Cobalt(II)chloride catalyzed chemoselective thioacetalization of aldehydes

Article abstract of DOI:10.1016/j.tetlet.2003.11.082

A mild and chemoselective dithioacetalization procedure for the protection of various aldehydes in the presence of catalytic amount of cobalt(II)chloride is described.

Full text of DOI:10.1016/j.tetlet.2003.11.082

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1035–1036
Cobalt(II)chloride catalyzed chemoselective thioacetalization
of aldehydes
Surya Kanta De*
Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195, USA
Received 12 November 2003; revised 18 November 2003; accepted 18 November 2003
Abstract—A mild and chemoselective dithioacetalization procedure for the protection of various aldehydes in the presence of
catalytic amount of cobalt(II)chloride is described.
Ó 2003 Elsevier Ltd. All rights reserved.
The protection of carbonyl functionality as a dithio-
acetal1 is a common practice in organic chemistry, as
they are quite stable under basic or mildly acidic con-
ditions.2 The dithioacetals are also utilized as masked
acyl anions3 or masked methylene functions4 in carbon–
carbon bond forming reactions. Generally, they are
prepared by condensation of carbonyl compounds with
thiols or dithiols employing strong acid catalysts such as
HCl,5 PTSA,6 BF3ÆOEt2,7 AlCl3,8 TiCl4,9 Mg(OTf)3,10
and LaCl3.11 A large number of these methods require
long reaction times, reflux temperature, and stoichio-
metric amount of catalyst and provide low yields. Most
recently, some methods employing LiBr,12 LiBF4,13
lytic amount of cobalt(II)chloride (5 mol %) in good to
excellent yields (Scheme 1). Treatment of 4-methoxy-
benzaldehyde with 1,3-propanedithiol in the presence of
cobalt(II)chloride (5 mol %) in acetonitrile at room
temperature afforded the desired 2-(4-methoxyphenyl)-
1,3-dithiane. Similarly, several activated and deactivated
aromatic aldehydes and aliphatic aldehydes underwent
the protection reactions to give the corresponding car-
bonyl derivatives (Table 1). Acetonitrile is the solvent of
choice as the best results were obtained. The experi-
mental procedure is very simple,18 more convenient, and
also the method has ability to tolerate a variety of other
protecting groups such as benzyl, allyl, and TBS ether.
16
InCl3,14 Sc(OTf)3,15 I2 have been reported. Interest-
ingly, only a few of these methods have demonstrated
for chemoselective protection of aldehydes in the pres-
ence of ketones. Some methods are incompatible with
other protecting groups such as TBS ethers7b;12b;13b;16b
and fail to protect deactivated aromatic substrates.15
Therefore, there is still a need to develop a simple and
efficient method for chemoselective protection of alde-
hydes.
It is noteworthy that ketones did not produce the
corresponding thioacetals under the same reaction
conditions. This result prompted me to explore the
chemoselective protection of aldehydes in the presence
of ketones. For example, when an equimolar mixture of
4-methoxybenzaldehyde and 4-methoxyacetophenone
was allowed to react with 1,2-ethanedithiol in the pres-
ence of catalytic amount of cobalt(II)chloride only the
1,3-ditholane derivative of the 4-methoxybenzaldehyde
was obtained (Scheme 2).
In my ongoing research program to develop new syn-
thetic methodologies17 for protection and deprotection
of carbonyl compounds,
I
have found that
In conclusion, I have developed a simple and efficient
method for chemoselective dithioacetalization of
various aldehydes in the presence of a wide range of
cobalt(II)chloride, which acts as a mild Lewis acid, can
be used for thioacetalization of carbonyl compounds. In
this letter, I wish to report a simple and efficient method
for chemoselective protection of various aldehydes as
1,3-dithianes, 1,3-ditholanes, and dithiols using a cata-
S
S
O
EtSH or HS-(CH2)n-SH
( )n
R
RCH(SEt)2 or
CoCl2 ( 5 mol%), CH3CN, rt
R
H
n = 2, 3
* Tel.: +1-206-5239498; fax: +1-206-6858665; e-mail: skd125@yahoo.
com
Scheme 1.
0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.11.082

1036
S. K. De / Tetrahedron Letters 45 (2004) 1035–1036
Table 1. Cobalt(II)chloride catalyzed protection of aldehydes as dithianes, dithiolanes, or diethyldithioacetals at room temperature
Entry
Substrate
Reagent
Time (h)
Yield a(%)
1
Benzaldehyde
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2SH
1
0.5
0.5
4
91
92
88
78
85
89
87
79
91
80
76
89
91
79
83
75
71
77
89
93
89
78
89
91
79
74
2
4-Methoxybenzaldehyde
4-Chlorobenzaldehyde
4-Nitrobenzaldehyde
Furfural
3
4
5
1
6
4-Benzyloxybenzaldehyde
Cinnamaldehyde
1.5
0.5
5
7
8
2-Naphthaldehyde
Thiophene 2-carboxaldehyde
4-Hydroxybenzaldehyde
2-Nitrobenzaldehyde
4-Methylbenzaldehyde
4-Allyloxybenzaldehyde
Hexaldehyde
9
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
2.5
5
1
0.5
5
4-TBSO-benzaldehyde
1-Octanal
Butyraldehyde
1.5
1
2
Decylaldehyde
Benzaldehyde
2
2.5
2
4-Methoxybenzaldehyde
4-Bromobenzaldehyde
Hexaldehyde
HSCH2CH2SH
HSCH2CH2SH
2
HSCH2CH2SH
HSCH2CH3
5
Benzaldehyde
5
4-Methoxybenzaldehyde
4-Chlorobenzaldehyde
2-Naphthaldehyde
HSCH2CH3
HSCH2CH3
HSCH2CH3
4
4
12
a Yields refer to pure isolated products, characterized by IR, 1H NMR, and MS.
6. Djerassi, C.; Gorman, M. J. Am. Chem. Soc. 1953, 75,
3704.
S
CHO
7. (a) Fieser, L. F. J. Am. Chem. Soc. 1954, 76, 1945; (b)
Nakata, T.; Nagao, S.; Mori, S.; Oishi, T. Tetrahedron
Lett. 1985, 26, 6461.
8. Ong, B. S. Tetrahedron Lett. 1980, 21, 4225.
9. Kumar, V.; Dev, S. Tetrahedron Lett. 1983, 24, 1289.
10. Corey, E. J.; Shimoji, K. Tetrahedron Lett. 1983, 24, 169.
11. Garlaschelli, L.; Vidari, G. Tetrahedron Lett. 1990, 31,
5815.
S
CoCl2 (5 mol%)
MeO
MeO
92%
HSCH2CH2SH
O
S
CH3CN, rt, 30 min.
CH3
S
CH3
MeO
MeO
0%
12. (a) Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synthesis
1999, 58; (b) Tandon, M.; Begley, T. P. Synth. Commun.
1997, 27, 2953.
Scheme 2.
13. (a) Yadav, J. S.; Reddy, B. V. S.; Pandey, S. K. Synlett
2001, 238; (b) Metcalf, B. W.; Burkhart, J. P.; Jund, K.
Tetrahedron Lett. 1980, 21, 35.
14. Madhuswamy, S.; Arulananda Babu, S.; Gunanatham, C.
Tetrahedron Lett. 2001, 42, 359.
other protecting groups using a catalytic amount of
CoCl2. Moreover, highly deactivated aromatic alde-
hydes can be converted to their corresponding dithio-
acetals without any difficulty.
15. Kamal, A.; Chouhan, G. Tetrahedron Lett. 2002, 43, 1347.
16. (a) Samajdar, S.; Basu, M. K.; Becker, F. F.; Banik, B. K.
Tetrahedron Lett. 2001, 42, 4425; (b) Vaino, A. R.; Szarek,
W. A. J. Chem. Soc., Chem. Commun. 1996, 2351.
17. De, S. K. Tetrahedron Lett. 2003, 44, 9055.
18. A Typical Procedure: To a stirred mixture of 4-methoxy-
benzaldehyde (681 mg, 5 mmol) and 1,3-propanedithiol
(645 mg, 6 mmol) in acetonitrile (15 mL) was added CoCl2
(30 mg, 5 mol %) at room temperature. The reaction
mixture was stirred for 30 min. (TLC monitored) then
concentrated in vacuo. The residue was purified by silica
gel column chromatography (20% ethyl acetate in hexane)
to afford pure 2-(4-methoxyphenyl)-1,3-dithiane (92%). 1H
NMR (500 MHz, CDCl3) d 1.86–1.99 (m, 1H), 2.10–2.18
(m, 1H), 2.85–2.95 (m, 2H), 2.98–3.11 (m, 2H), 3.80 (s,
3H), 5.12 (s, 1H), 6.86 (d, J ¼ 8:5 Hz, 2H), 7.40 (d,
J ¼ 8:5 Hz, 2H).
References and notes
1. Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis. 3rd ed. John Wiley and Sons: New
York, 1999. pp 329–344.
2. (a) Corey, E. J.; Seebach, D. J. Org. Chem. 1966, 31, 4097;
(b) Eliel, E. L.; Morris-Natschke, S. J. Am. Chem. Soc.
1984, 106, 2937.
3. (a) Seebach, D. Angew. Chem., Int. Ed. Engl. 1969, 8, 639;
(b) Grobel, B. T.; Seebach, D. Synthesis 1977, 357; (c)
Bulman Page, P. C.; Van Niel, M. B.; Prodger, J. C.
Tetrahedron 1989, 45, 7643.
4. Pettit, G. R.; Van Tamelen, E. E. Org. React. 1962, 12,
356.
5. Ralls, J. W.; Dobson, R. M.; Reigel, B. J. Am. Chem. Soc.
1949, 71, 3320.