LETTER
1335
‘Metal Ion Electrophilic Catalysis’ in Ring-Opening Reactions of 1,2-Epoxides
by Metal Halides in Ionic Liquids
‘
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ns Betti,a Dario Landini,*a Angelamaria Maia*b
a
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy
Fax +39(02503)14159; E-mail: dario.landini@unimi.it
b
Istituto CNR-ISTM, Via Golgi 19, 20133 Milano, Italy
E-mail: angelamaria.maia@istm.cnr.it
Received 8 February 2006
friendly methodologies for the regioselective ring-open-
ing of oxiranes.
Abstract: Metal ion electrophilic catalysis (Li+ > Na+ >> K+) has
been found in ring-opening reactions of 1,2-epoxides 1–5 by metal
halides MHal in ionic liquids. The results have been rationalized on
the basis of a transition state where the cation M+ stabilizes the
negative charge developing on the oxygen atom of the oxirane ring
while favoring the nucleophilic attack at the adjacent carbon by the
ion-paired anion Hal–.
At present, room temperature ionic liquids (RTILs) are
considered one of the most powerful alternatives to con-
ventional more volatile organic solvents.11 Negligible
vapor pressure combined with excellent stability and ease
of recycle makes RTILs possible sustainable media for a
number of stoichiometric and catalytic processes.11 If the
presence of the complexing agent is necessary for the
solubilization of the salts in the low polar medium,10 in the
ionic liquid on the contrary a number of organic and inor-
ganic materials are highly soluble as such. Ionic liquids
have properties completely different from those of molec-
ular solvents and the medium is well known to play a fun-
damental role in determining the rate and outcome of a
chemical process. This is particularly evident in reactions
where ionic species are involved as in the case of the
opening of oxirane rings. Recently, the synthesis in ILs of
vic-halohydrins from oxiranes has been realized, but
exclusively with lithium halides.12
Key words: epoxides, vic-halohydrins, oxirane ring-opening, ionic
liquids, metal ion catalysis
The most common method for the synthesis of 1,2-halo-
hydrins is the ring-opening of 1,2-epoxides either with hy-
drogen halides or with hydrohalogenic acid.1 These
procedures, however, suffer from limitations when protic
acid sensitive substrates are used and many efforts have
been made in the last years to develop new and milder
methodologies for converting epoxides into halohydrins.
For example, chloro-, bromo- and iodohydrins were
obtained by treatment of epoxide with the appropriate
halogen in the presence of triphenylphosphine,2 phenyl-
hydrazine3 or thiourea4 in aprotic media (acetonitrile,
dichloromethane) at room temperature. In addition, inor-
ganic salts like alkali metal halides,5 lithium6 and
magnesium7 iodides and perchlorates8 in weakly polar
solvents or supported on silica gel,9 have been successful-
ly utilized in the ring-opening of epoxides and epoxy al-
cohols. The products, obtained under mild conditions and
in good yields, often present high regio- and stereoselec-
tivities, much higher than those obtained with traditional
methods.5–9 Very recently, we revealed ‘metal ion electro-
philic catalysis’ in reactions of 1,2-epoxides promoted by
complexes of polyether ligands (crown ethers, PEGs) with
alkali metal halides in apolar media (chlorobenzene and
1,2-dichlorobenzene). The catalytic effect was found to
depend on both the Lewis acid character of the cation (K+
<< Na+ < Li+) and the topology of the ligand (open-chain
> cyclic polyether).10 vic-Halohydrins are very useful
synthetic intermediates and have found wide applications
in organic processes. For this reason there is a growing
interest in the development of new environmentally
Here we report preliminary results about a very simple
and highly regioselective method for the ring-opening of
typical 1,2-epoxides to vic-halohydrins by alkali metal
(Li+, Na+, K+) and ammonium halides (I–, Br–, Cl–) in ionic
liquids (Scheme 1). When 1,2-epoxides 1–5 were treated
with
2
equivalents of metal halides MHal in
[hexmim][ClO4] at 25–80 °C they were converted into the
corresponding b-halohydrins 6–10a–c in high to excellent
yields (Table 1, Table 2, Table 3).13 The use of 2 equiva-
lents of MHal was found to be an optimal compromise for
reaching the highest yields in relatively short reaction
times. The data of Tables 1– 3 evidence the effect of the
metal halide nature in determining the reaction conditions.
With the lithium iodide the vic-iodohydrins 6–10c are ob-
tained in quantitative yields after 1–5 hours at room tem-
perature (entries 1, 24, 38, 43, 46). Changing to sodium
iodide the ring-opened products are obtained in 3–8 hours
(entries 3, 25, 48).
Finally, with the potassium salts the conversions are in-
complete (33%) even after prolonged times (24 h, entry
6). As expected, by increasing the temperature to 60 °C,
lower reaction times (3–5 h) were necessary for obtaining
the vic-iodohydrins (80–93%) from NaI (entries 5, 26, 39,
44). At that temperature NH4I afforded the products in
comparable yields (78–85%) in 14–26 hours (entries 7,
SYNLETT 2006, No. 9, pp 1335–1338
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Advanced online publication: 22.05.2006
DOI: 10.1055/s-2006-941562; Art ID: G03306ST
© Georg Thieme Verlag Stuttgart · New York