Pr(OTf)3 as an efficient and recyclable catalyst for chemoselective thioacetalization of aldehydes

Article abstract of DOI:10.1055/s-2004-834858

Praseodymium triflate has been found to be an efficient and recyclable catalyst for chemoselective protection of aldehydes.

Full text of DOI:10.1055/s-2004-834858

PAPER
2837
Pr(OTf) as an Efficient and Recyclable Catalyst for Chemoselective
3
Thioacetalization of Aldehydes
P
S
r(OTf) as Ca
u
talyst for Ch
r
emosele
y
c
tive Thioac
a
etalization of
Ald
K
ehydes anta De*
3
Department of Chemistry, University of Washington, Seattle, WA 98195, USA
Fax +1(765)4941414; E-mail: skd125@yahoo.com
Received 13 May 2004; revised 5 August 2004
ethyldithioacetals from carbonyl compounds. While most
conventional Lewis acids are decomposed or deactivated
Abstract: Praseodymium triflate has been found to be an efficient
and recyclable catalyst for chemoselective protection of aldehydes.
in the presence of water or protic solvent, Pr(OTf) is sta-
3
Key words: praseodymium triflate, aldehydes, 1,3-dithiolanes,
ble in water and does not decompose under aqueous work-
up conditions. Thus, recyclization is often possible. These
unique properties of praseodymium triflate make this
method eco-friendly, and environmentally acceptable.
1
,3-oxathiolanes, 1,3-dithianes, dithioacetals
The protection of carbonyl functionality as a dithioacetal1
is important in the total synthesis of complex natural and
non-natural products due to the group’s inherent stability
under both acidic and basic conditions. Among different
carbonyl protecting groups, 1,3-dithianes, 1,3-oxathio-
lanes, 1,3-dithiolanes have long been used as protective
groups, and an acyl anion equivalent in carbon-carbon
In this letter, various types of aldehydes are reported to be
rapidly converted to the corresponding cyclic or acyclic
thioacetals under mild conditions in the presence of a cat-
alytic amount of Pr(OTf) at room temperature. Interest-
3
ingly, the experimental procedure is very simple and does
not require the use of anhydrous solvents or an inert atmo-
sphere.
2
bond forming reactions. In the literature there is quite a
plethora of procedures reported for the protection of car- A catalytic amount of praseodymium triflate (5 mol%) is
3
bonyl compounds as dithioacetals employing HCl,
sufficient to obtain the desired carbonyl derivatives in ex-
cellent yields (Scheme 1). The method has the ability to
4
5
6
7
8
BF ·OEt , PTSA, Bu NBr , TMSOTf, i-Pr SiOTf,
3
2
4
3
3
14
9
10
11
12
13
SO , LiBr, LiBF , InCl , AlCl , TiCl4, 5 M tolerate a variety of other protecting groups such as ben-
2
4
3
17
3
18
LiClO4, ZrCl4,16 Sc(OTf)3, and I2 as catalyst or as zyloxy, allyloxy, methoxy, ester, TBS ether. As shown in
1
5
stoichiometric reagents. However, many of these methods6 Table 1, various activated and deactivated aromatic alde-
have some drawbacks such as low yields of the products,
hydes, heterocyclic aldehydes and aliphatic aldehydes un-
1
6
3–5
long reaction times, harsh reaction conditions, diffi- dergo the protection reactions using 2-mercaptoethanol,
1
3,14
culties in work-up,
the requirement for an inert atmo- 1,2-ethanedithol, 1,3-propanedithiol or ethanethiol in the
1
5
4,9
sphere, and the use of stoichiometric or relatively presence of catalytic amount of Pr(OTf) in MeCN at
expensive reagents.
3
6
–8,15,16
Interestingly, only a few of room temperature to afford the corresponding 1,3-oxathi-
these methods have demonstrated chemoselective protec- olanes, 1,3-dithiolanes, 1,3-dithianes or diethyldithioace-
tion of aldehydes in the presence of ketones. Some of the tals in good to excellent yields.
methods mentioned above are incompatible with other
protecting groups such as TBS ethers4
b,10b,11b,18b
and fail to
S
1
7
protect deactivated aromatic aldehydes. Moreover, the
main disadvantage of almost all existing methods is that
SHCH2CH2OH
SHCH2CH2SH
R
O
S
H
2
–16,18
the catalysts are destroyed
in the work-up procedure
S
and cannot be recovered or reused. Therefore, there is still
a need to search for a better catalyst that could be superior
to the existing ones with regards to toxicity, handling,
easy availability, economic viability, recyclability, great-
er selectivity, and operational simplicity.
O
Pr(OTf)3 (5 mol%)
CH3CN, r.t.
R
R
H
H
S
SHCH2CH2CH2SH
EtSH
R
S
H
Recently, there has been growing interest in the use of lan-
thanide triflates as potential Lewis acids in various organ-
ic reactions because they are quite stable in water and
are reusable. The catalyst praseodymium triflate
1
9
RCH(SEt)2
Scheme 1
[
Pr(OTf) ] is commercially available and can be used for
3
preparation of oxathiolanes, dithiolanes, dithianes, and di-
It is interesting to note that ketones did not produce the
corresponding thioacetals under the same reaction condi-
tions. With this objective, a set of competitive protection
reactions was conducted between aldehydes and ketones,
the results of which are shown in Scheme 2. These results
SYNTHESIS 2004, No. 17, pp 2837–2840
x
x.
x
x
.
2
0
0
4
Advanced online publication: 07.10.2004
DOI: 10.1055/s-2004-834858; Art ID: M03504SS
Georg Thieme Verlag Stuttgart · New York
©

2
838
S. K. De
PAPER
indicate that the presented protocol is potentially applica-
ble for the chemoselective protection of aldehydes to the
corresponding dithioacetals in the presence of ketone
functions in multi-functional compounds. The aldehyde
functionality of a keto-aldehyde was protected chemose-
lectively under identical condition (Scheme 3).
S
CHO
S
Pr(OTf)3 (5 mol%)
8
9%
HSCH2CH2SH
O
S
CH3CN, r.t., 30 min
CH3
S
CH3
Most recently, I reported the thioacetalization of alde-
2
0
21
22
hydes using ScCl , CoCl , Y(OTf)3 as catalysts and
3
2
0%
2
3
RuCl3 as a catalyst for acetalization of alcohols. Metal
halides such as CoCl , ScCl , RuCl or other are generally
O
S
2
3
3
Pr(OTf)3 (5 mol%)
H
O
decomposed during work-up and could not reused. Metal
triflates are stable in water and do not decompose under
aqueous work-up conditions. In this context, Sc(OTf)3
S
8
5%
H
HSCH2CH2SH
CH3
S
CH3CN, r.t., 30 min
and Y(OTf) work well for thioacetalization of aldehydes.
S
3
CH3
%
The catalyst Sc(OTf) is five times more expensive than
3
0
Pr(OTf) and it did not work well with deactivated aro-
3
1
7
Scheme 2
matic aldehydes. The reused catalytic activity of
Pr(OTf) is better than that of Y(OTf) and is identical to
3
3
that of Sc(OTf) . The activity of recovered catalyst,
3
O
S
Y(OTf) , decreases after two runs whereas Pr(OTf) can
3
3
be used five times without any loss of catalytic activity
Table 2). These results indicate that Pr(OTf) is superior
to the other metal triflates with regards to recyclability
H
HSCH2CH2SH
S
(
H3C
3
H3C
O
Pr(OTf)3, CH3CN, r.t.,
0 min
3
O
89%
S
and economic viability.
In conclusion, a very simple and convenient protocol for
the protection of various aldehydes as dithioacetals using
a catalytic amount of praseodymium triflate has been
demonstrated. Further, the catalyst can be readily recov-
ered and reused, thus making this method eco-friendly
and environmentally acceptable. Moreover, highly deacti-
vated aromatic aldehydes can be converted to the corre-
O
O
O
HSCH2CH2SH
S
H
Pr(OTf) , CH CN, r.t.,
3
3
8
5%
3
0 min
Scheme 3
sponding dithioacetals without any difficulty. A high 2-(4-Methoxyphenyl)-1,3-dithiane; Typical Procedure
To a stirred mixture of 4-methoxybenzaldehyde (681 mg, 5 mmol)
and 1,3-propanedithiol (649 mg, 6 mmol) in MeCN (25 mL) was
degree of chemoselectivity, high product yields, and reus-
ability are the main advantages of this new method, which
will make it a useful and important addition to the present
methodologies.
added Pr(OTf) (146 mg, 5 mol%) at r.t. The resulting mixture was
3
stirred at r.t. for 30 min, then diluted with EtOAc (150 mL), washed
with water (60 mL), dried (MgSO ) and concentrated. The residue
4
was chromatographed over silica gel, eluted with 10% EtOAc in
hexane to afford pure 2-(4-methoxyphenyl)-1,3-dithiane. The aque-
ous layer containing the catalyst could be evaporated under reduced
pressure to give a white solid. The IR spectrum of the recovered cat-
alyst was identical to that of the commercially available catalyst
(Aldrich), which could be reused for the next thioacetalization reac-
tion, without losing any significant activity (Table 2, entries 2, 3,
and 17).
1H NMR spectra were recorded on a Bruker 500 MHz spectrometer
in CDCl as the solvent and TMS as internal standard. Mass spectra
3
were recorded with a Bruker ion trap spectrometer. All products are
known and were determined using comparison of their physical and
spectral data with those reported in the literature (see refs20,24–29).
Table 1 Pr(OTf) Catalyzed Protection of Aldehydes as Dithianes, Dithiolanes, Oxathiolanes or Diethyldithioacetals at Room Temperature
3
Entry
Catalysts
Pr(OTf)3
Y(OTf)3
Sc(OTf)3
CoCl2
1st,a
89
90
92
90
86
2nd
87
84
87
52
50
3rd
90
70
92
–
4th
88
65
82
–
5th
93
60
91
–
Average
89.4
1
2
3
4
5
73.8
88.8
28.4
ScCl3
–
–
–
27.2
a
1
Isolated yield (for first run only), and conversion of starting material (for other runs, based on H NMR).
Synthesis 2004, No. 17, 2837–2840 © Thieme Stuttgart · New York

PAPER
Pr(OTf) as Catalyst for Chemoselective Thioacetalization of Aldehydes
2839
3
Table 2 The Thioacetalization of Benzaldehyde with 1,3-Dithiolane in the Presence of Catalysts and Recycled Catalysts
a
Entry
Substrate
Reagent
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
Benzaldehyde
HSCH CH CH SH
0.5
0.5
1
89
2
2
2
4-Methoxybenzaldehyde
4-Chlorobenzaldehyde
4-Nitrobenzaldehyde
Furfural
HSCH CH CH SH
91/85b
89/86b
84
2
2
2
HSCH CH CH SH
2
2
2
HSCH CH CH SH
3
2
2
2
HSCH CH CH SH
1
86
2
2
2
4-Benzyloxybenzaldehyde
Cinnamaldehyde
HSCH CH SH
1
88
2
2
HSCH CH SH
0.5
1
87
2
2
Thiophene-2-carboxaldehyde
4-Hydroxybenzaldehyde
Butyraldehyde
HSCH CH SH
91
2
2
HSCH CH SH
5
78
2
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
HSCH CH SH
1
82
2
2
4-Allyloxybenzaldehyde
Hexaldehyde
HSCH CH SH
1
83
2
2
HSCH CH SH
0.5
1
85
2
2
4-TBSO-benzaldehyde
4-Carbomethoxybenzaldehyde
4-Methylbenzaldehyde
4-Nitrobenzaldehyde
Benzaldehyde
HSCH CH SH
83
2
2
HSCH CH SH
1
91
2
2
HSCH CH SH
1
92
2
2
HSCH CH SH
4
80
2
2
HSCH CH SH
0.5
1
89/82b
93
2
2
4-Methoxybenzaldehyde
4-Bromobenzaldehyde
Decylaldehyde
HSCH CH SH
2 2
HSCH CH SH
1
89
2
2
HSCH CH SH
1
80
2
2
Benzaldehyde
HSCH CH OH
2
79
2
2
4-Methoxybenzaldehyde
Hexaldehyde
HSCH CH OH
2
81
2
2
HSCH CH OH
3
79
2
2
Benzaldehyde
CH CH SH
6
89
3
2
4-Chlorobenzaldehyde
4-Methoxybenzaldehyde
Butyraldehyde
CH CH SH
5
91
3
2
CH CH SH
5
85
3
2
CH CH SH
6
79
3
2
a
1
Yields refer to pure isolated products, characterized by IR, H NMR and MS.
Isolated yields with the reused catalyst.
b
References
(3) Ralls, J. W.; Dobson, R. M.; Reigel, B. J. Am. Chem. Soc.
949, 71, 3320.
4) (a) Fieser, L. F. J. Am. Chem. Soc. 1954, 76, 1945.
b) Nakata, T.; Nagao, S.; Mori, S.; Oishi, T. Tetrahedron
1
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3 rd ed.; John Wiley and Sons: New York, 1999,
(
(
329–344.
Lett. 1985, 26, 6461.
(2) (a) Seebach, D. Angew. Chem., Int. Ed. Engl. 1969, 8, 639.
(
(
5) Djerassi, C.; Gorman, M. J. Am. Chem. Soc. 1953, 75, 3704.
6) Mondal, E.; Sahu, P. R.; Bose, G.; Khan, T. Tetrahedron
Lett. 2002, 43, 2843.
(
(
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. (d) Pettit, G. R.; Van Tamelen,
E. E. Org. React. 1962, 12, 356.
Synthesis 2004, No. 17, 2837–2840 © Thieme Stuttgart · New York

2
840
S. K. De
PAPER
(
(
(
7) Ravindranathan, T.; Chavan, S. P.; Dante, S. W.
(19) (a) Kobayashi, S. Eur. J. Org. Chem. 1999, 15.
Tetrahedron Lett. 1995, 36, 2285.
8) Streinz, L.; Koutek, B.; Saman, D. Collect. Czech. Chem.
Commun. 1977, 62, 665.
(b) Kobayashi, S. Synlett 1994, 689. (c) Kobayashi, S.;
Tomaaki, H.; Nagayama, S.; Manabe, K. Org. Lett. 2001, 3,
165. (d) Hamada, T.; Manabe, K.; Nagayama, S.; Shiro, S.;
Kobayashi, S. J. Am. Chem. Soc. 2003, 125, 2989.
(20) De, S. K. Synthesis 2004, 828.
9) Burezyk, B.; Kortylewicz, Z. Synthesis 1982, 831.
(
(
(
10) (a) Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synthesis 1999,
5
8. (b) Tandon, M.; Begley, T. P. Synth. Commun. 1997, 27,
(21) De, S. K. Tetrahedron Lett. 2004, 45, 1035.
(22) De, S. K. Tetrahedron Lett. 2004, 45, 2339.
(23) De, S. K. Tetrahedron Lett. 2004, 45, 2919.
(24) Robbe, Y.; Fernandez, J. P.; Dubiel, R.; Chapat, J. P.;
Senteac, H.; Fatome, M.; Denis, J. Eur. J. Med. Chem. 1982,
17, 235.
(25) Prabhat, A.; Samson, C.; Lesage, M.; Goiller, D. J. Org.
Chem. 1990, 55, 648.
(26) Kamitori, Y.; Hojo, M.; Mashuda, R.; Kimura, T.; Yoshida,
T. J. Org. Chem. 1986, 51, 1427.
2953.
11) (a) Jadav, J. S.; Reddy, B. S.; Pandey, S. K. Synlett 2001,
38. (b) Metcalf, B. W.; Burkhart, J. P.; Jund, K.
2
Tetrahedron Lett. 1980, 21, 35.
12) Madhuswamy, S.; Arulananda Babu, S.; Gunanathan, C.
Tetrahedron Lett. 2001, 42, 359.
(13) Ong, B. S. Tetrahedron Lett. 1980, 21, 4225.
(14) Kumar, V.; Dev, S. Tetrahedron Lett. 1983, 24, 1289.
(15) Saraswathy, V. G.; Geetha, V.; Sankaranan, S. J. Org. Chem.
1
994, 52, 4665.
(27) Toshikazu, H.; Ohshiro, S.; Agawa, Y. Bull. Chem. Soc. Jpn.
1983, 56, 1569.
(28) Degani, S.; Regondi, R. Synthesis 1981, 51.
(29) Gonnella, N. C.; Lakshmikantham, M. V.; Cava, M. P.
Synth. Commun. 1997, 9, 17.
(
(
(
16) Karimi, B.; Seradj, H. Synlett 2000, 805.
17) Kamal, A.; Chouhan, G. Tetrahedron Lett. 2002, 43, 1347.
18) (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.
Synthesis 2004, No. 17, 2837–2840 © Thieme Stuttgart · New York