Intramolecular asymmetric cyclopropanation with (nitroso)(salen)-ruthenium(II) complexes as catalysts

Article abstract of DOI:10.1055/s-2001-9733

Intramolecular cyclopropanation of (E)-2-alkenyl α-diazoacetates was carried out with good to high enantioselectivity by using (nitroso)(salen)ruthenium(II) complexes as catalysts under photo-irradiation.

Full text of DOI:10.1055/s-2001-9733

114
LETTER
Intramolecular Asymmetric Cyclopropanation with (Nitroso)(salen)-
ruthenium(II) Complexes as Catalysts
Biswajit Saha, Tatsuya Uchida, Tsutomu Katsuki*
Department of Chemistry, Faculty of Science, Graduate School, Kyushu University 33, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Fax +81 92 642 2607
Received 10 October 2000
cient catalysts for intermolecular AC.2,9 Therefore, we
Abstract: Intramolecular cyclopropanation of (E)-2-alkenyl a-di-
were intrigued by metallosalen-catalyzed intramolecular
azoacetates was carried out with good to high enantioselectivity by
AC. Here, we report our preliminary results.
using (nitroso)(salen)ruthenium(II) complexes as catalysts under
photo-irradiation.
We first examined the cyclization of (E)-3-phenylallyl
Key words: intramolecular asymmetric cyclopropanation, g-lac- a-diazoacetate using complexes (1-3)10 as catalysts.
tone, (salen)ruthenium complex
(Salen)cobalt complexes (1 and 3) showed no catalytic ac-
tivity. On the other hand, (nitroso)(salen)ruthenium com-
plex 2 promoted the desired reaction under irradiation
with incandescent lamp but formation of maleic and fu-
malic esters due to dimerization of substrate was also ob-
served.2b In the following reactions, therefore, substrate
was added dropwise to the reaction medium over 24 h to
suppress the dimerization. Under these conditions, good
enantioselectivity (70% ee) and acceptable chemical
yields were obtained (Table 1, entry 1). As 2"-substituent
on the C3(3′)-naphthyl ring of 2 was recently found to
have a strong influence on trans-cis selectivity of intermo-
lecular AC,2d we also examined the reactions using com-
plexes (4 and 5) as catalysts and 5 was found to show
enantioselectivity as high as 82% ee (entry 3).11 Further-
more, configurations of the products of these reactions are
found to be all 1S,5R and this suggests that the olefinic
unit approaches from ethylenediamine side of the cata-
lysts, since the olefinic unit approaching from C3(3′)-side
should cause steric repulsion with 3- and 3′-substituents
(Fig.).
Cyclopropane is a strained three-membered ring and un-
dergoes ring-opening reaction under mild reaction condi-
tions. Thus, cyclopropane derivatives, especially optically
active ones, serve as potent synthetic intermediates in or-
ganic synthesis. Although there are many synthetic meth-
ods of cyclopropanes, cyclopropanation of olefins is the
most important from synthetic view point. Accordingly,
many efforts have been directed toward this object and
highly stereoselective cyclopropanation reactions have
been developed: both high trans- and cis-selectivity to-
gether with excellent enantioselectivity has been achieved
for intermolecular cyclopropanation reactions.1,2 On the
other hand, excellent catalysts for asymmetric cyclopro-
panation (denoted as AC here) such as Cu[bis(oxazo-
line)s],3 Cu(aza-semicorrin),3a Cu(diamine),4 Ru(Pybox),5
Rh(MEPY) and their related complexes,6 Rh2(S-DOSP)2,7
have also been successfully applied to intramolecular
AC.1b,8 However, enantioselectivity of the reactions varies
with substrates examined to a considerable extent and
there is still strong demand for development of a new cat-
alyst for intramolecular AC.
O
H
N2CH
Ph
O
catalyst (5 mol%), hν
We recently found that optically active (salen)cobalt and
(nitroso)(salen)ruthenium complexes (1-3) served as effi-
1
5
Ph
O
O
THF (7 ml), 37 °C, 32-35 h
H
(74 µmol)
Table 1 Asymmetric Intramolecular Cyclopropanation of (E)-3-
Phenylallyl a-Diazoacetate using (Salen)ruthenium Complexes as
Catalysts
Ph
N
Ph
N
Co
MeO
O
O
OMe
Br
(R)
N
O
N
1
M
O
Ph
Ph
(R)
a) Enantiomeric excess was determined by GLC analysis using
CHIRAL b-DEX column operated at 160 °C.
b) Determined by comparison with the reported specific optical rota-
tion. [a]D24.5 -90 (c 0.25, chloroform) (82% ee), [Lit.6a [a]D23+130 (c
0.29, chloroform) for 1R,5S-isomer].
2: M= Ru(NO)Cl
3: M= Co
Synlett 2001, No. 1, 114–116 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Intramolecular Asymmetric Cyclopropanation
115
O
H
N2CH
R
O
catalyst (5 mol%), hν
R
O
O
NO
Ru
Cl
THF (7 ml), 32-35 h
N
O
N
O
H
(74 µmol)
3
R
R
Table 2 Intramolecular Cyclopropanation of trans-Substituted Al-
lyl a-Diazoacetates
2"
4: R= Me
5: R= H
top view
side view
R2
O
O
a) Absolute configuration has not been determined.
b) Reaction was carried out with starting material (0.1 mmol) and
THF (9 ml).
c) Enantiomeric excess was determined by HPLC analysis using
chiral column (DAICEL CHIRALPAK AD,
hexane:isopropanol = 19:1, Temperature = 40 °C)
d) Enantiomeric excess was determined by HPLC analysis using
chiral column (DAICEL CHIRALPAK ADx2,
hexane:isopropanol = 15:1, rt)
R1
N
N
O
CO
C
H
O
R2
O
R3
3'
3
Ru
Cl
Salen ligand is
R
R
2"
schematically drawn with
bold line.
e) Enantiomeric excess was determined by HPLC analysis using
chiral column (DAICEL CHIRALPAK AD,
hexane:isopropanol = 15:1, rt).
(Approach from ethylenediamine side)
f) Enantiomeric excess was determined by HPLC analysis using
chiral column (DAICEL CHIRALCEL OD-H,
hexane:isopropanol = 50:1, Temperature = 40 °C.)
g) Amount of THF was 1 ml.
top view
N
N
O
R= Ph, Me, H
C
H
O
= ruthenium ion
3'
3
R
R
R2
tation and depress enantioselectivity. Z-Substituent (R1)
does not sustain steric hindrance upon approach of
the olefinic unit but it was considered to suffer some
hindrance upon rotation and, therefore, depression of
enantioselectivity to some extent. To evaluate the mecha-
nistic model, we examined the reactions of Z- and 2-sub-
stituted substrates (Table 3). The presence of 2-substituent
decayed enantio-selectivity, even though its steric re-
quirement is small (entries 3 and 4). Introduction of
Z-substituent also diminished enantioselectivity (entries 1
and 2) but the substrate bearing small methyl group
showed modest selectivity.14
(Approach from C3 side)
Figure
We also examined the reactions of other trans-substituted
allyl a-diazoacetate (Table 2). The reaction of p-chlo-
rophenyl derivative was better effected with complex 5
(entry 1). However, the reactions of p-bromophenyl,
p-methoxyphenyl and phenylethynyl derivatives were
better effected with complex 4, though the sense of enan-
tioselection by 4 and 5 was identical (entries 2-5). Elec-
tronic nature of p-substituent seemed to little affect
enantioselectivity (entries 2 and 3).
In summary, we were able to demonstrate that Ru-salen
complexes served as good catalysts for intramolecular
asymmetric cyclopropanation reactions of trans-substitut-
ed allyl a-diazoacetates under photo-irradiated condi-
tions.
Ligand of (nitroso)(salen)ruthenium complex has been
determined to have a distorted stepped conformation.12
Although the detailed mechanism of the present reaction
was unclear, olefinic unit was considered to approach
with an orientation perpendicular to Ru-C bond13 and to
rotate anti-clockwise to give the product (See the side
view in the Figure).1b E-substituent (R2) does not cause
severe steric repulsion due to the distorted conformation
of salen ligand. However, the model suggested that intro-
duction of 2-substituent (R3) would destabilize the orien-
Acknowledgement
Financial support from a Grant-in-Aid for Scientific Research
(Priority Areas, No. 706: Dynamic Control of Stereochemistry)
from the Ministry of Education, Science, Sports, and Culture,
Japan, is gratefully acknowledged. B. S. is grateful to Scholarship
from the Ministry of Education, Science, Sports, and Culture,
Japan.
Synlett 2001, No. 1, 114–116 ISSN 0936-5214 © Thieme Stuttgart · New York

116
B. Saha et al.
LETTER
(3) a) Pique, C.; Fahndrich, B.; Pfaltz, A. Synlett 1995, 491-492.
b) Gant, T. G.; Noe, M. C.; Corey, E. J. Tetrahedron Lett.
1995, 36, 8745.
(4) Cho, D.J.; Jeon, S.-J.; Kim, H.-S.; Cho, C.-S.; Shim, S.-C.;
Kim, T.-J. Tetrahedron: Asymmetry 1999, 10, 3833-3848.
(5) Park, S.-B.; Murata, K.; Matsumoto, H.; Nishiyama, H.
Tetrahedron: Asymmetry 1995, 6, 2487-2494.
(6) a) Doyle, M P.; Austin, R. E.; Bailey, A. S.; Dwyer, M. P.;
Dyatkin, A. B.; Kalinin, A. V.; Kwan, M. M. Y.; Liras, S.;
Oalmann, C. J.; Pieters, R. J.; Protopopova, M. N.; Raab, C.
E.; Roos, G. H.; Zhou, Q.-L.; Martin, S. F. J. Am. Chem. Soc.
1995, 117, 5763-5765. b) Doyle, M. P.; Hu, W.; Chapman, B.;
Marnett, A. B.; Peterson, C. S.; Vitale, J. P.; Stanley, S. A. J.
Am. Chem. Soc. 2000, 122, 5718-5728. c) Doyle, M. P.;
Davies, S. B.; Hu, W. Org. Lett. 2000, 2, 1145-1147.
(7) Davies, H.M.L., Brion, D. D. J. Org. Chem. 1999, 64, 8501-
8508.
O
H
R2
R3
R1
catalyst (5 mol%), hν
R1
R2
O
2
CHN2
O
THF (7 ml), 37 °C, 32-35 h
R3
O
(74 µmol)
Table 3 Effect of Olefinic Substituent on Enantioselectivity in the
Reactions using 5 as the Catalyst
(8) Doyle, M. P.; Peterson, C. S.; Se, Q.-L.; Nishiyama, H. J.
Chem. Soc. Chem. Commun. 1997, 211-212.
(9) a)Fukuda, T.; Katsuki, T. Synlett 1995, 825-826. b) Idem,
Tetrahedron 1997, 53, 7201-7208.
a) Enantiomeric excess was determined by HPLC analysis using
chiral column (DAICEL CHIRALCEL AD,
hexane:isopropanol = 15:1, rt).
(10) Complexes (1-5) used in this study were prepared according
to the reported procedure (reference 2).
b) Enantiomeric excess was determined by HPLC analysis using
chiral column (DAICEL CHIRALCEL OB-H,
hexane:isopropanol = 15:1, rt)
c) Enantiomeric excess was determined by GLC analysis using
CHIRAL b-DEX column operated at 200 °C.
d) Enantiomeric was determined by HPLC analysis using chiral co-
lumn (DAICEL CHIRALCEL OD-H, hexane:isopropanol = 100:1,
rt).
(11) Typicalexperimentalprocedure: (Nitroso)(salen)ruthenium
complex 5 (5 mol%) was dissolved in 9 mL of THF under N2
and a THF solution (1.5 mL) of (E)-3-(p-chlorophenyl)allyl
a-diazoacetate (24 mg, 0.1 mmol) was added slowly to the
mixture over 24 h using syringe pump under irradiation of
incandescent light. The reaction mixture was stirred for
another 11 h and concentrated in vacuo. The residue was
chromatographed on silica gel using hexane and ethyl acetate
as eluent to give bicyclic lactone (13 mg) in 62% yield. The ee
of the product was determined as described in the footnote c
of Table 2.
(12) Takeda, T.; Irie, R.; Katsuki, T. Synlett 1999, 1166-1168.
(13) Doyle et al. have proposed that the carbonyl oxygen of the
intermediate carbenoid is positioned anti to metal ion in
intramolecular AC with rhodium complex as a catalyst.
Doyle, M. P.; Winchester, W. R.; Hoorn, J. A. A.; Lynch, V.;
Simonsen, S. H. J. Am. Chem. Soc. 1993, 115, 9968-9978.
(14) High enantioselectivity has been achieved in the reaction of
these classes of substrates. Z-substituted substrates: reference
6a; 2-substituted substrates: a) Martin, S. F.; Spaller, M. R.;
Liras, S.; Hartmann, B. J. Am. Chem. Soc. 1994, 116, 4493-
4494. b) Doyle, M. P.; Zhou, Q.-L.; Dyatkin, A. B.; Ruppar,
D. A. Tetrahedron Lett. 1995, 36, 7579-7582, and references
7 and 8.
References and Notes
(1) For some recent reviews, see: a) Aratani, T.
"Cyclopropanation" in Comprehensive Catalysis III" ed by
Jacobsen, E.N.; Pfaltz, A.; Yamamoto, H., Springer, Berlin
(1999), Chapter 41.3. b) Doyle, M. P.; McKervey, M. A.; Ye,
T. "Modern Catalytic Methods for Organic Synthesis with
Diazo Compounds," John Wiley & Sons (New York), 1998. c)
Pfaltz, A.; Lydon, K. M.; McKervey, M. A.; Charette, A. B.;
Lebel, H. "Cyclopropanation and C-H Insertion Reactions," in
"Comprehensive Catalysis II" ed by Jacobsen, E.N.; Pfaltz,
A.; Yamamoto, H., Springer, Berlin (1999), Chapter 16.
(2) For cis-selective asymmetric cyclopropanation, see: a)
Uchida, T.; Irie, R.; Katsuki, T. Synlett 1999, 1163-1165. b)
Uchida, T.; Irie, R.; Katsuki, T. Tetrahedron 2000, 56, 3501-
3509. c) Niimi, T.; Uchida, T.; Irie, R.; Katsuki, T.
Tetrahedron Lett. 2000, 41, 3647-3651, d) Ibid., Advanced
Synthesis & Catalysis 2001, 1, in press, and references cited
therein.
Article Identifier:
1437-2096,E;2001,0,01,0114,0116,ftx,en;Y17600ST.pdf
Synlett 2001, No. 1, 114–116 ISSN 0936-5214 © Thieme Stuttgart · New York