Highly stereoselective Ru(ii)-Pheox catalyzed asymmetric cyclopropanation of terminal olefins with succinimidyl diazoacetate

Article abstract of DOI:10.1039/c2cc32706f

The Ru(ii)-Pheox complex is an efficient catalyst for the intermolecular cyclopropanation of various terminal olefins with succinimidyl diazoacetate. This catalytic system can perform under mild conditions, and the desired cyclopropane products are obtain

Full text of DOI:10.1039/c2cc32706f

View Online / Journal Homepage
Dynamic Article Links
ChemComm
Cite this: DOI: 10.1039/c2cc32706f
www.rsc.org/chemcomm
COMMUNICATION
Highly stereoselective Ru(II)–Pheox catalyzed asymmetric
cyclopropanation of terminal olefins with succinimidyl diazoacetatew
Soda Chanthamath, Kesiny Phomkeona, Kazutaka Shibatomi and Seiji Iwasa*
Received 17th April 2012, Accepted 8th June 2012
DOI: 10.1039/c2cc32706f
The Ru(II)–Pheox complex is an efficient catalyst for the inter-
molecular cyclopropanation of various terminal olefins with
succinimidyl diazoacetate. This catalytic system can perform
under mild conditions, and the desired cyclopropane products are
obtained in high yields with excellent diastereoselectivity and
enantioselectivity.
Recently, we reported the efficient use of a novel macro-
porous polymer-supported chiral Ru(II)–Pheox catalyst in
inter- and intramolecular cyclopropanation reactions.5 Despite
the high reactivity, enantioselectivity, and reusability of our macro-
porous catalyst, the development of a highly trans-stereoselective
carbene transfer process that can proceed effectively in the presence
of this catalyst under mild conditions remains a challenge.
Herein, we report a highly stereoselective Ru(II)–Pheox catalyzed
asymmetric cyclopropanation of olefins with succinimidyl
diazoacetate as the carbene source. Ru(II)–phenyloxazoline
complexes (Ru(II)–Pheox) 2a and 2b were synthesized in high
yield from inexpensive, commercially available benzoyl chloride
and amino alcohols (Scheme 1).6
Optically active cyclopropane derivatives play an important
role in natural product synthesis and are valuable synthetic
intermediates in organic and pharmaceutical chemistry.1 After
the pioneering work by Nozaki et al.,2 significant efforts have
been devoted to the development of transition-metal-catalyzed
asymmetric cyclopropanation of alkenes with diazoesters, and
many excellent results have been reported.3 Nevertheless, the
challenge to develop the catalytic systems still remains, with
easy manipulation and under convenient conditions, from the
viewpoint of practicality while still affording high yield and
high stereoselectivity. Among the various reported catalytic
systems,3 only a few can catalyze asymmetric cyclopropanation
under practically desirable conditions (carried out at room
temperature and without slow addition of diazoesters) while
affording high diastereoselectivity and enantioselectivity. In
2009, Zhang et al. reported the general synthesis of optically
active cyclopropyl carboxamide derivatives via cyclopropanation
of terminal olefins with succinimidyl diazoacetate (N2CHCO2Su)
in the presence of a Co(II)–porphyrin catalyst under practically
desirable conditions.4 Although the cyclopropanation by using this
catalyst afforded excellent trans-diastereoselectivity, moderate yields
(50–90%) and good enantioselectivity (in most cases 89–95% ee) in
reaction time of two days were achieved. In addition, the porphyrin
ligand is expensive and time-consuming; further, an additive such as
DMAP is necessary to control the enantioselectivity. These
drawbacks prompted us to explore a simple and highly
efficient catalyst that can promote the cyclopropanation of a
wide range of olefins with diazo reagents and afford the
desired product in excellent yields and high stereoselectivity.
Initially, we compared the activity of the symmetric Ru(II)-
dm-Pheox catalyst 2a with that of the popularly used Cu and
Rh metals in the intermolecular cyclopropanation of styrene
with succinimidyl diazoacetate 4. The results are shown in
Table 1. No product was formed when the reaction was
carried out at room temperature in the presence of the Cu
catalyst (copper powder) (entry 5), but the desired product
could be isolated in 63% yield when the temperature was
increased to 45 1C and 20 mol% Cu was used (entry 6).
Rh2(OAc)4 gave the desired product in good yield (82%) in
less than 1 min, but the diastereoselectivity was low (74 : 26)
(entry 7). Interestingly, 2a afforded succinimidyl 2-phenyl
cyclopropylcarboxylate 5 in very high yield (99%) and excellent
trans diastereoselectivity (499 : o1) in less than 1 min at room
temperature (entry 4). Dichloromethane was found to be the
solvent of choice.
Encouraged by the results obtained with 2a, we prepared the
chiral catalyst Ru(II)-Ph-Pheox complex 2b and used it for the
asymmetric cyclopropanation. We compared the catalytic
efficiency of 2b at room temperature with that of RuCl2((S),
(S)pybox-ip)(C2H4) 6,7 which was synthesized by Nishiyama’s
group and broadly used in cyclopropanation reactions.3d
Department of Environmental and Life Sciences, Toyohashi University
of Technology, 1-1 Tempaku-cho, Toyohashi, Aichi 441-8580, Japan.
E-mail: iwasa@ens.tut.ac.jp; Fax: +81-523-44-6817;
Tel: +81-532-44-6817
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization data for Ru(II)–Pheox catalysts and
products. See DOI: 10.1039/c2cc32706f
Scheme 1
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun.

View Online
Table 1 Optimization of reaction conditionsa
Table 2 Ru(II)-Ph-Pheox catalyzed asymmetric cyclopropanation of
various olefins with succinimidyl diazoacetate and subsequent
reduction of the corresponding cyclopropane derivatives
Temp.
Solvent (1C)
Yieldb
(%)
eed
Entry Cat.
Time
24 h
trans : cisc (%)
1
2
3
4
2a
2a
2a
2a
CH3CN 25
25
73
499 : o1 —
499 : o1 —
499 : o1 —
499 : o1 —
THF
Acetone 25
CH2Cl2 25
o1 min 81
o1 min 89
o1 min 99
Entry
R
Product Yielda (%) trans : cisb eec (%)
5
Cu (powder) CH2Cl2 25
Cu (powder) CH2Cl2 45
Rh2(OAc)4 CH2Cl2 25
48 h
48 h
0
63
—
59 : 41
74 : 26
—
—
—
6e
7
1
2
5a
7a
98
78e
499 : o1 —
499 : o1 95
o1 min 82
8f
9
10
11
6
CH2Cl2 25
CH2Cl2 25
48 h 87
499 : o1 87
499 : o1 95
499 : o1 98
499 : o1 99
2b
2b
2b
o1 min 98
15 min 99
30 min 97
CH2Cl2
0
3
4
5b
7b
95
78e
499 : o1 —
499 : o1 99
CH2Cl2 À10
a
Reactions were carried out under an argon atmosphere on a
0.2 mmol scale with a cat./N2CHCO2Su/styrene molar ratio of
0.01 : 1 : 5. Isolated yield. Determined by 1H NMR analysis.
5
6
5c
7c
97
84e
499 : o1 —
499 : o1 91
b
c
d
After reduction to alcohols, as confirmed by chiral HPLC using a
e
Chiralcel OD-H column. With 20 mol% catalyst. With 5 mol%
catalyst.
f
7
8
5d
7d
92
67e
499 : o1 —
499 : o1 91
9
10
5e
7e
98
79e
499 : o1
—
499 : o1 92
2b gave higher product yields and enantioselectivity within a
very short time than did RuCl2((S),(S)pybox-ip)(C2H4)
(Table 1, entries 8 and 9). Pleasingly, enantioselectivity was
improved to 99% by decreasing the temperature to À10 1C
(Table 1, entry 11).
11
12
5f
7f
92
75e
499 : o1 —
499 : o1 99
To gain further insight into the catalytic activity of 2b, we
studied the 2b-catalyzed intermolecular cyclopropanation of
various terminal olefins with succinimidyl diazoacetate under
the optimized conditions and subsequent reduction of the
cyclopropane derivatives into valuable cyclopropylmethanol
derivatives,8 as shown in Table 2. Electron-donating (o-, m-,
and p-positions) and electron-withdrawing styrene derivatives
(Table 2, entries 1, 3, 5, 7, 9, and 11) could be easily
cyclopropanated with succinimidyl diazoacetate 4 in less than
1 min and without any further additive to afford the desired
products in excellent yields (92–98%) and 499% trans-
diastereoselectivity. Further, no side products resulting from
dimerization of the diazo compound were observed.
13
14d
5g
7g
99
89e
499 : o1
—
499 : o1 98
15
16
5h
7h
94
66e
499 : o1 —
499 : o1 99f
499 : o1 —
499 : o1 99f
17
18
5i
7i
94
81e
Isolated yield. Determined by 1H NMR analysis. Determined
a
b
c
d
by chiral HPLC using Chiralcel OD, OD-H, or OK columns. THF
e
f
was used as a solvent. Total yield of two steps. Determined by
benzoylation using benzoyl chloride (see ESI).
Subsequent reduction of compounds 5a–f could be easily
carried out to afford the corresponding cyclopropylmethanol
derivatives with superior enantioselectivity (91–99% ee).
Other substrates such as N-vinyl carbazole and n-butyl- and
isobutyl vinyl ethers also afforded the corresponding products
in high yields, with excellent diastereoselectivity and enantio-
selectivity after reduction. In all the cases, the alcoholic
cyclopropane products were obtained in a total yield of
66–89% with excellent enantioselectivity (91–99% ee).9
The preferred prochiral face for the attack of the Ru–
carbene species by styrene is chosen on the basis of the vacant
metal coordination site and the less crowded steric space, as
shown in Scheme 2. The seven-member ring formed as a result
of coordination between the succinimidyl carbonyl group and
the Ru metal center prevented the attack from the G direction,
while the bulky phenyl group prevented the Si-face attack. In
addition, attack from the H and F directions was prevented by
the succinimidyl and phenyl rings, respectively. The previous
explanation led us to understand the high trans-selectivity of
this reaction.10
From the abovementioned observations and the atom economy
point of view, we state that our Ru(II)–Pheox catalysts offer the
following advantages: (a) low cost of preparation; (b) mild reaction
conditions (the reaction proceeds rapidly at room temperature
without the need for slow addition of the diazo reagent);
(c) non-requirement of further additives; (d) the shortest possible
reaction time (less than 1 min); (e) low catalyst loading; and
(f) excellent yields, enantioselectivity, and diastereoselectivity
(92–99%, 99% in most cases, and 499 : o1, respectively).
In conclusion, we have established a protocol for the highly
stereoselective Ru(II)–Pheox catalyzed asymmetric cyclo
propanation of terminal olefins with (N2CHCO2Su). The reaction
can be carried out smoothly under practically desirable conditions,
c
Chem. Commun.
This journal is The Royal Society of Chemistry 2012

View Online
1990, 31, 6613; (b) R. E. Lowenthal, A. Abiko and S. Masamune,
Tetrahedron Lett., 1990, 31, 6005; (c) D. A. Evans, K. A. Woerpel,
M. M. Hinman and M. M. Faul, J. Am. Chem. Soc., 1991,
113, 726; (d) H. Nishiyama, Y. Itoh, H. Matsumoto, S.-B. Park
and K. Itoh, J. Am. Chem. Soc., 1994, 116, 2223; (e) M. M.-C. Lo
and G. C. Fu, J. Am. Chem. Soc., 1998, 120, 10270; (f) J. A. Miller,
W. Jin and S. T. Nguyen, Angew. Chem., Int. Ed., 2002, 41, 2953;
(g) M. Itagaki and Y. Yamamoto, Tetrahedron Lett., 2006, 47, 523;
(h) V. D. M. Hoang, P. A. N. Reddy and T.-J. Kim, Tetrahedron
Lett., 2007, 48, 8014; (i) Y. Chen and X. P. Zhang, J. Org. Chem.,
2007, 72, 5931; (j) H. Suematsu, S. Kanchiku, T. Uchida and
T. Katsuki, J. Am. Chem. Soc., 2008, 130, 10327; (k) A. DeAngelis,
O. Dmitrenko, G. P. A. Yap and J. M. Fox, J. Am. Chem. Soc.,
2009, 131, 7230.
4 J. V. Ruppel, T. J. Gauthier, N. L. Snyder, J. A. Perman and
X. P. Zhang, Org. Lett., 2009, 11, 2273.
5 A.-M. Abu-Elfotoh, K. Phomkeona, K. Shibatomi and S. Iwasa,
Angew. Chem., Int. Ed., 2010, 49, 8439.
Scheme 2
6 See the ESIw for the detailed explanation.
7 The structure of the RuCl2((S),(S)pybox-ip)(C2H4) catalyst, which
was synthesized by Nishiyama’s group
and succinimidyl cyclopropylcarboxylates in significantly enhanced
yields, diastereoselectivity, and enantioselectivity can be obtained.
Subsequent reduction of these cyclopropane products readily
affords the corresponding cyclopropylmethanol derivatives with
superior enantioselectivity.
This work was supported by a Grant-in-Aid for Scientific
Research (C) (No. 23550179) from Japan Society for the
Promotion of Science.
8 (a) J. Pietruszka and T. Wilhelm, Synlett, 2003, 1698;
(b) J. M. Vega-Perez, I. Perinan, C. Palo-Nieto, M. Vega-Holm
´ ´
Notes and references
1 (a) J. Pietruszka, Chem. Rev., 2003, 103, 1051; (b) W. A. Donaldson,
Tetrahedron, 2001, 57, 8589; (c) L. A. Wessjohann, W. Brandt and
T. Thiemann, Chem. Rev., 2003, 103, 1625; (d) H. Lebel,
J.-F. Marcoux, C. Molinaro and A. B. J. Charette, Chem. Rev.,
2003, 103, 1051; (e) A. Armstrong and J. N. Scutt, Chem. Commun.,
2004, 510; (f) H. Pellissier, Tetrahedron, 2008, 64, 7041.
and F. Iglesias-Guerra, Tetrahedron: Asymmetry, 2010, 21, 81;
(c) N. Koyata, T. Miura, Y. Akaiwa, H. Sasaki, R. Sato, T. Nagai,
H. Fujimori, T. Noguchi, M. Kirihara and N. Imai, Tetrahedron:
Asymmetry, 2009, 20, 2065.
9 All the racemic product versions were prepared in high yields and
499% trans-selectivity (see ESIw).
2 H. Nozaki, H. Takaya, S. Moriuti and R. Noyori, Tetrahedron,
1968, 24, 3655.
3 (a) M. P. Doyle, B. D. Brandes, A. P. Kazala, R. A. Pieters,
M. B. Jarstfer, L. M. Watkins and C. T. Eagle, Tetrahedron Lett.,
10 Experiments with other diazo compounds are being carried out for
comparing the results with those obtained for the succinimidyl
diazoacetate and thus clarifying the importance of the carbonyl
group.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun.