Selective aromatic carbon-oxygen bond cleavage of trifluoromethoxyarenes: a trifluoromethoxy group as a convertible directing group

Article abstract of DOI:10.1016/j.tetlet.2008.08.002

An efficient method for selective activation of aromatic C-O bonds in trifluoromethoxyarenes is developed. Upon treatment with a metallic sodium/chlorotrimethylsilane system, trifluoromethoxyarenes undergo reductive dealkoxylation to provide the corresponding arylsilanes. Also the synthetic applications of the present reactions combined with ortho-metallation are described.

Full text of DOI:10.1016/j.tetlet.2008.08.002

Tetrahedron Letters 49 (2008) 6013–6015
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Selective aromatic carbon–oxygen bond cleavage of trifluoromethoxyarenes:
a trifluoromethoxy group as a convertible directing group
*
Akinori Iijima, Hideki Amii
Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe 657-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient method for selective activation of aromatic C–O bonds in trifluoromethoxyarenes is devel-
oped. Upon treatment with a metallic sodium/chlorotrimethylsilane system, trifluoromethoxyarenes
undergo reductive dealkoxylation to provide the corresponding arylsilanes. Also the synthetic applica-
tions of the present reactions combined with ortho-metallation are described.
Ó 2008 Published by Elsevier Ltd.
Received 11 June 2008
Revised 24 July 2008
Accepted 1 August 2008
Available online 7 August 2008
Selective activation of carbon–oxygen bonds has received
increasing attention because of its fundamental scientific interest
and its potential utility in organic synthesis.1 Generally, the cleav-
age of aryl C–O bonds in aryl ethers is not easy due to their large
bond energies (ca. 420 kJ/mol).2 However, several late transition
metal complexes were found to be effective to activate aryl C–O
bonds,3 and recently anisole derivatives have been utilized for
C–C bond formation as a cross-coupling partner.4 Besides transi-
tion metal catalyses, reductive breakage of C–O bonds in aryl
ethers has been widely investigated so far.
leads to phenols 2,5 whereas that of aryl–oxygen bonds (b) delivers
aromatic hydrocarbons 3.6 In these reductive transformations, the
fates of anisoles 1 (dealkylation or dealkoxylation) are dictated by
reaction conditions such as solvents and low-valent metals.7
Among alkoxy functionalities, a trifluoromethoxy substituent is
spotlighted in the fields of medicinal, agricultural, and material sci-
ences.8 Introducing a trifluoromethoxy group into organic mole-
cules holds
a considerable promise for the fine-tuning of
technical and biological properties. Trifluoromethoxyarenes 4 are
per se stable compounds whose Ar–OCF3 bonds are generally unre-
active. However, to the best of our knowledge, there exists one
report on electrochemical behaviors of aryl C–O bonds in
trifluoromethoxyarenes under reductive conditions.9 From the
viewpoint of synthetic organic chemistry, herein we report new
useful transformations of trifluoromethoxyarenes 4 by virtue of
their aryl carbon–oxygen bonds (Scheme 2).
Anisole derivatives 1 possess two kinds of C–O bonds (a and b)
possibly susceptible to fission (Scheme 1). Alkali metal-induced
reactions of 1 afford the different products, depending on which
bonds are cleaved; the breakage of the alkyl–oxygen bonds (a)
First, we examined a variety of low-valent metals to evaluate
their ability on C–O bond fission of trifluoromethoxybenzene.
Metallic lithium, magnesium, and zinc were totally inactive due
to their low reduction potentials. However, when trifluorometh-
oxybenzene (4a) was treated with metallic sodium and chlorotri-
methylsilane in THF at 80 °C, the reductive dealkoxy-silylation
reaction proceeded smoothly to give phenyltrimethylsilane (5a)
in 92% NMR yield (Table 1, entry 1).10 In the present reaction, the
cleavage of the aryl C–O bond in 4a occurred predominantly over
that of the CF3–O bond; the formation of phenol (the dealkylated
product) was not detected.
R
HO
H
(a)
(b)
(a) (b)
R
R
2
Me
O
R
1
3
CF3
O
OCF3
SiMe3
4
Na
Me3Si_Cl
R
R
THF
Scheme 1.
C–O Bond Activation
5
4
* Corresponding author. Tel./fax: +81 78 803 5799.
E-mail address: amii@kobe-u.ac.jp (H. Amii).
Scheme 2.
0040-4039/$ - see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2008.08.002

6014
A. Iijima, H. Amii / Tetrahedron Letters 49 (2008) 6013–6015
Table 1
Table 2
Sodium-promoted dealkoxy-silylation of trifluoromethylarenes 4a–d
Dealkoxy-silylation of ortho-substituted trifluoromethylarenes 4e–h
Na (4 eq)
Me3SiCl (5 eq)
OCF3
OCF3
R
R
OCF3
R
SiMe3
THF
80 ºC, 24 h
4e_h
4a
4a_d
5a_d
Na (4 eq)
Entry
R
Product
Yielda (%)
SiMe3
R
Me3Si_Cl (10 eq)
1
2
3
4
H
MeO
Ph
t-Bu
5a
5b
5c
5d
76 (92)b
59 (67)
30 (38)c
64 (71)
THF
80 ºC, 24 h
5e_h
a
Isolated yields.
Entry
R
Product
Yielda (%)
b
The numbers in parentheses are NMR yields calculated by 1H NMR integration
1
2
3
4
Me
Ph
5e
5f
5g
5h
84 (91)b
72 (85)
82 (92)
91
of products 5 relative to trioxane internal standard.
c
35% of biphenyl was obtained as a by-product.
CH2–CH@CH2
Bn
The reactions of para-substituted trifluoromethoxyarenes 4b–d
also afforded the corresponding arylsilanes 5b–d in moderate
yields (Table 1, entries 2–4). In each case, C–O bond cleavage took
place in a chemoselective manner; it is noteworthy that the meth-
oxy grouping (OMe) in 4b was compatible with the present reduc-
tion system (entry 2). This chemoselectivity would be attributed to
the poorer leaving group ability of a methoxy group compared
with that of a trifluoromethoxy group which bears electron-with-
drawing fluorine atoms. In entry 3, the aromatic C–O bond break-
age of 4-trifluoromethoxybiphenyl (4c) with sodium afforded the
desired arylsilane 5c in 30% isolated yield, accompanied by biphen-
yl (Ph-Ph) in 35% yield.
The reductive cleavage of C–O bonds in 4 using metallic sodium
can be explained by assuming the pathway. Initially, one-electron
transfer to Ar–OCF3 (4) gives the radical anion intermediates,
which participate in decomposition to aryl radicals with release
of a CF3O anion.11 Next, further one-electron reduction of the rad-
ical intermediates (ArÅ) provides the aryl anion species (Ar–), which
are trapped by Me3SiCl leading to the corresponding arylsilanes
5.12
Thus, sodium-promoted selective C–O bond activation of trifluo-
romethoxyarenes 4 supplies a route to arylsilanes 5. Next, we
show new reaction sequences involving the dealkoxy-silylation
of trifluoromethoxyarenes 4, in which the trifluoromethoxy sub-
stituents fulfill a dual role in imparting both an ortho-directing
group and a leaving group (Scheme 3).
An alkoxy group attached to an aryl ring acts as a neighboring
group which controls ortho-selective metallation and the subse-
quent electrophilic substitution of the aromatic ring.13 In 2001,
Castagnetti and Schlosser reported the neighboring group-assisted
hydrogen/metal permutation of trifluoromethoxybenzene (4a) by
the action of sec-butyllithium.14 Using the Schlosser’s method-
ology, diverse substituents were introduced into 2-position of 4a
a
Isolated yields from 4e–h.
b
The numbers in parentheses are NMR yields calculated by 1H NMR integration
of products 5 relative to trioxane internal standard.
to furnish 4e–h. Then, ortho-substituted trifluoromethoxyarenes
4e–h were subjected to sodium-promoted reductive C–O bond
cleavage (Table 2). By the use of 10 equiv of Me3SiCl, alkoxy-silyla-
tion reactions of 4e–h proceeded cleanly to give the corresponding
ortho-substituted arylsilanes 5e–h in high yields. In the case of
substrate 4g, possessing an alkene moiety, neither intra- nor inter-
molecular addition of the intermediate radical species with the
C–C double bond moiety,15 selective formation of allylic product
5g was accomplished in an isolated yield of 82% (entry 3).
In conclusion, we have demonstrated the useful transformation
of trifluoromethoxyarenes 4 in which trifluoromethoxy groups are
able to function as convertible directing groups.16–18 Trifluoro-
methoxyarenes 4 are readily prepared from the corresponding
phenols.19 Compared to sulfonate groupings, trifluoromethoxy
moieties in arenes 4 partake in selective ortho-metallation without
side reactions such as benzyne formation20 or anionic thia-Fries
rearrangement.21 The present procedure for dealkoxy-silylation is
simple, and metallic sodium as a reducing agent is inexpensive.
And the resultant arylsilanes 5 are general and versatile building
blocks for nucleophilic introduction of aryl groups.22,23 Thus, inge-
nuity to leverage the nature of aromatic C–O bond would ensure to
achieve highly regioselective synthesis of polysubstituted
aromatics.
Acknowledgments
The financial support of the Ministry of Education, Culture,
Sports, Science and Technology of Japan (Grant-in-Aid for Scientific
Research (B), No. 18350054 and Grant-in-Aid for Scientific
Research on Priority Areas ‘Chemistry of Concerto Catalysis’, No.
20037050) is gratefully acknowledged. We would like to thank
Professor Masahiko Hayashi (Kobe University) for his useful
suggestions.
ortho_Directing Group
Leaving Group
OCF3
ortho-Metallation
OCF3
R
R
E1
Supplementary data
4
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.08.002.
E2
E1
SiMe3
R
R
E1
Dealkoxy
-Silylation
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A
typical procedure: synthesis and characterization of (o-allylphenyl)-
trimethylsilane (5g). To a mixture of chlorotrimethylsilane (0.103 g, 10 mmol)
in anhydrous THF (2.0 mL) and Na (92 mg, 4.0 mmol) stirring under argon
atmosphere was added 4 g (202 mg, 1.0 mmol) dropwise. The reaction mixture
was stirred at 80 °C for 24 h and quenched carefully with methanol and then
water. The aqueous layer was extracted with ether and the combined organic
phase was dried over MgSO4. Evaporation of solvents and Kugelrohr distillation
afforded 5g as a colorless oil (156 mg, 82%): bp 102 °C (10 mmHg); 1H NMR
(CDCl3, 400 MHz) d 7.48 (d, 1H, J = 7.2 Hz), 7.32 (t, 1H, J = 7.6 Hz), 7.22–7.18
(m, 2H), 5.78 (ddt, 1H, J = 17.2, 10.4, 6.4 Hz), 5.08 (dd, 1H, J = 10.4, 2.0 Hz), 7.48
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