Cu-catalyzed coupling of aryl iodides with thiols using carbonyl-phosphine oxide ligands

Article abstract of DOI:10.1016/S1872-2067(10)60243-4

A series of carbonyl-phosphine oxide ligands were synthesized from 2-bromophenylaldehyde and used in Cu-catalyzed C-S coupling reactions. Aryl iodide and aryl bromide reacted with thiols efficiently upon catalysis under mild reaction conditions and a yiel

Full text of DOI:10.1016/S1872-2067(10)60243-4

CHINESE JOURNAL OF CATALYSIS
Volume 32, Issue 7, 2011
Online English edition of the Chinese language journal
Cite this article as: Chin. J. Catal., 2011, 32: 1129–1132.
SHORT COMMUNICATION
Cu-Catalyzed Coupling of Aryl Iodides with Thiols Using
Carbonyl-Phosphine Oxide Ligands
WANG Haolong, WAN Boshun*
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, Liaoning, China
Abstract: A series of carbonyl-phosphine oxide ligands were synthesized from 2-bromophenylaldehyde and used in Cu-catalyzed C–S
coupling reactions. Aryl iodide and aryl bromide reacted with thiols efficiently upon catalysis under mild reaction conditions and a yield
of up to 99% was obtained.
Key words: Cu; carbonyl-phosphine oxide; carbon-sulfur bond formation; cross-coupling reaction; iodide aryl; thiol
Sulfide ethers are backbones in a very important class of
organic compounds that play a significant role in a number of
chemical, material, and pharmaceutical industries [1–8]. For
this reason the formation of C–S bonds is a subject of interest in
organic chemistry. However, the traditional Ullmann-type C–S
cross-coupling reaction which involves the condensation of
thiols with aryl halides usually requires harsh conditions such
as more than stoichiometric amounts of copper salts and
temperatures above 200 °C. In 1980, Migita and co-workers [9]
reported a palladium catalyzed C–S cross-coupling of aryl
halides with thiols to overcome these difficulties and this
resulted in C–S bond formation receiving plenty of interest.
Over the past few years, several transition metals such as
palladium [10,11], nickel [12,13], cobalt [14], and iron [15]
have been used for this purpose. However, the development of
traditional Cu-catalyzed Ullmann-type C–S cross-coupling
reactions is still attractive because of the low price and the
minor toxicity of copper.
and good results were obtained. The phosphine oxide was an
important functional group in these catalytic processes. To
develop more efficient phosphine-oxide ligands we synthe-
sized a series of ligands that contain a phosphine-oxide and
carbonyl groups and these were applied to the Cu-catalyzed
C–S cross-coupling reaction. Excellent yields of up to 99%
were observed.
In the first stage, we synthesized the carbonyl
phosphine-oxide ligands 1a–1c, as shown in Scheme 1.
2-Bromophenylaldehyde (2) was used as a starting material to
synthesize 3 as described by Xu et al. [32], which was reacted
with the Grignard reagent to synthesize 4. 1a and 1b were
obtained by the oxidation of 4. 1c was synthesized by the
oxidation of 6, which was obtained by the reaction of 5 with
lithium diphenylphosphide.
To determine the best ligand, the coupling of iodobenzene
and n-butylthiol was selected as a model reaction (Table 1). It
Ph
Ph
Over the last few years several Cu-catalyzed processes have
been developed in which the C–S coupling reaction was ac-
celerated by special ligands such as phosphazene [16], ethylene
glycol [17,18], neocuproine [19,20], N-methylglycine [21], the
tripod ligand [22], benzotriazole [23], 1,2-diaminocyclohexane
[24,25], ȕ-ketoester [26], L-proline [27], BINAM [28], cate-
chol violet [29], and Ƞ-aminophenol [30]. Recently, we de-
veloped an oxime-phosphine oxide ligand [31], which was
used in Cu-catalyzed C–N and C–S cross-coupling reactions
Ph
Ph
Ph
Ph
P
P
Br
P
PCC
RMgBr
Ether
O
OH
O
O
O
CH2Cl2
CHO
CHO
R
R
2
3
4
1a R = Me
1b R = Bn
Ph
Ph
Cl
PPh2
O
H2O2
P
Ph2PLi
ether
O
O
O
CH2Cl2
Ph
Ph
Ph
5
1c
6
Scheme 1. Synthesis of the studied ligands.
Received 1 April 2011. Accepted 5 May 2011.
*Corresponding author. Tel: +86-411-84379260; Fax: +86-411-84379223; E-mail: bswan@dicp.ac.cn
Copyright © 2011, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(10)60243-4

WANG Haolong et al. / Chinese Journal of Catalysis, 2011, 32: 1129–1132
Table 1 Ligand screening for Cu catalyzed C–S cross-coupling
Table 2 Effect of Cu source, bases, and solvents
n-Bu
n-Bu
I
S
I
S
CuI/Ligand
Cs CO /CH CN
[Cu]/1c
+ n-BuSH
n-BuSH
+
2
3
3
Base/Solvent
Entry
Ligand
1a
Yielda (%)
Entry
[Cu source]
CuI
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
DMF
Base
Yielda (%)
1
2
3
89
92
91
1
2
Cs2CO3
Na2CO3
K2CO3
92
—
37
63
72
69
3
1b
CuI
1c
3
CuI
Reaction conditions: 0.5 mmol iodobenzene, 0.6 mmol n-butyl thiol, 0.05
mmol Cu catalyst, 0.05 mmol ligand, 2 mmol base, 80 oC, 12 h.
aGC yield using n-dodecane as the internal standard.
4
CuI
K3PO4
5
CuI
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
6
CuI
DMSO
toluene
CH3CN
CH3CN
CH3CN
CH3CN
7
CuI
was exciting to find that all carbonyl phosphine-oxide ligands
were useful for the C–S coupling reaction giving high yields
and the best result was obtained when using 1b as ligand.
The reaction was screened using several bases, solvents, and
Cu sources and the results are summarized in Table 2.
Preliminary results show that Cs2CO3 was a superior base
compared with Na2CO3, K2CO3, and K3PO4. The solvent effect
was then investigated and polar solvents gave better results in
this reaction while CH3CN was found to be the best solvent.
The Cu sources were also evaluated and CuBr, CuCl, Cu2O,
and Cu were found to be inferior to CuI. Therefore, the best
reaction conditions are CuI/1b/Cs2CO3/CH3CN/80°C.
8
CuBr
CuCl
Cu
87
87
84
91
9
10
11
Cu2O
Reaction conditions: 0.5 mmol iodobenzene, 0.6 mmol n-butyl thiol, 0.05
mmol Cu catalyst, 0.05 mmol ligand 1b, 2 mmol base 80 oC, 12 h.
tolerated to give the corresponding thioethers in very high
yields. Sterically hindered aryl iodides such as 2-methylphenyl
iodide and 2-hydroxyphenyl iodide readily coupled with
n-butyl thiol (entries 5 and 6). Aryl iodides bearing an addi-
tional halogen atom in the aryl ring could convert exclusively
to the desired product without being affected by the chloro or
fluoro groups (entries 12, 13, and 15). Moreover, the reaction
showed chemoselectivity for the thiol, for example, C–S cou-
pling was preferred in the presence of amino and hydroxyl
With the optimized reaction conditions in hand, various aryl
iodides and thiols were applied to this reaction to explore its
scope. As shown in Table 3, both iodides with either an elec-
tron-donating group or an electron-withdrawing group were
Table 3 Coupling of aryl iodides with thiols
R'
I
S
CuI/1b
+
R'SH
R
Cs2CO3/CH3CN
R
Yielda
Yielda
(%)
Entry Aryl iodide
Thiol
Product
Entry
Aryl iodide
Thiol
Product
(%)
NC
F
I
NC
I
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
MeO
S
n-Bu
n-Bu
n-Bu
1
99
11
12
13
14
15
16
17
18
19
20
95
81
98
95
97
92
87
60
94
91
S
n-Bu
MeO
I
F
I
Me
S
2
98
99
98
82
73
99
77
99
88
n-Bu
S
Me
Cl
I
Cl
I
H2N
S
3
S
n-Bu
n-Bu
H2N
Me
I
Me
I
S
4
5
n-Bu
S
Cl
Cl
I
I
S
n-Bu
Cl
F
S n-Bu
Me
I
Me
OH
Cl
I
I
I
S
n-Bu
n-Bu
S
F
SH
6
OH
I
S
MeO
SH
MeO
S
7
I
n-Bu
F3C
Ac
S
SH
SH
SH
S
8
F3C
I
Br
S
S
n-Bu
9
NC
NC
Ac
I
Br
S
n-Bu
S
MeOOC
10
MeOOC
MeOOC
MeOOC

WANG Haolong et al. / Chinese Journal of Catalysis, 2011, 32: 1129–1132
dron Lett, 2008, 49: 1484
groups (entries 3 and 6).
14 Wong Y C, Jayanth T T, Cheng C H. Org Lett, 2006, 8: 5613
15 Correa A, Carril M, Bolm C. Angew Chem, Int Ed, 2008, 47:
2880
The reactivity of aryl bromides was also evaluated (Table 3,
entries 19 and 20), and aryl bromides with elec-
tron-withdrawing groups afforded the products in good yields
whereas no reaction took place when electron-donating aryl
bromides were used.
16 Palomo C, Oiarbide M, Lopez R, Gomez-Bengoa E. Tetrahedron
Lett, 2000, 41: 1283
17 Kwong F Y, Buchwald S L. Org Lett, 2002, 4: 3517
18 Enguehard-Gueiffier C, Thery I, Gueiffier A, Buchwald S L.
Tetrahedron, 2006, 62: 6042
In summary, a series of carbonyl phosphine-oxide ligands
1a–1c was synthesized and used in the Cu-catalyzed coupling
reaction of aryl iodides with thiols in good to excellent yields.
Further studies to extend the application of this method to
other catalytic reactions are currently under way.
19 Gujadhur R K, Bates C G, Venkataraman D. Org Lett, 2001, 3:
4315
20 Bates C G, Gujadhur R K, Venkataraman D. Org Lett, 2002, 4:
2803
21 Deng W, Zou Y, Wang Y F, Liu L, Guo Q X. Synlett, 2004:
References
1254
22 Chen Y J, Chen H H. Org Lett, 2006, 8: 5609
23 Verma A K, Singh J, Chaudhary R. Tetrahedron Lett, 2007, 48:
7199
1
Jones D N. In: Barton D H, Ollis D W eds. Comprehensive
Organic Chemistry. Vol. 3. New York: Pergamon, 1979. 33
Tiecco M. Synthesis-stuttgart, 1988: 749
2
3
4
5
6
7
8
9
24 Rout L, Sen T K, Punniyamurthy T. Angew Chem, Int Ed, 2007,
46: 5583
Rayner C M. Contemp Org Synth, 1996, 3: 499
Baird C P, Rayner C M. J Chem Soc, Perkin Trans 1, 1998: 1973
Procter D J. J Chem Soc, Perkin Trans 1, 1999: 641
Procter D J. J Chem Soc, Perkin Trans 1, 2000: 835
Procter D J. J Chem Soc, Perkin Trans 1, 2001: 335
Herradura P S, Pendola K A, Guy R K. Org Lett, 2000, 2: 2019
Migita T, Shimizu T , Asami Y, Shiobara J I , Kato Y , Kosugi
M. Bull Chem Soc Jpn, 1980, 53: 1385
25 Ranu B C, Saha A, Jana R. Adv Synth Catal, 2007, 349: 2690
26 Carril M, SanMartin R, Dominguez E, Tellitu I. Chem Eur J,
2007, 13: 5100
27 Lv X, Bao W. J Org Chem, 2007, 72: 3863
28 Prasad D J C, Naidu A B, Sekar G. Tetrahedron Lett, 2009, 50:
1411
29 Basu B, Mandal B, Das S, Kundu S. Tetrahedron Lett, 2009, 50:
5523
10 Fernández-Rodríguez M A, Shen Q L, Hartwig J F. Chem Eur J,
2006, 12: 7782
30 Feng Y, Wang H F, Sun F F, Li Y M, Fu X M, Jin K.
Tetrahedron, 2009, 65: 9737
11 Fernández-Rodríguez M A, Shen Q, Hartwig J F. J Am Chem
Soc, 2006, 128: 2180
31 Zhu D, Xu L, Wu F, Wan B. Tetrahedron Lett, 2006, 47: 5781
32 Xu L, Zhu D, Wu F, Wan B. Tetrahedron, 2005, 47: 6553
12 Zhang Y, Ngeow K N, Ying J Y. Org Lett, 2007, 9: 3495
13 Jammi S, Barua P, Rout L, Saha P, Punniyamurthy T. Tetrahe-