Chiral (ON)Ru-salen catalyzed cyclopropanation: High cis- and enantio-selectivity

Article abstract of DOI:10.1055/s-1999-2782

(R,R)-(ON⁺)(Salen)ruthenium(II) complex 2 was found to be an effective catalyst for cis-selective asymmetric cyclopropanation (up to 89% ee) which was performed under sunlight coming through a window or incandescent light. Furthermore, (R,R)-(O

Full text of DOI:10.1055/s-1999-2782

LETTER
1163
Chiral (ON)Ru-Salen Catalyzed Cyclopropanation: High Cis- and Enantio-
selectivity
Tatsuya Uchida, Ryo Irie, Tsutomu Katsuki*
Department of Molecular Chemistry, Graduate School of Science, Kyushu University 33, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Fax+81 (92) 642 2607
Received 14 April 1999
metric cyclopropanation using (ON)Ru-salen complexes
Abstract: (R,R)-(ON+)(Salen)ruthenium(II) complex 2 was found
as catalysts.
to be an effective catalyst for cis-selective asymmetric cyclopropa-
nation (up to 89% ee) which was performed under sunlight coming
We first examined the reaction of styrene and t-butyl a-di-
through a window or incandescent light. Furthermore, (R,R)-
azoacetate in the presence of 1. The reaction proceeded
(ON+)(hydroxo)-(salen)ruthenium(II) complex 5 was also found to
slowly to give cyclopropanation products but the stere-
show good cis- and enantio-selectivities (up to 92% ee) in the reac-
ochemistry observed was not reproducible. However, in
tion in the dark.
Key words: (ON+)(salen)ruthenium(II) complex, photo-activation,
present reaction was also accelerated when the reaction
cyclopropanation, cis-selectivity
accord with the other reactions using 1 as the catalyst, the
was carried out under incandescent light and showed the
reproducible stereochemistry,1) though selectivity was
poor (Table 1, entry 1). Being encouraged with this result,
We disclosed the unusual asymmetric catalysis of (R,S)-
we examined cyclopropanation using (R,R)-(ON)Ru-
(ON+)(salen)ruthenium(II) complex [(R,S)-(ON)Ru-salen
salen complex 2 and complexes 3 and 4 as catalysts also
complex] 1 under sunlight or incandescent light.1) With
under incandescent light. To be surprised, complex 2
showed high cis-selectivity as well as good enantioselec-
tivity (entry 2). In contrast to this, complexes 3 and 4
showed usual trans-selectivity, though enantioselectivi-
this complex as a catalyst, high enantioselectivity has
been achieved in asymmetric epoxidation and hetero
Diels-Alder reaction and also in kinetic resolution of race-
mic epoxides. On the other hand, we had found that chiral
ties were moderate (entries 3 and 4). The stereoselectivi-
metallosalen complexes [(salen)manganese(III) or
ties observed in these reactions are probably the minimum
(salen)-cobalt(III) complexes) serve as catalysts not only
ones, because the uncatalyzed cyclopropanation occurred
for oxene transfer (oxo transfer) reaction but also for car-
under the present reaction conditions (entry 5). The reac-
tion in the dark was very slow and cis-trans selectivity
bene transfer reaction.2) Thus it was expected that chiral
(salen)ruthenium complex would also serve as a catalyst
was poor (entry 6). Although the mechanism of asymmet-
for enantioselective cyclopropanation. Although there
ric induction by (ON)Ru-salen complexes is unclear at
have been many metal-catalyzed asymmetric cyclopropa-
present, it is worth mentioning that the axial chirality in
nation reactions3) including ruthenium complexes4) such
the ligand plays a very important role in determining the
sense of asymmetric induction (cf., entries 1 and 2).8) We
next examined the reactions in benzene or in dichlo-
romethane. Although chemical yield was decreased, both
enantio- and cis-selectivities were further increased (up to
89% ee) (entries 7 and 8).
as Ru-Pybox and Ru-porphyrin reported, most of these
metal-catalyzed reactions show moderate to high trans-
selectivity and few cis-selective cyclo-propanations are
known.5)
Chiral (5,5’-methoxysalen)cobalt(III) complex bearing no
substituent at C3(C3’) is an excellent catalyst for asym-
metric cyclopropanation and shows high enantio- and
trans-selectivity, while (salen)cobalt(III) complexes bear-
ing substituents at C3(C3’) show no catalytic activity.6)
However, it has been well known that, in the asymmetric
epoxidation using (salen)manganese(III) complexes as
catalysts, the chirality in C3(C3’)-substituents strongly af-
fects asymmetric induction by the complexes. Therefore it
was expected that the stereochemistry of metallosalen-
catalyzed asymmetric cyclopropanation could be modi-
fied by introducing chiral substituents at C3(C3’)-carbons.
Although the presence of C3(C3’)-substituents in
(salen)cobalt(III) complexes ruins their catalytic activity,
we considered that metallosalen complexes having longer
metal-oxygen(eq) bond would allow the presence of
C3(C3’)-substituents.7) Therefore, we examined asym-
The complex 2 was purified by silica gel column chroma-
tography upon its synthesis. However, it was found that a
new Ru-species was generated during this procedure (vide
infra). The new species was isolated and identified as (hy-
droxo)Ru-salen complex 5 by measurement of FABMS
(m-nitrobenzyl alcohol): m/z 973(M+), 956(M+-OH). We
were intrigued by the catalysis of complex 5. Thus, we ex-
amined the reaction of styrene and t-butyl a-diazoacetate
in the presence of 5 (Table 2). The reaction proceeded
even in the dark and showed high cis- (89:11) and enantio-
selectivities (92% ee). On the other hand, the reaction un-
der incandescent light showed a similar level of cis- and
enantio-selectivities to those observed with the complex 2
under incandescent light (cf., Table 1, entry 2 and Table 2,
entry 2). Effect of light observed in the above and this re-
Synlett 1999, No. 07, 1163–1165 ISSN 0936-5214 © Thieme Stuttgart · New York

1164
T. Uchida et al.
LETTER
actions is considered to be attributable to a ligand dissoci-
ation induced by irradiation.9)
We also examined the cyclopropanation of p-chlorosty-
rene using 2 and 5 as catalysts under the irradiated and
unirradiated conditions, respectively (Scheme 1). Again
the reaction with 2 showed good cis- and enantio-selectiv-
ities,10) while the reaction with 5 exhibited diminished cis-
and enantio-selectivities to some extent.
Scheme 1
Preparation of complexes 2 and 5 and the typical proce-
dure of ruthenium-catalyzed cyclopropanation were de-
scribed below. All the reactions except for the synthesis of
complex 5 were carried out under nitrogen atmosphere.
Preparation of complex 2: (NO)RuCl3•H2O (383.2 mg,
1.5 mmol) was dissolved in dry N,N-dimethylformamide
(DMF) (10 ml) and the solvent was removed azeotropical-
ly at 110 °C. The resulting anhydrous (NO)RuCl3 was re-
dissolved in dry DMF (10 ml).
NaH (60% dispersion in mineral oil, 80 mg, 2.2 mmol)
was weighed into a flask and washed with dry hexane
(3 x 1.0 ml). Dry DMF (10 ml) and subsequently salenH2
(827 mg, 1.0 mmol) were added to the flask and stirred for
1 h. To this mixture, was added the above DMF solution
of (NO)RuCl3. The whole mixture was stirred at 110 °C
for 48 h. The solvent was removed under vacuum and the
residue was quickly chromatographed on silica gel col-
umn (CH2Cl2/acetone = 50/1) to give the (ON)Ru-salen
complex 2 as red-brown crystals (593 mg, 60%).
Preparation of complex 5: Ru-salen complex 2 (115.2 mg,
0.12 mmol) was dissolved in CHCl3. To the solution was
Synlett 1999, No. 07, 1163–1165 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Chiral (ON)Ru-Salen Catalyzed Cyclopropanation: High Cis- and Enantio-selecitivity
1165
added silica gel (3 g) and the mixture was stirred for 1 day.
The suspension was filtered and the filtrate was concen-
trated in vacuo. The residue was chromatographed on sil-
ica gel column (CH2Cl2/acetone/MeOH = 50/1/1) to give
(ON)Ru-salen complex 5 as red crystals (53.6 mg, 47%).
References and Notes
(1) The preceding communications.
(2) a) Katsuki, T. J. Mol. Cat. A: Chem. 1996, 113, 87-107. b) Ito,
Y. N.; Katsuki, T. Bull. Chem. Soc. Jpn. 1999, 72, 603-619.
(3) a) Doyle, M. P. Chem. Rev. 1986, 86, 919-939. b) Padwa, A.;
Hornbuckle, S. F. Chem. Rev. 1991, 91, 263-309.
(4) a) Nishiyama, H.; Itoh, Y.; Matsumoto, H.; Park, S.-B.; Itoh,
K. J. Am. Chem. Soc. 1994, 116, 2223-2224. b) Nishiyama,
H.; Itoh, Y.; Sugawara, Y.; Matsumoto, H.; Aoki, K.; Itoh, K.
Bull. Chem. Soc. Jpn. 1995, 68, 1247-1262. c) Frauenkron,
M.; Berkessel, A. Tetrahedron Lett. 1997, 38, 7175-7176.
d) Lo, W.-C.; Che, Che, C.-M.; Cheng, K.-F.; Mak, T. C. W.
Chem. Commun. 1997, 1205-1206.
(5) a) Maxwell, J. L.; O’Malley, S.; Brown, K. C.; Kodadek. T.
Organometallics 1992, 11, 645-652. b) It has reported that
cyclopropanation using a cyclopentadienyl iron complex as
the catalyst shows high cis-selectivity, though in a non-
enantioselective manner: Seitz, W. J.; Saha, A. K.; Hossain,
M. M. Organometallics 1993, 12, 2604-2608.
Asymmetric cyclopropanation of styrene with complex 2:
To a suspension of complex 2 (5.0 mg, 5.0 mmol) in sty-
rene (0.35 ml) was added t-butyl a-diazoacetate (14 ml, 0.1
mmol) and the suspension was stirred at room temperature
for 1 day under incandescent light (100V, 60W). The sus-
pension was directly subjected to a short silica gel column
eluting with hexane/diisopropyl ether (4/1) to remove sty-
rene and the catalyst. The eluate including cis- and trans-
products, di-t-butyl fumarate and di-t-butyl maleate was
concentrated and diluted with CDCl3 (0.7 ml). 1-Bro-
monaphthalene (4 ml) was added to the CDCl3 solution as
1
an internal standard and analyzed by H NMR analysis
(6) a) Fukuda, T.; Katsuki, T. Synlett 1995, 825-826. b) Fukuda,
T.; Katsuki, T. Tetrahedron 1997, 53, 7201-7208.
(7) In (salen)cobalt(III) complexes, the lengths of Co-equatorial
oxygen atom are in the range of 1.84-1.91 Å. (ON)Ru-salen
complex 1 has a longer Ru-oxygen bond: see the following
communication.
(270 MHz) to determine the chemical yield of cis- and
trans-products and cis-trans ratio. An aliquot of the eluate
was concentrated and submitted to preparative TLC to
yield the cis- and trans-products which were used for the
determination of their enantiomeric excesses.
(8) In accord with this observation, the complex bearing the
chirality only at the binaphthyl part and ethylenediamine as
the diamine unit also showed good cis-trans selectivity
(79:21) and high enantioselectivity (91% ee, cis-isomer; 0%
ee, trans-isomer). However, due to its very poor solubility to
organic solvent, the yield of the cyclopropanation products
was low (<5%).
Asymmetric cyclopropanation of styrene with complex 5:
To a solution of complex 5 (18.5 mg, 7.6 mmol) in styrene
(1.33 ml) was added t-butyl a-diazoacetate (53 ml, 0.38
mmol) and the solution was stirred at room temperature
for 1 day in the dark. The mixture was directly submitted
to column chromatography (silica gel, hexane/diisopropyl
ether = 30/1) to give the cis- (45.6 mg, 55%) and trans-
products (6.0 mg, 7.2%).
In connection to this problem, it is noteworthy that the
reactions of styrene and diazoacetate in the presence of chiral
Cu, Co, and Rh complexes give trans and cis products, the
configurations at C1 of which are the same (reference 3),
while the present reaction provided the trans and cis products
isomeric at C1. The reason for this unusual selectivity is
unclear at present.
In conclusion, we were able to achieve the first highly cis-
and enantioselective cyclopropanation by using (R,R)-
(ON)Ru-salen complex. Further study is now proceeding
in our laboratory.
(9) It has been reported that flash photolysis of Ru(TPP)(NO)Cl
presumably generates a transient species, Ru(TPP)Cl:
Lorkovic, I. M.; Miranda, K. M.; Lee, B.; Bernhard, S.;
Schoonover, J. R.; Ford, P. C. J. Am. Chem. Soc. 1998, 120,
11674-11683. However, we can not remove the possibility
that the chloro and hydroxo ligands in 2 and 5 dissociate,
respectively, under the present reaction conditions to give the
same transient species.
Acknowledgement
Financial supports from a Grant-in-Aid for Scientific Research
from the Ministry of Education, Science, Sports, and Culture, Ja-
pan, is gratefully acknowledged.
(10) Absolute configuration of the products has not been
determined.
Article Identifier:
1437-2096,E;1999,0,07,1163,1165,ftx,en;Y07699ST.pdf
Synlett 1999, No. 07, 1163–1165 ISSN 0936-5214 © Thieme Stuttgart · New York