A new method for the synthesis of dithiocarbamates by CuI-catalyzed coupling reaction

Article abstract of DOI:10.1016/j.tetlet.2007.03.168

The Ullmann-type coupling reaction of sodium dithiocarbamates with aryl iodides and vinyl bromides catalyzed by CuI/N,N-dimethylglycine proceeds smoothly in DMF at 110 °C to give corresponding dithiocarbamates in good yields.

Full text of DOI:10.1016/j.tetlet.2007.03.168

Tetrahedron Letters 48 (2007) 4785–4788
A new method for the synthesis of dithiocarbamates by
CuI-catalyzed coupling reaction
Yunyun Liu and Weiliang Bao*
Department of Chemistry, Xi Xi Campus, Zhejiang University, Hangzhou, Zhejiang 310028, PR China
Received 18 January 2007; revised 9 March 2007; accepted 30 March 2007
Available online 4 April 2007
Abstract—The Ullmann-type coupling reaction of sodium dithiocarbamates with aryl iodides and vinyl bromides catalyzed by CuI/
N,N-dimethylglycine proceeds smoothly in DMF at 110 °C to give corresponding dithiocarbamates in good yields.
Ó 2007 Published by Elsevier Ltd.
Organic dithiocarbamates have received much attention
due to their pivotal role in agriculture1 and their intrigu-
ing biological activities.2 They have also been used as
protection groups in peptide synthesis,3 as linkers in
solid-phase organic synthesis4 and recently in the syn-
thesis of ionic liquids.5 Furthermore, dithiocarbamates
are broadly employed in medicinal chemistry and have
been used in cancer treatment.6 Therefore, the synthesis
of dithiocarbamates has attracted a lot of attention
recently. Conventionally, protocols for the synthesis of
dithiocarbamates involve the use of costly and toxic
reagents, such as thiophosgene and its substituted deriv-
atives.7 The one-pot reaction of amines with carbonyl
sulfide and alkyl halides in organic solvents or without
solvent was reported by Chaturvedi, Saidi and their
co-workers recently.8,9 However, most of the above
described methods focused on the alkylation of dithio-
carbamic acid and obtained alkyl dithiocarbamate.
General methods for the synthesis of aryl and vinyl
esters of dithiocarbamic acids are based upon the reac-
tions of hypervalent iodine compounds with sodium salt
of dithiocarbamic acid,10 or certain organometallic
reagents with tetramethylthiuram disulfide.11 The
synthesis of vinyl esters of dithiocarbamic acids can also
be achieved by the reactions of allyl esters of dithio-
carbamic acids under strong basic conditions,12 and
phosphonium ylides with aldehydes.13
reported the formation of aryl-carbon, aryl-nitrogen,
aryl-oxygen and aryl-sulfur bonds based on copper(I)
catalysts as alternatives to palladium(0) catalysts.14 Ma
et al. found that a- and b-amino acids could accelerate
copper-catalyzed coupling reactions. By using these spe-
cial ligands many reactions could be carried out at rela-
tively low temperatures.15 As far as we know, the
application of copper-catalyzed coupling reaction of
aryl and vinyl halides with dithiocarbamates has not
been developed. Herein, we wish to report a novel and
efficient method for the synthesis of dithiocarbamates
using CuI as the catalyst and amino acids as the ligands.
As indicated in Table 1, we chose the coupling of phenyl
iodide with sodium dimethylcarbamodithioate as a
model reaction to optimize the reaction condition.
Because effective activities of amino acids were recently
found in the coupling reactions catalyzed by CuX,15c,e
N,N-dimethylglycine and L-proline were checked as the
ligands for the present reaction. It was found that the
reaction proceeded at 90 °C in DMF in the presence
of 15 mol % CuI , 30 mol % N,N-dimethylglycine and
K2CO3 (entry 1). The reaction also worked well without
the addition of K2CO3 (entry 3), and gave the coupling
product in excellent yield by raising the reaction temper-
ature (entry 8). Among the solvents tested, DMSO and
[Bmim]BF4 were effective (entries 4 and 6) and DMF
gave the best result (entry 3), while no conversion was
observed in toluene and dioxane (entries 5 and 7).
During the past years, great progress has been achieved
on the development of copper-catalyzed Ullmann-type
coupling reaction. Buchward and other groups have
On the basis of the above results, the scope and the
limitations of the coupling reaction were explored with
various aryl and vinyl halides and other sodium dithio-
carbamates, and the results are summarized in Table 2.
*
Corresponding author. Fax: +86 571 88911554; e-mail: wlbao@
css.zju.edu.cn
0040-4039/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2007.03.168

4786
Y. Liu, W. Bao / Tetrahedron Letters 48 (2007) 4785–4788
Table 1. CuI-Catalyzed coupling reaction of phenyl iodide with sodium dimethylcarbamodithioate under different catalytic conditions
S
I
S
N
CuI/ligand/base
solvent/ 22 h
N
S
Na
+
S
Entry
Solvent
Base
Ligand
Temperature (°C)
Yielda,c (%)
1
2
3
4
5
6
7
8
DMF
DMF
DMF
DMSO
Toluene
[Bmim]BF4
Dioxane
DMF
K2CO3
K2CO3
No
No
No
No
No
No
N,N-Dimethylglycine
L-Proline
90
90
90
90
90
90
90
110
70
55
70
50
0
N,N-Dimethylglycine
N,N-Dimethylglycine
N,N-Dimethylglycine
N,N-Dimethylglycine
N,N-Dimethylglycine
N,N-Dimethylglycine
60b
0
95
a Isolated yield.
b Bmim = 1-butyl-3-methylmidazolium.
c Reaction conditions: CuI (15 mol %); N,N-dimethylglycine (30 mol %); K2CO3 (2 mmol); aryl iodide (1 mmol); sodium dimethylcarbamodithioate
(1.2 mmol); solvent (2 mL).
Table 2. Coupling reaction of aryl and vinyl halides with sodium dithiocarbamates under the catalysis of CuI/N,N-dimethylglycine
Entry
Substrates
Product
Yielda,c (%)
E:Zb
S
S
S
S
I
I
1
95
N
S
Na
Na
N
N
S
S
S
2
3
82
75
N
S
S
S
S
Na
N
N
I
S
S
S
I
4
5
6
83
82
87
N
S
Na
Na
Na
N
Me
MeO
Br
Me
MeO
Br
S
S
S
S
I
N
S
S
N
S
S
I
N
N
S
S
S
I
7
8
9
91
N
S
Na
Na
N
Cl
Cl
S
S
S
Br
Trace
75
N
S
N
S
S
S
Br
90:10
5:95
N
S
S
Na
N
S
S
S
10
90
N
Na
Br
N

Y. Liu, W. Bao / Tetrahedron Letters 48 (2007) 4785–4788
4787
Table 2 (continued)
Entry
Substrates
Product
Yielda,c (%)
E:Zb
S
S
S
S
Br
Na
Na
11
12
70
90:10
N
N
N
S
S
S
S
S
77
3:97
N
Br
Br
S
S
13
81
90
7:93
6:94
Cl
N
N
S
Na
Cl
N
S
S
S
14
Cl
S
Na
Br
Cl
N
a Isolated yield.
b The ratio was based on 1H NMR spectrum.
c CuI (15 mol %); N,N-dimethylglycine (30 mol %); aryl iodide or vinyl bromides (1 mmol); sodium dithiocarbamates (1.2 mmol); in DMF (2 mL) at
110 °C for 22 h.
Aryl iodide delivered arylation products in good yields
by coupling with sodium piperidine-1-carbo-dithioate,
sodium 2-phenylpropanedithioate (entries 2 and 3).
The electron-deficient aryl iodides (entries 6 and 7) were
generally superior to the electron-rich ones (entries 4
and 5), as demonstrated by better yields. Unfortunately,
bromobenzene gave only trace amounts of product
under the conditions described (entry 8). Because the
general methods for the synthesis of vinyl esters of
dithiocarbamic acids have some disadvantages such as
difficult accessible starting materials, or lack of stereo-
selectivity, we wish to report a milder, more stereoselec-
tive and convenient method for the synthesis of vinyl
esters of dithiocarbamic acids from vinyl bromides
catalyzed by CuI/N,N-dimethylglycine in DMF. It was
found that both (E)- and (Z)-vinyl bromides were
suitable for this reaction, giving the desired coupling
products in good yields and high stereoselectivities
(entries 9–14). The (Z)-vinyl bromides gave a higher
stereoselectivity in comparison to the (E)-vinyl bromides
(comparing entries 9 and 10, as well as entries 11 and
12). The steric hindrance of vinyl bromides is slightly
disfavoured for this reaction. For example, when
(Z)-1-(2-bromovinyl)-2-chlorobenzene was used as the
substrate, the reaction gave a relatively lower yield in
comparison to that of less hindered vinyl bromide
(compare entries 13 and 14). The mechanism of the
reaction maybe similar with that described by Ma and
co-workers.16
vinyl bromides. The yields are from good to excellent,
and the stereoselectivity is satisfactory.
Acknowledgement
This work was financially supported by the Natural
Science Foundation of China (No. 20372058).
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