Amberlyst 15 as a mild, chemoselective and reusable heterogeneous catalyst for the conversion of carbonyl compounds to 1,3-oxathiolanes

Article abstract of DOI:10.1055/s-2001-17532

The synthesis of 1,3-oxathiolanes from carbonyl compounds has been performed in good yields using Amberlyst15 as a convenient, reusable, heterogeneous catalyst. The procedure can be applied for the chemoselective protection of aldeydes in the presence of

Full text of DOI:10.1055/s-2001-17532

1826
PAPER
Amberlyst® 15 as a Mild, Chemoselective and Reusable Heterogeneous
Catalyst for the Conversion of Carbonyl Compounds to 1,3-Oxathiolanes
Conversion of
C
a
o
rbonyl Com
b
pounds to 1,3
e
-
Oxathiola
r
nes to Ballini,*a Giovanna Bosica,a Raimondo Maggi,*b Alessandro Mazzacani,b Paolo Righi,c Giovanni Sartorib
a
b
c
Dipartimento di Scienze Chimiche dell'Università, Via S. Agostino 1, 62032 Camerino (MC), Italy
Dipartimento di Chimica Organica e Industriale dell'Università, Parco Area delle Scienze 17A, 43100 Parma, Italy
Dipartimento di Chimica Organica 'A. Mangini' dell'Università, V.le Risorgimento 4, 40136 Bologna, Italy
Fax +39(737)637345; E-mail: ballini@camserv.unicam.it
Received 23 May 2001; revised 12 July 2001
Polystyryl diphenylphosphine/iodine complex11 and natu-
ral Kaolinitic Clay have been employed as heterogeneous
catalysts12 for the title conversion. Nevertheless, the
above methods present important drawbacks such as the
Abstract: The synthesis of 1,3-oxathiolanes from carbonyl com-
pounds has been performed in good yields using Amberlyst®15 as a
convenient, reusable, heterogeneous catalyst. The procedure can be
applied for the chemoselective protection of aldeydes in the pres-
ence of a ketone function. In addition, Amberlyst®15 can be recy- pre-preparation of the catalyst, the demand of inert atmo-
sphere,11 the need for benzene (highly toxic) as solvent12c,d
cled without loss of activity and can be even employed in the
regeneration of carbonyl group.
and the help of microwave irradiation in a complex appa-
ratus.12a,b Moreover with multifunctional compounds the
Key words: aldehydes, ketones, protecting groups, catalysis, het-
erocycles
reaction does not show good selectivity, i.e. with keto es-
ters both transesterification and ketone protection are ob-
served.12b Additionally, the possibility of recycling the
The electrophilic nature of the carbonyl group is a domi- catalyst has not been reported.
nant feature of their extensive chemistry. One of the major
In connection with our studies on reactions carried out
challenging problems during many multistep syntheses is
with heterogeneous catalysts for the preparation of fine
how to protect a carbonyl from nucleophilic attack until
chemicals following environmentally acceptable
its electrophilic properties can be exploited. For this rea-
methodologies13 we have found that commercial Am-
son, the protection and deprotection of the carbonyl
berlyst® 15, a macroreticular ion-exchange resin which
groups remain crucial challenges to organic chemists.
contains sulfonic groups,14 can be utilised as an excellent
Among the carbonyl protecting groups, 1,3-oxathiolanes
catalyst for the conversion of carbonyl compounds to 1,3-
have a special place. They are considerably more stable
oxathiolanes.
than the corresponding O,O-acetals under acidic condi-
Our procedure (Scheme 1) is performed by stirring an
equimolecular mixture of the carbonyl compound 1, the
tions and compared with S,S-acetals are more easily
deprotected.1 Moreover, 1,3-oxathiolanes constitute an
mercaptoethanol 2 in dichloromethane in the presence of
important class of compounds as acyl anion equivalents in
C–C bond formation, although a new stereogenic center
Amberlyst® 15 (activated at 130 °C for 2 h) for the select-
ed reaction time (Table).
can be formed which may complicate the spectral inter-
pretation.2 As with most protecting groups, therefore, a
variety of methods should be available for the formation
and deprotection of the title compounds. However, in con-
trast to many methods available for the well-known O,O-
and S,S-acetals,1 only a few are reported for the oxathio-
acetals formation employing HCl,3 p-toluenesulfonic ac-
O
Amberlyst® 15
CH2Cl2
O
R
S
R1
SH
+
HO
R
R1
1
2
3
Scheme 1
8
id,4 TMSCl/NaI,5 BF3◊OEt2,6 SO2,7 ZrCl4 and TMSOTf,9
as homogeneous solutions.
As shown in the Table, different types of carbonyl com-
pounds can be efficiently transformed into their corre-
sponding 1,3-oxathiolanes 3 and, because the conversion
of aldehydes is faster than ketones, the chemoselective
protection of aldehyde in the presence of ketone function
can be performed in high yield and with excellent
chemoselectivity (97%) [Scheme 2, 4 to 5].
In recent years, there has been a tremendous upsurge of in-
terest in various chemical transformations mediated by
heterogeneous catalysts. Environmental and economical
considerations prompt an urgent need to redesign com-
mercially important processes and, in this context, hetero-
geneous catalysis plays a dramatic role.10
Synthesis 2001, No. 12, 25 09 2001. Article Identifier:
1437-210X,E;2001,0,12,1826,1829,ftx,en;Z05501ss.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

PAPER
Conversion of Carbonyl Compounds to 1,3-Oxathiolanes
1827
Table 1,3-Oxathiolanes 3 Prepared
Product
3a
R
H
H
H
H
H
H
H
H
R1
Reaction Time (h)
Yield (%)a
84b
Ph
1
1
1
1
1
1
1
1
3b
p-NO2C6H4
p-ClC6H4
(E)-PhCH=CH
i-Pr
88b
3c
84b
3d
78b
3e
81b
3f
Ph(CH2)2
Et2CH
95b
3g
85b
3h
88b
CH2
3i
H
H
H
PhCH2
1
1
1
5
91b
85b
75
3j
3k
3l
c-C6H11
CH3(CH2)12
95b
(CH2)2CH(CH2)2
CH(CH3)3
3m
3n
3o
Me
Me
Pr
PhCH2
15
84b
88
84
90
MeO2C(CH2)2
Pr
8 + 2c
8 + 2c
2 + 2c
3p
Me
(CH3)2C(CH2)2
NO2
3q
15
92
(CH2)2CH(CH2)2
C6H5
a Isolated yield.
b These products were characterised by comparison of their IR, 1H NMR and Mass spectra with those of the authentic samples.7,8,12b,15–18
c The reaction mixture was further heated at 45 °C for the indicate time.
O
O
alyst, washing with dichloromethane and heating at 130
°C for 1 hour. In fact, the conversion of benzaldehyde (1a)
into its 1,3-oxathiolane 3a has been repeated three times,
through the same catalyst, with the following yields: 84%,
82% and 83%.
SH
+
HO
H
NO2
2
4
Amberlyst® 15
CH2Cl2
90%
Finally, we tried the regeneration of the carbonyl group
from 1,3-oxathiolane 3a, by the same catalyst (Scheme 3),
simply by refluxing (8 h) a solution of 3a in acetone–wa-
ter (99:1) in the presence of Amberlyst®15; the aldehyde
1a was isolated in 90% yield.
O
S
S
S
O
O
O
H
H
NO2
NO2
5(97%)
6(3%)
Amberlyst® 15
O
Scheme 2
Me2CO-H2O
reflux, 90%
O
S
Ph
H
It is important to point out that in the protection of the keto
Ph
H
1a
ester 1n no transesterification process was observed.
3a
In addition, we found that Amberlyst® 15 could be recy-
cled without loss of the activity simply by filtering the cat-
Scheme 3
Synthesis 2001, No. 12, 1826–1829 ISSN 0039-7881 © Thieme Stuttgart · New York

1828
R. Ballini et al.
PAPER
MS (EI, 70 eV): m/z (%) = 272 (M+), 194, 89 (100), 61, 60, 55, 43,
41.
In conclusion, we have described a new, mild, efficient
heterogeneous catalysis for the conversion of carbonyl
compounds to 1,3-oxathiolanes. Furthermore, we have Anal. Calcd for C16H32OS: C, 70.53; H, 11.84; S, 11.76. Found: C,
found that Amberlyst® 15 (i) shows high chemoselectivi-
70.48; H, 11.88; S, 11.65.
ty, (ii) can be efficiently recycled, and (iii) can even be
3n
employed in the regeneration of carbonyl function from
IR (neat): 1710 cm–1.
1,3-oxathiolanes.
1H NMR (CDCl3): d = 1.61 (s, 3 H), 2.1–2.2 (m, 2 H), 2.4–2.6 (m,
2 H), 3.0–3.1 (m, 2 H), 3.68 (s, 3 H), 4.0–4.3 (m, 2 H).
1H NMR spectra were recorded in CDCl3 at 200 MHZ on a Varian
13C NMR (CDCl3): d = 28.90, 29.35, 33.99, 35.00, 51.44, 70.24,
Gemini instrument; J values are given in Hz. IR spectra were re-
95.71, 174.13.
corded with a Perkin Elmer 257 spectrophotometer. Mass spectra
MS (EI, 70 eV): m/z (%) = 190 (M+), 175, 159, 131, 115, 103, 99,
60 (100), 43.
were determined on a capillary GC/MS operating in the split mode
with He carrier gas and fitted with a mass-selective detector (MDS).
The reactions were monitored by TLC or GC performed on a Carlo
Erba Fractovap 4160 using a capillary column of Duran Glass, sta-
tionary phase OV1. Microanalyses were performed using a Fisons
model EA 1108. The products were purified by flash chromatogra-
phy on Merck silica gel with EtOAc–cyclohexane as eluent.
Anal. Calcd for C8H14O3S: C, 50.50; H, 7.41; S, 16.85. Found: C,
50.61; 7.34; S, 16.94.
3o
1H NMR (CDCl3): d = 0.9 (t, 6 H, J = 7.3 Hz), 1.3–1.5 (m, 4 H),
1.65–1.85 (m, 4 H), 2.98 (t, 2 H, J = 5.8 Hz), 4.1 (t, 2 H, J = 5.8 Hz).
1,3-Oxathiolanes 3; General Procedure
13C NMR (CDCl3): d = 14.33, 18.38, 33.66, 43.18, 70.52, 98.71.
MS (EI, 70 eV): m/z (%) = 174 (M+), 131(100), 71, 60, 43.
Amberlyst® 15 (220 mg, activated at 130 °C for 2 h) was added to a
stirred solution of carbonyl compound 1 (5 mmol) in CH2Cl2 (6
mL), then 2-mercaptoethanol 2 (5 mmol), in CH2Cl2 (6 mL) was
added dropwise over a few minutes. The obtained solution was
stirred at r.t. (for some ketones heating at 45 °C was needed) for the
appropriate time (see Table). After completion of the reaction (TLC
and GC), the solution was washed with aq 2 N NaOH (2 ¥ 5 mL),
dried (MgSO4), evaporated and the crude product was purified by
flash chromatography (EtOAc–cyclohexane) to afford the pure
compound 3.
Anal. Calcd for C9H18OS: C, 62.02; H, 10.41; S, 18.39. Found: C,
62.26; H, 10.29; S, 18.52.
3p
IR (neat): 1537 cm–1.
1H NMR (CDCl3): d = 1.58 (br s, 9 H), 1.72–1.84 (m, 2 H), 1.9–2.23
(m, 2 H), 2.95–3.18 (m, 2 H), 4.01–4.26 (m, 2 H).
13C NMR (CDCl3): d = 25.96, 26.26, 29.51, 34.41, 36.47, 37.51,
70.65, 88.07, 94.36.
Spectral data of some of the representative purified compounds are
given below.
MS (EI, 70 eV): m/z (%) = 219 (M+), 173, 113, 103, 95, 60, 43
(100).
3g
1H NMR (CDCl3): d = 0.91 (t, 3 H, J = 7.4 Hz), 0.92 (t, 3 H, J = 7.4
Hz), 1.30–1.70 (m, 5 H), 2.80 (ddd, 1 H, J = 13.7, 6.3, 6.0 Hz), 2.89
(ddd, 1 H, J = 13.7, 5.5, 5.7 Hz), 3.74 (td, 1 H, J = 6.0, 9.0Hz), 4.36
(ddd, 1 H, J = 2.7, 6.3, 9.0 Hz), 5.07 (d, 1 H, J = 6.31 Hz).
Anal. Calcd for C9H17NO3S: C, 49.29; H, 7.81; N, 6.39; S, 14.62.
Found: C, 49.16; H, 7.89; N, 6.25; S, 14.92.
3q (as a 57:43 diastereomeric mixture of E/Z)
13C NMR (CDCl3): d = 10.96, 11.08, 22.60, 22.66, 32.09, 45.96,
71.26, 90.41.
MS (EI, 70 eV): m/z (%) = 160 (M+), 115, 101, 83, 55, 41 (100).
1H NMR (CDCl3): d = 1.56–2.28 (m, 8 H), 2.46–2.6 (m, 1 H), 3.0–
3.1 (m, 2 H), 4.18 (dt, 2 H, J = 5.9, 5.8 Hz), 7.1–7.3 (m, 6 H).
13C NMR (CDCl3): d = 31.63, 33.05, 33.45, 39.85, 40.24, 43.02,
43.45, 69.82, 70.09, 93.59, 97.32, 126.20, 126.33, 127.00, 128.51,
128.56, 146.34, 146.85.
Anal. Calcd for C8H16OS: C, 59.95; H, 10.06; S, 20.00. Found: C,
59.86; H, 10.19; S, 20.12.
MS (EI, 70 eV): m/z (%) = 234 (M+), 174, 115 (100), 104, 91, 60.
3h (as a 50:50 diastereomeric mixture)
1H NMR (CDCl3): d = 0.75 (s, 3 H), 0.78 (s, 3 H), 1.42 (s, 3 H), 1.50
(s, 3 H), 1.53 (s, 3 H), 1.61 (s, 3 H), 0.7–1.8 (m, 7 H), 2.85–3.10 (m,
2 H), 3.9–4.1 (m, 2 H), 4.89 (m, 1 H), 5.01 (m, 1 H).
13C NMR (CDCl3): d = 17.25, 19.3, 19.8, 22.18, 24.0, 25.1, 25.26,
25.32, 26.03, 30.77, 34.01, 36.0, 37.1, 37.36, 40.45, 44.1, 71.80,
74.4, 85.23, 87.2, 124.6, 125.8, 130.3, 133.2.
Anal. Calcd for C14H18OS: C, 71.75; H, 7.74; S, 13.68. Found: C,
71.69; H, 7.82; S, 13.60.
5
IR (neat): 1719, 1543 cm–1.
1H NMR (CDCl3): d = 1.7–2.3 (m, 6 H), 2.13 (s, 3 H), 2.47 (t, 2 H,
J = 7.1 Hz), 2.9–3.1 (m, 2 H), 3.7–3.8 (m, 1 H), 4.2–4.4 (m, 1 H),
4.4–4.6 (m, 1 H), 5.0–5.2 (m, 1 H).
MS (EI, 70 eV): m/z (%) = 214 (M+), 154, 137, 81 (100), 69, 59.
Anal. Calcd for C12H22OS: C, 67.24; H, 10.34; S, 14.95. Found: C,
67.30; H, 10.29; S, 14.52.
13C NMR (CDCl3): d = 28.67, 28.85, 29.13, 31.45, 34.01, 39.15,
71.80, 85.97, 89.01, 205.33.
MS (EI, 70 eV): m/z (%) = 246 (M+ – 1), 199, 139, 102, 89 (100),
60, 43.
3k
1H NMR (CDCl3): d = 0.88 (t, 3 H, J = 6.2 Hz), 1.7–1.2 (m, 24 H),
3.0 (m, 2 H), 3.9 (m, 2 H), 5.05 (t, 1 H, J = 5.1 Hz);
Anal. Calcd for C10H17NO4S: C, 48.57; H, 6.93; N, 5.66; S, 12.96.
Found: C, 48.66; H, 6.89; N, 5.72; S, 13.01.
13C NMR (CDCl3): d = 14.11, 22.7, 23.5, 26.4, 27.5, 29.1, 32.6,
33.7, 36.4, 71.18, 87.12.
Synthesis 2001, No. 12, 1826–1829 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Conversion of Carbonyl Compounds to 1,3-Oxathiolanes
1829
(11) Caputo, R.; Ferreri, C.; Palumbo, G. Synthesis 1987, 386.
(12) (a) Pério, B.; Dozias, M.-J.; Hamelin, J. Org. Proc. Res. Dev.
1998, 2, 428. (b) Pério, B.; Hamelin, J. Green Chemistry
2000, 2, 252. (c) Ponde, D.; Borate, H. B.; Sudalai, A.;
Ravindranathan, T.; Deshpande, V. H. Tetrahedron Lett.
1996, 37, 4605. (d) Ponde, D. E.; Deshpande, V. H.;
Bulbule, V. J.; Sudalai, A.; Gajare, A. S. J. Org. Chem. 1998,
63, 1058.
Acknowledgement
This work was carried out in the framework of the National Project
’Stereoselezione in Sintesi Organica. Metodologie ed Applicazioni’
supported by Ministero dell'Università e della Ricerca Scientifica e
Tecnologica, Rome-Italy and by Fondazione della Cassa di Rispar-
mio della Provincia di Macerata-Italy.
(13) (a) Ballini, R.; Bosica, G.; Maggi, R.; Sartori, G. Synlett
1997, 795. (b) Ballini, R.; Bosica, G. In Recent Research
Development in Organic Chemistry, Vol. 1; Transworld
Research Network: Trivandrum, 1997, 11–24. (c) Ballini,
R.; Bosica, G.; Parrini, M. Tetrahedron Lett. 1998, 39,
7963. (d) Ballini, R.; Bordoni, M.; Maggi, R.; Sartori, G.
Tetrahedron Lett. 1998, 39, 7587; and references cited
therein. (e) Ballabeni, M.; Ballini, R.; Bigi, F.; Maggi, R.;
Parrini, M.; Predieri, G.; Sartori, G. J. Org. Chem. 1999, 64,
1029. (f) Ballini, R.; Bigi, F.; Gogni, E.; Maggi, R.; Sartori,
G. J. Catal. 2000, 191, 348.
(14) Cainelli, G.; Manescalchi, F.; Contento, M. Organic
Synthesis: Today and Tomorrow; Trost, B. M.; Hutchinson,
C. R., Eds.; Pergamon: London, 1980, 19.
(15) Yadav, J. S.; Reddy, B. V. S.; Pandey, S. K. Synlett; 2001,
238.
(16) (a) Musavirov, R. S.; Nedogrei, E. P.; Larionov, V. I.;
Zlotskii, S. S.; Kantor, E. A.; Rakhmankulov, D. L. J. Gen.
Chem. USSR 1982, 52, 1229. (b) Chem. Abstr. 1982, 97,
109945.
(17) Eliel, E. L.; Pilato, L. A.; Badding, V. G. J. Am. Chem. Soc.
1962, 84, 2377.
(18) (a) Eliel, E. L.; Doyle, T. W. J. Org. Chem. 1970, 35, 2716.
(b) Vainiotalo, P.; Nevalainen, V. Org. Mass Spectrom.
1986, 21, 467.
References
(1) (a) Greene, T. W. Protective Groups in Organic Synthesis,
2nd ed.; Wiley: New York, 1991. (b) Kocienski, P. J.
Protecting Groups; Thieme: Stuttgart, 1994.
(2) (a) Lynch, J. E.; Eliel, E. L. J. Am. Chem. Soc. 1984, 106,
2943. (b) Eliel, E. L.; Morris-Natsche, S. S. J. Am. Chem.
Soc. 1984, 106, 2937. (c) Utimoto, K.; Nakamura, A.;
Motsubara, S. J. Am. Chem. Soc. 1990, 112, 8189.
(3) Ralls, J. W.; Dodson, R. M.; Riegel, B. J. Am. Chem. Soc.
1949, 71, 3320.
(4) Djerassi, C.; Gorman, M. J. Am. Chem. Soc. 1953, 75, 3704.
(5) Yadav, V. K.; Fallis, A. G. Tetrahedron Lett. 1988, 29, 897.
(6) Wilson, G. E. Jr.; Huang, M. G.; Schloman, W. W. Jr. J. Org.
Chem. 1968, 33, 2133.
(7) Burczyk, B.; Kortylewicz, Z. Synthesis 1982, 831.
(8) Karimi, B.; Seradj, H. Synlett 2000, 805.
(9) Ravindranathan, T.; Chavan, S. P.; Dantale, S. W.
Tetrahedron Lett. 1995, 36, 2285.
(10) (a) Laszlo, P. Acc. Chem. Res. 1986, 19, 121. (b) Ley, S. V.;
Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.;
Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storter, R. J.;
Taylor, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3815.
(c) Fricke, R.; Hosslick, H.; Lischke, G.; Richter, M. Chem.
Rev. 2000, 100, 2303.
Synthesis 2001, No. 12, 1826–1829 ISSN 0039-7881 © Thieme Stuttgart · New York