Cu-Mediated arylselenylation of aryl halides with trifluoromethyl aryl selenonium ylides

Article abstract of DOI:10.1039/c9ob01506j

An unprecedented arylselenylation of aryl halides with trifluoromethyl aryl selenonium ylides in the presence of copper is described. The reaction proceeded at 100-140 °C under ligand- and additive-free conditions for 3-20 h to form a variety of unsymmetrical diaryl selenides in good to high yields. Arylselenylation is easy to operate, has good functional group tolerance, and demonstrates the different reaction profiles of trifluoromethyl aryl selenonium ylides from the homologous trifluoromethyl aryl sulfonium ylides.

Full text of DOI:10.1039/c9ob01506j

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DOI: 10.1039/C9OB01506J
ARTICLE
Cu-Mediated Arylselenylation of Aryl Halides with Trifluoromethyl
Aryl Selenonium Ylides
Received 00th January 20xx,
Accepted 00th January 20xx
Shuai Wu, Jin Shi and Cheng-Pan Zhang*
DOI: 10.1039/x0xx00000x
An unprecedented arylselenylation of aryl halide with trifluoromethyl aryl selenonium ylide in the presence of copper is
described. The reaction proceeded at 100-140 oC under ligand- and additive-free conditions for 3-20 h to form a variety of
unsymmetrical diaryl selenides in good to high yields. The arylselenylation is easy to operate, has good functional group
tolerance, and demonstrates the different reaction profiles of trifluoromethyl aryl selenonium ylides from the homologous
trifluoromethyl aryl sulfonium ylides.
trifluoromethylthiol ethers with dimethyl diazomalonate
formed trifluoromethyl sulfonium ylides, which could be used as
a new type of electrophilic trifluoromethylation reagents for β-
Introduction
Selenium-containing compounds have gained great interest in the
recent decades because of their specific characteristics and
biological activities displayed in material and life sciences.1
Selenium is much associated with human health and diseases and is
an essential element that is critical to many cellular processes.2 The
beneficial nature of selenium and organoselenides has motivated
chemists to design and synthesize various selenium-based
ketoesters and aryl iodides (Scheme 1a).9 The results revealed that
trifluoromethyl sulfonium ylides had very different reactivities from
the non-fluorinated sulfonium ylides which behaved as nucleophiles
or diazocarbonyl equivalents to form heterocycles or
rearrangement products.10 The interesting reactivities of
trifluoromethyl sulfonium ylides imparted by fluorine inspired us to
study their analogues, trifluoromethyl selenonium ylides, as a part
of our interest in SeCF3 chemistry.11 Recently, Shen and our group
independently reported the preparation of trifluoromethyl aryl
selenonium ylide in the 15th China’s national meeting on fluorine
chemistry.12 They found that trifluoromethyl aryl selenonium ylides
(1) were applicable electrophilic trifluoromethylation reagents for a
variety of nucleophiles including β-ketoesters and silyl enol ethers,
aryl/heteroaryl boronic acids, electron-rich heteroarenes and
sulfinates, which exhibited higher reactivity and broader substrate
scope than their sulfonium ylide analogues.13 In this article, we
discovered that reaction of trifluoromethyl aryl selenonium ylide
with aryl halides in the presence of copper salts surprisingly
constructed diaryl selenides in good yields rather than the expected
trifluoromethylated arenes (Scheme 1b).
pharmaceuticals,
including
anticancer,
antioxidant,
antihypertensive, antiviral, immunosuppressive, and antimicrobial
agents.1,2 Among all selenium-containing organic compounds, the
diaryl selenide scaffolds are increasingly attractive in the drug
design and development.3 Considerable efforts have been made on
the development of new synthetic methods for diaryl selenides.4
Direct arylselenylation using ArSe reagents represents a practical
and useful approach for these compounds. The effective ArSe
sources include diaryl diselenides, aryl selenols or selenolates, aryl
selenocyanates, aryl tributylstannyl selenides, arylselenium halides,
and others.4-6 Despite the great advancements, the search for
general, convenient, and environment-benign methodologies to
construct diverse selenium-containing compounds under mild
conditions is still highly desirable as some of the known strategies
suffered from harsh conditions, toxic materials, and limited
substrate scopes, which remains significant challenges.4-6
On the other hand, organofluorine chemistry has been one of
the most active disciplines, modernizing various areas.7 Except
the power of molecular editing of pharmaceuticals,
agrochemicals and functional materials, fluorine has an
inimitable ability to modulate the chemical reactivities of
organic molecules owing to its unique features.7,8 In 2015, Shen
and coworkers reported that Rh-catalyzed reactions of
Scheme 1. Cu-mediated reactions of aryl halides with
trifluoromethyl aryl sulfonium or selenonium ylides
a) Cu-mediated trifluoromethylation of aryl iodides with trifluoromethyl aryl sulfonium ylides
Cu
CF3
Ar CF3
Ar
I
+
DMF, 100 oC, 3 h
S
2
3'
MeO2C
CO2Me
1a'
b) Cu-mediated arylselenylation of aryl halides with trifluoromethyl aryl selenonium ylides
R
Cu or CuOAc
R
CF3
Ar
X
+
Se
1
Ar
DMSO or DMF
Se
2
100-140 oC, 3 or 20 h
a. School of Chemistry, Chemical Engineering and Life Science, Wuhan University of
Technology, 205 Luoshi Road, Wuhan 430070, China.
MeO2C
CO2Me
3
(X = I, Br)
†
Electronic
supplementary
information
(ESI)
available.
See
DOI:10.1039/x0xx00000x
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
biphenyl]-4-yl(4-nitrophenyl)selane (3b, tR = 15.24 min) and 4-(trifluoromethyl)-
1,1'-biphenyl (3a’, tR = 8.54 min) as external standardDs,OreI:sp10ec.1t0iv3e9ly/.C9OB01506J
Results and discussion
By following Shen’s procedure, the reaction of trifluoromethyl
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phenyl sulfonium ylide (1a’) with 4-iodo-1,1'-biphenyl (2a) and
Considering the low cost and easy preparation of the starting
materials, we continued our study by using 1b and 2a as the model
substrates (Table 1). A survey of the reaction conditions showed
that the copper reagents such as Cu, CuOAc, CuOTf, Cu(OAc)2,
CuSO4, and Cu(acac)2 were comparably effective in arylselenylation
of 2a with 1b (1 equiv) at 100 oC, which gave 3b in moderate yields
after 24 h (Table 1, entries 1-8). Taking CuOAc as an example, the
reaction of 2a with 1b (1.0 equiv) and CuOAc (1.0 equiv) in DMF at
100 oC for 24 h afforded 3b in 54% yield and 3a’ in 6% yield (Table 1,
entry 2). Increasing the molar equivalents of 1b and CuOAc from 1.0
equiv to 1.2 or 2.0 equiv in the same reaction led to 3b in 56% or
68% yield (Table 1, entries 9-10). When 2a reacted with 1b (2 equiv)
and CuOAc (2 equiv) in DMSO at 100 oC for 24 h provided 3b in 92%
yield (Table 1, entry 11). Prolonging the reaction time from 24 h to
36 h did not obviously change the yield of 3b (Table 1, entry 12). To
our delight, the reaction of 2a and 1b (2 equiv) with CuOAc (2 equiv)
copper powder in DMF at 100 oC for
3 h furnished 4-
(trifluoromethyl)-1,1'-biphenyl (3a’) in 87% yield as the sole product
(Scheme 2). If the homologous trifluoromethyl phenyl selenonium
ylide (1a) was mixed with 4-iodo-1,1'-biphenyl (2a) and copper
under the same conditions, [1,1'-biphenyl]-4-yl(phenyl)selane (3a)
was obtained in 64% yield and 3a’ was detected in only 5% yield.
Moreover, the copper-mediated reactions of dimethyl 2-((4-
nitrophenyl)(trifluoromethyl)-λ4-selanylidene)malonate (1b) with 2a
did not form 3a’ as the major product either (Table 1). Instead, the
arylselenylated product, [1,1'-biphenyl]-4-yl(4-nitrophenyl)selane
(3b), was predominantly produced even in the presence of different
copper agents (Table 1 and the supporting information). These
results showed the diverse reactivities between trifluoromethyl aryl
selenonium ylides and trifluoromethyl aryl sulfonium ylide in the
copper-mediated reactions with aryl iodide.
o
at 100 C for 20 h furnished 3b in 94% yield when using DMSO as a
Scheme 2. Comparing the reactions of 1a’ and 1a with 2a under the
same conditions
solvent (Table 1, entry 13). Further shortening the reaction time
from 20 h to 16 h resulted in a decrease in the yield of 3b (Table 1,
entry 14).
CF3
I
S
CF3
Cu (2 equiv)
DMF, 100 oC, 3 h
S
+
a)
b)
+
Ph
Ph
Ph
Ph
Ph
MeO2C
CO2Me
3a'
87%
Scheme 3. Cu-mediated arylselenylation of aryl iodides or bromides
(2) by 1b.a
2a
0%
1a'
(0.2 mmol)
(0.7 mmol)
O2N
CF3
I
Se
O2N
CF3
Cu (2 equiv)
DMF, 100 oC, 3 h
Se
+
CF3
CuOAc
+
Ar
X
+
Se
DMSO, 100 oC, 20 h
Ar
Ph
2
Se
Se
MeO2C
CO2Me
3a'
5%
3a
64%
2a
MeO2C
1b
CO2Me
(X = Br, I)
3
1a
(0.2 mmol)
(0.7 mmol)
Se
Se
Se
Table 1. Optimization of the reaction conditions for 1b and 2a.
R
NO2
NO2
NO2
NO2
3c
3d
3e
, R = H, 97%
NO2
3r
, 77%
O2N
3q
3s
, 85%
, 84%
, R = CH3, 85%
, R = OMe, 78%
, R =OBn, 63%
I
Se
CF3
[Cu] source
100 o
solvent, time
CF3
+
Se
1b
+
Se
C
3f
Ph
Ph
NO2
Ph
2a
3b
MeO2C
CO2Me
3g, R = t-Bu, 95%
3a'
O
R
NO2
Se
3h
, R = F, 70%
, R = Cl, 84 %
, R = Br, 56%
Se
d
3b
3c
3d
3e
3i
3j
, R = Ph, 55%
Time
(h)
Yield (3b,
Yield (3a’,
d
e
Entry a
[Cu]
Cu
Solvent
2a:1b:[Cu]
, R = H, 70% , 0%
O2N
c
%) b
%) b
3t
, 79%
d
O2N
3k
, R = CH3, 58%
, R = CF3, 71%
d
d,f
3u
, 78%
3l
, R = OMe, 37% , 52%
, R = CO2Et, 82%
1
2
3
4
5
6
7
DMF
DMF
DMF
DMF
DMF
DMF
DMF
24
24
24
24
24
24
24
1:1:1
1:1:1
1:1:1
1:1:1
1:1:1
1:1:1
1:1:1
48
54
27
18
40
45
36
3
6
d
b
3f
3m
, R = OBn, 62%
, R = COMe, 33% , 49%
, R = CONMe2, 61%
, R = CN, 45%
d
3g
3n
3o
3p
, R = t-Bu, 60%
CuOAc
CuCl
d
S
3l
, R = CO2Et, 60%
d
Se
NO2
e
3o
, R = CN, 53% , 0%
, R = CHO, 88%
10
3
3v
, 78%
a Reaction conditions: 1b (0.4 mmol), 2 (0.2 mmol), CuOAc (0.4 mmol), DMSO (2
mL), N2, 100 oC, 20 h. Isolated yield. DMF was used instead of DMSO. Cu (2
equiv), DMF (2 mL), N2, 100 oC, 3 h. ArBr was used instead of ArI at 140 oC.
ArCl was used instead of ArI at 140 oC. f 48 h.
CuCN
b
c
CuOTf
6
d
e
Cu(OAc)2
CuSO4
0
0
8
9
Cu(acac)2
CuOAc
DMF
DMF
24
24
1:1:1
44
56
2
6
With the optimized reaction conditions established (Table 1, entry
13), we next examined the substrate scope of this process. Various
aryl iodides (2b-r) bearing either electron-donating groups (e.g. CH3
(2c), OCH3 (2d), OBn (2e), t-Bu (2f)) or electron-withdrawing groups
(e.g., F (2g), Cl (2h), Br (2i), CF3 (2j), CO2Et (2k), CONMe2 (2m), CN
(2n), CHO (2o), NO2 (2q)) on the aryl rings were smoothly converted
to give the corresponding arylselenylated products (3c-s) in good to
high yields (Scheme 3). The functional groups such as chloride,
bromide, ester, amide, aldehyde, cyano and nitro groups were well
1:1.2:1.2
10
11
12
CuOAc
CuOAc
CuOAc
DMF
DMSO
DMSO
24
24
36
1:2:2
1:2:2
1:2:2
68
92
93
10
4
5
13
14
CuOAc
CuOAc
DMSO
DMSO
20
16
1:2:2
1:2:2
94 (94)
69
5
4
a Reaction conditions: A mixture of 1b (0.2, 0.24, 0.3 or 0.4 mmol), 2a (0.2 mmol)
and Cu source (0.2, 0.24, 0.3 or 0.4 mmol) reacted in DMF or DMSO (2 mL) at 100
oC under N2 for 3-36 h. Isolated yield was depicted in the parenthesis.
were determined by HPLC (λ = 253 nm, H2O / CH3OH = 15 : 85 (v/v)) using [1,1'-
b
Yields
o
tolerated in the reaction at 100 C (3i-j, 3l, 3n-p, 3r). Nevertheless,
reaction of 1-(4-iodophenyl)ethan-1-one (2l) with 1b and CuOAc
2 | J. Name., 2012, 00, 1-3
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ARTICLE
under the optimized conditions provided a complicated mixture, λ4-selanylidene)malonate (1d), 2-((4-chlorophenyl)(trifluoromethyl)-
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which was not identified. If the same combination reacted in DMF λ4-selanylidene)malonate
(1e),
DOI:21-0(.[110,319'-/bCi9pOhBe0n1y5l]0-64J-
at 100 C for 20 h, 1-(4-((4-nitrophenyl)selanyl)phenyl)ethan-1-one yl(trifluoromethyl)-λ4-selanylidene)malonate (1f), and 2-((4-
(3m) was formed in 33% yield. Use of Cu instead of CuOAc in the cyanophenyl)(trifluoromethyl)-λ4-selanylidene)malonate (1g) with
reaction of 2l, 1b and DMF at 100 oC could further enhance the 2a supplied the respective arylselenylated products (3w-aa) in good
reaction, leading to 49% of 3m after 3 h. The steric hindrance of the yields. It appeared that the electron-rich aryl groups on the
substituents on the aryl rings of the iodides had little influence on trifluoromethyl selenonium ylides (1c-d) slowed down the
the reaction as treatment of 1b with 1-iodo-2-methylbenzene (2p) transformation, affording relatively low yields of the desired
and 2-iodo-1,3,5-trimethylbenzene (2r) in the presence of CuOAc at products (3w-x) under the standard conditions. Elevating the
o
o
100 C for 20 h furnished 3q and 3s in 84-85% yields, which were reaction temperature from 100 oC to 120 oC could considerably
comparable to that of 1-iodo-4-methylbenzene (3d, 85% yield). 1- improve the arylselenylation, leading to higher yields of 3w-x. The
Iodonaphthalene (2s) and heteroaryl iodides such as (2t) and (2u) position of substituents on the aryl rings of trifluoromethyl
were also readily arylselenylated under the standard conditions, selenonium ylides had an impact on the reaction. When dimethyl 2-
affording 3t-v in good yields. Furthermore, the reaction was ((3-nitrophenyl)(trifluoromethyl)-λ4-selanylidene)malonate
(1h)
applicable to aryl bromides. A mixture of 4-bromo-1,1'-biphenyl (2v) reacted with 2a at 100 oC for 20 h, the arylselenylated product (3ab)
and 1b at 140 oC for 20 h provided 3b in 55% yield. Similar was constructed in 67% yield (vs 3b in 94% yield from 1b, Table 1,
treatment of bromobenzene (2w), 1-bromo-4-methylbenzene (2x), entry 13). If the more sterically hindered dimethyl 2-((2-
1-bromo-4-methoxybenzene (2y), 1-(benzyloxy)-4-bromobenzene nitrophenyl)(trifluoromethyl)-λ4-selanylidene)malonate (1i) reacted
(2z), 1-bromo-4-(tert-butyl)benzene (2aa), ethyl 4-bromobenzoate with 2a under the same conditions, the arylselenylated product,
(2ab), and 4-bromobenzonitrile (2ac) with 1b gave 3c in 70% yield, [1,1'-biphenyl]-4-yl(2-nitrophenyl)selane (3ac), was formed in only
3d in 58% yield, 3e in 37% yield, 3f in 62% yield, 3g in 60% yield, 3l 39% yield. Additionally, treatment of diethyl 2-((4-
in 60% yield, and 3o in 53% yield, respectively (Scheme 3). In the nitrophenyl)(trifluoromethyl)-λ4-selanylidene)malonate (1j) with 2a
case of 1-bromo-4-methoxybenzene (2y), elongation of the reaction under the standard conditions, 3b was obtained in 84% yield. All
time from 20 h to 48 h improved the yield of 3e, indicating that the these results suggested that trifluoromethyl aryl selenonium ylides
strong electron-donating group on the aryl ring would retard the could be effective arylselenylation reagents in the copper-mediated
conversion. Unfortunately, the reaction was not amenable to aryl reactions.
chlorides as the reactions of chlorobenzene (2ad) and 4-
chlorobenzonitrile (2ae) with 1b/CuOAc in DMSO at 140 oC for 20 h Scheme 5. Control experiments for mechanistic insights.
gave no desired products.
Se
)
(Ph
2
CuOAc
CF3
Ph
MeO2C
CO2Me
CO2Me
Se
CO2Me
5
, 39%
Se
(1 equiv)
a)
Ph
+
+
DMSO
+
CO2Me
Scheme 4. Cu-mediated arylselenylation of 2a by different
trifluoromethyl aryl selenonium ylides (1).a
100 oC, 20 h
MeO2C
CO2Me
MeO2C
Se
4
, 7%
1a
Ph
CF3
7
, 13%
6
, 38%
I
CuOAc (1 equiv)
DMSO, 100 oC, 20 h
R
Se
b)
c)
4
CF3
5
54%
CuOAc (2 equiv)
DMSO, 100 oC, 20 h
+
Se
R
Ph
Ph
MeO2C
CO2Me
2a
3
1
Se
3a
I
CuOAc (2 equiv)
100 oC, 20 h
Ph
Se
Se
Se
4
+
(2 equiv)
Ph
Ph
Ph
Ph
MeO
Ph
2a
, 88%
b
b
b
3a
3w
3x
, 67%, 72%
, 47%, 65%
, 25%, 54%
CuOAc (2 equiv)
DMSO, 100 oC, 20 h
Se
Se
Se
d)
e)
5
2a
+
3a
92%
(1 equiv)
Cl
Ph
Ph
Ph NC
Ph
3y
Se
, 81%
b
3aa
, 95%
3z
, 61%, 66%
CuOAc (2 equiv)
100 oC, 20 h
6
2a
3a
0%
+
NO2
Se
(2 equiv)
Se
Ph
, 67%
O2N
Ph
R
Ph
c
CuOAc (2 equiv)
DMSO, 100 oC, 20 h
NO2
3ab
3b
, 84%
f)
3ac
4
, 39%
2a
2a
+
+
TMSCF3 / CsF
(2 equiv)
Ph
3a
a Reaction condition: 1 (0.4 mmol), 2a (0.2 mmol), CuOAc (0.4 mmol), and DMSO
(2 mL), N2, 100 oC, 20 h. Isolated yield.
nitrophenyl)(trifluoromethyl)-λ4-selanylidene)malonate (1j) was used as
(2 equiv / 2 equiv)
Se
Ph, 92%
, R = CF3, 5%
, R =
3a'
b
c
120 oC.
Diethyl 2-((4-
a
CuOAc (2 equiv)
DMSO, 100 oC, 20 h
g)
5
+
+
TMSCF3 / CsF
3a
97%
+
3a'
2%
reagent instead of 1b.
(1 equiv)
(2 equiv / 2 equiv)
In addition to 1b, other trifluoromethyl aryl selenonium ylides (1)
were also suitable coupling participants in the Cu-mediated
arylselenylation of aryl iodide (Scheme 4). Dimethyl 2-
(phenyl(trifluoromethyl)-λ4-selanylidene)malonate (1a) reacted
with 2a and CuOAc under the standard conditions to give 3a in 67%
yield. Analogously, reactions of 2-(4-tolyl(trifluoromethyl)-λ4-
selanylidene)malonate (1c), 2-((4-methoxyphenyl)(trifluoromethyl)-
O2N
Se
CF3
CuOAc (2 equiv)
DMSO, 100 oC, 20 h
h)
Se
+
2a
O2N
Ph
radical trap
MeO2C
CO2Me
3b
1b
(2 equiv)
3b
3b
1) 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) 97% (
)
)
radical trap:
2) 1,1-diphenylethylene
3) N,N-diallyl-4-methylbenzenesulfonamide
99% (
>99% (
3b
)
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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ARTICLE
Journal Name
combined suggested that the •CF3 radicals might be generated in
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Scheme 6. A proposed reaction mechanism for Cu-mediated the arylselenylation reactions.14
arylselenylation of aryl halides with trifluoromethyl aryl selenonium
DOI: 10.1039/C9OB01506J
On the basis of the above results and previous reports,8a,15
a
plausible reaction mechanism was suggested for the copper-
mediated arylselenylation of aryl halides with trifluoromethyl aryl
selenonium ylides (Scheme 6). First, trifluoromethyl aryl
selenonium ylide is reduced by copper via single electron transfer to
form a radical intermediate (I). Intermediate I is highly reactive and
rapidly decomposes to release a •CF3 radical and an anion
intermediate (II). Then, II undergoes α-elimination to produce an
Ar1Se‒ anion, which combines with copper(I) salt by ligand exchange
to generate Ar1SeCu complex (III) and release tetramethyl ethene-
1,1,2,2-tetracarboxylate (7) (path a). In addition, protonation of II
by residual moisture in the solvent is possible, which forms
dimethyl 2-(arylselanyl)malonate (IV) (path b). Reduction of IV by
copper yields (phenylselanyl)copper (III) and/or diaryl diselenide (V).
The latter species is likely further converted to III by copper salts
according to the control experiments (Scheme 5). Finally, Ar1SeCu
(III) reacts with aryl halide via oxidative addition to afford a Cu(III)
complex (VI), which undergoes reductive elimination to produce
diaryl selenide and regenerate Cu(I) species for the next catalytic
cycle. On the other hand, the •CF3 radical can be further reduced
via single electron transfer to form ‒CF3 anion, which bonds to Cu(I)
to yield CuCF3 as a reactive intermediate. Coupling of CuCF3 with
aryl halide via oxidative addition and reductive elimination supplies
the trifluoromethylated product. Since only trace amounts of ArCF3
were detected in the reactions, the trifluoromethylation pathway
might proceed very slowly and not be the main process under the
standard conditions. Besides, the formation of a small amount of
Ar1SeCF3 and 7 in the standard reactions of 1 and aryl halides
implied the direct cleavage of the Ar1(CF3)Se‒C(CO2Me)2 bonds,
which was determined by 19F NMR analysis of the reaction mixture
(see SI) and isolation of the side product (7), respectively. This
pathway was believed to be harmful for both the arylselenylation
and trifluoromethylation reactions. Nonetheless, the exact reaction
mechanism is still unclear.
ylides (1)
Ar1
CF3
Se
Ar1
CF3
Ar1
CF3
CF3
+
7
+
other
CO2Me
CO2Me
Se
1
[Cu]
+ e
Se
I
1Se
Ar
MeO2C
CO2Me
MeO2C
CO2Me
II
byproducts
7
CO2Me
CO2Me
CO2Me
CO2Me
H2O
path b
[Cu]
1Se
1Se
Ar
II
1Se
Ar
Ar
Cu(I)
Cu(I)
path a
III
IV
II
[Cu]
[Cu]
1Se
V
(Ar
)
2
Ar2
I
Ar2X
O.A.
R.E.
1Se
Cu
1Se
Ar
2
1Se
Ar
Ar
Ar
Cu
III
fast
VI
Ar2
I
Ar2X
O.A.
R.E.
[Cu]
e
Cu(I)
CF3
CF3
CuCF3
Ar2 CF3
slow
F3C Cu
VII
To probe the possible reaction mechanism, several control
experiments were carried out (Scheme 5). When dimethyl 2-
(phenyl(trifluoromethyl)-λ4-selanylidene)malonate (1a) reacted
with CuOAc (1 equiv) in DMSO in the absence of 2a at 100 oC for 20
h, dimethyl 2-(phenylselanyl)malonate (4), 1,2-diphenyldiselane (5),
phenyl(trifluoromethyl)selane (6), and tetramethyl ethene-1,1,2,2-
tetracarboxylate (7) were formed in 7%, 39%, 38%, and 13% yield,
respectively (Scheme 5a). Further reaction of 4 or 5 (2 or 1 equiv)
with 2a and CuOAc (2 equiv) under the standard conditions
furnished the phenylselenylated product (3a) in 88% or 92% yield
(Scheme 5c and Scheme 5d) (vs 67% yield from 1a in Scheme 4). If 6
(2 equiv) was treated with 2a and CuOAc (2 equiv) under the same
conditions, no products were constructed (Scheme 5e). The results
indicated that compounds 4 and 5 other than 6 were the possible
reaction intermediates for the Cu-mediated arylselenylation of 2a
by 1a. Since 4 reacted with CuOAc (1 equiv) in DMSO in the absence
o
of 2a at 100 C for 20 h to give 5 in 54% yield (Scheme 5b), which
hinted at
Conclusions
a slow conversion, the major intermediate for
In summary, we have disclosed that trifluoromethyl aryl selenonium
ylides can be used as efficient arylselenylation reagents for aryl
halides in the copper-mediated reactions. The reaction proceeded
at 100-140 oC under ligand- and additive-free conditions and
showed good functional group tolerance. Consequently, a number
of unsymmetrical diaryl selenides were readily synthesized in good
to high yields. The control experiments showed that dimethyl 2-
(phenylselanyl)malonate (4) and 1,2-diphenyldiselane (5) might be
the reactive intermediates for the arylselenylation. This unexpected
reactivity of trifluoromethyl aryl selenonium ylides in comparison
with the analogous trifluoromethyl aryl sulfonium ylides indicated
interesting differences between these two types of ylides despite S
and Se being elements of the same main family.
arylselenylation of 2a by 1a under the standard conditions might be
compound 4 but not 5. Moreover, the competitive reaction of 2a
with 4 (2 equiv) and TMSCF3/CsF (2 equiv) in the presence of CuOAc
(2 equiv) provided 3a in 92% yield and 3a’ in 5% yield (Scheme 5f).
Similar treatment of 2a with 5 (1 equiv), TMSCF3/CsF (2 equiv), and
CuOAc (2 equiv) in one pot gave 3a in 97% yield and 3a’ in 2% yield
(Scheme 5g). These findings demonstrated again that the
arylselenylation was the predominant process in those copper-
mediated reactions. Furthermore, arylselenylation of 2a by
1b/CuOAc in the presence of 2,2,6,6-tetramethylpiperidine 1-oxyl
(TEMPO),
1,1-diphenylethylene,
and
N,N-diallyl-4-
methylbenzenesulfonamide under the standard conditions
produced 3b in 97% to >99% yield, implying that the radical traps
had no influence on the transformation (Scheme 5h). However, 19F
NMR analysis of the reaction mixtures showed that some CF3-
adducts were formed in the reactions using 1,1-diphenylethylene
and N,N-diallyl-4-methylbenzenesulfonamide (see SI). These results
Experimental
A general experimental procedure is described as follows:
4 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
Journal Name
ARTICLE
In a nitrogen-filled glovebox, a sealed tube was charged with aryl 5. Selected examples: (a) L. Wang, M. Wang, F. HuangV,iSewynAlretitctle2O0n0lin5e,
DOI: 10.1039/C9OB01506J
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Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
We thank the Wuhan University of Technology, the National
Natural Science Foundation of China (21602165), the “Chutian
Scholar” Program from Department of Education of Hubei Province,
and the “Hundred Talent” Program of Hubei Province for financial
support.
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