Iridium-catalyzed alternative of the Meinwald rearrangement

Article abstract of DOI:10.1016/S0040-4039(03)01593-4

A novel and easy to handle procedure for the regioselective rearrangement of epoxides has been developed, based on an iridium catalyst.

Full text of DOI:10.1016/S0040-4039(03)01593-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7687–7689
Iridium-catalyzed alternative of the Meinwald rearrangement
Iyad Karame´, M. Lorraine Tommasino and Marc Lemaire*
Laboratoire de Catalyse et Synthe`se Organique, UCBL, UMR 5622, CPE, 43, bd du 11 novembre 1918,
69622, Villeurbanne cedex, France
Received 10 June 2003; revised 24 June 2003; accepted 26 June 2003
Abstract—A novel and easy to handle procedure for the regioselective rearrangement of epoxides has been developed, based on
an iridium catalyst.
© 2003 Elsevier Ltd. All rights reserved.
Epoxides are very important and versatile intermediates
in organic synthesis since they can be readily trans-
formed into a variety of functional groups.1 One of the
useful synthetic routes to aldehydes and ketones from
epoxides is the Meinwald rearrangement.2 This reaction
could be performed in the presence of various Lewis
acids. The nature of the obtained product depends on
the migratory aptitude of the substituents on the epox-
ide group but also on the nature of the Lewis acid and
the solvent (Scheme 1).3–6
Some examples of catalytic Meinwald rearrangements
have been reported in the last decade. Kulasegaram and
Kulawiec7 reported the isomerization of epoxides to
carbonyl compounds with catalytic amounts of palla-
dium species (5% mol) formed in situ from Pd(OAc)2
and a phosphine ligand. Recently, Mohan et al.8
employed a bismuth-based catalyst8b for the rearrange-
ment of epoxides with good regioselectivities. We report
in this paper the first use of an iridium species as
regiospecific catalyst for the Meinwald rearrangement
of epoxides under mild reaction conditions.
The Meinwald rearrangement is usually carried out
with methylaluminium bis(4-bromo-2,6-di-tert-butyl-
phenoxide) (MABR),3 BF3·Et2O,4 MgBr2,4 lithium
salts5 or indium chloride6 in stoichiometric amounts or
even in excess. As some of these reactants are air-sensi-
tive, corrosive or toxic, anhydrous conditions and inert
atmosphere are generally needed.
Iridium trichloride was used in 1% molar ratio relative
to the epoxide (THF, 50°C; Table 1). Rearrangement of
styrene oxide gave pure phenylacetaldehyde (entry 1).
trans-b-Methylstyrene oxide and a-methylstyrene oxide
(entries 2–3) rearranged selectively and quantitatively
into phenylacetone and 2-arylpropanal, respectively.
For trans and cis-stilbene (entries 4–5), diphenylac-
etaldehyde was the only formed product. In this later
case, iridium lead to the aldehyde, while Pd(OAc)2,
combined to PPh3, gave7a the ketone, deoxybenzoin.
The only case in which IrCl3·xH2O lead to some traces
of a secondary product was the reaction with dihy-
dronaphtalene oxide (entry 6). Only 4% of cyclohexene
oxide rearranges into cyclopentane carboxaldehyde
(entry 7). Several tests were realized in order to improve
this result by increasing the temperature to 100°C in
toluene or DMF, without success. It was reported that
LiBr–HMPA allowed more than 90% yield of cyclopen-
tane carboxaldehyde in benzene at 80°C.5a
Scheme 1. Meinwald rearrangement.
The optically active a-arylpropanoic acid derivatives
are effective nonsteroidal analgesics9 and synthetic
routes to the corresponding enantiopure aldehydes are
thus of high interest. As 2-arylpropanal was easily
Keywords: Meinwald rearrangement; epoxides; iridium catalyst.
* Corresponding author. E-mail: marc.lemaire@univ-lyon1.fr
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01593-4

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I. Karame´ et al. / Tetrahedron Letters 44 (2003) 7687–7689
Table 1. Rearrangement of epoxides with IrCl3·xH2O catalyst (1% mol)a
prepared by a Meinwald rearrangement (Table 1, entry
2) we focused on the chiral version. We first prepared
the (R)-a-methylstyrene oxide in 60% ee with Jacobsen
catalyst10 at −78°C. The rearrangement of this epoxide,
was carried out with iridium trichloride in THF at 50°C
but almost racemic aldehyde was obtained (Scheme 2).
When the epoxide bears on the same carbon atom a
methyl and a bulkier group, such as phenyl or
Scheme 2. Rearrangement of chiral a-methylstyrene oxide.

I. Karame´ et al. / Tetrahedron Letters 44 (2003) 7687–7689
7689
adamantly, distinct migratory aptitudes of the two
References
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use of a bulky and chiral Lewis acid, or of a chiral
iridium catalyst, may lead to a stereoselective control
for this reaction.
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In summary, this work presents a new effective and
regioselective alternative for the Meinwald rearrange-
ment of epoxides catalyzed by iridium(III) species. The
hydrated iridium complex used is very stable and the
reaction can be run under mild conditions (no inert
atmosphere or high temperature are required). This
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Representative procedure for the isomerization of epox-
ides: The epoxide (40 ml, 0.335 mmol for styrene epox-
ide) was added to a solution of IrCl3·xH2O (1 mg,
3.35×10−3 mmol) in THF (1 mL) and the reaction
mixture stirred at room temperature. The reaction time
was determined by GC analysis. After 2 h at 50°C, the
solvent was removed and phenylacetaldehyde was
recovered. Its purity (>99%) was determined by GC,
13C and 1H NMR. Conversions and ee values were
determined by GC on a chiral column (b-dex-225
column, 30 m). All the final products were isolated in
almost quantitative yields and characterized by com-
1
parison of their 13C and H NMR spectra with already
reported data.