Scandium(III) Triflate as an Efficient and Recyclable Catalyst for Chemoselective Conversion of Carbonyl Compounds to 1,3-Oxathiolanes

Article abstract of DOI:10.1055/s-2003-42436

A variety of carbonyl compounds can be easily and rapidly converted to the corresponding 1,3-oxathiolanes in the presence of a catalytic amount of scandium(III) triflate [Sc(OTf)₃] in CH₂Cl₂. After completion of the reacti

Full text of DOI:10.1055/s-2003-42436

PAPER
2503
Scandium(III) Triflate as an Efficient and Recyclable Catalyst for Chemo-
selective Conversion of Carbonyl Compounds to 1,3-Oxathiolanes
S
candium(III) Tr
a
a
C
b
a
talyst for
C
a
onversion
k
K
undsto1,3-Oxath
a
iolanes rimi,* Leila Ma’mani
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), P. O. Box 45195-159, Gava Zang, Zanjan, Iran
Received 17 March 2003; revised 21 July 2003
Recently, scandium triflate [Sc(OTf)3] has been intro-
Abstract: A variety of carbonyl compounds can be easily and rap-
duced as a promising mild and selective reagent for a va-
idly converted to the corresponding 1,3-oxathiolanes in the pres-
riety of functional group transformations.15 While most
Lewis acids are decomposed or deactivated in the pres-
ence of a catalytic amount of scandium(III) triflate [Sc(OTf)3] in
CH2Cl2. After completion of the reaction, the catalyst can straight-
forwardly be recovered using standard methods. Moreover, by em- ence of water or protic solvent, Sc(OTf)3 is stable and
works as a Lewis acid even in aqueous solutions.16 Thus,
ploying this protocol, chemoselective oxathioacetalization of
aldehydes in the presence of ketones can be achieved.
unlike other traditional Lewis acids, Sc(OTf)3 does not
Key words: heterocycles , protecting groups , acetals, , scandium ,
aldehydes, ketones, catalysis
decompose in aqueous work-up conditions and its recov-
ery is often possible. This creates a relatively environmen-
tally acceptable picture for Sc(OTf)3 as a catalyst in
functional group transformations. Along with these prop-
In view of the electrophilic properties of carbonyl group erties, this catalyst has successfully been used for a wide
in aldehydes and ketones, one of the major challenging range of synthetic organic reactions,15 especially as a
problems during many multi-step syntheses is how to pro- Lewis acid in aldol condensation reactions,17 Diels–Al-
tect a carbonyl group from a specific nucleophilic attack der,18 Friedel–Crafts acylation,19 Michael reactions,20 and
until its electrophilic nature can be exploited. Among dif- Fries rearrangement.21A literature search clearly shows
ferent carbonyl protecting groups, 1,3-oxathioacetals that there is no report on the application of Sc(OTf)3 as a
have long been used as a protective group,1 and an acyl catalyst for the preparation of oxathioacetals. Based on
anion equivalent in C–C bond forming reactions.2 More- knowledge regarding the formation of water upon the re-
over, they are considerably more stable than the corre- action of 2-mercaptoethanol with carbonyl compounds
sponding O,O-acetals under acidic conditions and also and also the amazing water stability of Sc(OTf)3, we con-
easier to remove than S,S-acetals. On the other hand, the ceived that this catalyst might be better suited for cata-
elegant work of Eliel,3 and the others4 using chiral 1,3-ox- lyzing the oxathioacetalization of carbonyl compounds.
athioacetals as chiral auxiliaries for the enantioselective
In this paper, we wish to report that various type of carbo-
synthesis of -hydroxy acids and glycols have clearly es-
nyl compounds were rapidly converted to the correspond-
tablished the use of oxathioacetals in organic synthesis.
ing 1,3-oxathiolanes under mild and selective conditions
Though there is quite a plethora of procedures available
in the presence of a catalytic amount Sc(OTf)3 in CH2Cl2
for the protection and deprotection of carbonyl com-
as solvent at room temperature (Scheme 1).
pounds as S,S-acetals, only a few methods have been de-
veloped for oxathioacetals.1 The existing methods employ
O
HCl,5 HClO4,6 refluxing with TsOH,7 BF3·OEt2,8
SH
S
O
(1.5-2.5 equiv.)
HO
Bu4NBr3,9 TMSOTf,10 i-Pr3SiOTf,11 SO2,12 ZrCl4,13 or
ZnCl2–Na2SO414 as catalyst or as stoichiometric reagents.
However many of these methods have certain drawbacks
such as low yields of the products,9 harsh reaction condi-
tions,5,7,8 long reaction times,13 or use of either
stoichiometric8,12 or expensive 9–11 reagents. Moreover the
main disadvantage of almost all existing procedures is that
the catalysts are destroyed in the work-up procedure and
thus cannot be recovered or reused. Therefore, the search
for a better catalyst that could be superior to the existing
ones especially with regard to recyclability and selectivity
is still a need.
R1
R2
Sc(OTf)3 (1-5 mol%), CH2Cl2, rt
R1
R2
R1 = aryl, alkyl, allyl
R2 = aryl, alkyl, or H
Scheme 1
As shown in Table 1, various types of aromatic and ali-
phatic aldehydes including both activated and deactivated
aldehydes are efficiently and rapidly converted to their
corresponding 1,3-oxathilanes in the presence of 2-mer-
captoethanol (1.5 equiv) and Sc(OTf)3 (1 mol%) under
mild reaction conditions (entries 1–10). In the case of al-
dehydes, the reactions were rapid and the yields of the
products were considerably higher than the recent proto-
cols.6,9 Efficient protection of 4-nitrobenzaldehyde (entry
5) is worth mentioning, and the aromatic and aliphatic ke-
tones also furnished excellent yields of the corresponding
SYNTHESIS 2003, No. 16, pp 2503–2506
x
x.
x
x
.
2
0
0
3
Advanced online publication: 23.10.2003
DOI: 10.1055/s-2003-42436; Art ID: Z04003SS
© Georg Thieme Verlag Stuttgart · New York

2504
B. Karimi, L. Ma’mani
PAPER
1,3-oxathiolanes in the presence of 2-mercaptoethanol 1,3-oxathiolane. Therefore, we have conducted a set of
(1.5–2.5 equiv) and Sc(OTf)3 (5 mol%), although after competitive protection reactions between aldehydes and
relatively longer reaction times (Table 1, entries 11–20). ketones the results of which are shown in Scheme 2.
Also, in contrast to many of the previously reported Lewis
These results show that the presented protocol is poten-
acid catalyzed methods for the preparation of 1,3-oxathio-
tially applicable for the chemoselective conversion of al-
lanes which utilize stoichiometric amounts of catalyst,8,12
dehydes to the corresponding 1,3-oxathiolanes in the
in this method a small amount of Sc(OTf)3 (0.01–0.05
presence of ketone functions in multi-functional com-
equiv) is enough for the reaction to proceed cleanly. It is
pounds.
also noteworthy that in this method no dehydrating agent
In summary, it is notable that due to the utility of this pro-
is necessary and after completion of the reactions scandi-
cedure, ie reusable catalyst, high degree of chemoselectiv-
um triflate can be easily recovered. As shown in Table 1,
ketones need more time and reagent to be converted into
Table 1 Sc(OTf)3 Catalyzed Preparation of 1,3-Oxathiolanes under Mild Reaction Conditions
Entry
R1
R2
Substrate/
Time
Yielda (%)
HO(CH2)2SH/
Sc(OTf)3
1
2
Ph
H
H
H
H
H
H
H
H
H
1:1.5:0.01
1:1.5:0.01
1:1.5:0.01
1:1.5:0.01
1:1.5:0.01
1:1.5:0.01
1:1.5:0.01
1:1.5:0.01
1:1.5:0.01
1:1.5:0.01
1:2.5:0.05
1:2.5:0.05
1:2.5:0.05
1:2.5:0.05
10 min
10 min
10 min
10 min
15 min
5 min
7 min
5 min
20 min
20 min
10 h
9022
95
4-MeC6H4
3-MeC6H4
4-BrC6H4
4-NO2C6H4
2,5-MeO2C6H4
4-PhCOOC6H4
PhCH=CH
n-C3H7
3
94
4
9823
9523
96
5
6
7
92b
8923
918
95b
9024
8523
9523
95
8
9
10
11
12
13
14
Citronellal
Ph
Me
Me
Et
4-NO2C6H4
Ph
17 h
10 h
2 h
Ph
O
15
1:2.5:0.05
5 h
89
O
16
17
18
PhCH2CH2
Ph
Me
1:2.5:0.08
1:2.5:0.05
1:2.5:0.05
6 h
91
C6H11
20 h
7 h
82
857
O
Me
Me
HO
19
20
Ph
Ph
Ph
1:3:0.05
1:3:0.05
24 h
24 h
65b
55b
4-(Cl)C6H4
a Yields refer to isolated products unless otherwise stated.
b Yields were determined by NMR.
Synthesis 2003, No. 16, 2503–2506 © Thieme Stuttgart · New York

PAPER
Scandium(III) Triflate as a Catalyst for Conversion of Carbonyl Compounds to 1,3-Oxathiolanes
2505
2-Phenyl-2-phenylethyl-1,3-oxathiolane
S
1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 7.32–7.35 (m, 2 H),
7.22–7.28 (m, 3 H), 4.26–4.28 (m, 1 H), 4.16–4.18 (m, 1 H), 3.10–
3.15 (m, 2 H), 2.80–2.86 (m, 3 H), 2.17–2.12 (m, 2 H), 1.71 (s, 3 H).
CHO
O
100
0
SH
(1.1 equiv.)
Sc(OTf)3, CH2Cl2, 10 min
HO
O
S
13C NMR (125 MHz, CDCl3, 25 ºC, TMS): = 142.15, 128.52,
128.43, 125.94, 95.03, 70.56, 45.24, 34.30, 31.81, 29.39.
O
Me
8-Phenyl-1-oxa-4-thiaspiro[4.5]decane
1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 7.25–7.28 (m, 2 H),
7.20–7.24 (m, 2 H), 7.18–7.22 (tt, J = 1.4, 7.2 Hz, 1 H), 4.09–4.11
(t, J = 12 Hz, 2 H), 3.00–3.02 (t, J = 12.0 Hz, 2 H), 2.50–2.55 (tt,
J = 4.5, 12 Hz, 1 H), 1.74–1.81 (m, 6 H), 1.40–1.52 (m, 2 H).
13C NMR (125 MHz, CDCl3, 25 ºC, TMS): = 152.80, 128.20,
126.71, 125.52, 104.22, 72.59, 35.20, 35.40, 33.79, 26.71.
S
CHO
O
100
0
SH
(1.5equiv.)
HO
O
Sc(OTf)3, CH2Cl2, 10 min
S
O
Ph
Ph
Scheme 2 Product ratios were determined by NMR
1-Oxa-4-thiaspiro[4.11]hexadecane
1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 4.12–4.14 (t, J = 6.0
Hz, 2 H), 3.02–3.04 (t, J = 6.0 Hz, 2 H), 2.44–2.46 (pseudo-t,
J = 6.2 Hz, 2 H), 1.98–2.03 (m, 2 H), 1.69–1.80 (m, 4 H), 1.45–1.48
(m, 3 H), 1.26–1.44 (br m, 9 H).
ity, high product yields, this can be considered an
attractive methodology.
13C NMR (125 MHz, CDCl3, 25 ºC, TMS): = 95.06, 71.40, 44.30,
43.80, 33.80, 31.20-31.40 (7 peaks), 21.20 (2 peaks).
1H and 13C NMR spectra were recorded on a Bruker 500 MHz spec-
trometer in CDCl3 as the solvent and TMS as internal standard.
Most of the products are known and were determined using compar-
ison of their physical data with those reported in the literature.
2-Cyclohexyl-2-phenyl-1,3-oxathiolane
1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 7.43–7.45 (d, J = 8.0
Hz, 2 H), 7.30–7.33 (t, J = 7.7 Hz, 2 H), 7.23–7.27 (dd,
J = 5.5, 13.8 Hz, 1 H), 4.36–4.39 (dt, J = 14.4, 2.4 Hz, 1 H), 3.76–
3.80 (dt, J = 9.3, 5.7 Hz, 1 H), 1.91–1.96 (pseudo-t, J = 11.3 Hz, 1
H), 1.71–1.78 (m, 3 H), 1.60–1.62 (d, J = 12.6, 1 H), 1.13–1.25 (m,
3 H), 1.03–1.09 (quintt, J = 12.6, 3.3 Hz, 1 H), 089–0.95 (qd,
J = 12.6, 3.3 Hz, 1 H).
1,3-Oxathiolanes; General Procedure
To a magnetically stirred solution of aldehyde or ketone (1 mmol)
and 2-mercaptoethanol (1.5–2.5 mmol) in CH2Cl2 (10 mL) was add-
ed scandium triflate (0.01–0.05 mmol). The mixture was stirred at
r.t. The end of reaction was monitored using TLC (silica gel plate;
n-hexane–THF, 5:1). After completion, the reaction was quenched
with H2O (20 mL), and the mixture was extracted with CH2Cl2 (2 ×
30 mL). The aq layer was separated and evaporated under reduced
pressure to afford the catalyst. The organic layer was washed suc-
cessively with aq NaOH (10%; 15 mL) and H2O (3 × 25 mL) and
dried (Na2SO4). Evaporation of organic solvent afforded crude
product(s). Further purification of products can be achieved by vac-
uum distillation or recrystallization to afford the corresponding pure
1,3-oxathiolanes (Table 1).
13C NMR (125 MHz, CDCl3, 25 ºC, TMS): = 144.63, 127.61,
127.09, 126.82, 103.23, 70.59, 50.11, 33.54, 29.22, 28.60, 26.49,
26.41, 26.37.
Acknowledgement
The authors gratefully acknowledge the Institute for Advanced Stu-
dies in Basic Sciences (IASBS) Research council for partial support
of this work.
2-(4-Methylphenyl)-1,3-oxathiolane
1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 7.38–7.39 (d, J = 7.8
Hz, 2 H), 7.17–7.19 (d, J = 7.8 Hz, 2 H), 6.04 (s, 1 H), 4.50–4.53
(m, 1 H), 3.90–3.96 (m, 1 H), 3.24–3.29 (m, 1 H), 3.17–3.20 (m, 1
H), 2.36 (s, 3 H).
13C NMR (125 MHz, CDCl3, 25 ºC, TMS): = 138.56, 136.27,
129.51, 126.77, 87.17, 71.93, 34.10, 21.27.
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1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 7.08–7.32 (m, 4 H),
6.04 (s, 1 H), 4.51–4.53 (quint, J = 3.4 Hz, 1 H), 3.91–3.96 (m, 1 H),
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1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 7.04–7.05 (d, J = 3.0
Hz, 1 H), 6.87–6.89 (dd, J = 9.0 Hz, 3.0 Hz, 1 H), 6.82–6.84 (d,
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B. Karimi, L. Ma’mani
PAPER
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Synthesis 2003, No. 16, 2503–2506 © Thieme Stuttgart · New York