Deprotection of benzyl ethers using 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) under photoirradiation

Article abstract of DOI:10.1016/j.tetlet.2005.08.132

The deprotection of benzyl ethers was effectively realized in the presence of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) in MeCN under photoirradiation using a long wavelength UV light.

Full text of DOI:10.1016/j.tetlet.2005.08.132

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7307–7309
Deprotection of benzyl ethers using
,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ)
under photoirradiation
2
Mohammad Abdur Rahim, Shuichi Matsumura and Kazunobu Toshima*
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi,
Kohoku-ku, Yokohama 223-8522, Japan
Received 30 July 2005; revised 26 August 2005; accepted 26 August 2005
Available online 12 September 2005
Abstract—The deprotection of benzyl ethers was effectively realized in the presence of 2,3-dichloro-5,6-dicyano-p-benzoquinone
(
DDQ) in MeCN under photoirradiation using a long wavelength UV light.
Ó 2005 Elsevier Ltd. All rights reserved.
The popularity and extensive use of benzyl (Bn) ethers as
protecting groups for alcohols arise from their ease of
formation and removal, and their stability under wide
hν
R OBn
Cl
Cl
R OH
CN
CN
1
range of reaction conditions. A variety of methods have
O
been developed for their removal. Catalytic hydrogenoly-
sis using Pd–C, Raney-Ni or Rh–Al O is the most
2
3
common for deprotecting benzyl ethers. As an alterna-
tive method, 2,3-dichloro-5,6-dicyano-p-benzoquinone
O
DDQ
MeCN
(
DDQ) was reported to be a good reagent in the presence
2
,3
or absence of water. However, the use of DDQ for
deprotecting benzyl ethers cannot be always applicable.
In view of the importance of benzyl ethers in organic syn-
thesis, the search for novel methods for the effective
deprotection is of considerable importance. On the other
hand, a photochemical reaction using DDQ has been
Figure 1. Photodeprotection of benzyl ethers using DDQ.
4
hν
DDQ
reported for deprotecting thioacetals and ketals. DDQ
PvO
PvO
1
1
is a well-known electron acceptor and forms charge
OBn
5
100% MeCN
rt., 4 h
MeCN >90%
rt., 4 h
transfer (CT) complexes with a variety of donors. Based
1
on these facts, we were interested in the investigation of
benzyl ethers as donors and quinones as acceptors lead-
ing to the photochemical deprotection of benzyl ethers.
Herein, we report a novel deprotection method of benzyl
ethers using DDQ under photoirradiation (Fig. 1).
hν
DDQ
MeCN
rt., 4 h
OH
2
88%
Based on our hypothesis, we first examined the depro-
tection of benzyl ether in 1, possessing a pivaloyl (Pv)
Figure 2. Photodeprotection of the benzyl ether in 1 using DDQ.
Keywords: Protecting group; Benzyl ether; 2,3-Dichloro-5,6-dicyano-p-
benzoquinone; Photoirradiation; Alcohol.
ester as another protecting group, using DDQ in MeCN
with or without photoirradiation (Fig. 2). The photo-
irradiation was carried out using a long wavelength
*
Corresponding author. Tel.: +81 45 566 1576; fax: +81 45 566
576; e-mail: toshima@applc.keio.ac.jp
1
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.08.132

7308
M. A. Rahim et al. / Tetrahedron Letters 46 (2005) 7307–7309
UV light (365 nm, 100 W) placed at 15 cm from the
reaction mixture. We found, for the first time, that the
deprotection of the benzyl ether in 1 using 1.5 equiv of
DDQ in MeCN at room temperature during the photo-
irradiation proceeded smoothly to give the alcohol 2 in
(MOM), carbonate or isopropylidene group, or a func-
tional group, such as double or triple bond. These results
are summarized in Table 2. It was found that the depro-
tections of the benzyl ethers in 7–9 effectively proceeded,
as well as 1, to provide the corresponding alcohols in
good to high yields. In the cases of 10 and 11 possessing
an isopropylidene group and a double bond, respec-
tively, the yields were not very high and even moderate
8
8% yield. In drastic contrast, it was found that the
deprotection of the benzyl ether in 1 using DDQ in
MeCN without the photoirradiation occurred very
slightly, and the reactant 1 was recovered in more than
in the presence of BaCO . Unfortunately, it was con-
3
9
0% yield. Furthermore, it was confirmed that the
firmed that a triple bond is not a good substrate for the
deprotection reaction as shown in the reaction using
12. These unfavorable results came from the partial
deprotection of the isopropylidene group in 10, and the
generation of the significant amounts of by-products
from 11 and 12. Furthermore, as Tanemura et al. have
deprotection of the benzyl ether in 1 in MeCN during
the photoirradiation in the absence of DDQ was not
performed at all. These results clearly indicated that
the combined use of DDQ and the photoirradiation is
indispensable, and the UV light functioned as a trigger
to initiate the benzyl group deprotection using DDQ.
In addition, it was revealed that MeCN was quite super-
ior to other solvents such as MeOH, THF and PhMe.
Actually, the photodeprotection using DDQ proceeded
very slowly or did not take place at all in MeOH,
THF and PhMe.
6
demonstrated, silyl groups were readily deprotected by
DDQ with and without photoirradiation.
We finally compared the reactivity of the benzyl ether
with that of the p-methoxybenzyl ether (MPM) using
13, which had both benzyl and p-methoxybenzyl ethers,
under the stated reaction conditions (Fig. 3). p-Meth-
oxybenzyl ether is well known to be easily deprotected
With these results in hand, we investigated the scope and
limitation of the photodeprotection reaction. For this
purpose, we first examined the deprotections of the
benzyl ethers of several substances 3–6, each of which
possesses a primary or a secondary benzyl ether. These
results are summarized in Table 1. We found that all
the deprotection reactions using DDQ and photoirradi-
ation proceeded smoothly to give the corresponding
alcohols in good yields. These results also showed that
the deprotection method is applicable to not only pri-
mary benzyl ethers but also to secondary ones. In addi-
tion, it was found that the addition of BaCO3 is
sometimes effective (entries 1 and 4 in Table 1), probably
due to the quenching effect for small amounts of acidic
products coming from the minor DDQ decomposition
under the reaction conditions.
7
by DDQ in the presence of water. It was found that
the p-methoxybenzyl ether in 13 was selectively removed
using DDQ in MeCN under the photoirradiation and
anhydrous conditions within a short time to give the
monool 14 in high yield. In addition, it was confirmed
that a longer reaction time led to the deprotection of
both benzyl and p-methoxybenzyl ethers in 13 that pro-
duces the diol 15 in good yield.
The typical experimental protocol for the deprotection
of the benzyl ether in 1: To a stirred solution of 1
(0.1 mmol) in dry MeCN (15 mL) was added DDQ
(0.15 mmol). After stirring at room temperature for
4 h under the photoirradiation using a UV lamp
(365 nm, 100 W) placed at 15 cm from the reaction mix-
ture, the mixture was poured into saturated aqueous
We next tested the deprotections of the benzyl ethers
of several compounds 7–12, which possess another pro-
tecting group, such as benzoyl (Bz), methoxymethyl
NaHCO solution and then the resulting mixture was
3
extracted with CHCl . The extracts were dried over
3
anhydrous Na SO and concentrated in vacuo. Purifica-
2
4
Table 1. Photodeprotection of the benzyl ethers in 3–6 using DDQ
hν
R OBn
R OH
DDQ
MeCN, rt.
Entry
R-OBn
DDQ (equiv)
BaCO
3
(equiv)
Time/h
Yield/%
1
2
3
4
3
4
5
6
1.1
1.5
1.5
1.1
1.1
—
—
24
15
16
22
78
76
74
75
1.1
OBn
H
3
OBn
H
OBn
H
H
BnO
4
H
5
6

M. A. Rahim et al. / Tetrahedron Letters 46 (2005) 7307–7309
Table 2. Photodeprotection of the benzyl ethers in 1 and 7–12 using DDQ
7309
hν
R OBn
R OH
DDQ
MeCN, rt.
Entry
R-OBn
DDQ (equiv)
BaCO
3
(equiv)
Time/h
Yield/%
1
2
3
4
5
6
7
1
1.5
1.1
1.5
1.5
1.5
1.5
1.5
—
—
—
—
1.5
1.5
—
4
8
5
88
87
93
97
65
52
12
7
8
9
5
10
11
12
10
16
5
O
O
O
O
O
OBn
OBn
PO
OBn
9
11
12
1
7
8
: P=Pv
: P=Bz
: P=MOM
OBn
OBn
10
HO
Acknowledgements
OBn
1
4
84%
This research was partially supported by a Grant-in-Aid
for the 21st Century COE Program ÔKEIO Life Conju-
gate ChemistryÕ from the Ministry of Education, Cul-
ture, Sports, Science, and Technology, Japan. M.A.R.
thanks the JSPS Postdoctoral Fellowship for Foreign
Researchers and Grant-in Aid for JSPS Fellows from
Japan Society for the Promotion of Science (JSPS).
hν
DDQ
1.5 equiv.)
MeCN
rt., 2 h
(
MPMO
OBn
1
3
hν
MeCN
rt., 24 h
DDQ
(
3.0 equiv.)
References and notes
HO
OH
1
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Synthesis; John Wiley & Sons: New York, 1999; (b)
Kocienski, P. J. Protecting Groups; Thieme: Stuttgart, 1994.
1
5
72%
Figure 3. Deprotection of the benzyl and p-methoxybenzyl ethers in 13
using DDQ with photoirradiation.
2. (a) Tanaka, T.; Oikawa, Y.; Nakajima, N.; Hamada, T.;
Yonemitsu, O. Chem. Pharm. Bull. 1987, 35, 2203; (b)
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Am. Chem. Soc. 1989, 111, 8430.
tion of the residue by column chromatography (2:1 hex-
ane–ethyl acetate) gave the alcohol 2 in 88% yield.
In summary, we demonstrated here, for the first time,
the novel photodeprotection method of benzyl ethers
using DDQ in MeCN under photoirradiation using a
long wavelength UV light. DDQ, MeCN and the photo-
irradiation were found to be indispensable for the
deprotection reaction. Although the precise reaction
mechanism is not clear at this stage, and the present
method has some limitations, this novel photodeprotec-
tion protocol of benzyl ethers should find alternative
applications in organic synthesis.
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6
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