Desilylative carboxylation of aryltrimethylsilanes using CO2 in the presence of catalytic phosphazenium salt

Article abstract of DOI:10.1246/cl.131108

An efficient method for the desilylative carboxylation of aryltrimethylsilanes with CO₂ catalyzed by phosphazenium salt has been developed. This protocol can provide various arylcarboxylic acids that are important structural motifs in biologically active chemical compounds.

Full text of DOI:10.1246/cl.131108

Received: November 27, 2013 | Accepted: December 14, 2013 | Web Released: December 21, 2013
CL-131108
Desilylative Carboxylation of Aryltrimethylsilanes Using CO2
in the Presence of Catalytic Phosphazenium Salt
Misato Yonemoto-Kobayashi, Kiyofumi Inamoto, and Yoshinori Kondo*
Graduate School of Pharmaceutical Sciences, Tohoku University,
6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578
(
E-mail: ykondo@m.tohoku.ac.jp)
Table 1. Carboxylation of 2-trimethylsilylthiophene with CO2a
An efficient method for the desilylative carboxylation of
aryltrimethylsilanes with CO2 catalyzed by phosphazenium
salt has been developed. This protocol can provide various
arylcarboxylic acids that are important structural motifs in
biologically active chemical compounds.
Onium salt (X mol%)
Base (2 equiv)
S
S
1 atm CO (closed)
2
SiMe3
COOH
2a
solvent, 100 °C, 24 h
1a
Onium salt
X mol %)
Base
(2 equiv)
Entry
Solvent
Yield/%b
Synthetic application in the construction of the C­C bond
involving fixations of carbon dioxide into useful molecules has
been widely developed in recent years because CO2 is an
environmentally friendly, nontoxic, nonflammable, and abun-
(
1
2
3
4
5
6
7
8
9
none
P5Cl (10)
TBABr (10) CsF
TMABr (10) CsF
PPh4Cl (10)
CsF
CsF
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
dioxane
trace
(89)
58
5
0
0
23
63
34
48
60
60
46
52
1
dant resource.
Arylcarboxylic acids are important structural motifs in the
research and development of fine chemicals, including bio-
CsF
2
PPh4Br (10) CsF
TMAF (110) none
logically active molecules. For instance, numerous chemical
compounds that are widely used for medical treatment contain
carboxylic acid motif, such as anti-inflammatory drugs. It has
been well known that the most straightforward and well-studied
approaches for the syntheses of arylcarboxylic acids are the
P5Cl (10)
P5Cl (10)
P5Cl (10)
P5Cl (10)
P5Cl (10)
P5Cl (10)
P5Cl (10)
KF
t-BuOK
CsF
CsF
CsF
1
0
3­10
11
cyclohexane
toluene
DMF
fixation of carbon dioxide into certain carbon nucleophiles.
1
2
In this context, highly reactive organometallic reagents such as
organolithium and Grignard reagents have been employed for
the nucleophilic addition to CO2 as low-cost syntheses of
arylcarboxylic acids; however, these methods are not compatible
with various electrophilic functional groups. As an alternative
13
14
CsF
CsF
DMSO
a
b
Reaction was carried out on a 0.1 mmol scale. Yields were
1
determined by H NMR. Isolated yields is in parentheses.
approach for functional-group compatibility, less nucleophilic
organozinc3 and organoboron4 reagents were successfully
NMe2
Me N
P
N
NMe2 Cl
NMe2
2
employed for the carboxylation reaction catalyzed by transi-
tion-metal or by transition-metal-free processes. The carbo-
NMe2
Me
N
Me N
P
N
P
N
P
N
P
NMe2 Me
Me
X
N
2
xylation of aryl halides with CO is also accomplished in the
2
NMe2
NMe2
Me
5
Br
presence of suitable transition-metal catalysts. Direct carbo-
Me N
NMe2
2
xylation of activated C­H bond using CO2 coupling reactions
NMe2
6
TMAF (X = F)
was reported by the transition-metal-catalyzed process, base-
P5Cl
TBABr
7
TMABr (X = Br)
mediated deprotonative addition, or the Friedel­Crafts-type
8
carboxylation. In addition to these methods, carboxylation of
arylsilanes is considered to be attractive because of their low
toxicity, chemical stability, and ease of handling. In 1985,
Effenberger and co-workers demonstrated KF-mediated carbo-
our recent work on the investigation of CO2-fixation reactions,12
we report here the development of phosphazenium-salt-cata-
lyzed carboxylation of aryltrimethylsilanes in the presence of
CsF, providing arylcarboxylic acids with the atmospheric
9
xylation of aryltrimethylsilanes using HMPA as a solvent.
However, the substrate of this reaction was limited to o-Cl and
o-NO2 phenyltrimethylsilane, and the reaction required rela-
tively high pressure of CO2 (5 MPa). As another type of
carboxylation of arylsilanes, Hattori et al. disclosed that the
utilization of trihaloaluminum was effective for the electrophilic
carboxylation of aryltrimethylisilanes with CO2.10 To smoothly
perform this Lewis acidic system, it is also necessary to carry out
the reaction under high pressure (3 MPa).
1
3
pressure of carbon dioxide.
We started our investigation with an examination of
carboxylation of 2-trimethylsilylthiophene (1a) with CO2
(1 atm) at 100 °C in a closed system (sealed tube) (Table 1).
12a
Unlike the CO2 fixation into alkynylsilanes, the use of CsF
1
4
afforded only trace amounts of carboxylated product (Entry 1).
To our surprise, the combination of 10 mol % phosphazenium
chloride (P5Cl) and 2 equivalents of CsF in o-xylene dramat-
ically increased the reactivity to afford 2-thiophenecarboxylic
We have recently focused our interest on the potential
applicability of organic onium salt for the catalytic in situ
generation of highly reactive nucleophiles.11 In connection with
15
acid (2a) in 89% yield (Entry 2). The use of 10 mol % of other
Chem. Lett. 2014, 43, 477–479 | doi:10.1246/cl.131108
© 2014 The Chemical Society of Japan | 477

Table 2. Carboxylation of aryltrimethylsilanes with CO a
2
P5Cl
CsF
Ar
Me
Me
P5 CO2
P5Cl (10 mol%), CsF (2 equiv)
SiMe3
COOH
Ar SiMe3
Me Si
Ar COO P5
1 atm CO (closed)
2
CsCl
B
Ar
Ar
SiMe3F
1
F
A
o-xylene
CsF
P5F
1b-i
Conditions
2b-i
Products
ArCOOCs
H+
ArSiMe3
COOH
COOH
COOH
ArCOOH
F
Cl
CF3
2
2
b, 53%
2c, 48%
(150°C, 24h)
2d, 51%
(150°C, 24h)
(
150°C, 24h)
Scheme 1. Plausible mechanism of the phosphazenium-salt-
catalyzed carboxylation of aryltrimethylsilane with CO2.
COOH
COOH
F3C
organic onium salts such as TBABr showed less reactivity
compared to P5Cl; other salts such as TMABr did not activate
the reaction (Entries 3 and 4) and phosphonium catalyst did not
afford the desired product (Entries 5 and 6). On the other hand,
when the reaction was carried out with 110 mol % of TMAF in
the absence of CsF, the product was obtained in 23% yield
showing some activity (Entry 7). Compared to KF or t-BuOK,
the use of CsF showed better performance for the desilylative
carboxylation reaction (Entries 2, 8, and 9). The screening of
solvents revealed that o-xylene is the best solvent for this
carboxylation reaction (Entries 2 and 10­14).
A plausible mechanism for the carboxylation promoted by
phosphazenium catalyst is shown in Scheme 1. Initially, highly
reactive silicate A forms by P5Cl and CsF, which attacks CO2 to
generate phosphazenium carboxylate intermediate B. The sub-
sequent reaction of B with CsF affords cesium carboxylate and
the P5F catalyst; the former then afford carboxylic acid 2 by the
workup with acid. We considered that the phosphazenium cation
may play an important role in acceleration of desilylation as well
as addition to carbon dioxide.16
2
e, 53%
2f, 30%
b
(150°C, 24h)b
(
150°C, 24h)
O
COOH
COOH
allyl
O
N
2
g, 64%
(150°C, 24h)
2h, 66%
(150°C, 24h)b
2i, 36%
(100°C, 24h)c
a
Reaction was carried out on a 0.1 mmol scale. bCsF (3.0
equiv) was used. Allyl bromide (12 equiv) was used as a
quenching agent.
c
P5Cl (10 mol%), CsF (3 equiv)
Si
COOH
1
atm CO2 (closed)
o-xylene, 150 °C, 24 h
1
f
2f
Si=
SiMe3
31%
Si(OEt)3 0%
SiCl3 0%
Under the optimized reaction conditions employed for
Entry 2 in Table 1, we examined the desilylative carboxylation
of various aryltrimethylsilanes (Table 2).17 Although higher
Scheme 2. Substituent effect on the silyl group of phenyl-
silane.
temperatures varying from 100 to 150 °C were required, it
was found that the carboxylation reactions proceed using the
combination of CsF and catalytic amount of P5Cl. Arylsilanes
with halogen such as o-F and p-Cl were first examined to afford
the corresponding carboxylic acids 2b and 2c in moderate yield.
P5Cl (10 mol%)
CsF (2 equiv)
1 atm CO2 (closed)
o-xylene
O
SiMe3
Cl
COOH
Cl
The reaction of phenyltrimethylsilane bearing CF on the o- and
O
3
1
50 °C, 24 h
1
j
2j, trace
3, 40%
p-positions afforded the desired products 2d and 2e in 51% and
5
3% yields. Unsubstituted phenyltrimethylsilane was also
Scheme 3. Reaction of o-chlorophenyltrimethylsilane with
CO2.
reacted with CO , affording benzoic acid (2f) in 30% yield.
2
The use of 1- and 2-naphthyltrimethylsilanes (1g and 1h)
proceeded smoothly to generate 2g or 2h as a single regioisomer,
respectively. The reaction of 2-(trimethylsilyl)pyridine (1i)
afforded allyl ester 2i using allyl bromide as a quenching agent.
We further investigated the influence of the silyl substituent
on phenylsilane 1f (Scheme 2). Arylsilanes that have Si(OEt)3 or
synthesis through the reaction of o-halobenzoic acids with
1
9
benzyne precursor. Based on the mechanism proposed on the
1
9a
literature, the reaction pathway was assumed (Scheme 4). The
carboxylate intermediate B formed by the carboxylation of 1j
SiCl on the aromatic ring decomposed under the carboxylation
with CO can react with benzyne A, which is also generated
3
2
condition and did not afford the desired benzoic acid 2f. This is
in sharp contrast to the fact that trialkoxysilanes have been
widely used for the Hiyama cross-coupling reaction.18
Interestingly, in the reaction of o-chlorophenyltrimethyl-
silane (1j) with CO2 under the reaction conditions, unexpected
xanthone (3) was isolated as a major product (Scheme 3).
Larock and co-workers have developed a novel xanthone
from 1j through fluoride activation. The aryl anion C undergoes
intramolecular addition to carbonyl and the rearrangement
produces phenoxide D. Finally, xanthone (3) could arise from
an intramolecular nucleophilic aromatic substitution of phenox-
ide D. This protocol could provide a facile one-pot synthesis
of xanthone, which shows a wide variety of pharmacological
2
0
activities.
478 | Chem. Lett. 2014, 43, 477–479 | doi:10.1246/cl.131108
© 2014 The Chemical Society of Japan

Benzyne formation
cat. P5Cl
5
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1
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9
1
1
This work was partly supported by a Grant-in-Aid for
Scientific Research (B) (No. 23390002), a Grant-in-Aid for
Challenging Exploratory Research (No. 23659001), and a
Grant-in-Aid for Young Scientists (B) (No. 23790002) from
Japan Society for the Promotion of Science, and a Grant-in-Aid
for Scientific Research on Innovative Areas “Advanced Mo-
lecular Transformations by Organocatalysis” (No. 23105009)
from The Ministry of Education, Culture, Sports, Science, and
Technology, Japan.
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2
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Chem. Lett. 2014, 43, 477–479 | doi:10.1246/cl.131108
© 2014 The Chemical Society of Japan | 479