Palladium-catalyzed arylation of aryl sulfonamides with cyclohexanones

Article abstract of DOI:10.1016/j.molcata.2013.11.023

Pd-catalyzed intermolecular aerobic dehydrogenative aromatizations have been developed for the arylation of aryl sulfonamides with cyclohexanones. Various N-aryl sulfonamides were selectively obtained in good yields using molecular oxygen as oxidant. The reaction tolerated a wide range of functionalities.

Full text of DOI:10.1016/j.molcata.2013.11.023

Journal of Molecular Catalysis A: Chemical 383–384 (2014) 94–100
Contents lists available at ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Palladium-catalyzed arylation of aryl sulfonamides with
cyclohexanones
Xiangxiang Caoa, Yang Baia, Yanjun Xiea, Guo-Jun Denga,b,∗
a Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University,
Xiangtan 411105, China
b Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Pd-catalyzed intermolecular aerobic dehydrogenative aromatizations have been developed for the ary-
lation of aryl sulfonamides with cyclohexanones. Various N-aryl sulfonamides were selectively obtained
in good yields using molecular oxygen as oxidant. The reaction tolerated a wide range of functionalities.
© 2013 Elsevier B.V. All rights reserved.
Received 3 August 2013
Received in revised form
12 November 2013
Accepted 16 November 2013
Available online 4 December 2013
Keywords:
Aromatization
Arylation
Cyclohexanones
Dehydrogenation
Sulfonamides
Recently, there has been significant interest in the transition-
1. Introduction
metal-catalyzed N-alkylation of amines using cheap, readily
available and non-toxic alcohols as the alkylation reagent via
hydrogen autotransfer (or borrowing hydrogen) strategy. In this
process, the alcohol was oxidized in situ and two hydrides were
transferred into the metal catalyst. The metal-hydride complex
could be used as reducing reagent to reduce the imine inter-
mediate [8]. Since the seminal work reported by Grigg et al. [9]
and Watanable et al. [10], great progress has been made in the
transition-metal-catalyzed direct amination of amines, sulfona-
mides [11] or even nitro arenes [12] with alcohols. However, the
borrowing hydrogen methodology using alcohols as starting mate-
rials is limited for the alkylation of amines and not suitable for
arylations. Inspired by pioneering work [13], the group of Stahl
succeeded in the utilization of molecular oxygen in catalytic oxida-
tive aromatization reactions. Cyclohexanone derivatives have been
transferred into the corresponding phenols [14] and cyclic enones
[15] in the presence of a Pd-catalyst under mild reaction condi-
tions. We and others have developed the intermolecular arylation
reactions of amines and alcohols using cyclohexanones as the
reducing reagents and aryl sources via dehydrogenation and tau-
tomerization [16]. Nitro arenes were also successfully used as the
hydrogen acceptors to further form diaryl amines with cyclohex-
anones [17]. In continuation of our interest in using cyclohexanones
as hydrogen donors and aryl sources, herein, we report a Pd-
catalyzed arylation of aryl sulfonamides with cyclohexanones using
molecular oxygen as oxidant (Scheme 1c).
N-Aryl sulfonamides are of great importance as building
blocks for pharmaceuticals and bioactive compounds [1]. In
particular, they are widely used as antibacterial, anticancer, anti-
inflammatory and antiviral agents and HIV protease inhibitors [2].
Thus, the search for general and efficient routes for construction
of sulfonamides under mild conditions is of great continuing inter-
est for organic chemists. Although many efforts have been put into
the development of novel sulfonamide synthesis [3], the conven-
tional synthesis mainly relies on the reaction of amino compounds
and sulfonyl chlorides in the presence of organic or inorganic bases
because of the reactivity and simplicity (Scheme 1a) [4]. Over
the last few decades, the transition-metal-catalyzed cross cou-
pling reactions of aryl halides or pseudohalides with sulfonamides
has become a more attractive approach to form N-aryl sulfo-
namides. (Scheme 1b). Arguably, the most prominent reactions
include Buchwald–Hartwig-coupling [5], Ullmann-type reactions
[6] and Chan–Lam-type aminations [7]. For pharmaceutical pur-
poses, the use of non-toxic coupling reagents under mild reaction
conditions is highly desirable.
∗
Corresponding author at: Key Laboratory of Environmentally Friendly Chemistry
and Application of Ministry of Education, College of Chemistry, Xiangtan University,
Xiangtan 411105, China. Tel.: +86 731 58298601; fax: +86 731 58292251.
E-mail address: gjdeng@xtu.edu.cn (G.-J. Deng).
1381-1169/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2013.11.023

X. Cao et al. / Journal of Molecular Catalysis A: Chemical 383–384 (2014) 94–100
95
CDCl3, ppm) ı 156.8, 136.8, 136.3, 129.3, 127.1, 126.0, 125.1, 121.3,
35.1, 31.0; MS (EI) m/z (%) 289, 168, 133 (1 0 0), 92, 65.
Compound 3e: 1H NMR (400 MHz, CDCl3, ppm) ı 7.78–7.74
(m, 2H), 7.27 (d, J = 7.6 Hz, 2H), 7.16–7.05 (m, 5H), 6.50 (s, 1H);
13C NMR (100 MHz, CDCl3, ppm) ı 165.3 (d, J = 253.8 Hz), 136.2,
135.2 (d, J = 2.9 Hz),130.0 (d, J = 9.4 Hz), 129.4, 125.7, 122.0, 116.3
(d, J = 22.5 Hz); MS (EI) m/z (%) 251, 186, 159, 92 (1 0 0), 65.
Compound 3f: 1H NMR (400 MHz, CDCl3, ppm) ı 7.70 (d,
J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 7.14 (s,
1H), 7.07 (d, J = 7.6 Hz, 2H), 6.92 (s, 1H); 13C NMR (100 MHz, CDCl3,
ppm) ı 139.6, 137.6, 136.2, 129.5, 129.4, 128.7, 125.8, 121.9; MS
(EI) m/z (%) 267, 168, 111, 92 (1 0 0), 65.
Compound 3g: 1H NMR (400 MHz, CDCl3, ppm) ı 7.61–7.56 (m,
3H), 7.29–7.25 (m, 3H), 7.16 (t, J = 7.4 Hz, 1H), 7.06 (d, J = 7.6 Hz, 2H),
6.45 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm) ı 138.2, 136.0, 132.3,
129.5, 128.8, 128.1, 125.9, 122.1; MS (EI) m/z (%) 313, 168, 156, 92
(1 0 0), 65.
Scheme 1. Pathways for N-aryl sulfonamide formation.
Compound 3h: 1H NMR (400 MHz, CDCl3, ppm) ı 7.80 (d,
J = 8.4 Hz, 2H), 7.29–7.20 (m, 4H), 7.15 (t, J = 7.4 Hz, 1H), 7.07 (d,
J = 8.0 Hz, 2H), 6.67 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm) ı
152.4 (d, J = 1.9 Hz), 137.4, 136.1, 129.7, 125.8, 120.2 (q, J = 258.0 Hz),
122.0, 120.8 (d, J = 1.1 Hz), 118.9; MS (EI) m/z (%) 317, 225, 161, 92
(1 0 0), 65; HRMS calcd. for: C18H20NaO [M+Na]+ 275.1406, found
275.1409.
2. Experimental
2.1. General remarks
All experiments were carried out under an atmosphere of
oxygen. Flash column chromatography was performed over sil-
ica gel 48–75 ␮m. 1H NMR and 13C NMR spectra were recorded
on Bruker-AV (400 and 100 MHz, respectively) instrument inter-
nally referenced to SiMe4 or chloroform signals. MS analyses were
performed on Agilent 5975 GC–MS instrument (EI). The new com-
pounds were characterized by 1H NMR, 13C NMR, MS and HRMS.
The structure of known compounds was further corroborated by
comparing their 1H NMR, 13C NMR data and MS data with those
of literature. All reagents were used as received from commercial
sources without further purification. Palladium (II) trifluoroacetate
was purchased from Alfa Aesar.
Compound 3i: 1H NMR (400 MHz, CDCl3, ppm) ı 7.96 (d,
J = 7.6 Hz, 1H), 7.43 (t, J = 7.2 Hz, 1H), 7.32–7.19 (m 4 H), 7.07 (t,
J = 7.3 Hz, 2H), 7.01 (d, J = 8.0 Hz, 1H), 6.72 (s, 1H), 2.65 (s, 3H); 13
C
NMR (100 MHz, CDCl3, ppm) ı 137.6, 137.2, 136.5, 133.1, 132.6,
130.0, 129.3, 126.3, 125.0, 120.8, 29.7; MS (EI) m/z (%) 247, 182,
155, 92 (1 0 0), 65.
Compound 3j: 1H NMR (400 MHz, CDCl3, ppm) ı 7.99 (d,
J = 8.0 Hz, 1H), 7.51–7.43 (m, 2H), 7.32 (t, J = 7.4 Hz, 1H), 7.21 (t,
J = 7.6 Hz, 2H), 7.12–7.07 (m, 3H), 7.00 (s, 1H); 13C NMR (100 MHz,
CDCl3, ppm) ı 136.3, 135.8, 134.0, 132.0, 131.6, 131.4, 129.3, 127.2,
125.8, 121.7; MS (EI) m/z (%) 267, 168, 111, 92 (1 0 0), 65.
Compound 3k: 1H NMR (400 MHz, CDCl3, ppm) ı 7.34–7.11 (m,
4H), 7.14–7.12 (d, J = 3.8 Hz, 2H), 6.84–6.83 (d, J = 2.0 Hz, 1H), 6.51 (s,
1H); 13C NMR (100 MHz, CDCl3, ppm) ı 137.9, 137.4, 135.8, 132.3,
129.5, 126.7, 126.2, 122.1; MS (EI) m/z (%) 273, 181, 174, 92 (1 0 0),
65.
2.2. General procedure: 4-methyl-N-phenylbenzenesulfonamide
(3a)
A 25 mL oven-dried reaction vessel was charged with Pd(TFA)2
(2.3 mg, 0.01 mmol), 1,10-phenanthroline (3.6 mg, 0.02 mmol), p-
toluene sulfonamide (1a, 34.2 mg, 0.2 mmol), cyclohexanone (2a,
32 ␮L, 0.3 mmol). The reaction vessel was flushed with oxygen
three times and then sealed. Toluene (0.7 mL) was added by syringe
and the resulting solution was stirred at 140 ◦C for 40 h. After
cooling to room temperature, the volatiles were removed under
vacuum and the residue was purified by column chromatography
(silica gel, petroleum ether/ethyl acetate = 4:1) to give the corre-
sponding product 3a (39.9 mg) as white solid in 81% yield.
Compound 3a: 1H NMR (400 MHz, CDCl3, ppm) ı 7.65 (d,
J = 8.0 Hz, 2H), 7.26–7.23 (m, 5H), 7.15–7.12 (m, 1H), 7.07 (d,
J = 7.6 Hz, 1H), 6.42 (s, 1H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3,
ppm) ı 143.9, 136.7, 136.1, 129.7, 129.3, 127.3, 125.2, 121.4, 21.5;
MS (EI) m/z (%) 247, 182, 155, 91 (1 0 0).
Compound 3l: 1H NMR (400 MHz, CDCl3, ppm) ı 7.39–7.35 (t,
J = 7.5 Hz, 2H), 7.24–7.19 (m, 3H), 6.57 (s, 1H), 3.02 (s, 3H); 13C NMR
(100 MHz, CDCl3, ppm) ı 136.9, 129.7, 125.5, 120.9, 39.3; MS (EI)
m/z (%) 171, 140, 106, 92 (1 0 0), 65.
Compound 3m: 1H NMR (400 MHz, CDCl3, ppm) ı 7.63 (d,
J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.95
(d, J = 8.0 Hz, 2H), 6.38 (s, 1H), 2.39 (s, 3H), 2.29 (s, 3H); 13C NMR
(100 MHz, CDCl3, ppm) ı 143.7, 136.0, 135.2, 133.9, 129.8, 129.6,
127.3, 122.2, 21.6, 20.9; MS (EI) m/z (%) 261, 106 (1 0 0), 91, 77.
Compound 3n: 1H NMR (400 MHz, CDCl3, ppm) ı 7.67 (d,
J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 3H), 7.13 (t, J = 7.6 Hz, 1H),
6.95–6.91 (m, 1H), 6.85 (d, J = 8.0 Hz, 1H), 6.48 (s, 1H), 2.40 (s, 3H),
2.29 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) ı 143.8, 139.3, 136.6,
136.2, 129.7, 129.1, 127.3, 126.0, 122.0, 118.2, 21.6, 21.4; MS (EI)
m/z (%) 261, 106 (1 0 0), 91, 77.
Compound 3b: 1H NMR (400 MHz, CDCl3, ppm) ı 7.77 (d,
J = 7.6 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H),7.45–7.41 (m, 2H), 7.23 (d,
J = 7.6 Hz, 2H), 7.14–7.05 (m, 3H), 6.65 (s, 1H); 13C NMR (100 MHz,
CDCl3, ppm) ı 139.2, 136.5, 133.0, 129.3, 129.0, 127.3, 125.5, 121.8;
MS (EI) m/z (%) 233, 168, 92 (1 0 0), 77, 65.
Compound 3p: 1H NMR (400 MHz, CDCl3, ppm) ı 7.64 (d,
J = 7.6 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 6.97 (d,
J = 8.0 Hz, 2H), 6.39 (s, 1H), 2.59 (q, J = 7.6 Hz, 2H), 2.40 (s, 3H), 1.19
(t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3, ppm) ı 143.7, 141.6,
136.3, 134.1, 129.6, 128.6, 127.3, 122.2, 28.2, 21.6, 15.4; MS (EI) m/z
(%) 275, 260, 120 (1 0 0), 91, 77.
Compound 3c: 1H NMR (400 MHz, CDCl3, ppm) ı 7.69 (d,
J = 8.0 Hz, 2H), 7.24–7.22 (m, 4H), 7.11–7.07 (m, 3H), 6.79 (s, 1H),
2.66 (q, J = 7.6 Hz, 2H), 1.22 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3, ppm) ı 149.9, 136.7, 136.5, 129.3, 128.5, 127.4, 125.2, 121.5,
28.8, 14.9; MS (EI) m/z (%) 261, 105 (1 0 0), 92, 77, 65.
Compound 3q: 1H NMR (400 MHz, CDCl3, ppm) ı 7.62 (d,
J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.1 Hz, 2H), 6.95
(d, J = 8.4 Hz, 2H), 6.47 (s, 1H), 2.52 (t, J = 7.6 Hz, 2H), 2.38 (s, 3H),
1.58–1.53 (m, 2H), 1.32–1.25 (m, 4H), 0.87 (t, J = 6.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3, ppm) ı 146.9, 143.6, 136.6, 133.7, 129.5,
Compound 3d: 1H NMR (400 MHz, CDCl3, ppm) ı 7.70 (d,
J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 7.6 Hz, 2H),
7.11–7.07 (m, 3H), 6.68 (s, 1H), 1.30 (s, 9H); 13C NMR (100 MHz,

96
X. Cao et al. / Journal of Molecular Catalysis A: Chemical 383–384 (2014) 94–100
Table 1
Optimization of the reaction conditions.a
O
S
O
O
S
O
O
catalyst
NH
NH2
ligand
+
solvent
140 o
C
Entry
Catalyst
Ligand
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18c
19d
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
2,2-Dipyridine
DABCO
DMAP
PPh3
Xantphos
4,5-Diazafluoren-9-one
1,10-Phen
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Xylene
0
8
12
11
6
Pd(acac)2
Pd2(dba)3
PdCl2
PdBr2
Pd(OAc)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
45
95
65
34
16
17
19
90
52
12
14
10
53
5
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
Diglyme
Anisole
DMF
Toluene
Toluene
1,10-Phen
The significance of bold (entry 7) means the best reaction conditions for this transformation.
a
Conditions: 1a (0.2 mmol), 2a (0.3 mmol), catalyst (5 mol%), ligand (10 mol%), solvent (0.7 mL), 140 ◦C, 40 h under oxygen unless otherwise noted.
GC yield based on 1a.
Under air.
b
c
d
Under argon.
127.3, 126.8, 121.8, 35.2, 31.4, 30.9, 22.5, 21.5, 14.0; MS (EI) m/z (%)
317, 260 (1 0 0), 160, 106, 92.
reacted with 1.5 equiv. of cyclohexanone in the absence of any cat-
alyst, no desired product 3a was observed as determined by GC–MS
and 1H NMR methods (Table 1, entry 1). Then various palladium
salts were investigated for this transformation. Palladium salts such
as Pd(acac)2, Pd2(dba)3, PdCl2 and PdBr2 were ineffective when
1,10-phenanthroline was used as ligand (entries 2–5). The use of
Pd(OAc)2 could improve the reaction yield to 45% (entry 6). Among
the various palladium salts examined, Pd(TFA)2 was the most effec-
tive, and its use resulted in the formation of 3a in 95% yield (entry 7).
The use of ligands was crucial for this reaction. Other nitrogen and
phosphine ligands were also employed for this reaction. The use of
DMAP, PPh3 and DABCO significantly decreased the reaction yield
(entries 8–12). 4,5-Diazafluoren-9-one also showed good efficiency
and the desired product was obtained in 90% yield (entry 13). Sol-
vents also played an important role and the effect of solvents on this
reaction was also investigated. The use of diglyme, DMF and anisole
all prohibited the arylation of sulfonamide (entries 14–17). A mod-
erate yield was obtained when the reaction was carried out under
an atmosphere of air, and the reaction in argon further decreased
the reaction yield to 5% (entries 18 and 19).
Compound 3r: 1H NMR (400 MHz, CDCl3, ppm) ı 7.61 (d,
J = 7.6 Hz, 2H), 7.22–7.18 (m, 4H), 6.96 (d, J = 8.4 Hz, 2H), 6.27 (s,
1H), 2.38 (s, 3H), 1.54–1.60 (m, 2H), 1.22 (s, 6H), 0.61 (t, J = 7.4 Hz,
3H); 13C NMR (100 MHz, CDCl3, ppm) ı 143.7, 140.4, 136.4, 134.0,
129.6, 129.2, 127.3, 122.3, 37.6, 36.8, 28.3, 21.5, 9.0; MS (EI) m/z (%)
317, 302, 288 (1 0 0), 106, 91; HRMS calcd. for: C18H24NO2S [M+H]+
318.1522, found 318.1530.
Compound 3s: 1H NMR (400 MHz, CDCl3, ppm) ı 7.68 (d,
J = 8.4 Hz, 2H), 7.52 (d, J = 7.6 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.42 (t,
J = 7.6 Hz, 2H), 7.34 (d, J = 7.2 Hz, 1H), 7.24 (m, 2H), 7.13 (d, J = 8.4 Hz,
2H), 6.47 (s, 1H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) ı
144.0, 140.1, 138.1, 136.1, 136.0, 131.0, 129.8, 128.8, 127.9, 127.4,
126.8, 121.7, 21.6; MS (EI) m/z (%) 166 (1 0 0), 119, 152, 91.
Compound 3t: 1H NMR (400 MHz, CDCl3, ppm) ı 7.92 (d,
J = 8.4 Hz, 2H), 7.70 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 7.11 (d,
J = 8.4 Hz, 2H), 6.71 (s, 1H), 4.33 (q, J = 7.2 Hz, 2H), 2.38 (s, 3H), 1.36
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3, ppm) ı 165.9, 144.4,
140.9, 136.0, 131.8, 131.0, 129.8, 127.3, 119.2, 61.0, 21.5, 14.3; MS
(EI) m/z (%) 289, 274, 155, 91 (1 0 0), 65.
Compound 3u: 1H NMR (400 MHz, CDCl3, ppm) ı 7.59 (d,
J = 8.0 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 7.10
(s, 1H), 7.00 (d, J = 8.4 Hz, 2H), 6.34 (s, 1H), 2.38 (s, 3H), 2.15 (s, 3H);
13C NMR (100 MHz, DMSO, ppm) ı 168.1, 143.1, 136.8, 136.0, 132.6,
129.6, 126.7, 121.5, 119.8, 23.8, 21.0; MS (EI) m/z (%) 223, 205, 149
(1 0 0), 103, 76.
3.2. Reaction of 2a with various sulfonamides
With the optimized reaction conditions established, the scope
of the reaction with respect to cyclohexanone (2a) and vari-
ous sulfonamides (1) was investigated (Table 2). The reactions
with aryl sulfonamides bearing electron-donating groups at the
para position proceeded smoothly to give the desired products
in high yields (entries 1, 3 and 4). Halogens such as fluoro,
chloro and bromo were tolerated under the optimized reaction
conditions (entries 5–7). The desired product was obtained in
87% yield when 4-(trifluoromethoxy)benzene sulfonamide was
used (entry 8). The position of the substituents on the phenyl
ring of aryl sulfonamides affected the reaction yield signifi-
cantly. Moderate yields were achieved when 2-methylbenzene
3. Results and discussion
3.1. Initial optimization
We begin our study by examining the reaction of commer-
cially available p-toluene sulfonamide (1a) and cyclohexanone (2a)
in toluene at 140 ◦C under oxygen. When p-toluene sulfonamide

X. Cao et al. / Journal of Molecular Catalysis A: Chemical 383–384 (2014) 94–100
97
Table 2
Reaction of 2a with various sulfonamides.a
O
Pd(TFA)2
1,10-phen
O
S
O
O
S
O
H
N
R
R
NH2
+
O2, toluene
140 oC, 40 h
Entry
1
Sulfonamide
Product
Yield (%)b
SO2NH2
SO2NH Ph
SO2NH Ph
SO2NH Ph
SO2NH Ph
1a
3a
3b
3c
81
78
79
SO2NH2
2
3
1b
1c
SO2NH2
SO2NH2
4
1d
3d
86
SO2NH2
SO2NH Ph
SO2NH Ph
SO2NH Ph
SO2NH Ph
5
6
7
1e
1f
3e
3f
67
84
61
F
F
SO2NH2
SO2NH2
Cl
Cl
1g
3g
Br
Br
SO2NH2
8
9
1h
3h
87
F3CO
F3CO
SO2NH2
SO2NH Ph
1i
1j
3i
3j
50
68
SO2NH2
Cl
SO2NH Ph
Cl
10
S
S
Cl
Cl
SO2NH2
SO2NH Ph
11c
1k
1l
3k
3l
40
65
12c,d
CH3SO2NH2
CH3SO2NHPh
a
Conditions: 1 (0.2 mmol), 2a (0.3 mmol), Pd(TFA)2 (5 mol%), 1,10-phen (10 mol%), toluene (0.7 mL), 140 ◦C, 40 h.
Isolated yield based on 1.
Cu(TFA)2 0.2 mmol.
b
c
d
1l (0.4 mmol), 2a (0.2 mmol).
sulfonamide (1i) and 2-chlorobenzene sulfonamide (1j) were
with 1a. Varying the position of the methyl substituted on
the cyclohexanone had profound effect on the outcome of the
reaction; the corresponding 3m, 3n and 3o were obtained in
80%, 73% and 21% yields, respectively (Table 3, entries 1–3).
Furthermore, no product was obtained when 2-phenyl cyclo-
hexanone was used. Other functional groups including ethyl,
amyl, tert-pentyl, acetyl-amino, and ester were well tolerated
under the optimized reaction conditions and gave the desired
products in moderate to good yields (entries 4–9). In gen-
eral, the arylation of aryl sulfonamides with cyclohexanones
showed very good selectivity and no over arylation byproducts
observed.
used, and the desired products were obtained in 50% and 68%
yields, respectively (entries 9–10). In the presence of equal
amount of Cu(TFA)2, heteroaromatic sulfonamide 1k and aliphatic
sulfonamide 1l smoothly reacted with 2a and afforded the
corresponding products 3k and 3l in moderate yields (entries 11
and 12).
3.3. Reaction of 1a with various cyclohexanones
To further explore the scope of the reaction, a number of
substituted cyclohexanone derivatives were employed to react

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X. Cao et al. / Journal of Molecular Catalysis A: Chemical 383–384 (2014) 94–100
Table 3
Reaction of 1a with various cyclohexanones.a
O
O
S N
O
O
H
Pd(TFA)2
1,10-phen
R
S NH2
O
R
+
O2, toluene
140 oC, 40 h
Entry
1
Cyclohexanone
Product
Yield (%)b
O
O
SO2NH
SO2NH
2b
2c
2d
2e
2f
3m
3n
3o
3p
3q
80
2
3
4
5
73
41
71
77
O
SO2NH
SO2NH
O
O
O
SO2NH
SO2NH
C5H11
C5H11
6
2g
3r
70
O
SO2NH
SO2NH
SO2NH
Ph
7
8
2h
2i
3s
3t
65
67
76
Ph
O
O
CO2Et
NHAc
EtO2C
AcHN
9
2j
3u
Conditions: 1a (0.2 mmol), 2 (0.3 mmol), Pd(TFA)2 (5 mol%), 1,10-phen (10 mol%), toluene (0.7 mL), 140 ◦C, 40 h under oxygen.
Isolated yield based on 1a.
a
b
3.4. Proposed mechanism
tentative mechanism to rationalize this transformation
is illustrated in (Scheme 2) [16a]. Condensation of cyclo-
hexanone with sulfonamide generates an imine intermedi-
Subsequent tautomerization and ␤-hydride-enamination will
generate cyclohexenone V. The cyclohexenone can afford
the final product VIII via dehydrogenation and tautomer-
ization. The palladium-hydride species VI could be regenerated
into the initial active catalyst III in the presence of oxygen
[19].
a
A
ate
I which can further form an enamine species II [18].

X. Cao et al. / Journal of Molecular Catalysis A: Chemical 383–384 (2014) 94–100
99
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4. Conclusion
In summary, we have developed a palladium-catalyzed direct
arylation of aryl sulfonamides with cyclohexanone derivatives
under oxygen atmosphere. Cyclohexanones act as the aryl sources
via dehydrogenation and tautomerization. Various N-aryl sulfona-
mides were formed in moderate to good yields selectively. The
cyclohexanone dehydrogenation, tautomerization and imine for-
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This work was supported by the National Natural Science Foun-
dation of China (21172185), the Hunan Provincial Natural Science
Foundation of China (11JJ1003, 12JJ7002), the New Century Excel-
lent Talents in University from Ministry of Education of China
(NCET-11-0974) and the Research Fund for the Doctoral Program
of Higher Education of China, Ministry of Education of China
(20124301110005).
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Appendix A. Supplementary data
Supplementary material related to this article can be found,
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