Palladium-Catalyzed Desilylative Acyloxylation of Silicon-Carbon Bonds on (Trimethylsilyl)arenes: Synthesis of Phenol Derivatives from Trimethylsilylarenes

Article abstract of DOI:10.1021/acs.orglett.5b02336

A strategy for desilylative acetoxylation of (trimethylsilyl)arenes has been developed in which (trimethylsilyl)arenes are converted into acetoxyarenes. The direct acetoxylation is performed in the presence of 5 mol % of Pd(OAc)₂ and PhI(OCOCF₃)₂ (1.5 equiv) in AcOH at 80°C for 17 h. The acetoxyarenes are obtained in good to high yields (67-98%). The synthetic utility is demonstrated with a one-pot transformation of (trimethylsilyl)arenes to phenols by successive acetoxylation and hydrolysis. Furthermore, desilylative acyloxylation of 2-(trimethylsilyl)naphthalene using several carboxylic acids has been conducted.

Full text of DOI:10.1021/acs.orglett.5b02336

Letter
pubs.acs.org/OrgLett
Palladium-Catalyzed Desilylative Acyloxylation of Silicon−Carbon
Bonds on (Trimethylsilyl)arenes: Synthesis of Phenol Derivatives
from Trimethylsilylarenes
Keisuke Gondo, Juzo Oyamada, and Tsugio Kitamura*
Department of Chemistry and Applied Chemistry, Graduate School of Science and Engineering, Saga University, Honjo-machi, Saga
840-8502, Japan
*
S Supporting Information
ABSTRACT: A strategy for desilylative acetoxylation of (trimethylsilyl)-
arenes has been developed in which (trimethylsilyl)arenes are converted
into acetoxyarenes. The direct acetoxylation is performed in the presence
of 5 mol % of Pd(OAc) and PhI(OCOCF ) (1.5 equiv) in AcOH at 80
2
3 2
°
9
C for 17 h. The acetoxyarenes are obtained in good to high yields (67−
8%). The synthetic utility is demonstrated with a one-pot transformation
of (trimethylsilyl)arenes to phenols by successive acetoxylation and
hydrolysis. Furthermore, desilylative acyloxylation of 2-(trimethylsilyl)-
naphthalene using several carboxylic acids has been conducted.
ilyl groups are important functional groups in organic
synthesis and widely used for protection of OH and NH
Catalytic activation of the C−Si bond of arylsilanes has been
S
widely studied in the cross-coupling reactions with aryl
derivatives affording biaryls, where such conversions take
place only in the cases of activated silyl groups such as
1
2
groups, the Peterson olefination, the Tamao−Fleming
3
4
oxidation, and the Hiyama coupling. Recently, the use of a
9
10
11
pentafluorosilicate, trialkoxysilyl, triallylsilyl, and aryl[2-
silyl group as a directing group in Pd-catalyzed C−H
12
5
hydroxymethyl]phenyldimethylsilanes. The cross-coupling of
functionalization reactions is reported where the silyl group
13
arenes with (trimethylsilyl)arenes is very limited. On the
other hand, the Pd-catalyzed acetoxylation of C−H bonds of
arenes has been recently studied as the synthesis of oxygenated
arenes. However, there are no examples that (trimethylsilyl)-
arenes are converted into the oxygenated arenes. Thus, we
started to explore a novel and direct transformation of
trimethylsilyl-substituted arenes into phenol derivatives and
can be removed by some reagents to introduce a new
functionality.
Among the above reactions, the Tamao−Fleming oxidation
14
is the most important reaction for converting organosilicon
3
compounds to alcohols, i.e., transformation of C−Si bonds to
C−O bonds. Various alcohols can be prepared using the
Tamao−Fleming oxidation. However, the silyl groups used for
the Tamao oxidation are limited to those where the silicon
atom has a heteroatom or hydrogen. Similarly, in the Fleming
oxidation the aryl group of arylsilanes is in situ converted to
hydrogen by protonolysis and then oxidized to alcohols.
Therefore, these oxidations have not been applied to the
oxidation of arylsilanes for the synthesis of phenols. Recently,
the Fleming oxidation was applied to the synthesis of phenol
derivatives, but this only occurred when strained siletanes were
succeeded in the transformation by using Pd(OAc) as a
2
catalyst and PhI(OCOCF ) as an oxidant. Here we wish to
3
2
report the palladium-catalyzed reaction transforming trimethyl-
silyl group into acyloxy groups as the first example.
First, we chose 1-fluoro-4-(trimethylsilyl)benzene (1a) as a
model substrate, which is suitable for monitoring the reaction
19
by F NMR. Before optimizing the reaction conditions for the
Pd(OAc) -catalyzed acetoxylation of 1a, we examined several
2
solvents using PhI(OAc) as an oxidant, since PhI(OAc) has
2
2
6
used. In addition, the conversion of arylsilanes to phenols has
been recently received much attention as an excellent, terminal
7
15
been reported, but the silyl groups necessarily contain
oxidant in the Pd-catalyzed reactions. We found that AcOH
heteroatoms or hydrogen. The outline concerning the
Tamao−Fleming oxidation (a) and phenol synthesis from
arylsilanes (b and c) is shown in Scheme 1.
Although the trimethylsilyl group is a readily available and8
popular functional group and widely used in organic synthesis,
it has not been applied to such oxidations giving phenols due to
the stability of trimethylsilyl group. Therefore, direct trans-
formation of an easily available trimethylsilyl group into the
corresponding C−O bond is an important reaction in organic
synthesis and is still challenging (Scheme 1, d).
was the best solvent giving the product, 4-fluorophenyl acetate
(2a), in 32% yield (Scheme 2). Product 2a was not formed in
other solvents such as DMF, MeCN, DCE, THF, and DME.
Addition of Ac O in AcOH decreased product 2a to 16%. The
2
details are given in the Supporting Information.
As we obtained 2a in 32% yield in the reaction with
PhI(OAc) as an oxidant in AcOH, we next examined the
2
Received: August 11, 2015
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02336
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 1. C−O Bond Formation from Arylsilanes
Table 1. Acetoxylation of 1a by Pd-Catalyzed Reaction
b
entry
hypervalent iodine reagent
temp (°C)
yield (%)
1
2
3
4
5
6
7
8
9
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
80
100
120
100
100
80
32
67
81
c
PhI(OAc)2
69
d
PhI(OAc)2
78
PhI(OH)OTs
PhIO
24
80
33
PhI(OCOCF3)2
80
80
c
PhI(OCOCF3)2
80
>99
>99
91
c
,
,
e
f
1
1
1
0
1
2
PhI(OCOCF3)2
PhI(OCOCF3)2
3
80
c
80
80
>99
a
Conditions: 1a (0.2 mmol), hypervalent iodine reagent (0.2 mmol),
b
Pd(OAc) (0.02 mmol), solvent (1 mL), 80 °C, and 17 h. Yield was
determined by F NMR using hexafluorobenzene as an internal
standard. A hypervalent iodine reagent (0.3 mmol) was added.
hypervalent iodine reagent (0.4 mmol) was added. Pd(OAc) (5 mol
2
19
c
d
A
e
2
f
%
) was used. Pd(OAc) (1 mol %) was used.
2
a
Table 2. Acetoxylation of 1 by Pd-Catalyzed Reaction
Scheme 2. Desilylative Acetoxylation of 1a Using PhI(OAc)2
reaction temperature. The results are given in Table 1. When
the reaction was conducted at 100 °C, the yield of 2a was
increased to 67% (entry 2). Furthermore, the yield was reached
to 81% by elevating the temperature to 120 °C (entry 3). The
amount of PhI(OAc) was increased in the reaction at 100 °C,
2
but the yield of 2a was not improved (entries 4 and 5). Other
hypervalent iodine reagents such as Koser’s salt, PhI(OH)OTs,
and PhIO were tested for this acetoxylation at 80 °C, but we
found that these reagents were not effective (entries 6 and 7).
Surprisingly, the use of bis(trifluoroacetoxy)iodobenzene PhI-
(
OCOCF ) much improved the yield of 2a under the mild
3 2
conditions (80 °C), giving 2a in 80% yield (entry 8). The
increase of the amount of PhI(OCOCF ) provided 2a in a
3
2
quantitative yield (entry 9). Even in the cases of less loading
Pd(OAc) catalyst (5 and 1 mol %), product 2a was formed in
2
high yields (entries 10 and 11). Similarly, μ-oxo-bridged
reagent, μ-oxodiphenylbis(trifluoroacetato-O)diiodine [[PhI-
a
(
OCOCF )] O] (3), played an excellent role and gave 2a in
Conditions: 1 (0.4 mmol), PhI(OCOCF
) (0.6 mmol), Pd(OAc)
3 2 2
b
3
2
(0.02 mmol), AcOH (1 mL), 80 °C, and 17 h. Isolated yield from
a quantitative yield (entry 12). Among the hypervalent
column chromatography on silica gel.
oxidants, we adopted PhI(OCOCF ) as the terminal oxidant
3
2
because it was easily available.
With the optimized conditions in hand, we examined a
variety of (trimethylsilyl)arenes to determine the scope of this
acetoxylation reaction. The results are given in Table 2. Various
the para position underwent the desilylative acetoxylation
reaction to give the corresponding p-acetoxyarenes 2 in high
yields (88−98%). It is noteworthy that iodo and bromo
substituents are inert under the optimized conditions.
(
trimethylsilyl)arenes 1 bearing alkyl groups and halogens at
B
DOI: 10.1021/acs.orglett.5b02336
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Trimethylsilyl)arene 1h with an electron-withdrawing ethox-
Letter
(
Table 3. Desilylative Acyloxylation of 1i with Various
a
ycarbonyl group showed less reactivity but gave p-acetoxyarene
Carboxylic Acids
2
h in 91% yield when the reaction was conducted at 100 °C.
This desilylative acetoxylation could be applied to naphthalene
and biphenyl derivatives 1i and 1j, affording 2i and 2j in 92 and
9
4% yields, respectively. However, this desilylative acetoxyla-
tion could not be applied to strongly electron-rich 1-methoxy-
-(trimethylsilyl)benzene and 1-(dimethylamino)-4-
trimethylsilyl)benzene. The desilylative acetoxylation reaction
efficiently proceeded in the cases of meta-substituted
trimethylsilyl)arenes. (Trimethylsilyl)arenes 1 bearing methyl,
4
(
(
bromo, and chloro substituents at the meta position were
converted into the corresponding m-acetoxyarenes 2 in high
yields (86−90%). However, the presence of substituents (Ph,
Cl, and F) at the ortho position inhibited the desilylative
acetoxylation reaction completely. Furthermore, we examined
synthesis of acetoxyarenes with trimethylsilyl group as a
sensitive functional group since trimethylsilyl group can be
transformed to various useful functional groups. Bis-
a
Conditions: 1i (0.4 mmol), PhI(OCOCF ) (0.6 mmol), Pd(OAc)
2
3
2
b
(
trimethylsilyl)arenes (1n and 1o) were used for the
(0.02 mmol), RCOOH (1 mL), 80 °C, and 17 h. Isolated yield from
column chromatography on silica gel. PhCOOH (0.5 g) and DCE
c
desilylative acetoxylation reaction. Only one of two trimethyl-
silyl groups was converted into acetoxy group to give
acetoxyarenes 2n and 2o in 67 and 85% yields, respectively.
In order to examine the synthetic usefulness of acetoxylated
products 2, we tried to convert (trimethylsilyl)arenes 1 into
phenols 3 directly. Since the acetoxy group of 2 is removed by
hydrolysis, the acetoxylated products obtained in situ under the
optimized conditions was refluxed in water after addition of
water. Actually, phenols 3a and 3b were obtained in 90 and
(0.5 mL) were used instead of RCOOH.
Scheme 4. Possible Mechanism for Desilylative
Acetoxylation of (Trimethylsilyl)arenes
92% yields, respectively, by the one-pot reactions (Scheme 3).
Scheme 3. One-Pot Transformation of Trimethylsilylarenes
1
to Phenols 3
15
ylation of C−H bonds of arenes with PhI(OAc) . According
2
to this mechanism, a (trimethylsilyl)arene is considered to
undergo the C−Si bond cleavage by Pd(OAc) to give an
2
ArPd(II)OAc intermediate, which is oxidized by PhI-
(
OCOCF ) to a ArPd(IV) intermediate. However, the Pd-
3 2
catalyzed reaction of 1a without PhI(OCOCF ) in AcOH did
3
2
Furthermore, we explored the possibility for transformation
not proceed and 1a was recovered unchanged. In addition, the
reaction of 1a with styrene or tert-butyl acrylate in the presence
of (trimethylsilyl)arenes 1 using other carboxylic acids. We
examined the reaction of 2-(trimethylsilyl)naphthalene (1i) as a
model substrate with various carboxylic acids under the
optimized conditions. The results are given in Table 3.
Propanoic acid, pentanoic acid, 2-methylpropanoic acid,
cyclohexanecarboxylic acid, cyclopropanecarboxylic acid, and
benzoic acid underwent the desilylative acyloxylation of 1i to
give the corresponding 2-acyloxynaphthalenes 4 in good to
high yields. In the case of a sterically hindered pivalic acid, the
desilylative acyloxylation reaction did not proceed.
of Pd(OAc) (5 mol % or 1 equiv) was conducted at 80 °C for
2
17 h in AcOH, but no coupling products were formed. These
results suggest that the reaction of 1a with Pd(OAc) does not
2
occur. Although the reaction mechanism for the desilylative
acetoxylation is not clear at present, the ArPd(IV) species may
be formed by oxidation of Pd(OAc) with PhI(OCOCF )
2
3 2
followed by electrophilic substitution of ArSiMe . Recently, it
3
has been reported that the Pd-catalyzed acetoxylation of
14i
pyrroles proceeds via phenyliodonium acetates. Although we
The desilylative acetoxylation of a (trimethylsilyl)arene 1
conducted the reaction of 1a with PhI(OAc)2 or PhI-
using Pd(OAc) as a catalyst and PhI(OCOCF ) as a terminal
(OCOCF ) in AcOH, we could not obtain diphenyliodonium
2
3 2
3 2
oxidant may be considered to proceed via Pd-induced C−Si
bond activation generating an arylpalladium(IV) intermediate
followed by reductive elimination, as shown in Scheme 4. This
kind of mechanism involving a high oxidation state Pd(IV)
salts in the reaction at 80 °C. In the present case, therefore, the
possibility of the acetoxylation via phenyliodonium salts is ruled
out.
In summary, we have demonstrated that desilylative
acetoxylation of (trimethylsilyl)arenes proceeds efficiently in
species has been proposed for Pd(OAc) -catalyzed acetox-
2
C
DOI: 10.1021/acs.orglett.5b02336
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
the presence of Pd(OAc) (5 mol %) and PhI(OCOCF ) in
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AcOH at 80 °C. Various substituted (trimethylsilyl)arenes
undergo the desilylative acetoxylation to give the corresponding
acetoxyarenes in high yields. This acetoxylation is applied to
one-pot synthesis of phenols from (trimethylsilyl)arenes.
Furthermore, the possibility for acyloxylation using several
carboxylic acids has been demonstrated. The use of “non-
activated” (trimethylsilyl)arenes for acetoxylation or acylox-
ylation provides a practical and efficient synthesis of phenol
derivatives. Therefore, further studies concerning the applica-
tion and the mechanistic elucidation are future subjects.
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ASSOCIATED CONTENT
Supporting Information
■
*
S
(15) (a) Yoneyama, T.; Crabtree, R. H. J. Mol. Catal. A: Chem. 1996,
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.5b02336.
108, 35−40. (b) Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem.
Soc. 2004, 126, 2300−2301. (c) Dick, A. R.; Kampf, J. W.; Sanford, M.
S. J. Am. Chem. Soc. 2005, 127, 12790−12791. (d) Racowski, J. M.;
Dick, A. R.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 10974−10983.
Additional data and NMR spectra of the products (PDF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: kitamura@cc.saga-u.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was partly supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology of Japan (25410048).
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