Rhodium-catalyzed cleavage reaction of aryl methyl ethers with thioesters

Article abstract of DOI:10.1021/ol2033724

A rhodium complex catalyzed the reaction of aryl methyl ethers and thioesters giving the corresponding aryl esters and methyl sulfides. S-(p-Chlorophenyl) p-(dimethylamino)benzothioate was used for the reaction of methyl aryl ethers with electron-withdrawing groups, and an S-(p-tolyl) derivative was used for those with electron-donating groups. Polymethoxybenzenes were converted to the esters in a regioselective manner.

Full text of DOI:10.1021/ol2033724

ORGANIC
LETTERS
2012
Vol. 14, No. 3
855–857
Rhodium-Catalyzed Cleavage Reaction of
Aryl Methyl Ethers with Thioesters
Mieko Arisawa,* Yuri Nihei, Takaaki Suzuki, and Masahiko Yamaguchi*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences,
Tohoku University, Aoba, Sendai, 980-8578, Japan
yama@m.tohoku.ac.jp, arisawa@m.tohoku.ac.jp
Received December 16, 2011
ABSTRACT
A rhodium complex catalyzed the reaction of aryl methyl ethers and thioesters giving the corresponding aryl esters and methyl sulfides.
S-(p-Chlorophenyl) p-(dimethylamino)benzothioate was used for the reaction of methyl aryl ethers with electron-withdrawing groups, and an
S-(p-tolyl) derivative was used for those with electron-donating groups. Polymethoxybenzenes were converted to the esters in a regioselective manner.
The cleavage of unactivated CH3ÀO bonds of aryl
methyl ethers catalyzed by transition-metal complexes
can have significant applications in organic synthesis.
For example, the method can be used for the protection/
deprotection of phenols.1 Several examples of stoichio-
metric ether bond cleavage reactions have been reported.2
However, catalytic transformations remain unknown. De-
scribed in this study is the rhodium-catalyzed reaction of
aryl methyl ethers and thioesters,3 which gives aryl esters
and methyl sulfides. Unlike conventional methods of aryl
methyl ether cleavage, the reaction proceeds without using
a stoichiometric amount of a strong acid or a base.4À6
When a mixture of p-cyanoanisole 1 (2 equiv) and
S-(p-chlorophenyl) p-(dimethylamino)benzothioate 2 was
heated without a solvent at 130 °C for 12 h in the presence of
RhH(CO)(PPh3)3 (1 mol %) and 1,2-bis(diphenylphosphino)-
ethane (dppe, 2 mol %), p-cyanophenyl p-(dimethylamino)-
benzoate 3 (94%) and p-chlorothioanisole 4 (94%) were
obtained (Table 1, entry 1).7 The rhodium complex and
dppe were both essential for the reaction; no reaction
occurred in the absence of either substance. The yields of
3 and 4 decreased to 68% and 66% using equimolar
amounts of 1 and 2, respectively.
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3rd ed.; John Wiley: New York, 1999.
(2) (a) Choi, J.; Choliy, Y.; Zhang, X.; Emge, T. J.; Krogh-Jespersen,
K.; Goldman, A. S. J. Am. Chem. Soc. 2009, 131, 15627. (b) van der
Boom, M. E.; Liou, S.-Y.; Ben-David, Y.; Vigalok, A.; Milstein, D.
Angew. Chem., Int. Ed. Engl. 1997, 36, 625. (c) Tolman, C. A.; Ittel, S. D.;
English, A. D.; Jesson, J. P. J. Am. Chem. Soc. 1979, 101, 1742.
(3) (a) Arisawa, M.; Igarashi, Y.; Kobayashi, H.; Yamada, T.;
Bando, K.; Ichikawa, T.; Yamaguchi, M. Tetrahedron 2011, 67, 7846.
(b) Arisawa, M.; Yamada, T.; Yamaguchi, M. Tetrahedron Lett. 2010,
51, 6090. (c) Arisawa, M.; Kubota, T.; Yamaguchi, M. Tetrahedron Lett.
2008, 49, 1975.
(4) Use of strong Lewis acids: (a) Kawamura, Y.; Takatsuki, H.;
Torii, F.; Horie, T. Bull. Chem. Soc. Jpn. 1994, 67, 511. (b) Parker, K. A.;
Petraitis, J. J. Tetrahedron Lett. 1981, 22, 397. (c) Node, M.; Nishide, K.;
Fuji, K.; Fujita, E. J. Org. Chem. 1980, 45, 4275. (d) Vickery, E. H.;
Pahler, L. F.; Eisenbraun, E. J. J. Org. Chem. 1979, 44, 4444. (e)
Minamikawa, J.; Brossi, A. Tetrahedron Lett. 1978, 19, 3085. (f) Jung,
M. E.; Lyster, M. A. J. Org. Chem. 1977, 42, 3761. (g) McOmie, J. F. W.;
West, D. E. Organic Syntheses; Wiley: New York, 1973; Vol. V, p 412.
(5) Use of protic acids: (a) Kamal, A.; Gayatri, N. L. Tetrahedron
Lett. 1996, 37, 3359. (b) Li, G.; Patel, D.; Hruby, V. J. Tetrahedron Lett.
1993, 34, 5393. (c) Kawasaki, I.; Matsuda, K.; Kaneko, T. Bull. Chem.
Soc. Jpn. 1971, 44, 1986.
The reactivities of the thioesters were compared using
the reaction of 1 (1 equiv) in chlorobenzene (2 M) in the
presence of the rhodium complex (2.5 mol %) and dppe
(6) Use of nucleophilic metal salts in polar solvents at high tempera-
tures: (a) Chakraborti, A. K.; Nayak, M. K.; Sharma, L. J. Org. Chem.
2002, 67, 1776. (b) McCarthy, J. R.; Moore, J. L.; Cregge, R. J.
Tetrahedron Lett. 1978, 19, 5183. (c) Feutrill, G. I.; Mirrington, R. N.
Tetrahedron Lett. 1970, 11, 1327.
(7) In a one-neck, round-bottom flask equipped with a reflux con-
denser were placed RhH(CO)(PPh3)3 (1.0 mol %, 9.2 mg), 1,2-bis-
(diphenylphosphino)ethane (2.0 mol %, 8.0 mg), p-cyanoanisole 1
(2.0 mmol, 266 mg), and S-(4-chlorophenyl) (4-dimethylamino)
benzoate 2 (1.0 mmol, 291 mg) under an argon atmosphere. Then, the
mixture was heated at 150 °C for a few minutes to dissolve the rhodium
complex and allowed to react at 130 °C for 12 h. After being cooled to
room temperature, the mixture was purified by flash column chromato-
graphy on silica gel giving p-cyanophenyl (p-dimethylamino)benzoate
3 (250.5 mg, 94%) as a colorless solid and p-chlorothioanisole 4
(149.1 mg, 94%) as a colorless oil.
r
10.1021/ol2033724
2012 American Chemical Society
Published on Web 01/24/2012

(5 mol %). The aryl ester and 4 were obtained in compar-
able yields for each thioester as follows: 2, 71% and 70%;
S-(p-chlorophenyl) p-methylbenzothioate, 26% and
23%; S-(p-chlorophenyl) benzothioate, 19% and
17%; S-(p-chlorophenyl) p-chlorobenzoate, 7% and
trace; S-(p-tolyl) p-(dimethyamino)benzothioate 5, 44%
and 42% (also see Table 1, entry 3). The results indicated
the requirement of an electron-donating group at the
benzoyl moiety and an electron-withdrawing group at
the arylthio moiety in the thioesters.
The reaction was applicable to aryl methyl ethers with
electron-withdrawing groups such as formyl, benzoyl,
acetyl, chloride, and ethoxycarbonyl groups at the o-, m-,
and p-positions in the presence of the rhodium complex
(1À5 mol %) (entries 1À14). The reaction proceeded
efficiently without affecting the functional groups.
1- and 2-Methoxynaphthalenes showed similar reac-
tions (entries 15À17). The reaction mechanism cannot
be a nucleophilic substitution reaction at the methyl
group, which should require better leaving phenoxy
groups with strong electron-withdrawing groups at the
o- or p-position.
When o-dimethoxybenzene (5 equiv) and S-(p-tolyl) p-
(dimethylamino)benzothioate 5 were heated at 130 °C
for 12 h in the presence of RhH(CO)(PPh3)3 (8 mol %)
and dppe (16 mol %), o-methoxyphenyl p-(dimethylamino)-
benzoate (92%) and p-tolyl methyl sulfide (86%) were
obtained (Scheme 1). The use of 2, S-(p-trifluoromethyl-
phenyl) p-(dimethylamino)benzothioate, or S-(p-cyano-
phenyl) p-(dimethylamino)benzothioate in place of 5 re-
sulted in lower yields (71%, 50%, 24%) of the correspond-
ing esters. m-Dimethoxybenzene and 5 showed similar
reaction properties (91%). Anisole and m- and p-(tert-
butyl)anisoles also gave the corresponding aryl esters.
Notably, p-dimethoxybenzene gave a mixture of mono-
and didemethylated products in 42% and 30% yields
[based on the (p-dimethylamino)benzoyloxy group], re-
spectively. The result indicated that the second demethyla-
tion was much faster than the first one.
Scheme 1
Table 1. Reactions of Various Aryl Methyl Ethers with Elec-
tron-Withdrawing Groups
yield (%)
It is shown that aryl methyl ethers with electron-with-
drawing groups reacted efficiently with 2 and those with
electron-donating groups with 5. This may be due to the
polarity of thioesters and anisoles: Polar aryl methyl ethers
with electron-withdrawing groups reacted with polar
thioesters 2 having electron-withdrawing groups at the
arylthio moiety; less polar aryl methyl ethers with elec-
tron-donating groups reacted with less polar thioester 5
having electron-donating groups at the arylthio moiety.
This is probably related to the metal-catalyzed nature of
this reaction.
The reaction was applied to polymethoxybenzenes to
examine regioselectivity in demethylation (Scheme 2). The
reaction of 1,3,5-trimethoxybenzene and 1,2,4,5-tetra-
methoxybenzene with 5 in the presence of a rhodium
catalyst gave monoesters in 90% and 89% yields, respec-
tively. The reactions of polymethoxybenzenes with meth-
oxy groups in different environments are also summarized.
The reactions occurred in one methyl group, and no
didemethoxylated products were obtained. In general,
demethylation occurred at methoxy groups with one or
two adjacent methoxy groups. However, the steric effect
appeared to be nonessential, as observed in the reaction of
1,2,3,4-tetramethoxybenzene and pentamethoxybenzene.
entry
R
x (mol %) aryl esters
4
1
p-CN (1)
p-CN (1)
p-CN (1)
p-CHO
p-COPh
p-COMe
p-Cl
1
94
68
64
92
99
91
87
78
90
90
82
95
90
87
81
92
63
94
66
60
94
98
86
88
73
87
88
75
94
90
85
79
90
60
2a
3b
4
1
1
1
5
1
6
2.5
2.5
2.5
1
7
8
p-CO2Et
o-CN
9
10
11
12
13
14
15
16
17
o-COMe
o-Cl
2.5
2.5
5
o-Cl
m-CN
2.5
5
m-COPh
1-MeO-naphthalene
4-NC-1-MeO-naphthalene
2-MeO-naphthalene
2.5
1
2.5
a Thioester (1 equiv) was used. b S-(p-Tolyl) p-(dimethyamino)-
benzothioate 5 was used.
The reaction of aryl methyl ethers with electron-
donating groups also proceeded under slightly forced
conditions when another thioester was employed.
856
Org. Lett., Vol. 14, No. 3, 2012

Scheme 2
Scheme 3
S-(p-dimethylaminophenylcarbonyl)-p-dimethylamino-
benzothioate 9 (10%) and p-methoxythioanisole 10 (8%)
(Scheme 3).
In summary, a rhodium complex catalyzed the reaction of
aryl methyl ethers and thioesters, giving the corresponding
aryl esters and methyl sulfides. The use of appropriate thio-
esters was critical for efficient reaction, and notable regios-
electivity was observed in the reaction of polymethoxyben-
zenes. It should be emphasized that rhodium catalysis could
be used for transformation involving the cleavage of the
unactivated sp3-CÀO bond of aryl methyl ethers: demethyla-
tion of aryl methyl ethers and methylation of thioesters.
These results showed a tendency to provide 1,4-dimethoxy
derivatives as products, which might minimize the polarity
of the product. This notable selectivity may also reflect the
transition-metal-catalyzed nature. Regioselectivity in the
demethylation of polymethoxybenzenes could not be clearly
examined using conventional acid- or base-promoted
methods, with some exceptions, e.g., o-methoxyacetophe-
none derivatives.4b,8
A formal intramolecular reaction was conducted using
S-(p-methoxyphenyl) p-(dimethylamino)benzothioate 7.
The rhodium-catalyzed reaction gave p-methylthiophenyl
p-(dimethylamino)benzoate 8 (78%) along with small
amounts of intermolecular reaction products, i.e.,
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research (No. 21229001), the GCOE
program, and the WPI Initiative from JSPS. M.A. expresses
her appreciation for financial support from a Grant-in-Aid
for Scientific Research (No. 22689001), the Japan Science
Technology Agency, and the Asahi Glass Foundation.
Supporting Information Available. General experimen-
tal procedures and characterization details. This material
is available free of charge via the Internet at http://pubs.
acs.org.
(8) (a) Alonso, R.; Brossi, A. Tetrahedron Lett. 1988, 29, 735. (b) Lal,
K.; Ghosh, S.; Salomon, R. G. J. Org. Chem. 1987, 52, 1072.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 3, 2012
857