Ultrasound-assisted, transition-metal-free synthesis of diaryl tellurides from aryl boronic acids: A possible free-radical mechanism

Article abstract of DOI:10.1055/s-0034-1378334

The first rapid, catalyst-free synthesis of diphenyl tellurides from readily available diphenyl ditelluride and aryl boronic acids is reported. The high efficiency, general applicability and wide substrate scope, including heterocycles and other functional groups, make this method superior. The technique, which utilizes dimethyl sulfoxide solvent and ultrasound promotion, opens the door for the synthesis of diphenyl tellurides at 100 °C in air within a short time in high yields. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0034-1378334

2078▌
LETTER
lUettlertrasound-Assisted, Transition-Metal-Free Synthesis of Diaryl Tellurides
from Aryl Boronic Acids: A Possible Free-Radical Mechanism
Metal-Free Synthesis of Diphenyl Tellurides
Balaji Mohan, Sori Hwang, Seongwan Jang, Kang Hyun Park*
Department of Chemistry, Pusan National University, Busan, 609735, South Korea
Fax +82(51)9805200; E-mail: chemistry@pusan.ac.kr
Received: 09.05.2014; Accepted after revision: 27.05.2014
protocols have been reported. A general method involves
Abstract: The first rapid, catalyst-free synthesis of diphenyl tellu-
the cross-coupling of diphenyl ditelluride with phenyl bo-
rides from readily available diphenyl ditelluride and aryl boronic
ronic acids or halobenzenes.
acids is reported. The high efficiency, general applicability and
wide substrate scope, including heterocycles and other functional
Te
groups, make this method superior. The technique, which utilizes
dimethyl sulfoxide solvent and ultrasound promotion, opens the
door for the synthesis of diphenyl tellurides at 100 °C in air within
a short time in high yields.
MO3S(H2C)3O
O(CH2)3SO3M
Te
1
Key words: arylation, cross-coupling, free radicals, diphenyl tellu-
ride, transition metals
THPO
O(CH2)3SO3M
2
During the past decade, organotellurium chemistry has at-
tracted considerable, ongoing attention due to its impor-
tance in different areas of chemistry. In organic synthesis,
organotellurium compounds are well known as intermedi-
ates1a in group transfer cyclization reactions. For example,
as group transfer agents, secondary alkyl phenylorgano-
tellurium compounds have been shown to be effective
radical precursors in terms of chemoselectivity and yield
in dialkylzinc-mediated radical addition reactions.1b Nu-
merous applications of organotellurium compounds as
novel initiators for controlled/living radical polymeriza-
tion2a,b have been described. Organotellurium-based li-
gands have been reported as efficient metal complexation
reagents in inorganic chemistry due to their ‘soft’ donor
nature, and they can function as either Lewis acids or
Lewis bases.2c The use of organochalcogen compounds in
asymmetric synthesis is also a most curious development
that has led to a new direction in the area of organometal-
lic chemistry.3
Te
+
NMe2
M = Li, Na, K or NMe4
Cl–
THPO
OH
3
Figure 1 Some biologically active organotellurium compounds
Due to the difficulty in activating carbon–halogen bonds,
cross-couplings between halobenzenes and diaryl dichal-
cogens usually require copper salts,5 ligands,5 reducing
agents,5b and strong bases. In contrast, phenyl boronic ac-
ids are commercially available, are easily activated, and
are also able to couple with diaryl dichalcogens. Wang et
al.6a reported an iron-catalyzed, ligand-free coupling of
diphenyl dichalcogens with aryl boronic acids in DMSO
after 20 hours at high temperature (130 °C). Recently,
Ranu and co-workers6b utilized CuFe2O4 nanoparticles in
combination with DMSO (1.5 equiv) in polyethylene gly-
col (PEG) to catalyze similar couplings after 12 hours at
100 °C. Taniguchi6c reported the copper iodide/bipyridyl-
catalyzed coupling of diphenyl dichalcogens with aryl bo-
ronic acids in a DMSO/water mixture in 12 hours at
100 °C. Alves and co-workers6d utilized glycerol as sol-
vent, copper iodide as catalyst, and DMSO as an additive
to promote the coupling of diphenyl dichalcogens with
aryl boronic acids at 110 °C for 30 hours. The Wang
group6e introduced InBr3 as a new catalytic system for the
coupling of diphenyl dichalcogens with aryl boronic acids
at elevated temperature. All these methods used DMSO as
the solvent and a copper source as the catalyst, and re-
quired long reaction times.
Organotellurium compounds also exhibit diverse biologi-
cal activities and, indeed, anticancer activity of such com-
pounds have been shown.4a Much attention has therefore
been paid to the synthesis of organotellurium compounds
that can be used as enzyme mimics and chemotherapeutic
agents and, particularly, water-soluble organotellurium
compounds 1–3 (Figure 1), which have been shown to be
potent thiol peroxidase and antioxidants.4b Tellurium-
based drugs such as ammonium trichloro(dioxoethylene-
O,O′)tellurate and 4,4′-dihydroxydiphenyltelluride are
used as enzyme inhibitors for cysteine proteases and as re-
dox modulators for glutathione,4c respectively. To synthe-
size the aforementioned tellurium compounds, various
Most of the foregoing catalytic systems require a catalyst
and long reaction time of at least 12 hours. Surprisingly,
we found that a test reaction between diphenyl ditelluride
and an aryl boronic acid in DMSO proceeded smoothly,
affording the corresponding diphenyl telluride-coupled
product in high yield in the absence of the usual necessary
SYNLETT 2014, 25, 2078–2082
Advanced online publication: 07.07.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1378334; Art ID: st-2014-u0405-l
© Georg Thieme Verlag Stuttgart · New York

LETTER
Metal-Free Synthesis of Diphenyl Tellurides
2079
conv. heat
B(OH)2
OMe
92%, 6 h
Te
Te
DMSO
100 °C
microwave
+
Te
88%, 30 min
OMe
3aa
ultrasound
96%, 10 min
Scheme 1 Model reaction under three different conditions
additives. Interestingly, the related reaction using diphe- between diphenyl ditelluride and 4-methoxyphenylboron-
nyl diselenide was ineffectual. Given the time required for ic acid in DMSO (3 mL) proceeded smoothly in air with
the test reaction, we were prompted to utilize the findings ultrasound assistance.9 The expected cross-coupled prod-
from our previous reports on ultrasound irradiation7 and uct, bis(4-methoxyphenyl)telluride, was obtained in 96%
organochalcogen chemistry8 to examine activation by yield, again without the use of any additives. Other sol-
physical effects to obtain higher yields of diphenyl tellu- vents such as N,N′-dimethylpropyleneurea (DMPU), di-
rides in shorter times. Thus, we surveyed the reactions of methylformamide (DMF), N-methylpyrrolidone (NMP)
diphenyl ditelluride and 4-methoxyphenylboronic acid and dimethylacetamide (DMAC) resulted in lower yields
promoted by conventional heating, microwave, and ultra- (entries 3–6). Unfortunately, none of the desired product
sound. All the reactions were performed at the same tem- was detected when the reaction was carried out in the
perature (100 °C) and open to the air (Scheme 1). The green solvents glycerol or PEG 200 (entries 7 and 8). The
ultrasound-assisted coupling afforded good yields within reaction was sluggish in ethylene glycol (EG; entry 9).
10 min, compared with conventional heating (6 hours), Product formation was easily identified by a change in the
and microwave (30 min). A slight decrease in temperature reaction color from an initial dark-orange to light-yellow
to 80 °C for 30 min resulted in lower yield (Table 1, at completion (Figure 2).
entry 2).
To optimize the experimental conditions, we screened a
wide range of solvents at 100 °C (Table 1). The reaction
Table 1 Optimization of Reaction Conditions
Entry
Solvent
Temp. (°C) Time (min) Yield (%)a
1
2
DMSO
DMSO
DMPU
DMF
100
80
10
30
10
10
10
10
10
10
10
30
360
30
96
65
Figure 2 Progress of the reaction: (A) Reaction at the beginning, and
(B) at the end (10 min)
3
100
100
100
100
100
100
48
4
81
5
NMP
25
The optimized conditions were applied to various substi-
tuted aryl boronic acids to probe the substrate scope and
reactivity. For all the cases in Table 2, the corresponding
ultrasound-promoted cross-coupled products were ob-
tained in good to moderate yields without employing any
further additives. The coupling reactions between unsub-
stituted phenyl and naphthyl boronic acids with diphenyl
ditelluride gave nearly quantitative yields (entries 1 and
6). Interestingly, the yield when using 4-methylphenyl bo-
ronic acid (entry 2) decreased somewhat, but was still
good compared with 4-methoxyphenyl boronic acid,
which afforded excellent yields. Substrates with electron-
withdrawing groups on the aryl boronic acid, such as p-tri-
fluoromethyl, p-cyano, p-fluoro, or p-ethoxycarbonyl,
furnished coupled products in moderate yields along with
6
DMAc
PEG 200
glycerol
49
7
ND
ND
8
8
9
ethylene glycol 100
10
11
12
DMSO
DMSO
DMSO
100
100
100
88b
92c
<1d
a Determined by GC-MS analysis (with reference to diphenyl disele-
nide).
b Reaction with microwave (300 W).
c Reaction under conventional heating.
d Reaction under N2 atmosphere.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2078–2082

2080
B. Mohan et al.
LETTER
diphenyl telluride as a side product, which was confirmed
by GC-MS analysis. Furthermore, the reaction with five-
membered heterocycle 3-thiophene boronic acid provided
the corresponding coupled product in high yields (entry
8). However, the fact that reactions with isopropyl and vi-
nyl boronic acids did not proceed well under the present
conditions (entries 9 and 10), indicates that the aromatic
ring plays an important electronic role in the reaction. We
also note that only a trace amount of product was detected
when the experiments were conducted with phenyl boron-
ic acids containing electron-withdrawing substituents
(Table 2) under conventional heating even after prolonged
reaction time. This result shows the significant impor-
tance of ultrasound irradiation technology in organochal-
Table 2 Ultrasound-Promoted Cross-Coupling of Diphenyl Ditellu-
rides and Substituted Phenyl Boronic Acids
Entry Boronic acid
Product
Time Yield
(min) (%)a
HO
HO
OH
OH
B
Te
1
2
10 99
B
Te
15 87
cogen
chemistry,
particularly
to
synthesize
unsymmetrical aryl tellurides. It is noted that, to our
knowledge, this is the first report describing the coupling
of diphenyl ditelluride with aryl boronic acids without
metal sources, ligands, bases, or reducing agents with
straightforward ultrasound assistance.
HO
HO
OH
B
Te
3
4
15 72
CF3
CF3
Regarding the mechanism of this reaction, experiments
were conducted in the presence of radical scavengers hy-
droquinone and thiourea (2 equiv with respect to diphenyl
ditelluride). Under these conditions, formation of desired
product was observed in 8 and 7% yields, respectively,
whereas 42% of the cross-coupled product was identified
with the scavenger 2,2,6,6-tetramethylpiperidine-1-oxyl
(TEMPO) (Scheme 2). An increase in yield with TEMPO
might be due to its instability in an air atmosphere. We
therefore propose that the reaction proceeds through a
free-radical pathway (Scheme 3). Furthermore, conduct-
ing the reaction under a N2 atmosphere provided less than
1% cross-coupled product (Table 1, entry 12), which indi-
cates that air is mandatory and plays an important role,
presumably as oxidant.
OH
B
Te
Te
15 72
CN
CN
B(OH)2
5
6
7
15 70
F
F
B(OH)2
Te
Te
15 91
B(OH)2
COOEt
In conclusion, we successfully achieved the cross-cou-
pling of diphenyl ditelluride and aryl boronic acids in the
absence of additives, and with the assistance of solvent,
temperature, and ultrasonication.11 The commercial avail-
ability of the reagents, exceptional functional group toler-
ance, and good to moderate yields make this an interesting
alternative for the synthesis of unsymmetrical diaryl tellu-
rides.
5
64
COOEt
B(OH)2
Te
Te
8
9
S
10 90
S
OH
Acknowledgment
B
20 NR
OH
This research was supported by the Basic Science Research Pro-
gram through the National Research Foundation of Korea (NRF)
funded by the Ministry of Science, ICT & Future Planning
(No.2013R1A1A1A05006634). K.H.P thanks the TJ Park Junior
Faculty Fellowship and LG Yonam Foundation.
OH
Te
B
OH
10
20 NR
a Determined by GC-MS analysis, based on average of two indepen-
dent runs.
Synlett 2014, 25, 2078–2082
© Georg Thieme Verlag Stuttgart · New York

LETTER
Metal-Free Synthesis of Diphenyl Tellurides
2081
hydroquinone
B(OH)2
OMe
8%
Te
DMSO, )))
thiourea
7%
Te
+
Te
100 °C, 30 min
OMe
TEMPO
42%
Scheme 2 Mechanistic investigations in the presence of radical scavengers
OH
Te
B
OH
Te
Te
+
2
ArTeAr
Te
– B(OH)3
Scheme 3 Proposed free-radical mechanism for the synthesis of unsymmetrical aryl tellurides
(11) General Description: Reagents were purchased from
References and Notes
Aldrich Chemical Co., TCI and Strem Chemical Co. and
were used as received. Reaction products were analyzed by
GC-MS (Shimadzu-QP2010 SE), 1H NMR and 13C NMR
(Varian Mercury Plus, 300 MHz). Chemical shift values are
recorded as parts per million relative to tetramethylsilane as
internal standard, unless otherwise indicated, and coupling
constants are given in Hertz. A Fisher Scientific Sonic
Dismembrator (model 500, 230 V, 50/60 Hz) was used for
ultrasonication.
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Cross-Coupling Reaction; General Procedure: Diphenyl
ditelluride (0.12 mmol, 50 mg) and phenylboronic acid
(0.27 mmol, 32 mg) were dissolved in DMSO (3 mL)
followed by ultrasonication at 100 °C until color change
from dark-orange to light-yellow (sometimes colorless) was
observed. After usual work up, the crude product was
analyzed by GC-MS and then purified by silica gel column
chromatography. The purified products were characterized
by 1H and 13C NMR spectroscopy. All synthesized
compounds are known and their spectroscopic data were
consistent with reported values.
4-Methoxyphenyl Phenyl Telluride: 6a 1H NMR
(300 MHz, CDCl3): δ = 7.72 (d, J = 9 Hz, 2 H), 7.59–7.56
(m, 2 H), 7.21–7.17 (m, 3 H), 6.82 (d, J = 8.7 Hz, 2 H), 3.80
(s, 3 H); 13C NMR (75 MHz, CDCl3): δ = 160.0, 141.3,
136.6, 129.5, 127.4, 115.8, 115.7, 103.2, 55.3.
Diphenyl Telluride: 10 1H NMR (300 MHz, CDCl3): δ =
7.71 (d, J = 6.6 Hz, 4 H), 7.35–7.19 (m, 6 H); 13C NMR
(75 MHz, CDCl3): δ = 138.2, 129.7, 128.1, 114.
4-Tolyl Phenyl Telluride:6b 1H NMR (300 MHz, CDCl3): δ
= 7.64 (d, J = 7.8 Hz, 3 H), 7.29–7.17 (m, 4 H), 7.07 (d, J =
7.5 Hz, 2 H), 2.35 (s, 3 H); 13C NMR (75 MHz, CDCl3): δ =
138.9, 137.5, 137.4, 130.6, 129.7, 127.7, 115.4, 110.5, 21.5.
4-Trifluoromethyl Phenyl Phenyl Telluride:5d 1H NMR
(300 MHz, CDCl3): δ = 7.82 (m, 2 H), 7.68 (m, 2 H), 7.42
(m, 3 H), 7.28 (m, 2 H); 13C NMR (75 MHz, CDCl3): δ =
139.6, 138.2, 136.6, 130.0, 129.7, 128.9, 126.1 (q),
122.3,113.5.
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Synthesis 2010, 2990. (c) Timothy, J. M. Chem. Soc. Rev.
1997, 26, 443.
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54, 2452.
4-Cyanophenyl Phenyl Telluride: 5d 1H NMR (300 MHz,
CDCl3): δ = 7.85–7.82 (m, 2 H), 7.56 (d, J = 8.4 Hz, 2 H),
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2078–2082

2082
B. Mohan et al.
LETTER
4-Ethoxycarbonylphenyl Phenyl Telluride: 6b 1H NMR
7.42–7.29 (m, 5 H); 13C NMR (75 MHz, CDCl3): δ = 140.3,
135.9, 132.4, 130.0, 129.4, 124.5, 118.9, 113.0, 110.8.
4-Fluorophenyl Phenyl Telluride: 6b 1H NMR (300 MHz,
CDCl3): δ = 7.74–7.63 (m, 4 H), 7.31–7.19 (m, 3 H), 6.99–
6.90 (m, 2 H); 13C NMR (75 MHz, CDCl3): δ = 164.9, 161.6,
140.7, 138.2, 132.1, 129.8, 129.7, 128.0, 117.0, 114.8.
2-Naphthyl Phenyl Telluride: 6b 1H NMR (300 MHz,
CDCl3): δ = 8.25 (d, J = 6.3 Hz, 1 H), 7.82–7.66 (m, 7 H),
7.49–7.45 (m, 2 H), 7.32–7.19 (m, 3 H); 13C NMR (75 MHz,
CDCl3): δ = 138.1, 138.0, 137.9, 134.9, 134.5, 132.8, 129.7,
128.8, 128.0, 127.9, 127.6, 126.6, 126.5, 115.0, 112.2.
(300 MHz, CDCl3): δ = 7.80 (m, 3 H), 7.62 (d, J = 8.1 Hz,
2 H), 7.40–7.25 (m, 4 H), 4.33 (q, J = 6.9, 7.2 Hz, 2 H), 1.37
(t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3): δ = 166.6,
139.5, 136.2, 130.2, 130.0, 129.7, 128.8, 123.1, 113.7, 61.1,
14.5.
3-Thiophenyl Phenyl Telluride: 6b 1H NMR (300 MHz,
CDCl3): δ = 7.72–7.70 (m, 1 H), 7.61–7.57 (m, 3 H), 7.31–
7.16 (m, 4 H); 13C NMR (75 MHz, CDCl3): δ = 138.2, 137.0,
136.9, 136.7, 134.7, 129.7, 129.6, 128.0, 127.7, 127.4,
115.4, 104.0.
Synlett 2014, 25, 2078–2082
© Georg Thieme Verlag Stuttgart · New York

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