Formation of C(sp2)-S bonds through decarboxylation of α-oxocarboxylic acids with disulfides or thiophenols

Article abstract of DOI:10.1039/c4ra15751f

Copper-catalyzed decarboxylative coupling between α-oxocarboxylic acids and diphenyl disulfides or thiophenols is presented, which provided an effective and direct approach for the preparation of useful thioesters through C(sp²)-S bond formatio

Full text of DOI:10.1039/c4ra15751f

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Formation of C(sp2)–S bonds through
decarboxylation of a-oxocarboxylic acids with
Cite this: RSC Adv., 2015, 5, 26461
disulfides or thiophenols†
a
Guangwei Rong, Jincheng Mao, ab Defu Liu,a Hong Yan,a Yang Zhenga and Jie Chena
Received 3rd December 2014
Accepted 10th March 2015
*
DOI: 10.1039/c4ra15751f
www.rsc.org/advances
Copper-catalyzed decarboxylative coupling between a-oxocarboxylic Aer that, many researches focused on the combination of
acids and diphenyl disulfides or thiophenols is presented, which decarboxylation and C–H activation or functionalization, since
provided an effective and direct approach for the preparation of useful this is a more straightforward way.5e–5i In 2009, Ge and co-
thioesters through C(sp2)–S bond formation.
workers just described a Pd-Catalyzed decarboxylative ortho-
acylation of acetanilides with a-oxocarboxylic acids.5j From then
on, a series of works on C–C formation via directed ortho-
direction from decarboxylation of a-oxocarboxylic acids came
out.5k–5r Recently, Duan and co-workers disclosed silver-
catalyzed decarboxylative acylarylation of acrylamides with
a-oxocarboxylic acids in aqueous media.5s Based on the above
examples, it can be seen that C–C formation reactions were
performed smoothly via decarboxylation of a-oxocarboxylic
acids. However, researches on carbon–heteroatom formation
were less reported till now. Thus, in this paper, we will present
our results on copper-catalyzed decarboxylation of a-oxo-
carboxylic acids with disuldes or thiophenols to prepare the
useful thioesters through C(sp2)–S bond formations.
In recent years, transition-metal-catalyzed decarboxylative
cross-coupling has attracted great attention in the formation of
carbon–carbon and carbon–heteroatom bonds, since acids and
their derivatives are usually stable, low-cost and commercially
available substrates.1 Different from the traditional cross-
coupling methods, which need pre-activated partners such as
organometallic reagents and thus generate toxic metal wastes,
transition-metal-catalyzed decarboxylative cross-coupling reac-
tions generally prefer to employ a catalytic amount of metal
catalysts such as palladium, copper, iron salts, etc.2 Among
these atom economical and green protocols, arylcarboxylic
acids or arylcarboxylates were oen used as aryl sources.3
Excellent work on decarboxylative coupling reactions using
benzoic acids and cinnamic acids has been extensively studied
in the past several years.4 However, the area of decarboxylative
reactions of benzoylformic acids has not been fully explored.5 It
was rstly reported by Elena Vismara and his coworkers about
silver-catalyzed decarboxylative acylation reaction in 1991.5a
Then, the related decarboxylative couplings were developed by
different groups as shown in Scheme 1. For example, Goossen
and co-workers have reported Cu/Pd-catalyzed decarboxylation
of a-oxocarboxylates and aryl bromides.5b,5c Ge and Li showed an
example of Pd(II)-catalyzed decarboxylative cross-coupling of
potassium aryltriuoroborates with a-oxocarboxylic acids.5d
As we know that thioesters play pivotal roles in biology as
they are important structure units in various natural
compounds. Besides, they also serves as essential synthetic
intermediates for a range of acyl transfer reactions.6 Tradi-
tionally, thioester was prepared from benzoyl chloride and
aKey Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science, Soochow University, Suzhou 215123,
P. R. China. E-mail: jcmao@suda.edu.cn
bState Key Laboratory of Oil and Gas Reservoir Geology and Exploitation, Southwest
Petroleum University, Chengdu 610500, P. R. China
† Electronic supplementary information (ESI) available: Experimental procedures,
1H, 13C, spectral data and analytical data for the products. See DOI:
10.1039/c4ra15751f
Scheme 1 Decarboxylation of benzoylformic acid.
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thiophenol. Considering the hygroscopicity and instability of various co-solvent such as DMSO/CH3CN and DMSO/dioxane in
benzoyl chloride, more practical approaches were developed a ratio of 10 : 1. We were pleased to nd that 3a was obtained in
using benzaldehydes as starting materials in recent years.7 74% yield when DMSO/H2O as solvent (Table 1, entry 15).
Unlike previous reported protocols, thioesterication also can Through the adjustment of the proportion of solvent, we found
also be achieved through a-oxocarboxylic acids and disuldes that the optimum solvent ratio of DMSO/H2O was 5 : 1 and the
with our method, which provides an alternative way to access yield was increased to 83% (Table 1, entry 18). The amount of 2a
thioesters.
was also tested (Table 1, entries 19 and 20) and 2 equivalents
In our initial attempt, benzoylformic acid and diphenyl proved to be the best. S-Phenyl benzenesulfonothioate was
disulde were chosen as model substrates to screen the optimal detected aer the reaction which can explain why disulde
reaction conditions and the results are shown in Table 1. Using should be excessive.
20 mol% of cupric acetate as catalyst, stoichiometric (NH4)2S2O8
With optimized reaction conditions in hand, we next
as oxidant and acetonitrile as solvent, desired product was investigated the scope of different a-oxocarboxylic acids. As
achieved in the yield of 28% (Table 1, entry 1). Controlled shown in Table 2, various substituted a-oxocarboxylic acids,
experiments conrmed that the reaction can not occur without including methyl, halogen and methoxy groups, were
catalyst or oxidant. The reaction also can not proceed smoothly tolerable under the optimal conditions. Generally,
using the traditional system of Ag(I)/(NH4)2S2O8. Then, we a-oxocarboxylic acids bearing an electron-donating group
screened various copper catalysts and CuO showed best cata- gave the products in higher yields than those with electron-
lytic efficiency, affording the product 3a in 33% yield (Table 1, withdrawing analogues. Methyl-substituted from 3b to 3d
entry 7). Different oxidant were tested and (NH4)2S2O8 was all proceeded well and gave in good yields (Table 2, entries
proved to be one of the best (Table 1, entires 12–14). Most 2–4). The yields of p-halogen substrates were decreased from
solvents were not suitable to this reaction during the process of 3e to 3g (Table 2, entries 5–7). It is the same situation for
optimization, only DMSO showed good effect and 65% 3a was o-halogen substrates 3k and 3l (Table 2, entries 11 and 12).
achieved (Table 1, entry 12). Given that mixed solvent was Meta-bromine benzoylformic acid afforded product (Table 2,
widely adopted in decarboxylative reactions, we next tried entry 8) in lower yield than ortho and para-bromine acids. We
guess that the poor conjugated effect perhaps caused the
difference when bromine located in the meta position. For
heterocyclic and fused ring substrates, 3m and 3n can be
achieved in good yields of 79% and 82%, respectively.
Furthermore, aliphatic a-oxocarboxylic acid was also suitable
Table 1 Optimization of reaction conditions for the decarboxylative
coupling of benzoylformic acid with diphenyl disulfidea
Table 2 Copper-catalyzed decarboxylative coupling between various
a-oxocarboxylic acids and diphenyl disulfide (2a)a
Entry
Cat.
Oxidant
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
Cu(OAc)2
Cu
CuI
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
K2S2O8
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Dioxane
Toluene
DCE
DMF
DMSO
DMSO
DMSO
DMSO/H2O ¼ 20/1
DMSO/H2O ¼ 10/1
DMSO/H2O ¼ 7/1
DMSO/H2O ¼ 5/1
DMSO/H2O ¼ 5/1
DMSO/H2O ¼ 5/1
28
29
Trace
<10
31
Entry
R
Product
Yieldb [%]
CuCl2
CuSO4
CuF2
CuO
CuO
CuO
CuO
CuO
CuO
CuO
CuO
CuO
CuO
CuO
CuO
CuO
CuO
31
33
1
2
3
4
5
6
7
8
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
83
84
86
82
81
60
51
34
54
86
60
53
79
82
56
4-MeC6H4
3-MeC6H4
2-MeC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
3-BrC6H4
2-BrC6H4
4-MeOC6H4
2-FC6H4
NR
NR
NR
NR
65
50
45
74
78
82
83
72
83
9
10
11
12
13
14
15
16
17
18
19c
20d
Na2S2O8
9
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
10
11
12
13
14
15
2-ClC6H4
2-Thienyl
2-Naphtyl
Methyl
a
a
Catalytic conditions: benzoylformic acid (0.3 mmol), diphenyl
Catalytic conditions: benzoylformic acid (0.3 mmol), diphenyl
disulde (0.3 mmol), cat. (20 mol%), oxidant (0.6 mmol), solvent disulde (0.3 mmol), (NH4)2S2O8 (0.6 mmol), CuO (20 mol%),
b
c
d
(2 mL), 80 ꢀC, 12 h, air. Isolated yield. 2a (0.15 mmol). 2a (NH4)2S2O8 (0.6 mmol), DMSO/water (5/1) (2 mL), 80 ꢀC, 12 h, air.
b
(045 mmol).
Isolated yield.
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Table 3 Copper-catalyzed decarboxylation of benzoylformic acid
and various disulfidesa
Entry
R
Product
Yieldb [%]
Scheme 2 Plausible mechanism.
1
2
3
4
5
4-MeC6H4
4-MeOC6H4
4-NO2C6H4
Benzyl
3p
3q
—
3r
80
86
NR
65
52
yields as shown in Table 4. It is obvious to nd that the desired
thiols show less efficiency in thioesterication compared to
disuldes. Anyway, it provides alternative choice of substrates
as thiols are more cheaper and commercially available. It was
found that disulde was detected aer reaction, which indi-
cated that the reaction may go through a process that thio-
phenol was converted into the corresponding disulde before
reacting with benzoylformic acid.
n-Propyl
3s
a
Catalytic conditions: benzoylformic acid (0.3 mmol), disulde (0.3
mmol), CuO (20 mol%), (NH4)2S2O8 (0.6 mmol), DMSO/water (5/1)
(2 mL), 80 ꢀC, 12 h, air. b Isolated yield.
Based on previous reports about decarboxylations,5a,7 we
proposed a possible mechanism as shown in Scheme 2. Firstly
benzoylformic acid generates benzoyl radical in the presence of
copper(II) catalyst. The radical then further reacts with disulde
or thiophenol to give the thioester. The copper(I) ion will be next
oxidized to copper(II) by ammonium persulfate and back into
the reaction.
In conclusion, we have presented an efficient method to
prepare thioesters involving C(sp2)–S bonds formation through
decarboxylative coupling of a-oxocarboxylic acids and disuldes
or thiophenols. Furthermore, the thioesters prepared by our
method will show valuable properties such as nucleophile
acceptors, which means they can serve as one of the most
important intermediates in organic synthesis.8 Further appli-
cation of the reaction will be the key point of our future work.
substrate in this reaction, giving a moderate yield (3o)
(Table 2, entry 15).
As shown in Table 3, we then applied the optimal reaction
conditions to decarboxylations of benzoylformic acid with
various disuldes. Aromatic disuldes can afford the desired
esters in good yields. Disulde bearing strong electron donating
group such as methoxy was converted into the corresponding
thioester 3q in 86% yield (Table 3, entry 2). However, the reac-
tion was almost inhibited when p-nitro substituted disulde
was chosen as the substrate (Table 3, entry 3). It is pleased to
nd that aliphatic disuldes are good substrates, giving
moderate yields (3r and 3s) (Table 3, entries 4 and 5).
As we know that thiols have disadvantages of operating
inconvenience and unpleasant odour in comparison to disul-
des. Considering the similarity of their structure, we further
extended the reaction to a series of thiols. Various substituted
thiols all gave the corresponding products in moderate to good
Acknowledgements
We are grateful to the grants from the Scientic Research
Foundation for the Returned Overseas Chinese Scholars, State
Education Ministry, the Priority Academic Program Develop-
ment of Jiangsu Higher Education Institutions, and the Key
Laboratory of Organic Synthesis of Jiangsu Province.
Table 4 Copper-catalyzed decarboxylative coupling between ben-
zoylformic acid and various thiophenols (2a)a
Notes and references
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Entry
R
Product
Yieldb [%]
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6
C6H5
3a
3t
3u
3v
3w
3x
74
73
75
66
72
45
2-MeC6H4
2,6-Me2C6H3
2-ClC6H4
2-FC6H4
2-Thienyl
a
Catalytic conditions: benzoylformic acid (0.3 mmol), thiophenol (0.6
mmol), CuO (20 mol%), (NH4)2S2O8 (0.6 mmol), DMSO/water (5/1)
(2 mL), 80 ꢀC, 12 h, air. b Isolated yield.
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