Highly efficient and enantioselective cyclopropanation of styrene with diazoacetates using a new copper-(Schiff-base) catalyst

Article abstract of DOI:10.1016/S0957-4166(00)00037-9

A new copper-(Schiff-base) complex, derived from (S)-2-amino-1,1-di(3,5-di-t-butylphenyl)propanol, 2-hydroxy-5-nitrobenzaldehyde and copper acetate monohydrate, was used as an efficient catalyst for the cyclopropanation of styrene with diazoacetates, affo

Full text of DOI:10.1016/S0957-4166(00)00037-9

Tetrahedron: Asymmetry 11 (2000) 1157±1163
Highly ecient and enantioselective cyclopropanation of
styrene with diazoacetates using a new copper-(Schi€-base)
catalyst
Zhengning Li,* Zhuo Zheng and Huilin Chen
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China
Received 21 December 1999; accepted 11 January 2000
Abstract
A new copper-(Schi€-base) complex, derived from (S)-2-amino-1,1-di(3,5-di-t-butylphenyl)propanol, 2-
hydroxy-5-nitrobenzaldehyde and copper acetate monohydrate, was used as an ecient catalyst for the
cyclopropanation of styrene with diazoacetates, a€ording ees of up to 98%. # 2000 Elsevier Science Ltd.
All rights reserved.
1. Introduction
Catalytic asymmetric cyclopropanation of diazoacetates with ole®ns has attracted much
attention.1 Catalysts containing various metals and optically active ligands have been employed,
and styrene has been used as a benchmark ole®n for this reaction. High enantioselectivities have
been achieved by using Cu-(Schi€-base),2 Co-dioximate,3 and copper complexes with a C2 sym-
metry, such as Cu-semicorrin,4 Cu-bisoxazoline,5 Cu-bipyridine,6 Ru-(bisoxazolinyl)pydridine,7
Rh2(5S-MEPY)4,8 etc.,9,10 as catalysts. Although a Cu-(Schi€-base) complex emerged 30 years
ago as the ®rst catalyst for the asymmetric cyclopropanation of styrene,11 this kind of catalyst is
not as e€ective as the catalysts which have appeared over the last decade.4±10 However, there has
been a renaissance of this kind of catalyst in recent years. For example, Co(III)-Salen complexes
were found by Fukuda and Katsuki and a cobalt complex, MPAC, by Yamada et al. to be e-
cient catalysts for the asymmetric cyclopropanation of styrene with t-butyl diazoacetate.12,13
Yamada et al. also reported that nitrogen-containing cyclic compounds such as N-methylimidazole
could be used as e€ective additives to accelerate this reaction and to improve the enantio-
selectivity.13 However, the e€ectiveness of these catalysts is unknown when a small alkyl diazo-
acetate is employed, since, as a general rule, a higher enantioselectivity is achieved when a
* Corresponding author. Fax: +86-411-4684746; e-mail: lizn@ms.dicp.ac.cn
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00037-9

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diazoacetate containing a bulkier alkyl group is used. On the other hand, Cu-(Schi€-base) com-
plexes are not as e€ective as Co-Salen complexes with a C2 symmetry in catalyzing the asym-
metric cyclopropanation of styrene, although Cu-(Schi€-base) catalysts have achieved great
successes in the cyclopropanation of trisubstituted ole®ns with various diazoacetates, which is one
of the greatest achievements in asymmetric catalysis. For example, for the reaction of styrene
with l-menthyl diazoacetate catalyzed by S-16482b, 79% ee and 81% ee for cis and trans products,
respectively, were obtained. This was the best result in the asymmetric cyclopropanation of
styrene catalyzed by Cu-(Schi€-base) complexes before 1999. Very recently, Cai et al. reported
that copper-(Schi€-base) complexes were ecient for the asymmetric cyclopropanation of styrene
by changing the size of the alkoxyl group of Aratani's catalyst.15
In the widely exploited mechanism for the catalytic asymmetric cyclopropanation, a carbene±
copper intermediate is proposed. The steric interaction of this intermediate with an ole®n during
electrophilic attack controls the regioselectivity in the metallacyclobutane formation and the ee of
the cyclopropane derivatives. Therefore, substituents on the ligand are of great importance for
the enantioselectivity. Based on this consideration, we synthesized a new Schi€-base ligand and a
new Cu-(Schi€-base) complex. Here we report the application of this new copper (Schi€-base) on
the reaction of styrene with diazoacetates. The ee reached 98% when i-butyl diazoacetate was
used. This catalyst is di€erent from the catalysts reported in other studies in that it has 3,5-dialkyl
substituents rather than a 2-alkoxyl and a 5-alkyl substituent.2,15
2. Results and discussion
The reaction was ®rst carried out with 1,2-dichloroethane as the solvent, and an ee up to 89%
was obtained. The choice of the solvent was not limited to 1,2-dichloroethane. As shown in Table 1,
many solvents, in addition to 1,2-dichloroethane, were tested for this reaction and high ee values
were obtained in most solvents. In particular, good yields and excellent enantioselectivities
were obtained when benzene, nitrobenzene, chlorobenzene, hexane, THF, nitroethane and ethyl
acetate were used. Generally, the ee values were higher than 88% for the cis-isomer and higher
than 75% for the trans-isomer. These results are quite di€erent from those over most copper
catalysts reported before, which give higher ees for the trans-isomer than for the cis-isomer. It is
also found that acetonitrile, acetone and pyridine were ine€ective under the same conditions.
When pyridine was employed as the solvent, no cyclopropyl derivatives were detected at 40ꢀC.
Increasing the temperature to 80ꢀC only resulted in a very low yield of the product, and the
con®guration of the dominant isomer in the trans-isomers became inverted when pyridine was
used. A similar phenomenon was reported by Nakamura et al. when Co-dioximate was used as
the catalyst and some nitrogen-containing compounds were used as the additives.3 Acetonitrile
and pyridine have strong coordinating abilities and may coordinate with metal ions and change

Z. Li et al. / Tetrahedron: Asymmetry 11 (2000) 1157±1163
1159
Table 1
The e€ect of solvents on the asymmetric cyclopropanation of styrene
the transition state of the products, so that ee values of the products change dramatically when
these two solvents are employed. The low ee values obtained with acetone as the solvent may be
due to the exchange reaction occurring between the catalyst and the large excess of acetone,
which may give rise to copper salicylaldehydate, an achiral catalyst. The low yield with acetone as
the solvent may be explained by the side reaction of the diazoacetate with acetone.
It is worth noting that our results are di€erent from the results recently reported by Cai et al.,
i.e. high ees were achieved for cyclopropanation in a solvent with a strong polarity, such as
acetonitrile and DMF, in Cai's work.15
Secondary interactions among ligand±metal±substrate are of importance in some asymmetric
catalytic reactions such as hydrogenation.16 All ecient copper-(Schi€-base) catalysts used in
asymmetric cyclopropanation so far have a similar structure in that they have alkoxyphenyl
groups as substituents. Whether an alkoxyphenyl group is essential or not to achieve a high ee has
not been reported. In contrast to those catalysts derived from chiral aminoalcohols reported so
far, the catalyst in this work does not contain alkoxyl groups and gives high ees. This demon-
strates that an alkoxyl group in an aminoalcohol is not vital for this reaction. Thus, the secondary
interactions among the alkoxyl group±copper±ole®n do not play a crucial role in the catalytic
process. The substituent(s) in the aminoalcohol a€ects the enantioselectivity only via steric
repulsion rather than by electronic e€ects or coordination.

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A higher yield can be obtained at a higher temperature, as shown in Table 2. However, a lower
ee was obtained on increasing the temperature. Enantiomeric excesses of 93 and 84% for the cis
and trans products, respectively, were obtained at 0ꢀC, but only with low yields. According to
these data, the preferable temperature range for this reaction is 20 to 60ꢀC. A similar dependence
of the yield on the temperature was observed in the early days with achiral catalysts as well as
with chiral catalysts,15,17,18 and discussion has been made on this phenomenon.17 This catalyst is
highly e€ective, as shown in Table 3. An ee of 51% could be obtained when only 0.1 mol% of the
catalyst was used.
Table 2
The in¯uence of temperature on the reaction of styrene
Table 3
The in¯uence of the amount of catalyst on the reaction of styrene
A bulky group in the diazoacetate favors the enantioselectivity and diastereoselectivity. When
i-butyl diazoacetate was used, the ees reached 98 and 85% for the cis and trans products,
respectively (Table 4). On the other hand, when l-menthyl diazoacetate was used, 95 and 98% ees
for the cis- and trans-esters, respectively, were obtained. These are much higher than the results

Z. Li et al. / Tetrahedron: Asymmetry 11 (2000) 1157±1163
1161
Table 4
The in¯uence of alkyls in diazoacetate on the reaction of styrene
reported in the literature using other copper-(Schi€-bases) as the catalysts.2,14 It is worth noting
that when methyl diazoacetate is used, there are more of the cis-isomers in the product than of the
trans-isomers, which is rarely observed in the cyclopropanation of styrene.
This catalyst was also applied to the asymmetric cyclopropanation of other ole®ns, and the
results are listed in Table 5. An ee of 85% was achieved for the reaction of 1,1-diphenylethene.
Higher diastereoselectivities were obtained with 1-octene and allyl bromide as the ole®ns, whereas
lower diastereoselectivities were obtained when vinyl acetate and 2-methyl-1-pentene were
employed, and the enantioselectivities were not as high as with styrene.
Table 5
Asymmetric cyclopropanation of some other ole®ns
In conclusion, the new catalyst in this work is ecient for the asymmetric cyclopropanation of
styrene.
3. Experimental
Unless otherwise stated, all reactions were carried out under an argon atmosphere. Optical
rotations were measured by a SEPA-200 high sensitivity polarimeter. NMR spectra were recorded

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by a Bruker DRX-400 NMR spectrometer with a BBI probe. The yields and ee values were
determined by GC analyses with a chiral capillary column (30Â0.25 mm permethyl cyclodextrin,
ID, 0.25 m ®lm) at 130ꢀC. Con®gurations of phenylcyclopropanecarboxylate were determined
with a GC by comparing the GC elution order of the enantiomers with an authentic sample pre-
pared according to the literature.
3.1. (S)-2-Amino-1,1-di(3,5-di-t-butylphenyl)propanol
At 0ꢀC, 1.5 g (10.8 mmol) of methyl ester hydrochloride of l-alanine was added with vigorous
stirring to a Grignard reagent derived from 13.8 g (50.2 mmol) of 3,5-di-t-butylbromobenzene
and 1.40 g (57.6 mmol) of magnesium. The mixture was re¯uxed overnight and then cooled to
room temperature. A saturated aqueous solution (50 ml) of ammonium chloride was added to the
cooled mixture and the organic phase was separated. The aqueous phase was extracted with
3Â50 ml of chloroform. The combined organic solution was washed with aqueous sodium
bicarbonate and saturated brine, then dried and concentrated. The residue was puri®ed with a
silica gel column and ether±petroleum ether as the eluent and 2.30 g of the product was obtained.
1
Yield 42.8%, [ꢀ]D= 40.61 (c 1.108, CHCl3); H NMR (CDCl3) ꢁ 7.49±7.44 (m, 2H), 7.36±7.34
(m, 2H), 7.22±7.19 (m, 2H), 4.12 (q, 1H), 2.16 (s, br, 3H), 1.31 (s, 9H), 1.30 (s, 9H), 1.28 (s, 9H),
1.28 (s, 9H), 1.25 (d, 1H), 0.94 (d, 3H).
3.2. The Schi€-base
A solution of 0.289 g (0.641 mmol) of (S)-2-amino-1,1-di(3,5-di-t-butylphenyl)propanol and
0.103 g (0.616 mmol) of 2-hydroxy-5-nitrobenzaldehyde19 were dissolved in 10 ml of ethanol and
the mixture was stirred for 6 h. Most of the ethanol was removed in vacuo and the residue was
puri®ed by a chromatographic column to give 0.365 g of pure Schi€-base, yield 97.8%. Mp 138±
139ꢀC; [ꢀ]D=+85.5 (c 0.994, CHCl3); H NMR (CDCl3) ꢁ 14.55 (s, 1H), 8.01 (dd, J1=9.48 Hz,
1
J2=2.68 Hz, 1H), 7.92 (d, J=2.76 Hz, 1H), 7.75 (s, 1H), 7.32 (d, J=6.64 Hz, 2H), 7.28 (s, 2H),
7.21 (d, J=6.32 Hz, 1H), 6.63 (d, J= Hz, 2H), 4.52 (m, 1H), 3.53 (s, br, 1H), 1.42 (d, J=6.52 Hz,
3H), 1.28 (s, 18H), 1.18 (s, 18H); 13C NMR (CDCl3) ꢁ 173.6, 163.7, 150.5,150.4, 143.0, 142.1,
136.8, 129.7, 128.8, 121.2, 121.1, 120.8, 120.6, 114.9, 80.8, 68.9, 34.9, 34.9, 31.5, 31.4, 16.3.
3.3. The catalyst
The Schi€-base was dissolved in 30 ml of ethanol and 0.139 g (6.95 mmol) of copper acetate
monohydrate solution was added to the above solution. The mixture was stirred and an aqueous
sodium hydroxide solution was added, and stirring was continued for 1 h. Water (50 ml) was
added to the mixture and the mixture was extracted with 3Â10 ml of benzene. After the solution
was washed with water, dried and the benzene removed in vacuo, the catalyst was obtained. Yield
74.6%, [ꢀ]D= 290 (c 0.100, C6H6).
3.4. Cyclopropanation
Under an argon atmosphere, a few drops of a solution of 0.114 g (1.00 mmol) of ethyl
diazoacetate in 2.0 ml of solvent was added to a mixture of 6.0 mg (0.01 mmol) of the catalyst, 1.0
ml of styrene and 2.0 ml of the solvent at 80ꢀC to initiate the reaction. After the mixture was

Z. Li et al. / Tetrahedron: Asymmetry 11 (2000) 1157±1163
1163
cooled to 40ꢀC, the rest of the diazoacetate solution was added slowly and the mixture was stirred
for another 4 h after all the diazoacetate was added. The solvent was removed in vacuo and
passed through a short silica gel column to remove the catalyst, then analyzed by GC (permethyl
b-cyclodextrin chiral capillary column, 30Â0.25 mm ID, 0.25 m ®lm, column temperature 130ꢀC)
using the internal method with ethyl adipate as a standard. Con®gurations of the enantiomers
were determined by comparison of the GC elution order with an authentic sample prepared
according to the literature.
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