Integration of oxidative arylation with sulfonyl migration: One-pot tandem synthesis of densely functionalized (NH)-pyrroles

Article abstract of DOI:10.1039/c7nj01709j

A one-pot synthesis of 2-aryl-3-alkyl/aryl-sulfonyl-(NH)-pyrroles from N-sulfonylpyrroles, developed for the first time, via palladium-catalyzed oxidative C-2 arylation followed by sulfonyl migration is described. The simple, easy access to the highly functionalized free-NH pyrroles secures opportunities for the preparation of compounds with promising biological activities in contemporary organic synthesis. The event of sulfonyl migration from pyrrole-N to C-3 is thermodynamically favored as revealed by density functional methods. The different plausible mechanisms for the migration of the sulfonyl group are also discussed.

Full text of DOI:10.1039/c7nj01709j

View Article Online
View Journal
NJC
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: J. K. Laha, S.
Sharma, R. A. Bhimpuria, N. Dayal, G. Dubey and Prasad. V. Bharatam, New J. Chem., 2017, DOI:
1
0.1039/C7NJ01709J.
Volume 40 Number
1
January 2016 Pages 1–846
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
NJC
New Journal of Chemistry
www.rsc.org/njc
A journal for new directions in chemistry
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
rsc.li/njc

Page 1 of 14
New Journal of Chemistry
Please do not adjust margins
View Article Online
DOI: 10.1039/C7NJ01709J
Journal Name
ARTICLE
Integration of Oxidative Arylation with Sulfonyl Migration: One-
Pot Tandem Synthesis of Densely Functionalized (NH)-Pyrroles
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
a
a
a
a
b
www.rsc.org/
Joydev K. Laha,* Shubhra Sharma, Rohan A. Bhimpuria, Neetu Dayal, Gurudutt Dubey, and
b
Prasad V. Bharatam*
A one-pot synthesis of 2-aryl-3-alkyl/aryl-sulfonyl-(NH)-pyrroles from N-sulfonylpyrroles, developed first time, via
palladium-catalyzed oxidative C-2 arylation followed by sulfonyl migration is described. The simple, easy access to the
highly functionalized free-NH pyrroles secures opportunities for the preparation of compounds with promising biological
activities in contemporary organic synthesis. The event of sulfonyl migration from pyrrole-N to C-3 is thermodynamically
favored as revealed by density functional methods. The different plausible mechanisms for the migration of the sulfonyl
group are also discussed.
CH3
O
N
Introduction
CH3
SO2NH
Many biaryl compounds containing an ortho-sulfonyl group
have been identified as medicinal agents in therapeutic
discovery with a proven track record of druggability, for
N
O
(
H3C)3CH2C(H3C)NOCH2C
BMS-207940 (1)
H3C
CH3
example BMS-207940 (
1) and (2), while each requiring an
N
N
O2S
N
ortho-sulfonyl functionality for demonstrated pharmacophoric
SO -R
2
SO2NHCONH
CO2CH3
N
1,2
N
activities (Figure 1). Structurally related heterobiaryls are
especially interesting as they could encompass the flexibility to
accommodate an ortho-sulfonyl group on aryl or heteroaryl
F
N
N
H
N
H
N
CH3
(
2) Platelet Activating Factor
(3) 2-arylsulfonyl pyrrole
(4) Heribicidal agent
antagonist
3
ring. Despite pyrrole being the common integral part of
Figure 1. Biaryls and Heterobiaryls with an ortho-sulfonyl functionality.
natural pigments, pharmaceuticals and performance
4
a
materials,
(NH)-2-arylpyrroles containing
a
sulfonyl
4
) are less abundant. More
d
diversification and new opportunities in drug discovery.
functionality on pyrrole ring (
3
While 2-arylpyrroles have been prepared using classical
importantly, the understanding of the positional effect of
sulfonyl group on pharmacological properties is only
4a,5
reactions involving multi-steps,
6
arylations, and elegantly by oxidative coupling reactions, the
synthesis of (NH)-2-arylpyrroles containing sulfonyl-
widely by direct C-H
7
4d
superficial.
Therefore, ready availability of (NH)-2-
a
arylpyrroles containing a sulfonyl functionality could provide
extended opportunities for understanding the comparative
beneficial effect of the sulfonyl group on aryl and pyrrole rings,
direct comparison of their biological and pharmacokinetic
properties, functionalization of free (NH) group for late-stage
functionality is limited only to a few reports. Oxidation of a
thiol functionality already present on the aryl or pyrrole ring of
4
d,e
(
NH)-2-arylpyrroles,
prepared in steps, and multi-
using building blocks are the
4
b,c,f
component reactions
4b,c,e,f
procedures currently available in literature (Scheme 1).
Nevertheless, the installation of sulfonyl functionality on (NH)-
-arylpyrroles has invariably been resorted to using a classical
2
a.
Department
National
S. A. S. Nagar, Punjab 160062, India; E-mail: jlaha@niper.ac.in
of
Pharmaceutical
of Pharmaceutical
Technology
(Process
Chemistry) approach.
Research
Institute
Education
and
b.
Department
National
S. A. S. Nagar, Punjab 160062, India; E-mail: pvbharatam@niper.ac.in
of
Medicinal
Pharmaceutical Education
Chemistry
Research
Institute
of
and
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

P
N
le
e
a
w
se
J
d
o
o
ur
n
n
o
a
t
l
a
o
d
f
ju
C
s
h
t
e
m
m
a
i
r
s
g
t
i
r
n
y
s
Page 2 of 14
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C7NJ01709J
Scheme 1. Approaches for (NH)-2-arylpyrroles with a sulfonyl group.
The practice of protecting a group would be particularly
valuable if the protecting group is retained as desired
8
functionality in the product. In this regard, regioselective
migration of a sulfonyl group from one position to a different
position could be a useful tool, especially when ready
installation of the sulfonyl group at the desired position could
possess a significant challenge. The arylsulfonyl groups are
commonly used as protecting groups in pyrrole chemistry,
which are ultimately removed after the desired
8a,b
transformation. The event of sulfonyl migration is reported
in the synthesis of 3-sulfonylindole or pyrazoles 5a (Scheme 2)
via an anionic thia-Fries rearrangement in the presence of a
9
strong base, AlCl mediated sulfonyl migration in indoles 5b
3
10
from N- to C-7 position, Lewis base catalyzed annulations of
11
,
N-propargylic sulfonylhydrazones to 4-sulfonylpyrazoles 5c
gold(I)-catalyzed cycloisomerization of N-substituted N- Scheme 2. Selected Examples of Sulfonyl migration observed in Heterocycles.
12
sulfonyl-aminobut-3-yn-2-ols or base catalyzed regioselective
13
migration of sulfonyl group to the synthesis of 3-sulfonyl-
NH)-pyrroles 5d,e. Many conditions that have been largely
(
Results and discussion
Our initial investigations, largely focused on finding
used to trigger the N- to C-sulfonyl migration require the use
a
of a base, noble metal catalyst, or Lewis acid, which is believed
condition that could effect thermal induced sulfonyl migration
from N- to C-3 position in pyrroles, ultimately secured a
condition for desired sulfonyl migration. The attempts of
sulfonyl migration with 2,5-disubstituted-N-tosylpyrrole 6a at
room temperature or above (up to 60 °C) did not secure a
traceable sulfonyl migration. The event of sulfonyl migration
was noticeable only when compound 6a was heated at or
above 80 °C in DMF (Table 1, entry 1). A significantly improved
conversion of compound 6a to 7aa was observed at 130 °C in
DMF in 4 h affording 7aa in 75% yield (entry 2). Other solvents
including o-xylene, DCB, quinoline, nitrobenzene, DMSO,
ethylene glycol, and pivalic acid were also compatible
producing 7aa in varying yields (entries 3-9). For example, a
non-polar solvent, o-xylene gave 7aa in 42% yield (entry 3).
Both DMSO (a polar aprotic solvent) and ethylene glycol (a
polar protic solvent) gave comparable yields of 7aa (entries 7-
10-14
to proceed via an ion-pair mechanism.
However, a few
reports describing thermal induced N- to C-sulfonyl migration
use a high temperature (>150 °C), which is known to involve
1
5
radical generation. While a sulfonyl migration in pyrrole
nucleus is scarcely reported, integration of sulfonyl migration
with oxidative coupling remains unexplored. Realization of a
reaction condition for oxidative arylation in N-sulfonylpyrroles
followed by sulfonyl migration while elusive could give a direct
16
access to C-sulfonylated (NH)-pyrroles. Leveraging our
17
experiences in oxidative couplings and installation of a
18
sulfonyl functionality on heterobiaryls, we envisaged a
tandem approach that could feature event of sulfonyl
migration and meet the preparative challenges of highly
functionalized (NH)-2-arylpyrroles containing a C-3 sulfonyl
functionality on pyrrole ring.
Herein, we describe a novel tandem approach to the
8
). However, pivalic acid produced somewhat inferior results
synthesis of (NH)-2-arylpyrroles containing
a C-sulfonyl
(entry 9). Interestingly, pivalic acid is proved comparable at
functionality on pyrrole via palladium-catalyzed regioselective
C-2 arylation of N-sulfonylpyrroles followed by intramolecular
N(1)- to C(3)-sulfonyl migration. The distinctive features of this
work include a) realization, for the first time, of a novel N- to
C-3 sulfonyl migration in pyrrole nucleus, b) does not require
any base, acid, or metal-catalyst for sulfonyl migration, c)
integration of the sulfonyl migration with oxidative coupling,
and d) probable mechanism among the different possible
mechanisms proposed in this study.
higher concentrations (entry 10). The yield of the reaction is
not affected in the presence of a radical quencher TEMPO,
suggesting that the reaction does not involve the formation of
a free-radical (entry 11). Notably, another sulfonyl migrated
product 7ab was obtained in many of these experiments albeit
in low quantities.
2
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 14
Please do not adjust margins
New Journal of Chemistry
Journal Name
ARTICLE
View Article Online
DOI: 10.1039/C7NJ01709J
a
Table 1. Optimization Study for Sulfonyl Migration.
Table 2. Approaches for (NH)-2-Arylpyrroles with a Sulfonyl Group.
Entry
Solvent
Temp
°C)
% 7a
a
% 7a
b
(
1
2
3
4
5
6
7
8
DMF
DMF
80
15
75
42
62
40
73
87
85
60
85
72
-
12
5
130
130
130
130
130
130
130
130
130
130
o-xylene
DCB
8
Quinoline
Nitrobenzene
DMSO
4
15
-
Ethylene glycol
Pivalic acid
Pivalic acid
Pivalic acid
3
9
12
5
A challenge was to find a reaction condition for one-pot
oxidative regioselective C-2 arylation that could be compatible
with the reaction conditions of sulfonyl migration. Reaction of
b
1
0
b,c
1
1
5
a
b
c
8a and benzene (10 mL/mmol) in the presence of Pd(OAc)
mol%), CsOPiv (20 mol%), and AgOAc (3 equiv) in pivalic acid
10 mL/mmol) at 130 °C for 16 h gave 7c in 52% yield (Table 3,
A single crystal X-ray structure was sought for 7aa, which is entry 1). A reduced volume of benzene further improved the
2
(10
6
a
(0.1 mmol), solvent (0.25 mL); solvent (1 mL); In the
presence of TEMPO (1.2 equiv).
(
shown in Figure 2.
yield affording 7c in 70% yield (entry 2). Further reduced
volume (4 mL/mmol) of benzene together with a slightly
reduced volume of pivalic acid (8 mL/mmol) resulted the best
yield of the product (entry 3). However, use of nearly a
stoichiometric amount of benzene reduced the yield
significantly (entry 4). DMSO, a solvent that appeared excellent
for sulfonyl migration, was not found compatible in
combination with pivalic acid (entries 5-6). A different
palladium-catalyst, strong oxidant, or exclusion of CsOPiv did
not improve the yield further (entries 7-9). Reaction of ethyl
(NH)-pyrrole-2-carboxylate and benzene under the standard
conditions did not give the corresponding 5-arylated pyrrole.
This experiment suggests that the tosyl group at nitrogen not
only serves the purpose of protection in pyrroles, but also
facilitates the arylation at the 2-position. Interestingly,
reaction of pyrrole 8b in the absence of benzene gave pyrrole-
19
a
Figure 2. ORTEP diagram of 7a .
Next, we explored briefly the substrate scope that could
participate in the reaction (Table 2). Both aryl or alkyl sulfonyl
groups are capable of migrating from pyrrole-N to C-3 position
affording sulfonylated (NH)-2-arylpyrroles in good to excellent
yields. A qualitative comparison of sulfonyl migration involving
aryl fused sultam
9 in 65% yield via a palladium-catalyzed
intramolecular oxidative coupling.
Using the optimized conditions, we prepared various C-3
sulfonyl (NH)-2-arylpyrroles that are otherwise difficult to
prepare by literature procedure (Table 4). The readily
accessible N-Ts-pyrroles containing a C-2 substituent reacted
with benzene under the optimized conditions affording good
three different sulfonyl groups, viz. tosyl
(7aa), 4-
fluorobenzenesulfonyl (7b), and mesyl (7g) can be made from
our investigation. It reveals that migratory aptitude of sulfonyl
groups occurring with these groups is comparable, although
compound 7h with a C-3 mesyl group was isolated albeit in low
yield. Central to this investigation was the key role of
temperature that enables regioselective sulfonyl migration in
pyrroles in the absence of any base, metal or Lewis acid
catalyst.
to excellent yields of the products (7a , 7c, 7d and 7i).
a
Reaction of 8d and a mono-substituted arene, such as
nitrobenzene gave an easily separable mixture of 3-
arylsulfonyl-2-arylpyrroles 7ja and 7jb in
Disubstituted arenes were also viable substrates affording
various substituted 3-arylsulfonyl-2-arylpyrroles 7e 7f and 7k-
a 7:3 ratio.
,
7n.
To explore further the preparative value of the regioselective
sulfonyl migration in pyrroles, we next investigated the
possibility of integrating the two steps, viz. oxidative C-2
arylation and sulfonyl migration, into a one-pot domino
approach to the synthesis of C-3 sulfonylated 2-arylpyrroles.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

P
N
le
e
a
w
se
J
d
o
o
ur
n
n
o
a
t
l
a
o
d
f
ju
C
s
h
t
e
m
m
a
i
r
s
g
t
i
r
n
y
s
Page 4 of 14
ARTICLE
Journal Name
Table 4. Substrate Scope for One-Pot Arylation/Migration.
View Article Online
DOI: 10.1039/C7NJ01709J
a
Table 3. Optimization Study for One-pot Synthesis.
En
try
1
Pd-
Oxidant
AgOAc
AgOAc
Additive
CsOPiv
CsOPiv
Solvent
PivOH
PivOH
PhH
7c
(%)
52
catalyst
Pd(OAc)
2
2.5
mL
1.5
mL
1 mL
1.5
equi
v
2
Pd(OAc)
2
70
b
3
Pd(OAc)
Pd(OAc)
2
2
AgOAc
AgOAc
CsOPiv
CsOPiv
PivOH
PivOH
85
25
4
c
5
Pd(OAc)
Pd(OAc)
2
2
AgOAc
AgOAc
AgOAc
CsOPiv
CsOPiv
PivOH:
DMSO
2.5
mL
0
0
(
3:1)
c
6
PivOH:
DMSO
2.5
mL
(
1:1)
7
Pd(TFA)
2
CsOPiv
CsOPiv
-
PivOH
PivOH
PivOH
1 mL
1 mL
1 mL
76
0
c
Interestingly, the formation of 10 from 11, presumably
obtained by hydrolysis of 12, suggests that a competitive
sulfonyl migration from N- to O- instead of N- to C-3 position
has occurred. This experiment suggests that the migration of
sulfonyl group from N-1 to the C-3 position could be prohibited
in the presence of an electron-donating methoxymethyl group
8
Pd(OAc)
Pd(OAc)
2
2
2 2 8
K S O
9
AgOAc
65
a
8a (0.25 mmol), Pd-catalyst (10 mol%), CsOPiv (20 mol%), oxidant (3.0
c
b
equiv), solvent (2.5 mL); PivOH (2 mL); only trace amount of C-2
arylated product formed.
The regioselective migration of sulfonyl group to the C-3 at C-5 position.
position is particularly notable with an exception to the
formation of 7kb. The migratory aptitude of different aryl or
alkyl sulfonyl group was also investigated. While many of them
are indeed capable of migration from pyrrole-N to the C-3
position, 2,4-dinitroarylsulfonyl group was not compatible
(7q). It is noteworthy that strongly electron-deficient arenes
failed to undergo the one-pot domino reaction (7s).
Interestingly, reaction of N-Ts-2-phenylpyrrole 8k and p-xylene Scheme 3. Competitive Sulfonyl Migration from N- to -CH OH Group.
2
gave an inseparable regioisomeric mixture of C-3 and C-4
sulfonylated 2,5-diarylpyrroles 7ta and 7tb. This suggests that
the sulfonyl migration becomes competitive when two
different aryl groups are present at 2- and 5-positions. In case
of mono substituted arenses such as anisole and benzonitrile
as expected, anisole furnished two products (7ua) and (7ub) in
The mechanism of sulfonyl migration from N-1 position to the
C-3 position in pyrrole nucleus would be especially interesting,
as a similar migration in pyrroles is unknown. The sulfonyl
migration could occur via different pathways as shown in
Figure 3. A direct N- to C-3 transfer could occur via
a
2:1 ratio. Likewise, benzonitrile gave an inseparable
intermolecular reaction. The capture of electrophilic SO Ar
2
regioisomeric mixture of C-3 sulfonylated product (7v) albeit in
low yield.
group by another pyrrole could give C-3 sulfonylated product
(
Pathway A). Heterolytic or homolytic cleavages of pyrrole-N–
-
SO Ar bond could give an ion-pair pyrrole-N SO Ar, or free
+
13
Pyrrole 8l containing a methoxymethyl group did not give any
C-3 sulfonylated pyrrole 7w under the standard conditions,
2
2
15
radicals, respectively (Pathways B and C). N-Desulfonation of
pyrrole could occur by arene at C-2 position, which upon
subsequent C-desulfonation by pyrrole at C-3 position could
give the desired sulfonyl product (Pathway D).
although 2-arylpyrroles 10, 11 and 12 were isolated in varying
yields (Scheme 3).
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 14
Please do not adjust margins
New Journal of Chemistry
Journal Name
ARTICLE
N-desulfonation product 15 or 15c was observeVidewiAnrticalenOynlionef
these cases. The sulfonyl migration is
Intermolecular pathways
Intramolecular pathway
D
n
O
o
I:
t
10
a
.1
f
0
f e3 9
c
/
t
C
e
7
d
NJ
i
0
n
17
t
09J
h
e
A = Nucleophilic displacement
B = Intimate ion-pair
C = Radical mechanism
D1 = N-desulfonylation by arene C-2
D2 = Rotation around single bond
D3 = C-desulfonylation by pyrrole C-3
presence of a radical quencher TEMPO, suggesting that the
reaction does not involve the formation of a free-radical (eq.
A
B
C
D
3
). Thus, the two widely accepted pathways (B and C) are
Ts
seemingly least likely in this case.
R
R
R
R
R
N
Ph
N
N
H
Ph
N
Ph
N
When N-tosylpyrroles (unsubstituted, 2-substituted, or 2, 5-
disubstituted without an aryl substituent) were heated at 130
°C for 12 h, no reaction occurred (eq. 4). Similarly, N-Ts-2-
pentaflurophenylpyrrole 6h also did not give any product (eq.
+
Ts
Ts
Ts
D1
Ts
D3
Ph
R
N
H
N
R
Ts
Ts
D2
5
). These experiments suggest that an arene group is required
Figure 3. Possible Pathways (A, B, C and D) For Sulfonyl Migration.
at the 2-position in pyrroles, and additionally there should be
at least one unoccupied ortho-position in the arene.
To elucidate a plausible mechanism for the sulfonyl migration,
the following experiments were carried out. In a crossover
experiment, reaction of 6a and 6g under the standard
conditions gave 7aa and 7h (Scheme 4, eq. 1). However, any
intermolecular reaction that could lead to crossover products
Furthermore, wherein
a C-3 position is blocked as in
compound 6i, sulfonyl migration was not observed (Scheme 5).
Similarly, compound 21 also did not give any C-3
sulfonylpyrrole.
1
3
and 14 was not observed. Based on this experiment, the
pathway A is least probable. Heating 2-arylpyrrole 6a, 6b or 6f
in pivalic acid at 130 °C for 4 h in the presence of CsF, benzyl
sulfonate or benzene sulfonylchloride gave only the
corresponding C-3 sulfonylated products 7aa, 7c and 7g (eq. 2)
+
respectively. The capture of SO Ar by the nucleophile (F and
-
2
-
benzyl sulfonyl anion), or pyrrole-N by the electrophile
(benzenesulfonyl chloride) would be the competitive reactions
Scheme 5. Control Experiments to study Arene-Assited Sulfonyl Migration.
in Pathway B, which could result in the formation of N-
desulfonation product 15 or 15c, respectively. However, no
To investigate further the involvement of C-H bond breaking
during migration, both the arylated products 6a and 6j were
heated independently in pivalic acid at 130 °C (Scheme 6).
During the experiment, various aliquots were withdrawn from
the reaction mixtures at an interval of 5, 10, 15, 20 and 30 min
and subjected to HPLC analysis.
Scheme 6. Kinetic Study.
At each time interval, only an insignificant difference in
product formation was observed (Figure 4) suggesting that C–
H bond breaking is not involved during migration. A similar
1
conclusion can be drawn from the H NMR spectrum of 7z
lacking any aromatic phenyl proton. Had there been any C-H
bond breaking, the aromatic phenyl proton would have
1
appeared in the H NMR spectrum. Overall, our mechanistic
study indicates that a C-2 arene is essential for sulfonyl
migration, the question was whether this arene group could
act as the putative sulfonyl carrier.
Scheme 4. Control Experiments to Establish Mechanism of Sulfonyl Migration.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

P
N
le
e
a
w
se
J
d
o
o
ur
n
n
o
a
t
l
a
o
d
f
ju
C
s
h
t
e
m
m
a
i
r
s
g
t
i
r
n
y
s
Page 6 of 14
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C7NJ01709J
%
Formation of 7aa
% Formation of 7z
8
6
4
2
0
0
0
0
0
Scheme 8. Thermodynamics of C-S bond formation.
5
10
15
20
25
Intramolecular C-2 aryl group assisted sulfonyl migration is
proposed in Figure 5 and Gibbs free energy changes (∆G) at
each step is indicated. At the first step, N-desulfonation of
pyrrole by arene at C-2 position is energetically favorable by
Time (min)
a
Figure 4. Comparison of HPLC Yields of 7a and 7z.
5
.1 kcal/mol yielding comparatively stable intermediate VI.
To understand the mechanism of sulfonyl group migration
from pyrrole-N to pyrrole C-3 position computationally,
Density Functional Theory (DFT) calculations on reactants,
possible intermediates and product, were carried out using
parameterized hybrid meta-GGA functional M06/6-
Subsequently, intermediate VI undergoes C-C bond rotation
around C-2 to C-aryl bond to give intermediate VII, which is
marginally more stable by 0.4 kcal/mol. Next C-desulfonation
by C-3 of pyrrole further stabilizes the product 7aa by 3.8
kcal/mol. The sum of free energy changes at each step of
reaction (Figure 5) is 9.3 kcal/mol, which is the equal to the
3
11++G(d,p) level of theory. Energy calculation and geometry
optimization of reactants and products show that C-3
sulfonylpyrrole 7aa is relatively more stable than N-
sulfonylpyrrole 6a by 9.3 kcal/mol and C-4 sulfonylpyrrole 7ab
is relatively more stable than 6a by 9.0 kcal/mol. This indicates
that sulfonyl group migration from N to C-3 position or C-4 is
an energetically favorable process. To prove intermolecular
energy released for stabilizing C-3 sulfonylated product 7aa
.
Energetics of reaction pathway indicates that the
transformation of 6a to 7aa via intermediates VI followed by
VII is continually stabilizing. However, the necessary transition
states with their respective energy barrier (Ea) could not be
identified on the potential energy surface. Because of limited
experiments carried out to understand the mechanism and the
complexity of the mechanism, it is hard to depend exclusively
on a particular pathway described above.
13
pathway for sulfonyl migration through ion-pair formation,
15
or free radical mechanism, the bond dissociation energies
were calculated and attempts were made to obtain the
transition states. The bond dissociation energy of N-S bond in
6
a to generate ion-pairs (pyrrole-N- and +SO Ar) is ~150
2
kcal/mol, which is ~180 kcal/mol smaller than the bond
dissociation energy of N-H bond in pyrrole (~330 kcal/mol).
The homolytic cleavage of N-S bond in 6a to generate free
radicals, requires only 17.5 kcal/mol (Scheme 7). This signifies
that N-S bond is very fragile in 6a. The energy associated with
6a
C- +SO Ar bond formation is -211 kcal/mol exergonic whereas
2
through radical pathway (C• •SO Ar) it is -63.3 kcal/mol
2
exergonic (Scheme 8).
∆G
kcal/mol)
(
VII
VI
7ab
7a
a
Figure 5. Proposed intermediary steps to establish pathway for C-2 aryl assisted
Scheme 7.Thermodynamics of N-S bond cleavage.
sulfonyl migration quantum chemically.
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 14
Please do not adjust margins
New Journal of Chemistry
Journal Name
ARTICLE
22
2
. Procedure for C-2 arylation of pyrrole (8ka)
Conclusions
View Article Online
DOI: 10.1039/C7NJ01709J
Following a literature procedure, in an oven-dried screw cap
vial equipped with a magnetic stir bar, pyrrole substrate (0.5
We have developed an expedient approach to the preparation
of (NH)-2-arylpyrroles containing a sulfonyl functionality on
pyrrole ring via oxidative coupling followed by migration of
sulfonyl group from N-1 to C-3 position. The one-pot tandem
approach features an unprecedented C-3 sulfonylation in
pyrroles. The high preparative value of our protocol may be
justified by considering the ease of preparation of 2-aryl-3-
sulfonyl-(NH)-pyrroles that have invariably been prepared in
multi-steps. A detailed understanding of the mechanism of
sulfonyl migration and biological evaluation of the (NH)-2-
arylpyrroles prepared herein are in progress.
mmol), Pd(OAc) (10 mol%), phenyl boronic acid (1.5 equiv)
2
and acetic acid (5 mL) as solvent under O atmoshpere was
2
stirred at room temperature for 8 h. The reaction mixture was
quenched by the addtion of saturated solution of NaHCO (10
3
mL). Then, it was extracted with ethyl acetate (2 x 10 mL). The
combined organic layer was dried (Na SO ), concentrated
2
4
under reduced pressure, and purified by column
chromatography on silica using (dichloromethane/ hexane:1:4)
as an eluent to give the desired product.
3
. Procedure for N-mesylation of pyrroles (8h-8j, 8m)
To the cooled solution of pyrrole (2 mmol) in THF, NaH (1.2
equiv) was added slowly with vigorous stirring. After 10 mins
methane sulfonyl chloride (1.5 equiv) was added dropwise to
Experimental Section
General: Unless noted otherwise, all reagents and solvents
were purchased from commercial sources and used as
received. All palladium-catalyzed reactions were performed in
the reaction mixture. Upon completion of reaction, H O (10
2
mL) was added and extracted with ethyl acetate (2 x 10 mL).
Then, combined organic layer was dried over sodium sulphate
and concentrated under reduced pressure followed by
chromatography [silica, EtOAc-hexanes = 0.5:9.5 ~ 2:8] gave
corresponding N-mesylated pyrroles (28-30).
1
13
a screw-cap sealed tube. The H and C NMR spectra were
obtained with Me Si as an internal standard. Coupling
4
constants (J values) are reported in Hz. Column
chromatography was performed using silica gel (100-200
mesh). High resolution mass spectra (HRMS) were obtained
using electron spray ionisation (ESI) technique and as TOF
mass analyser. All melting points were taken using a melting
point apparatus equipped with a calibrated thermometer and
are uncorrected. New compounds were characterized by
18
4
. Procedure for C-2 arylation of pyrroles (6a-6j, 6k)
Following a literature procedure, in an oven-dried screw cap
vial equipped with a magnetic stir bar, pyrrole substrate (0.5
mmol), Pd(TFA)2 (10 mol%), AgOAc (1.5 mmol), PivOH (5
equiv), 1.5 mL arene as solvent was heated at 80 °C for 12 h.
The reaction mixture was allowed to cool to room
temperature and neutralized by the addition of saturated
solution of Na CO (10 mL). Then, it was extracted with ethyl
1
13
melting point, IR, H NMR, C NMR, and HRMS data.
Computational methods
2
3
All quantum chemical studies were performed using
acetate (2 x 10 mL). The combined organic layer was dried
Na SO ), concentrated under reduced pressure, and purified
20a
Gaussian09 suite
of program on acluster computer with
(
2
4
Intel octacore processors. The geometry and energy of all
structures wereoptimized without any symmetry constraints
by column chromatography on silica using (ethyl acetate/
hexane) as an eluent to give the desired product.
20b,c
using M06 level of theory with 6-311++G(d,p)
basis set.
Vibrational frequencies were calculated for all optimized
geometries at the same level to confirm the nature of the
stationary points as either minima or transition states. The
energy values provided in themanuscript are thermally
corrected free energy (∆G) changes.
5
. Procedure for reduction of aldehyde by sodium
borohydride (8la)
To a solution of N-tosyl pyrrole-2-carboxaldehyde (23) in
ethanol was added NaBH4 (1.5 equiv) and stirred at room
temperature for 30 mins. Water (20 mL) was added and the
aqueous layer was extracted with EtOAc (3 × 20 mL). The
combined organic layer was dried (Na SO ) and concentrated,
1
8
. Typical Procedure for N-sulfonylation of pyrroles (8a-8h,
21
k, 8n)
2
4
Following a literature procedure, to a solution of 2-substituted
pyrrole (0.5 mmol) in dichloromethane (2.5 mL) was added
KOH (1.5 equiv) and tetrabutylammonium hydrogensulfate (10
mol%) and was allowed to stir for 15 mins followed by addition
of solution of sulfonyl chloride (1.2 equiv) in dichloromethane
which upon column chromatography [silica, EtOAc -hexanes =
1
: 4] gave the desired product.
6
. Procedure for alkylation of hydroxyl group (8l)
A dried round bottom flask equipped with a magnetic stirrer
bar was charged with (1-Tosyl-1H-pyrrol-2-yl)methanol and
THF (5 mL) under nitrogen atmosphere. The reaction mixture
(1.0 mL) and the mixture was stirred at room temperature till
the starting material was consumed. Water (20 mL) was added
and the aqueous layer was extracted with EtOAc (3 × 20 mL).
The combined organic layer was dried (Na SO ) and
°
was cool down to 0 C and NaH (1.2 equiv) was added and
2
4
stirred for 15 mins. After which alkyl halide (1.1 equiv) was
added and continued the stirring for 1 h. After completion of
the reaction, it was quenched with water (10 mL) and was
extracted with ethyl acetate (3 x 20 mL). The combined organic
concentrated, which upon chromatography [silica, EtOAc -
hexanes = 1: 19 to 1: 9] gave the N-sulfonylated pyrroles.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

P
N
le
e
a
w
se
J
d
o
o
ur
n
n
o
a
t
l
a
o
d
f
ju
C
s
h
t
e
m
m
a
i
r
s
g
t
i
r
n
y
s
Page 8 of 14
ARTICLE
Journal Name
layer was dried over Na SO4 and the solvent was removed In an oven-dried screw cap vial equipped with a VmieawgAnrteictleicOnsltinier
2
DOI: 10.1039/C7NJ01709J
under reduced pressure to give 32.
bar, a solution of substrate (0.1mmol) in THF (1 mL) was
treated with phenylmagnesium chloride (0.5 mL, 1M solution
in Me-THF) at room temperature for 5 mins. After completion,
23
7
. Procedure for synthesis of 3,4-disubstituted pyrrole (8ma)
Following a literature procedure, to a solution of sodium tert- saturated solution of ammonium chloride (2 mL) was added
butoxide (2 equiv) in THF (10 mL), solution of p- and the mixture was diluted with H O (5 mL) and extracted
2
toluenesulfonylmethylisocyanide (10 mmol) and diethyl with EtOAc (10 mL x 2). The combined organic layer was dried
fumarate (10 mmol) in THF (10 mL) was added dropwise. As (Na SO ) and concentrated, which upon chromatography
2
4
reaction mixture turned brownish upon addition,reaction was [silica, EtOAc -hexanes = 2:8] gave 63.
allowed to continue overnight. Following which water (10 mL)
was added and it was extracted with EtOAc (3 x 10 mL). The Methyl 5-phenyl-1-tosyl-1H-pyrrole-2-carboxylate (6a).
23
-1
combined organic layer was concentrated under reduced Colorless solid (115 mg, 65%); IR (KBr, cm ): 2922, 1706, 1478,
1
371, 763; H NMR (CDCl ): δ 7.41-7.37(m, 3H), 7.31(dt, J = 8.5,
1
1
6
2
pressure and washed with hexane to give 3,4-disubstituted
pyrrole as a yellow solid.
3
.4 Hz, 2H), 7.21(dd, J = 8.0, 1.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H),
.92 (d, J = 3.5 Hz, 1H), 6.12 (d, J = 3.5 Hz, 1H), 3.96 (s, 3H),
.40 (s, 3H).
8
.
Procedure for synthesis of pyrrole sultam by
1
intramolecular cyclization (9)
8
Methyl 5-phenyl-4-tosyl-1
Colorless solid (31 mg, 87%); mp. 189-190 °C; IR (KBr, cm ):
H
-pyrrole-2-carboxylate
a
(7a ).
Following a literature procedure, in an oven-dried screw cap
vial equipped with a magnetic stir bar, pyrrole substrate (0.5
mmol), Pd(OAc)2 (10 mol%), AgOAc (1.5 mmol), CsOPiv (20
mol%), 3 mL pivalic acid as solvent was heated at 130 ºC for 12
h. The reaction mixture was allowed to cool to room
temperature and neutralized by the addition of saturated
solution of Na CO (10 mL). Then, it was extracted with ethyl
-
1
1
244, 2929, 1703, 1312, 1145, 774; H NMR (CDCl ): δ 9.73 (bs,
3
1
3
3
1
5
3
3
H), 7.54-7.51 (m, 2H), 7.49 (d, J = 8.2 Hz, 2H), 7.44-7.40 (m,
H), 7.37 (d, J = 2.8 Hz, 1H), 7.11 (d, J = 8.0 Hz, 2H), 3.78 (s,
13
H), 2.32 (s, 3H); C NMR (CDCl ): δ 161.1, 143.5, 139.6, 138.3,
3
29.7, 129.6, 129.3, 129.1, 128.2, 127.0, 124.3, 121.7, 117.4,
+
2
3
2.0, 21.4; HRMS (ESI) m/z calcd for C H NO S [M+H]
4
19
18
acetate (2 x 10 mL). The combined organic layer was dried
Na SO ), concentrated under reduced pressure, and purified
56.0957, found 356.0955.
(
2
4
by column chromatography on silica using (EtOAc/ hexanes =
Methyl 5-phenyl-3-tosyl-1
Colorless semi-solid (2 mg, 5%); IR (KBr, cm ): 3193, 2920,
H
-pyrrole-2-carboxylate
-1
b
(7a ).
2
:8) as an eluent to give the desired product.
1
1
701, 1320, 746; H NMR (CDCl ): δ 9.67 (bs, 1H), 7.83 (d, J =
3
9
. Synthesis of C-3 sulfonylated compounds (7a -h)
a
8.3 Hz, 2H), 7.58 (d, J = 7.4 Hz, 2H), 7.47 (t, J = 7.2, 2H), 7.40 (t,
J = 7.2 Hz, 1H), 7.32 (d, J = 8.1 Hz, 2H), 7.22 (s, 1H), 3.85 (s, 3H),
In an oven-dried screw capped vial equipped with magnetic
13
stir bar, 2,5-substituted pyrrole substrate (0.1 mmol) in PivOH 2.44 (s, 3H); C NMR (CDCl ): δ 176.4, 143.8, 130.9, 129.3,
3
°
(
0.5 mL) was heated at 130 C for 4 h. The reaction mixture was 129.1, 128.9, 127.9, 124.9, 111.2, 52.1, 21.6; HRMS (ESI) m/z
+
allowed to cool to room temperature and neutralized by the calcd for C H NO S [M+H] 356.0957, found 356.0950.
1
9
18
4
addition of saturated solution of Na CO (5 mL). Then, it was
2
3
extracted with ethyl acetate (2 x 5 mL). The combined organic 1-(5-Phenyl-1-tosyl-1
H
-pyrrol-2-yl)ethan-1-one
layer was dried (Na SO ), concentrated under reduced Colorless solid (123 mg, 73%); mp.132-133 °C; IR (KBr, cm ):
(6b).
-
1
2
4
1
pressure, and purified by column chromatography on silica 2922, 1716, 1291, 1121, 770; H NMR (CDCl
): δ 7.41 (d, J = 8.3
Hz, 3H), 7.37-7.29 (m, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.15 (d, J =
.0 Hz, 2H), 6.93 (d, J = 3.4 Hz, 1H), 6.13 (d, J = 3.4 Hz, 1H), 2.49
3
using (EtOAc/ hexanes = 2:8) as an eluent to give the desired
product.
8
1
3
(s, 3H), 2.40 (s, 3H); C NMR (CDCl ): δ 161.8, 144.9, 143.8,
3
1
1
3
35.6, 131.3, 130.6, 130.1, 129.1, 128.8, 127.6, 127.6, 121.8,
+
1
0. Synthesis of C-2 arylated C-3 sulfonylated compounds
14.4, 26.9, 21.6; HRMS (ESI) m/z calcd for C H NO S [M+H]
18
19
3
(
7a , 7c-v)
a
40.1007, found 340.1006.
In an oven-dried screw cap vial equipped with a magnetic stir
bar, pyrrole substrate (0.25 mmol), Pd(OAc) (10 mol%), AgOAc
2
5
solid (125 mg, 77%); mp. 163-169 °C; IR (KBr, cm ): 2912,
-Phenyl-1-tosyl-1
H-pyrrole-2-carbaldehyde (6c). Dark brown
-
(0.75 mmol), CsOPiv (20 mol%), 1 mL arene and 2 mL pivalic
1
acid as solvent was heated at 130 ºC for 16 h. The reaction
mixture was allowed to cool to room temperature and
neutralized by the addition of saturated solution of Na CO (10
1
1670, 1467, 1369, 760; H NMR (CDCl ): δ 10.37(s, 1H), 7.45 (t,
3
J = 7.2 Hz, 1H), 7.39 (t, J = 8.0 Hz, 2H), 7.32 (d, J = 7.2 Hz, 2H),
2
3
7
.25-7.21(m, 3H), 7.14 (d, J = 8.2 Hz, 2H), 6.25 (d, J = 3.6 Hz,
mL). Then, it was extracted with ethyl acetate (2 x 10 mL). The
combined organic layer was dried (Na SO ), concentrated
13
H), 2.38 (s, 3H); C NMR (CDCl ): δ 182.2, 145.6, 144.2, 137.8,
34.9, 130.6, 130.6, 129.5, 129.3, 127.6, 126.9, 122.9, 116.6,
1
3
2
4
1
under reduced pressure, and purified by column
chromatography on silica using (EtOAc/ hexanes = 2:8) as an
eluent to give the desired product.
+
1.6; HRMS (ESI) m/z calcd for C H NO S [M+H] 326.0851,
2
found 326.0851.
18
16
3
1
-(5-(3,4-Dimethylphenyl)-1-tosyl-1
6d). Colorless solid (111 mg, 61%); mp. 125-127 °C; IR (KBr,
H-pyrrol-2-yl)ethanone
1
1. Synthesis of ortho-sulfonylated compound 21 by
(
cm ): 2924, 2851, 1705, 1455, 834; H NMR (CDCl ): δ 7.34 (d,
-
1
1
nucleophilic ring opening
3
8
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 9 of 14
Please do not adjust margins
New Journal of Chemistry
Journal Name
ARTICLE
J = 8.4 Hz, 2H), 7.27 (d, J = 3.6 Hz, 1H), 7.22 (d, J = 8.1 Hz, 2H), (dd, J = 1.6, 7.7 Hz, 1H), 7.25 (s, 1H), 7.18-7.15 (m, 3H), 2.48 (s,
View Article Online
13
7
3
1
1
.18-7.12 (m, 2H), 6.66 (s, 1H), 6.18 (d, J = 3.7 Hz, 1H), 2.48 (s, 3H), 2.37 (s, 3H), 2.32 (s, 3H), 2.28 (s, 3H C NMR (CDCl ): δ
D) ;O I: 10.1039/C7NJ01709J
3
13
H), 2.37 (s, 3H), 2.32 (s, 3H), 2.28 (s, 3H); C NMR (CDCl ): δ 187.9, 143.5, 139.7, 139.6, 138.9, 136.7, 130.2, 130.1, 129.7,
3
81.9, 145.5, 142.3, 136.8, 136.0, 135.4, 134.0, 133.8, 130.2, 129.3, 127.0, 126.7, 126.2, 123.9, 118.4, 25.2, 21.4, 19.7, 19.6;
+
30.1, 129.6, 127.4, 122.1, 115.8, 25.3, 21.6, 20.7, 19.7; HRMS: HRMS (ESI) m/z calcd for C H NO S [M+H] 368.1320, found
21
22
3
+
calcd for C H NO S [M+H] 368.1320, found 368.1323.
2
368.1323.
1
22
3
5
-(3,4-Dichlorophenyl)-1-tosyl-1
H
-pyrrole-2- carbaldehyde 5-(3,4-Dichlorophenyl)-4-tosyl-1
H
-pyrrole-2-carbaldehyde
6e). Colorless solid (110 mg, 56%); mp. 143-145 °C; IR (KBr, (7f). Colorless solid (31 mg, 80%); mp.207-208 °C; IR (KBr, cm
-
(
cm ): 2922, 1672, 1169, 812, 592; H NMR (CDCl ): δ 10.35 (s,
-
1
1
1
1
): 3247, 2924, 2853, 1650, 755; H NMR (CDCl ): δ 10.02 (bs,
3
3
1
Hz, 1H), 2.41 (s, 3H); C NMR (CDCl ): δ 181.9, 146.0, 141.0, 2H), 7.50-7.47 (m, 3H), 7.20 (d, J = 8.0 Hz, 2H), 2.37 (s, 3H);
H), 7.50 (d, J = 8.2 Hz, 1H), 7.29-7.19 (m, 7H), 6.28 (d, J = 3.6 1H), 9.55 (s, 1H), 7.60 (d, J = 1.6 Hz, 1H), 7.56 (d, J = 8.3 Hz,
13
13
C
38.1, 134.7, 133.7, 131.9, 131.9, 130.5, 130.0, 129.8, 129.6, NMR (CDCl ): δ 179.4, 144.3, 138.8, 137.2, 134.8, 132.9, 131.1,
3
1
1
3
26.9, 122.6, 117.0, 21.6; HRMS (ESI) m/z calcd for 131.0, 130.6, 129.3, 128.7, 128.2, 127.1, 126.2, 122.1, 21.5;
+
+
C H Cl NO S [M+H] 394.0071, found 394.0069.
14
HRMS (ESI) m/z calcd for C H Cl NO S [M+H] 394.0071,
18 14 2 3
18
2
3
found 394.0069.
Methyl
carboxylate (6f). White Solid (96 mg, 69%); IR (KBr, cm ): Methyl
1-(methylsulfonyl)-5-phenyl-1H-pyrrole-2-
-1
2
3
4-(methylsulfonyl)-5-phenyl-1
017, 2938, 1723, 1472, 753; H NMR (CDCl ): δ 7.44-7.41(m, carboxylate (7g). Colorless solid (19 mg, 70%); mp. 180-185 °C;
H-pyrrole-2-
1
3
5
3
3
-
1
1
H), 7.04 (d, J = 3.6 Hz, 1H), 6.23 (d, J = 3.6 Hz, 1H), 3.92 (s, IR (KBr, cm ): 3443, 2922, 1716, 1291, 1121, 770; H NMR
H), 3.78 (s, 3H). (CDCl ): δ 9.72 (bs, 1H), 7.76-7.75 (m, 2H), 7.52-7.51 (m, 3H),
3
1
3
7
.42 (d, J = 2.8 Hz, 1H), 3.88 (s, 3H), 2.89 (s, 3H); C NMR
(CDCl ): δ 160.9, 137.5, 130.1, 129.2, 128.9, 127.6, 123.4,
6g). Brown Solid (93 mg, 75%); IR (KBr, cm ): 1663, 1377, 121.9, 117.2, 52.2, 44.3; HRMS (ESI) m/z calcd for C13H14NO S
4
7
52; H NMR (CDCl ): δ 9.88 (s, 1H), 7.48-7.45 (m, 5H), 7.25 (d, [M+H] 280.0644, found 280.0639.
3
J = 3.7 Hz, 1H), 6.39 (d, J = 3.7 Hz, 1H), 3.46 (s, 3H).
1
-(Methylsulfonyl)-5-phenyl-1
H
-pyrrole-2-carbaldehyde
3
22
-1
(
1
+
4
-(Methylsulfonyl)-5-phenyl-1
Yellow solid (5 mg, 21%); mp. 130-135 °C; IR (KBr, cm ): 3239,
H-pyrrole-2-carbaldehyde (7h).
-
1
1
-(4-((4-fluorophenyl)sulfonyl)-5-phenyl-1
H-pyrrol-2-
1
yl)ethanone (7b). Colorless solid (29 mg, 83%); mp. 158-160 2923, 1668, 1297, 1129, 764; H NMR (CDCl
1
): δ 9.93 (bs, 1H),
C; IR (KBr, cm ): 3246, 1698, 1477, 1320, 1169, 777; H NMR 9.59 (s, 1H), 7.80-7.78 (m, 2H), 7.53-7.49 (m, 4H), 2.88 (s, 3H);
3
-
1
°
1
3
(
CDCl ): δ 9.89 (bs, 1H), 7.61-7.57 (m, 2H), 7.54-7.52 (m, 2H),
C NMR (CDCl
.50-7.41 (m, 4H), 7.00-6.95 (m, 2H), 2.62 (s, 3H); C NMR 125.6, 124.4, 122.2, 44.1; HRMS (ESI) m/z calcd for C12H12NO S
3
3
): δ 179.4, 131.1, 130.8, 130.6, 129.1, 128.4,
3
13
7
+
(
CDCl ): δ 188.2, 166.3 (d, J = 253 Hz), 139.4, 138.2 (d, J = 3 Hz), [M+H] 250.0538, found 250.0539.
3
1
J = 22 Hz), 25.3; HRMS (ESI) m/z calcd for C H FNO S [M+H]
30.4, 130.1, 129.8, 129.7, 129.5, 128.6, 124.0, 118.2, 116.0 (d,
+
1-(1-Tosyl-1H-pyrrol-2-yl)ethanone (8a). Colorless solid (117
mg, 89%); mp. 93-94 °C; IR (KBr, cm ): 3050, 1672, 1593, 1442,
18
15
3
-1
3
44.0757, found 344.0759.
1
1
367, 1173, 744; H NMR (CDCl ): δ 7.92 (d, J = 8.4 Hz, 2H),
3
1
solid (29 mg, 85%); mp. 186-188 °C; IR (KBr, cm ): 3245, 2924, = 3.7, 1.7 Hz, 1H), 6.35 (t, J = 3.4 Hz, 1H), 2.43 (s, 3H), 2.37 (s,
-(5-Phenyl-4-tosyl-1
H
-pyrrol-2-yl)ethanone (7c). Brownish 7.84 (dd, J = 3.2, 1.7 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.07 (dd, J
1
-
1
13
2
7
7
854, 1739, 1651, 1139, 841; H NMR(CDCl ): δ 9.69 (bs, 1H), 3H); C NMR (CDCl
3
): δ 185.8, 144.7, 135.9, 133.2, 130.3,
.56-7.54 (m, 2H), 7.51 (d, J = 8.3 Hz, 2H), 7.47-7.40 (m, 4H), 129.3, 128.3, 124.3, 110.2, 26.9, 21.6; HRMS (ESI) m/z calcd for
3
1
.13 (d, J = 8.0 Hz, 2H), 2.47 (s, 3H), 2.34 (s, 3H); C NMR
3
+
S [M+H] 264.0694, found 264.0693.
C
H
13
14NO
3
(CDCl ): δ 188.0, 143.6, 139.4, 139.1, 130.3, 130.0, 129.4,
3
1
m/z calcd for C H NO S [M+H] 340.1007, found 340.1009.
29.3, 128.8, 128.4, 127.0, 124.5, 118.1, 25.3, 21.4; HRMS (ESI) Methyl 1-tosyl-1H-pyrrole-2-carboxylate (8b). Colorless solid
(125 mg, 90%); mp. 104-106 °C; IR (KBr, cm ): 2923, 1728,
+
-1
1
9
18
3
1
1
594, 1358, 1146, 742; H NMR (CDCl ): δ 7.90 (d, J = 8.4 Hz,
3
5
solid (27 mg, 84%); mp. 191-192 °C; IR (KBr, cm ): 3244, 2924, (dd, J = 3.5, 1.8 Hz, 1H), 6.32 (t, J = 3.5 Hz, 1H), 3.74 (s, 3H),
-Phenyl-4-tosyl-1
H
-pyrrole-2-carbaldehyde (7d). Yellowish 2H), 7.74 (dd, J = 3.1, 1.8 Hz, 1H), 7.35 (d, J = 8.2 Hz, 2H), 7.07
-
1
1
13
2
834, 1651, 707; H NMR (CDCl ): δ 9.95 (bs, 1H), 9.57 (s, 1H), 2.44 (s, 3H); C NMR (CDCl
3
): δ 159.1, 144.9, 135.8, 129.4,
.59 (d, J = 6.8 Hz, 2H), 7.57-7.42 (m, 6H), 7.15 (d, J = 8.0 Hz, 129.1, 128.2, 124.8, 123.3, 110.3, 51.7, 21.7; HRMS (ESI) m/z
3
7
13
+
S [M+H] 280.0644, found 280.0639.
2
H), 2.35 (s, 3H); C NMR (CDCl ): δ 179.3, 143.8, 140.4, 139.1, calcd for C13
3
H
14NO
4
1
30.7, 130.2, 129.4, 129.4, 128.5, 127.1, 125.5, 122.3, 119.1,
+
1.4; HRMS (ESI) m/z calcd for C H NO S [M+H] 326.0851, Methyl
2
found 326.0852.
8-methylbenzo[d]pyrrolo[1,2-b]isothiazole-3-
18
16
3
18
carboxylate 5,5-dioxide (9). White-crystalline solid (94 mg,
−
1
1
6
8%); IR (KBr, cm ): 3421, 2949, 1632, 1421, 1160, 1033; H
NMR (CDCl ): δ 7.68 (d, J = 8.0 Hz, 1H), 7.40 (s, 1H), 7.30 (d, J =
7e). Colorless solid (24 mg, 65%); mp. 191-193 °C; IR (KBr, cm 8.0 Hz, 1H), 7.05 (d, J = 3.7 Hz, 1H), 6.48 (d, J = 3.7 Hz, 1H), 3.97
)
: 3257, 2924, 2853, 1666, 1465, 822; H NMR (CDCl ): δ 9.62 (s, 3H), 2.48 (s, 3H).
bs, 1H), 7.58 (d, J = 8.2 Hz, 2H), 7.44 (d, J = 2.8 Hz, 1H), 7.31
1
-(5-(3,4-Dimethylphenyl)-4-tosyl-1
H
-pyrrol-2-yl)ethanone
3
-
(
1
1
3
(
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
Please do not adjust margins

P
N
le
e
a
w
se
J
d
o
o
ur
n
n
o
a
t
l
a
o
d
f
ju
C
s
h
t
e
m
m
a
i
r
s
g
t
i
r
n
y
s
Page 10 of 14
ARTICLE
Journal Name
2
3
1
-Tosyl-1
H-pyrrole-2-carbaldehyde (8c). Bluish solid, (105 mg, 1-(Methylsulfonyl)-1H-pyrrole (8j). Brown liquid; (128 mg,
View Article Online
-1
-1
1
8
1
9
1
5%); mp. 107-109 °C; IR (KBr, cm ): 2895, 1666, 1538, 1421, 44%); IR (ATR, cm ): 3025, 2933, 1730 ,D O1 4I : 10.1039/C7NJ01709J
1
363, 1251, 1153, 1086, 1056, 776, 670; H NMR (CDCl ): δ (CDCl ): δ 7.15(t, J = 2.3 Hz, 2H), 6.39(t, J = 2.3 Hz, 2H), 3.16(s,
56, 739; H NMR
3
3
.98 (s, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.63 (dd, J = 3.0, 1.8 Hz, 3H).
H), 7.34 (d, J = 8.1 Hz, 2H), 7.17 (dd, J = 3.7, 1.7 Hz, 1H), 6.41
13
(t, J = 3.3 Hz, 1H), 2.43 (s, 3H); C NMR (CDCl ): δ 178.9, 145.9, 2-Phenyl-1-tosyl-1
3
H-pyrrole (8k). Brown solid (100 mg, 68%);
-1
1
35.2, 133.5, 130.1, 129.4, 127.4, 124.4, 112.4, 21.6; HRMS mp. 112-114 °C; IR (KBr, cm ): 2923, 1634, 1368, 1169, 761; H
1
+
ESI) m/z calcd for C H NO S [M+H] 250.0538, found NMR (CDCl ): δ 7.46 (dd, J = 3.2, 1.8 Hz, 1H), 7.40-7.36 (m, 1H),
(
12
12
3
3
2
50.0537.
7.35-7.30 (m, 2H), 7.25 (d, J = 8.4 Hz, 4H), 7.12 (d, J = 8.1 Hz,
2
H), 6.33 (d, J = 3.3 Hz, 1H), 6.18 (dd, J = 1.8, 3.1 Hz, 1H), 2.37
13
Ethyl 1-tosyl-1H-pyrrole-2-carboxylate (8d). Off-white solid (s, 3H); C NMR (CDCl ): δ 144.4, 136.0, 135.6, 131.4, 130.9,
3
-1
(121 mg, 83%); mp. 105-107 °C; IR (KBr, cm ): 2929, 1728, 129.4, 128.2, 127.3, 127.1, 124.0, 115.7, 112.0, 21.5; HRMS
1
443, 1360, 1144, 754; H NMR (CDCl ): δ 7.90 (d, J = 8.3 Hz, (ESI) m/z calcd for C H NO S [M+H] 298.0902, found
+
1
2
3
17 16
2
H), 7.73 (dd, J = 3.2, 1.8 Hz, 1H), 7.34 (d, J = 8.3 Hz, 2H), 7.06 298.0904.
(dd, J = 3.6, 1.8 Hz, 1H), 6.31 (t, J = 3.4 Hz, 1H), 4.22 (q, J = 7.1
Hz, 2H), 2.44 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H); C NMR (CDCl ): δ (1-Tosyl-1
13
3
H-pyrrol-2-yl)methanol (8la). Colorless solid (114
-1
1
6
2
58.7, 144.8, 135.9, 129.4, 129.0, 128.1, 125.2, 123.0, 110.2, mg, 91%); mp. 131-132 °C; IR (KBr, cm ): 3785, 3389, 2924,
0.7, 21.6, 14.1; HRMS (ESI) m/z calcd for C H NO S [M+H]
94.0800, found 294.0798.
+
1
1597, 1366, 812; H NMR (CDCl ): δ 7.74 (d, J = 8.4 Hz, 2H),
1
4
16
4
3
7.33 (d, J = 8.1 Hz, 2H), 7.31 (m, 1H), 6.28-6.24 (m, 2H), 4.62 (d,
13
J = 7.0 Hz, 2H), 2.74 (t, J = 7.1 Hz, 1H), 2.43 (s, 3H); C NMR
1-((3,5-dimethylphenyl)sulfonyl)-1H-pyrrole-2- (CDCl ): δ 145.2, 136.1, 134.5, 130.1, 126.6, 123.6, 115.2,
Methyl
carboxylate (8e). Yellowish solid (95 mg, 65%); mp. 120-122 111.8, 56.8, 21.6; HRMS: calcd for C H NO S [M+H]
3
+
12
14
3
-
C; IR (KBr, cm ): 3142, 2923, 1732, 1450, 1147, 757; H NMR 252.0694, found 252.0698.
1
1
°
(CDCl ): δ 7.47 (dd, J = 3.1, 1.8 Hz, 1H), 7.57 (s, 2H), 7.25 (s,
3
1
(
H), 7.09 (dd, J = 3.6, 1.8 Hz, 1H), 6.35 (t, J = 3.4 Hz, 1H), 3.74 2-(Methoxymethyl)-1-tosyl-1
H-pyrrole (8l). Off-white solid
1
s, 3H), 2.40 (s, 6H); C NMR (CDCl ): δ 159.0, 138.9, 138.6, (101 mg, 76%): mp. 102-103 °C; IR (KBr, cm ): 2925, 1596,
3
-1
3
1
1
m/z calcd for C H NO S [M+H] 294.0800 found 294.0804.
35.6, 129.2, 125.3, 124.9, 123.3, 110.3, 51.7, 21.2; HRMS (ESI) 1397, 1366, 1175, 949, 669; H NMR (CDCl ): δ 7.79 (d, J = 8.4
3
+
1
4
16
4
Hz, 2H), 7.34 (dd, J = 1.8, 3.2 Hz, 1H), 7.29 (d, J = 8.1 Hz, 2H),
.28 (dd, J = 1.8, 3.2 Hz, 1H), 6.24 (t, J = 3.2 Hz, 1H), 4.56 (s,
6
13
Methyl
carboxylate (8f). Off-white solid (108 mg, 77%); mp. 128-130 131.2, 129.6, 127.1, 123.8, 115.9, 111.1, 65.8, 57.3, 21.6;
1-((3-fluorophenyl)sulfonyl)-1H-pyrrole-2- 2H), 3.20 (s, 3H), 2.41 (s, 3H); C NMR (CDCl ): δ 144.6, 136.4,
3
-1
1
C; IR (KBr, cm ): 3077, 2962, 1762, 1597, 1365, 1147, 794; H HRMS (ESI) m/z calcd for C H NO S [M+H] 266.0851, found
+
°
NMR (CDCl ): δ 7.82-7.79 (m, 1H), 7.73-7.69 (m, 2H), 7.57-7.51 266.0850.
13 16 3
3
(
m, 1H), 7.37-7.32 (m, 1H), 7.10 (q, J = 1.8 Hz, 1H), 6.37 (t, J =
13
3
Hz), 159.0, 140.7 (d, J = 29 Hz), 130.6 (d, J = 31 Hz), 129.1, Brown solid (421 mg, 73%); mp. 132-134 °C; IR (KBr, cm ):
1
1
.4 Hz, 1H), 3.75 (s, 3H); C NMR (CDCl ): δ 163.2 (d, J = 251 Diethyl 1-(methylsulfonyl)-1
H-pyrrole-3,4-dicarboxylate (8m).
3
-
1
1
25.0, 123.8 (d, J = 13 Hz), 123.6, 121.2 (d, J = 21 Hz), 115.6, 2930, 1730, 1175, 1067, 770; H NMR (CDCl ): δ 7.65 (s, 2H),
3
1
15.3, 110.0, 51.8; HRMS (ESI) m/z calcd for C H FNO S 4.33(q, J = 7.1 Hz, 4H), 1.36 (t, J = 7.2 Hz, 6H); C NMR (CDCl3):
3
12
11
4
+
[
M+H] 284.0393, found 284.0396.
δ 162.1, 125.3, 120.1, 61.0, 43.3, 14.1; HRMS (ESI) m/z calcd
+
for C H NO S [M+H] 290.0698, found 290.0699.
11
16
6
1
-((2,4-Dinitrophenyl)sulfonyl)-1
8g). Yellowish solid (84 mg, 52%); mp. 142-143 °C; IR (KBr, cm 1-(1-((4-Fluorophenyl)sulfonyl)-1
H-pyrrole-2-carbaldehyde
-
(
H-pyrrol-2-yl)ethanone (8n).
1
1
: 2923, 2852, 1675, 1539, 1349, 745; H NMR (CDCl ): δ 9.49 White solid (85 mg, 62%); mp. 105-107 °C; IR (KBr, cm ): 3044,
-1
)
s, 1H), 8.86 (d, J = 8.0 Hz, 1H), 8.66-8.63 (m, 2H), 7.80-7.78 (m, 1701, 1442, 1385, 1176, 737; H NMR (CDCl ): δ 8.07-8.03 (m,
3
1
(
3
1
3
C
1
NMR (CDCl ): δ 177.0, 150.6, 148.3, 136.4, 135.9, 133.4, 132.6, 1.7, 3.7 Hz, 1H), 6.36 (t, J = 3.5 Hz, 1H), 2.36 (s, 3H); C NMR
H), 7.27 (dd, J = 3.6, 1.7 Hz, 1H), 6.57 (t, J = 3.5 Hz, 1H);
2H), 7.81 (dd, J = 1.7, 3.1 Hz, 1H); 7.21 (m, 2H), 7.07 (dd, J =
13
3
1
C H N O S [M+H] 326.0083, found 326.0080.
30.6, 126.3, 120.1, 112.3; HRMS(ESI) m/z calcd for (CDCl ): δ 185.9, 166.8 (d, J = 256 Hz), 134.7 (d, J = 3 Hz), 133.3,
3
+
11
8
3
7
131.4, 131.3, 130.3, 124.5, 116.1 (d, J = 22 Hz), 110.5, 26.9;
+
HRMS (ESI) m/z calcd for C H FNO S [M+H] 268.0444, found
268.0447.
1
2
11
3
23
Methyl 1-(methylsulfonyl)-1
Colorless liquid; (285 mg, 77%); IR (ATR, cm ): 2924, 2853,
H
-pyrrole-2-carboxylate (8h).
-
1
1
1
7
722, 1150, 757; H NMR (CDCl ): δ 7.53-7.52 (m, 1H), 7.12- Ethyl 5-phenyl-4-tosyl-1
H-pyrrole-2-carboxylate (7i). Off-
3
-1
.11 (m, 1H), 6.29 (t, J = 3.4 Hz, 1H), 3.89(s, 3H), 3.73(s, 3H).
white solid (81 mg, 88%); mp. 192-194 °C; IR (KBr, cm ): 3239,
1
2
H-pyrrole-2-carbaldehyde (8i). Brown 7.56-7.53 (m, 2H), 7.52 (d, J = 8.3 Hz, 2H), 7.48-7.40 (m, 4H),
981, 1698, 1509, 1312, 714; H NMR (CDCl ): δ 9.65 (bs, 1H),
3
23
1
solid; (283 mg, 82%); IR (KBr, cm ): 3017, 2933, 2843 2793, 7.14 (d, J = 8.0 Hz, 2H), 4.29 (q, J = 7.6 Hz, 2H), 2.35 (s, 3H),
-(Methylsulfonyl)-1
-1
1
13
1
7
3
674, 1362, 743; H NMR (CDCl ): δ 9.69 (d, J = 0.84 Hz, 1H), 1.36 (t, J = 7.1 Hz, 3H); C NMR (CDCl ): δ 160.5, 143.4, 139.7,
3 3
.62-7.61 (m, 1H), 7.23-7.22 (m, 1H), 6.42(t, J = 3.3 Hz, 1H), 137.9, 129.5, 129.3, 129.1, 128.3, 127.0, 124.3, 122.1, 117.1,
.64(s, 3H).
1
0 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 11 of 14
Please do not adjust margins
New Journal of Chemistry
Journal Name
ARTICLE
7.16-7.06 (m, 4H), 6.82 (s, 1H), 3.70 (s, 3H), 2.37 (s, 3H), 2.27
+
6
3
1.2, 21.4, 14.2; HRMS(ESI) m/z calcd for C H NO S [M+H]
20 20 4
View Article Online
1
3
70.1113, found 370.1114.
1.1, 143.3, 139.5,
(s, 3H), 1.85 (s, 3H); C NMR (CDCl ): δD O1 6I : 10.1039/C7NJ01709J
3
1
-pyrrole-2-carboxylate 125.0, 121.4, 115.8, 51.9, 21.5, 20.7, 19.0; HRMS (ESI) m/z
38.0, 135.1, 134.6, 131.5, 130.6, 129.7, 129.1, 128.3, 127.3,
Ethyl
5-(4-nitrophenyl)-4-tosyl-1
H
7ja). Yellowish solid (41 mg, 40%); mp. 122-127 °C; IR (KBr, cm calcd for C21
-
+
S [M+H] 384.1270, found 384.1271.
(
H22NO
4
1
)
1
: 3220, 1721, 1533, 1105, 715; H NMR (CDCl ): δ 10.09 (bs,
3
1
Hz, 1H), 7.58 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 2.6 Hz, 1H), 7.19 (d, carboxylate (7n). Off-white solid (62 mg, 63%); mp. 212-213
H), 8.31-8.28 (m, 2H), 8.04 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 8.3 Ethyl
5-(2,5-dimethylphenyl)-4-tosyl-1 -pyrrole-2-
H
-
J = 8.1 Hz, 2H), 4.27 (q, J = 7.1 Hz, 2H), 2.38 (s, 3H), 1.34 (t, J = °C; IR (KBr, cm ): 3240, 2982, 1681, 1484, 1316, 816; H NMR
1
1
1
3
7
1
1
.1 Hz, 3H); C NMR (CDCl ): δ 160.3, 147.9, 144.1, 139.3, (CDCl ): δ 9.41 (bs, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.39 (d, J = 8.2
3 3
35.9, 134.6, 130.6, 129.6, 129.5, 127.0, 125.5, 124.2, 124.2, Hz, 2H), 7.16-7.06 (m, 4H), 6.80 (s, 1H), 4.25 (q, J = 7.1 Hz, 2H),
23.2, 117.3, 61.5, 21.5, 14.2; HRMS (ESI) m/z calcd for 2.35 (s, 3H), 2.26 (s, 3H), 1.85 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H);
+
13
C H N O S [M+H] 415.0964, found 415.0959.
19
C NMR (CDCl ): δ 160.5, 143.3, 139.5, 137.8, 135.1, 134.7,
3
20
2
6
1
31.5, 130.6, 129.7, 129.1, 128.3, 127.4, 125.0, 121.8, 115.6,
-pyrrole-2-carboxylate 61.1, 21.4, 20.7, 19.1, 14.2; HRMS (ESI) m/z calcd for
Ethyl
5-(4-nitrophenyl)-4-tosyl-1
H
7jb). Yellowish semi-solid (17 mg, 17%); IR (KBr, cm ): 3239,
-1
+
S [M+H] 398.1426, found 398.1424.
(
C
H
22
24NO
4
1
1
8
714, 1534, 1350, 1140, 701; H NMR (CDCl ): δ 10.05 (bs, 1H),
3
.28 (d, J = 8.7 Hz, 2H), 7.80 (d, J = 8.7 Hz, 2H), 7.55 (d, J = 8.3 Methyl
4-((3,5-dimethylphenyl)sulfonyl)-5-phenyl-1H-
Hz, 2H), 7.39 (d, J = 2.6 Hz, 1H), 7.19 (d, J = 8.1 Hz, 2H), 4.25 (q, pyrrole-2-carboxylate (7o). Off-white solid (69 mg, 75%); mp.
1
3
-1
176-178 °C; IR (KBr, cm ): 3244, 2928, 1733, 1490, 868; H
1
J = 7.1 Hz, 2H), 2.37 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H);
NMR(CDCl ): δ 160.3, 148.2, 144.1, 139.2, 135.2, 134.7, 130.6, NMR (CDCl ): δ 9.71 (bs, 1H), 7.55-7.52 (m, 2H), 7.47-7.40 (m,
C
3
3
13
1
m/z calcd for C H N O S [M+H] 415.0964, found 415.0960.
29.6, 127.0, 125.7, 123.5, 117.4, 61.5, 21.5, 14.2; HRMS (ESI) 4H), 7.18 (s, 2H), 7.05 (s, 1H), 3.81 (s, 3H), 2.21 (s, 6H);
+
C
NMR (CDCl ): δ 160.9, 142.0, 138.6, 138.1, 134.3, 129.7, 129.7,
3
2
0
19
2
6
1
29.1, 128.3, 124.6, 121.6, 117.2, 52.0, 21.0; HRMS (ESI) m/z
+
Methyl
carboxylate (7k ). Colorless solid (63 mg, 60%); mp. 218-219
°
5-(3,4-dichlorophenyl)-4-tosyl-1H
4
-pyrrole-2- calcd for C20H20NO S [M+H] 370.1113, found 370.1110.
a
-
1
1
C; IR (KBr, cm ): 3292, 2924, 1733, 1460, 810; H NMR Methyl 4-((3-fluorophenyl)sulfonyl)-5-phenyl-1
H-pyrrole-2-
CDCl ): δ 9.93 (bs, 1H), 7.55-7.53 (m, 3H), 7.50 (d, J = 8.2 Hz, carboxylate (7p). Colorless solid (70 mg, 78%); mp. 161-163 °C;
(
3
-
1
1
H), 7.46 (dd, J = 8.3, 2.1Hz, 1H), 7.35 (d, J = 2.8 Hz, 1H), 7.19 IR (KBr, cm ): 3248, 1699, 1474, 1318, 1172, 777; H NMR
1
1
d, J = 8.0 Hz, 2H), 3.80 (s, 3H), 2.36 (s, 3H); C NMR (CDCl ): δ (CDCl ): δ 10.06 (bs, 1H), 7.53 (d, J = 3.6 Hz, 2H), 7.49-7.37 (m,
3
(
3 3
1
1
60.8, 144.0, 139.2, 134.9, 134.2, 132.7, 131.0, 130.4, 129.5, 4H), 7.32-7.24 (m, 2H), 7.16 (dt, J = 1.7, 8.1 Hz, 1H), 3.75 (s,
13
29.0, 128.8, 127.1, 125.2, 122.4, 117.3, 52.2, 21.5; HRMS (ESI) 3H); C NMR (CDCl ): δ 163.3 (d, J = 250 Hz), 161.0, 144.5 (d, J
3
+
m/z calcd for C H Cl NO S [M+H] 424.0177, found 424.0176. = 26 Hz), 138.8, 130.5 (d, J = 29 Hz), 129.9, 129.6, 128.8, 128.3,
1
9
16
2
4
1
23.3, 122.7 (d, J = 12 Hz), 122.0, 119.9 (d, J = 84 Hz), 117.4,
+
Methyl
5-(3,4-dichlorophenyl)-3-tosyl-1H
4
-pyrrole-2- 114.5, 52.1; HRMS (ESI) m/z calcd for C18H15FNO S [M+H]
carboxylate (7k ). Off-white solid (26 mg, 25%); mp. 238-240 360.0706, found 360.0707.
b
-
C; IR (KBr, cm ): 3214, 1724, 1417, 773; H NMR (CDCl ): δ
1
1
°
3
9
7
8
.90 (bs, 1H), 7.92 (d, J = 8.2 Hz, 2H), 7.68 (d, J = 2.0 Hz, 1H), 3-(Methylsulfonyl)-2,5-diphenyl-1H-pyrrole (7r). Buff-color
-
.54 (d, J = 8.3 Hz, 1H), 7.43 (dd, J = 8.3, 2.0 Hz, 1H), 7.33 (d, J = solid (51%, 38 mg); mp. 120-125 °C; IR (KBr, cm ): 3257, 1286,
1
1
.1 Hz, 2H), 7.21 (d, J = 3.1 Hz, 1H), 3.83 (s, 3H), 2.44 (s, 3H); 1116, 762; H NMR(CDCl ): δ 9.02(s, 1H), 7.74 (d, J = 7.9 Hz,
3
1
3
C NMR (CDCl ): δ 158.7, 144.0, 138.8, 133.6, 132.9, 132.1, 2H), 7.54 (d, J = 7.6 Hz, 2H), 7.50-7.42 (m, 5H), 7.33 (t, 1H, J =
3
13
1
5
4
31.2, 131.1, 129.5, 129.2, 127.9, 126.8, 124.1, 121.7, 112.0, 7.4 Hz), 6.98 (d, 1H, J = 3 Hz), 2.88 (s, 3H); C NMR: δ 134.4,
+
2.2, 21.6; HRMS (ESI) m/z calcd for C H Cl NO S [M+H]
4
132.0, 130.6, 129.9, 129.2, 129.1, 129.1, 128.8, 127.7, 124.3,
122.5, 108.1, 44.5; HRMS (ESI) m/z calcd for C H NO S
19
16
2
24.0177, found 424.0180.
17
16
2
+
M+H] 298.0902, found 298.0909.
[
5
-(2,5-Dimethylphenyl)-4-tosyl-1
H-pyrrole-2-carbaldehyde
-
1
(
7l). Buff-color solid (53 mg, 61%), mp. 89-91 °C; IR (KBr, cm ): 5-(2,5-dimethylphenyl)-2-phenyl-3-tosyl-1
H
-pyrrole & 2-(2,5-
239, 2948, 2853, 1650, 710; H NMR (CDCl ): δ 9.79 (bs, 1H), dimethylphenyl)-5-phenyl-3-tosyl-1H-pyrrole (1:1 mixture)
3
1
3
9
7
2
1
1
-
.54 (s, 1H), 7.59 (d, J = 8.3 Hz, 2H), 7.49 (d, J = 2.76 Hz, 1H), (7t). Off-white solid (82 mg, 82%): mp. 244-245 °C; IR (KBr, cm
1
.35 (dd, J = 1.7, 7.7 Hz, 1H), 7.30 (s, 1H), 7.20-7.16 (m, 3H),
): 3775, 3302, 2924, 2854, 1735, 1598, 1450, 1156, 1082, 812,
13
1
.37 (s, 3H), 2.33 (s, 3H), 2.29 (s, 3H); C NMR (CDCl ): δ 179.3, 709; H NMR (CDCl ): δ 8.54 (bs, 1H), 8.49 (bs, 1H), 7.60-7.58
3
3
43.5, 139.5, 138.1, 135.1, 134.6, 131.5, 130.6, 129.8, 129.0, (m, 4H), 7.49-7.38 (m, 9H), 7.31-7.29 (m, 1H), 7.19-7.12 (m,
28.1, 127.3, 125.0, 121.4, 115.7, 21.5, 20.7, 19.0; HRMS (ESI) 8H), 7.09 (d, J = 7.6 Hz, 1H), 7.04 (d, J = 3.0 Hz, 1H), 6.92 (s,
+
m/z calcd for C H NO S [M+H] 354.1164, found 354.1168.
2
1H), 6.84 (d, J = 3.0 Hz, 1H), 2.44 (s, 3H), 2.38 (s, 3H), 2.36-2.35
(m, 6H), 2.31 (s, 3H), 1.97 (s, 3H); C NMR (CDCl ): δ 142.9,
0
20
3
13
3
Methyl
(
cm ): 3251, 2955, 1686, 1484, 1315, 816; H NMR (CDCl ): δ 128.7, 128.3, 127.4, 127.2, 126.9, 123.9, 122.6, 111.0, 21.4
5-(2,5-dimethylphenyl)-1H
-pyrrole-2-carboxylate 140.5, 140.3, 135.7, 134.6, 134.2, 132.3, 132.0, 131.3, 131.2,
7m). Buff-color solid (67 mg, 71%); mp. 198-199 °C; IR (KBr, 130.9, 130.3, 129.7, 129.4, 129.3, 129.2, 129.1, 129.0, 128.9,
-
1
1
3
9
.85 (bs, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.40 (d, J = 8.1 Hz, 2H),
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 11
Please do not adjust margins

P
N
le
e
a
w
se
J
d
o
o
ur
n
n
o
a
t
l
a
o
d
f
ju
C
s
h
t
e
m
m
a
i
r
s
g
t
i
r
n
y
s
Page 12 of 14
ARTICLE
Journal Name
1
3
2
0.8, 20.7, 20.6, 19.3; HRMS (ESI) m/z calcd for C H NO S 3.44 (s, 3H), 2.35 (s, 3H); C NMR (CDCl ): δ 144.4, 138.6,
24
25
2
3
View Article Online
+
M+H] 402.1528, found 402.1532.
[
7 , 127.0, 115.3,
136.3, 134.5, 132.4, 131.0, 129.2, 128.1 ,D O1 2I : 1 0. 1. 1039/C7NJ01709J
1
-pyrrole-2- [M+H] 342.1164, found 342.1161.
14.9, 68.1, 58.0, 21.5; HRMS (ESI) m/z calcd for C H NO S
19 20 3
+
Methyl 5-(4-methoxyphenyl)-4-tosyl-1
carboxylate (7u ). Yellow semi-solid (53 mg, 54%); IR (KBr, cm
H
-
a
1
1
: 3195, 2927, 1680, 1277; H NMR (CDCl ): δ 9.57 (s, 1H), Methyl
.53-7.50(m, 4H), 7.38 (d,J = 2.7 Hz, 1H), 7.15 (d, J = 8.0 Hz, carboxylate (16). Colorless liquid (15%); IR (ATR, cm ): 2950,
)
5-formyl-1-(methylsulfonyl)-1H-pyrrole-2-
3
-1
7
2
3
1
5
1
H), 6.96 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.84 (s, 3H), 2.35 (s, 2932, 2580, 1710, 1730, 770; H NMR(CDCl ): δ 9.94 (s, 1H),
3
1
3
H); C NMR (CDCl ): δ 160.9, 160.7, 143.4, 139.7, 138.2, 7.08 (d, J = 3.8 Hz, 1H), 6.91 (d, J = 3.8 Hz, 1H), 3.95 (s, 3H),
3
1
30.9, 129.3, 127.0, 123.7, 121.4, 121.3, 117.4, 113.8, 55.4, 3.87 (s, 3H); C NMR(CDCl ): δ 179.7, 160.3, 139.1, 133.2,
3
3
2.1, 21.5; HRMS (ESI) m/z calcd for C H NO S 122.1, 119.3, 52.9, 43.7; HRMS (ESI) m/z calcd for C H NO S
20
20
5
8
10
5
+
+
[M+H] 232.0280, found 232.0281.
[
M+H] 386.1062, found 386.1060.
Methyl
carboxylate (7u ). Yellow semi-solid, (26 mg, 26%); IR (KBr, cm Yellowish liquid (35 mg, 17%); IR (ATR, cm ): 2978, 2675, 2580,
5-(3-methoxyphenyl)-4-tosyl-1H-pyrrole-2- 5-(Perfluorophenyl)-1-tosyl-1H-pyrrole-2-carbaldehyde (6h).
-1
-
b
1
)
1
: 3255, 2919, 1661, 766; H NMR (CDCl ): δ 10.04 (s, 1H), 1704, 1484, 1201, 937, 589, 546; H NMR (CDCl ): δ 10.30 (s,
1
3
3
7
1
1
1
1
.53(d, J = 8.3 Hz, 2H), 7.39 (d,J = 2.7 Hz, 1H), 7.30-7.28 (m, 1H), 7.48 (d, 2H, J= 8.4 Hz), 7.30 (d, 2H, J = 8.2 Hz), 7.27 (d, 1H,
13
H), 7.16-7.12(m, 3H),7.09 (d, J = 8 Hz, 1H), 6.99 – 6.97 (m, J = 3.8 Hz), 6.48 (d, 1H, J = 3.7 Hz), 2.44 (s, 3H); C NMR
13
H), 3.83 (s, 3H), 3.80 (s, 3H), 2.34 (s, 3H); C NMR (CDCl ): δ (CDCl ): δ 180.9, 146.4, 137.5, 135.0, 134.6, 133.2, 130.3,
3
3
61.0, 159.2, 143.5, 139.5, 138.0, 130.2, 129.4, 129.3, 127.0, 130.2, 127.7 (d, J = 236 Hz), 126.6, 122.1, 118.9, 21.7
24.2, 121.6, 121.6, 117.5, 115.9, 114.8, 55.4, 52.1, 21.5;
+
+
HRMS (ESI) m/z calcd for C H NO S [M+H] 386.1062, found ; HRMS (ESI) m/z calcd for C H F NO S [M+H] 416.0380,
20
20
5
18 11
5
3
3
86.1055.
found 416.0385.
Methyl
5-(cyanophenyl)-4-tosyl-1
H
7v :7v ). Yellow semi-solid, (26 mg, 23%); IR (KBr, cm ): 3195, dicarboxylate (6i). Brownish liquid (27 mg, 15%); IR (ATR, cm
-pyrrole-2-carboxylate Diethyl
1-(methylsulfonyl)-2-phenyl-1H-pyrrole-3,4-
-
-
1
(
a
b
1
230, 2927, 1680, 1277; H NMR(CDCl ): δ 10.01 (s, 1H),
1
1
2
7
2
3
1
1
1
): 2980, 2932, 1730, 1175, 1069, 770; H NMR (CDCl ): δ 7.88
3
3
.93(d, J = 8.0 Hz, 0.6 H), 7.76-7.74 (m, 2.5 H), 7.61-7.53 (m, (s, 1H), 7.50-7.43 (m, 5H), 4.34 (q, J = 7.2 Hz, 2H), 4.12 (q, J =
.6 H), 7.39 (d, J = 8.3 Hz, 1H), 7.21-7.18 (m, 2H), 3.89 (s, 3H), 7.2 Hz, 2H), 2.96 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H), 1.05 (t, J = 7.2
13
.50 (s, 1.6H), 2.39 (s, 3.2H); C NMR (CDCl ): δ161.6, 160.8, Hz, 3H); C NMR (CDCl ): δ 163.6, 162.3, 131.6, 129.9, 128.2,
13
3
3
44.1, 139.3, 139.2, 134.2, 133.0, 132.7, 132.1, 130.4, 130.2, 128.0, 127.9, 126.2, 121.2, 117.0, 61.1, 60.9, 43.2, 14.2, 13.7;
+
29.6, 129.6, 129.4, 128.6, 127.3, 127.0, 127.0, 125.4, 122.7, HRMS (ESI) m/z calcd for C H NO S [M+H] 366.1011, found
17.3, 114.0, 112.8, 53.2, 52.3, 22.7, 21.5; HRMS (ESI) m/z 366.1003.
17
20
6
+
calcd for C H N O S [M+H] 381.0909, found 381.0900.
4
2
0
17
2
Methyl 5-(4-methyl-2-(phenylsulfonyl)phenyl)-1
H-pyrrole-2-
-
1
(
5-Phenyl-1
10). Colorless semi-solid (8 mg, 11%); IR (ATR, cm ): 3434, 3420, 1660, 1470, 748; H NMR (CDCl ): δ 10.42 (s, 1H), 8.32
H-pyrrol-2-yl)methyl 4-methylbenzenesulfonate carboxylate (21). Yellowish liquid (5 mg, 15%); IR (ATR, cm ):
1
-
(
3
1
924, 1371, 1189, 763; H NMR (CDCl ): δ 9.12 (bs, 1H), 7.56- (d, J = 8.2 Hz, 1H), 7.54 (s, 1H), 7.43-7.25 (m, 6H), 6.79-6.77 (m,
2
7
3
.51 (m, 4H), 7.43-7.40 (m, 4H), 7.15 (d, J = 8.0 Hz, 2H), 6.75 (d, 1H), 6.01-5.99 (m, 1H), 3.95 (s, 3H), 2.45 (s, 3H); HRMS (ESI)
+
13
J = 2.8 Hz, 1H), 5.01 (s, 2H), 2.35 (s, 3H); C NMR (CDCl ): δ m/z calcd for C H NO S [M+H] 356.0957, found 356.0947.
3
19 18
4
1
1
44.6, 138.8, 136.2, 132.6, 131.0, 129.3, 128.2, 127.2, 126.7,
15.7, 114.9, 60.4, 21.5; HRMS (ESI) m/z calcd for C H NO S Deuterated
1
8
18
3
Methyl 5-phenyl-1-tosyl-1H-pyrrole-2-
carboxylate (6j). Colorless solid, (127 mg, 71%); mp.124-126
+
[
M+H] 328.1007, found 328.1010.
-
1
1
C; IR (KBr, cm ): 2924, 2853, 1716, 1374, 1174, 667, 587; H
°
H-pyrrol-2-yl)methanol (11). Colorless NMR (CDCl ): δ 7.37 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 8.1 Hz, 2H),
(
semi-solid (12 mg, 15%); IR (ATR, cm ): 3389, 2924, 1597, 6.91 (d, J = 3.4 Hz, 1H), 6.11 (d, J = 3.4 Hz,1H), 3.94 (s, 3H), 2.37
1
5-Phenyl-1-tosyl-1
3
-1
1
13
371, 1174, 663, 590; H NMR (CDCl ): δ 7.38 (t, J = 7.3 Hz, 1H), (s, 3H); C NMR (CDCl ): δ 161.8, 143.8, 135.5, 131.0, 130.6,
3
3
7
.31-7.26 (m, 4H), 7.20 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 8.1 Hz, 129.6, 129.1, 127.5, 127.4, 121.8, 124.4, 52.5, 21.0; HRMS (ESI)
+
H), 6.37 (d, J = 3.3 Hz, 1H), 6.11 (d, J = 3.3 Hz, 1H), 5.43 (s, m/z calcd for C H D NO S [M+H] 361.1270, found 361.1272.
H), 2.38 (s, 3H); C NMR (CDCl ): δ 144.6, 138.8, 136.2, 132.0,
3
2
1
9
12
5
4
13
2
1
31.0, 129.3, 128.2, 127.1, 126.7, 115.7, 114.9, 60.4, 60.2, Deuterated
Methyl
5-phenyl-3-tosyl-1H-pyrrole-2-
+
2
found 328.1008.
1.5; HRMS (ESI) m/z calcd for C H NO S [M+H] 328.1007, carboxylate (7z). Colorless solid, (25 mg, 86%); mp. 184-185
18
18
3
-
°C; IR (KBr, cm ): 3431, 2924, 1716, 1375, 1174, 667, 591; H
1
1
NMR (CDCl ): δ 9.84 (bs, 1H), 7.51 (d, J = 8.3 Hz, 2H), 7.39 (d, J
3
2
-(Methoxymethyl)-5-phenyl-1-tosyl-1
H
Yellowish semi-solid (53 mg, 63%); IR (ATR, cm ): 2924, 1735,
-pyrrole
(12). = 2.8 Hz, 1H), 7.13 (d, J = 7.9 Hz, 2H), 3.81 (s, 3H), 2.34 (s, 3H);
13
-1
C NMR (CDCl ): δ 161.0, 143.5, 139.5, 138.1, 129.3, 129.1,
3
1
1
7
6
445, 1371, 1174, 1093, 811, 660, 590; H NMR (CDCl ): δ 7.37- 128.9, 127.0, 124.3, 121.7, 117.4, 52.1, 21.5; HRMS (ESI) m/z
3
+
.29 (m, 5H), 7.26 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.1 Hz, 2H), calcd for C H D NO S [M+H] 361.1270, found 361.1269.
.32 (d, J = 3.3 Hz, 1H), 6.18 (d, J = 3.3 Hz, 1H), 4.74 (s, 2H),
1
9
12
5
4
1
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 13 of 14
Please do not adjust margins
New Journal of Chemistry
Journal Name
ARTICLE
1
yl)ethanone (6k). Semi-solid (82 mg, 48%); IR (DCM, cm ):
-(1-((4-Fluorophenyl)sulfonyl)-5-phenyl-1
H
-pyrrol-2-
Seregin and V. Gevorgyan, Chem. Soc. Rev. 20V0i7ew, A3r6tic,le1O1n7li3ne;
c) D. Alberico, M. E. Scott and M. Lautens, Chem. Rev. 2007,
107, 174; and references cited therein.
For oxidative arylation of pyrroles see: (a) E. M. Beck and M.
J Gaunt, Top. Curr. Chem. 2010, 292, 85; (b) D. R. Stuart, E.
-1
(
DOI: 10.1039/C7NJ01709J
1
2969, 2681, 2559, 1708, 1484, 1201, 985, 727; H NMR (CDCl ):
3
δ 7.63-7.59 (m, 2H), 7.44-7.34 (m, 3H), 7.25-7.23 (m, 2H), 7.07-
7
8
7
2
1
1
.03 (m, 2H), 6.91 (d, J = 3.4 Hz, 1H), 6.18 (d, J = 3.4 Hz, 1H),
Villemure and K. Fagnou, J. Am. Chem. Soc. 2007, 129
,
1
.62 (s, 3H); C NMR (CDCl ): δ 190.2, 167.0 (d, J = 255 Hz),
3
3
12072; (c) T. Itahara, J. Chem. Soc., Chem. Commun. 1981,
254.
(a) P. Nandi, M. Y. Redko, K. Peterson, J. L. Dye, M. Lefenfeld,
P. F. Vogt and J. E. Jackson, Org. Lett. 2008, 10, 5441; (b) P.
G. M. Wuts and T. W. Greene, Fourth Ed. John wiley & Sons,
44.8, 139.8, 134.3 (d, J = 3 Hz), 131.2, 130.8, 130.7, 129.9,
29.1, 127.8, 122.4, 115.9 (d, J = 22 Hz), 114.9, 29.3; HRMS
+
(ESI) m/z calcd for C H FNO S [M+H] 344.0757, found
3
18
15
3
44.0762
2006, Chapter 7, pp. 916; (c) C. M. Haskins and D. W. Knight,
Tetrahedron Lett. 2004, 45, 599; (d) G. Theodoridis,
Tetrahedron 2000, 56, 2339; (e) A. Yasuhara, M. Kameda and
T. Sakamoto, Chem. Pharm. Bull. 1999, 47, 809; (f) A. C.
Brown and L. A. Carpino, J. Org. Chem. 1985, 50, 1749.
X. H. Xu, X. Wang, G. Liu, E. Tokunaga and N. Shibata, Org.
Lett. 2012, 14, 2544.
Acknowledgements
The financial support from the SERB, New Delhi is greatly
appreciated. RAB, ND, SS, and GD thank to the UGC, New Delhi
9
and NIPER S.A.S. Nagar for the award of Senior Research 10 B. Prasad, R. Adepu, S. Sandra, D. Rambabu, G. R. Krishna, C.
Fellowships, respectively. We thank Mr. Kamal Verma, IIT
Ropar for his assistance in the X-ray crystallographic studies.
M. Reddy, G. S. Deora, P. Misra and M. Pal, Chem. Commun.
012, 48, 10434.
1 Y. Zhu, W. T. Lu, H. C. Sun and Z. P. Zhan, Org. Lett. 2013, 15
146.
2 W. T. Teo, W. Rao, M. J. Koh and P. W. H. Chan, J. Org. Chem.
013, 78, 7508.
2
1
1
,
4
2
Notes and references
13 (a) Y. Zhao, H. Wang, X. Li, D. Wang, X. Xin and B. Wan, Org.
Biomol. Chem. 2016, 14, 526; (b) X. Xin, D. Wang, X. Li and B.
Wan, Angew. Chem. Int. Ed. 2012, 51, 1693.
1
(a) A. V. Ivachtchenko, Russ. Chem. Rev. 2014, 83, 439; (b) X.
Chen, S. Hussain, S. Praveen, S. Chang, Y. Zhang and C. Zhu,
Curr. Med. Chem. 2012, 19, 3578; (c) A. Kalgutkar, R. Jones
and A. Sawant, in Metabolism Pharmacokinetics and Toxicity
of Functional Groups; (Ed. D. A. Smith) RSC: Cambridge, UK,
1
4 (a) K. Hojczyk, P. Feng, C. Zhan and M. Ngai, Angew. Chem.
Int. Ed. 2014, 53, 14559; (b) Y. Kikugawa and M. Shimada, J.
Chem. Soc., Chem. Commun. 1989, 1450.
1
1
5 J. Wang, K. I. Son and J. Xu, Montash. Chem. 2016, 1 and
references cited therein.
2
(
010; RSC Drug Discovery Series No. 1, Chapter 5, pp. 210;
d) C. Hansch, P. G. Sammes and J. B. Taylor, Comprehensive
Medicinal Chemistry; Pergamon Press: Oxford, UK, 1990; Vol.
, Chapter 7.1.
6 (a) A. S. Deeming, C. J. Russell and M. C. Willis, Angew. Chem.
Int. Ed. 2015, 54, 1168; (b) G. Lonzia and L. A. López, Adv.
Synth. Catal. 2013, 355, 1948; (c) A. A. Fesenko and A. D.
Shutalev, J. Org. Chem. 2013, 78, 1190; (d) K. D. Barnes, R. E.
Diehl, S. H. Trotto and Y. Hu, US005817691A, 1998; (e) K. D.
Barnes and R. Ward, J. Heterocyclic Chem. 1995, 32, 871.
7 For intermolecular oxidative coupling see: (a) J. K. Laha, R. A.
Bhimpuria, D. V. Prajapati, N. Dayal and S. Sharma, Chem.
Commun. 2016, 52, 4329; (b) J. K. Laha and N. Dayal, Org.
Lett. 2015, 17, 4742; For intramolecular oxidative coupling
see: (c) J. K. Laha, K. P. Jethava and S. Patel, Org. Lett. 2015,
2
2
(a) N. Murugesan, Z. Gu, S. Spergel, M. Young, P. Chen, A.
Mathur, L. Leith, M. Hermsmeier, E. C. K. Liu, R. Zhang, E.
Bird, T. Waldron, A. Marino, B. Koplowitz, W. G. Humphreys,
S. Chong, R. A. Morrison, M. L. Web, S. Moreland, N.
Trippodo and J. C. Barrish, J. Med. Chem. 2003, 46, 125; (b)
N. Murugesan, Z. Gu, P. D. Stein, S. Spergel, A. Mathur, L.
Leith, E. C. K. Liu, R. Zhang, E. Bird, T. Waldron, A. Marino, R.
A. Morrison, M. L. Webb, S. Moreland and J. C. Barrish, J.
Med. Chem. 2000, 43, 3111; (c) N. Murugesan, Z. Gu, P. D.
Stein, S. Bisaha, S. Spergel, R. Girotra, V. G. Lee, J. Lloyd, R. N.
Misra and J. Schmidt, J. Med. Chem. 1998, 41, 5198.
1
17, 5890; (d) J. K. Laha, K. P. Jethava and N. Dayal, J. Org.
Chem. 2014, 79, 8010.
1
1
8 For intramolecular oxidative coupling and N-desulfonylation
see: J. K. Laha, N. Dayal, K. P. Jethava and D. V. Prajapati,
Org. Lett. 2015, 17, 1296.
9 CCDC 1544189 contains the supplementary crystallographic
data for the compound 7a. This data can be obtained free of
charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
3
(a) M. Fares, M. A. Said, M. A. Alsherbiny, R. A. Eladwy, H.
Almahli, M. M. Abdel-Aziz, H. A. Ghabbour, W. M. Eldehna
and H. A. Abdel-Aziz, Molecules 2016, 21, 114; (b) C. B.
Bheeter, R. Jin, J. K. Bera and H. Doucet, RSC Adv. 2013,
987; (c) C. E. Stephens, T. M. Felder, Sr. J. W. Sowell, G.
Andrei, J. Balzarini, R. Snoeck and E. D. Clercq, Bioorg. Med.
Chem. 2001, , 1123; (d) B. F. Zimmerman, EP0070698A1,
983; (e) G. S. Sheppard, S. K. Davidson, J. B. Summers and
3,
5
9
2
0 (a) M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M.
A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B.
Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.
P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L.
Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J.
Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H.
Nakai, T. Vreven, J. A. Montgomery, Jr. J. E. Peralta, F.
Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V.
N. Staroverov, T. Keith, R. Kobayashi, J. Normand, K.
Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi,
M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J.
B.Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J.
W.Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G.
A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D.
1
Jr. G. M. Carrera, WO1996033196A1, 1996.
(a) V. Bhardwaj, D. Gumber, V. Abbot, S. Dhiman and P.
Sharma, RSC Adv. 2015, 5, 15233; (b) A. A. Fesenko and A. D.
4
Shutalev, J. Org. Chem. 2013, 78, 1190; (c) G. Lonzi and L. A.
Lopez, Adv. Synth. Catal. 2013, 355, 1948; (d) M. Kajino, A.
Hasuoka and H. Nishida, PCT Int. Appl., 2007026916, 2007;
(
e) K. D. Barnes, R. E. Diehl, S. H. Trotto and Y. Hu,
US5817691, 1998; (f) K. D. Barnes and R. J. Ward, Heterocycl.
Chem. 1995, 32, 871.
5
6
(a) V. Estevez, M. Villacampa and J. C. Menedez, Chem. Soc.
Rev. 2010, 39, 4402; (b) N. Gros and S. Gronowitz, Acta
Chem. Scand. 1971, 25, 2595.
For direct arylation of pyrroles see: (a) J. Farnaz, R. Soraya
and H. Hamideh, J. Org. Chem. 2010, 75, 3109; (b) I. V.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 13
Please do not adjust margins

P
N
le
e
a
w
se
J
d
o
o
ur
n
n
o
a
t
l
a
o
d
f
ju
C
s
h
t
e
m
m
a
i
r
s
g
t
i
r
n
y
s
Page 14 of 14
ARTICLE
Journal Name
Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski,
and D. J. Fox, Gaussian 09: EM64L-G09RevB.01,Gaussian,
Inc., Wallingford CT, 2010; (b) Y. Zhao and D. G.Truhlar,
Theor. Chem. Acc. 2008, 120, 215; (c) R. G. Parr, W. Yang,
Density-Functional Theory of atoms and molecules Oxford
University Press, New York, 1989.
View Article Online
DOI: 10.1039/C7NJ01709J
2
2
1 K. Wang and Z. Liu, Synth. Commun. 2010, 40, 144.
2 S. D. Yang, C. L. Sun, Z. Fang, B. J. Li, Y. Z. Li and Z. J. Shi,
Angew. Chem. Int. Ed. 2008, 47, 1473.
2
3 C. Guo, B. Sun and Y. Li, Poly. Chem. 2014, 5, 5247.
1
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins