Co(II)-salen-catalyzed highly cis- and enantioselective cyclopropanation

Article abstract of DOI:10.1016/S0040-4039(00)00433-0

The reactions of styrene derivatives and t-butyl α-diazoacetate using (R,R)-(salen)cobalt(II) complex 6 as a catalyst in the presence of N- methylimidazole gave the corresponding cyclopropanecarboxylates with excellent enantio- (>95% ee) and high cis-ster

Full text of DOI:10.1016/S0040-4039(00)00433-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3647–3651
Co(II)–salen-catalyzed highly cis- and enantioselective
cyclopropanation
∗
Tatsuo Niimi, Tatsuya Uchida, Ryo Irie and Tsutomu Katsuki
Department of Molecular Chemistry, Graduate School of Science, Kyushu University, 33 Hakozaki, Higashi-ku,
Fukuoka 812-8581, Japan
Received 17 February 2000; accepted 10 March 2000
Abstract
The reactions of styrene derivatives and t-butyl α-diazoacetate using (R,R)-(salen)cobalt(II) complex 6 as a
catalyst in the presence of N-methylimidazole gave the corresponding cyclopropanecarboxylates with excellent
enantio- (>95% ee) and high cis-stereoselectivity (98%) as well as good chemical yields. © 2000 Elsevier Science
Ltd. All rights reserved.
Keywords: chiral Co(II)–salen complex; asymmetric cyclopropanation; cis- and enantioselectivity.
Cycloaddition of oxenoide and its isoelectronic species, nitrenoide and carbenoide, to a π-bond
constitutes an important class of olefinic transformations, for example, epoxidation, aziridination and
cyclopropanation. Differentiation of the enantiotopic faces of double bonds is the main stereochemical
issue in this class of reaction. Different from epoxidation and aziridination, however, another stereo-
chemical issue, cis–trans selectivity, is imposed on the cyclopropanation reaction due to the presence of
a substituent at the carbenoid carbon. Thus, simultaneous control of these two stereochemical problems
is indispensable for achieving highly efficient cyclopropanation.
In 1965, Nozaki et al. first dealt with the stereochemical issue in cyclopropanation by using a
1
chiral copper complex as the catalyst, although stereoselectivity was only modest. This pioneering
study was improved by Aratani et al. into a highly enantioselective process by modifying the chiral
2
copper complex. Subsequent to these studies, many excellent metal-catalyzed methodologies have been
3
developed for asymmetric cyclopropanation, but most of them are trans-selective. Only a few examples
4
show cis-selectivity.
We have recently disclosed that chiral metallosalen complexes (hereafter referred to as M-salen
complexes) are excellent catalysts for asymmetric transfer reactions of oxenoide and its isoelectronic
5
species. As a part of this study, we examined asymmetric cyclopropanation using Co–salen com-
plexes as catalysts. Originally, Co–salen-catalyzed asymmetric cyclopropanation was started by using
∗
Corresponding author. Fax: +81 92 642 2586; e-mail: katsuscc@mbox.nc.kyushu-u.ac.jp (T. Katsuki)
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00433-0
tetl 16713

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a chiral Co(II)–salen complex as a catalyst but enantioselectivity was low. Later, we found that chiral
0
Co(III)–salen complexes 1 bearing an electron-donating methoxy group at C5 and C5 and an apical
bromo ligand showed high trans- and enantioselectivity together with good chemical yields (Scheme
7
1
). It is, however, noteworthy that Co(III)–salen complexes bearing substituents like a methyl or t-
0
butyl group at C3 and C3 showed no catalytic activity. This is probably because olefins approach
0
0
the intermediary Co(V)-carbenoid species from its C3 and C3 side and the presence of 3- and 3 -
substituents intercepts the olefin’s approach from the side. This assumption prompted us to use a
chiral Ru–salen complex as the catalyst for asymmetric cyclopropanation for the following reason: the
Ru–Oequat bond in a Ru–salen complex is ca. 0.2 Å longer than that in Co(III)–salen complexes, and
the elongated distance between C3- and C3 -carbons in the Ru–salen complex may allow the olefin’s
approach from the C3 and C3 side even if there are substituents at C3 and C3 . As expected, Ru–salen
complexes bearing 3,3 -substituents served as the catalyst for cyclopropanation and, among them, (R,R)-
ON )(salen)ruthenium(II) complex 2 was for the first time found to show high cis- and enantioselectivity
in cyclopropanation, but its chemical yield was less than satisfactory due to the undesired reaction of
the intermediary Ru–carbenoid and α-diazoacetate to give undesired fumaric and maleic acid esters. To
achieve high cis- and enantioselectivity and high chemical yields, we again examined Co–salen-catalyzed
asymmetric cyclopropanation.
0
0
0
0
+
(
8
Scheme 1. Highly enantio- and diastereoselective cyclopropanation using metallosalen complexes as catalysts. Co(III)–salen:
trans-selective; Ru(II)–salen: cis-selective
The Co(II)–Oequat bond in a Co(II)–salen complex is roughly equal to that in a Co(III)–salen complex.
However, the Co(II)–salen complex can adopt various ligand conformations, depending on its ligand
9
substituent or apical ligand. Thus, we expected that a suitably substituted Co(II)–salen complex would
show specific catalysis for asymmetric cyclopropanation. To explore this possibility, we prepared five
chiral Co(II)–salen complexes (3–7) and examined the reaction of styrene and t-butyl α-diazoacetate
(Table 1). Complex 3 which has the same ligand as 1 showed moderate trans- and enantioselectivity,
although the reaction was slow (entry 1). It is noteworthy that enantiomeric excess of the cis-isomer is
good (86% ee), although it is a minor product and that the sense of enantioselection by 3 is opposite to that
10
by 1, suggesting that the conformation of the salen ligand differs in 3 and 1. To our delight, complexes
0
4
and 5 bearing substituents at C3 and C3 were found to catalyze cyclopropanation, although their
stereochemistry was moderately trans- and enantioselective and the formation of fumaric and maleic acid
esters was detected (entries 2 and 3). In these reactions, enantiomeric excesses of minor cis-isomers were

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also good to high. Encouraged by these results, we next examined the reaction with (R,R)-Co(II)–salen
complex 6 that has the same ligand as complex 2. Differing from the reaction with complexes 4 and 5,
the reaction with complex 6 proceeded smoothly with excellent cis- and enantioselectivity and only a
trace amount of fumaric and maleic acid esters (<1%) was detected (entry 4).
Table 1
a)
Asymmetric cyclopropanation of styrene using Co(II)–salen complexes as catalysts
It is noteworthy that the sense of enantioselection by complex 6 was opposite to that by complex
2
bearing the same ligand as 6, although the reaction conditions were the same. This also suggests
that complexes 2 and 6 have different ligand-conformation to each other, but further experimentation is
10
required to draw any conclusion on the ligand-conformation. Quite recently, Yamada et al. reported that
the rate and the enantioselectivity of the cyclopropanation using a chiral aldiminato cobalt(II) complex
as the catalyst were improved by adding N-methylimidazole to the reaction medium.11 Based on this
report, we also performed the reaction in the presence of N-methylimidazole and found that both cis-
and enantioselectivity were further improved up to a ratio of 98:2 and 98% ee (entry 5). We examined
the reaction using (R,S)-Co(II)–salen complex 7 in the presence of N-methylimidazole. The reaction
also exhibited excellent cis- and enantioselectivity, but the reaction was slow even in the presence of
N-methylimidazole (entry 6).
Under the optimized conditions, we examined the cyclopropanation of other substrates (Table 2). All
the reactions examined also showed good to excellent cis- and enantioselectivity. The chemical yields of
the desired cyclopropanes were good, except for the reaction of α-methylstyrene, and only a trace amount
of fumaric and maleic acid esters was detected in all the reactions. Although asymmetric configuration
of the products has not been determined, the configuration of the major cis-isomers was also found to
be opposite to the configuration of the corresponding cis-isomers obtained with complex 2 by HPLC
analyses (vide supra). It is, however, noteworthy that the catalysts 2 and 6 showed the same sense of
enantioselection only in the cyclopropanation of α-methylstyrene.

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Table 2
a)
Asymmetric cyclopropanation of various olefins using complex 6 as the catalyst
12
Asymmetric cyclopropanation of styrene with complex 6: To a THF solution (5 ml) of Co(II)–salen
1
3
complex 6 (44 mg, 50 µmol) was added a THF solution of N-methylimidazole (0.2 ml, 0.5 M, 0.1
mmol) under a nitrogen atmosphere and the mixture was stirred for 2 min. Styrene (550 µl, 4.8 mmol)
was added to this solution and the mixture was stirred for another 3 min before being treated with t-
butyl α-diazoacetate (140 µl, 1.0 mmol). The whole mixture was stirred for 24 h at room temperature
and then concentrated in vacuo. The residue was chromatographed on silica gel (hexane:AcOEt=1:0 to
9:1) to give a 98:2 mixture of cis and trans products in a 89% yield. An aliquot of the mixture was
submitted to preparative TLC (silica gel, hexane:i-Pr O=4:1) to yield the cis product which was used for
2
the determination of its enantiomeric excess (98% ee).
In conclusion, we were able to disclose that Co(II)– and Co(III)–salen complexes show considerably
different asymmetric catalytic activity and, by taking advantage of each cobalt complex, we achieved
both cis- and trans-selective asymmetric cyclopropanations. Further study on the reaction mechanism is
now proceeding in our laboratory.

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Acknowledgements
Financial support from a Grant-in-Aid for Scientific Research (09440220 and Priority Areas, No.
06: Dynamic Control of Stereochemistry) from the Ministry of Education, Science, Sports and Culture,
7
Japan, is gratefully acknowledged.
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1
1
0. The sense and magnitude of enantioselection by metallosalen complexes are dependent on the conformation of their ligands
Ref. 14). The sense of enantioselection by 2 was dependent on the solvent used (Ref. 8b): the complex 2 dissolved in the
reaction medium showed the opposite sense of enantioselection to the complex suspended in the reaction medium. The
change in the sense of enantioselection from homogeneous to heterogeneous catalysts was attributed to the change of the
ligand-conformation caused by the association of the complex. The sense of enantioselection by 6 and 2 in THF that is the
solvent of choice for the present reaction is opposite to each other.
(
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12. A typical experimental procedure was carried out in a 10-fold scale of the experiments described in Tables 1 and 2.
13. All the Co(II)–salen complexes used in this study were prepared according to the reported procedure (Ref. 7b).
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