A Highly Efficient CuCl 2 -Catalyzed C-S Coupling of Aryl Iodides with Tetraalkylthiuram Disulfides: Synthesis of Aryl Dithiocarbamates

DOI: 10.1055/s-0036-1589166

Source and publish data:

Synthesis p. 1527 - 1534 (2018)

Update date:2022-07-31

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Authors:

Cao, Qiang

Peng, Han-Ying

Cheng, Yu

Dong, Zhi-Bing

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Article abstract of DOI:10.1055/s-0036-1589166

A highly efficient copper(II)-catalyzed C-S cross-coupling reaction of aryl iodides with tetraalkylthiuram disulfides was developed. With only 1 mol% of CuCl ₂ as catalyst, zinc powder as reductant, and K ₂ CO ₃ as base, aryl iodides reacted with tetraalkylthiuram disulfides in DMSO furnishing the corresponding aryl dithiocarbamates in good to excellent yields. This protocol is an improvement of previous work, it features convenient performance, low addition of catalyst, no requirement for any ligand, and provides good yields. The method has a broad substrate scope and uses cheap and readily available starting materials.

Full text of DOI:10.1055/s-0036-1589166

SYNTHESIS

2018, 50, A–H

paper

Q. Cao et al.

Paper

Synthesis

A Highly Efficient CuCl₂-Catalyzed C–S Coupling of Aryl Iodides

with Tetraalkylthiuram Disulfides: Synthesis of Aryl Dithiocarba-

mates

Qiang Cao^‡

Han-Ying Peng^‡

R²

efficient, ligand free

R²

Yu Cheng

CuCl₂(0.01 equiv)/Zn (0.4 equiv)

DMSO, K₂CO₃(0.3 equiv), 110 °C

R²

R¹

R²

Zhi-Bing Dong*

School of Chemistry and Environmental Engineering,

Wuhan Institute of Technology, Wuhan 430205,

P. R. of China

R²: Me, Et, ⁿBu

cheap and efficient

21 examples

Yield: 39–96%

R¹: Me, MeO, ⁿBu, Br

Cl, NO₂, CF₃, CN

dzb04982@wit.edu.cn

dithiocarbamate source

^‡These authors contributed equally to this work

Received: 21.11.2017

Accepted after revision: 10.12.2017

Published online: 11.01.2018

rates,¹⁶pentafluorobenzonitrile,¹⁷and arylboronic acids.¹⁸

However, these methods are still limited by the need for

multiple reaction steps, air-sensitive organometallic re-

agents, flammable and explosive substrates or reagents,

and high substrate molar ratios. Recently, we described the

synthesis of aryl dithiocarbamates catalyzed by Cu₂O in the

presence of Cs₂CO₃.¹⁹To improve this methodology (using

less catalyst and cheaper base), and as continuing interests

for developing disulfides and relevant applications,²⁰we

hereby report a more efficient method for the preparation

of aryl dithiocarbamates through C–S coupling.

DOI: 10.1055/s-0036-1589166; Art ID: ss-2017-z0744-op

Abstract A highly efficient copper(II)-catalyzed C–S cross-coupling re-

action of aryl iodides with tetraalkylthiuram disulfides was developed.

With only 1 mol% of CuCl₂as catalyst, zinc powder as reductant, and

K₂CO₃as base, aryl iodides reacted with tetraalkylthiuram disulfides in

DMSO furnishing the corresponding aryl dithiocarbamates in good to

excellent yields. This protocol is an improvement of previous work, it

features convenient performance, low addition of catalyst, no require-

ment for any ligand, and provides good yields. The method has a broad

substrate scope and uses cheap and readily available starting materials.

We began the study by examining the cross-coupling

reaction of iodobenzene (1a) with tetramethylthiuram di-

sulfide (2a, TMTD) under open air conditions. A series of re-

action parameters, such as catalyst, base, additive, and sol-

vent, as well as their loadings, were surveyed. The reaction

did not proceed under ‘super base’²¹conditions (Table 1,

entry 1). The addition of a catalyst (CuCl₂or CuO, 5 mol%)

did not promote the reaction (entries 2–4). To our delight,

with the addition of a catalyst (CuO, 5 mol%) and zinc pow-

der (0.6 equiv), the desired aryl dithiocarbamate was ob-

tained in 71% yield (entry 5). Thus, a series of copper sourc-

es were examined (entries 5–12) and this revealed that Cu-

Cl₂was the best catalyst (entry 8). The base screening

(entries 8, 13–17) showed that K₂CO₃and Na₂CO₃were

helpful for the reaction and K₂CO₃was slightly better (entry

8). Control experiments listed in entries 17 and 18 showed

that copper and K₂CO₃were crucial for the model reaction.

The addition of other additives, such as Mg or Fe (entries 19

and 20) which serve as a reductant, also had a positive ef-

fect on the reaction, but they were inferior to Zn. The exam-

ination of solvents (entries 8, 21, and 22) and temperatures

(entries 8, 23 and 24) showed that DMSO was the best sol-

vent, and 110 °C was the optimal reaction temperature.

Surprisingly, the yield dropped very little when the catalyst

loading was decreased from 10 mol% to 1 mol% (entries 8,

Key words coupling, aryl iodide, disulfide, synthesis, dithiocarbamate

Organic dithiocarbamates (carbamodithioates) are pop-

ular in organic chemistry due to their versatile applications.

They have attracted wide attention since they serve as im-

portant synthetic intermediates.¹Moreover, they are popu-

lar blocks in biologically active compounds, such as mono-

acylglycerol lipase inhibitors,²leukemic cells inhibitors,³

thymocytes inhibitors,⁴antitumor agents,⁵and antibacteri-

al agents.⁶Compared to methods developed for other car-

bon–heteroatom bonds, the highly desirably efficient and

selective construction of C–S bonds in transition-metal-cat-

alyzed transformations remains relatively rare. In recent de-

cades, several excellent catalytic systems involving transi-

tion metals (palladium,⁷nickel,⁸copper,⁹and iron¹⁰) have

been found for C–S bond formation, leading to the develop-

ment of practical procedures for organic synthesis. Conven-

tionally, protocols for the synthesis of dithiocarbamates in-

volve the use of organometallic reagents with tetrameth-

ylthiuram disulfide¹¹sodium salt of dithiocarbamic acid

with diaryliodonium salts¹²or haloarenes.¹³In recent years,

one-pot three-component reactions have been reported us-

ing amines and carbon disulfide with electrophiles, includ-

ing alkyl¹⁴or aryl halides,¹⁵arenediazonium fluorobo-

Q. Cao et al.

Paper

Synthesis

Table 1 (continued)

25, and 26). The screening for base loading (entries 27–30)

and zinc loading (entries 31–34) demonstrated that 0.3

equiv of base and 0.4 equiv of Zn was the best loading

amount. The optimal reaction conditions are summarized

in entry 32.

Entry [Cu]

(mol%)

Additive

(equiv)

Base

(equiv)

Solvent

Temp. Yield

(°C)

110

(%)^b

CuCl₂(1)

Zn (0.8)

Zn (1)

K₂CO₃(0.3)

DMSO

^aReaction conditions: iodobenzene (1a, 1.0 mmol), tetramethylthiuram di-

sulfide (2a, 0.6 mmol), [Cu] (mol%), additive (equiv), base (equiv), DMSO

(2 mL), sealed tube, heat, 18 h.

Table 1 Optimization of the Reaction Conditions^a

^bIsolated yields.

^cNo reaction.

copper/additive/base

solvent, temperature, 18 h

With the optimal reaction conditions in hand, the sub-

strate scope was investigated. As shown in Table 2, a variety

of substituted iodobenzenes were coupled with tetramethyl-

thiuram disulfide (2a, TMTD), giving the desired products

with good to excellent yields (Table 2, entries 1–13). Elec-

tron-donating groups (Me, MeO, Bu) attached to the aryl

ring promoted the reaction slightly (entries 2–6), and elec-

tron-withdrawing groups (Br, NO₂, CN) deactivated the aryl

iodides, and provided the products in lower yields (entries

7, 8, 10, 11, and 13). ortho Steric hindrance also influenced

the reaction and slightly decreased the yields (entries 8, 10,

and 11). In addition, tetraethylthiuram disulfide (2b, TETD)

and tetrabutylthiuram disulfide (2c, TBTD) were also suit-

able for S-arylation under standard reaction conditions. The

corresponding products were obtained in slightly lower

yields due to the possible steric hindrance from the alkyl

group of the disulfide (entries 14–19). Subsequently, a

fused-ring compound (entry 20) and a heterocyclic sub-

strate (entry 21) underwent the C–S coupling, giving the

target molecules in moderate yields. Aryl bromides and

chlorides (entries 22 and 23) did not undergo C–S cou-

plings, indicating some limitations of the method.

A possible mechanism is proposed in Scheme 1 accord-

ing to experiments and previous literature.^18,22First, oxida-

tive addition of the aryl iodide with the copper catalyst may

provide intermediate a. Then, the disulfide coordinates to

the catalyst to provide intermediate b, which undergoes a

bond breaking to generate intermediate species c and the

thiolate d. Intermediate c easily provides the desired C–S

cross-coupled product e by reductive elimination. Interme-

diate d together with intermediate a regenerate the cop-

per(III) species c and then provide the desired product e.

Zinc plays the role of reductant.

Entry [Cu]

Additive

(equiv)

Base

(equiv)

Solvent

Temp. Yield

(°C)

(mol%)

(%)^b

–

KOH (1)

DMSO

DMF

110

–

CuCl₂(5)

CuO (5)

CuBr₂(5)

–

KOH (1)

110

130

–

K₂CO₃(1)

Na₂CO₃(1)

KOH (1)

–

Zn (0.6)

Cu(OAc)₂(5) Zn (0.6)

CuCl₂(5)

CuBr (5)

Cu₂O (5)

CuCl (5)

CuI (5)

Zn (0.6)

Mg (0.6)

Fe (0.6)

Zn (0.6)

Zn (0.2)

Zn (0.4)

CuCl₂(5)

–

trace

NaOH (1)

NaHCO₃(1)

–

trace

–

K₂CO₃(1)

K₂CO₃(0.1)

K₂CO₃(0.3)

K₂CO₃(0.5)

K₂CO₃(0.7)

K₂CO₃(0.3)

–

CuCl₂(5)

CuCl₂(10)

CuCl₂(1)

DMAc

DMSO

110

In summary, we developed a highly efficient copper-

catalyzed C–S coupling by using tetraalkylthiuram disul-

fides as starting materials. In the presence of the Cu-

Cl₂/Zn/K₂CO₃system, with no additional ligand, aryl iodides

reacted with tetraalkylthiuram disulfides in DMSO to give

the corresponding aryl dithiocarbamates in good to excel-

lent yields. This method features easy performance, low ad-

dition of catalyst, no requirement for any ligand, good

yields, broad substrate scope, and the use of cheap and

readily available starting materials, illustrating its potential

32 CuCl₂(1)

Q. Cao et al.

Paper

Synthesis

synthetic value for the convenient preparation of some po-

tentially biologically active compounds.²²Currently, the

protocol could not be applied to the less reactive aryl bro-

mides or chlorides. Further details of this protocol and the

related applications are under study in our laboratory.

Table 2 Synthesis of Aryl Dithiocarbamates^a

R²

CuCl₂(0.01 equiv)/Zn (0.4 equiv)

DMSO, K₂CO₃(0.3 equiv), 110 °C

R²

R¹

R²

Entry

Substrate 1

Substrate 2

Product 3

Yield (%)^b

MeO

Q. Cao et al.

Paper

Synthesis

Table 2 (continued)

Entry

Substrate 1

Substrate 2

Product 3

Yield (%)^b

NO₂

MeO

NO₂

MeO

NO₂

F₃C

MeO

Q. Cao et al.

Paper

Synthesis

Table 2 (continued)

Entry

Substrate 1

Substrate 2

Product 3

Yield (%)^b

22^c

23^d

^aReaction conditions: iodobenzene 1 (1.0 mmol), tetraalkylthiuram disulfide (0.6 mmol), [Cu] (1 mol%), zinc (0.4 mmol), K₂CO₃(0.3 mmol), DMSO (2 mL),

sealed tube, 110 °C, 18 h.

^bIsolated yields.

^cA less reactive aryl bromide was used.

^dA less reactive aryl chloride was used.

Cu^II

ArSR

(Merck 60, F-254) and visualized with UV light at 254 nm. Column

chromatography was performed on silica gel (200–250 mesh) with

petroleum ether (PE)/EtOAc as eluent.

ArI

Ar-Cu^III-I

R =

Phenyl Dimethylcarbamodithioate (3a) (Table 2, Entry 1); Typical

Procedure

RSSR

CuCl₂(1.4 mg, 0.01 mmol), zinc (powder) (26 mg, 0.4 mmol), DMSO

(2.0 mL), K₂CO₃(41.4 mg, 0.3 mmol), tetramethylthiuram disulfide

(2a, 144 mg, 0.6 mmol), and iodobenzene (1a, 204 mg, 1 mmol) were

added to a sealed tube equipped with a septum and magnetic stirring

bar, the mixture was stirred at 110 °C and monitored (TLC) until con-

sumption of the starting material (about 18 h). The mixture was

cooled to r.t., quenched with sat. NH₄Cl solution and then extracted

with EtOAc. The crude solution was dried (anhyd Na₂SO₄) and evapo-

rated under vacuum. The residue was purified by flash column chro-

matography (silica gel, PE/EtOAc 5:1) to give 3a (185 mg, 94%) as a

white solid; mp 90–92 °C.

Ar-Cu^III-I

S-S

Zn K₂CO₃

Cu^IIISR

I^–

Zn²⁺

RSK

Scheme 1 Possible reaction mechanism for C–S coupling of aryl iodide

and disulfide

¹H NMR(400 MHz, CDCl₃): δ = 7.41–7.50 (m, 5 H), 3.55 (s, 3 H), 3.49 (s,

3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 197.6, 136.9, 131.7, 130.0, 129.1, 45.7,

41.9.

All starting materials were purchased from commercial suppliers and

used without further purification unless otherwise stated. Yields re-

fer to isolated compounds estimated to be >95% pure as determined

by ¹H NMR and capillary GC analysis. NMR spectra were recorded on

a Bruker AM400 or Bruker AM 300 NMR instrument in CDCl₃using

TMS as an internal standard. Melting points were determined on a

Kofler micro melting point apparatus without correction. HRMS were

recorded on a Finnigan MAT 95Q or Finnigan 90 mass instrument

(ESI). TLC was performed using aluminum plates coated with silica gel

HRMS (ESI): calcd for C₉H₁₁NS₂(197.0333); found: 197.0339.

p-Tolyl Dimethylcarbamodithioate (3b) (Table 2, Entry 2)

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 7:1) to give 3b (194 mg, 92%) as a white sol-

id; mp 107–111 °C.

Q. Cao et al.

Paper

Synthesis

¹H NMR (400 MHz, CDCl₃): δ = 7.35 (d, J = 8.0 Hz, 2 H), 7.25 (d, J = 8.0

¹³C NMR (100 MHz, CDCl₃): δ = 196.5, 138.4, 132.3, 130.7, 124.9, 45.7,

Hz, 2 H), 3.55 (s, 3 H), 3.49 (s, 3 H), 2.40 (s, 3 H).

42.0.

¹³C NMR (100 MHz, CDCl₃): δ = 198.1, 140.3, 136.7, 130.0, 128.2, 45.7,

HRMS (ESI): calcd for C₉H₁₀BrNS₂(274.9438); found: 274.9445.

41.9, 21.5.

2-Bromophenyl Dimethylcarbamodithioate (3h) (Table 2, Entry 8)

HRMS (ESI): calcd for C₁₀H₁₃NS₂(211.0489); found: 211.0490.

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 7:1) to give 3h (203 mg, 80%) as a white sol-

id; mp 90–92 °C.

4-Methoxyphenyl Dimethylcarbamodithioate (3c) (Table 2, Entry

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 7:1) to give 3c (202 mg, 89%) as a white solid;

mp 97–99 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.37–6.95 (m, 4 H), 3.83 (s, 3 H), 3.54

¹H NMR (400 MHz, CDCl₃): δ = 7.69 (d, J = 8.0 Hz, 1 H), 7.55 (d, J = 8.0

Hz, 1 H), 7.31–7.22 (m, 2 H), 3.52 (s, 3 H), 3.48 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 194.9, 139.7, 133.5, 133.1, 131.8,

131.6, 128.1, 45.5, 42.1.

(s, 3 H), 3.48 (s, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 198.7, 161.1, 138.4, 122.6, 114.7, 55.3,

HRMS (ESI): calcd for C₉H₁₀BrNS₂(274.9438); found: 274.9436.

45.8, 41.9.

2-Chlorophenyl Dimethylcarbamodithioate (3i) (Table 2, Entry 9)

HRMS (ESI): calcd for C₁₀H₁₃NOS₂(227.0439); found: 227.0445.

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 7:1) to give 3i (222 mg, 96%) as a white solid;

mp 105–107 °C.

o-Tolyl Dimethylcarbamodithioate (3d) (Table 2, Entry 4)

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 7:1) to give 3d (190 mg, 90%) as a white sol-

id; mp 81–82 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.43–7.23 (m, 4 H), 3.53 (s, 3 H), 3.49

¹H NMR (400 MHz, CDCl₃): δ = 7.57–7.52 (m, 2 H), 7.45–7.39 (m, 1 H),

7.36–7.30 (m, 1 H), 3.55 (s, 3 H), 3.52 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 194.9, 140.5, 139.1, 131.7, 131.0,

130.2, 127.4, 45.6, 42.1.

(s, 3 H), 2.40 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 196.5, 143.8, 137.7, 133.7, 131.1,

HRMS (ESI): calcd for C₉H₁₀ClNS₂(230.9943); found: 230.9947.

130.7, 126.72, 45.5, 42.0, 20.9.

2-Nitrophenyl Dimethylcarbamodithioate (3j) (Table 2, Entry 10)

HRMS (ESI): calcd for C₁₀H₁₃NS₂(211.0489); found: 211.0469.

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 4:1) to give 3j (203 mg, 84%) as a yellow sol-

id; mp 124–126 °C.

¹H NMR(400 MHz, CDCl₃): δ = 8.00–7.97 (m, 1 H), 7.67–7.60 (m, 3 H),

3,5-Dimethylphenyl Dimethylcarbamodithioate (3e) (Table 2, En-

try 5)

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 5:1) to give 3e (211 mg, 94%) as a white solid;

mp 84–85 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.10 (s, 3 H), 3.55 (s, 3 H), 3.48 (s, 3 H),

3.53 (s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 193.9, 139.6, 132.6, 131.0, 126.5,

124.9, 45.6, 42.4.

HRMS (ESI): calcd for C₉H₁₀N₂O₂S₂(242.0184); found: 242.0191.

2.34 (s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 198.0, 138.6, 134.4, 131.9, 131.0, 45.6,

42.0, 21.2.

4-Methoxy-2-nitrophenyl Dimethylcarbamodithioate (3k) (Table

2, Entry 11)

HRMS (ESI): calcd for C₁₁H₁₅NS₂(225.0646); found: 225.0655.

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 4:1) to give 3k (199 mg, 73%) as a yellow sol-

id; mp 115–117 °C.

4-Butylphenyl Dimethylcarbamodithioate (3f) (Table 2, Entry 6)

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 7:1) to give 3f (243 mg, 96%) as a white solid;

mp 61–62 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.36–7.34 (m, 2 H), 7.25–7.23 (m, 2 H),

3.54 (s, 3 H), 3.48 (s, 3 H), 2.65 (m, 2 H), 1.65–1.58 (m, 2 H), 1.39–1.33

(m, 2 H), 0.92 (m, 3 H).

¹H NMR (300 MHz, CDCl₃): δ = 7.55–7.52 (d, J = 9 Hz, 1 H), 7.49 (d, J =

3 Hz, 1 H), 7.17–7.13 (m, 1 H), 3.91 (s, 3 H), 3.53 (s, 6 H).

¹³C NMR (75 MHz, CDCl₃): δ = 195.4, 161.5, 154.0, 141.0, 118.6, 116.7,

110.4, 56.0, 45.7, 42.2.

HRMS (ESI): calcd for C₁₀H₁₂N₂O₃S₂(272.0289); found: 272.0294.

¹³C NMR (100 MHz, CDCl₃): δ = 198.1, 145.2, 136.7, 129.2, 128.4, 45.6,

41.9, 35.5, 33.2, 22.3, 13.9.

4-(Trifluoromethyl)phenyl Dimethylcarbamodithioate (3l) (Table

2, Entry 12)

HRMS (ESI): calcd for C₁₃H₁₉NS₂(253.0959); found: 253.0962.

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 4:1) to give 3l (244 mg, 92%) as a white solid;

mp 85–86 °C.

4-Bromophenyl Dimethylcarbamodithioate (3g) (Table 2, Entry 7)

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 7:1) to give 3g (246 mg, 89%) as a white sol-

id; mp 120–121 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.56 (d, J = 8.0 Hz, 2 H), 7.32 (d, J = 8.0

¹H NMR (400 MHz, CDCl₃): δ = 7.67 (d, J = 8.0 Hz, 2 H), 7.59 (d, J = 8.0

Hz, 2 H), 3.54 (s, 3 H), 3.49 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 195.6, 137.1, 136.0, 131.7 (t, J = 33 Hz),

125.8 (t, J = 4 Hz), 123.8 (d, J = 270 Hz), 45.6, 42.0.

Hz, 2 H), 3.55 (s, 3 H), 3.49 (s, 3 H).

HRMS (ESI): calcd for C₁₀H₁₀F₃NS₂(265.0207); found: 265.0211.

Q. Cao et al.

Paper

Synthesis

4-Cyanophenyl Dimethylcarbamodithioate (3m) (Table 2, Entry

13)

p-Tolyl Dibutylcarbamodithioate (3r) (Table 2, Entry 18)

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 5:1) to give 3m (164 mg, 74%) as a white sol-

id; mp 125–126 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.72–7.68 (m, 2 H), 7.60–7.57 (m, 2 H),

phy (silica gel, PE/EtOAc 20:1) to give 3r (239 mg, 81%) as a brown oil.

¹H NMR (400 MHz, CDCl₃): δ = 7.31 (d, J = 4.0 Hz, 2 H), 7.19 (d, J = 8.0

Hz, 2 H), 3.89 (t, J = 4.0 Hz, 2 H), 3.71 (t, J = 8.0 Hz, 2 H), 2.35 (s, 3 H),

1.76–1.68 (m, 4 H), 1.41–1.27 (m, 4 H), 0.96 (t, J = 8.0 Hz, 3 H), 0.89 (t,

J = 8.0 Hz, 3 H).

3.55 (s, 3 H), 3.51 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 194.9, 137.5, 137.4, 132.4, 118.2,

¹³C NMR (100 MHz, CDCl₃): δ = 196.8, 140.1, 136.9, 129.9, 128.3, 55.4,

113.6, 45.6, 42.1.

53.0, 29.6, 28.4, 21.5, 20.2, 13.9, 13.8.

HRMS (ESI): calcd for C₁₀H₁₀N₂S₂(222.0285); found: 222.0291.

HRMS (ESI): calcd for C₁₆H₂₅NS₂(295.1428); found: 295.1433.

Phenyl Diethylcarbamodithioate (3n) (Table 2, Entry 14)

4-Methoxyphenyl Dibutylcarbamodithioate (3s) (Table 2, Entry

19)

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 10:1) to give 3n (183 mg, 81%) as pale yellow

According to the TP, the residue was purified by flash chromatogra-

oil.

phy (silica gel, PE/EtOAc 20:1) to give 3s (255 mg, 82%) as a yellow oil.

¹H NMR (400 MHz, CDCl₃): δ = 7.48 (d, J = 12.0 Hz, 5 H), 4.02 (d, J = 4.0

Hz, 2 H), 3.84 (d, J = 8.0 Hz, 2 H), 1.39 (t, J = 4.0 Hz, 3 H), 1.29 (d, J = 4.0

Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 195.9, 137.2, 131.6, 130.0, 129.0, 49.9,

47.3, 12.8, 11.6.

¹H NMR (400 MHz, CDCl₃): δ = 7.29 (d, J = 8.0 Hz, 2 H), 6.87 (d, J = 12.0

Hz, 2 H), 3.86 (s, 2 H), 3.75 (s, 3 H), 3.69 (t, J = 4.0 Hz, 2 H), 1.76–1.72

(m, 4 H), 1.38–1.23 (m, 4 H), 0.93 (t, J = 8.0 Hz, 3 H), 0.86 (t, J = 8.0 Hz,

3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 197.4, 161.0, 138.6, 122.6, 114.6, 55.5,

55.3, 52.9, 29.6, 28.4, 20.1, 13.9, 13.8.

HRMS (ESI): calcd for C₁₁H₁₅NS₂(225.0646); found: 225.0652.

HRMS (ESI): calcd for C₁₆H₂₅NOS₂(311.1378); found: 311.1382.

p-Tolyl Diethylcarbamodithioate (3o) (Table 2, Entry 15)

Phenanthren-9-yl Dimethylcarbamodithioate (3t) (Table 2, Entry

20)

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 15:1) to give 3o (199 mg, 83%) as a white sol-

id; mp 75–76 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.28 (d, J = 8.0 Hz, 2 H), 7.16 (d, J = 4.0

Hz, 2 H), 3.94 (d, J = 8.0 Hz, 2 H), 3.76 (d, J = 4.0 Hz, 2 H), 2.32 (s, 3 H),

1.31 (t, J = 4.0 Hz, 3 H), 1.20 (t, J = 4.0 Hz, 3 H).

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 4:1) to give 3t (157 mg, 53%) as a white solid;

mp >175 °C (dec.).

¹H NMR (400 MHz, CDCl₃): δ = 8.73–8.69 (m, 2 H), 8.32 (m, 1 H), 8.09

(s, 1 H), 7.89 (m, 1 H), 7.73–7.59 (m, 4 H), 3.64 (s, 3 H), 3.57 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 196.5, 140.2, 137.0, 129.9, 128.1, 49.9,

47.2, 21.5, 12.7, 11.6.

¹³C NMR (100 MHz, CDCl₃): δ = 196.4, 138.8, 132.4, 131.6, 131.5,

131.0, 130.1, 129.1, 128.2, 127.7, 127.1, 126.8, 126.7, 123.0, 122.7,

45.5, 42.1.

HRMS (ESI): calcd for C₁₂H₁₇NS₂(239.0802); found: 239.0812.

HRMS (ESI): calcd for C₁₇H₁₅NS₂(297.0646); found: 297.0652.

4-Methoxyphenyl Diethylcarbamodithioate (3p) (Table 2, Entry

16)

Thiophen-2-yl Dimethylcarbamodithioate (3u) (Table 2, Entry 21)

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 7:1) to give 3p (204 mg, 80%) as a white sol-

id; mp 73–75 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.23 (d, J = 8.0 Hz, 2 H), 6.80 (d, J = 8.0

Hz, 2 H), 3.87 (d, J = 8.0 Hz, 2 H), 3.68 (s, 5 H), 1.24 (t, J = 6.4 Hz, 3 H),

1.13 (t, J = 6.4 Hz, 3 H).

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 4:1) give 3u (79 mg, 39%) as a white solid;

mp 94–95.2 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.63 (m, 1 H), 7.23 (m, 1 H), 7.13 (m, 1

H), 3.54 (s, 3 H), 3.48 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 197.1, 161.0, 138.6, 122.4, 114.6, 55.3,

¹³C NMR (100 MHz, CDCl₃): δ = 197.3, 138.7, 133.4, 129.1, 127.8, 46.0,

50.0, 47.1, 12.7, 11.6.

41.7.

HRMS (ESI): calcd for C₁₂H₁₇NOS₂(255.0752); found: 255.0759.

HRMS (ESI): calcd for C₇H₉NS₃(202.9897); found: 202.9904.

Phenyl Dibutylcarbamodithioate (3q) (Table 2, Entry 17)

Funding Information

According to the TP, the residue was purified by flash chromatogra-

phy (silica gel, PE/EtOAc 20:1) to give 3q (230 mg, 82%) as a brown oil.

National Natural Science Foundation of China (21302150), Hubei Pro-

vincial Department of Education (D20131501), Scientific Research

Foundation for the Returned Overseas Chinese Scholars, State Educa-

tion Ministry [2012]1707, foundation of Chutian distinguished fellow

from Hubei Provincial Department of Education, foundation of High-

end Talent Cultivation Program from Wuhan Institute of Technology.

Z.-B. D. acknowledges the Humboldt Foundation and China Scholar-

¹H NMR (400 MHz, CDCl₃): δ = 7.40–7.33 (m, 5 H), 3.85 (t, J = 4.0 Hz, 2

H), 3.67 (t, J = 4.0 Hz, 2 H), 1.72–1.64 (m, 4 H), 1.35–1.25 (m, 4 H), 0.93

(t, J = 4.0 Hz, 3 H), 0.85 (t, J = 8.0 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 196.2, 137.1, 131.8, 129.9, 129.0, 55.3,

53.1, 29.6, 28.4, 20.2, 13.9, 13.8.

HRMS (ESI): calcd for C₁₅H₂₃NS₂(281.1272); found: 281.1278.

ship Council for a fellowship.

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Paper

Synthesis

Acknowledgment

(10) (a) Correa, A.; Carril, M.; Bolm, C. Angew. Chem. Int. Ed. 2008, 47,

2880. (b) Wu, J. R.; Lin, C. H.; Lee, C. F. Chem. Commun. 2009,

4450. (c) Wu, W. Y.; Wang, J. C.; Tsai, F. Y. Green Chem. 2009, 11,

326.

We thank Prof. Aiwen Lei at Wuhan University for generous NMR

analysis support.

(11) (a) Gronowitz, S.; Hornfeldt, A. B.; Temciuc, M. Synthesis 1993,

483. (b) Krasovskiy, A.; Gavryushin, A.; Knochel, P. Synlett 2005,

2691. (c) Krasovskiy, A.; Malakhov, V.; Gavryushin, A.; Knochel,

P. Angew. Chem. Int. Ed. 2006, 45, 6040. (d) Krasovskiy, A.;

Gavryushin, A.; Knochel, P. Synlett 2006, 792.

Supporting Information

Supporting information for this article is available online at

https://doi.org/10.1055/s-0036-1589166.

ortiInfogrmoaitn

ortioInfgrmoaitn

(12) Chen, Z. C.; Jin, Y. Y.; Stang, P. J. J. Org. Chem. 1987, 52, 4117.

(13) Closely related to the work reported here are Ullmann-type

couplings of aryl iodides and vinyl bromides with sodium dith-

iocarbamates. However, this method requires more catalyst

(CuI, 15 mol%) and ligand (N,N-dimethylglycine, 30 mol%). Fur-

thermore, sodium dithiocarbamates are generally more expen-

sive than the thiuram reagent used in the present work. See:

Liu, Y. Y.; Bao, W. L. Tetrahedron Lett. 2007, 48, 4785.

(14) Azizi, N.; Aryanasab, F.; Saidi, M. R. Org. Lett. 2006, 8, 5275.

(15) Bhadra, S.; Saha, A.; Ranu, B. C. Green Chem. 2008, 10, 1224.

(16) Chatterjee, T.; Bhadra, S.; Ranu, B. C. Green Chem. 2011, 13,

1837.

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