A novel method for the deoxygenation of sulfoxides with the PPh 3/Br2/CuBr system

Article abstract of DOI:10.1246/cl.2007.1324

It was found that the combination of PPh₃/Br₂/CuBr was an effective promoter for the deoxygenation of sulfoxides and gave the corresponding sulfides in excellent yield in acetonitrile under refluxing conditions. It is worth mentioning that this reagent system is chemoselective, tolerating various functional groups such as carbon-carbon double bond and ketone. Copyright

Full text of DOI:10.1246/cl.2007.1324

1324
Chemistry Letters Vol.36, No.11 (2007)
A Novel Method for the Deoxygenation of Sulfoxides with the PPh3/Br2/CuBr System
Kiumars Bahrami,ꢀ Mohammad Mehdi Khodaei,ꢀ and Mohammad Khedri
Department of Chemistry, Razi University, Kermanshah 67149, Iran
(Received July 30, 2007; CL-070805)
Table 1.
It was found that the combination of PPh3/Br2/CuBr was an
effective promoter for the deoxygenation of sulfoxides and gave
the corresponding sulfides in excellent yield in acetonitrile under
refluxing conditions. It is worth mentioning that this reagent
system is chemoselective, tolerating various functional groups
such as carbon–carbon double bond and ketone.
O
S
PPh3/Br2/CuBr
Solvent, reflux
Ph
Ph
Ph
S
Ph
Entry
Solventa
Time/h
Yield/%b
1
2
3
4
CH3CN
PhCH3
CH2Cl2
MeOH
45
45
45
45
97
20
25
40
The deoxygenation of sulfoxides to the corresponding sul-
fides is an important reaction that has found considerable utility
in organic synthesis1 and in biochemical reactions.2 In most cas-
es, sulfoxides are removed from the target molecules and they
are usually eliminated by a two-step process involving deoxyge-
nation to sulfides,3 which are then reductively cleaved by cata-
lytic hydrogenation or other chemical methods.4 This transfor-
mation has been accomplished in a variety of ways,5–12 however,
many of these transformations are limited by side reactions, low
yields, the use of expensive reagents, functional group incompat-
ibility, difficult work-up procedures, or harsh reaction condi-
tions. For example, the use of hydrogen halides is somewhat
restricted with acid-sensitive substrates, the reductions with
the strong hydride systems LiAlH4–TiCl4 and NaBH4–CoCl2
are incompatible with several functional groups.
As a consequence, the introduction of new methods and/or
further work on technical improvements to overcome the limita-
tions is still an important experimental challenge. Herein, we
describe the successful use of the PPh3/Br2/CuBr system as a
method to deoxygenation of sulfoxides to the corresponding
sulfides. The route for the synthesis of sulfides is shown in
Scheme 1.
aSulfoxide:PPh3:Br2CuBr = 1:1.2:1.2:2.2. Isolated yields.
b
Table 2. Deoxygenation of sulfoxides to their corresponding
sulfides using PPh3/Br2/CuBr system
Entry
R
R0
Time/min Yield/%a,b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
C6H5
C6H5
C6H5CH2 C6H5CH2
C6H5
C6H5
C6H5
4-MeC6H4 C6H5CH2
4-BrC6H4 C6H5CH2
4-ClC6H4 C6H5CH2
4-MeC6H4 4-BrC6H4CH2
4-BrC6H4 4-BrC6H4CH2
4-MeC6H4 4-MeC6H4CH2
C6H5
C6H5CH2
41
30
45
34
30
36
29
26
27
35
27
35
30
28
39
48
98
97
94
97
96
93
96
97
95
93
96
95
92
95
90
93
4-MeC6H4CH2
4-BrC6H4CH2
4-NO2C6H4CH2
C6H5
C6H5
Me
CH2CH=CH2
To evaluate the solvent effect, the deoxygenation of diphen-
yl sulfoxide was carried out under similar reaction conditions
using various organic solvents such as toluene, dichloromethane,
methanol, and acetonitrile (Table 1). Among the various solvents
studied acetonitrile was found to be the best solvent for this
transformation.
2-C6H4-CO-2-C6H4
n-C4H9 n-C4H9
aThe products were characterized by comparison of their spec-
troscopic and physical data with those reported in literature.
bYields refer to pure isolated products.
A ratio of 1:1.2:1.2:2.2 sulfoxide/PPh3/Br2/CuBr was
found to be optimum for the deoxygenation of sulfoxides and
the results are presented in Table 2. The applicability of the
PPh3/Br2/CuBr system was then examined for the deoxygena-
tion of diaryl, dibenzyl, aryl benzyl, dialkyl, and cyclic sulfox-
ides in acetonitrile under refluxing conditions.13 The results
are presented in Table 2. As shown, all the reactions were com-
pleted within a short time and the sulfides were obtained in al-
most quantitative yields as the sole deoxygenation products.
It is worth mentioning that the Ph3P/Br2/CuBr system is
chemoselective, tolerating various functional groups such as car-
bon–carbon double bond and ketone (Table 2, Entries 14 and
15). These observations clearly suggest that this method can
be applied for the chemoselective deoxygenation of these sulfox-
ides in the presence of the above-mentioned functional groups in
multifunctional molecules.
We investigated the deoxygenation of diphenyl sulfoxide
(Table 2, Entry 1) as a model compound with Ph3P, Ph3P/Br2,
Ph3P/CuBr, or CuBr in refluxing acetonitrile. Under these
conditions, the reaction did not proceed at all after 2 h and the
starting material was isolated intact from the reaction mixture.
In order to show the efficiency of this method, the results of
deoxygenation of dibenzyl sulfoxide to dibenzyl sulfide (Table 2,
Entry 3) by our method are compared with those reported by
O
PPh3/Br2/CuBr
R
S
R'
R
S
R'
CH3CN, reflux
R, R' = Alkyl, aryl
Scheme 1.
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.11 (2007)
1325
Table 3. Comparison of deoxygenation of dibenzyl sulfoxide
to dibenzyl sulfide (Table 2, Entry 3) by the Ph3P/Br2/CuBr
system with some of those reported in the literature
1996, 26, 3619. e) Y. Wang, M. Koreeda, Synlett 1996,
885. f) M. Shimizu, K. Shibuya, R. Hayakawa, Synlett
2000, 1437. g) M. Abo, M. Dejima, F. Asano, A. Okubo,
S. Yamazaki, Tetrahedron: Asymmetry 2000, 11, 823. h)
K. C. Nicolaou, A. E. Kuombis, S. A. Synder, K. B.
Simonsen, Angew. Chem., Int. Ed. 2000, 39, 2529. i) B.
Karimi, D. Zareyee, Synthesis 2003, 335. j) D. R. Boyd,
N. D. Sharma, S. A. Haughey, M. A. Kennedy, J. F. Malone,
S. D. Shepherd, C. C. R. Allen, H. Dalton, Tetrahedron
2004, 60, 549.
S. Black, E. M. Harte, B. Hudson, L. Wartofsky, J. Biol.
Chem. 1960, 235, 2910.
M. Madesclaire, Tetrahedron 1988, 44, 6537.
a) H. O. House, Modern Synthetic Reactions, 2nd ed.,
Benjamin cummings, California, 1972, pp. 15–16. b) H. O.
House, Modern Synthetic Reactions, 2nd ed., Benjamin
cummings, California, 1972, pp. 215–216.
Reagent (Oxidant/Substrate)
Yield/% (Time)
Ph3P/Br2/CuBr/CH3CN/reflux
NiCI2/NaBH4/THF/0 ꢁC (3:9)14
PhSiH3/MoO2Cl2/PhCH3/reflux15
94 (45 min)
81 (2 h)
95 (20 h)
2,6-Dihydroxypyridine/CH3CN/reflux16 98 (4 h)
Ph3P/TiCl4/THF/rt17
96 (2 h)
TiI4/CH3CN/0 ꢁC1f
85 (10 min)
98 (20 min)
91 (40 min)
2
18
.
BF3 Et2O/NaI/CH3CN/rt
BBr3/CH2Cl2/ꢂ23{0 ꢁC19
3
4
+
–
Ph3PBr/Br
Ph3P
+
Br2
R'
1
O
S
5
6
7
8
M. Madesclaire, Tetrahedron 1988, 44, 6537.
–
+
V. Y. Kukushkin, Coord. Chem. Rev. 1995, 139, 375.
J. H. Espenson, Coord. Chem. Rev. 2005, 249, 329.
B. R. Raju, G. Devi, Y. S. Nongpluh, A. K. Saikia, Synlett
2005, 358.
R. Sanz, J. Escribano, R. Aguado, M. R. Pedrosa, F. J.
Arnaiz, Synthesis 2004, 1629.
1
+
R2S
O
PPh3Br/Br
R
2
2CuBr
R
S
R'
Ph3P
O
2
+
+
-2CuBr2
9
Scheme 2. Proposed mechanism for the deoxygenation of
sulfoxide.
10 D. J. Harrison, N. C. Tam, C. M. Vogels, R. F. Langler, R. T.
Baker, A. Decken, S. A. Westcott, Tetrahedron Lett. 2004,
45, 8493.
11 B. W. Yoo, K. H. Choi, D. Y. Kim, K. I. Choi, J. H. Kim,
Synth. Commun. 2003, 33, 53.
other methods. The results show that this method is superior to
some previously reported methods in terms of yields, reaction
times, and the amount of the reagent used for successful deoxy-
genation (Table 3).
The enthalpies of formation of triphenylphosphine and
triphenylphosphine oxide are ꢀfHꢁ ¼ þ207:02 kJ molꢂ1 and
ꢀfHꢁ ¼ ꢂ116:41 kJ molꢂ1, respectively.20 On the basis of this
fact, the formation of Ph3P=O is the major driving force in
the proposed mechanism. Treatment of Ph3P with Br2 forms
the intermediate 1. Addition of sulfide to 1 produces the inter-
mediate 2 and this intermediate in the presence of CuBr can then
be converted to a sulfide (Scheme 2).
In conclusion, the present investigation has demonstrated
the use of the Ph3P/Br2/CuBr system as a very simple mixed-re-
agent system for the efficient deoxygenation of sulfoxides in ex-
cellent yields and short reaction times. In addition, wide applica-
bility and also excellent chemoselectivity make this reagent sys-
tem a good choice for the use in the deoxygenation of sulfoxides.
12 K. C. Nicolaou, A. E. Koumbis, S. A. Snyder, K. B.
Simonsen, Angew. Chem., Int. Ed. 2000, 39, 2529.
13 General procedure for the deoxygenation of sulfoxides: To a
flask containing a stirring mixture of Ph3P (1.2 mmol,
0.314 g) and Br2 (1.2 mmol, 0.07 mL) in dry acetonitrile
(5 mL), sulfoxide (1 mmol) was added. CuBr (2.2 mmol,
0.315 g) was then added to the reaction mixture. The reaction
mixture was stirred at reflux temperature for the time indicat-
ed in Table 2. The progress of the reaction was monitored pe-
riodically by TLC. Upon completion, the reaction mixture
was evaporated and purified by silica-gel column chroma-
tography with the appropriate mixture of n-hexane and ethyl
acetate to afford the sulfides.
14 J. M. Khurana, A. Ray, S. Singh, Tetrahedron Lett. 1998, 39,
3829.
15 A. C. Fernandes, C. C. Romao, Tetrahedron 2006, 62, 9650.
16 S. J. Miller, T. R. Collier, W. Wu, Tetrahedron Lett. 2000,
41, 3781.
We are thankful to the Razi University Research Council for
partial support of this work.
17 S. Kikuchi, H. Konishi, Y. Hashimoto, Tetrahedron 2005,
61, 3587.
References and Notes
18 Y. D. Vankar, C. T. Rao, Tetrahedron Lett. 1985, 26, 2717.
19 Y. Guindon, J. G. Atkinson, H. E. Morton, J. Org. Chem.
1984, 49, 4538.
20 D. R. Kirklin, E. S. Domalski, J. Chem. Thermodyn. 1988,
20, 743.
1
a) M. Madesclaire, Tetrahedron 1988, 44, 6537. b) E.
Nicolas, M. Vilaseca, E. Giralt, Tetrahedron 1995, 51,
5701. c) V. Y. Kukushkin, Coord. Chem. Rev. 1995, 139,
375. d) K. Fujiki, S. Kurita, E. Yoshida, Synth. Commun.
Published on the web (Advance View) October 6, 2007; doi:10.1246/cl.2007.1324