Iridium-Catalyzed ortho-C?H Amidation of Benzenesulfonamides with Sulfonyl Azides

Article abstract of DOI:10.1002/adsc.201900573

We developed herein an iridium-catalyzed direct C?H activation/ C?N bond formation reaction of benzenesulfonamides with sulfonyl azides. The amidation reaction provides a protocol for the synthesis of 2-aminobenzesulfonamides in good to excellent yields. This strategy features a wide substrate scope, tolerates a broad range of functional groups under external oxidant-free conditions and only releases molecular nitrogen as the sole by-product. Moreover, the preliminary mechanism was investigated and the proposed reaction pathway was provided. (Figure presented.).

Full text of DOI:10.1002/adsc.201900573

Title: Iridium-Catalyzed ortho-C-H Amidation of Benzenesulfonamides
with Sulfonyl Azides
Authors: Hongcen Hou, yongli zhao, Shou-Ri Sheng, and Junmin Chen
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201900573
Link to VoR: http://dx.doi.org/10.1002/adsc.201900573

10.1002/adsc.201900573
Advanced Synthesis & Catalysis
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Iridium-Catalyzed ortho-C-H Amidation of Benzenesulfonamides with Sulfonyl Azides
Hongcen Hou,a Yongli Zhao,a Shouri Sheng,ab* and Junmin Chen,ab*
a Key Laboratory of Functional Small Organic Molecules, Ministry of Education
b College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330022, China
Tel./fax:+86 0791 8812 0380; e-mail address: shengsr@jxnu.edu.cn; junminchen@jxnu.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
chlorosulfonylation of aromatic amine and ammonolysis
Abstract. We developed herein an iridium-catalyzed
with chlorosulfonic acid[9] and the reaction of aromatic
direct C-H activation/ C-N bond formation reaction of
amine with chlorosulfonyl isocyanate followed by
benzenesulfonamides with sulfonyl azides. The
cyclization of the resulting chlorosulfonylureas with
amidation reaction provides a protocol for the synthesis
Lewis acids.[10] Although these methods are efficient
of 2-aminobenzesulfonamides in good to excellent
and reliable, they still suffer from several disadvantages
yields. This strategy features a wide substrate scope,
such as harsh reaction conditions, moisture sensitivity,
tolerates a broad range of functional groups under
narrow scope of substrates, and isomer formation.
external oxidant-free conditions and only releases
Recently, Hanson reported a copper-catalyzed C-N
molecular nitrogen as the sole by-product. Moreover, the
bond coupling reactions of 2-halobenzenesulfonamides
preliminary mechanism was investigated and the
with different amines to afford the corresponding 2-
proposed reaction pathway was provided.
aminobenzenesulfonamides deraivatives.[11] For the
Keywords: sulfonamides; C-H amidation; iridium; 2-
coupling reaction, it is essential that one halide group be
aminobenzesulfonamides; sulfonyl azides
installed at the ortho positions. The multistep sequence
and the prefunctionalization of starting materials make
Introduction
the synthesis complicated and non-economical. Thus,
Sulfonamides are important structural motifs with wide
applications in pharmaceuticals, agrochemical,
development of a straightforward and convenient
method to access 2-aminobenzenesulfonamides with
various substituents on the arene moiety remains a great
challenge.
biological and medicinal studies.[1] Among them,
benzothiadiazine 1,1-dioxides (benzosultams) and their
analogues are found to very important heterocyclic
scaffolds in drug discovery due to their promising
bioactivities including hypoglycemic,[2] selective
antagonists of CXR2,[3] AMPA receptors potentiators,[4]
antidepressant,[5] Glut-1 transporter inhibitors,[6] and
HCV polymerase inhibitors[7] (Figure 1). Specifically,
2-aminobenzenesulfonamides act as a key precursor for
the synthesis of benzothiadiazine 1,1-dioxides.[8] Classic
O
O
O
O
O
O
Cl
S
F
S
Cl
S
NH
NH
N
N
H
O
N
H
N
H
N
H
OH
AMPA receptors potentiators
hypoglycemic agent
CXCR2 antagonists
O
S
O
O
S
O
N
O
O
N
S
N
OH
N
N
N
N
O
H
N
O
N
H
N
HCV polymerase inhibitors
Glut-1 transporter inhibitors
antidepressant
methods
for
the
synthesis
include
of
2-
aminobenzenesulfonamides
sequential
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900573
Advanced Synthesis & Catalysis
Figure 1. Selected biologically active benzothidiazine-
direct ortho-C-H amidation of benzenesulfonamides has
not been reported. Herein, we report an efficient and
broadly applicable protocol for the synthesis of 2-
sulfonylaminobenzylsulfonamides via Ir-catalyzed
ortho-C(sp2)-H amidation of benzenesulfonamides with
aryl sulfonyl azides.
1,1-dioxides
containing
the
2-
aminobenzenesulfonamides motif.
In recent years, transition metal-catalyzed directing
group-controlled ortho-C(sp2)-H amination of arenes
with organic azides, pioneered by Chang and others,
have been established as straightforward and step-
economical processes in the construction of various C-N
bonds.[12] A range of directing groups including
imine,[13] ketone,[14] ester,[15] carboxylic acid,[16] and
amide[17] have successfully facilitated the desired ortho-
C(sp2)-H amination reactions under various metal
catalyzed reaction manifolds. Recently, sulfonamide as
a directing group has been explored in promoting C-H
activation. However, only limited examples of direct C-
O
O
O
O
S
C F
6
5
S
MPA/Ac
Pd or Rh
Pd
N
H
N
H
1
1
R
R
2
Yu (ref. 18)
R
Chen (ref. 22)
2
R
and You (ref. 23)
O
S
O
S
O
S
O
O
O
Ac/AQ
Ac
R
Rh
N
Rh or Co
N
H
N
1
1
R
1
R
R
H
3
Chen (ref. 24)
R
Cramer (ref. 19)
Ribas (ref. 21a)
Rao (ref. 21b)
H
2
2
2
R
R
R
O
O
O
Ir
O
S
Ac
Rh
S
N
1
H
R
1
N
Ac
R
Li (ref. 20a)
Peng (ref. 20b)
NHTs
2
This work
R
Scheme 1. Ortho-C-H functionalization of aryl
sulfonamides
C
formation on benzenesulfonamides have been
To examine the above hypothesis, we optimize the
amidation conditions for the reaction of N-acetyl-
benzenesulfonamide (1a) with TsN3 (2a) under various
catalytic conditions (Table 1). When we used
[IrCp*Cl2]2 (4 mol%) as the catalyst in presence of
AgNTf2 (16 mol%), the reaction occurred in 1,2-
dichloroethane (DCE) at 80 °C for 12 h under air to
furnish ortho-amidated benzenesulfonamide (3a) in
32% yield (Table 1, entry 1). To our delight, the yield
was increased to 63% by employing HOAc (0.2 equiv)
as additive (Table 1, entry 2). When we increase the
amounts of HOAc to 0.5 and 1.0 equiv, the desired
product 3a was obtained in 77% and 86% yields,
respectively (Table 1, entries 3,4). Therefore, we
decided to use 1.0 equiv of HOAc for subsequent
reaction studies. Subsequently, we screened various
silver salts under the similar conditions. It was found
AgOAc and AgNO3 are inefficient and very low yields
were obtained (Table 1, entries 5,6). Notably, amidation
does not take place when AgSbF6 is used as silver salt
(Table 1, entry 7). In additon, only moderate yields were
obtained by employing AgOTf and AgTFA as silver
salts (Table 1, entries 8,9). Remarkably, the Ag2CO3
showed excellent activity and gave 92% yield (Table 1,
entry 10). Specifically, an increase or decrease of the
explored (Scheme 1). For example, In 2011, Yu
reported Pd-catalyzed ortho-C-H olefination of aryl
sulfonamides with the assistance of SO2NHC6F5 as a
directing group.[18] In 2012, Cramer reported the
synthesis of sultam scaffolds through Rh-catalyzed C-H
functionalization of acylated aryl sulfonamides with
alkynes, affording the six-member benzosultam
compounds.[19] In 2014, Li and Peng independently
reported Rh-catalyzed regioselective oxidative C-H
olefination using SO2NHAc as a directing group.[20]
Later, Ribas and Rao developed a Co-catalyzed C-H/N-
H functionalization of aryl sulfonamides with alkynes
and allenes, respectively.[21] In 2016, our group
developed an efficient synthetic route to access biaryl
sulfonamide derivatives via Pd-catalyzed C-H arylation
of benzenesulfonamides by employing an amino acid
moiety as the bidentate directing group.[22] Recently,
You reported an alternative method for synthesis of
biaryl sulfonamide via Rh‑ catalyzed oxidative C-H/C-
H cross-coupling of aromatic sulfonamides with
arenes.[23] More recently, we have developed an
efficient Rh-catalyzed direct ortho-alkynylation of aryl
sulfonamides with bromoalkyne, affording the 2-
alkynylated arylsulfonamides.[24] Despite this progress,
to the best of our knowledge, transition metal-catalyzed
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900573
Advanced Synthesis & Catalysis
amounts of Ag2CO3 led to a decrease of the product
yield (Table 1, entries 11 and 12). Next, various
solvents were tested, it was found that DCE proved to
be superior over a range of solvents (i.e., DMF, toluene,
1,4-dioxane, and THF) (Table 1, entries 13-16).
Temperature also has a great impact on this reaction;
only 73% yield was obtained at 60 °C (Table 1, entry
17). Decreasing the catalyst loading to 2 mol % gave
inferior results (Table 1, entry 18). Control experiments
revealed that no reaction occurred when Ag2CO3 was
removed, which revealed the sliver salt to be essential
for this transformation (Table 1, entry 19). Interestingly,
other previously reported [RhCp*Cl2]2, [CoCp*Cl2]2
and [RuCp*Cl2]2 catalytic systems were not effective
(Table 1, entries 20-22). Finally, the optimized reaction
conditions were identified as follows: [IrCp*Cl2]2 (4
mol %), Ag2CO3(16 mol %), and HOAc (1 equiv) in
DCE at 80 °C for 12 h under air.
10
11c
12 d
13
Ag2CO3 HOAc (1.0)
Ag2CO3 HOAc (1.0)
Ag2CO3 HOAc (1.0)
Ag2CO3 HOAc (1.0)
DCE
DCE
DCE
DMF
92
68
71
trace
74
14
Ag2CO3 HOAc (1.0) Toluene
15
Ag2CO3 HOAc (1.0)
Ag2CO3 HOAc (1.0)
Ag2CO3 HOAc (1.0)
Ag2CO3 HOAc (1.0)
1,4-
Dioxane
trace
trace
73
16
THF
DCE
DCE
DCE
DCE
DCE
DCE
17 e
18 f
19
67
/
HOAc (1.0)
NR
NR
trace
trace
20g
21h
22i
Ag2CO3 HOAc (1.0)
Ag2CO3 HOAc (1.0)
Ag2CO3 HOAc (1.0)
Table 1 Optimization of the reaction parametersa
O
S
O
O
S
O
[IrCp*Cl ]
Silver salt
2 2
O
O
N
N
TsN
3
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol),
[IrCp*Cl2]2 (4 mol%), silver salt (16 mol%), additive
(0-1.0 equiv), and Solvent (1mL) heated at 80 °C for 12
h under air.
H
H
Additive, Solvent, T
NHTs
1a
2a
3a
[b] Isolated yields.
Entry
Sliver
salt
Additive
/
Solvent Yield(%)b
[c] Ag2CO3 (10 mol%).
[d] Ag2CO3 (20 mol%).
[e] at 60 oC.
1
2
3
4
5
6
7
8
9
AgNTf2
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
32
63
[f] [IrCp*Cl2]2 (2 mol %).
[g] [RhCp*Cl2]2.
[h] [CoCp*Cl2]2.
AgNTf2 HOAc (0.2)
AgNTf2 HOAc (0.5)
AgNTf2 HOAc (1.0)
AgOAc HOAc (1.0)
AgNO3 HOAc (1.0)
AgSbF6 HOAc (1.0)
[i] [RuCp*Cl2]2.
N.R. = no reaction.
77
With the optimized reaction conditions in hand, we
next explored the generality and scope of aryl
sulfonamides 1 with aryl sulfonyl azides 2 under the
optimized conditions. As shown in Table 2, this
protocol is applicable to a large variety of aryl
sulfonamides 1 with various substituents. For instance,
N-acetyl-benzenesulfonamides bearing methyl (1b),
86
35
26
trace
54
ethyl
(1c),
tert-butyl
(1d),
methoxy
(1e),
AgOTf
HOAc (1.0)
trifluoromethoxyl (1f) and trifluoromethyl (1g) at the
para position reacted smoothly with 2a to afford the
desired products (3b-g) in 79-95% yields. Furthermore,
AgTFA HOAc (1.0)
62
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900573
Advanced Synthesis & Catalysis
O
O
N-acetyl-benzenesulfonamides containing halides such
as fluoro (1h), chloro (1i) and bromo (1j) were
successfully amidated to afford the desired products
(3h-j) in good yields. Remarkably, meta-substituted N-
O
S
[IrCp*Cl2]2 (4 mol %)
Ag2CO3 (16 mo l% )
S
R2
O
N
R3
O
S
R2
R1
H
N
H
N3
R1
NH
S
HOAc (1.0 equiv)
R3
O
O
O
DCE
80 oC, 12 h
3
1
2
O
S
O
O
S
O
O
S
O
O
S
O
O
O
O
O
N
N
H
N
N
H
NHTs
H
H
NHTs
NHTs
NHTs
acetyl-benzenesulfonamides
benzenesulfonamide 1k
such
and
as
3-choro-
3-bromo-
3c, 87%
3a, 92%
3d, 93%
3b, 91%
O
O
O
O
O
O
O
O
O
O
O
O
S
S
S
S
N
N
N
N
H
H
H
H
F3C
benzenesulfonamide 1l can be regioselectively amided
at the less hindered position and gave the desired
products (3k, 3l) in very high yields. The structure of 3l
was confirmed by removal of the tosyl and acyl groups
(see the Supporting Information for the details).
Furthermore, N-acetyl-benzenesulfonamides bearing
methyl (1m), chloro(1n), or trifluoromethoxyl (1o)
groups at the ortho-position underwent the desired
amidation in 82-86% yields (3m-3o). Substrates
containing disubstituents at othro and para positons can
also afford the desired products in satisfactory yields
(3p-3q). It is noteworthy that the halide substituents
were tolerated, as this is advantageous for further
synthetic elaborations with transition metal catalysis,
thereby broadening the diversity of the products. 4-
Diphenylsulfonamade 1r also worked well, affording
the desired product 3r in 82% yield. Next, we
investigated the scope of aryl sulfonyl azides 2 in the
amidation of 1a under the optimized conditions. It was
found that phenylsulfonyl azide 2b worked well and
gave the desired product 3s in 91% yield. Moreover,
phenylsulfonyl azide 2c bearing a para-methoxy group
can afford the desired product 3t in 84% yield. The
phenylsulfonyl azide with an othro-methyl group (1d)
exhibited slightly decreased reactivity and also gave a
good yield, presumably due to steric hindrance. Finally,
it was found that no target products were obtained when
other N-substituted benzenesulfonamides such as
methoxy 1v, methyl 1w, and tert-butyl 1x were used as
the substrates under the optimized conditions.
O
NHTs
F3C
NHTs
F
NHTs
O
NHTs
3h, 77%
3e, 95%
3g, 79%
3f, 87%
O
O
O
O
S
O
O
O
O
O
O
O
O
Br
S
Cl
S
S
N
N
N
N
H
H
H
H
NHTs
Br
NHTs
3j, 76%
NHTs
Cl
NHTs
3l, 82%
3k, 84%
3i, 74%
O
O
S
O
Cl
O
S
O
O
S
O
F3C
O
O
O
O
O
S
O
O
N
N
N
H
H
N
H
H
O
NHTs
NHTs
NHTs
NHTs
3o, 85%
3m, 82%
3n, 86%
3p, 81%
O
S
O
O
S
O
O
O
O
O
O
S
O
O
O
N
S
N
H
N
N
H
H
H
NH
S
NH
S
O
O
NHTs
F
NHTs
O
O
O
3t, 84%
3r, 82%
3s, 91%
3q, 75%
O
O
O
O
O
O
O
O
O
S
N
S
S
O
S
H
N
N
N
H
H
H
NH
O
S
NHTs
NHTs
NHTs
O
3u, 71%
3w, 0%
3v, 0%
3x, 0%
[a]
Reaction conditions: 1 (0.2 mmol), 2 (0.24 mmol),
[IrCp*Cl2]2 (4 mol%), Ag2CO3 (16 mol%), HOAc (1.0
equiv), and DCE (1mL) heated at 80 °C for 12 h under
air.
[b] Isolated yields.
After completing the above investigation, several
transformations
of
the
resultant
2-
aminobenzenesulfonamides were conducted. For
instance, the tosyl group could selectively be easily
removed in 30% H2SO4 solution, giving 4 in 98% yield
(Scheme 2a). Upon reflux in KOH/MeOH for 12 h, the
acyl group deprotection of 4 would occur rapidly to
generate 2-aminobenzenesulfonamide 5 in 86% yield
(Scheme 2b). Benzothidiazine-1,1-dioxide 6, [25] which
exhibited excellent micromolar affinity and activity on
SUR2B-type KATP channels, can facilely be obtained
via one-pot cyclization/oxidation reactions of 2-
Table 2. Substrate scope of aryl sulfonamides and aryl
sulfonyl azides in the C-H amidation.[a,b]
aminobenzenesulfonamide
5
with benzaldehyde
(Scheme 2c).
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900573
Advanced Synthesis & Catalysis
O
S
O
O
S
O
of sulfonamide to afford a five-membered iridacycle
species B. Then, TsN3 coordination with the Ir atom and
subsequent N2 dissociation lead to the formation of a
metal-nitrenoid intermediate C, The intermediate C
underwent intramolecular migratory insertion to
generate D. Finally, the complex D was protonated in
the presence of HOAc to give the desired product 3a
and regenerate the active Ir (III) catalyst for the next
cycle.
O
O
H2SO4 (30%)
reflux, 1h
N
N
(a)
H
H
NH2
NHTs
98%
4
3a
O
S
O
O
S
O
O
N
KOH (30 euqiv)
NH2
H
(b)
MeOH
reflux, 12 h
NH2
NH2
4
86%
O
5
O
S
O
CHO
O
S
(c)
NaHSO3
NH2
NH
+
DMA,
150 oC, 5 h
NH2
N
6
5
[Cp*IrCl ]
2 2
93%
O
S
O
Ag CO
O
S
O
2
3
O
O
Scheme 2. Removal of protecting groups and synthesis
of benzothidiazine-1,1-dioxide 6
N
H
N
Cp*IrL
2
H
A
NH
Ts
1a
3a
To shed light on the mechanistic aspects of the
present C-H amidation reaction, H/D exchange
experiments were performed. Under the standard
O
S
O
O
S
O
O
O
N
N
Ir
L
Ir
N
Cp*
Cp*
O
O
Ts
O
B
D
S
N
Ir
TsN
conditions,
the
reaction
of
N-acetyl-
3
2a
Cp*
TsN
benzenesulfonamides 1m with 20 equiv of D2O in the
presence of DOAc for 12 h led to deuterated 1m-D in
81% yield (Scheme 3a). The result suggested that the
cleavage of ortho-C-H bond of sulfonamide 1m is a
reversible process. Next, kinetic isotope effects (KIE)
was determined in an intermolecular competition
experiment with 1m/ 1m-D and 2a (Scheme 3b). A
kH/kD value of 1.3 was observed, the value differs
significantly from the KIE of 2.6 that was determined
for a similar reaction.[24] As such, the C−H bond
cleavages is likely not involved in the rate-determining
step.
C
Scheme 4. Plausible reaction pathway
Conclusions
In summary, we have developed the first example of
an efficient Ir-catalyzed direct C-H amination of
benzosulfonamides with aryl sulfonyl azides as the
amino source. This efficient protocol proceeds with the
advantages of operational simplicity, excellent
functional group tolerance and high efficiency, provides
a
facile access to various substituted 2-
aminobenzenesulfonamides. Further exploration of the
mechanism and synthetic utility of these transformations
are in progress in our laboratory.
O
S
O
O
S
O
O
O
[IrCp*Cl ] (4 mol %)
2 2
Ag CO (16 mo l% )
N
N
2
3
(a)
H
+
D O
2
H
DOAc (1.0 equiv)
DCE
H
(20 equiv)
D
81%
o
1m
1m-D
80 C, 12h
Experimental Section
TsN (2 equiv) 2a
3
O
S
O
O
O
O
S
O
O
O
O
[IrCp*Cl ] (4 mol %)
2 2
S
General Information
Ag CO (16 mo l% )
N
N
N
2
3
(b)
H
H
H
+
DOAc (1.0 equiv)
DCE
(H)D
NHTs
H
All reactions were carried out under air atmosphere
in oven-dried glassware with magnetic stirring. All
other reagents and solvents were purchased from
Energy Chemical or J&K Chemical Company and used
without any further purification. TLC information was
recorded on GF-254 (Qingdao Haiyang Chemical Co.,
Ltd. P. R. China) plates. Purification of reaction
o
1m-D
3m
1m
80 C, 12 h
K / K = 1.3
H D
Scheme 3. Mechanistic studies
Based on these results and literature precedents,[26]
a
possible reaction mechanism is described in Scheme 4.
Initially, an active species A was formed via the
reaction of [IrCp*Cl2]2 with silver salt. The cationic
Ir(III) catalyst A undergoes C-H insertion with the aid
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900573
Advanced Synthesis & Catalysis
products was carried out by flash chromatography using
Silica gel (200-300 mesh, Qingdao Haiyang Chemical
e) C. Valente, R. C. Guedes, R. Moreira, J. Iley, J.
Gut, P. J. Rosenthal, Bioorg. Med. Chem. Lett. 2006,
16, 4115-4119; f) R. Silvestri, G. Marfe, M. Artico,
G. La Regina, A. Lavecchia, E. Novellino, M.
Morgante, C. Di Stefano, G. Catalano, G. Filomeni,
E. Abruzzese, M. R. Ciriolo, M. A. Russo, S.
Amadori, R. Cirilli, F. La Torre, P. Sinibaldi Salimei,
J. Med. Chem. 2006, 49, 5840-4844; g) N. Lebegue,
S. Gallet, N. Flouquet, P. Carato, B. Pfeiffer, P.
Renard, S. Leonce, A. Pierre, P. Chavatte, P.
Berthelot, J. Med. Chem. 2005, 48, 7363-7373; h) P.
Francotte, P. De Tullio, E. Goffin, G. Dintilhac, E.
Graindorge, P. Fraikin, P. Lestage, L. Danober, J.-Y.
Thomas, D.-H. Caignard, B. Pirotte, J. Med. Chem.
2007, 50, 3153-3157; i) C. T. Supuran, Nature Rev.
Drug Discovery 2008, 7, 168-181.
1
Co. Ltd. P. R. China). H NMR (400 MHz) and 13C
NMR (100 MHz) spectra were determined with DMSO-
d6 or CDCl3 as solvent and tetramethylsilane (TMS) as
internal standard. Chemical shifts were reported in ppm
from internal TMS (δ). All coupling constants (J values)
were reported in hertz (Hz). High-resolution mass
spectra (HRMS) were recorded on a Bruker Apex IV
FTMS mass spectrometer using ESI (electrospray
ionization). Melting points were measured uncorrected.
General procedure for iridium-catalyzed direct C-H
bond amidation
A mixture of N-acylated aryl sulfonamide 1 (0.20
mmol), azide 2 (0.24 mmol, 1.2 equiv), [IrCp*Cl2]2 (6.3
mg, 0.008 mmol, 4 mol %) , Ag2CO3 (8.8 mg, 0.032
mmol, 16mol%), HOAc (30 mg, 0.2 mmol, 1 equiv),
and DCE (1 mL) were charged into a reaction tube. The
reaction mixture was stirred at 80 °C for 12 h. After the
mixture cooled to room temperature, the solvent was
removed under reduced pressure and the residue was
purified by column chromatography on silica gel (ether
/EtOAc) to give the desired product 2-
aminobenzenesulfonamides 3.
[2] J. K. Wales, S. V. Krees, A. M. Grant, J. K. Vikroa,
F. W. Wolff, J. Pharm. Exp. Ther. 1968, 164, 421-
432.
[3]
Y.
Wang,
W. Fu,
J. Busch-Petersen, F.
Wang,
M.
L. Ma,
J. K. Kerns, J. Jin,
R. Palovic, J.-K. Shen, M. Burman, J. J. Foley, D.
B. Schmidt, G. E. Hunsberger, H. M. Sarau, K.
L. Widdowson,
Bioorg.
Med.
Chem.
Lett. 2007, 17, 3864-3867.
[4] B. Pirotte, P. Francotte, E. Goffin, P. Fraikin, L.
Danober, B. Lesur, I. Botez, D. H. Caignard, P.
Lestage, P. de Tullio, Curr. Med. Chem. 2010, 17,
3575-3582.
Acknowledgements
This work is financially supported by the National
Natural Science Foundation of China (21762022) and
the Foundation of Jiangxi Educational Committee
(Grant No. GJJ160287).
[5] D. Giannotti, G. Viti, P. Sbraci, V. Pestellini, G.
Volterra,
F. Borsini,
A. Lecci, A. Meli, P.
Dapporto, P. Paoli, J. Med. Chem. 1991, 34, 1356-
1362.
References
[1] a) J. Drews, Science 2000, 287, 1960-1964; b) A.
Scozzafava, T. Owa, A. Mastrolorenzo; C. T.
Supuran, Curr. Med. Chem. 2003, 10, 925-953; c) G.
A. Thakur, A. R. Kulkarni, J. R. Deschamps, R. L.
Papke, J. Med. Chem. 2013, 56, 8943-8947; d) M.
Zia-ur-Rehman, J. A. Choudary, S. Ahmad, H. L.
Siddiqui, Chem. Pharm. Bull. 2006, 54, 1175-1158;
[6] J. Chen, W. Sun, J. Yang, H. Sun, Z. Wang, L. Dong,
C. Qiao, C. Xia, Bioorg. Med. Chem. Lett. 2013, 23,
3785-3787.
[7] R. Tedesco, A. N. Shaw, R. Bambal, D. Chai, N. O.
Concha, M. G. Darcy, D. Dhanak, D. M. Fitch, A.
Gates, W. G. Gerhardt, D. L. Halegoua, C. Han, G.
A. Hofmann, V. K. Johnston, A. C. Kaura, N. Liu, R.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900573
Advanced Synthesis & Catalysis
M. Keenan, J. Lin-Goerke, R. T. Sarisky, K.J.
[15] K. Shin, Y. Baek, S. Chang, Angew. Chem. Int. Ed.
2013, 52, 8031-8036.
Wiggall, M. N. Zimmerman, K. J. Duffy, J. Med.
Chem. 2006, 49, 971-983.
[16] a) D. Lee, S. Chang, Chem. Eur. J. 2015, 21, 5364-
5368; b) M. Wei, L. Wang, Y. Li, X. Cui, Chin.
Chem. Lett. 2015, 26, 1336-1340.
[8] a) H. S. James, B. Ursula J. Am. Chem. Soc. 1960,
82, 1135-1138; b) Y. Sui, P. Cui, S. Liu, Y. Zhou, P.
Du, H. Zhou, Eur. J. Org. Chem. 2018, 215-218; c)
D. Zhao, Y. Zhou, Q. She, J. Li, RSC Adv., 2014, 4,
6486-6489; d) P. Du, H. Zhou, Y. Sui, Q. Liu, K.
Zou, Tetrahedron 2016, 72, 1573-1578; e) L.Troisi,
C. Granito, S. Perrone, F. Rosato, Tetrahedron Lett.
2011, 52, 4330-4332; f) J. A. Christopher, S. J. Aves,
J. Brown, J. C. Errey, S. S. Klair, C. J. Langmead, O.
J. Mace, R. Mould, J. C. Patel, B. G. Tehan, A.
Zhukov, F. H. Marshall, M. Congreve, Med. Chem.
Commun. 2015, 6, 947-955; g) M. Sharif, J. Opalach,
P. Langer, M. Beller, X. Wu, RSC Adv., 2014, 4, 8-
17; h) D. Wang, X. Li, Y. Zhao, J. Chen, Synth.
Commun. 2017, 47, 351-356; i) L. Cao, H. Huo, H.
Zeng, Y. Yu, D. Lu, Y. Gong, Adv. Synth. Catal.
360, 2013, 4764-4773.
[17] a) G. N. Hermann, P. Becker, C. Bolm, Angew.
Chem. Int. Ed. 2016, 55, 3781-3784; b) J. Ryu, J.
Kwak, K. Shin, D. Lee, S. Chang, J. Am. Chem. Soc.
2013, 135,12861-12868l; c) D. Lee, Y. Kim, S.
Chang, J. Org. Chem. 2013, 78, 11102-11109; d) H.
Kim, G. Park, J. Park, S. Chang, ACS Catal. 2016, 6,
5922-5929; e) H. Kim, J. Park, J. G. Kim, S. Chang,
Org. Lett. 2014, 16, 5466-5469.
[18] H.-X. Dai, A. F. Stepan, M. S. Plummer, J.-Q. Yu,
J. Am. Chem. Soc. 2011, 133, 7222-7228.
[19] M. V. Pham, B. Ye, N. Cramer, Angew. Chem., Int.
Ed. 2012, 51, 10610-10614.
[20] a) W. Xie, J. Yang, B. Wang, B. Li, J. Org. Chem.
2014, 79, 8278-8287; b) Q. Ding, T.Liu, Q.g Zheng,
Y. Zhang, L. Long, Y. Peng. RSC Adv. 2014, 4,
51309-51314.
[9] E. Schlittler, G. De Stevens, L. Werner, Angew.
Chem. Internat. Ed. 1962, 1, 235-245.
[21] a) O. Planas, C. J. Whiteoak, A. Company, X.
Ribas, Adv. Synth. Catal. 2015, 357, 4003-4012; b)
T. Lan, L. Wang, Y. Rao, Org. Lett. 2017, 19, 972-
975.
[10] Y. Girard, J. G. Atkinson, J. Rokach, J. Chem. Soc.,
Perkin Trans. 1 1979, 1043-1047.
[11] a) A. Rolfe, P. R. Hanson, Tetrahedron Lett. 2009,
50, 6935-6937. (b) A. Rolfe, G. H. Lushington, P. R.
Hanson, Org. Biomol. Chem. 2010, 8, 2198-2203.
[12] Related reviews: a) Y. Park, Y. Kim, S. Chang,
Chem. Rev. 2017, 117, 9247-9301; b) K. Shin, H.
Kim, S. Chang, Acc. Chem. Res. 2015, 48,1040-
1052.
[22] W. Liu, D. Wang, Y. Zhao, F. Yi, J. Chen, Adv.
Synth. Catal. 2016, 358, 1968-1974.
[23] Y. Ran, Y. Yang, H. You, J. You, ACS Catal. 2018,
8, 1796-1801.
[24] H. Hou, Y. Zhao, S. Pu, J. Chen, Org. Biomol.
Chem. 2019, 17, 2948-2953.
[13] Y. Lian, J. R. Hummel, R. G. Bergman, J. A.
Ellman, J. Am. Chem. Soc. 2013, 135, 12548-12551.
[14] a) Q. Zheng, Y. Liang, C. Qin, N. Jiao, Chem.
Commun. 2013, 49, 5654-5656; b) K. Shin, S.
Chang, J. Org. Chem. 2014, 79, 12197-12204.
[25] L. Stefan, F. Andreas, S. Claas, W. Marcus, R.
Achim, L. Horst, B. Manfred, ChemMedChem 2009,
4, 1850-1858.
[26] J. Kim, S. Chang, Angew. Chem. Int. Ed. 2014, 53,
2203-2207.
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900573
Advanced Synthesis & Catalysis
UPDATE
Iridium-Catalyzed ortho-C-H Amidation of
Benzenesulfonamides with Sulfonyl Azides
O
O
2
O
S
[IrCp*Cl ] (4 mol %)
2 2
S
R
O
3
N
O
S
2
Ag CO (16 mo l% )
1
R
2
3
R
R
H
Adv. Synth. Catal. Year, Volume, Page – Page
N
N
3
1
R
H
NH
S
HOAc (1.0 equiv)
DCE
3
O
O
O
R
o
Hongcen Hou,a Yongli Zhao,a Shouri Sheng,ab* and
Junmin Chen,ab*
R
= H, Me, Et; Bu, F,Cl, Br, OMe.OCF ,CF , Ph
1
t
80 C, 12 h
3
3
2
t
R
R
= Ac, OMe, Me, Bu
21 examples
up to 95% yield
3
= H, Me, OMe
8
This article is protected by copyright. All rights reserved.