Highly cis- and enantioface-selective cyclpropanation using (R,R)-Ru- salen complex: Solubility dependent enantioface selection

Article abstract of DOI:10.1055/s-1999-2955

The reaction of styrene and t-butyl α-diazoacetate in the presence of (R,R)-(ON⁺)(salen)ruthenium(II) complex 1 under the irradiation of incandescent light in THF gave the corresponding (IS,2R)- cyclopropanecarboxylate with high stereoselectivi

Full text of DOI:10.1055/s-1999-2955

LETTER
1793
Highly cis- and Enantioface-Selective Cyclpropanation Using (R,R)-Ru-Salen
Complex: Solubility Dependent Enantioface Selection
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 18 August 1999
Abstract: The reaction of styrene and t-butyl a-diazoacetate in the
+
presence of (R,R)-(ON )(salen)ruthenium(II) complex 1 under the
irradiation of incandescent light in THF gave the corresponding
(
9
1S,2R)-cyclopropanecarboxylate with high stereoselectivity of
9% ee (cis : trans = 96 : 4), while the same reaction in hexane gave
the enantiomeric (1R,2S)-cyclopropanecarboxylate preferentially
(83% ee, cis : trans = 68 : 32).
+
Key words: (ON )(salen)ruthenium(II) complex, photo-activation,
cyclopropanation, cis-selectivity
Compound 1
Optically active metallosalen complexes have been well-
recognized as excellent catalysts for enantioselective
transfer reactions of oxene and its isoelectronic species
1
such as nitrene and carbene. We have recently reported tivity (entry 5). The reaction under irradiation of the light
+
that (R,R)-(ON )(salen)ruthenium(II) [(R,R)-Ru-salen] of ~440 nm showed excellent cis- and enantioselectivity
complex 1 catalyzed the unprecedented high cis- and (entry 2). The reaction irradiated by the light of ~390 nm
enantioselective cyclopropanation of styrene (89% ee, cis showed the diminished selectivity, probably because de-
:
trans = 84 : 16) when the reaction was carried out under composition of a-diazoacetate was caused by the irradia-
2
the irradiation of incandescent light. However, these irra- tion (entry 1). Furthermore the reaction irradiated by the
diated conditions caused undesired decomposition of a- incandescent light of wavelength mostly >400 nm was
diazoacetate and brought about non-catalyzed cyclopro- found to show an excellent level of stereoselectivity sim-
panation which is non-stereoselective and diminishes the ilar to the reaction irradiated by the light of ~440 nm.
enantiomeric excess of the desired cyclopropane product.2 Therefore, with an incandescent lamp (National/Panason-
To overcome this side reaction and to improve the stereo- ic LW100v57w) as a light source, we next examined the
selectivity of the reaction, we examined the relationship effect of solvent.
between wavelength of the irradiated light and stereose-
We examined the reaction in three different kinds of sol-
lectivity. On the other hand, we recently found that the
vents: i) solvents of high dissolving power such as THF,
ligands of the metallosalen complexes are highly flexible
dimethoxyethane (DME), ethyl acetate, and dichlo-
and their conformation is affected even by a weak bond
romethane; ii) solvents of high dissolving power and high
3
interaction such as CH-p or OH-p interaction. Therefore,
we expected that the association state (monomeric or ag-
gregated) of the catalyst would have influence on the con-
formation of the salen ligand and, in turn, the enantioface
selection by the metallosalen complex. Thus we also ex-
amined the effect of solvent on the stereoselectivity of the
Ru-salen catalyzed cyclopropanation in order to know
whether the monomeric and aggregated catalysts behave
in a different way.4
coordinating ability such as acetonitrile and pyridine; iii)
solvents of poor dissolving power such as hexane, hep-
tane, and diisopropyl ether (Table 2). Catalyst 1 was dis-
solved in the first class of solvents and the reactions in
these solvents all showed high enantio- and cis-selectivity
to give the (1S,2R)-isomer preferentially, though ethereal
solvents gave slightly better results (entries 1-4). On the
other hand, no reaction occurred in the second class of sol-
vents, though 1 was dissolved in these solvents (entries 5
,5
We first examined the effect of wavelength on the stereo- and 6). These results agreed with the proposed mechanism
selectivity of the reaction in THF (Table 1). The light of on metal-catalyzed diazo decomposition, in which the
wavelength >500 nm did not efficiently activate the cata- diazo compound is coordinated to the metal ion and gen-
4a
lyst and the reaction irradiated by the light of such wave- erates a metal-carbene complex. A coordinating solvent
length was slow (entry 3). Thus the reaction competed should disturb the coordination of a-diazoacetate to ruthe-
with the reaction catalyzed by non-activated catalyst and nium ion. Complex 1 was insoluble to the third class of
showed moderate selectivity (c.f. entries 3 and 5). Non-ir- solvents and the reaction was carried out with suspended
radiated catalyst also slowly catalyzed cyclopropanation 1 in the solvents. These reactions also showed moderate
with moderate enantioselectivity but poor cis-trans selec- cis- and good enantio-selectivity (entries 7-9). However,
Synlett 1999, No. 11, 1793–1795 ISSN 0936-5214 © Thieme Stuttgart · New York

1
794
T. Uchida et al.
LETTER
petitively and caused some diminishment of enantioselec-
tivity in this reaction.
The reaction between the intermediary Ru-carbenoid and
styrene was considered to be slow, since a considerable
amount of the mixture of fumaric and maleic acid esters
the sense of enantioselection in the formation of the major
cis-isomer is opposite to that observed in the reactions in
the first class of solvents (c.f. entries 1-4 and 7-8). The re-
versal of enantioselection does not seem to relate to the
functionality of solvents or to their polarity. The follow-
ing explanation seems to be the most rational at this mo-
ment. Complex 1 is dissolved completely in the first class
of solvents and gives a monomeric activated species
which decomposes a-diazoacetate, upon irradiation,
while 1 is not dissolved in the third class of solvents and
the activation should occur on the surface of the insoluble
8
was formed during the reaction. Therefore, improvement
of the yield of cyclopropanecarboxylate was expected to
be attained by the enhancement of substrate-concentra-
tion. Thus, we tried to reduce the amount of THF which
was the best solvent for the present reaction in terms of
stereoselectivity (Table 3). As expected, chemical yield
increased to a considerable extent as the ratio of THF was
reduced but stereoselectivity was slightly decreased (en-
9
tries 1,2). We also examined the cyclopropanation of oth-
er olefins with high substrate-concentration and could
achieve excellent enantioselectivity (>95% ee) as well as
high cis-selectivity (entries 3-8). Again, reduction of THF
content increases the chemical yields of the desired prod-
ucts (entries 4,5 and 6-8).
6
solid 1. It is reasonable to consider that these monomeric
and aggregated active species may have different ligand-
conformation which is correlated with the sense of asym-3
metric induction, since salen ligands are highly pliable.
The reaction in styrene without solvent showed cis- and
enantio-selectivity of cis : trans = 84 : 16 and 89% ee, re-
Although the experiments described in Tables 1, 2, and 3
were carried out on 0.1 mmol scale about t-butyl a-diaz-
oacetate, the following experiment was carried out on 1
mmol scale. Large-scale experiment showed a slightly di-
minished enantioselectivity (94% ee).
2
spectively. As discussed in the beginning of this paper,
we had attributed this unsatisfactory result to the interven-
7
tion of non-catalyzed reaction. However, as the solubility
of complex 1 to styrene is not very high, it was not com-
pletely dissolved in the reaction medium. Therefore, we Asymmetric cyclopropanation of styrene with complex 1:
can not exclude the possibility that both monomeric and To a THF solution (2.4 ml) of complex 1 (49 mg, 50 mmol)
aggregated catalysts 1 catalyzed cyclopropanation com- and styrene (1.2 ml) was added t-butyl a-diazoacetate
Synlett 1999, No. 11, 1793–1795 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Solubility Dependent Enantioface Selection
1795
(
(
3) Punniyamurthy, T.; Irie, R.; Katsuki, T.; Akita, M.; Moro-oka,
Y. Synlett, 1999, 1049-1052.
4) For the review of metal-catalyzed asymmetric
(
0.14 ml, 1 mmol) and the mixture was stirred at room
temperature for 2 days under the incandescent light
100V, 57W) and nitrogen. The mixture was concentrated
in vacuo and passed through a short silica gel column
hexane/diisopropyl ether=1/0 to 4/1) to remove styrene
(
cyclopropanation, see: a) Doyle, M. P.; McKervey, M. A.; Ye,
T. "Modern Catalytic Methods for Organic Synthesis with
diazo Compounds," John Wiley & Sons (New York), 1998.
b) Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998, 54,
(
and the catalyst. The fraction including cis- and trans-
products, di-t-butyl fumarate and di-t-butyl maleate was
concentrated and an aliquot of the sample was diluted
with CDCl (0.7 ml). Cis-trans ratio was determined to be
9
ples were combined and submitted to silica gel chroma-
tography (hexane/diisopropyl ether=30/1) to yield the cis-
(
7919-7946. c) Padwa, A.; Hornbuckle, S. F. Chem. Rev. 1991,
91, 263-309.
(
5) For ruthenium-catalyzed asymmetric cyclopropanation, see:
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, C.-M.; Cheng, K.-F.; Mak, T. C. W. Chem.
Commun. 1997, 1205-1206. e) Song, J.-H.; Cho, D.-J.; Kim,
Y.-H.; Kim, T.-J. Inorg. Chem. 1999, 38, 893-896.
3
1
7 : 3 by H NMR analysis (400 MHz). Then all the sam-
76.3 mg, 35%) and trans-products (2.1 mg, 1%). Enanti-
omeric excesses of the cis- and trans-products were deter-
mined by HPLC analysis to be 94 and 10% ee’s,
respectively.
(6) Catalyst has been considered to be activated by dissociation of
the apical ligand which is promoted by irradiation (reference
In conclusion, we were able to demonstrate that stereose-
lection by the catalyst of high pliability is dependent on
the association state (monomeric or aggregated) which in
turn depends on the solubility of the catalyst to solvent.
Taking this fact into consideration, high cis- and enantio-
selective cyclopropanation was realized. Further study is
now proceeding in our laboratory.
2
and reference 10).
(
7) We observed that non-catalyzed reaction actually occurred in
the absence of the catalyst 1 (reference 2).
8) The yield of a mixture of maleic and fumaric acid esters was
32%, when the reaction was performed in THF-styrene (10/1).
(
(9) The reaction with ethyl a-diazoacetate in the presence of the
catalyst 1 (5 mol %, based on a-diazoacetate used) at room
temperature in a mixture of THF and styrene (2/1) under
irradiation of incandescent light also proceeded with high cis-
and enantio-selectivity [cis : trans = 93 : 7, 95% ee (cis-
isomer)].
10) 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,
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.
(
11674-11683.
References and Notes
(
1) 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.
2) Uchida, T.; Irie, R.; Katsuki, T. Synlett 1999, 1163-1165.
Article Identifier:
437-2096,E;1999,0,11,1793,1795,ftx,en;Y16999ST.pdf
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Synlett 1999, No. 11, 1793–1795 ISSN 0936-5214 © Thieme Stuttgart · New York