successively added. The reaction
mixture was evacuated by vacuum-argon cycles (5 times)
and stirred at 1408C (oil bath temperature) for 16 h to
afford 28 in 61% (0.158 g) yield.
1H NMR (400 MHz, CDCl3): d 8.07 (d, J=8.6 Hz, 2H),
7.33 (dd, J=8.6, 1.9 Hz, 4H), 6.76 (brs, 1H), 6.74 (brs, 2H),
6.36 (dd, J=3.7, 1.7 Hz, 1H), 6.24 (dd, J=3.7, 2.8 Hz, 1H),
5.07 (s, 2H).
13C NMR (100 MHz, CDCl3): d 146.4, 139.6, 137.2, 132.7,
132.2, 128.5, 128.0, 125.8, 124.1, 121.8, 112.1, 109.9, 50.8.
Elemental analysis: calcd (%) for C17H13BrN2O2 (357.21):
C 57.16, H 3.67; found: C 56.82 H 3.88.
1H NMR (400 MHz, CDCl3): d 8.23 (d, J=8.6 Hz, 2H),
7.50 (d, J=8.6 Hz, 2H), 6.96 (d, J=3.9 Hz, 1H), 6.25 (d, J=
3.9 Hz, 1H), 3.86 (s, 3H), 3.79 (s, 3H).
2-(4-Chlorophenyl)-5-(4-methoxyphenyl)-1-methylpyrrole
(29): 1-Methyl-2-(4-methoxyphenyl)pyrrole 10 (0.187 g,
1 mmol) and 4-chlorobenzenesulfonyl chloride (0.317 g,
1.5 mmol) affords 29 in 93% (0.276 g) yield.
1-(4-Bromobenzyl)-2-(3,5-dichlorophenyl)pyrrole (23): 1-
(4-Bromobenzyl)pyrrole (0.472 g, 2 mmol) and 3,5-dichloro-
benzenesulfonyl chloride (0.245 g, 1 mmol) affords 23 in
87% (0.331 g) yield as a yellow oil.
1H NMR (400 MHz, CDCl3): d 7.31 (s, 4H), 7.30 (d, J=
8.6 Hz, 2H), 6.89 (d, J=8.6 Hz, 2H), 6.21 (d, J=3.6 Hz,
1H), 6.16 (d, J=3.6 Hz, 1H), 3.78 (s, 3H), 3.48 (s, 3H).
13C NMR (100 MHz, CDCl3): d 157.8, 136.1, 133.9, 131.5,
131.1, 129.1, 128.7, 127.6, 124.9, 112.9, 107.8, 107.1, 54.3,
33.1.
1H NMR (400 MHz, CDCl3): d 7.35 (d, J=8.4 Hz, 2H),
7.18 (dd, J=3.3, 1.7 Hz, 1H), 7.08 (d, J=1.9 Hz, 2H), 6.77
(d, J=8.4 Hz, 2H), 6.69 (dd, J=2.8, 1.8 Hz, 1H), 6.23 (dd,
J=3.6, 1.8 Hz, 1H), 6.19 (dd, J=3.6, 2.8 Hz, 1H), 5.00 (s,
2H).
13C NMR (100 MHz, CDCl3): d 137.3, 136.1, 135.1, 132.2,
132.2, 128.3, 127.1, 127.0, 124.5, 121.8, 110.9, 109.4, 50.7.
Elemental analysis: calcd (%) for C17H12BrCl2N (381.09):
C 53.58, H 3.17; found: C 53.19 H 2.81.
Elemental analysis: calcd (%) for C18H16ClNO (297.78): C
72.60, H 5.42; found: C 72.71, H 5.30.
2-(4-Cyanophenyl)-5-(4-methoxyphenyl)-1-methylpyrrole
(30): 1-Methyl-2-(4-methoxyphenyl)pyrrole 10 (0.187 g,
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1 mmol) and 4-cyanobenzenesulfonyl chloride (0.303 g,
1.5 mmol) affords 30 in 61% (0.176 g).
1H), 3.78 (s, 3H), 3.55 (s, 3H), 2.95 (q, J=7.5 Hz, 2H), 2.45
(s, 3H), 1.35 (t, J=7.5 Hz, 3H).
13C NMR (100 MHz, CDCl3): d 170.3, 158.8, 146.9, 137.2,
135.6, 132.8, 130.7, 130.6, 130.1, 129.1, 128.6, 126.0, 113.9,
108.9, 108.2, 55.3, 34.3, 26.9, 16.2, 14.3.
1H NMR (400 MHz, CDCl3): d 7.61 (d, J=8.6 Hz, 2H),
7.48 (d, J=8.6 Hz, 2H), 7.31 (d, J=8.6 Hz, 2H), 6.91 (d, J=
8.6 Hz, 2H), 6.35 (d, J=3.6 Hz, 1H), 6.20 (d, J=3.6 Hz,
1H), 3.79 (s, 3H), 3.53 (s, 3H).
Elemental analysis: calcd (%) for C24H24N2OS (388.53): C
74.19, H 6.23; found: C 74.18, H 6.40.
13C NMR (100 MHz, CDCl3): d 159.1, 139.0, 137.9, 134.4,
132.3, 130.2, 128.2, 125.4, 119.0, 114.0, 110.8, 109.4, 108.8,
55.3, 34.5.
Elemental analysis: calcd (%) for C19H16N2O (288.34): C
79.14, H 5.59; found: C 79.28, H 5.69.
Acknowledgements
2-(4-Nitrophenyl)-5-(4-methoxyphenyl)-1-methylpyrrole
(31): 1-Methyl-2-(4-methoxyphenyl)pyrrole 10 (0.187 g,
1 mmol) and 4-nitrobenzenesulfonyl chloride (0.333 g,
1.5 mmol) affords 31 in 59% (0.182 g) yield.
We thank the Ministꢀre de la Recherche for a fellowship to
K. Y. and the Centre National de la Recherche Scientifique
and “Rennes Metropole” for providing financial support.
1H NMR (400 MHz, CDCl3): d 8.20 (d, J=8.6 Hz, 2H),
7.53 (d, J=8.6 Hz, 2H), 7.32 (d, J=8.6 Hz, 2H), 6.92 (d, J=
8.6 Hz, 2H), 6.42 (d, J=3.6 Hz, 1H), 6.22 (d, J=3.6 Hz,
1H), 3.79 (s, 3H), 3.57 (s, 3H).
References
13C NMR (100 MHz, CDCl3): d 159.2, 145.7, 139.8, 139.6,
134.1, 130.2, 127.8, 125.3, 124.1, 114.1, 111.5, 109.1, 55.4,
34.7.
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Elemental analysis: calcd (%) for C18H16N2O3 (308.33): C
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3-(4-Bromophenyl)-1-methylindole (32a):[22] 1-Methylin-
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1H NMR (400 MHz, CDCl3): d 7.81 (d, J=8.6 Hz, 1H),
7.47 (d, J=8.6 Hz, 2H), 7.44 (d, J=8.6 Hz, 2H), 7.30 (d, J=
8.6 Hz, 1H), 7.22 (t, J=8.0 Hz, 1H), 7.15 (s, 1H), 7.13 (t,
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(33a):[23]
1-Methylindole
(0.131 g, 1 mmol) and 2-mesitylenesulfonyl chloride (0.328 g,
1.5 mmol) affords 33a in 48% (0.120 g) yield.
1H NMR (400 MHz, CDCl3): d 7.39 (d, J=8.4 Hz, 1H),
7.30–7.23 (m, 2H), 7.08 (t, J=7.4 Hz, 1H), 7.00 (s, 2H), 6.89
(s, 1H), 3.86 (s, 3H), 2.37 (s, 3H), 2.09 (s, 6H).
2-(4-Bromophenyl)-5-(4-methoxyphenyl)-1-methylpyrrole
(34): 1-Methyl-2-(4-methoxyphenyl)pyrrole 10 (0.187 g
1 mmol) and 4-bromobenzenesulfonyl chloride (0.509 g,
2 mmol) affords 34 in 86% (0.294 g) yield.
1H NMR (400 MHz, CDCl3): d 7.47 (d, J=8.6 Hz, 2H),
7.31 (d, J=8.6 Hz, 2H), 7.26 (d, J=8.6 Hz, 2H), 6.89 (d, J=
8.6 Hz, 2H), 6.22 (d, J=3.6 Hz, 1H), 6.16 (d, J=3.6 Hz,
1H), 3.78 (s, 3H), 3.49 (s, 3H).
13C NMR (100 MHz, CDCl3): d 158.9, 137.2, 135.0, 132.6,
131.6, 130.1, 130.0, 125.9, 120.7, 113.9, 108.9, 108.2, 55.3,
34.1.
Elemental analysis: calcd (%) for C18H16BrNO (342.23):
C 63.17, H 4.71; found: C 63.19, H 4.48.
2-Ethyl-5-(4-(5-(4-methoxyphenyl)-1-methylpyrrol-2-yl)-
phenyl)-4-methylthiazole (35): 2-(4-Bromophenyl)-5-(4-me-
thoxyphenyl)-1-methylpyrrole 34 (0.342 g, 1 mmol), 2-ethyl-
4-methylthiazole (0.191 g, 1.5 mmol) KOAc (0.294 g,
3 mmol), DMA (2 mL) and PdCl(C3H5)(dppb) (12.2 mg,
0.02 mmol) were successively added. The reaction mixture
was evacuated by vacuum-argon cycles (5 times) and stirred
at 1308C (oil bath temperature) for 20 h to afford 35 in
80% (0.310 g) yield.
1H NMR (400 MHz, CDCl3): d 7.43 (d, J=8.6 Hz, 2H),
7.39 (d, J=8.6 Hz, 2H), 7.35 (d, J=8.6 Hz, 2H), 6.90 (d, J=
8.6 Hz, 2H), 6.28 (d, J=3.6 Hz, 1H), 6.19 (d, J=3.6 Hz,
10
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11
ÞÞ
These are not the final page numbers!

FULL PAPERS
12 Palladium-Catalysed Direct Desulfitative Arylation of
Pyrroles using Benzenesulfonyl Chlorides as Alternative
Coupling Partners
Adv. Synth. Catal. 2014, 356, 1 – 12
Rongwei Jin, Kedong Yuan, Emmanuelle Chatelain,
Jean-FranÅois Soulꢀ,* Henri Doucet*
12
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