Chan-lam-type s-arylation of thiols with boronic acids at room temperature

DOI: 10.1021/jo300100x

Source and publish data:

Journal of Organic Chemistry p. 2878 - 2884 (2012)

Update date:2022-07-29

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Authors:

Xu, Hua-Jian

Zhao, Yong-Qiang

Feng, Teng

Feng, Yi-Si

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Article abstract of DOI:10.1021/jo300100x

In this work, an efficient CuSO₄-catalyzed S-arylation of thiols with aryl and heteroaryl boronic acids at room temperature is established. This catalytic system can tolerate a wide variety of thiols and arylboronic acids in the presence of only 5 mol % of CuSO₄ as the catalyst and inexpensive 1,10-phen?H₂O as the ligand. Moreover, this catalytic system used environment-friendly solvent (EtOH) and oxidant (oxygen).

Full text of DOI:10.1021/jo300100x

Article

pubs.acs.org/joc

Chan−Lam-Type S-Arylation of Thiols with Boronic Acids at Room

Temperature

Hua-Jian Xu,*^,†Yong-Qiang Zhao,^†Teng Feng,^†and Yi-Si Feng*^,‡

‡

^†School of Medical Engineering and School of Chemical Engineering, Hefei University of Technology, Hefei 230009, P. R. China

* Supporting Information

ABSTRACT: In this work, an efficient CuSO₄-catalyzed S-

arylation of thiols with aryl and heteroaryl boronic acids at

room temperature is established. This catalytic system can

tolerate a wide variety of thiols and arylboronic acids in the

presence of only 5 mol % of CuSO₄as the catalyst and

inexpensive 1,10-phen·H₂O as the ligand. Moreover, this catalytic system used environment-friendly solvent (EtOH) and oxidant

(oxygen).

THF as the solvent at 50 °C (Scheme 1b). Recently,

Tamiguchi^16a,band Li^16calso reported copper-catalyzed C−S

cross-coupling reaction of boronic acids with diaryldisulfane

using DMSO/H₂O as solvent at 100 °C (Scheme 1c,d). The

development of a general room-temperature S-arylation of

thiols with arylboronic acids (particularly in environment-

friendly solvents) remains a challenge for this field. Herein, we

wish to develop a general protocol to achieve the oxidative

cross-coupling reactions of diverse boronic acids with thiols

using a simple copper catalyst in environment-friendly solvent

at room temperature.

INTRODUCTION

■

Transition-metal-catalyzed carbon−heteroatom cross-coupling

reactions have made a great contribution to the recent growth

of organic synthesis.¹Although the aryl sulfides have broad

application in the pharmaceutical industry and material science²

and as intermediates in organic synthesis,³the formation of

carbon−sulfur bonds has received less attention. Difficulties in

C−S bond formation can be attributed to the sulfur species

rapidly and irreversibly deactivating the catalyst.⁴So the

efficient formation of the C−S bond is a most important

aspect of organic chemistry. Many research groups have made

great effort to overcome this problem in recent years, and

several excellent catalytic systems that used Pd,⁵Cu,⁶Ni,⁷

Fe,^4b,8and other metals as catalysts have been found for C−S

bond formation by couplings of aryl halides with thiols or

disulfides.⁹However, the high cost and air sensitivity of Pd

catalyst systems limit their applications in large-scale processes,

and the scope of Cu and other transition-metal catalyst systems

are suitable only for aryl bromides/iodides or triflates. So the

development of a milder (room temperature), environment-

friendly, cheap, and efficient catalyst system is still desirable.

With the wide variety of commercially available boronic acids

and derivatives, the Chan−Lam reaction is emerging as an

efficient and valuable alternative to traditional cross-couplings

in the construction of carbon−heteroatom bonds.¹⁰Copper-

promoted (mediated or catalyzed) coupling of amines¹¹and

phenols¹²with organoboronic acids and derivatives has made

significant progress in the past few years since the initial report

of Chan and Lam, which has found wide applications because

of the mildness of the reaction conditions. However, few

protocols for the direct coupling of arylboronic acid with thiols

have been published.¹³In 2000, Guy et al.¹⁴reported the first

C−S cross-coupling reaction of boronic acids with electron-rich

alkyl thiols, albeit promoted by stoichiometric Cu(OAc)₂,

which made progress in this field (Scheme 1a). Later, a

protocol for the copper-catalyzed (20−30 mol %) synthesis of

thioethers employing thioimide as a sulfide surrogate was

described,¹⁵which used expensive CuMeSal as the catalyst and

RESULTS AND DISCUSSION

■

Optimization of Reaction Conditions for Cu-Catalyzed

Coupling of Phenylboronic Acid and Thiophenol. Our

initial attempt to explore an effective catalytic system for the

reaction of phenylboronic acid with thiophenol in the presence

of CuSO₄and 1,10-phenanthroline monohydrate under O₂

atmosphere at room temperature is shown in Table 1. It was

observed that traditional inorganic bases only gave yields from

26% to 35% (Table 1, entries 1−3). Fortunately, when we

switched to tetra-n-butylammonium hydroxide (nBu₄NOH

(40% aq)), the yield increased to 48% (entry 4). To our

surprise, the yield could be significantly increased when

changing the ratio of nBu₄NOH (40% aq) and MeOH. We

were pleased to find that the use of a 1:1 mixture of nBu₄NOH

(40% aq) and MeOH gave the highest yield, and any other

ratios resulted in lower yields (Table 1, entries 5−8). No

significant improvement of the yield of the desired product 1a

was observed when other copper and iron salts, such as CuI,

CuCl₂, and FeCl₃, were used as the catalysts (Table 1, entries

9−11). To improve the yield, different solvents were examined,

and EtOH gave the best yield compared with other solvents

(Table 1, entries 13−16). Interestingly, when the reaction time

was shortened to 8 h, the yield increased slightly to 88% (Table

Received: January 13, 2012

Published: February 17, 2012

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Scheme 1. C−S Cross-Coupling Reaction of Boronic Acids

Table 1. Optimization of the Reaction Conditions

entry

cat.

base

solvent

t (h)

yield (%)

CuSO₄

CuI

Na₂CO₃(5 equiv)

MeOH (2.0 mL)

MeOH (1.5 mL)

MeOH (0.6 mL)

MeOH (0.4 mL)

MeOH (0.5 mL)

Cs₂CO₃(5 equiv)

KO^tBu (5 equiv)

nBu₄NOH (40% aq, 0.5 mL)

nBu₄NOH (40% aq, 0.4 mL)

nBu₄NOH (40% aq, 0.6 mL)

nBu₄NOH (40% aq, 0.5 mL)

nBu₄NOH (40% aq, 1.0 mL)

nBu₄NOH (40% aq, 0.5 mL)

MeOH (0.5 mL)

EtOH (0.5 mL)

DMSO (0.5 mL)

THF (0.5 mL)

DMF (0.5 mL)

EtOH (0.5 mL)

CuCl₂

FeCl₃

CuSO₄

Unless otherwise noted, the reactions were carried out with phenylboronic acid (0.5 mmol), thiophenol (0.75 mmol), catalyst (20 mol %), ligand

(1,10-phen·H₂O) (20 mol %), under O₂atmosphere. Determined by GC. Ligand (2,2′-bipyridyl) (20 mol %), 5 mol % of CuSO₄, 5 mol % of

1,10-phen·H₂O were used. 2 mol % of CuSO₄, 2 mol % of 1,10-phen·H₂O were used. 1.4 equiv of thiophenol was used. 1.3 equiv of thiophenol

was used. Under air atmosphere.

1, entry 17). Further experiments indicated that the amount of

CuSO₄and 1,10-phenanthroline monohydrate could be

decreased respectively to 5 mol % (Table 1, entries 19 and

20). Optimization of the amount of thiophenol showed that 1.4

equiv (with comparison of 1.0 equiv of phenylboronic acid)

were necessary to achieve high yield (Table 1, entries 21 and

22). Note that only 57% desired product was obtained when

using air as oxidant (Table 1, entry 23).

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a b

Scope of Cu-Catalyzed Chan−Lam-Type S-Arylation

of Thiols with Boronic Acids at Room Temperature. To

examine the scope and limitation of this protocol, the reactions

of different aryl thiols (1.4 equiv of phenylboronic acid) with

phenylboronic acid (0.5 mmol) were carried out under the

optimized conditions (5 mol % CuSO₄, 5 mol % 1,10-

phen·H₂O, nBu₄NOH (40% aq 0.5 mL), EtOH (0.5 mL), rt),

and the results are summarized in Table 2. Both electron-rich

Table 3. Reaction of Arylboronic Acid with Thiols

Table 2. Reaction of Phenylboronic Acid with

a b

Thiophenols

Reactions were carried out using aryl or heteroaryl boronic acids (0.5

mmol) and thiols (0.7 mmol) at room temperature under O₂

atmosphere for 8 h. Yields are given for isolated products. nBu₄NOH

(40% aq, 1.0 mL), EtOH (1.0, 24 mL), 24 h. 24 h.

Reactions were carried out using phenylboronic acid (0.5 mmol) and

thiols (0.7 mmol) at room temperature under O₂atmosphere for 8 h.

Yields are given for isolated products. Phenylboronic acid (20

sterically hindered the yields also could reach to 65−82% (2t−

v). Furthermore, the bromo or chloro group does not interfere

with the transformation, which made additional cross-couplings

at the halogenated positions (2w−aa). In addition, naphthale-

neboronic acids with different substituted positions exhibited

slightly different reactivities (2ab−ae). We were pleased to find

that heteroaryl boronic acids such as 2-benzofuranboronic acid

and 3-thiopheneboronic acid also provided the corresponding

products in good yields (2af−ag), and 2-furanboronic acid gave

a moderate yield (2ah). However, the reaction of 3-

thiopheneboronic acid with thiophenol only gave a trace

amount of product. It should be noted that this catalyst system

is not suitable for alkyl boronic acids as substrates.

Proposed Reaction Mechanism of the Copper-

Catalyzed Coupling of Thiols with Boronic Acids. On

the basis of the experimental observations, we propose the

mechanism as follows (Scheme 2). Initially, CuSO₄is quickly

coordinated to 1,10-phen·H₂O to form Cu(II) intermediate A,

followed by a transmetalation of the aryl group from boron to

copper. Then there would be two paths to achieve the catalytic

cycle. Because thiols are easily oxidized to disulfides by Cu (II)

under O₂atmosphere,¹⁵Cu(II) intermediate C and products

are produced by the reaction of 1,2-diaryldisulfane with Cu(II)

intermediate B.^16aThen the Cu(II) intermediate C is proposed

to undergo transmetalation with the aryl boronic acid to form

intermediate D. Compared with the path A, another path is

possible, because the reaction of 1,2-diphenyldisulfane with

phenylboronic acid gave only diphenyl sulfide in 67% isolated

yield under the aforementioned conditions (Scheme 3). This

Cu(II) species B may undergo another transmetalation to

mmol), thiophenol (28 mmol), nBu₄NOH (40% aq, 20.0 mL), EtOH

(20.0 mL). nBu₄NOH (40% aq, 1.0 mL), EtOH (1.0 mL), 24 h.

CuSO₄(20 mol %), 1,10-phen·H₂O (20 mol %), 60 °C, 24 h.

and electron-poor substrates could give good to excellent yields

of the corresponding desired products (1a−h). More

importantly, the coupling of phenylboronic acid with

thiophenol on a 20 mmol (gram) scale also gave 70% isolated

yield, which made this protocol suitable for industrial

application. To our delight, 4-hydroxythiophenol containing

an OH group was also successfully coupled in good yield,

avoiding oxidative C−O coupling (1i). Although 2-methyl-

benzenethiol gave excellent yield of cross-coupled product (1j),

the more sterically hindered 2,6-dimethylbenzenethiol and 2-

metrcaptobenzoic acid generated only moderate amounts of the

S-arylation products (1k,l). Furthermore, reactions to generate

aryl heteroaryl sulfides also occurred in high yields (1m,n),

although a higher temperature and a longer reaction time were

required for the 2-benzothiazolethiol. Unfortunately, aliphatic

thiols (1o) were not suitable for this catalytic system.

The coupling of various arylboronic acids with an electron-

rich thiophenol (m-toluenethiol), electron-neutral thiophenol

(thiophenol), and electron-poor thiophenol (4-fluorobenzene-

thiol) were next investigated under the aforementioned

optimized conditions (Table 3). The coupling appears to be

insensitive to the electronic properties of the substrates. All

reactions of both electron-rich and electron-poor arylboronic

acids with thiophenols such as m-toluenethiol and 4-

fluorobenzenethiol proceeded efficiently (2a−r). It was noted

that for aryl boronic acids with ortho substitutents tthat are

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oven-dried Schlenk tube was charged with CuSO₄(5 mol %, 4.0

mg), 1,10-phen·H₂O (5 mol %, 4.9 mg), aryl or heteroaryl

boronic acids (0.5 mmol), and thiols (0.70 mmol) (if solid).

The tube was evacuated and filled with oxygen (this procedure

was repeated three times). Then EtOH (0.5 mL) was added

with a syringe under a counter flow of oxygen. After 2 min,

nBu₄NOH (40% aq) (0.5 mL) was added with a syringe under

a counter flow of oxygen. Next, thiol (0.70 mmol) (if liquid)

was added with a syringe under a counter flow of oxygen. The

resulting reaction mixture was stirred at 25 °C for 8 h. The

reaction mixture was then diluted with Et₂O, filtered through

silica gel with copious washings (Et₂O or EtOAc), concen-

trated, and purified by column chromatography.

Scheme 2. Proposed Mechanism

General Procedure B. A 25 mL oven-dried Schlenk tube was

charged with CuSO₄(5 mol %, 4.0 mg), 1,10-phen·H₂O (5 mol %, 4.9

mg), aryl or heteroaryl boronic acids (0.5 mmol), and thiols (0.70

mmol) (if solid). The tube was evacuated and filled with oxygen (this

procedure was repeated three times). Then EtOH (1.0 mL) was added

with a syringe under a counter flow of oxygen. After 2 min, nBu₄NOH

(40% aq) (1.0 mL) was added with a syringe under a counter flow of

oxygen. Next, thiol (0.70 mmol) (if liquid) was added with a syringe

under a counter flow of oxygen. The resulting reaction mixture was

stirred at 25 °C for 24 h. The reaction mixture was then diluted with

Et₂O, filtered through silica gel with copious washings (Et₂O or

EtOAc), concentrated, and purified by column chromatography.

General Procedure C. A 25 mL oven-dried Schlenk tube was

charged with CuSO₄(20 mol %, 16.0 mg), 1,10-phen·H₂O (20 mol %,

20.0 mg), aryl or heteroaryl boronic acids (0.5 mmol), and thiols (0.70

mmol) (if solid). The tube was evacuated and filled with oxygen (this

procedure was repeated three times). Then EtOH (0.5 mL) was added

with a syringe under a counter flow of oxygen. After 2 min, nBu₄NOH

(40% aq) (0.5 mL) was added with a syringe under a counter flow of

oxygen. Next, thiol (0.70 mmol) (if liquid) was added with a syringe

under a counter flow of oxygen. The resulting reaction mixture was

stirred at 60 °C for 24 h. The reaction mixture was then diluted with

Et₂O, filtered through silica gel with copious washings (Et₂O or

EtOAc), concentrated, and purified by column chromatography.

General Procedure D. A 25 mL oven-dried Schlenk tube was