Intermolecular asymmetric cyclopropanation with diazoketones catalyzed by chiral ruthenium porphyrins

Article abstract of DOI:10.1016/j.tetlet.2008.01.129

The asymmetric addition of diazoacetophenone to styrene derivatives to give optically active cyclopropyl ketones (ee up to 86%) was carried out by using chiral ruthenium porphyrins as homogeneous catalysts.

Full text of DOI:10.1016/j.tetlet.2008.01.129

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2111–2113
Intermolecular asymmetric cyclopropanation with
diazoketones catalyzed by chiral ruthenium porphyrins
Ir e` ne Nicolas, Paul Le Maux, G e´ rard Simonneaux *
Ing e´ nierie Chimique et Mol e´ cules pour le Vivant, UMR 6226, Universit e´ de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France
Received 28 December 2007; revised 25 January 2008; accepted 29 January 2008
Available online 2 February 2008
Abstract
The asymmetric addition of diazoacetophenone to styrene derivatives to give optically active cyclopropyl ketones (ee up to 86%) was
carried out by using chiral ruthenium porphyrins as homogeneous catalysts.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Diazoacetophenone; Ruthenium porphyrins; Optically active cyclopropyl ketone; Chiral porphyrins
Optically active metalloporphyrins have been reported
to be efficient catalysts for carbene transfer reactions, espe-
meso-Tetraphenylporphyrin carbonyl ruthenium (TPP)-
Ru(CO) catalyzed decomposition of diazo acetophenone
(DAP) in the presence of styrene in dichloromethane
resulted in the formation of the corresponding cyclopro-
pane in 70% yield with a good stereoselectivity (trans/cis
ratio: 95/5) (Scheme 1) and (20%) of olefin resulting in
the dimerization of the carbene. To extend the scope of this
cyclopropanation, the reaction of a number of styrene
derivatives with DAP in the presence of (TPP)Ru(CO) at
25 °C in dichloromethane was studied. The results are sum-
marized in Table 1. Then, cyclopropanation competition
experiments were conducted with a large excess of each
substrate and limiting quantities of diazo acetophenone
(substrate/DAP = 10:1) (Table 2). The relative reactivities
were measured by the molar ratio in gas chromatography
of cyclopropyl ketones derived from styrene and from
other substrates. In all these experiments, cyclopropanes
are the major products, usually obtained with carbene
dimers as by-products. Electron-rich styrenes (4-methoxy
or 4-methyl styrene) are cyclopropanated more efficiently
than styrenes bearing electron-withdrawing groups (4-Cl
1
,2
cially with ethyl diazoacetate. Despite high asymmetry
inducing ability of chiral metalloporphyrins to cyclopropa-
nation reactions, their application is essentially limited to
diazoester addition to styrene derivatives. In the course
of our study on asymmetric cyclopropanation, we also
found however, that other diazo derivatives, rarely used
in asymmetric cyclopropanation, such as diazophospho-
3
4
5
nates, trifluorodiazoethane and diazoacetonitrile showed
high asymmetric additions to alkenes. Thus, achievements
in asymmetric catalytic metal carbene transformations are
impressive, but they are however, by no means complete.
Surprisingly, if many chiral complexes have proven to be
selective catalysts for intramolecular cyclopropanation
6
with diazoketones, they have not been extended to inter-
molecular asymmetric cyclopropanation except for one
example with chiral bis [camphorquinone-a-dioximato]
7
cobalt complex (20% enantiomeric excess). To extend the
utility of metalloporphyrin complexes as cata- lysts, we
examined herein the use of ruthenium complexes of chiral
porphyrins as catalysts for intermolecular asymmetric
cyclopropanation with diazo ketones.
or 4-CF ). In the latter two cases, a significant amount of
3
olefins, resulting from dimerization of the carbenes, were
also detected (20–28%).
*
The data were fit to a Hammett plot of log(k /k ) ver-
X H
sus r with a good correlation (r = 0.955), which allowed
Corresponding author. Tel.: +33 2 23 23 62 85; fax: +33 2 23 23 56 37.
E-mail address: gerard.simonneaux@univ-rennes1.fr (G. Simonneaux).
2
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.129

2112
I. Nicolas et al. / Tetrahedron Letters 49 (2008) 2111–2113
O
Ru catalyst
R
+
+
CHN2
R
CH Cl2
2
O
O
R
Scheme 1. Cyclopropanation of styrene with diazo acetophenone catalyzed by Ru porphyrin complex.
Table 1
Cyclopropanation of styrene with diazo acetophenone by meso-tetra-
phenylporphyrin carbonyl ruthenium complex: (TPP)Ru(CO) (0.5 ml
CH
2
Cl
2
, 0.5 mmol alkene, 0.1 mmol DAP in 0.5 ml of CH
2
Cl
2
, reaction
time 24 h, rt)
L
N
N
N
N
Entry
Catalyst
p-R-Styrene
Yield
GC %)
Ratio
(trans/cis)
Dimer
(%)
M
(
1
2
3
4
5
(TPP)Ru(CO)
(TPP)Ru(CO)
(TPP)Ru(CO)
(TPP)Ru(CO)
(TPP)Ru(CO)
H
70
70
75
40
60
95:5
98:2
99:1
96:4
96:4
20
9
0.5
20
28
Me
OMe
Cl
CF
3
Fig. 1. Chiral metalloporphyrin catalysts (M–L: RuCO 1, M–L:
RuCH(COPh) 2).
Table 2
Competition studies of the cyclopropanation of various substituted
styrenes (substrates A) and styrene (substrate B) with DAP catalyzed by
Table 3
Asymmetric cyclopropanation of styrene with diazoacetophenone by
chiral complex (P )Ru(CO) 1 (see Fig. 1)
(
TPP)Ru(CO) in 0.5 ml CH
2
Cl
2
(catalyst: 1 mg, styrenes: 0.5 mmol; DAP
*
0.05 mmol; 24 h; rt)
a
b
Entry
p-R-Styrene Yield
Ratio
ee
Dimer
Substrate A
Ratio of products derived from A/B
(
GC %) (trans/cis) (% trans HPLC) (%)
4
4
4
4
-Methoxystyrene
-Methylstyrene
-Chlorostyrene
2.95
1.65
0.78
0.53
1
2
3
4
5
a
H
Me
OMe
CF
Cl
57
83
80
46
45
95:5
98:2
99:1
95:5
95:5
83
83
84
86
84
10
13.8
1
30
15
-Trifluoromethylstyrene
3
Catalyst: Carbonyl-{5,10,15,20-tetrakis[1S,4R,5R,8S-1,2,3,4,5,6,7,8-
octahydro-1,4:5,8-dimethanoanthracene-9-yl]porphyrinato}ruthenium (II),
experimental conditions as in Table 1.
us to calculate a q value of ꢀ1.08 ± 0.16. A similar negative
value was observed for cyclopropanation reaction with
ethyl diazoacetate catalyzed by (TPP)Ru(CO) (q =
b
Determined by chiral GC (CP-Chiracel OC).
1
ꢀ
1.29 ± 0.08). This value is also similar to that reported
for the cyclopropanation of substituted styrenes and ethyl-
8
diazoacetate by Kodadeck and Woo et al. (q = ꢀ0.68)
for the trans isomer (entry 1). We also investigated the
cyclopropanation of para-substituted styrenes (Table 3).
As shown in Table 3, para-substitution (p-Y-styrene,
Y = MeO, Br and H) does not have a significant effect
upon the enantioselectivity of styrene cyclopropanation
(83–86%) but better yields (80–83%) were obtained with
electron-rich styrenes (4-methoxy or 4-methyl styrene).
In rutheniumporphyrin catalyzed cyclopropanation, the
corresponding carbene complexes which take octahedral
coordination in the presence of axial ligand (solvent) are
considered as the active intermediates. As an example, we
reported the first X-ray structure of a ruthenium porphyrin
carbene complex with a methanol as an axial ligand trans
9
using iron porphyrin and by Perez and Brookhart et al.
(
q = ꢀ 0.85) using copper pyrazoylborate complexes. The
small negative value of q suggests only a moderate positive
charge build-up at the carbene atom in the transition state
according to an electrophilic metal-carbene complex inter-
mediate (vide infra).
The asymmetric version was also tested using Halterman
1
0
porphyrin as chiral ligand (Fig. 1). To evaluate the reac-
tivity of the diazoacetophenone, its ruthenium-catalyzed
decomposition was examined in the presence of styrene in
dichloromethane at room temperature by using 1 as the
catalyst (Table 1). The diazo derivatives were added slowly
to the reaction mixture over 30 min and the reaction was
stopped after 24 h. The cyclopropane was formed in 57%
yield, with 95/5 trans/cis ratio and 83% enantioselectivity
1
to the Ru–carbon bond. Since ketocarbenes are found to
be easily inserted in metal–nitrogen bond of iron porp-
1
1,12
hyrin,
preparation of the ruthenium ketocarbene

I. Nicolas et al. / Tetrahedron Letters 49 (2008) 2111–2113
2113
complex was undertaken. Thus, the reaction of the chiral
carbonyl ruthenium complex 1 with excess of diazoaceto-
phenone in dichloromethane results in the displacement
of the CO ligand and generation of the brown carbene
complex 2 (Fig. 1). The carbene complex was not stable
enough to be purified by chromatography on silica gel
but can be characterized by HMQC NMR at low temper-
ature (193 K). Analysis of the NMR spectrum shows a low-
field cross-peak between the carbene carbon at 234.7 ppm
9. Diaz-Requejo, N. M.; Perez, P. J.; Brookhart, M.; Templeton, J. L.
Organometallics 1997, 16, 4399–4404.
1
1
0. Halterman, R. L.; Jan, S. T. J. Org. Chem. 1991, 56, 5253–5254.
1. Komives, E. A.; Tew, D.; Olmstead, M. M.; Ortiz de Montellano, P.
R. Inorg. Chem. 1988, 27, 3112–3117.
12. Artaud, I.; Gregoire, N.; Battioni, J. P.; Dupr e´ , D.; Mansuy, D.
J. Am. Chem. Soc. 1988, 110, 8714–8716.
1
3. Simonneaux, G.; Le Maux, P. Carbene complexes of metallopor-
phyrins and heme proteins. In Kadish, K. M., Smith, K. M., Guilard,
R., Eds.; The Pophyrin Handbook; Academic Press: San Diego, 2003;
1
1, pp 133–159.
1
and the carbene proton at 13.26 ppm. The H chemical
14. For a recent paper, see: Hoang, V. D. M.; Reddy, P. A. N.; Kim, T. J.
Tetrahedron Lett. 2007, 48, 8014–8017.
15. Nishiyama, H.; Itoh, Y.; Matsumoto, H.; Park, S. B.; Itoh, K. J. Am.
Chem. Soc. 1994, 116, 2223–2224.
shift is in the range of those previously reported for such
1
3
Ru@CHR porphyrin complexes.
To date, several chiral ruthenium complexes, in parti-
1
4
1
1
6. Nishiyama, H. Top. Organomet. Chem. 2004, 11, 81–92.
7. Cornejo, A.; Fraile, J. M.; Garcia, J. I.; Gil, M. J.; Luis, S. V.;
Martinez-Merino, V.; Mayoral, J. A. J. Org. Chem. 2005, 70, 5536–
5544.
1
5,16
cular, ruthenium–pybox compounds
are also excellent
catalysts for homogeneous asymmetric intermolecular
cyclopropanation of alkenes with diazo compounds, giving
high enantioselectivity and diastereoselectivity but they
suffer mainly from low catalyst turnover. Immobilization
of these systems on solid supports has also received a great
deal of attraction with some success in terms of recyclabi-
1
8. All new compounds reported here gave spectral data consistent with
the assigned structures. Selected data: For trans-1-benzoyl-2-phenyl-
1
cyclopropane: [a]
D
+390 (c 1, CH
2
Cl
2
). H NMR (CDCl
3
, 200 MHz):
d 8.05 (d, 2H, J = 7.8 Hz, Ph); 7.66–7.22 (m, 8H, COPh and Ph); 2.95
(m, 1H, CH(COPh)); 2.75 (m, 1H, CHPh); 2.02–1.56 (m, 2H, CH ).
2
1
7
13
lity. However, high catalyst turnovers could be obtained
with metalloporphyrins due to the relative chemical and
thermal stability of the porphyrin ring and these complexes
do not suffer from the problem of the low accessibility to
the catalytic sites inherent to immobilized catalysts.
3
C (CDCl , 75 MHz): d 198.79 (CO); 139.10 (Ph); 136.20 (COPh);
1
32.91 (COPh); 128.56 (COPh); 128.56 (Ph); 128.11 (COPh); 126.60
Ph); 126.23 (Ph); 30.01 (CH–Ph); 29.30 (CH–COPh); 19.24 (CH ).
14O (M ): 222.10447. Found: 222.1037.
+240 (c
1, CH Cl ). H NMR (CDCl , 200 MHz): d 8.03 (d, 2H, J = 8 Hz,
(
2
þÅ
HR-MS (m/z): calcd for C16
H
For trans-1-benzoyl-2-(p-methoxyphenyl)cyclopropane: [a]
D
1
2
2
3
In summary, the asymmetric cyclopropanation using
diazoacetophenone catalyzed by chiral metalloporphyrins
occurs in a good stereoselective manner, offering for
the first time, a general access to optically active
Ph); 7.64–7.46 (m, 3H, Ph); 7.18–6.87 (dd, 4H, J = 10 Hz, J = 76 Hz,
p-OMePh); 3.84 (s, 3H, OMe); 2.87 (m, 1H, CH(COPh)); 2.69 (m,
1
3
1
(
1
H, CH(p-OMePh)); 2.39 (s, 3H, CH
CDCl , 75 MHz): d 199.15 (CO); 158.84 (p-OMePh); 138.21 (Ph);
33.29 (Ph); 130.49 (p-OMePh); 128.97 (Ph); 128.52 (CH–COPh);
3
); 1.98–1.51 (m, 2H, CH
2
).
C
3
18
cyclopropylketones.
21.03 (CH3); 19.41 (CH2). For trans-1-benzoyl-2-(p-methyl-
1
phenyl)cyclopropane: [a]
2
7
D
+270 (c 1, CH
00 MHz): d 8.01 (d, 2H, J = 8.1 Hz, Ph); 7.65–7.45 (m, 3H, Ph);
.20–7.09 (dd, 4H, J = 6 Hz, J = 13.8 Hz, p-MePh); 2.90 (m, 1H,
); 1.95–1.59
, 75 MHz): d 198.68 (CO); 137.77
p-MePh); 137.42 (Ph); 136.26 (p-MePh); 133.55 (Ph); 129.54 (Ph);
2 2 3
Cl ). H NMR (CDCl ,
Acknowledgement
CH(COPh)); 2.71 (m, 1H, CH(p-MePh)); 2.39 (s, 3H, CH
3
1
3
I.N. thanks the Girex company for a doctoral
fellowship.
2 3
(m, 2H, CH ). C (CDCl
(
1
2
29.24 (p-MePh); 128.10 (Ph); 126.15 (p-MePh); 30.93 (CH-p-MePh);
9.32 (CH–COPh); 21.03 (CH ); 19.09 (CH ). HR-MS (m/z): calcd
3
2
þÅ
References and notes
for C17H16O (M ): 236.12012. Found: 236.1216. For trans-1-benzoyl-
-(p-trifluoromethylphenyl) cyclopropane: [a] +216.8 (c 1, CH Cl ).
, 200 MHz): d 8.05 (d, 2H, J = 6.6 Hz, Ph); 7.66–
7.47 (m, 3H, Ph); 7.34–7.30 (d, 4H, J = 7.6 Hz, p-CF Ph); 2.97(m, 1H,
CH(COPh)); 2.77 (m, 1H, CH(p-CF Ph)); 2.05–1.50 (m, 2H, CH ).
, 75 MHz): d 198.43 (CO); 145.15 (p-CF Ph); 137.88 (Ph);
133.60 (Ph); 129.10 (p-CF Ph); 128.99 (p-CF Ph); 128.56 (Ph); 128.40
(p-CF Ph); 126.88 (Ph); 125.92 (CF ); 29.85 (CH–p-CF
(CH–COPh); 19.89 (CH ). HR-MS (m/z): calcd for C17
2
D
2
2
1
1
. Simonneaux, G.; Le Maux, P. Coord. Chem. Rev. 2002, 228, 43–
0.
H NMR (CDCl
3
6
3
2
. Che, C. M.; Huang, J. S.; Lee, F. W.; Li, Y.; Lai, T. S.; Kwong, H. L.;
Teng, P. F.; Lee, W. S.; Lo, W. C.; Peng, S. M.; Zhou, Z. Y. J. Am.
Chem. Soc. 2001, 123, 4119–4129.
3
2
1
3
C (CDCl
3
3
3
3
3
4
5
6
7
8
. Ferrand, Y.; Le Maux, P.; Simonneaux, G. Org. Lett. 2004, 6, 3211–
3
3
3
Ph); 29.63
þÅ
3
214.
. Le Maux, P.; Juillard, S.; Simonneaux, G. Synthesis 2006, 10, 1701–
704.
. Ferrand, Y.; Le Maux, P.; Simonneaux, G. Tetrahedron: Asymmetry
005, 16, 3829–3836.
2
H
13OF
3
(M ):
290.09185. Found: 290.0902. For trans-1-benzoyl-2-(p-chloro-
1
1
D 2 2 3
phenyl)cyclopropane: [a] +298.8 (c 1, CH Cl ). H NMR (CDCl ,
200 MHz): d 8.03 (d, 2H, J = 7.2 Hz, Ph); 7.66–7.46 (m, 3H, Ph);
7.34–7.12 (dd, 4H, J = 8.44 Hz, J = 34 Hz, p-ClPh); 2.91 (m, 1H,
2
1
3
. Barberis, M.; P e´ rez-Prieto, J.; Herbst, K.; Lahuerta, P. Organo-
metallics 2002, 21, 1667–1673.
. Nakamura, A.; Konishi, A.; Tatsuno, Y.; Otsuka, S. J. Am. Chem.
Soc. 1978, 100, 3443–3448.
. Wolf, J. R.; Hamaker, C. G.; Djukic, J. P.; Kodadek, T.; Woo, L. K.
J. Am. Chem. Soc. 1995, 117, 9194–9199.
CH(COPh)); 2.69 (m, 1H, CH(p-ClPh)); 1.96–1.57 (m, 2H, CH
2
).
C
(CDCl , 75 MHz): d 198.23 (CO); 139.01 (p-ClPh); 137.16 (Ph);
3
133.05 (Ph); 130.38 (p-ClPh); 128.91 (p-ClPh); 128.62 (Ph); 128.50
(p-ClPh); 127.96 (Ph); 29.24 (CH-p-ClPh); 29.15 (CH–COPh); 19.16
3
5
þÅ
(CH
Found: 256.0664.
2
). HR-MS (m/z): calcd for C16H O Cl (M ): 256.06549.
1
3