Copper-Catalyzed S-Arylation Starting from Arylboronic Acids and Tetraalkylthiuram Disulfide

DOI: 10.1002/ejoc.201701757

Source and publish data:

European Journal of Organic Chemistry p. 821 - 828 (2018)

Update date:2022-08-04

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Authors:

Xu, Wan Xu, Wan

Gao, Fan

Dong, Zhi-Bing

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Article abstract of DOI:10.1002/ejoc.201701757

A convenient and useful protocol for the synthesis of diverse S-aryl dithiocarbamates was studied. Starting from arylboronic acid and tetraalkylthiuram disulfide, copper-catalyzed C–S coupling proceeds smoothly to give the desired S-aryl dithiocarbamates in good to excellent yields. The broad substrate scope, short reaction time, easy performance, cheap substrates, and nice yields make this approach attractive, showing its practical synthetic value for the preparation of some biologically or pharmaceutically active compounds.

Full text of DOI:10.1002/ejoc.201701757

A Journal of

Accepted Article

Title: Copper Catalyzed S-arylation starting from Aryl Boronic Acids

and Tetraalkylthiuram Disulfide

Authors: Zhi-Bing Dong, Wan Xu, and Fan Gao

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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701757

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Copper Catalyzed S-arylation starting from Aryl Boronic Acids and Tetraalkylthiuram Disulfide

Wan Xu,^[+]Fan Gao,^[+]Zhi-Bing Dong^*

Abstract: A convenient and useful protocol for the synthesis of

diverse S-aryl dithiocarbamates was studied. Starting from aryl

boronic acid and tetraalkylthiuram disulfide, the C-S coupling

proceeds smoothly catalyzed by copper, giving the desired S-aryl

dithiocarbamates in good to excellent yield. The broad substrate

scope, short time reaction, easy performance, cheap substrates and

nice yields make this approach attractive, showing its practical

synthetic value for the preparation of some biologically or

pharmaceutically active compounds.

synthesis of aryl dithiocarbamates starting from aryl idodides

and tetraalkylthiuram disulfide.²⁰To further extend our work, and

due to our investigating on disulfides and relevant applications,²¹

we would like to report herein a facile, mild and convenient

protocol for the synthesis of S-aryl dithiocarbamates through the

C-S coupling starting from aryl boronic acid and

tetramethylthiuram disulfide, which affords an alternative way for

the synthesis of this important building block.

Cu O, pyridine

DMF, 100 C, 1.5-6 h

open air

23 examples

yield: 78-94%

Introduction

wide substrate scope

easy performance

R =Cl, Br, F, NO , CN,

CF , OCH , Bu, Me, et al

short time reaction

Organic dithiocarbamates are significant structural motifs

occurring in numerous natural products, pharmaceuticals and

agrochemicals that received increasing attention.¹They are

found to possess intriguing biological activities and diverse

Results and Discussion

pharmacological

properties

such

antitumors,²

To optimize the reaction condition of this C-S coupling, initial

optimization studies were carried out by using phenyl boronic

acid (1a) and tetramethylthiuram disulfide (TMTD, 2a) as the

starting material. Gratifyingly, the desired product phenyl

dithiocarbamate (3a) was obtained in 42 % yield when the

reaction was conducted in presence of CuI/K₂CO₃in DMF at 80

^oC under open air (Table 1, entry 1). The evaluation of other

copper sources showed that Cu₂O could promote the reaction

efficiently, while other copper such as CuBr, CuCl₂, CuSO₄,

Cu(OTf)₂, Cu(OAc)₂exhibited lower or no activity (entries 2-7).

No desired product was detected when other metal salts such as

Pd(OAc)₂, PdCl₂and FeCl₃were employed as catalysts (entries

monoacylglycerol lipase inhibitors,³antibacterials.⁴They also

served as fusarium oxysporum agent,⁵crop anti-diseases drugs⁶

in agriculture field. Moreover, they can be used as linkers in

solid phase organic synthesis,⁷protecting groups in peptide

synthesis,⁸and recently in the synthesis of ionic liquids.⁹Their

versatile application and biological properties actuated the

development of synthetic procedures for these compounds. The

most commonly used method is the reaction of amines with

thiophosgene or isothiocyanates.¹⁰

A couple of metal-free

procedures involving the reaction of the sodium salt of

dithiocarbamic acid with diazonium chloride¹¹and diaryl

diazonium salts in the presence of hypervalent iodine,¹²the

reaction of certain organometallic reagents with tetramethyllitium

disulfide,¹³coupling of sodium dithiocarbamates with aryl iodides

or halobenzene.¹⁴Other protocols such as one-pot three

component reactions of amines, carbon disulfide with

electrophiles including alkyl halide¹⁵or aryl halide,¹⁶aryl

diazonium fluoroborate,¹⁷pentafluorobenzonitrile,¹⁸benzene

boronic acid¹⁹were reported. However, these methods suffered

high cost, environmental issues, difficulty in preparing the

reagent, high reaction temperature or multiple reaction steps,

which limit their applications. Recently, we described the

8-10). Then, various bases such as Cs₂CO₃, KOH, BuOK, NEt₃

were screened (entries 11-14). The result revealed that Cs₂CO₃

was the most efficient, giving the desired product in 65 % yield

(entry 11). We further checked the ligand efficiency. Thus, PPh₃,

pyridine, bipyridine and 1,10-phenanthroline (entries15-18) were

surveyed, and the results showed that pyridine was the best.

The product yield increased significantly when the reaction

temperature increased (entries 19-21), and 100 °C was chosen

as the optimal reaction temperature. The solvent screening

(entries 20, 22-24) showed that DMF was the most suitable. The

yield of product dropped slowly as the catalyst loading

decreased (entries 25-26). The later study on the base loading

(entries 27-28) revealed that the product could be obtained with

90% isolation yield in the absence of Cs₂CO₃, which is quite

unexpected. The optimal reaction conditions were summarized

in entry 28 (Cu₂O: 30 mol%, pyridine: 1.0 mL, DMF: 1.5 mL,

100°C, open air). It should be noted that the reaction conversion

drops significantly when the reation is performed under sealed

tube or nitrogen atmosphere (entry 29, 30).

[*]

W. Xu, F. Gao, Prof. Dr. Z. B. Dong

School of Chemistry and Environmental Engineering

Wuhan Institute of Technology

Liufang Campus, No. 206, Guanggu 1st Road, Donghu New & High

Technology Development Zone, Wuhan 430205, Hubei Province, P.

R. China

E-mail: dzb04982@wit.edu.cn

http://cee.wit.edu.cn/info/1052/1538.htm

These authors contributed equally to this work.

[+]

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Table 1. Screening of reaction conditions.^[a]

Subsequently, we examined the scope of this copper

catalyzed C-S bond formation reaction by selecting a wide range

of aryl boronic acids and tetraalkylthiuram disulfides under the

optimal reaction conditions. In general, all aryl boronic acid

reacted well independently furnishing aryl dithiocarbamates in

good to excellent yields. Neither electronic factors induced by

substituents nor the position of the groups had significant effect.

Both electron-donating and electron-withdrawing substituents

were tolerated. For substrate 1 either bearing weak electron-

withdrawing group (F, Cl, Br) or strong electron-withdrawing

group (CF₃, NO₂, CN), could furnish the corresponding products

in nice yields (3b-3i, entries 2-9, yield: 80%-94%). Similarly,

substrate 1 bearing electron donating group such as methyl,

methoxyl, butyl group also provided the desired product in high

yields (3j-3o, entries 10-15, yield: 85%-94%). To our delight,

substrate 1p and 1q bearing ortho methyl groups had little

stereo influence to the C-S coupling, affording 3p and 3q in 82%,

91 % yield respectively (entries 16-17). Naphthalenyl boronic

acid was found also suitable for the C-S coupling, giving 3r in

78 % yield (entry 18). It is noting that dithiocarbamates

containing olefin compounds (3s-3u) could be synthesized

smoothly with 88%, 81% and 80% yields, respectively (entries

19-21). To further expand the diversity of the products, several

tetraalkylthiuram disulfides (2b and 2c) were submitted for

investigation. We are glad to find that these disulfides were also

good coupling partners, furnishing the corresponding products in

good yields (3v-3qc, entries 22-27). However, heterocyclic

boronic acids or chained boronic acid were not suitable for the

coupling, indicating some limitations (3va, 3wa, entries 28-29).

conditions

Entry

Catalyst

Ligand

Base

Solvent

Yield^[b]

(%)

CuI

Cu₂O

CuBr

CuCl₂

CuSO₄

Cu(OTf)₂

Cu(OAc)₂

Pd(OAc)₂

PdCl₂

FeCl₃

Cu₂O

K₂CO₃

Cs₂CO₃

KOH

DMF

mess

^tBuOK

NEt₃

Cu₂O

PPh₃

bipyridine

1,10-

Cs₂CO₃

phenanthroline

pyridine

Cu₂O

Cs₂CO₃

DMF

19^[c]

20^[d]

21^[e]

DMF

DMSO

DMAC

PhCH₃

DMF

25^[f]

26^[g]

27^[h]

29^[i]

30^[j]

trace

[a]Reaction condition: 1a (1 mmol), 2a (0.65 mmol), [Cat]: 30 mol%, ligand (10

mol%), base (2 equiv.), pyridine: (for the entries which pyridine was added, 1.0

mL), solvent (1.5 mL), 80 °C, 10 h, open air. [b]Isolated yield. [c]Reaction at

60 °C. [d]Reaction at 100°C. [e]Reaction at 120 °C. [f][Cat]: 20 mol%. [g][Cat]:

10 mol%. [h]Base (1 equiv.). [i]Sealed system.[j] Under nitrogen atmosphere.

[a]

Table 2. C-S coupling scope of aryl boronic acid with tetraalkylthiuram disulfides

R₂

Cu₂O (30 mol%), pyridine

R₂

R₁

DMF, 100^oC, 1.5 h-6 h

open air

R₁

R₂

Entry

Aryl boronic acid

Tetraalkylthiuram disulfide

Product

Yield^[b](%)

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O N

F₃C

F C

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OCH₃

OCH

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3qc

3va

t-Bu

3wa

[a]Reaction conditions: 1 (1.0 mmol), 2 (0.65 mmol), Cu₂O (30 mol%), pyridine (1.0 mL), DMF (1.5 mL), 100°C, 1.5-6 hours, open air. [b]Isolated yield.

Based on the above results and related literatures,²²the

mechanism of this reaction is proposed as shown in Scheme 1.

Initially, Cu(I) A is oxidized to Cu(III) spieces which is then

complexed with disulfide to give intermediate B. Phenyboronic

acid reacts with B to give the transmetallated intermediate C

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which is ready for reductive elimination, furnishing the desired

product D and recycled catalyst Cu(I) A.

material was finished. The reaction was cooled down to room

temperature, quenched with sat. NH₄Cl solution (10 mL) and

extracted with ethyl acetate, dried over anhydrous Na₂SO₄and

then evaporated under vacuum. The residue was purified by

flash column chromatography to afford the desired product.

Experimental Data

Phenyl dimethylcarbamodithioate (3a)

181 mg (yield: 90 %), a white solid. MP: 90-92 ^oC, ¹H NMR (400

MHz, CDCl₃) δ: 7.49-7.45 (m, 5H), 3.56 (s, 3H), 3.50 (s, 3H). ¹³

NMR (100 MHz, CDCl₃) δ: 197.6, 137.0, 131.7, 130.0, 129.1,

45.7, 42.0. HRMS (ESI) Calcd for C₉H₁₁NS₂(197.0333); found:

197.0342.

4-Chlorophenyl dimethylcarbamodithioate (3b)

201 mg (yield: 87%), a white solid. MP: 101-102 ^oC. ¹H NMR

(400 MHz, CDCl₃) δ: 7.42-7.37 (m, 4H), 3.54 (s, 3H), 3.48 (s,

3H). ¹³C NMR (100 MHz, CDCl₃) δ: 196.7, 138.2, 136.6, 130.1,

129.4, 45.7, 42.0, 43.0. HRMS (ESI) Calcd for C₉H₁₀ClNS₂

(230.9943); found: 230.9972.

Scheme 1. Proposed reaction mechanism.

Conclusions

4-Bromophenyl dimethylcarbamodithioate (3c)

256 mg (yield: 93 %), a white solid. MP: 120-122 ^oC. ¹H NMR

(400 MHz, CDCl₃) δ: 7.58 (s, 1H), 7.55 (s, 1 H), 7.33 (s, 1H),

7.31 (s, 1H), 3.54 (s, 3H), 3.49 (s, 3H). ¹³C NMR (100 MHz,

CDCl₃) δ: 196.5, 138.4, 132.4, 130.8, 125.0, 45.8, 42.0. HRMS

(ESI) Calcd for C₉H₁₀BrNS₂(274.9438); found: 274.9472.

In summary, we have developed an efficient and useful method

for the synthesis of various substituted S-aryl dithiocarbamates.

In the presence of Cu₂O and pyridine, aryl boronic acids coupled

with tetraalkylthiuram disulfides smoothly to furnish the

desiredproducts in good to excellent yields. The broad substrate

scope, short reaction time, commercially available cheap

substrates, easy performance and nice yields make this

approach attractive, showing its practical synthetic value for the

preparation of some biologically or pharmaceutically active

compounds. Further investigation of this protocol and the related

applications are under studied in our laboratory.

4-Fluorophenyl dimethylcarbamodithioate (3d)

202 mg (yield: 94 %), a white solid. MP: 92-93 ^oC. ¹H NMR (400

MHz, CDCl₃) δ: 7.44-7.39 (m, 2H), 7.14-7.09 (m, 2 H), 3.53 (s,

3H), 3.48 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 197.4, 165.2,

162.7, 139.1 (d, J_C-F= 8 Hz), 127.15 (d, J_C-F= 3 Hz), 116.36 (d,

J_C-F= 22 Hz), 45.8, 41.9. HRMS (ESI) Calcd for C₉H₁₀FNS₂

(215.0239); found: 215.0272.

Experimental Section

2-Chlorophenyl dimethylcarbamodithioate (3e)

205 mg (yield: 89 %), a pale gray solid. MP: 104-106 ^oC. ¹H

NMR (400 MHz, CDCl₃) δ: 7.57-7.53 (m, 2H), 7.43 (td, J = 9.0

Hz, 3.0 Hz, 1H), 7.42 (td, J = 6.0 Hz, 3.0 Hz, 1H), 3.55 (s, 3H),

3.52 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 195.0, 140.5, 139.2,

131.8, 131.0, 130.3, 127.5, 45.6, 42.2. HRMS (ESI) Calcd for

C₉H₁₀ClNS₂(230.9943); found: 230.9948.

General Information. Nuclear magnetic resonance (NMR)

spectra were obtained on a Bruker AC 400 MHz spectrometer

(¹H NMR at 400 MHz, ¹³C NMR at 100 MHz) in CDCl₃using

tetramethylsilane as an internal standard. Chemical shifts are

given in ppm and coupling constants (J) are given in Hz.

Electrospray ionization-high-resolution mass spectra (ESI-

HRMS) were determined on an Ion Spec (7.0 T) spectrometer.

All reactions were performed under dried glassware with

septums. All starting materials were purchased from commercial

suppliers and used without further purification unless otherwise

stated. Yield refers to isolated compounds estimated to be >

95% pure as determined by ¹H NMR and capillary GC analysis.

4-Nitrophenyl dimethylcarbamodithioate (3f)

194 mg (yield: 80 %), a light yellow solid. MP: 154-156 ^oC. ¹H

NMR (400 MHz, CDCl₃) δ: 8.29-8.24 (m, 2H), 7.67-7.63 (m, 2H),

3.56 (s, 3H), 3.53 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 194.6,

148.7, 139.5, 137.7, 133.9, 45.7, 42.2. HRMS (ESI) Calcd for

C₉H₁₀N₂O₂S₂(242.0184); found: 242.0180.

General Procedure. To a dried tube equipped with a magnetic

stirrer and a septum, phenyl boronic acid (1.0 mmol) and

tetraalkylthiuram disulfide (0.65 mmol) were dissolved in DMF

(1.5 mL). The mixture was stirred for 5 minutes, pyridine (1.0

mL) and Cu₂O (30 mol %) were added. The reaction mixture

was then heated at 100 °C and checked by TLC until the starting

4-Cyanphenyl dimethylcarbamodithioate (3g)

176 mg (yield: 80 %), a light yellow solid. MP: 126-128 ^oC. ¹H

NMR (400 MHz, CDCl₃) δ: 7.72-7.69 (m, 2H), 7.60-7.57 (m, 1H),

3.55 (s, 3H), 3.51 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 194.9,

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137.4, 132.4, 118.2, 113.6, 45.7, 42.2. HRMS (ESI) Calcd for

C₁₀H₁₀N₂S₂(222.0285); found: 222.0281.

2-Methylphenyl dimethylcarbamodithioate (3o)

190 mg (yield: 90 %), a white solid. MP: 83-85 ^oC. ¹H NMR (400

MHz, CDCl₃) δ: 7.43-7.32 (m, 3H), 7.27-7.23 (m, 2H), 3.54 (s,

3H), 3.50 (s, 3H), 2.40 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ:

196.5, 143.8, 137.7, 131.1, 130.7, 130.7, 126.7, 45.7, 42.0.

HRMS (ESI) Calcd for C₁₀H₁₃NS₂(211.0489); found: 211.0483.

3-(Trifluoromethyl)phenyl dimethylcarbamodithioate (3h)

244 mg (yield: 92 %), a white solid. MP: 87-89 ^oC. ¹H NMR (400

MHz, CDCl₃) δ: 7.72 (t, J = 8.0 Hz, 2H), 7.66 (d, J = 8.0 Hz, 1 H),

7.56 (t, J = 8.0 Hz, 1H), 3.55 (s, 3H), 3.50 (s, 3H). ¹³C NMR (100

MHz, CDCl₃) δ: 195.7, 136.0 (d, J_C-F= 2 Hz), 131.76 (d, J_C-F= 27

2,6-Dimethylphenyl dimethylcarbamodithioate (3p)

Hz), 125.84 (q, J_C-F=4 Hz), 125.17, 122.46, 114.99, 45.66, 42.07. 154 mg (yield: 82 %), a white solid. MP: 81-82 ^oC. ¹H NMR (400

HRMS (ESI) Calcd for C₁₀H₁₀F₃NS₂(265.0207); found: 265.0215. MHz, CDCl₃) δ: 7.30-7.26 (m, 1 H), 7.18 (d, J = 8.0 Hz, 2 H),

3.54 (s, 6 H), 2.40 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃) δ:

4-(Trifluoromethyl)phenyl dimethylcarbamodithioate (3i)

223 mg (yield: 84 %), a white solid. MP: 85-86 ^oC. ¹H NMR (400

MHz, CDCl₃) δ: 7.67 (d, J = 4.0 Hz, 2H), 7.58 (d, J = 8.0 Hz, 2H),

3.54 (s, 3H), 3.49 (s, 3H). ¹³C NMR (100 MHz, CDCl₃): δ: 196.7,

137.1, 136.0 (d, J = 2 Hz), 131.7 (d, 33 Hz), 125.8 (m, J = 4 Hz),

123.8 (d, J = 271 Hz), 45.6, 42.0. HRMS (ESI) Calcd for

C₁₀H₁₀F₃NS₂(265.0207); found: 265.0215.

195.43, 144.08, 130.96, 130.27, 128.28, 45.47, 42.01, 21.78.

HRMS (ESI) Calcd for C₁₁H₁₅NS₂(225.0646); found: 225.0656.

2,4,6-Trimethylphenyl dimethylcarbamodithioate (3q)

217 mg (yield: 91 %), a white solid. MP: 56-58 ^oC. ¹H NMR (400

MHz, CDCl₃) δ: 7.00 (s, 2H), 3.52 (s, 6H), 2.34 (s, 6H), 2.30 (s,

3H). ¹³C NMR (100 MHz, CDCl₃) δ: 195.9, 143.8, 140.4, 129.3,

127.6, 45.5, 42.0, 21.7, 21.4. HRMS (ESI) Calcd for C₁₂H₁₇NS₂

(239.0802); found: 239.0807.

4-Methylphenyl dimethylcarbamodithioate (3j)

190 mg (yield: 90 %), a white solid. MP: 110-112 ^oC. ¹H NMR

(400 MHz, CDCl₃) δ: 7.35 (t, J = 6.0 Hz, 2H), 7.26 (t, J = 6.0 Hz,

2H), 3.56 (s, 3H), 3.49 (s, 3H). 2.40 (s, 3H). ¹³C NMR (100 MHz,

CDCl₃) δ: 198.2, 140.4, 136.8, 130.0, 128.3, 45.7, 41.9, 21.5.

HRMS (ESI) Calcd for C₁₀H₁₃NS₂(211.0489); found: 211.0481.

Naphthalene-1-yl dimethylcarbamodithioate (3r)

192 mg (yield: 78 %), a colorless oil. H NMR(400 MHz, CDCl₃)

δ: 8.24 (d, J = 8 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1 H), 7.87 (d, J =

8.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.52 (q, 3H), 3.54 (s, 3H),

3.51 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 196.6, 137.0, 135.1,

134.2, 131.5, 129.0, 128.6, 127.2, 126.3, 125.7, 45.6, 42.1.

HRMS (ESI) Calcd for C₁₃H₁₃NS₂(247.0489); found: 247.0481.

3, 5-Dimethyphenyl dimethylcarbamodithioate (3k)

211 mg (yield: 94 %), a white solid. MP: 86-88 ^oC. ¹H NMR (400

MHz, CDCl₃) δ: 7.10 (s, 3H), 3.56 (s, 3H), 3.49 (s, 3H), 2.35 (s,

6H). ¹³C NMR (100 MHz, CDCl₃) δ: 198.1, 138.7, 134.5, 131.9,

131.0, 45.7, 42.0, 21.2. HRMS (ESI) Calcd for C₁₁H₁₅NS₂

(225.0646); found: 225.0642.

Styryldimethylcarbamodithioate (3s)

196 mg (yield: 88 %), a light yellow oil. ¹H NMR (400 MHz,

CDCl₃) δ: 7.46 (q, 5H), 7.31 (m, 1H), 6.75 (d, J = 16.0 Hz, 1H),

3.53 (s, 3H), 3.35 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 194.6,

136.2, 132.2, 128.7, 128.1, 126.6, 123.1, 45.1, 41.6. HRMS

(ESI) Calcd for C₁₁H₁₃NS₂(223.0489); found: 223.0492.

2-Methoxyphenyl dimethylcarbamodithioate (3l)

195 mg (yield: 86 %), a white solid. MP: 89-90 ^oC. ¹H NMR (400

MHz, CDCl₃) δ: 7.52-7.40 (m, 2H), 7.05-6.99 m, 2H), 3,86 (s,

3H), 3.54 (s, 3H), 3.52 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ:

196.8, 160.5, 138.8, 132.5, 121.2, 119.9, 111.9, 66.2, 45.7, 42.1.

HRMS (ESI) Calcd for C₁₁H₁₅NS₂(227.0439); found: 227.0432.

4-Methylstyryldimethylcarbamodithioate (3t)

192 mg (yield: 81 %), a light yellow oil. ¹H NMR (400 MHz,

CDCl₃) δ: 7.35 (t, J = 16.0 Hz, 3 H), 7.13 (d, J = 8.0 Hz, 2H),

6.72 (d, J = 16.0 Hz, 1H), 3.53 (s, 3H), 3.35 (s, 3H), 2.33 (s, 3H).

¹³C NMR (100 MHz, CDCl₃) δ: 194.9, 138.08, 133.5, 132.5,

129.4, 126.5, 121.8, 45.0, 41.6, 21.3. HRMS (ESI) Calcd for

C₁₂H₁₅NS₂(237.0646); found: 237.0642.

3-Methoxyphenyl dimethylcarbamodithioate (3m)

193 mg (yield: 85 %), a white solid. MP: 81-83 ^oC. ¹H NMR (400

MHz, CDCl₃) δ: 7.36 (d, J = 8.0 Hz, 1 H), 7.09-7.00 (m, 3 H),

3.82 (s, 3 H), 3.55 (s, 3H), 3.49 (s, 3H). ¹³C NMR (100 MHz,

CDCl₃) δ: 197.2, 159.7, 132.5, 129.8, 129.1, 121.9, 116.2, 55.4,

45.6, 42.0. HRMS (ESI) Calcd for C₁₀H₁₃NONS₂(227.0439);

found: 227.0436.

4-Chlorostyryldimethylcarbamodithioate (3u)

205 mg (yield: 80 %), a light yellow oil. ¹H NMR (400 MHz,

CDCl₃) δ: 7.46 (d, J = 16.0 Hz, 1H), 7.37 (d, J = 12.0 Hz, 2H),

7.29 (d, J = 8.0 Hz, 2H), 6.68 (d, J = 16.0 Hz, 1H), 3.54 (s, 3 H),

3.36 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 194.2, 134.7, 133.7,

130.5, 128.8,127.7, 124.1, 45.1, 41.6. HRMS (ESI) Calcd for

C₁₁H₁₂ClNS₂(257.0100); found: 257.0109.

4-Butylphenyl dimethylcarbamodithioate (3n)

222 mg (yield: 88 %), a white solid. MP: 63-65 ^oC. ¹H NMR (400

MHz, CDCl₃) δ: 7.35 (t, J = 4.0 Hz, 2H), 7.24 (t, J = 4.0 Hz, 2H),

3.54 (s, 3H), 3.48 (s, 3H), 2.65 (t, J = 4.0 Hz, 2 H), 1.66-1.58 (m,

2H), 1.39-1.33 (m, 2H), 0.94-0.90 (t, J = 8.0 Hz, 3H). ¹³C NMR

(100 MHz, CDCl₃) δ: 198.1, 146.2, 136.7, 129.3, 128.4, 45.7,

41.9, 36.5, 33.2, 22.4, 13.9. HRMS (ESI) Calcd for C₁₃H₁₉NS₂

(253.0959); found: 253.0950.

Phenyl diethylcarbamodithioate (3v).

186 mg (yield: 83 %), pale yellow oil. ¹H NMR (400 MHz, CDCl₃):

δ: 7.48 (d, J = 12.0 Hz, 5H), 4.02 (d, J = 4.0 Hz, 2H), 3.84 (d, J =

8.0 Hz, 2H), 1.39 (t, J = 4.0 Hz, 3H), 1.29 (d, J = 4.0 Hz, 3H). ¹³

NMR (100 MHz, CDCl₃) δ: 195.9, 137.2, 131.6, 130.0, 129.0,

10.1002/ejoc.201701757

European Journal of Organic Chemistry

FULL PAPER

49.9, 47.3, 12.8, 11.6. HRMS (ESI) calcd for C₁₁H₁₅NS₂

(225.0604), found: 225.0607.

Institute of Technology. Z.-B. D. acknowledges the

Humboldt Foundation and China Scholarship Council for a

fellowship.

4-Methylphenyl diethylcarbamodithioate (3w)

196 mg (yield: 82 %), white solid; mp: 75-76 C. H NMR (400

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

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

3H), 1.31 (t, J = 4.0 Hz, 3H), 1.20 (t, J = 4.0 Hz, 3H). 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. HRMS (ESI) calcd for C₁₂H₁₇NS₂

(239.0802), found: 239.0807.

Keywords: aryl boronic acid • tetraalkylthiuram disulfide • S-

arylation • dithiocarbamates • synthesis

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2, 4, 6-Trimethylphenyl diethylcarbamodithioate (3x)

211 mg (yield: 79 %), yellow solid; mp: 94-96 C. H NMR (400

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C₁₄H₂₁NS₂(267.1115), found: 267.1118.

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Phenyl dibutylcarbamodithioate (3y)

250 mg (yield: 81 %), brown oil. H NMR (400 MHz, CDCl₃) δ:

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7.40-7.33 (m, 5H), 3.85 (t, J = 4.0 Hz, 2 H), 3.67 (t, J = 4.0 Hz,

2H), 1.72-1.64 (m, 4H), 1.35-1.25 (m, 4H), 0.93 (t, J = 4 Hz, 3H),

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:

281.1282.

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4-Methylphenyl dibutylcarbamodithioate (3z)

262 mg (yield: 81 %), brown oil. H NMR (400 MHz, CDCl₃) δ:

7.31 (d, J = 4.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2 H), 3.89 (t, J = 4.0

Hz, 2H), 3.71 (t, J = 8.0 Hz, 2H), 2.35 (s, 3H), 1.76-1.68 (m, 4H),

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

3H). ¹³C NMR (100 MHz, CDCl₃) δ: 196.8, 140.1, 136.9, 129.9,

128.3, 55.4, 53.0, 29.6, 28.4, 21.5, 20.2, 13.9, 13.8. HRMS (ESI)

calcd for C₁₆H₂₅NS₂(295.1428), found: 295.1435.

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2, 4, 6-Trimethylphenyl dibutylcarbamodithioate (3qc)

274 mg (yield: 78 %), colorless oil. ¹H NMR (400 MHz, CDCl₃) δ:

6.94 (s, 2H), 3.90 (t, J = 8 Hz, 2 H), 3.75 (t, J = 8.0 Hz, 2H), 2.30

(s, 6 H), 2.25 (s, 3H), 1.76 (d, J = 8 Hz, 2H), 1.65 (d, J = 8.0 Hz,

2H), 1.42-1.36 (m, 2 H), 1.31-1.26 (m, 2H), 0.96 (t, J = 4.0 Hz,

3H), 0.89 (t, J = 8.0 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ:

194.7, 140.6, 143.8, 140.2, 129.2, 55.0, 52.9, 29.8, 28.6, 21.7,

21.4, 20.2, 13.9, 13.9. HRMS (ESI) calcd for C₁₈H₂₉NS₂

(323.1741), found: 323.1747.

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2017, DOI: 10.1039/c7gc02311a.

Acknowledgements

We thank the foundation support from National Natural

Science Foundation of China (21302150), foundation of

Chen-Guang program from Hubei Association for Science

and Technology, foundation of Chutian distinguished fellow

from Hubei Provincial Department of Education, foundation

of High-end Talent Cultivation Program from Wuhan

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Brage, Molecules 2017, 22, 1367.

10.1002/ejoc.201701757

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Entry for the Table of Contents (Please choose one layout)

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Copper-catalyzed S-arylation*

Wan Xu, Fan Gao, Zhi-Bing Dong^*

Cu O, pyridine

Page No. – Page No.

DMF, 100 C, 1.5-6 h

open air

27 examples

yield: 78-94%

Copper Catalyzed S-arylation starting

from Aryl Boronic Acids and

Tetraalkylthiuram Disulfide

wide substrate scope

easy performance

R =Cl, Br, F, NO , CN,

CF , OCH , Bu, Me, et al

short time reaction

*one or two words that highlight the emphasis of the paper or the field of the study

In the presence of Cu₂O and pyridine, aryl boronic acids coupled with tetraalkylthiuram disulfides smoothly to furnish the

desired phenyldithiocarbamates in good to excellent yields. The broad substrate scope, short reaction time, commercially

available cheap substrates, easy performance and nice yields make this approach attractive.

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Copper-Catalyzed S-Arylation Starting from Arylboronic Acids and Tetraalkylthiuram Disulfide

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