An efficient and chemoselective deprotection of aryl- and styrenyldithioketals (acetals)

Article abstract of DOI:10.1016/j.tetlet.2007.08.054

In this Letter, an efficient and chemoselective deprotection of aryl- and styrenyldithioketals (acetals) is described. After being carefully examined, 10% Pd/C and Amberlite 120 in refluxing methanol was found to be an excellent condition for the chemoselective deprotection of aryl- and styrenyldithioketals (acetals) in good yields. Under this condition, no deprotection and no reduction of alkyldithioketals (acetals) was observed.

Full text of DOI:10.1016/j.tetlet.2007.08.054

Tetrahedron Letters 48 (2007) 7706–7708
An efficient and chemoselective deprotection of aryl- and
styrenyldithioketals (acetals)
a
b
b
c
Eng-Chi Wang, Chien-Huang Wu, Shih-Chang Chien, Wen-Chang Chiang and
b,c,d,e,
*
Yueh-Hsiung Kuo
a
Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
b
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
Center for Food and Biomolecules, National Taiwan University, Taipei 106, Taiwan
c
d
Tsuzuki Institute for Traditional Medicine, College of Pharmacy, China Medical University, Taichung 404, Taiwan
e
Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan
Received 21 May 2007; revised 6 August 2007; accepted 14 August 2007
Available online 19 August 2007
Abstract—In this Letter, an efficient and chemoselective deprotection of aryl- and styrenyldithioketals (acetals) is described. After
being carefully examined, 10% Pd/C and Amberlite 120 in refluxing methanol was found to be an excellent condition for the
chemoselective deprotection of aryl- and styrenyldithioketals (acetals) in good yields. Under this condition, no deprotection and
no reduction of alkyldithioketals (acetals) was observed.
Ó 2007 Elsevier Ltd. All rights reserved.
Dithioketals (acetals), while treated with sodium hy-
dride or n-butyl lithium, as a carbanion source or as
(acetals), which has no effect on alkyldithioketals
(acetals). Various metals like Pd–C, Pt–C, and Ni
powder; catalytic acids like acetic acid, toluenesulfonic
1
protecting group for ketones and aldehydes have been
2
widely employed in organic synthesis. The deprotection
acid, BF Æetherate, and Amberlite IR-120; solvents like
3
of dithioketals (acetals) to corresponding ketones (alde-
hydes) also played an important role in organic synthe-
sis. Researches concerning about deprotecting of
methanol, ethanol, dioxane, and THF are, respectively,
examined for this study. The deprotection of p-hydroxy-
acetophenone-1,3-dithiane used as model reaction
toward various conditions was investigated (Scheme
1). The results are compiled in Table 1.
3
dithioketals (acetals) were variously documented in the
4
literatures. For example, metal salts like silver(I) salt,
5
6
7
copper salt, mercuric(II) salt; and so on were reported
for deprotecting purposes. Up to date chemoselective
deprotection of aryldithioketals and allyldithioketals is
paid little attention. Only few procedures such as
From the results obtained in Table 1, the condition of
10% Pd–C and TsOHÆH O in refluxing methanol is the
2
best one from the evaluation of percentage yield and
reaction time. However, from the environmental con-
8
a
8b
Tl(NO ) Æ3H O, tert-butyl hydroperoxide (TBHP),
3
2
2
9
and o-iodoxybenzoic acid (IBX) in DMSO as reagents
were employed to unmask aryldithioketals and ally-
ldithioketals with selectivity. However, some disadvan-
tages, such as low yield, toxicity to earth, and tedious
work-up procedures, commonly existed in those
reported methods. For chemistry interesting, herein,
we like to disclose an easy, efficient and chemoselective
deprotection method for aryl-, and styrenyldithioketals
cern, instead of 10% Pd/C and TsOHÆH O, the condition
2
of 10% Pd/C and Amberlite IR-120 which has good
deprotection results, is environmentally friendly and
S
S
O
Metal, acidic catalyst
Solvent
HO
HO
Keywords: Deprotection; Aryldithioketals; Palladium on charcoal;
Amberlite IR-120.
2a
1
a
*
Corresponding author. E-mail: yhkuo@ntu.edu.tw
Scheme 1.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.08.054

E.-C. Wang et al. / Tetrahedron Letters 48 (2007) 7706–7708
7707
Table 1. The results obtained from the deprotection of 1a (0.17 mmol) with various conditions
a
b
c
Entry
1
Metal
Catalyst
TsOHÆH
Solvent
Reaction temperature
Reaction time (h)
Yield (%)
10% Pd–C
2
O
Dioxane
EtOH
Reflux
Reflux
Reflux
Reflux
Reflux
6
7
4
39
8
8
89
90
92
82
88
88
81
84
MeOH
THF
MeOH
Amberlite IR-120
HOAc
BF
3
Æether
MeOH
MeOH
Reflux
Reflux
23
12
2
3
10% Pt–C
Ni
TsOHÆH
2
O
MeOH
MeOH
Reflux
Reflux
144
36
72
60
Amberlite IR-120
a
b
c
The amount of metals used in this study is 180 mg for 10% Pd–C, 200 mg for 10% Pt–C, and 900 mg for Ni powder, respectively.
The amount of acid for this study is 16 mg (0.084 mmol) for TsOHÆH O, 200 mg for Amberlite, 5.04 mg for HOAc, and five drops for BF
mL for each solvent was used.
2
3
Æether.
8
1
0
Table 2. The deprotection of 1,3-dithiaketals and 1,3-dithiaacetals by 10% Pd–C and Amberlite IR-120 in refluxing methanol
a
a
Substrate
Product
Time
Yield
(%)
Substrate
Product
Time
(h)
Yield
(%)
(
h)
O
O
O
S
S
S
S
8
88
87
H
H
36
30
74
70
H
HO
HO
2a
2b
1
a
2g
2h
1
g
O
S
S
S
S
5
5
H
1
b
c
OCH3
OCH3
1
h
O
H
S
S
S
S
86
81
Recovery of 1i
Recovery of 1j
48
48
0
0
2
c
1i
1
O
S
S
S
S
1
3
8
2
1
1
j
2
d
1
d
O
O
S
S
S
S
S
MeO
MeO
MeO
MeO
75
6
72
S
S
S
H
OMe
2
e
OMe
S
2k
1
e
k
S
O
H
O
S
S
H
MeO
HO
MeO
HO
H
8
86
8
73
S
S
S
2
f
1
f
O
O
S
2l
1
l
a
11c
3 3
Each 1,3-dithiane, prepared from corresponding ketone (acetal) and 1,3-propanedithiol in the presence of BF Æetherate in CH Cl at 0 °C, has a
satisfactory spectral data.
11

7708
E.-C. Wang et al. / Tetrahedron Letters 48 (2007) 7706–7708
can be recovered by simple filtration was chosen for this
deprotection of aryl- and styrenyldithioketals (acetals)
studies. Based on this reaction condition, various 1,3-
dithiaketals and 1,3-dithiaacetals for deprotection were
examined, and the results were compiled in Table 2.
316; (c) Kamal, A.; Laxman, E.; Reddy, P. S. M. M.
Synlett 2000, 1476–1478; (d) Ganguly, N. C.; Datta, M.
Synlett 2004, 659–662; (e) Ichige, T.; Miyake, A.; Kanoh,
N.; Nakata, M. Synlett 2004, 1686–1690; (f) Kirihara, M.;
Harano, A.; Tsukiji, H.; Takizawa, R.; Uchiyama, T.;
Hatano, A. Tetrahedron Lett. 2005, 46, 6377–6380; (g)
Desai, U. V.; Pore, D. M.; Tamhankar, B. V.; Jadhav, S.
A.; Wadgaonkar, P. P. Tetrahedron Lett. 2006, 47, 8559–
From the results of Table 2, 1-aryl-1,3-dithianes (1a–f)
and 2-styryl-1,3-dithianes (1g,h) can be deprotected to
regenerate the corresponding aldehydes and ketones in
8
561; (h) Hajipour, A. R.; Zarei, A.; Khazdooz, L.;
Pourmousavi, S. A.; Ruoho, A. E. Bull. Korean Chem.
Soc. 2005, 26, 808–810.
7
0–88% yields. On the other hand, 1-alkyl-1,3-dithianes
(
1i,j), which cannot be deprotected even after 48 h
8. (a) Smith, R. A. J.; Hannah, D. J. Synth. Commun. 1979,
9
, 301–311; (b) Barhate, N. B.; Shinde, P. D.; Mahajan, V.
A.; Wakharkar, R. D. Tetrahedron Lett. 2002, 43, 6031–
033.
refluxing were observed. In addition, compounds (1k
and 1l), in which 1-aryl and 1-alkyl-1,3-dithianes co-ex-
isted in the same molecules, are subjected to chemoselec-
tive deprotection to give 2k and 2l in 72–73% yields,
respectively. In conclusion, Amberlite IR-120 and 10%
Pd–C in refluxing methanol, which is a new, simple,
mild, and efficient procedure for the chemoselective
deprotection of aryl-, and styrenyldithioketals (acetals)
in yields of 70–88%, but has no effect to alkyldithioke-
tals (acetals) are established.
6
9
. (a) Wu, Y.; Shen, X.; Huang, J.-H.; Tang, C.-J.; Liu, H.-
H.; Hu, Q. Tetrahedron Lett. 2002, 43, 6443–6445; (b)
Nicolaou, K. C.; Mathison, C. J. N.; Montagnon, T. J.
Am. Chem. Soc. 2004, 126, 5192–5201; (c) Krishnaveni, N.
S.; Surendra, K.; Nageswar, Y. V. D.; Rao, K. R.
Synthesis 2003, 15, 2295–2297.
10. General procedure for the deprotection of compound 1a–l
to generate compound 2a–l: 1a–l (0.17 mmol) dissolved in
methanol (8 mL) were subsequently added 10% Pd–C
(
180 mg) and Amberlite IR-120 (200 mg). The resulting
mixture was stirred and heated to the reflux until the
consumption of starting material, which was monitored by
TLC. Then, the mixture was added with ethyl acetate
(150 mL) and stirred for few hour. Then, the given mixture
was filtered through Celite to remove Pd–C and Amber-
lite. The filtrate was concentrated in vacuo to give
compound 2a–l, respectively. The selected examples, 2k
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2
007.08.054.
ꢀ
1
(
34 mg, 72%) was obtained as colorless oil, IR m cm
(
liquid) 3030, 2909, 1701(C@O), 1601, 1455, 1365, 1324,
1
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