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Chemistry Letters Vol.32, No.8 (2003)
Eco-friendly and Highly Chemoselective 1,3-Oxathio- and 1,3-Dithioacetalization of Aldehydes
Using Ionic Liquids
J. S. Yadav,Ã B. V. S. Reddy, and G. Kondaji
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
(Received March 25, 2003; CL-030256)
Room temperature ionic liquids have been employed for the
O
first time as novel and recyclable reaction media for the chemo-
selective conversion of aldehydes into their corresponding 1,3-
oxathio-and dithioacetal derivatives in excellent yields under
mild and neutral conditions. A wide range of functional and
protecting groups such as TBDMS, PMB, THP, MOM, benzyl,
propargyl ethers, acetonides, carbamates and esters are survived
under these reaction conditions. The recovered activated ionic
liquids can be recycled for four to five subsequent runs with
consistency in activity.
[bmim]BF4
r.t.
SH
S
R
X
+
HX
R
R'
R'
X = O, S
3
1
2
Scheme 1.
of aromatic and aliphatic aldehydes were rapidly converted into
their corresponding 1,3-oxathio- and 1,3-dithiolane derivatives
in excellent yields by using this procedure without the need
of any acid catalyst. The reactions proceeded readily at room
temperature with high chemoselectivity. The reaction condi-
tions are mild enough not to induce isomerization of C–C multi-
ple bonds during thioacetalization of aldehydes bearing allylic
and propargylic systems and are selective enough to the protec-
tion of aldehyde functionality in the presence of other acid sen-
sitive protecting groups. These results encouraged us to extend
this process for the preparation of dithioacetals from aldehydes
and ethanethiol. Interestingly, thioethanol was also smoothly re-
acted with aldehydes to produce the corresponding dithioacetals
in excellent yields (Table 1). This method is highly chemoselec-
tive to protect aldehydes as thioacetals in the presence of ke-
tones in multi-functional compounds. The ketones such as ace-
tophenone, benzophenone, 3-pentanone and 2-heptanone did
not react with thiols under these reaction conditions. The che-
moselectivity of the present method was further illustrated by
using ketoaldehyde (Entry 17). It should be noted that the alde-
hydes bearing a-stereogenic centers gave thioacetals with com-
plete retention of the original configuration (Entries 9 and 11).
When compared to Lewis acid-promoted thioacetylization pro-
cedures, enhanced reaction rates, improved yields especially
with a; b-unsaturated aldehydes and high functional group com-
patibility are obtained by ionic liquids. Another advantage of
the use of ionic liquids is that these ionic liquids can be easily
recovered after completion of the reaction and can be reused in
subsequent reactions. Since the products were partially soluble
in the ionic phase, they were easily separated by simple extrac-
tion with ether. The rest of the ionic liquid was thoroughly
washed with ether and activated at 80 ꢀC under reduced pressure
and recycled in four to five subsequent runs without any loss of
activity. The products obtained were of the same purity as in the
first run and no decrease in yields was observed in runs carried
out using recovered ionic liquid after activation. For instance,
treatment of benzaldehyde with 2-mercaptoethanol in
[bmim]BF4 ionic liquid afforded 92%, 91%, 89%, 90%, and
89% yields over five cycles. However, in the absence of ionic
liquids, the reaction did not proceed in conventional solvents
even after long reaction times (15–20 h). In these reactions,
the activity of ionic liquid was strongly influenced by the nature
of anion. The reactivity of various aldehydes with ethanethiol
Protective groups play an important role in multi-step syn-
thesis of complex natural products; hence there are always de-
mands for selective reagents.1 1,3-Doxolane group is the most
widely used carbonyl protecting groups in the course of total
synthesis of biologically active molecules.2 Since the introduc-
tion of 1,3-dithianes as nucleophilic acylating agents by Corey
and Seebach,3 dithioacetals have become widely used tools for
carbon–carbon bond formation. Consequently, varoius methods
have been developed for the preparation of thioacetals from car-
bonyl compounds.4–8 Acid catalysts such as protic acids,5 Lewis
acids,6 solid acids7 and metal triflates8 are employed to promote
the reaction. Despite their potential utility in the protection of
simple carbonyl compounds, many of these methods have lim-
itations when applied to complex molecules containing acid-
sensitive functionalities and acid labile protecting groups.
In recent times, ionic liquids have emerged as a set of green
solvents with unique properties such as good solvating ability,
tunable polarity, wide liquid range, high thermal stability, neg-
ligible vapor pressure and ease of recycle.9 They are referred to
as ‘designer solvents’ as their properties such as hydrophilicity,
hydrophobicity, Lewis acidity, viscosity and density can be al-
tered by the fine-tuning of parameters such as the choice of or-
ganic cation, inorganic anion and the length of alkyl chain at-
tached to an organic cation. These structural variations offer
flexibility to the chemist to devise the most idealized solvent,
catering to the needs of any particular process. The use of room
temperature ionic liquids has made significant advancement in
the development of clean chemical processes in organic synthe-
sis targeted to avoid or at least minimize the use of toxic or
waste generating reagents or solvents.10
In view of the emerging importance of ionic liquids as
green solvents, we wish to report the use of ionic liquids as nov-
el and recyclable reaction media for the conversion of aldehydes
to 1,3-dithio- and oxathioacetals under mild and neutral condi-
tions (Scheme 1). Accordingly, treatment of benzaldehyde with
2-mercaptoethanol in 1-butyl-3-methylimidazolium tetraflouro-
borate ([bmim]BF4) ionic liquid for 2.5 h afforded the corre-
sponding 1,3-oxathiolane derivative in 92% yield. A variety
Copyright ꢀ 2003 The Chemical Society of Japan
Yadav
