Copper-catalyzed oxidative olefination of thiols using sulfones and phosphorous ylides

Article abstract of DOI:10.1002/bkcs.10347

Copper-catalyzed one-pot conversion of thiols to olefins was conducted under aerobic conditions. Thiols were oxidized to generate thioaldehydes, which reacted with sulfones or phosphorous ylides to form the corresponding olefins. The formation of thiosulfonates and phosphorous sulfides confirms that these olefination protocols proceed via thioaldehyde-sulfone and thioaldehyde-ylide adducts.

Full text of DOI:10.1002/bkcs.10347

Article
DOI: 10.1002/bkcs.10347
BULLETIN OF THE
P. K. Shyam et al.
KOREAN CHEMICAL SOCIETY
Copper-catalyzed Oxidative Olefination of Thiols Using Sulfones
and Phosphorous Ylides
Pranab K. Shyam,† Chan Lee,† and Hye-Young Jang†,‡,
*
†Division of Energy Systems Research, Ajou University, Suwon 443-749, Korea.
*E-mail: hyjang2@ajou.ac.kr
‡Korea Carbon Capture & Sequestration R&D Center, Daejeon 305-343, Korea
Received January 6, 2015, Accepted March 18, 2015, Published online June 26, 2015
Copper-catalyzed one-pot conversion of thiols to olefins was conducted under aerobic conditions. Thiols were
oxidized to generate thioaldehydes, which reacted with sulfones or phosphorous ylides to form the correspond-
ing olefins. The formation of thiosulfonates and phosphorous sulfides confirms that these olefination protocols
proceed via thioaldehyde-sulfone and thioaldehyde-ylide adducts.
Keywords: Copper, Oxidation, Olefination, Wittig, Julia
Introduction
assumed to form; these compounds might behave similar to
aldehydes during olefination.6 The utilization of thioalde-
hydes as synthetic building blocks has not received significant
attention because thioaldehydes are generally synthesized
from specific starting materials under limited reaction condi-
tions, e.g., photoreaction of β-keto sulfides, 1,5-sigmatropic
rearrangement of thiosulfinates, 1,2-elimination of sulfenyl
chloride, and the thermolysis of trithianes.7 Compared with
the previous methods, our conditions provide thioaldehydes
from thiols using relatively low-cost copper catalysts and eco-
nomical oxygen. In this study, we present the direct conver-
sion of thiols to a variety of olefins in good yields using
sulfones and phosphorous ylides (Scheme 1).
Olefination of carbonyl compounds is an efficient and
convenient method to provide synthetically useful olefins;
therefore, a variety of olefination methods such as Wittig,
Horner–Wadsworth–Emmons, Peterson, Julia olefination
reactions, and the olefination using Tebbe's reagent or tita-
nium metals (McMurry coupling) have been developed.1
Furthermore, carbonyl compounds generated in situ by oxida-
tion of alcohols and dehydrogenation of alcohols have been
used for such olefination reactions to directly generate
olefins from alcohols (Scheme 1).2–4 To promote catalytic
and economical processes, oxygen is used as the oxidant for
the oxidative olefination. Under nonoxidative conditions,
dehydrogenation was applied to generate aldehydes from
alcohols. Ruthenium complexes that are relatively expensive
are commonly used as aerobic oxidation and dehydrogenation
catalysts in the one-pot oxidation followed by olefination4;
therefore, development of more economical catalysts is highly
required.
Experimental
Representative Procedure for the Reaction of Thiols and
Sulfones. A mixture of benzyl mercaptan 1a (87 μL, 0.75
mmol), copper bromide (II) (1.1 mg, 0.005 mmol), 1,5,7-tria-
zabicyclo[4,4,0]dec-5-ene (53.2 mg, 0.375 mmol), and 1-
phenyl-2-(phenylsulfonyl)ethanone 1b (65.1 mg, 0.25 mmol)
in toluene (1 M, 0.25 mL) was taken in a 5 mL round bottom
flask and stirred at 100 ꢀC for 18 h under oxygen atmosphere.
The reaction mixture was evaporated and purified by flash sil-
ica gel column chromatography using 1% ether/hexane to
obtain 1c (38.2 mg, 73%).
Representative Procedure for the Reaction of Thiols and
Phosphorous Ylides. A mixture of benzyl mercaptan 1a
(116 μL, 1 mmol), copper chloride (II) (1.3 mg, 0.01 mmol),
1,8-diazabicyclo[5.4.0]undec-7-ene (75 μL, 0.5 mmol), and
phosphorous ylide 5b (174.2 mg, 0.5 mmol) in toluene
(0.5 M, 1 mL) was taken in a 5 mL round bottom flask and
stirredat 100ꢀCfor18 hunderoxygenatmosphere. Thereaction
mixture was evaporated and purified by flash silica gel column
chromatography using 1% ether/hexane to obtain 7c (64.1
mg, 73%).
Our research group recently reported copper-catalyzed oxi-
dative coupling of thiols and amines/alcohols under aerobic
conditions.5 During the reaction, transient thioaldehydes are
previous works
Ru catalysts
CO2R'
R'
+
CO2R'
R'
Ph3P
R
R
OH
OH
R
O2
O
Ru catalysts
+
S
R''
R''
R
-H2
O
this work
O
+
+
COR'
COR'
R
S
O
SH
Cu catalysts
COR'
R
O2
Ph3P
R
SH
Scheme 1. Olefin formation via tandem oxidation–olefination
protocols.
Bull. Korean Chem. Soc. 2015, Vol. 36, 1824–1827
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Wiley Online Library
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BULLETIN OF THE
Article
Copper-catalyzed Oxidative Olefination of Thiols
KOREAN CHEMICAL SOCIETY
Table 1. Oxidative olefination of 1a using sulfone 1b.
Table 2. Examples of the coupling of thiols and sulfones.
Entry
1
Reactants
Productsa
2
3
Entry
Metal complex
Base
Yielda(%)
20
73 (29b, 73c)
1
2
CuBr2 (2 mol %)
CuBr2 (2 mol %)
TBD (1 equiv)
TBD (1.5 equiv)
3
4
5
6
7
8
9
10
11
CuBr2 (2 mol %)
CuCl2 (2 mol %)
CuBr (2 mol %)
Cu(OTf )2 (2 mol %) TBD (1.5 equiv)
FeCl3Á6H2O (2 mol %) TBD (1.5 equiv)
TBD (2 equiv)
TBD (1.5 equiv)
TBD (1.5 equiv)
29
41
64
68
54
43
52
14
5
4
5
—
TBD (1.5 equiv)
DBU (1.5 equiv)
KOtBu (1.5 equiv)
—
CuBr2 (2 mol %)
CuBr2 (2 mol %)
CuBr2 (2 mol %)
a Isolated yield.
b The reaction was run under 1 atm of nitrogen.
c 5 mol % of CuBr2
6
a The reactions were run under the conditions of entry 2 (Table 1).
b Isolated yield.
Results and Discussion
The results of the optimization of the formation of olefin 1c are
listed in Table 1. Benzyl mercaptan 1a and sulfone 1b were
exposed to copper-catalyzed oxidative olefination conditions
involving CuBr2 and 1,5,7-triazabicyclo[4.4.0]dec-5-ene
(TBD) to afford the (E)-form of chalcone 1c in a 20% yield
(entry 1). Increasing the amounts of TBD to 1.5 equivalents
(equiv) increased the yield to 73% (entry 2). Under a nitrogen
atmosphere, product formation was not efficient (29% yield,
entry 2). With increased amounts of CuBr2 (5 mol %), the
yield of 1c was not changed (73%, entry 2). Further increasing
the TBD loading to 2 equiv was detrimental to the yield (29%
yield, entry 3). CuCl2, CuBr, and Cu(OTf)2 and FeCl3Á6H2O
were tested as catalysts and gave lower yields than CuBr2
(entries 4–7). In the absence of metal complexes, 1c formed
in a 43% yield (entry 8). In the presence of other organic
and inorganic bases, the yield did not increase (entries 9 and
10). In the absence of base, 1c was obtained in a 5% yield,
implying that the base is critical to the nucleophilicity of 1b
(entry 11). Phenyl thiosulfonate TBDH+ A was isolated as a
byproduct of this reaction.8
75% yields, respectively (entries 1 and 2). Furyl thiol 4a par-
ticipated in the reaction to give 4c in a 69% yield (entry 3).
Octyl thiol was subjected to the reaction conditions, but the
desired olefinwasnotobtained. Toinvestigate thesubstituents
other than phenyl, tert-butyl-substituted sulfone 2b was sub-
jected to the reaction conditions to afford 5c in a 63% yield
(entry 4). Electron-rich OMe-substituted phenyl sulfone 3b
reacted with 1a to afford 6c in a 69% yield (entry 5). To com-
pare the reactivities of the sulfones, octyl-substituted sulfone
4bwas subjected to thereaction conditions to form 1c in a57%
yield, which was slightly lower than that obtained using 1b
(entry 6). In addition to sulfones containing a carbonyl group,
dimethylsulfone was checked to show no product formation.
Oxidative olefination of 1a with phosphorous ylide 5b was
performed under listed conditions in Table 3. A combination
of CuCl2 catalyst (2 mol %) and TBD (1 equiv) promoted oxi-
dative olefination of 1a in a 56% yield (entry 1). Changing
the base to 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)
increased the yield of 7c to 73%, and Z-isomer was observed
as a minor product (entry 2). In contrast to oxidative olefina-
tion using sulfone 1b, no product wasisolated under a nitrogen
atmosphere (entry 2). With 5 mol % of CuCl2, the yield of 7c
was decreased to 67% (entry 2). Increasing or decreasing the
amount of bases did not improve the yield of 7c (entries 3 and
Subsequent to optimization, various thiols and sulfones
were exposed to a solution of CuBr2 (2 mol %) and TBD
(1.5 equiv) to afford the desired olefin products (Table 2).
p-Fluoro and p-chloro-substituted benzyl thiols 2a and 3a,
respectively, reacted with 1b to afford 2c and 3c in 64 and
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Copper-catalyzed Oxidative Olefination of Thiols
KOREAN CHEMICAL SOCIETY
Table 3. Oxidative olefination of 1a using phosphorous ylide 5b.
Entry
Metal complex
Base
Yielda (%)
(E):(Z) ratio
1
2
CuCl2 (2 mol %)
CuCl2 (2 mol %)
TBD (1 equiv)
DBU (1 equiv)
56
(E)-isomer only
1.00:0.18
73 (0b, 67c)
3
4
5
6
7
8
9
10
11
CuCl2 (2 mol %)
CuCl2 (2 mol %)
CuCl2 (2 mol %)
CuBr2 (2 mol %)
Cu(OTf )2 (2 mol %)
CuCl (2 mol %)
FeCl3Á6H2O (2 mol %)
—
DBU (1.5 equiv)
DBU (0.5 equiv)
—
66
67
42
70
68
62
62
55
73
1.00:0.17
1.00:0.19
1.00:0.29
1.00:0.16
1.00:0.18
1.00:0.14
1.00:0.08
(E)-isomer only
1.00:0.16
DBU (1 equiv)
DBU (1 equiv)
DBU (1 equiv)
DBU (1 equiv)
DBU (1 equiv)
DBU (1 equiv)
CuBr (2 mol %)
a Isolated yield.
b The reaction was run under 1 atm of nitrogen.
c 5 mol % CuCl2 Ph3P S.
B
Table 4. Examples of the coupling of thiols and phosphorous ylides.
4). In the absence of bases, 7c was isolated in a 42% yield
(entry 5). Compared with the reactions using sulfone 5b, oxi-
dative olefination using phosphorous ylide 5b appeared to be
less sensitive to the amount of base, because ylide 5b is suffi-
ciently basic not to require additional base for increased
nucleophilicity. Other copper catalysts (i.e., CuBr2, Cu
(OTf)2, and CuCl) showed similar catalytic activities and
afforded 7c in 70, 68, and 62% yields, respectively (entries
6–8). FeCl3Á6H2O catalyzed the reaction; however, the
yield was lower than those of the copper-catalyzed reactions
(entry 9). In the absence of metal catalyst, 7c formed in a
55% yield (entry 10). Phosphorous sulfide B was isolated as
a byproduct of this reaction.9
The optimized reaction conditions for the coupling of
benzyl mercaptan 1a and phosphorous ylide 5b were
applied to diverse thiols and phosphorous ylides, as
shown in Table 4. Fluoro- and chloro-substituted thiols 2a
and 3a, respectively, reacted with 5b to afford the desired
α,β-unsaturated esters 8c and 9c in 72 and 86% yield, respec-
tively (entries 1 and 2). Furyl thiol was converted to the cor-
responding unsaturated ester, 10c, in a 60% yield (entry 3).
As an aliphatic thiol example, octyl thiol was tested, but
desired products were not obtained. Sterically hindered
methyl-substituted phosphorous ylide 6b reacted with 1a to
form α-substituted α,β-unsaturated ester 11c in an 83% yield
(entry 4). Ylides possessing methyl-ester and nitrile groups
also participated in oxidative olefination to form the corre-
sponding products 12c and 13c, respectively, albeit in slightly
reduced yields (entries 5 and 6).
Entry
1
Reactants
Productsa
2
3
4
5
6
a The reactions were run under the conditions of entry 2 (Table 3).
b Isolated yield.
We proposed a possible reaction mechanism, which is
shown in Scheme 2. As we published earlier,5
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Copper-catalyzed Oxidative Olefination of Thiols
KOREAN CHEMICAL SOCIETY
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S
O
Ph
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COPh
O
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A
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Ph
Copper complex
O2 TBD
TBDH+
S
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1c
SH
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Ph3P
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PPh3
Ph
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TBD
Scheme 2. Plausible reaction mechanism for the formation of 1c
and 7c.
thiobenzaldehydes can form via the deprotonation of
dibenzyldisulfide, which is formed from 1a.10 Oxidation
can be accelerated by a copper catalyst and oxygen. Thioben-
zaldehydes react with either sulfones or phosphorous
ylides to afford corresponding olefin 1c and 7c, respectively.
The byproducts of each reaction account for the reaction
mechanism that includes the intermediates described in
Scheme 2.
Conclusion
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We reported the first example of copper-catalyzed one-pot
aerobic oxidation of thiols followed by olefinations with
sulfones and phosphorous ylides. The thiols underwent
direct oxidation to afford thioaldehydes, which underwent
Julia-type and Wittig-type olefination with sulfones and
phosphorous ylides, respectively. Low-cost copper catalysts
enhanced the oxidation of thiols, and the use of appropriate
amounts of organic bases appears to be critical for
obtaining a high yield of olefin products. Isolation of the
byproducts of each reaction supported the proposed reaction
mechanism.
Acknowledgments. This study was supported by the Korea
Research Foundation (Nos 2009-0094046 and 2013008819)
and a Korea CCS R&D Center (KCRC) grant from the Korea
Government (Ministry of Education, Science and Technol-
ogy; No. 2014M1A8A1049294).
Supporting Information. Experimental procedures and
spectra of 1c–13c.
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Bull. Korean Chem. Soc. 2015, Vol. 36, 1824–1827
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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