The first Corey-Chaykovsky epoxidation and cyclopropanation in ionic liquids

Article abstract of DOI:10.1016/S0040-4039(03)00732-9

The first Corey-Chaykovsky epoxidation and cyclopropanation using trimethyl sulfonium iodide/trimethyl sulfoxonium iodide and KOH as base in the recyclable ionic liquid, (bmim)PF₆ are described.

Full text of DOI:10.1016/S0040-4039(03)00732-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3629–3630
The first Corey–Chaykovsky epoxidation and cyclopropanation
in ionic liquidsꢀ
S. Chandrasekhar,* Ch. Narasihmulu, V. Jagadeshwar and K. Venkatram Reddy
Indian Institute of Chemical Technology, Hyderabad, India
Received 12 February 2003; revised 7 March 2003; accepted 14 March 2003
Abstract—The first Corey–Chaykovsky epoxidation and cyclopropanation using trimethyl sulfonium iodide/trimethyl sulfoxonium
iodide and KOH as base in the recyclable ionic liquid, (bmim)PF6 are described. © 2003 Elsevier Science Ltd. All rights reserved.
Cyclopropanes and epoxides are small, highly strained
skeletons and are present in several natural products.1
Besides this, epoxides also play a major role as building
blocks for ‘CꢀC’ and ‘CꢀX’ bond (X=N, O and S)
formation.2 Hence the synthesis of these classes of
compounds has attracted the interest of a wide range of
synthetic chemists. Generally cyclopropane rings are
constructed by the addition of a carbene to an olefin.3
Epoxides can be prepared by peracid oxidation of the
corresponding olefin. Alternatively cyclopropanes can
be prepared by addition of trimethyl sulfoxonium
iodides to enones whereas epoxides can be prepared by
addition of trimethyl sulfonium iodides to aldehydes/
ketones in the presence of a base such as sodium
hydride or n-BuLi4 (popularly called Corey–
Chaykovsky salts). These reactions are conventionally
carried out in THF or DMSO as solvents. Toda et al.5
have also proved that these reactions can be performed
in the absence of solvent albeit on small scale.
ease of recyclability, rapid reaction times and high
yields. Several conventional organic transformations
have been reported in ionic solvents as alternative
solvent media. Surprisingly however, there is no report
on epoxidation or cyclopropanation using a trimethyl
sulfoxonium salt in ionic liquids. Herein, we report for
the first time cyclopropanation and epoxidation in the
ionic solvent (bmim)PF6 (Scheme 1).
In the initial studies, cyclohex-2-enone (entry 1, Table
1) was subjected to cyclopropanation using trimethyl
sulfoxonium iodide and KOH as base in (bmim)PF6.
Within two hours at room temperature we observed
clean formation of product 1a in 95% yield.7 To gener-
alize this protocol, the readily available terpene (R)-car-
vone (entry 2, Table 1) was subjected to the above
reaction conditions to give cyclopropyl carvone 2a in
92% yield. Chalcone substrates (entries 3 and 4, Table
1) also behaved well and produced the expected targets
in high yields. 1-Phenylbut-2-en-1-one (entry 5, Table 1)
and 1,4-diphenylpent-2-en-1-one were also no
exceptions.
In recent years ionic liquids6 have proved themselves as
attractive solvents for organic synthesis because of their
To check the efficiency of recycling (bmim)PF6, cyclo-
hex-2-enone (Table 2) was subjected to cyclopro-
panation8 using KOH as base and, after four runs,
the yield of the corresponding cyclopropane was very
high.
Scheme 1.
To check the efficiency of epoxidations, several alde-
hydes and ketones were subjected to trimethyl sulfo-
nium iodide and KOH in (bmim)PF6 (Scheme 2 and
Table 3). To our satisfaction the aldehydes (entries 1–4)
and the ketone (entry 5) produced epoxides in 77–91%
Keywords: epoxidation; cyclopropanation; ionic liquids; trimethyl
sulfoxonium iodide; Corey–Chaykovsky reaction.
ꢀ IICT Communication No. 030129.
* Corresponding author. Tel.: +91-40-27193434; fax: +91-40-
27160512; e-mail: srivaric@iict.ap.nic.in
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00732-9

3630
S. Chandrasekhar et al. / Tetrahedron Letters 44 (2003) 3629–3630
Table 1. Cyclopropanation of olefins using Me3S(O)I and
KOH in (bmim)PF6
Scheme 2.
yields in 2 h. In the case of acetophenone, we observed
rearrangement of 5a to 2-phenylpropanaldehyde on
standing which may be attributed to the Lewis acidity
of the ionic liquid.
In conclusion, we have demonstrated for the first time,
epoxidation and cyclopropanation using sulfonium and
sulfoxonium salts can be achieved in the ionic liquid
(bmim)PF6 with recycling.
Acknowledgements
C.N. and V.J. thank the CSIR, New Delhi, for financial
assistance.
References
1. (a) Liu, H. W.; Walsh, C. T. In The Chemistry of the
Cyclopropyl Group; Patai, Rapoport, Eds. Biochemistry of
the Cyclopropyl Group. Wiley: New York, 1987; Chapter
16, p. 959; (b) Faust, R. Angew. Chem., Int. Ed. 2001, 40,
2251; (c) Donaldson, W. A. Tetrahedron 2001, 57, 8589.
2. Chandrasekhar, S.; Reddy, C. R.; Babu, B. N.; Chan-
drashekar, G. Tetrahedron Lett. 2002, 43, 3801 and refer-
ences cited therein.
3. Pfaltz, A. In Comprehensive Asymmetric Catalysis I–III;
Chapter 16.1; Lyden, K. M.; McKervey, M. A.; Chapter
16.2; Charette, A. B.; Lebel, H.; Chapter 16.2; Jacobsen,
E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer: Berlin,
2000.
Table 2. Cyclopropanation of cyclohex-2-enone showing
the recyclability of (bmim)PF6
Run
1
2
3
4
5
Isolated yield (%)
95
95
93
91
90
Table 3. Epoxidation of carbonyl compounds using Me3SI
and KOH in (bmim)PF6
4. (a) Corey, E. J.; Chakovsky, M. J. Am. Chem. Soc. 1965,
87, 1353; (b) Harwood, L. M.; Casy, G.; Sherlock, J.
Synth. Commun. 1990, 1287.
5. Toda, F.; Imai, N. J. Chem. Soc., Perkin Trans. 1 1994,
2674.
6. (a) Welton, T. Chem. Rev. 1999, 99, 2071; (b) Wasser-
scheid, P.; Keim, W. Angew. Chem., Int. Ed. 2000, 39,
3772; (c) Sheldon, R. Chem. Commun. 2001, 2399.
7. General procedure for cyclopropanation and epoxidation: A
25 mL flask was charged with (bmim)PF6 (2 mL), sub-
strate (2 mmol), trimethyl sulfonium iodide/trimethyl sul-
foxonium iodide (2.2 mmol) and KOH (2.4 mmol) and
stirred for 2 h at room temperature. After completion of
the reaction, the mixture was extracted with Et2O (3×10
mL). The combined ether extracts were concentrated on a
rotary evaporator and the crude product was purified by
column chromatography on silica gel to give the desired
product.
8. After every run, the product was isolated by extraction
with ether and additional KOH, olefin and salt were added
in one portion and reaction sequence repeated.