Tetrabutylammonium peroxydisulfate in organic synthesis; XI.1 A novel and selective approach to the oxidative deprotection of allyl ethers with tetrabutylammonium peroxydulfate

Article abstract of DOI:10.1055/s-2001-17515

A tetrabutylammonium peroxydisulfate-mediated oxidative procedure for the mild selective deprotection of allyl ethers to form the corresponding alcohols is described. The alcohols are obtained in yields of 81-85% and the method is compatible with several functional groups under these reaction conditions.

Full text of DOI:10.1055/s-2001-17515

1772
SHORT PAPER
Tetrabutylammonium Peroxydisulfate in Organic Synthesis; XI.1 A Novel and
Selective Approach to the Oxidative Deprotection of Allyl Ethers with
Tetrabutylammonium Peroxydisulfate
O
xidative De
p
e
rotection
o
n
A
llyl Ether
-
s
with Te
E
trabutylammon
r
iumPeroxydis
C
ulfate hen,* Xiou-Hong Ling, Yan-Ping He, Xiao-Hua Peng
Department of Chemistry, Fudan University, Shanghai 200433, People’s Republic of China
Fax +86(21)65642021; E-mail: rfchen@fudan.edu.cn
Received 7 May 2001; revised 18 June 2001
cess, other functionalities including acetal, trityl, triazoyl
Abstract: A tetrabutylammonium peroxydisulfate-mediated oxida-
tive procedure for the mild selective deprotection of allyl ethers to
form the corresponding alcohols is described. The alcohols are ob-
tained in yields of 81–85% and the method is compatible with sev-
eral functional groups under these reaction conditions.
and glycosidic methyl groups still stay intact. These en-
couraging results prompted us to explore the validity and
the eventual scope of this useful method in the cleavage of
other ethers. Herein we report that the (n-Bu4N)2S2O8-me-
diated oxidative deprotection of allyl ethers proceeds with
remarkable regeneration of the parent molecule under
mild conditions as shown in the Scheme.
Key words: tetrabutylammonium peroxydisulfate, allyl ethers,
protecting group, deprotection
The development of mild and selective methods for the
deprotection of functional groups continues to be a signif-
icant aspect in the synthetic chemistry of polyfunctional
molecules. Thus, a large variety of protective groups has
been developed along with numerous methods for their re-
moval. Among the various protecting groups, the allyl
group is commonly used as protecting group for hydroxyl
functions in organic synthesis and more specifically in
carbohydrate chemistry.2 This is largely due to its easy
formation and stability under reasonably strong acidic and
basic conditions. From the information available, the clas-
sic methods for removal of the allyl protection involve
double bond isomerization followed by acidic or oxida-
tive cleavage,3 but this procedure could not be applied to
allyl ethers containing other isomerizable double bonds.
(n-Bu4N)2S2O8
O
NaOMe
MeOH
ROH
RO
RO
MeCN
2a-k
3a-k
1a-k
Scheme
The deallylation reactions were first studied using 1a with
(n-Bu4N)2S2O8 (Table 1). When 1a was treated with (n-
Bu4N)2S2O8 in MeCN at 8 °C for 6 h, the oxidation pro-
ceeded smoothly to form the corresponding ester interme-
diate 2a, which was subsequently hydrolyzed with
NaOMe in MeOH at 20 °C to afford the deprotected alco-
hol 3a in 84% yield (Table 1, entry 2). In order to establish
the optimum reaction conditions, we have examined the
effects of the solvent on the oxidation. After a series of ex-
periments, the solvent was found to strongly influence the
yield of this oxidation. As shown in Table 1, poor results
were obtained with all solvents investigated other than ac-
etonitrile: dichloromethane (60%, entry 5), THF (45%,
entry 8), dioxane (42%, entry 11), DMF (51%, entry 14)
while the oxidation did not proceed at all when toluene
was used as solvent even at reflux temperature (entries 17
and 18). Moreover, significant temperature effects on the
oxidation were also observed. It was clear that a lower
temperature had a beneficial effect on the yield of 3a, e.g.
84% at 8 °C (entry 2) versus 50% at 25 °C (entry 4). How-
ever, the yield of 3a decreased to 32% (entry1) when the
reaction temperature dropped down to –10 °C. It is espe-
cially worthwhile to mention that the oxidation did not
take place when the reaction was performed under N2 (en-
Several new deallylation methods have been developed
using various reagent systems, which include NBS/hn,4
Ti(O-i-Pr)4/n-BuMgCl,5 DDQ,6 SmCl3/e–,7 Pd(PPh3)4/
TolSO2H,8 PdCl2/CuCl/O2,9 I(CF2)6F/Zn,10 CP2Zr,11
NaBH4/I2,12 (CH3)3Cl/NaI,13 solid-phase cleavage using
Pd(PPh3)4/TolSO2H14 etc. These procedures, however,
suffer from either one or more of the following draw-
backs: availability, high cost of the reagent, partial poi-
soning of the catalyst, cumbersome workup and
competitive reactions during the manipulation of poly-
functional molecules. Therefore, the introduction of effi-
cient and selective methods for the cleavage of allyl ethers
to their parent alcohols is of practical importance and is
still in demand.
Very recently, we have succeeded in the specific depro-
tection of O-benzyl protective groups of carbohydrates try 19). The yield of 3a increased to 90% when oxygen
via oxidation with tetrabutylammonium peroxydisulfate was bubbled through the solution during the reaction (en-
[(n-Bu4N)2S2O8] and subsequent hydrolysis.15 In this pro- try 20).
Synthesis 2001, No. 12, 25 09 2001. Article Identifier:
1437-210X,E;2001,0,12,1772,1774,ftx,en;F03801SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

SHORT PAPER
Oxidative Deprotection of Allyl Ethers with Tetrabutylammonium Peroxydisulfate
Table 1 Effect of Solvent, Temperature on the Oxidative Deallyla-
tion of 1a with (n-Bu4N)2S2O8
8). It is interesting to note that allyl ether 1d was deally-
lated to give menthol 3d in excellent yield with complete
retention of optical purity (entry 4).
a
O
O
O
O
O
O
O
O
In conclusion, our present approach that is carried out un-
der extremely mild conditions has provided a novel, effi-
cient and chemoselective protocol for cleavage of allyl
ethers to the parent alcohols. This method should, there-
fore, find extensive applications in the synthesis of natural
products where selective deprotection of allyl ethers is a
specific requirement.
O
(n-Bu4N)2S2O8
O
MeONa
MeOH
OH
OAll
O
O
MeCN
O
O
O
O
O
2a
1a
3a
Entry
Solvent
Temp (°C) Time (h)
Yield of 3a
(%)
Table 2 (n-Bu4N)2S2O8-Mediated Selective Deprotection of Allyl
Ethers (1a–k)a
1
2
MeCN
MeCN
MeCN
MeCN
CH2Cl2
CH2Cl2
CH2Cl2
THF
–10
8
8
3
32
84
57
50
60
48
43
45
40
33
42
38
29
51
43
30
0c
Entry Substrate
Time (h) Productb Yield of 3
(%)c
3
15
25
8
2
O
1
6
8
6
5
5
6
6
3a
3b
3c
3d
3e
3f
84
81
84
85
83
82
81
4
2
O
O
5
5
OAll
O
O
6
15
25
8
4
1a
7
4
2
3
4
5
6
7
O
O
8
6
O
9
THF
15
25
8
4
OAll
O
O
O
O
O
O
10
11
12
13
14
15
16
17
18
19
20
THF
4
1a
dioxane
dioxane
dioxane
DMF
6
O
15
25
8
4
O
O
OAll
4
O
1a
3
O
O
DMF
15
25
25
reflux
8
2
O
DMF
2
OAll
toluene
toluene
MeCN, N2
MeCN, O2
25
18
8
O
1a
0c
O
O
0c
O
OAll
8
2
90
O
1a
a All reactions were carried out according to the typical procedure.
b Yield of isolated pure product.
O
O
c Compound 1a was recovered unchanged from the reaction mixture.
O
OAll
Under the explored optimal conditions, ranges of allyl
ethers were evaluated as substrates for their cleavage, and
the results are summarized in Table 2. As can be seen in
Table 2, all the tested substrates smoothly deallylated to
afford the corresponding alcohols in excellent yields (en-
tries 1–11). As expected, commonly used protecting
groups such as isopropylidene (entries 1–3, 10 and 11),
tetrahydropyranyl (entry 5) and trityl (entry 9) were toler-
ant under the reaction conditions established here. When
deallylation of the 1f and 1i, both possessing C=C double
bonds, was conducted, the reaction occurred in excellent
yield with no effect on the olefinic linkage (entries 6 and
O
1a
3g
O
O
O
OAll
O
O
1a
Synthesis 2001, No. 12, 1772–1774 ISSN 0039-7881 © Thieme Stuttgart · New York

1774
F.-E. Chen et al.
SHORT PAPER
Table 2 (n-Bu4N)2S2O8-Mediated Selective Deprotection of Allyl
Ethers (1a–k)a (continued)
justed to 6–6.5 by the addition of 10% H2SO4 at 0 °C and extracted
with Et2O (3 ¥ 25 mL). The combined organic extracts were washed
with brine (3 ¥ 15 mL), and dried (Na2SO4). The solvent was evap-
orated under reduced pressure. The crude product was purified by
flash chromatography [eluent: EtOAc–petroleum ether (60–90 °C),
1:15 to 1:10] to give pure 3a (2.1g, 84%) as a white solid.
Entry Substrate
Time (h) Productb Yield of 3
(%)c
8
9
7
6
8
3h
3I
3j
83
82
81
O
O
20
Mp 110–112 °C; [a]D = -18.4 (c 1.0, H2O), [Lit.18 mp 110–
O
111 °C, [a]D20 = 18.5 (c 5.0, H2O)].
OAll
1H NMR (300 MHz, CDCl3): d = 1.30–1.57 (4 s, 12 H, 4¥Me),
4.00–4.21 (m, 5 H, 3-H, 4-H, 5-H and 6-2H), 2.91 (d, 1 H, OH), 4.58
(d, 1 H, J = 3.72 Hz, 2-H), 5.90 (d, 1 H, J = 3.7 Hz, 1-H).
O
O
O
O
O
1a
O
O
HRMS: m/z calcd for C12H20O6: 260.2864, found 260.2849.
O
OAll
References
O
1a
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Y. X. Synthesis 2000, 1519.
10
O
O
(2) (a) Green, T. W.; Wuts, P. G. M. Protective Groups in
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O
OAll
O
1a
11
6
3k
85
O
O
O
OAll
O
1a
a All reactions were performed according to the typical procedure.
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c Yield of isolated pure products.
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All mps were determined on a WRS-1 digital melting point appara-
tus and are uncorrected. 1H NMR spectra were recorded on a Bruker
DPX 300 spectrometer with TMS as the internal standard. High-res-
olution mass spectra (HRMS) were measured on a Finnigan MAT-
4021 instrument. All solvents were distilled directly prior to use
from the appropriate drying agents. All starting allyl ethers were
prepared under the usual allylation conditions.2,16 (n-Bu4N)2S2O8
was prepared by the method described in the literature.17
Deallylation of 3-O-Allyl-1,2:5,6-di-O-isopropylidene-D-glucose
(1a); Typical Procedure
To a stirred solution of the allyl ether 1a (3 g, 10 mmol) in MeCN
(15 mL) was added dropwise (n-Bu4N)2S2O813 (6.8 g, 10 mmol) in
MeCN (60 mL) at 8 °C, and the stirring was continued for 3 h at the
same temperature. The mixture was diluted with H2O (50 mL) and
extracted with CHCl3 (3 ¥ 15 mL). The combined organic extracts
were washed successively with 5% NaHCO3 (2 ¥ 10 mL), brine (10
mL), and dried (Na2SO4). The solvent was evaporated under re-
duced pressure to give the crude ester 2a, which was dissolved in
MeOH (20 mL), followed by the addition of a 15% solution of Me-
ONa in MeOH (35 mL). After stirring for 1 h at 20 °C, the mixture
was poured into H2O (100 mL) until the pH of the solution was ad-
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(18) Fischer, E. Ber. Dtsch. Chem. Ges. 1895, 28, 1145.
Synthesis 2001, No. 12, 1772–1774 ISSN 0039-7881 © Thieme Stuttgart · New York