Lutetium triflate as an efficient and recyclable catalyst for chemoselective thioacetalization of aldehydes

Article abstract of DOI:10.1081/SCC-200039488

Lutetium Inflate has been found to be an efficient and recyclable catalyst for chemoselective thioacetalization of aldehydes.

Full text of DOI:10.1081/SCC-200039488

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Lutetium Triflate as an
Efficient and Recyclable
Catalyst for Chemoselective
Thioacetalization of
Aldehydes
Surya Kanta De a
a Department of Medicinal Chemistry and
Molecular Pharmacology, School of Pharmacy ,
Purdue Cancer Center, Purdue University , West
Lafayette, Indiana, 47907, USA
Published online: 12 Jan 2011.
To cite this article: Surya Kanta De (2004) Lutetium Triflate as an Efficient and
Recyclable Catalyst for Chemoselective Thioacetalization of Aldehydes, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:23, 4401-4408, DOI: 10.1081/SCC-200039488
To link to this article: http://dx.doi.org/10.1081/SCC-200039488
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 23, pp. 4401–4408, 2004
Lutetium Triflate as an Efficient and
Recyclable Catalyst for Chemoselective
Thioacetalization of Aldehydes
*
Surya Kanta De
Department of Medicinal Chemistry and Molecular Pharmacology,
School of Pharmacy, Purdue Cancer Center, Purdue University,
West Lafayette, Indiana, USA
ABSTRACT
Lutetium triflate has been found to be an efficient and recyclable catalyst
for chemoselective thioacetalization of aldehydes.
Key Words: Aldehydes; Chemoselectivity; Lutetium triflate; Thio-
acetalization.
The protection of carbonyl compounds plays an important role during
multistep syntheses in organic, medicinal, carbohydrate, and drug design
chemistry. Among the different carbonyl protecting groups, 1,3-dithiolanes,
*
Correspondence: Surya Kanta De, Department of Medicinal Chemistry and Molecular
Pharmacology, School of Pharmacy, Purdue Cancer Center, Purdue University,
West Lafayette, IN 47907, USA; E-mail: skd125@yahoo.com.
4401
DOI: 10.1081/SCC-200039488
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

4402
De
1,3-dithianes, and diethyldithioacetals[1] are important, as they are stable
under both mildly acidic and basic conditions. In addition, these are utilized
as masked acyl anions or masked methylene functions in carbon–carbon
bond-forming reactions.[2] In the literature, there are numerous methods
reported for the preparation of thioacetals from carbonyl compounds employ-
ing PTSA,[3] BF3 OEt2,[4] Zn(OTf)2,[5] SO2,[6] TMSOTf,[7] AlCl3,[8] TiCl4,[9]
.
Cu(OTf)2,[10] SOCl2,[11] ZrCl4,[12] InCl3,[13] I2,[14] LiBr,[15] LiBF4,[16]
Sc(OTf)3,[17] and 5 M LiClO4.[18] However, many of these methods have
some drawbacks, such as low yields of the products, long reaction times,[12]
harsh reaction conditions,[3,4] difficulties in workup,[8,9] requirement
for an inert atmosphere,[18] and use of stoichiometric[4,6] or relatively
expensive reagents.[7,9,12,15] Some methods mentioned above are incompatible
with other protecting groups, such as tert-butyldimethylsilyl (TBS)
ethers[4b,15b,14b,16b] and fail to protect deactivated aromatic substrates.[17]
Moreover, the main disadvantage of all existing methods is that the catalysts
are decomposed in the workup procedure and cannot be recovered or reused.
Therefore, the search continues for a better catalyst, one superior to the exist-
ing ones with regard to recyclability, operational simplicity, economic viabi-
lity, and greater selectivity.
Recently, lanthanide triflates have been introduced as promising mild and
selective reagents in organic synthesis.[19] The catalyst lutetium triflate is
commercially available and can be used as catalyst in the preparation of
dithiolanes, dithianes, and dithioacetals from carbonyl compounds. While
most conventional Lewis acids decompose in the presence of water, Lu(OTf)3
is stable in water and does not decompose under aqueous workup conditions.
Thus, recyclization is often possible from aqueous workup (see the “Experi-
mental” section). A catalytic amount of Lu(OTf)3 is sufficient to obtain
the desired compounds in excellent yield (Scheme 1). Thus, various aromatic,
aliphatic, heterocyclic aldehydes undergo the protection reactions using
1,2-ethanedithiol, 1,3-propranedithiol or ethanethiol to give the corresponding
1,3-dithiolanes, 1,3-dithianes or diethyldithioacetals in good to excellent yield
(Table 1). The experimental procedure for these reactions is simple and does
not need the use of dry solvents or inert atmospheres. It is noteworthy that the
Scheme 1.

Lutetium Triflate as Catalyst
4403
Table 1. Lu(OTf)3 catalyzed protection of aldehydes as dithiolanes, dithianes, or
ethyldithioacetals at room temperature.
Time
(h)
Yielda
(%)
Entry
Substrate
Benzaldehyde
Reagent
1
2
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2CH2SH
HSCH2CH3
6
4
83
89
85/79b
72
86
4-Methoxybenzaldehyde
4-Chlorobenzaldehyde
4-Nitrobenzaldehyde
Furfural
3
5
4
10
3
5
6
4-Benzyloxybenzaldehyde
Cinnamaldehyde
2-Naphthaldehyde
5
80
91
7
2
8
12
3
70
9
Thiophene 2-carboxaldehyde
Piperonal
85/81b
83
80
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
8
2-Methoxybenzaldehyde
4-Carbomethoxybenzaldehyde
4-Allyloxybenzaldehyde
Hexaldehyde
7
7
85
91
4
6
83
88
4-TBSO-benzaldehyde
1-Octanal
Butyraldehyde
3
6
72
78
7
Decyl aldehyde
6
70
82
4-Acetyloxybenzaldehyde
4-Benzoyloxybenzaldehyde
4-Bromobenzaldehyde
Benzaldehyde
6
5
85
91
5
5
88
90
4-Methoxybenzaldehyde
4-Chlorobenzaldehyde
2-Naphthaldehyde
4
6
12
73
68
HSCH2CH3
aYields refer to pure isolated products, characterized by 1H NMR and mass spec-
trometry (MS).
bIsolated yields with reused catalyst.
conversion can be achieved in the presence of other protecting groups such as
benzyl, acetyl, allyl, esters, and TBS ethers. Moreover, highly deactivated
aromatic aldehydes can be protected as dithioacetals in good yield.
Also, note that the protocol can be extended for the chemoselective pro-
tection of an aldehyde in the presence of a ketone. For instance, when an equi-
molar mixture of 4-methoxybenzaldehyde and 4-methoxyacetophenone was
allowed to react with 1,2-ethanedithiol in the presence of a catalytic amount

4404
De
Scheme 2.
of Lu(OTf)3, only the dithiolane derivative of 4-methoxybenzaldehyde was
obtained in 89% yield after 2 h (Scheme 2).
In summary, a simple and efficient method has been developed by using a
catalytic amount of Lu(OTf)3 for protection of aldehydes as dithioacetals in
the presence of a wide range of other protecting groups. Further, the catalyst
can be readily recovered and reused, thus making the procedure environmen-
tally friendly and acceptable.
EXPERIMENTAL
Most of the products are known compounds and were identified by their
spectral data (1H NMR) and physical properties compared with those of auth-
entic samples. The progress of reaction was monitored by thin-layer chrom-
atography (TLC) on silica gel. All yields refer to isolated products.
A Typical Procedure
To a stirred mixture of 4-methoxybenzaldehyde (680 mg, 5 mmol) and
1,2-ethanedithiol (564 mg, 6 mmol) in acetonitrile (30 mL) was added
Lu(OTf)3 (312 mg, 10 mol%) at room temperature. The resulting mixture
was stirred for 1.5 h, then diluted with ethyl acetate (150 mL), washed with
water (60 mL), dried (MgSO4), and concentrated. The residue was chromato-
graphed over silica gel, eluted 15% ethyl acetate in hexane to afford pure 2-(4-
methoxyphenyl)-1,3-dithiolane. The aqueous layer containing the catalyst can

Lutetium Triflate as Catalyst
4405
be evaporated under reduced pressure (408C, 30 mm Hg pressure) to give a
white solid that was reused for the next thioacetalization reaction (Table 1).
Product Characterization Data
(Compounds are Numbered as the Entries—Table 1)
Compound 1: Bp 157–1598C/3 torr; lit.[20] 1608C/3 torr.
Compound 2: Bp 140–1428C/4 torr; lit.[20] 1408C/4 torr.
Compound 3: Mp 117–1188C; lit.[20] 1198C.
1
Compound 4: Mp 75–768C, H NMR (500 MHz, CDCl3) d 8.16 (d,
J ¼ 8.5 Hz, 2H), 7.67 (d, J ¼ 8.5 Hz, 2H), 5.65 (s, 1H), 3.56–3.45
(m, 2H), 3.43–3.36 (m, 2H). MS m/z 228 (M þ H)þ Anal. Calcd. for
C9H9NO2S2: C, 47.56; H, 3.99; N, 6.16. Found: C, 47.52; H, 4.01;
N, 6.14%.
Compound 5: Bp 110–1118C/5 torr; lit.[20] 1108C/5 torr.
1
Compound 6: Mp 86–878C; H NMR (500 MHz, CDCl3) d 7.48–7.30
(m, 7H), 6.90 (d, J ¼ 8.5 Hz, 2H), 5.63 (s, 1H), 5.05 (s, 2H), 3.51–
3.45 (m, 2H), 3.36–3.30 (m, 2H).
Compound 7: Mp 65–668C; lit.[20] 678C.
Compound 8: Mp 148–1508C; lit.[21] 1498C.
Compound 9: Oil; lit.[20] oil (identical NMR data).
Compound 10: Mp 45–478C; lit.[22] 448C.
Compound 11: Bp 138–1398C/0.6 torr; lit.[23] 1408C/0.6 torr.
Compound 12: Mp 110–1118C, 1H NMR (500 MHz, CDCl3) d 7.98 (d,
J ¼ 8 Hz, 2H), 7.57 (d, J ¼ 8 Hz, 2H), 5.64 (s, 1H), 3.90 (s, 3H),
3.54–3.46 (m, 2H), 3.39–3.35 (m, 2H).
1
Compound 13: Oil, H NMR (500 MHz, CDCl3) d 7.44 (d, J ¼ 8 Hz,
2H), 6.85 (d, J ¼ 8.5 Hz, 2H). 6.10–5.90 (m, 1H), 5.63 (s, 1H),
5.41–5.26 (m, 2H), 4.52 (d, J ¼ 4 Hz, 2H), 3.52–3.45 (m, 2H),
3.38–3.32 (m, 2H).
Compound 14: Bp 120–1228C/16 torr; lit.[8] 1258C/16 torr.
1
Compound 15: Oil, H NMR (500MHz, CDCl3) d 7.38 (d, J ¼ 8.5 Hz,
2H), 6.76 (d, J ¼ 8.5 Hz, 2H), 5.62 (s, 1H), 3.52–3.40 (m, 2H), 3.35–

4406
De
3.26 (m, 2H), 0.97 (s, 9H), 0.19 (s, 6H). MS m/z 313 (M þ H)þ Anal.
Calcd. for C15H24OS2Si: C, 57.64; H, 7.74. Found: C, 57.66; H, 7.78%.
Compound 16: Bp 2878C/760 torr; lit.[20] 2898C/760 torr.
Compound 17: Bp 64–668C/3 torr; lit.[20] 658C/3 torr.
Compound 18: Bp 3208C/760 torr; lit.[23] 3228C.
1
Compound 19: Mp 95–968C, H NMR (500 MHz, CDCl3) d 7.53 (d,
J ¼ 6.5 Hz, 2H), 7.03 (d, J ¼ 6.5 Hz, 2H), 5.63 (s, 1H), 3.49–3.40
(m, 2H), 3.35–3.32 (m, 2H), 2.29 (s, 3H).
Compound 20: Bp 1808C/5 torr; lit.[23] 1888C/5 torr.
Compound 21: Mp 61–628C; lit.[23] 618C.
Compound 22: Mp 74–758C; lit.[20] 758C.
Compound 23: Mp 114–1158C; lit.[20] 1158C.
Compound 24: Bp 1208C/5 torr; lit.[20] 125/5 torr.
Compound 25: Bp 150–1528C; lit.[23] 1508C.
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Received in the USA July 30, 2004