Deprotection of acetals and silyl ethers using a polymer-supported π- acid catalyst: Chemoselectivity and polymer effect

Article abstract of DOI:10.1055/s-1999-3000

A polymeric dicyanoketene acetal (DCKA), prepared from a styrene monomer bearing dicyanoketene acetal functionality, was found to be an effective and recyclable catalyst in the chemoselective deprotection of acetals and silyl ethers. A remarkable acceleration accountable for the polymer effect was observed.

Full text of DOI:10.1055/s-1999-3000

1960
LETTER
Deprotection of Acetals and Silyl Ethers Using a Polymer-Supported p-Acid
Catalyst: Chemoselectivity and Polymer Effect
Nobuyuki Tanaka, Yukio Masaki*
Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan
Fax+81-58-237-5979; E-mail: masaki@gifu-pu.ac.jp
Received 29 September 1999
First, we attempted cleavage of cinnamaldehyde dimethyl
Abstract: A polymeric dicyanoketene acetal (DCKA), prepared
acetal catalyzed by monomeric and polymeric forms of
from a styrene monomer bearing dicyanoketene acetal functional-
DCKA in CH3CN-H2O (9:1) at room temperature (Table
ity, was found to be an effective and recyclable catalyst in the
1). In the absence of catalyst, the conditions gave 11%
yield of deprotected cinnamaldehyde with a large amount
of recovered starting acetal (86%) (entry 1). With 0.2
equiv. of DCKEA (1) or a styrene derivative bearing dicy-
anoketene acetal moiety (monomeric DCKA 2),15 depro-
tection proceeded quantitatively, and we found that the
monomeric DCKA (2) was recoverable quantitatively af-
ter the reaction (entries 2, 3). With 50 mg of polymeric
DCKA 315 for 50 mg of the substrate, the reaction in aque-
ous media (CH3CN : H2O = 9:1) proceeded also quantita-
tively. After washing the recovered polymer successively
with water and ethyl acetate followed by drying at room
temperature in vacuo for 4 h, the catalyst could be reused
without loss of the activity (entry 4). Table 2 shows the
result of the deprotecting reaction of a variety of
dimethyl acetals and ethylene acetals derived from
aliphatic, allylic, and aryl aldehydes and ketones using
polymeric DCKA 3 as a catalyst. Most of the substrates
examined afforded the corresponding aldehydes and
ketones in good yields except for acetals of an aliphatic al-
dehyde, which gave a low yield of a deprotected aldehyde,
decanal (entries 1, 2).
chemoselective deprotection of acetals and silyl ethers. A remark-
able acceleration accountable for the polymer effect was observed.
Key words: polymeric p-acid catalyst, chemoselective deprotec-
tion, acetal, silyl ether, polymer effect
Acetals and silyl ethers find widespread applications as
protecting groups of carbonyl, hydroxy, and diol func-
tions in organic synthesis. 1 There are various methods for
regeneration of the parent carbonyl group and hydroxy
group from the acetals and silyl ethers: aqueous acid
hydrolysis1 and montmorillonite K-10 in aqueous metha-
nol,2 and non-aqueous methods including those based on
such promoters as [Ru(CH3CN)3(triphos)](OTf)2,3 silica-
supported guanidinium chloride-acetyl chloride,4 SiCl4-
NaI,5 montmorillonite K-10,6 Ph3P-CBr4,7 SnCl4,8
CuSO4-SiO2,9 CeCl3,10 oxidation methods.11 Tetrabuty-
lammonium fluoride (TBAF) in tetrahydrofuran (THF)
and other fluoride reagent/solvent combinations are com-
monly used especially for deprotection of silyl ethers.12
However, strong acids and/or TBAF often cause difficul-
ties in the workup and purification of products. It was
reported recently that 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ), tetracyanoethylene (TCNE),
and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimeth-
ane (TCNQF4) catalyze deprotection of acetals and tert-
butyldimethylsilyl (TBDMS) ether in aqueous media.13
Those catalysts, however, were found to decompose in
aqueous media and to turn their aqueous solution highly
acidic (e.g. pH 2.2 for 1.43 x 10-2 M aqueous solution of
DDQ or TCNE).13 In our investigation on catalytic activ-
ities of dicyanoketene acetals (DCKAs),14 a polymeric
DCKA prepared by copolymerization of a monomeric
DCKA bearing styrene moiety and ethylene glycol
dimethacrylate, was found to catalyze monothioacetaliza-
tion and carbon-carbon bond formation of acetals with si-
lylated nucleophiles under anhydrous conditions. 15 Now,
we found that dicyanoketene ethylene acetal (DCKEA)
(1) resists hydration by water at room temperature for 6 h,
and that DCKEA was recoverable quantitatively. Herein,
we report a simple deprotecting reaction of acetals and si-
lyl ethers catalyzed by the polymer-supported dicy-
anoketene acetal in aqueous media at room temperature.
Table 1 Deprotection of cinnamaldehyde dimethyl acetal
catalyst
OMe
OMe
(50 mg)
CHO
Ph
CH3CN / H2O (9 : 1), r.t., 1.5 h
Ph
Entry
Catalyst
none
Yield (%)
11 (S.M. 86%)
1
O
O
NC
NC
quant.
2
DCKEA (1) (0.2 equiv.)
99
3
4
O
O
NC
NC
(catalyst recovery : 99%)
monomeric DCKA (2) (0.2 equiv.)
O
O
O
1st.
2nd.
3rd.
O
quant. quant. quant.
O
O
NC
NC
polymeric DCKA (3) (50 mg)
Synlett 1999, No. 12, 1960–1962 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Chemoselectivity and Polymer Effect
1961
methoxymethyl (MOM), and triisopropylsilyl (TIPS)
were attempted (Table 4). Although the substrates bearing
ethylene acetal together with O-THP or O-TBDMS group
gave no or low yield of the desired protected hydroxyke-
tones, ethylene acetals having O-TBDPS and O-MOM
group afforded the corresponding ketones in good yields
(entries 1~4). With the substrates bearing both protected
primary and secondary hydroxy groups, both primary O-
TBDMS group and secondary one were found to be
cleaved selectively in the presence of O-THP, O-MOM,
and O-TBDPS groups, although fission of O-TIPS paral-
leled that of O-TBDMS group (entries 7, 11).
Table 2 Deprotection of acetals catalyzed by polymeric DCKA (3)
polymeric DCKA (3) (50 mg)
R1 OR
R1
R2
O
R2 OR
(50 mg)
CH3CN / H2O (9 : 1), r.t.
Substrate
OR
R
Time (h) Yield (%)
Entry
Product
CHO
1
2
0.5
20
Me
17 (S.M. 77%)
32 (S.M. 59%)
-CH2-
OR
O
OR
OR
Me
4
5
0.5
20
90
56
-CH2-
OR
OR
quant.
95
Me
6
7
0.5
20
CHO
Ph
-CH2-
Ph
8
9
Me
0.5
20
82
78
OR
OR
Ph
Ph CHO
-CH2-
Table 4 Selective deprotection of ethylene acetals and TBDMS ethers
quant.
92
10
11
OR Me
0.5
20
O
MeO
Cl
MeO
Cl
CHO
O
O
(50 mg)
-CH2-
OR
OR
OR
polymeric DCKA (3) (50 mg)
or
or
0.5
20
12
13
74 (S.M. 24%)
94
Me
OR
OR
CH3CN / H2O (9 : 1), r.t.
(50 mg)
CHO
R' OH
R' OTBDMS
-CH2-
Entry
1
Time (h)
10
Yield (%)
Substrate
Product
14
15
Me
0.5
20
93
96
O
RO OR
O
-CH2-
25 a)
not detected a)
quant.
O
O
Ph Me
Ph Me
OTHP
OTHP
O
O
O
2
3
4
1
4
6
OTBDMS
OTBDPS
OTBDMS
OTBDPS
O
Next, we attempted polymeric DCKA-catalyzed desilyla-
tion reaction of several silyl ethers (Table 3). With 50 mg
of polymeric DCKA, the reaction of 50 mg of trimethyl-
silyl (TMS) ether derived from dodecanol in aqueous me-
dia (CH3CN : H2O = 9:1) proceeded to give dodecanol in
98% yield. The recovered polymer could be reused with-
out loss of the activity (entry 2). Most of silyl ethers in-
cluding TMS and TBDMS ethers derived from aliphatic,
allylic, and benzyl alcohols examined afforded the corre-
sponding alcohols in good yields except for tert-butyl-
diphenylsilyl (TBDPS) ethers, which gave no or low yield
of a deprotected alcohol (entries 5, 8, 11, and 14).
O
O
O
O
O
71
OMOM
OH
OMOM
OTBDMS
5
6
1
78b)
79
OTHP
OTHP
OTBDMS
OH
0.5
OMOM
OMOM
OTBDMS
OH
57 (diol 38%)
7
8
0.5
0.5
OTIPS
OTIPS
OTBDMS
OH
94
OTBDPS
OTBDPS
OTHP
OTHP
9
12
1
86 b)
67
OTBDMS
OH
OH
OH
OMOM
OTBDMS
OTIPS
OTBDMS
OMOM
10
11
12
Table 3 Deprotection of silyl ethers catalyzed by polymeric DCKA (3)
polymeric DCKA (3) (50 mg)
OH
2.5
1
86
R
OSiR'3
R
OH
OTBDPS
OTBDPS
CH3CN / H2O (9 : 1), r.t.
(50 mg)
78
OTBDMS
OH
SiR'3
Entry
Substrate
Time (h)
Yield (%)
10a) (S.M. 90%)
1st. 2nd. 3rd.
a) No starting material was recovered. b) Reaction was carried at 0°C.
1
2
TMS
TMS
3
1
98 98 98
68 (S.M. 31%)
quant.
C12H25 OSiR'3
3
4
5
TBDMS
TBDMS
TBDPS
1
24
30
In our investigation of such deprotecting reactions as
deacetalization and desilylation, polymeric DCKA 3 was
observed to catalyze these transformations faster than mo-
nomeric DCKA 2. Then we surveyed this polymer effect
on deprotection of several acetals and silyl ethers in the
presence of 0.2 equiv. of catalyst (Table 5). Clearly, the
catalytic activity of polymeric DCKA 3 appeared higher
than that of monomeric DCKA 2. Although the reason of
this interesting phenomenon of the polymer effect 16 was
ambiguous, enhancement of the deprotecting reactions
may be responsible for a high local concentration of
no reaction
6
7
8
TMS
TBDMS
TBDPS
1
24
30
81
86
OSiR'3
no reaction
9
10
11
TMS
TBDMS
TBDPS
1
24
30
74
quant.
17 (S.M. 77%)
Ph
OSiR'3
12
13
14
TMS
TBDMS
TBDPS
1
24
30
83
98
BnOSiR'3
no reaction
a) No catalyst was used in this reaction.
17
the functionality of catalysis by attachment to a high-
loading support.
Then, chemoselective hydrolysis of ethylene acetals and
TBDMS ethers in the presence of acid-labile OH-protect-
ing groups, such as tetrahydropyranyl (THP), TBDPS,
Synlett 1999, No. 12, 1960–1962 ISSN 0936-5214 © Thieme Stuttgart · New York

1962
N. Tanaka, Y. Masaki
LETTER
References and Notes
Table 5 Polymer effect in deprotection of acetals and silyl ethers.
0.2 eq. catalyst
product
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, Wiley, New York 1991, pp. 68-86, 178-198.
Schelhaas, M.; Waldmann, H. Angew. Chem. Int. Ed. Engl.
1996, 35, 2056.
(2) Asakura, J.; Robins, M. J.; Asaka, Y.; Kim, T. H. J. Org.
Chem. 1996, 61, 9026.
(3) Ma, S.; Venanzi, L. M. Tetrahedron Lett. 1993, 34, 8071.
(4) Gros, P.; Perchec, P. L.; Senet, J. P. J. Chem. Res. (S) 1995,
196.
substrate
CH3CN / H2O (9 : 1), r.t.
Yield (%)
Substrate
Time (h)
Product
Catalyst
(2)
(3)
OMe
Ph
0.5
1
Ph CHO
9
54
69
OMe
O
Cl
Cl
CHO
1
O
(5) Elmorsy, S. S.; Bhatt, M. V.; Pelter, A. Tetrahedron Lett.
O
O
1992, 33, 1657.
O
20
60
73
(6) Gautier, E. C. L.; Graham, A. E.; McKillop, A.; Standen, S. P.;
Taylor, R. J. K. Tetrahedron Lett. 1997, 38, 1881 and
references cited therein.
(7) Johnstone, C.; Kerr, W. J.; Scott, J. S. Chem. Commun. 1996,
341.
n-C12H25 OTMS
n-C12H25 OH
n-C12H25 OH
1
5
68
8
95
97
n-C12H25 OTBDMS
(8) Ford, K. L.; Roskamp, E. J. J. Org. Chem. 1993, 58, 4142 and
references cited therein.
(9) Caballero, G. M.; Gros, E. G. Synth. Commun. 1995, 25, 395.
(10) Marcantoni, E.; Nobili, F.; Bartoli, G.; Bosco, M.; Sambri, L.
J. Org. Chem. 1997, 62, 4183.
(11) Firouzabadi, H.; Iranpoor, N.; Zolfigol, M. A. Bull. Chem.
Soc. Jpn. 1998, 71, 2169.
Nishiguchi, T.; Ohosima, T.; Nishida, A.; Fujisaki, S. J.
Chem. Soc., Chem. Commun. 1995, 1121.
(12) Zhang, W.; Robins, M. J. Tetrahedron Lett. 1992, 33, 1177
and references therein.
(13) Tanemura, K.; Horaguchi, T.; Suzuki, T. Bull. Chem. Soc.
Jpn. 1992, 65, 304. Tanemura, K.; Suzuki, T.; Horaguchi, T.
J. Chem. Soc., Chem. Commun. 1992, 979. Tanemura, K.;
Suzuki, T.; Horaguchi, T. J. Chem. Soc., Perkin Trans. 1 1992,
2997.
In summary, we have developed an efficient and
chemoselective deprotecting reactions of acetals and silyl
ethers in aqueous media. These methods for deprotection
of acetals and silyl ethers using polymeric DCKA 3 have
following advantages; 1) neutral reaction condition, 2)
high yields, 3) easy isolation of products, 4) recycle of
polymer catalyst, and 5) excellent chemoselectivity. It is
noteworthy that this paper shows a remarkable example of
enhancing effect on the catalytic activity achieved by
changing the catalyst from monomeric form to polymeric
one.
Oku, A.; Kinugasa, M.; Kamada, T. Chem. Lett. 1993, 165.
Tanemura, K.; Suzuki, T.; Horaguchi, T. Bull. Chem. Soc.
Jpn. 1994, 67, 290.
Tanemura, K.; Nishida, Y.; Suzuki, T.; Satsumabayashi, K.;
Horaguchi, T. J. Chem. Res. (S) 1999, 40.
Experimental procedure
General procedure for the deprotection of acetals.—Cinnamalde-
hyde dimethyl acetal (50.0 mg, 0.281 mmol) was added to a suspen-
sion of polymeric DCKA (50.0 mg) in MeCN/H2O (9:1, 1 ml), and
the mixture was stirred at room temperature for 1.5 h. After poly-
meric DCKA was filtered out, the residue was dried with Na2SO4
and concentrated to give pure cinnamaldehyde (37.1 mg, quant.)
without any purification (Table 1, entry 4).
(14) Masaki, Y.; Miura, T. Tetrahedron Lett. 1994, 35, 7961.
Masaki, Y.; Miura, T. Chem. Pharm. Bull. 1995, 43, 523.
Masaki, Y.; Miura, T. Synth. Commun. 1995, 25, 1981.
Masaki, Y.; Miura, T. Tetrahedron 1995, 51, 10477.
Masaki, Y.; Miura, T.; Ochiai, M. Bull. Chem. Soc. Jpn. 1996,
69, 195. Masaki, Y.; Tanaka, N.; Miura, T. Chem. Lett. 1997,
55.
General procedure for the deprotection of TBDMS ethers.—Dode-
canol TBDMS ether (50.0 mg, 0.166 mmol) was added to a suspen-
sion of polymeric DCKA (50.0 mg) in MeCN/H2O (9:1, 1 ml), and
the mixture was stirred at room temperature for 24 h. After polymer-
ic DCKA was filtered out, the residue was dried with MgSO4 and
concentrated to give a crude product, which was purified by silica
gel column chromatography (AcOEt-hexane, 1:10) to give dode-
canol (30.9 mg, quant.) (Table 3, entry 4).
(15) Masaki, Y.; Tanaka, N.; Miura, T. Tetrahedron Lett. 1998, 39,
5799.
Masaki, Y.; Tanaka, N. Synlett 1999, 1277.
The polymer (3) is estimated to contain the dicyanoketene
acetal moiety 2.74 mmol/g (polymer) from elemental analysis.
(16) Kobayashi, S.; Nagayama, S. Synlett 1997, 653.
(17) Annis, D. A.; Jacobsen, E. N. J. Am. Chem. Soc. 1999, 121,
4147.
Article Identifier:
1437-2096,E;1999,0,12,1960,1962,ftx,en;Y19299ST.pdf
Synlett 1999, No. 12, 1960–1962 ISSN 0936-5214 © Thieme Stuttgart · New York