Facile protection of carbonyl compounds as oxathiolanes and transoxathioacetalization of oxyacetals promoted by iron(III) trifluoroacetate or trifluoromethanesulfonate as chemoselective and recyclable catalysts

Article abstract of DOI:10.1016/j.jfluchem.2007.04.002

Oxathioacetalization of carbonyl compounds and transoxathioacetalization of O,O-acetals/ketals are reported under nearly neutral conditions promoted by iron(III) trifluoroacetate [Fe(CF₃CO₂)₃] or trifluoromethanesulfonate

Full text of DOI:10.1016/j.jfluchem.2007.04.002

Journal of Fluorine Chemistry 128 (2007) 679–682
www.elsevier.com/locate/fluor
Short communication
Facile protection of carbonyl compounds as oxathiolanes and
transoxathioacetalization of oxyacetals promoted by
iron(III) trifluoroacetate or trifluoromethanesulfonate as
chemoselective and recyclable catalysts
b,c
Hadi Adibi a, , Hadi Jafari
*
a Department of Medicinal Chemistry, School of Pharmacy, Kermanshah University of Medical Sciences,
Kermanshah 67149-67346, Islamic Republic of Iran
b Department of Chemistry, Faculty of Sciences, Razi University, Kermanshah 67149, Islamic Republic of Iran
c Department of Chemistry, Islamic Azad University, Science and Research Branch, Hessarak, Tehran 14515-775, Islamic Republic of Iran
Received 7 March 2007; received in revised form 1 April 2007; accepted 3 April 2007
Available online 6 April 2007
Abstract
Oxathioacetalization of carbonyl compounds and transoxathioacetalization of O,O-acetals/ketals are reported under nearly neutral conditions
promoted by iron(III) trifluoroacetate [Fe(CF3CO2)3] or trifluoromethanesulfonate [Fe(CF3SO3)3] as recyclable and highly efficient Lewis acid
catalysts.
# 2007 Elsevier B.V. All rights reserved.
Keywords: Iron trifluoroacetate; Trifluoromethanesulfonate; Oxathiolanes; Carbonyl compounds; Protection
1. Introduction
carbonyl compounds as 1,3-dithiolanes, only a few methods are
available for oxathioacetals [4]. A plethora of procedures are
reported for their formation employing protic acids or Lewis
acids such as HCl [5a], p-TsOH [5b], BF3ÁOEt2 [5c], TMSCl/
NaI [5d], TMSOTf [5e], Bu4NBr3 [5f], H3PW12O40/SiO2 [5g],
In(OTf)3 [5h], NBS [5i], Sc(OTf)3 [5j], ZrCl4 [5k], HClO4 [5l],
LiBF4 [5m], ZnCl2/Na2SO4 [5n], SO2 [5o], polystyryl
diphenylphosphine–iodine complex [5p], natural kaolinitic
clay [5q], MoO2(acac)2 [5r], Me2S/Br2 [5s], polyphosphoric
acid/SiO2 [5t], HClO4/SiO2 [5u], Pr(OTf)3 [5v], Yb(OTf)3/
ionic liquid [5w], 2,4,4,6-tetrabromo-2,5-cyclohexadienone
(TABCO)/Br2 [5x] and TaCl5/SiO2 [5y]. A number of these
methods suffer from certain drawbacks such as low yields,
relatively harsh reaction conditions and long reaction times,
reflux temperatures, expensive reagents, inconvenient proce-
dures, the use of stoichiometric amounts of catalyst, unwanted
side reactions, poor chemoselectivity and the use of catalysts
destroyed in the work-up procedure which cannot be recovered
and used again. Additionally, handling of some of these
catalysts is not easy in the laboratory apart from their
hygroscopic nature due to strong tendency for hydrolysis.
However, developments in this area demand further searches
One of the major challenging problems during multistep
syntheses is to protect carbonyl functionality from nucleophilic
attack until its electrophilic nature can be exploited. Among
carbonyl protecting groups, 1,3-oxathiolanes are an important
class of compounds for the following reasons. Firstly, they can
be used as acyl carbanion equivalents [1] for carbon–carbon
bond forming reactions. Secondly, the chiral 1,3-oxathiolanes
are valuable synthons for enantioselective synthesis of a-
hydroxyaldehydes, first demonstrated by Lynch and Eliel [2].
Later on, these compounds were further utilized by Utimoto
et al. [3] for studying diastereoselective reactions. Thirdly, the
use of O,S-acetals is more convenient than the corresponding
O,O-acetals or S,S-acetals because they are comparatively more
stable than O,O-acetals in acidic conditions and much easier to
remove than S,S-acetals. Though a large number of methods
have been developed for the protection and deprotection of
* Corresponding author. Tel.: +98 831 427 6482; fax: +98 831 427 6493.
E-mail address: hadibi@kums.ac.ir (H. Adibi).
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.04.002

680
H. Adibi, H. Jafari / Journal of Fluorine Chemistry 128 (2007) 679–682
To choose the most appropriate medium in this hetero-
cyclization reaction, we examined the protection of benzalde-
hyde 1a as a model compound with 2-mercaptoethanol using
Fe(CF3CO2)3 in various solvents (Table 1). The solvents
examined were dichloromethane, tetrahydrofuran, chloroform,
n-hexane and acetonitrile. The reactions were carried out by
stirring 1a with Fe(CF3CO2)3 (5 mol%) and 1.2 equiv of 2-
mercaptoethanol at room temperature. The reaction of 1a with
1.2 equiv of 2-mercaptoethanol in CH2Cl2 for 30 min afforded
2-phenyl-1,3-oxathiolane 2a in 60% conversion (Table 1, entry
1). When the reaction was carried out in CH3CN, the reaction
took place rapidly and 2a was obtained in 100% conversion
(Table 1, entry 2), it turned out to be one of the best choices in
view of high solubility of substrates within it. In the case of the
other solvents such as CHCl3, THF and n-hexane 2a was
obtained in lower conversions (Table 1, entries 3–5). Next, the
effect of the amount of the Fe(CF3CO2)3 was examined with 1a
(1 mmol) and 2-mercaptoethanol in acetonitrile. The optimum
molar ratio of 1a to 2-mercaptoethanol to Fe(CF3CO2)3
(1:1.2:0.05) was found to be ideal for complete conversion.
Similar reactions were carried out with Fe(CF3SO3)3 as shown
in Table 1. It should be noted that in the absence of catalyst no
conversion of 1a to 2a occurred after 24 h (Table 1, entry 6).
The generality of this protocol has been proved with a wide
range of aromatic, aliphatic and heterocyclic aldehydes
(Table 2, entries 1a–n) bearing Cl, OMe, NO2, OH and Me
groups whilst remaining strictly unchanged. It is worthy of note
that the oxathioacetalization of cinnamaldehyde and piperonal
as unsaturated and protected aldehydes proceeded successfully
by this method to afford the corresponding oxathioacetals in
high yields (Table 2, entries 1g, n). These reactions proceeded
quite cleanly under almost neutral conditions and practically
pure products were obtained after a simple work-up procedure
without any requirement to the use of inert atmosphere.
Moreover, neither the use of dehydrating agent nor the
azeotropic removal of water is necessary in our procedure.
Catalytic quantities of Fe(CF3CO2)3 or Fe(CF3SO3)3 (5 mol%)
were added to a stirred solution of the carbonyl compound and
the required 2-mercaptoethanol in acetonitrile and then the
mixture was stirred at room temperature. These catalysts have
been recovered almost quantitatively from the aqueous layers
and used again for the second runs and the yields of the second
ones were comparable to those of the first runs (Table 2).
Ketones were also oxathioacetalized to 1,3-oxathiolanes using
Fe(CF3CO2)3 or Fe(CF3SO3)3 (5 mol%) (Table 2, entries 1o–u)
Scheme 1. Conversion of carbonyl compounds to oxathiolanes and transox-
athioacetalization of oxyacetals catalyzed by Fe(CF3CO2)3 or Fe(CF3SO3)3.
for better catalysts that could be superior to the existing ones
with regard to environmental compatibility, efficiency, che-
moselectivity, operational simplicity, cost effectiveness, toxi-
city, handling and recyclability. In this respect, we are
interested in introducing better catalysts to overcome these
limitations.
Recently, we reported that solvolytic and non-solvolytic
ring-opening reactions of epoxides are facilitated in the
presence of iron(III) trifluoroacetate [6]. Also, iron(III) triflate
is a novel Lewis acid, which has attracted little attention as a
catalyst [7]. Very recently, Oriyama and co-workers reported
that iron(III) triflate catalyzes one-pot synthesis of acetal-type
protected cyanohydrins from carbonyl compounds [8]. To the
best of our knowledge, there is no report on the application of
Fe(CF3CO2)3 or Fe(CF3SO3)3 as Lewis acid catalysts for the
preparation of oxathioacetals. In this paper, we wish to disclose
an efficient method for oxathioacetalization of various
aldehydes and ketones and transoxathioacetalization of O,O-
acetals/ketals by reaction with 2-mercaptoethanol using
catalytic amounts of iron(III) trifluoroacetate or trifluoro-
methanesulfonate as powerful, recyclable and non-hygroscopic
Lewis acid catalysts under almost neutral conditions (Scheme
1).
2. Results and discussion
These reagents have several advantages over other conven-
tional Lewis acids, for example, they are stable in water and
therefore do not decompose under aqueous work-up conditions
and also recycling of Fe(CF3CO2)3 or Fe(CF3SO3)3 is often
possible with no loss in their potency and makes the procedure
environmentally acceptable by utilizing these properties. The
highly stable and non-hygroscopic nature, high chemoselec-
tivity, easy preparation, high yield, short reaction periods, easy
handling and work-up are other advantages of the catalysts.
Table 1
a
Oxathioacetalization of benzaldehyde 1a with 2-mercaptoethanol catalyzed by Fe(CF3CO2)3 or Fe(CF3SO3)3
Entry
Solvent
Reaction conditions
Molar ratio
Time (min)
Conversion (%)b
1
2
3
4
5
6
CH2Cl2
CH3CN
CHCl3
THF
Substrate/2-mercaptoethanol/Fe(CF3CO2)3
Substrate/2-mercaptoethanol/Fe(CF3CO2)3
Substrate/2-mercaptoethanol/Fe(CF3CO2)3
Substrate/2-mercaptoethanol/Fe(CF3CO2)3
Substrate/2-mercaptoethanol/Fe(CF3CO2)3
Substrate/2-mercaptoethanol
1/1.2/0.05
1/1.2/0.05
1/1.2/0.05
1/1.2/0.05
1/1.2/0.05
1/1
30 (30)
20 (15)
30 (30)
30 (30)
30 (30)
24 h
60 (68)
100 (99)
70 (75)
55 (60)
50 (58)
0 (0)
n-Hexane
CH3CN
a
The numbers in parenthesis are related to Fe(CF3SO3)3.
GC yield.
b

H. Adibi, H. Jafari / Journal of Fluorine Chemistry 128 (2007) 679–682
681
Table 2
Oxathioacetalization and transoxathioacetalization of carbonyl compounds catalyzed by Fe(CF3CO2)3 or Fe(CF3SO3)3 at room temperaturea
Entry
R1
R2
ZZ
Time (min)
Yield (%)b
Fe(CF3CO2)3
Fe(CF3SO3)3
Fe(CF3CO2)3
Fe(CF3SO3)3
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
1s
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
O
20, 25c
45
10, 15c
40
90, 92c
87
90, 81c
91
4-O2NC6H4
4-MeC6H4
O
O
20, 30c
10, 20c
92, 81c
94, 85c
4-MeOC6H4
4-OH-3-MeOC6H3
2-ClC6H4
O
15
10
91
92
O
10
10
89
90
O
25
25
87
87
PhCH CH
2-Naphthyl
3,4,5-(MeO)3C6H2
4-ClC6H4
O
20
15
91
89
O
15
15
89
93
O
20
15
93
92
O
20
10
90
92
2-Furyl
O
15
10
95
98
3,4-(MeO)2C6H3
n-Hexanal
O
10
10
91
91
O
30
20
90
86
Piperonal
O
25
25
87
93
a-Tetralone
Cyclopentanone
Cyclohexanone
4-Cholesten-3-one
Ph
–
70
60
89
90
–
80
70
89
92
–
95
80
85
85
–
180
190
200
75
180
180
180
70
90
90
Me
Ph
O
82
81
1t
Ph
O
89
85
1u
1v
1w
1x
1y
Ethyl acetoacetate
4-MeC6H4
–
88
90
H
H
O(CH2)2O
O(CH2)2O
O(CH2)2O
O(CH2)2O
20
15
92
94
C6H5
15
15
89
88
Cyclohexanone
4-MeOC6H4
100
15
90
92
97
H
15
91
93
a
Substrate/2-mercaptoethanol/catalyst (1/1.2/0.05).
Isolated yield.
b
c
Catalyst was recycled and reused for the second runs.
1
but considerably more slowly compared to aldehydes.
Protection of a-tetralone and cholestenone as cyclic and
steroidal ketones was catalyzed with Fe(CF3CO2)3 or
Fe(CF3SO3)3 under similar experimental conditions to afford
the respective oxathioacetal (Table 2, entries 1o, r). Interest-
ingly, ethyl acetoacetate also exhibited splendid selectivity
towards the acetyl moiety as an example of b-ketoester and was
smoothly protected in 88 and 90% yields under the above
conditions without formation of a transesterification product
(Table 2, entry 1u). To examine transoxathioacetalization, a
mixture of the O,O-acetal 1v and 2-mercaptoethanol was
allowed to react in the presence of Fe(CF3CO2)3 or
Fe(CF3SO3)3 (5 mol%) at room temperature. The reaction
mixture was worked up and purification of the crude product
afforded the oxathioacetal 2v in 92 and 94% yields (Table 2,
entry 1v).
and H NMR) with those of authentic samples reported in the
literature.
3.2. General procedure for oxathioacetalization and
transoxathioacetalization of carbonyl compounds catalyzed
by Fe(CF3CO2)3 or Fe(CF3SO3)3
To a solution of carbonyl compound or an O,O-acetal/ketal
(1 mmol) and 2-mercaptoethanol (1.2 mmol) in dry acetonitrile
(5 ml) was added 5 mol% of Fe(CF3CO2)3 or Fe(CF3SO3)3.
The reaction mixture was stirred at room temperature and
monitored by TLC until the disappearance of starting material.
After the appropriate period (Table 2), the solvent was
evaporated and the residue was diluted with dichloromethane
(10 ml) and water (15 ml). The organic phase was separated and
the aqueous layer was washed with dichloromethane (10 ml).
Concentration of the combined organic layer under reduced
pressure afforded the crude product, which was purified by
neutral silica gel column chromatography to afford the
corresponding oxathioacetal. The aqueous layer containing
Fe(CF3CO2)3 in the above work-up procedure was separated
and evaporated under reduced pressure to afford the crude
catalyst. The resulting solid residue was dried at 70 8C for 2 h to
give the pure Fe(CF3CO2)3 in 90% recovery. Work-up
procedure for recovery of Fe(CF3SO3)3 is similar to the
3. Experimental
3.1. Catalysts and general remarks
Iron(III) trifluoroacetate [6] and iron(III) trifluoromethane-
sulfonate [7] were prepared according to reported procedures.
Yields refer to isolated products after purification. The products
were characterized by comparing their spectral and physical
data (TLC, MS, melting point, combustion elemental analysis

682
H. Adibi, H. Jafari / Journal of Fluorine Chemistry 128 (2007) 679–682
(b) C. Djerassi, M. Gorman, J. Am. Chem. Soc. 75 (1953) 3704–3708;
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4. Conclusion
(f) E. Mondal, P.R. Sahu, G. Bose, A.T. Khan, Tetrahedron Lett. 43 (2002)
2843–2846;
In conclusion, iron(III) trifluoroacetate and trifluorometha-
nesulfonate which are stable and non-hygroscopic Fe3+
compounds, can be considered as bench-top reagents for
efficient oxathioacetalization and transoxathioacetalization of
carbonyl compounds and high chemoselectivity of the reaction
should be useful for selective protection of carbonyl group in
the presence of other carbonyl moieties. In addition, we have
developed catalysts as interesting alternatives to liquid,
hygroscopic and expensive reagents as mentioned in Section
1. Moreover, nearly neutral conditions, short reaction times,
high yields of the products, easy work-up, compatibility with
various functional groups, and the environmentally friendly
nature of the our procedure should make the presented protocol
useful and important in addition to the known methodologies.
(g) H. Firouzabadi, N. Iranpoor, A.A. Jafari, M.R. Jafari, J. Mol. Catal. A:
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Acknowledgement
(s) A.T. Khan, P.R. Sahu, A. Majee, J. Mol. Catal. A: Chem. 226 (2005)
207–212;
We gratefully acknowledge the Kermanshah University of
Medical Sciences Research Council for financial support.
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