ORGANIC
LETTERS
2005
Vol. 7, No. 17
3789-3791
Stereoselective Functionalization of
Cyclopropane Derivatives Using
Bromine/Magnesium and Sulfoxide/
Magnesium Exchange Reactions
Felix Kopp,† Genia Sklute,†,‡ Kurt Polborn,† Ilan Marek,‡ and Paul Knochel*,†
Department Chemie und Biochemie, Ludwig-Maximilians-UniVersita¨t, Butenandtstrasse
5-13, 81377 Munich, Germany, and Department of Chemistry, Technion - Israel
Institute of Technology, Technion City, Haifa 32000, Israel
Received June 22, 2005
ABSTRACT
The reaction of 2,2-dibromo-1-methyl-cyclopropanecarbonitrile (1) with i-PrMgCl in Et2O/CH2Cl2 provides the cis-magnesium-carbenoid (2),
which reacts with high retention of configuration with various electrophiles. If E
via a sequential Br/Mg- and sulfoxide/Mg-exchange can be achieved.
) SPh, a stereoselective generation of a quaternary center
The functionalization of cyclopropane derivatives has been
extensively investigated.1 Since gem-dibromocyclopropanes
are readily available,2 we have examined the stereoselective
magnesiation of the functionalized cyclopropane 2,2-di-
bromo-1-methyl- cyclopropanecarbonitrile (1).3 Whereas the
treatment of the dibromide 1 with i-PrMgCl in THF or Et2O4
at low temperature leads to products in low yields, it was
found that the reaction of 1 with i-PrMgCl in a mixture of
Et2O and CH2Cl2 (1:4) at -50 °C leads within 5 min to the
clean formation of the cis-cyclopropylmagnesium reagent 2.
The quenching of 2 with aqueous ammonium chloride affords
only the trans-2-bromocyclopropanecarbonitrile (3a) in 76%
yield with a diastereomeric ratio of >99:1 (entry 1 of Table
1). The high diastereoselectivity of the exchange reaction is
presumably caused by the nitrile function, which can direct
the exchange reaction by precoordination. The reaction of
magnesium reagent 2 with iodine provides the desired
iodobromocyclopropane 3b with a diastereoselectivity of 91:9
and a yield of 77% (entry 2). The reaction of the cyclopro-
pylmagnesium derivative 2 with MeSSO2Me and PhSSO2-
Ph provides the corresponding thioethers 3c (72%; dr ) 93:
7) and 3d (86%; dr ) 95:5; entries 3 and 4). An X-ray
analysis of the thioether 3d confirmed the cis configuration
of the cyano and thiophenyl groups (Figure 1). The reaction
of 2 with N,N-diethylaminomethylbenzotriazole5 provides the
aminomethylated product 3e in 79% yield (dr ) 96:4; entry
5). Finally, the reaction of the magnesium carbenoid 2 with
allyl bromide in the presence of CuCN‚2LiCl6 (0.5 mol %)
furnishes the allylated cyclopropane 3f in 78% yield (dr >
† Ludwig-Maximilians-Universita¨t.
‡ Technion - Israel Institute of Technology.
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Kozhushkov, S. I. Chem. ReV. 2000, 100, 93. (c) Liu, H.; Shook, C. A.;
Jamison, J. A.; Thiruvazhi, M.; Cohen, T. J. Am. Chem. Soc. 1998, 120,
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(2) Fedorynski, M. Chem. ReV. 2003, 103, 1099.
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recoechea, J. M.; Palenik, G. J.; Koziol A. E.; Szczesniak, M. J. Chem.
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(3) Dehmlow, E. V.; Lissel, M.; Heider, J. Tetrahedron 1977, 33, 363.
(4) (a) Vu, V. A.; Marek, I.; Knochel, P. Angew. Chem., Int. Ed. 2002,
41, 351. (b) Vu, V. A. Marek, I.; Knochel, P. Synthesis 2003, 1797. (c)
Baird, M. S.; Nizovtsev, A. V.; Bolesov, I. G. Tetrahedron 2002, 58, 1581.
10.1021/ol051452p CCC: $30.25
© 2005 American Chemical Society
Published on Web 07/23/2005