Co(II)-salen-catalyzed asymmetric intramolecular cyclopropanation

Article abstract of DOI:10.1016/S0040-4039(01)00218-0

Optically active Co(II)-salen complexes (5 and 7) were found to catalyze highly enantioselective intramolecular cyclopropanation of 2-alkenyl α-diazoacetates in the presence of N-methylimidazole under high substrate concentration.

Full text of DOI:10.1016/S0040-4039(01)00218-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2521–2524
Co(II)–salen-catalyzed asymmetric intramolecular
cyclopropanation
Tatsuya Uchida, Biswajit Saha and Tsutomu Katsuki*
Department of Chemistry, Faculty of Science, Graduate School, Kyushu University 33, Hakozaki, Higashi-ku,
Fukuoka 812-8581, Japan
Received 17 January 2001; accepted 2 February 2001
Abstract—Optically active Co(II)–salen complexes (5 and 7) were found to catalyze highly enantioselective intramolecular
cyclopropanation of 2-alkenyl a-diazoacetates in the presence of N-methylimidazole under high substrate concentration. © 2001
Elsevier Science Ltd. All rights reserved.
8
9
Intramolecular cyclopropanation is a useful methodol-
ogy for the construction of [n,1,0]bicyclic structures
that appear in various natural products as their sub-
units, and much effort has been directed to its asym-
high trans- and cis-selectivities together with excellent
enantioselectivity can be obtained by choosing a suit-
able metal center and appropriate tuning of the salen
ligand. Furthermore, we recently found that complex 2
and its modified complexes 4 and 6 served as catalysts
for intramolecular cyclopropanation of trans-cinnamyl
a-diazoacetates under photo-irradiated conditions and
good enantioselectivities were obtained with 4 and 6 as
1
2
metrization. Thus far, Cu[bis(oxazoline)s], Cu(aza-
2
a
3
4
semicorrin), Cu(diamine), Ru(Pybox), Rh(MEPY)
5
6
and its related complexes, Rh (S-DOSP) , have been
2
2
successfully applied to asymmetric intramolecular
cyclopropanation and high enantioselectivities have
10
catalysts. We also examined (salen)cobalt complex 3
as the catalyst under the same conditions (substrate
concentration=0.01 M, THF solution) without photo-
irradiation, but the desired reaction was not observed
(Scheme 1).
1
been achieved. However, enantioselectivities obtained
are dependent on the substrates used to a considerable
7
extent, and development of a new catalyst for asym-
metric cyclopropanation has been strongly desired.
We have demonstrated that (salen)cobalt and
However, we found that complex 3 also promoted
intramolecular cyclopropanation of trans-cinnamyl a-
diazoacetates at much higher substrate concentration
(
salen)ruthenium complexes (1, 3, and 2) serve as cata-
lysts for intermolecular cyclopropanation and that both
Ph
N
Ph
N
N
O
N
O
M
Co
R R
MeO
O Br O
1
OMe
2
3
4
: M= Ru(NO)Cl, R= Ph
: M= Co, R= Ph
: M= Ru(NO)Cl, R= Me 7: M= Co, R= H
5: M= Co, R= Me
6: M= Ru(NO)Cl, R= H
Keywords: chiral (salen)cobalt(II) complex; asymmetric intramolecular cyclopropanation; 2-alkenyl a-diazoacetates.
*
Corresponding author. Fax: +81 92 642 2607; e-mail: katsuscc@mbox.nc.kyushu-u.ac.jp
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00218-0

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522
T. Uchida et al. / Tetrahedron Letters 42 (2001) 2521–2524
O
H
N CH
2
O
catalyst (5 mol%), hν
1
5
Ph
O
Ph
O
THF (7 ml), 37 °C, 32-35 h
H
(0.074 mmol)
catalyst 2: 66%, 70% ee
6: 54%, 80% ee
3: 0% (no irradiation)
Scheme 1.
(
0.1 M, THF solution) in the presence of N-methyl
yielding excellent enantioselectivity as well as accept-
able chemical yields (Scheme 3). Although 5 showed
slightly better enantioselectivity than 7, 7 exhibited
1
1,12
imidazole,
though the reaction rate was still slow. In
this reaction, the diazoacetate was slowly added to the
reaction medium to avoid its dimerization, which was a
major side reaction when ruthenium complexes 2, 4,
and 6 were used as the catalysts, but no dimerization
was detected in this reaction. The reaction was next
examined with complex 7 as the catalyst under other-
wise the same conditions and much better enantioselec-
tivity was found to be achieved, though the chemical
yield was modest. Dimerization of the substrate was
also not observed (Scheme 2).
14
somewhat higher catalytic activity than 5.
The configuration of the product could be explained by
the model proposed for the Ru-catalyzed intramolecu-
1
3
10
lar cyclopropanation (Fig. 1), in which the carbonyl
oxygen of the intermediate carbenoid has been assumed
15
to be positioned anti to the cobalt ion and the olefinic
unit to approach along the CoꢀN bond with an orienta-
tion perpendicular to the CoꢀC bond, rotating clock-
9d
wise to give the major enantiomer. This transition
1
Thus, we examined Co complexes (5 and 7) as the
catalysts in the cyclopropanation of trans-cinnamyl a-
diazoacetate in the presence of 1 equivalent of N-
methylimidazole without using high-dilution technique,
state model suggests that E-allyl a-diazoacetates (R =
3
2
R =H, R "H) are the best substrates for this reaction.
1
The presence of Z-substituent R may cause some steric
repulsion upon the rotation of the olefinic unit, espe-
O
H
N CH
2
O
catalyst (5 mol%)
1
5
Ph
O
Ph
O
THF (0.1 ml), NMI (0.01 mmol), rt, 24 h
H
[
0.1 mmol, THF (1 ml )]
catalyst 3: 15%, 75% ee
7: 24%, 96% ee
Scheme 2.
O
H
N CH
2
O
catalyst (5 mol%)
1
5
Ph
O
Ph
O
THF (0.2 ml), NMI (0.1 mmol), rt, 24 h
H
(0.1 mmol)
catalyst 5: 67%, 97% ee
7: 75%, 95% ee
Scheme 3.
R3
C
top view
side view
R2
O
O
R1
N
N
O
R1
CO
H
O
R2
O
R3
3'
3
R R
Co
NMI
Salen ligand is
2
"
schematically drawn with
bold line.
R= Ph, Me, H
= cobalt ion
Figure 1.

T. Uchida et al. / Tetrahedron Letters 42 (2001) 2521–2524
2523
Table 1. Asymmetric intramolecular cyclopropanation using Co(II)–salen complexes (5 and 7) as catalysts
O
H
R2
R1
catalyst (5 mol%)
R1
R2
O
2
O
CHN2
R3
NMI (0.1 mmol), THF, rt, 24h
R3
O
(0.1 mmol)
Entry
Catalyst
R1
R2
R3
Yield (%)
% ee
1
2
3
4
5
6
7
8
5
7
5
7
5
7
5
7
7
7
7
5
7
5
7
7
7
5
5
7
7
H
H
H
H
H
H
H
H
H
H
H
H
p-ClC H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
72
88
70
93
70
52
32
24
10
48
81
18
34
70
47
23
65
35
16
24
12
98a
6
4
4
a
p-ClC H
96
98
96
97
96
93
84
91
82
79
73
75
90
91
79
74
6
a
p-MeOC H
p-MeOC H
6
4
a
6
4
b
p-BrC H
6
4
4
b
p-BrC H
6
c
PhꢀCꢁC
PhꢀCꢁC
c
d
9
PhCH CH
2
2
2
2
2
e
d
10
11
12
13
14
15
16
17
18
19
20
21
PhCH CH
2
f
d
PhCH CH
2
f
d
PhCH CH
2
e
g
H
(CH ) CH
3
2
h
Me
Me
Ph
Ph
Ph
Ph
Ph
H
Ph
Ph
Ph
Ph
Ph
H
h
i
e
i
i
81
74
68
a
a
H
Ph
f
d
38
a
b
c
d
e
f
Enantiomeric excess was determined by HPLC analysis using chiral column (Daicel Chiralpak AD, hexane:isopropanol=15:1).
Enantiomeric excess was determined by HPLC analysis using chiral column (Daicel Chiralpak ADx2, hexane:isopropanol=15:1).
Enantiomeric excess was determined by HPLC analysis using chiral column (Daicel Chiralpak AD, hexane:isopropanol=20:1).
Enantiomeric excess was determined by GLC analysis using Chiral b-DEX column operated at 160°C.
Reaction was carried out at 35°C in the presence of 0.2 mmol of N-methylimidazole.
Reaction was carried out at 45°C in the presence of 0.2 mmol of N-methylimidazole.
Enantiomeric excess was determined by GLC analysis using Chiral b-DEX column operated at 120°C.
Enantiomeric excess was determined by HPLC analysis using chiral column (Daicel Chiralcel OB-H hexane:isopropanol=15:1).
g
h
i
Enantiomeric excess was determined by HPLC analysis using chiral column (Daicel Chiralpak AD, hexane:isopropanol=9:1).
1
cially when R is sterically bulky, and depress enan-
tioselectivity to some extent. On the other hand, the
b-phenylcinnamyl a-diazoacetate showed enantioselec-
tivity of 81% ee. On the other hand, the reaction of
cis-cinnamyl a-diazoacetate was slow and less selective
(68% ee, entry 20), supporting the above hypothesis
that the E-aryl substituent has an advantageous effect
on enantioselectivity. A substrate bearing a substituent
3
presence of substituent R is considered to destabilize
the transition state strongly and to depress enantiose-
lectivity.
In accord with the transition state model, high enan-
tioselectivity was also achieved in the reactions of other
E-aryl-substituted substrates with complex 5 or 7 as the
catalyst (Table 1, entries 1–6). However, E-alkynyl- and
alkyl-substituted substrates were less reactive and their
reactions showed slightly diminished enantioselectivity
(R "H) showed poor reactivity and enantioselectivity
3
was poor, as the model anticipated (entry 21).
In summary, we were able to demonstrate that Co(II)–
salen complexes served as good catalysts for
intramolecular asymmetric cyclopropanation reactions
of 2-alkenyl a-diazoacetates under high substrate
concentration.
(
entries 7–13). Chemical yield was improved as reaction
temperature was raised, but enantioselectivity was
reduced to some extent (entries 9–11). These results
suggest that E-aryl substituents attractively interact
with the salen ligands. As anticipated from the model,
enantioselectivity was reduced by introduction of the
Z-substituent, reflecting its bulkiness: the reaction of
b-methylcinnamyl a-diazoacetate with 5 showed high
enantioselectivity of 90% ee that was slightly less than
the selectivity observed in the reaction of cinnamyl
a-diazoacetate itself (entry 14), while the reaction of
Acknowledgements
Financial support from a Grant-in-Aid for Scientific
Research (Priority Areas, No. 706: Dynamic Control of
Stereochemistry) from the Ministry of Education, Sci-
ence, Sports, and Culture, Japan, is gratefully acknowl-

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T. Uchida et al. / Tetrahedron Letters 42 (2001) 2521–2524
edged. B.S. is grateful for a Scholarship from the
Ministry of Education, Science, Sports, and Culture,
Japan.
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2. Enantioselectivity of intermolecular cyclopropanation
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reaction of (E)-cinnamyl a-diazoacetate using 7 as the
catalyst: (E)-3-Cinnamyl a-diazoacetate (0.1 mmol, 20.2
mg) was placed in a Schlenk tube and the tube was
purged with nitrogen. To the tube were added a 0.5 M
THF solution (0.2 ml) of N-methylimidazole and Co(II)–
salen complex (5 mol%, 3.6 mg) successively. The reac-
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(
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residue was chromatographed on silica gel using hexane
and ethyl acetate as eluent to give bicyclic lactone (13 mg)
in 75% yield. The ee of the product was determined by
GLC analysis using CHIRAL b-DEX column operated
at 160°C.
1
6
7
8
. Rh (4S-MPPIM)4 has been reported to be an efficient
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Lynch, V.; Simonsen, S. H. J. Am. Chem. Soc. 1993, 115,
9968–9978.
2
catalyst for intramolecular cyclopropanation of 2-alkenyl
a-diazoacetates of various substitution patterns: Doyle,
.
.