Yttrium triflate as an efficient and useful catalyst for chemoselective protection of carbonyl compounds

Article abstract of DOI:10.1016/j.tetlet.2004.01.106

Carbonyl compounds have been successfully converted into their corresponding oxathiolane, dithiolane, and dithiane derivatives with 2-mercaptoethanol, 1,2-ethanedithiol, and 1,3-propanedithiol using catalytic amount of yttrium triflate. In addition, by us

Full text of DOI:10.1016/j.tetlet.2004.01.106

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2339–2341
Yttrium triflate as an efficient and useful catalyst for chemoselective
protection of carbonyl compounds
Surya Kanta De*
Department of Chemistry, University of Washington, Seattle, WA 98195, USA
Received 29 October 2003; revised 21 January 2004; accepted 22 January 2004
This paper is dedicated to my mentor Prof. Niels H. Andersen, Department of Chemistry, University of Washington, for his valuable guidance
and constant encouragement
Abstract—Carbonyl compounds have been successfully converted into their corresponding oxathiolane, dithiolane, and dithiane
derivatives with 2-mercaptoethanol, 1,2-ethanedithiol, and 1,3-propanedithiol using catalytic amount of yttrium triflate. In addition,
by using this catalyst, high chemoselective protection of carbonyl compounds has been achieved.
Ó 2004 Elsevier Ltd. All rights reserved.
The protection of carbonyl compounds plays an
important role during multistep syntheses in organic,
medicinal, carbohydrate, and drug design chemistry.
Among carbonyl protecting groups, 1,3-diothiolanes,
Recently, there has been growing considerable interest
in the use of lanthanide triflates in organic synthesis as
they are water tolerable and reusable. The reagent
23
3
Y(OTf) is commercially available and can be used for
1
they are quite stable under both mildly acidic and basic
,3-oxathiolanes, and 1,3-dithianes are important as
preparation of oxathiolanes, dithiolanes, and dithianes
fromcarbonyl co mp ounds. Like lanthanide triflates,
Y(OTf) is also water tolerable, reusable, and chemo-
3
selective reagent for protection of carbonyl compounds.
Interestingly, the experimental procedure for these
reactions is very simple and does not need the use of dry
solvents or inert atmospheres. A catalytic amount of
yttriumtriflate (5 mo l %) is sufficient to obtain the
desired compounds in excellent yields (Scheme 1). Thus,
1
conditions. In addition, these are also utilized as
2
3
masked acyl anions or masked methylene functions in
carbon–carbon bond forming reactions. Several meth-
ods for preparation of thioacetals, dithiolanes, or
dithianes derivatives fromcarbonyl compounds such as
4
PTSA in refluxing benzene (removing the water as an
5
6
7
azeotrope with benzene), BF –OEt , ZnCl , SO2,
3
2
2
8
9
10
11
TMSCl–NaI, TMSOTf, AlCl
13
3
,
ZrCl
TiCl
–SiO
4
,
Cu(OTf)
2
–
15
12
14
SiO
2
,
Bi(NO ) ,
SOCl
2
–SiO
2
,
17
Bi(OTf) ,
4
2
,
LiBF4,
NiCl
2
,
16
18
19
20
LiBr,
22
InCl3,
have been reported.
3
3
3
21
molecular I
2
,
5 M LiClO
4
Although some of these methods are carried out under
mild reaction conditions, most of them require drastic
SH
HS
SH
S
S
7;13
4;17
conditions,
times, expensive, not readily available reagents, they
reflux temperature,
long reaction
R2
17
R
1
O
10;11
need to be prepared and tedious work-up procedure.
Interestingly, only a few methods are known for
Y(OTf) ( 5 mol%)
SH
3
S
S
R1
R2
12;13;15;18–22
CH CN, rt
3
chemoselective protection of aldehydes
in the
R1
R2
presence of ketones. So simple, efficient, and chemose-
lective methods are still desirable.
HO
SH
O
S
R2
R1
*
0
Tel.: +1-206-5239498; fax: +1-206-6858665; e-mail: skd125@yahoo.
com
Scheme 1.
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.01.106

2340
S. K. De / Tetrahedron Letters 45 (2004) 2339–2341
Table 1. Y(OTf)
3
catalyzed protection of carbonyl compounds as dithianes, dithiolanes, or oxathiolanes at room temperature
a
Entry
Substrate
Reagent
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
Benzaldehyde
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
HSCH
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
SH
SH
SH
SH
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
45
25
89
93/86
b
4-Methoxybenzaldehyde
4-Chlorobenzaldehyde
4-Nitrobenzaldehyde
Furfural
28
83
90
84
91
88
87
83
91
88
82
87
83
79
32
50
3-Methoxy-4-benzyloxybenzaldehyde
Cinnamaldehyde
45
2-Naphthaldehyde
Thiophene 2-carboxaldehyde
4-Hydroxybenzaldehyde
a-Tetralone
Cyclohexanone
Cyclopentanone
120
36
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
240
300
360
340
75
1-Hexanal
2-Heptanone
Acetophenone
c
140
120
85
83
91
c
c
4-Methoxyacetophenone
4-Chloroacetophenone
Benzaldehyde
92
89
c
90
90
92
93
4-Methoxybenzaldehyde
4-Bromobenzaldehyde
Cyclohexanone
45
55
b
89/85
390
110
120
340
115
81
79
81
79
71
Benzaldehyde
OH
OH
OH
OH
4-Methoxybenzaldehyde
1-Hexanal
Cinnamaldehyde
a
b
c
1
Yields refer to pure isolated products, characterized by IR, H NMR, and MS.
Isolated yields with reused catalyst.
Refluxed in acetonitrile.
various aromatic, aliphatic, and heterocyclic aldehydes
undergo the protection reactions using 1,3-propane-
dithiol, 1,2-ethanedithiol, or 2-mercaptoethanol in the
COCH3
CHO
R
S
(5 mol%)
3
S
Y(OTf)
CH CN, rt
S
S
+
presence of catalytic amount of Y(OTf) in acetonitrile
at roomte mp erature to give the corresponding 1,3-
dithianes, 1,3-dithiolanes, or 1,3-oxathilanes in good to
3
+
3
R
24
excellent yields. The results of these studies are sum-
marized in Table 1.
R
R
0
R = H, Cl, OMe
89-93%
%
It is noteworthy that aromatic or acyclic aliphatic ke-
tones did not undergo the reaction at roomtemperature.
This result prompted me to explore the chemoselective
protection of aldehydes in the presence of ketones. For
instance, when an equimolar mixture of aldehyde and
ketone was allowed to react with 1,3-propanedithiol in
Scheme 2.
fromthe solvents, substrates, and catalyst are not nec-
essary.
the presence of catalytic amount of Y(OTf) only the
3
1
,3-dithiane derivative of corresponding aldehyde was
obtained, ketone was recovered quantitatively (Scheme
). However, ketones are converted to the corresponding
2
dithianes derivatives at reflux temperature in excellent
yields.
References and notes
1
. (a) Corey, E. J.; Seebach, D. J. Org. Chem. 1966, 31, 4097;
b) Eliel, E. L.; Morris-Natschke, S. J. Am. Chem. Soc.
984, 106, 2937.
. (a) Seebach, D. Angew. Chem., Int. Ed. Engl. 1969, 8, 639;
b) Grobel, B. T.; Seebach, D. Synthesis 1977, 357; (c)
(
1
In conclusion, I have developed a simple and efficient
method for chemoselective protection of carbonyl
compounds as dithianes, dithiolanes, and oxathiolanes
using catalytic amount of yttrium triflate. Further, the
catalyst can be readily recovered and reused thus mak-
ing this procedure more environmentally acceptable.
The method has great advantage compared with con-
ventional Lewis acid-mediated reactions in dry organic
solvents, because tedious procedures to remove water
2
(
Bulman Page, P. C.; Van Niel, M. B.; Prodger, J. C.
Tetrahedron 1989, 45, 7643.
. Pettit, G. R.; Van Tamelen, E. E. Org. React. 1962, 12,
356.
4. Djerassi, C.; Gorman, M. J. Am. Chem. Soc. 1953, 75,
3704.
3

S. K. De / Tetrahedron Letters 45 (2004) 2339–2341
2341
5
. Wilson, G. E., Jr.; Huang, M. G.; Schloman, W. W., Jr. J.
Org. Chem. 1968, 33, 2133.
20. Madhuswamy, S.; Arulananda Babu, S.; Gunanathan, C.
Tetrahedron Lett. 2001, 42, 359.
6
. Evans, D. A.; Truesdale, L. K.; Grimm, K. G.; Nesbitt,
S. L. J. Am. Chem. Soc. 1977, 99, 5009.
21. Samajdar, S.; Basu, M. K.; Becker, F. F.; Banik, B. K.
Tetrahedron Lett. 2001, 42, 4425.
7
8
. Burezyk, B.; Kortylewticz, Z. Synthesis 1982, 8, 831.
. Yadav, V. K.; Fallis, A. G. Tetrahedron Lett. 1988, 29,
22. Saraswathy, V. G.; Geetha, V.; Sankararaman, S. J. Org.
Chem. 1994, 52, 4665.
8
97.
23. (a) Kobayashi, S. Eur. J. Org. Chem. 1999, 15; (b)
Kobayashi, S. Synlett 1994, 689.
24. A typical procedure: To a stirred mixture of 4-methoxy-
benzaldehyde (680 mg, 5 mmol) and 1,3-propanedithiol
(648 mg, 6 mmol) in acetonitrile (25 mL) was added
9
. Ravindranathan, T.; Chavan, S. P.; Dante, S. W. Tetra-
hedron Lett. 1995, 36, 2285.
0. Ong, B. S. Tetrahedron Lett. 1980, 21, 4225.
1. Kumar, V.; Dev, S. Tetrahedron Lett. 1983, 24, 1289.
2. Anand, R. V.; Sarvanan, P.; Singh, V. K. Synlett 1999,
1
1
1
Y(OTf)
3
(135 mg, 5 mol %) at room temperature. The
4
3. Kamitori, Y.; Hojo, M.; Masuda, R.; Kimura, T.;
Yoshida, T. J. Org. Chem. 1986, 52, 1427.
4. Pantey, H. K.; Margan, S. Tetrahedron Lett. 1996, 37,
13.
reaction mixture was stirred at room temperature for
25 min, diluted with ethyl acetate (100 mL), washed with
water (50 mL), dried (MgSO ), and concentrated in vacuo.
4
1
1
1
1
1
The crude product was purified by silica gel column
chromatography (15% ethyl acetate in hexane) to afford
4
621.
1
5. Khan, A. T.; Mondal, E.; Sahu, P. R.; Islam, S. Tetra-
hedron Lett. 2003, 44, 919.
6. Srivastava, N.; Dashgupta, S. K.; Banik, B. K. Tetra-
hedron Lett. 2003, 44, 1191.
7. Leonard, N. M.; Oswald, M. C.; Friederg, D. A.; Nattier,
B. A.; Smith, R. C.; Mohan, R. S. J. Org. Chem. 2002, 67,
pure 2-(4-methoxy)phenyl-1,3-dithiane (93%). H NMR
3
(500 MHz, CDCl ) d 1.86–1.98 (m, 1H), 2.10–2.18 (m,
1H), 2.85–2.95 (m, 2H), 2.98–3.10 (m, 2H), 3.79 (s, 3H),
5.13 (s, 1H), 6.86 (d, J ¼ 8:5 Hz, 2H), 7.39 (d, J ¼ 8:5 Hz,
2H). The aqueous layer containing the catalyst could be
evaporated under reduced pressure to give a white solid.
The IR spectrumof the recovered catalyst was identical to
that of the commercially available catalyst (Aldrich),
which could be reused for the next thioacetalyzation
reaction, without losing any significant activity (Table 1,
entries 2 and 21).
5
202.
8. Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synthesis 1999,
8.
9. Yadav, J. S.; Reddy, B. S.; Pandey, S. K. Synlett 2001,
38.
1
1
5
2