Construction of aryliridium-salen complexes: Enantio- and cis-selective cyclopropanation of conjugated and nonconjugated olefins

Article abstract of DOI:10.1021/ja802561t

Two stable and optically active iridium-salen complexes were synthesized by introducing a tolyl or phenyl ligand at the apical position, respectively, via the S_EAr mechanism, and they were found to be efficient catalysts for cis-selective asymm

Full text of DOI:10.1021/ja802561t

Published on Web 07/10/2008
Construction of Aryliridium-Salen Complexes: Enantio- and
Cis-Selective Cyclopropanation of Conjugated and
Nonconjugated Olefins
Hidehiro Suematsu, Shigefumi Kanchiku, Tatsuya Uchida, and Tsutomu Katsuki*
Department of Chemistry, Faculty of Science, Graduate School, Kyushu UniVersity, Hakozaki,
Higashi-ku, Fukuoka 812-8581, Japan
Received April 8, 2008; E-mail: katsuscc@chem.kyushu-univ.jp
Abstract: Two stable and optically active iridium-salen complexes were synthesized by introducing a tolyl
or phenyl ligand at the apical position, respectively, via the SEAr mechanism, and they were found to be
efficient catalysts for cis-selective asymmetric cyclopropanation. The scope of the cyclopropanation was
wide, and the reactions of not only conjugated mono-, di-, and trisubstituted olefins but also nonconjugated
terminal olefins proceeded with high enantio- and cis-selectivity, even in the presence of a functional group
such as an ether or ester. The utility of this cyclopropanation was demonstrated by a short step synthesis
of 8-[(1R,2S)-2-hexylcyclopropyl]octanoate, isolated from Escherichia coli B-ATCC 11303, using the reaction
as the key step.
1. Introduction
complexes as catalysts; however, the substrates are mostly
limited to conjugated mono- or 1,1-disubstituted olefins, and
cis-selective asymmetric cyclopropanation of conjugated olefins
having other substitution patterns and nonactivated olefins
remains a challenge. Recently, a modified Ru(PNNP) complex
was found to show good cis-selectivity (85: 15) and excellent
enantioselectivity (99% ee) in cyclopropanation of nonconju-
gated (nonactivated) olefins, though it was tested only toward
1-octene.10
Among group 9 metals, chiral cobalt and rhodium complexes
are well-recognized as asymmetric carbene transfer catal-
ysts.3g3h3i3m11,12 To our knowledge, however, there are no
reports on both asymmetric carbene transfer reactions using an
iridium complex and the synthesis of a stable Ir-salen com-
plex.13 Thus, we were intrigued by construction of a new, chiral
Ir-salen complex and its catalysis. Fortunately, we found that
Chiral metal-catalyzed asymmetric carbene transfer from
diazo compounds to olefins is a straightforward method for
preparation of optically active cyclopropanes.1 Since the seminal
report by Nozaki et al.,2 significant effort has been devoted to
the development of transition metal-catalyzed enantioselective
cyclopropanation, and many excellent catalysts have been
introduced. As a matter of course, there are many reports of
excellent methods for preparing thermodynamically stable trans-
cyclopropanes,3 while the methods for preparing cis-products
are rather limited.4–9 Recently, high cis- and enantioselectivity
have been achieved with Ru(salen),6 Co(salen),7 and Ru(PNNP)8
(1) (a) Maas, G. Chem. Soc. ReV. 2004, 33, 183. (b) Mu¨ller, P. Acc. Chem.
Res. 2004, 37, 243. (c) Lebel, H.; Marcoux, J.-F.; Molinaro, C.;
Charette, A. B. Chem. ReV. 2003, 103, 977. (d) Davies, H. M. L.;
Antoulinakis, E. Org. React. 2001, 57, 1. (e) Doyle, M. P.; McKervey,
M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis with
Diazo Compounds; John Wiley & Sons: New York, 1998. (f) Pfalz,
A. ComprehensiVe Asymmetric Catalysis, Vol. 2; Jacobsen, E. N.,P-
faltz, A., Yamamoto, H. Eds.; Springer: Berlin, 1999; pp 513-603.
(2) (a) Nozaki, H.; Takaya, H.; Noyori, R. Tetrahedron Lett. 1965, 6,
2563–2567. (b) Nozaki, H.; Takaya, H.; Moriuti, S.; Noyori, R.
Tetrahedron 1968, 24, 3655–3669.
(5) (a) Doyle, M. P.; Zhou, Q.-L.; Simonsen, S. H.; Lynch, V. Synlett
1996, 697–698. (b) Ishitani, H.; Achiwa, K. Synlett 1997, 781–782.
´
(c) Estevan, F.; Lloret, J.; Sanau´, M.; Ubeda, M. A. Organometallics
2006, 25, 4977–4984.
(6) (a) Uchida, T.; Irie, R.; Katsuki, T. Synlett 1999, 1163–1165. (b)
Uchida, T.; Irie, R.; Katsuki, T. Synlett 1999, 1793–1795. (c) Uchida,
T.; Irie, R.; Katsuki, T. Tetrahedron 2000, 56, 3501–3509.
(7) (a) Niimi, T.; Uchida, T.; Irie, R.; Katsuki, T. Tetrahedron Lett. 2000,
41, 3647–3651. (b) Niimi, T.; Uchida, T.; Irie, R.; Katsuki, T. AdV.
Synth. Catal. 2001, 343, 79–88.
(3) (a) Pfaltz, A. Acc. Chem. Res. 1993, 26, 339–345. (b) Nishiyama, H.;
Itoh, Y.; Matsumoto, H.; Park, S.-B.; Itoh, K. J. Am. Chem. Soc. 1994,
116, 2223–2224. (c) Munslow, I. J.; Gillespie, K. M.; Deeth, R. J.;
Scott, P. Chem. Commun. 2001, 1638–1639. (d) Lowenthal, R. E.;
Abiko, A.; Masamune, S. Tetrahedron Lett. 1990, 31, 6005–6008. (e)
Evans, D. A.; Woerpel, K. A.; Scott, M. J. Angew. Chem., Int. Ed.
Engl. 1992, 31, 430–432. (f) Davies, H. M. L.; Bruzinski, P. R.; Lake,
D. H.; Kong, N.; Fall, M. J. J. Am. Chem. Soc. 1996, 118, 6897–
6907. (g) Fukuda, T.; Katsuki, T. Synlett 1995, 825–826. (h) Fukuda,
T.; Katsuki, T. Tetrahedron 1997, 38, 3435–3438. (i) Bykowski, D.;
Wu, K.-H.; Doyle, M. P. J. Am. Chem. Soc. 2006, 128, 16038–16039.
(j) Denton, J. R.; Sukumaran, D.; Davies, H. M. L. Org. Lett. 2007,
9, 2625–2628. (k) Reddy, R. P.; Lee, G. H.; Davies, H. M. L. Org.
Lett. 2006, 8, 3437–3440. (l) Davies, H. M. L.; Lee, G. H. Org. Lett.
2004, 6, 2117–2120. (m) Ikeno, T.; Sato, M.; Sekino, H.; Nishikazu,
A.; Yamada, T. Bull. Chem. Soc. Jpn. 2001, 74, 2139–2150.
(8) Bachmann, S.; Furler, M.; Mezzetti, A. Organometallics 2001, 20,
2102–2108.
(9) Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem.
Soc. 2005, 127, 18002–18003.
(10) Bonaccorsi, C.; Mezzetti, A. Organometallics 2005, 24, 4953–4960.
(11) (a) Nakamura, A.; Konishi, A.; Tsujitani, R.; Kudo, M-A.; Otsuka, S.
J. Am. Chem. Soc. 1978, 100, 3449–3461. (b) Nakamura, A.; Konishi,
A.; Tsujitani, R.; Tatsuno, Y.; Otsuka, S. J. Am. Chem. Soc. 1978,
100, 3443–3448.
(12) (a) Doyle, M. P.; Brandes, B. D.; Kazala, A. P.; Pieters, R. J.; Jarstfer,
M. B.; Watkins, L. M.; Eagle, C. T. Tetrahedron Lett. 1990, 31, 6613–
6616. (b) Doyle, M. P.; Winchester, W. R.; Hoom, J. A. A.; Lynch,
V.; Simonsen, S. H.; Ghosh, R. J. Am. Chem. Soc. 1993, 115, 9968–
9978.
(4) (a) Aratani, T.; Yoneyoshi, Y.; Nagase, T. Tetrahedron Lett. 1982,
23, 685–688. (b) Ito, K.; Katsuki, T. Synlett 1993, 638–640.
9
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2008 American Chemical Society
J. AM. CHEM. SOC. 2008, 130, 10327–10337 10327

A R T I C L E S
Suematsu et al.
IrIII-salen complexes bearing an aryl ligand at the apical
position were stable and could be handled even in air at room
temperature. Moreover, some of the complexes showed potent
cis- and enantioselective cyclopropanation catalysis. In this
paper, we describe the synthesis of a new class of IrIII-salen
complexes and the full scope of asymmetric cyclopropanation
using the complexes as catalysts.14
2. Results and Discussion
2.1. Preparation of Optically Active Aryliridium-Salen
Complexes 2, 3, and 4. Most metal-salen complexes could be
easily synthesized by mixing a suitable metal salt and salen
ligand, followed, if required, by oxidation.15 We expected that
the IrIII-salen complex could also be prepared by mixing
[IrI(cod)(toluene)]+PF6- and the salen ligand in a conventional
manner, but the resultant complex 1 was unstable. Fortunately,
however, the stable IrIII-salen complex 2 was obtained while
attempting its crystallization from toluene. High-resolution fast
atom bombardment mass spectrometric analysis of 2 indicated
that a tolyl group was σ-coordinated to the iridium ion.14 Finally,
it was found that 2 could be synthesized in good yield by air
treatment of complex 1, followed by refluxing with toluene.16
Other Ir-salen complexes 3, 5, and 6 could be synthesized in
the same manner. When the air-treated complex 1 was refluxed
in benzene, complex 4 was synthesized, and its crystallization
from dichloromethane and methanol gave a single crystal
suitable for X-ray analysis (Figure 1).
Figure 1. Molecular formula of 1 and structure of aryliridium-salen
complexes 2-6.
Table 1. Asymmetric Cyclopropanation of Styrene Using Various
Iridium-Salen Complexes as Catalysta
2.2. Asymmetric Cyclopropanation of Conjugated Olefins.
With complexes 1 and 2 as catalysts, we examined asymmetric
cyclopropanation of styrene using tert-butyl R-diazoacetate in
tetrahydrofuran (THF). The reaction proceeded rapidly at room
temperature; however, the yield of the desired product was
unsatisfactory because of the competitive production of fumaric
and maleic esters. Therefore, to suppress this undesired diazo
coupling, we carried out the reaction in the presence of 10 equiv
of styrene: both complexes showed modest cis-selectivity, but
complex 2 showed superior enantioselectivity to complexes 1.
Hence, a further survey was conducted with complex 2.
Lowering the reaction temperature remarkably increased not
only the enantioselectivity but also the cis-selectivity, and the
best result was obtained when the reaction was carried out at
-78 °C. In addition, the formation of the diesters was almost
completely suppressed at that temperature (Table 1, entry 1).14
High enantio- and excellent diastereoselectivity were also
achieved, even with ethyl R-diazoacetate.14 Complex 4 showed
d
d
entry
catalyst
yield/%b
cis:transc
% eecis
% eetrans
1
2
3
4
5
2
3
4
5
6
99
44
99
43
25
>99:1
41:59
>99:1
58:42
29:71
>99e
63e
60f
98e
-37g
1
70f
1
a Reactions were carried out in THF for 24 h on a 0.1 mmol scale
with a molar ratio of iridium-salen/diazo ester/olefin ) 0.01/1/10.
b Total yield of the cis- and the trans-cyclopropanes. Yields were
determined on the basis of the amount of diazoacetate by 1H NMR
analysis using 1-bromonaphtharene as the internal standard. c Deter-
mined by 1H NMR analysis. d Determined by HPLC analysis using
chiral column (DAICEL CHIRALCEL OD-H). e The absolute
configuration was determined to be 1R,2S by comparison of the optical
rotation with the literature value (ref 10). f The absolute configuration
was determined to be 1R,2R by comparison of the optical rotation with
the literature value (ref 10). g The absolute configurations was 1S,2R.
identical catalysis with 2, while the catalysis of complexes 3,
5, and 6 was less efficient than that of complex 2 (entries 2, 4,
and 5).
Cyclopropanation of substituted styrenes also proceeded with
excellent enantio- (g95% ee) and cis-selectivity (g95%),
irrespective of the electronic and steric natures and the location
of the substituents, with the exception that the reaction of
p-bromostyrene showed a slightly reduced enantioselectivity of
93% ee (Table 2).
Cyclopropanation of R- and cis-ꢀ-methylstyrenes proceeded
with high stereoselectivity, although the yield of the latter
reaction was modest even under slow addition conditions (Table
3, entries 1 and 2). In contrast, the reaction of trans-ꢀ-
methylstyrene was sluggish (entry 3). On the other hand, cyclic
olefins, such as indene, and heterocyclic compounds, such as
benzofuran, also proceeded with high cis- and enantioselectivity
(13) For an example of a non-enantioselective carbene transfer reaction,
aziridination of imines, catalyzed by an Ir complex, in which the
complex served as a Lewis acid for activating imines, see: (a) Kubo,
T.; Sakaguchi, S.; Ishii, Y. Chem. Commun. 2000, 625–626. An Ir-
salen complex that was prepared in situ and incorporated into a zeolite
has been used as the catalyst for epoxidation: (b) Schuster, C.;
Mo¨llmann, E.; Tompos, A.; Ho¨lderich, W. F. Catal. Lett. 2001, 74,
69–75. Periana et al. reported that the IrIII(acac)2(OH) complex also
underwent aryl C-H activation: (c) Tenn, W. J., III; Young, K. J. H.;
Oxgaard, J.; Nielsen, R. J.; Goddard, W. A., III; Periana, R. A.
Organometallics 2006, 25, 5173–5175.
(14) A part of the study on asymmetric cyclopropanation has been
communicated: Kanchiku, S.; Suematsu, H.; Uchida, T.; Katsuki, T.
Angew. Chem., Int. Ed. 2007, 46, 3889–3891.
(15) Katsuki, T. Coord. Chem. ReV. 1995, 140, 189–214.
(16) A similar substitution of the aromatic C-H bond of toluene by an
SEAr mechanism via a RhIII(porphyrin) species to give the corre-
spondingRhIII(porphyrin)(C6H4CH3)complexhasbeenreported:Collman,
J. P.; Boulatov, R. Inorg. Chem. 2001, 40, 2461–2464.
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Cis-Selective Asymmetric Cyclopropanation of Olefins
A R T I C L E S
Table 2. Asymmetric Cyclopropanation of Styrene Derivatives with
2 as the Catalysta
Table 3. Asymmetric Cyclopropanation of Multisubstituted
Conjugated Olefins with 2 as the Catalysta
a Reactions were carried out in THF on a 0.2 mmol scale with a
molar ratio of 2/diazo ester/olefin
) 0.01/1/10, unless otherwise
mentioned. A THF solution of diazoacetate was added over the period
of 24 h. b Yields are based on the amount of diazoacetate used. Total
yields of the cis- and trans-cyclopropanes were determined by 1H NMR
analysis using 1-bromonaphtharene as an internal standard. c Determined
by 1H NMR analysis. d Determined as reported in the Experimental
Section. e Carried out in dichloromethane.
a Reactions were carried out in THF for 24 h on a 0.1 mmol scale
with a molar ratio of iridium-salen 2/diazo ester/olefin ) 0.01/1/10,
unless otherwise mentioned. b Yields are based on the amount of
diazoacetate used. Total yields of the cis- and trans-cyclopropanes were
determined by 1H NMR analysis using 1-bromonaphtharene as the
internal standard. c Determined by 1H NMR analysis. d Determined as
reported in the Experimental Section. e Reaction was carried out at -50
°C. f Five equivalents of olefin was used.
2.3. Asymmetric Cyclopropanation of Nonactivated Alkenes. The
above results prompted us to further examine the cyclopropa-
nation of nonactivated terminal olefins (Table 5). The reaction
of 4-phenyl-1-butene with tert-butyl R-diazoacetate was exam-
ined first. This reaction proceeded with high cis- and excellent
enantioselectivity, albeit with moderate yield (52%, entry 1).
Slow addition of the diazoacetate again significantly improved
the yield without eroding cis- and enantioselectivity (entry 2).
The reaction with ethyl R-diazoacetate also gave satisfactory
results (entry 3). Excellent cis- and high enantioselectivity were
also obtained for the reaction of 1-octene (entry 4). The
stereoselectivity was only slightly affected by the presence of
a functional group such as an ether or ester (entries 5-7).
Although the reaction of vinyl benzoate, a nucleophilic olefin,
with ethyl R-diazoacetate showed somewhat diminished ste-
reoselectivity, high cis- and enantioselectivity were obtained by
using tert-butyl R-diazoacetate instead (entries 8 and 9). On the
other hand, the reaction of phenyl acrylate, which is poorly
nucleophilic, was sluggish (entry 10). A terminal olefin branched
at the allylic carbon also reacted with high cis- and enantiose-
lectivity, albeit slowly (entry 11). Geminally disubstituted olefins
reacted with good to excellent enantioselectivity, but the
diastereoselectivity was modest (entries 12 and 13). Differentia-
and acceptable yields via the slow addition technique (entries
4 and 5). It is noteworthy that the reaction of 3-methylbenzo-
furan, a trisubstituted olefin, showed excellent cis- and enan-
tioselectivity, albeit with moderate yield even under the slow
addition conditions (entry 6).
Under the same conditions, reactions of enyne and diene were
also examined (Table 4). The reaction of 1-phenyl-3-buten-1-
yne proceeded with high enantio- and cis-selectivity (entries 1
and 2). (E)-1-Phenyl-1,3-butadiene was insufficiently soluble
at -78 °C, and its reaction was carried out at -45 °C. Although
the reaction of (E)-1-phenyl-1,3-butadiene was moderately cis-
selective, it was also highly enantioselective and occurred
exclusively at the terminal olefin (entries 3 and 4). The
stereoselectivity of these reactions was scarcely affected by the
carbene source used: reactions with tert-butyl and ethyl R-dia-
zoacetate showed similar levels of stereoselectivity (entries 1
vs 2 and 3 vs 4).
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A R T I C L E S
Suematsu et al.
Table 4. Asymmetric Cyclopropanation of Diene Derivatives and
Eneyne with 2 as the Catalysta
Table 5. Asymmetric Cyclopropanation of Nonactivated Olefins
with 2 as the Catalysta
a Reactions were carried out in THF on a 0.1 mmol scale with a
molar ratio of 2/diazo ester/olefin
) 0.01/1/10, unless otherwise
mentioned. b Yields are based on the amount of diazoacetate used. Total
yields of the cis- and trans-cyclopropanes were determined by 1H NMR
analysis using 1-bromonaphtharene as the internal standard. c Deter-
mined by 1H NMR analysis. d Determined as described in the
Experimental Section. e Carried out at -45 °C.
tion of methyl and simple alkyl groups was difficult, and the
reaction of 2-methyloctene was poorly diastereoselective (entry
13).
Electrophilic metal-carbenoid species have been postulated
as possible intermediates for metal-mediated cyclopropanation
using a diazo compound as the carbene precursor.1 The above-
described results (Table 5, entries 8-10) do not contradict the
assumption of the participation of an electrophilic intermediate.
We further investigated the reactions of nonconjugated 1,5- and
1,6-dienes. Although the internal olefin should be more nucleo-
philic than the terminal one, the reactions occurred only at the
terminal olefin with high cis- and enantioselectivity (Scheme
1). This indicated that the regioselectivity is mainly dictated
by a steric factor.
2.4. Enantioenriched Synthesis of Methyl 8-[(1R,2S)-2-
Hexylcyclopropyl]octanoate 14. The present reaction is a potent
tool for the construction of a cis-disubstituted cyclopropane
structure. In order to demonstrate its utility, we examined the
synthesis of methyl 8-[(1R,2S)-2-hexylcyclopropyl]octanoate 14,
which was isolated from Escherichia coli B-ATCC 11303,17,18
a Reactions were carried out in THF on a 0.2 mmol scale with a
molar ratio of 2/diazo ester/olefin
) 0.01/1/10, unless otherwise
mentioned. A THF solution of diazo ester was added over the period of
24 h. b Total isolated yield of cis- and trans-cyclopropanes. c Deter-
mined on the basis of the isolated yields of cis- and trans-products.
d Determined as described in the Supporting Information. e tert-Butyl
R-diazoacetate was used as the carbene source. f Diazoacetate was added
without using a slow addition technique. g The reaction was carried out
on a 9.5 mmol scale. h Absolute configuration was determined to be
1R,2S by comparison of the optical rotation with the literature value (ref
10). i The enantiomeric excess of the trans-isomer was determined to be
86%.
(17) For the isolation of 15 and other cyclopropyl fatty acids, see: (a)
Hofmann, K.; Lucas, R. A. J. Am. Chem. Soc. 1950, 72, 4328–4329.
(b) O’Leary, W. M. J. Bacteriol. 1959, 78, 709–713. (c) Kaneshiro,
T.; Marr, A. G. J. Biol. Chem. 1961, 236, 2615–2619. (d) Weinbaum,
G.; Panos, C. J. Bacteriol. 1966, 92, 1576–1577. (e) Grogan, D. W.;
Cronan, J. E., Jr Microbiol. Mol. Biol. ReV. 1997, 61, 429–441. (f)
Murakami-Murofushi, K.; Shioda, M.; Kaji, K.; Yoshida, S.; Muro-
fushi, H. J. Biol. Chem. 1992, 267, 21512–21517. (g) Stuart, L. J.;
Buck, J. P.; Tremblay, A. E.; Buist, P. H. Org. Lett. 2006, 8, 79–81.
(h) Stuart, L. J.; Buist, P. H. Tetrahedron: Asymmetry 2004, 15, 401–
403. (i) Brian, B. L.; Gardner, E. W. Appl. Microbiol. 1968, 16, 549–
522. (j) West, T. P. Can. J. Microbiol. 1998, 44, 1106–1109. (k)
Doumenq, P.; Guiliano, M.; Bertrand, J. C.; Mille, G. Appl. Spectrosc.
1990, 44, 1355–1359. (l) Termonia, M.; Wybauw, M.; Bronckart, J.;
Jacobs, H. J. High Resolut. Chromatogr. 1989, 12, 685–688.
starting from 1-octene (Scheme 2). The cyclopropanation of
1-octene gave a 98:2 mixture of cis- and trans-cyclopropan-
ecarboxylates, which was chromatographed on silica gel to give
the cis-product 10 in 98% ee. Lithium aluminum hydride
9
10330 J. AM. CHEM. SOC. VOL. 130, NO. 31, 2008

Cis-Selective Asymmetric Cyclopropanation of Olefins
A R T I C L E S
Scheme 1. Cyclopropanation of 1,5- and 1,6-Dienes Using 2 as
Catalyst
Figure 2. ORTEP drawing of 4. Hydrogen atoms and solvent molecules
were omitted for clarity (recrystallized from CH2Cl2:MeOH ) 1:1; Ir, gray;
C, black; N, blue; O, red).
Figure 3. X-ray structures of the two stereoisomers of complex 4.
Horizontal view from the binaphthyl side. Ir, violet; C, black; N, blue; O,
red.
perpendicular to the salen ligand, which is almost planar.20
Methanol is weakly bound to the ion at another apical position:
the lengths of the Ir-Oeq bonds range from 2.02 to 2.04 Å,
while the lengths of the Ir-Oap bond is ca. 2.5 Å (Figure 2).
The analysis also revealed that two complexes with different
conformations are present per unit cell, which are separately
shown for clarity in Figure 3 (S1 and S2). The two complexes
differ in the degree of distortion of the ONNO plane, the
conformation of the apical phenyl substituent, and the confor-
mation of the 2-phenyl substituent of the naphthyl ring on the
top side (the side opposite the apical phenyl group). That is,
these two complexes are conformational isomers to each other,
and they should be in equilibrium in a solution.
Scheme 2. Synthesis of Methyl 8-[(1R,2S)-2-Hexylcyclopropyl]-
octanoate 14a
Although the detailed mechanism of the stereochemical
control in the present cyclopropanation is unclear, we propose
a primitive model to explain its stereochemistry. Based on the
X-ray structure of 4, it is likely that a diazo compound replaces
a Reagents and conditions: (a) (aR,R)-Ir-salen 2 (1 mol %), N2CHCO2Et,
THF, -78 °C, 48 h, 68% (after silica gel chromatography); (b) LiAlH4,
THF, 0 °C to rt, 2 h, 99%; (c) 1-phenyl-1H-tetrazole-5-thiol, DEAD, PPh3,
THF, 0 °C to rt, 3 h, then H2O2, EtOH, H2O, (NH4)6Mo7O24 ·4H2O, 24 h,
90%; (d) LiHMDS, THF, -78 °C, then MeO2C(CH2)5CHO, -78 °C to rt,
73%; (e) KO2CNdNCO2K, AcOH, MeOH, reflux, 8 h, 88%. DEAD, diethyl
azodicarboxylate; HMDS, 1,1,1,3,3,3-hexamethyldisilazane.
(18) For the previous synthesis of 15 and its related compounds, see: (a)
Kobayashi, S.; Tokunoh, R.; Shibasaki, M.; Shinagawa, R.; Murakami-
Murofushi, K. Tetrahedron Lett. 1993, 34, 4047–4050. (b) Coxon,
G. D.; Dulayymi, J. R. A.; Morehouse, C.; Brennan, P. J.; Besra, G. S.;
Baird, M. S.; Minnikin, D. E. Chem. Phys. Lipids 2004, 127, 35–46.
(c) Coxon, G. D.; Al-Dulayymi, J. R.; Baird, M. S.; Knobl, S.; Roberts,
E.; Minnikin, D. E. Tetrahedron: Asymmetry 2003, 14, 1211–1222.
(19) (a) Charette, A. B.; Level, H. J. Am. Chem. Soc. 1996, 118, 10327–
10328. (b) Liu, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123,
10772–10773. (c) Smith, A. B., III; Brandt, B. M. Org. Lett. 2001,
1685–1688. (d) Blakemore, P. R.; Cole, W. J.; Kocien´ski, P. J.; Morley,
A. Synlett 1998, 26–28. (e) Julia, M.; Paris, J.-M. Tetrahedron Lett.
1973, 14, 4833–4836.
reduction of 10 gave alcohol 11, which was further carbon-
extended by using Kocien˜ski-Julia olefination19 to yield ester
13 via 12. Compound 13 was converted into 14 by using
Kobayshi’s procedure.18a Thus, 14 was obtained in a highly
enantioenriched manner in only five steps.
2.5. X-ray Structure of 4 and Mechanistic Considerations.
Although a single crystal of complex 2 could not be obtained,
the phenyliridium-salen complex 4, which showed an identical
catalysis with complex 2, produced a single crystal upon
crystallization from dichloromethane and methanol. X-ray
analysis of the crystal clearly showed that the phenyl group was
σ-coordinated to the iridium ion at the apical position and
(20) CCDC 625076 contains the supplementary crystallographic data of
4. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif.
(21) A methyl group was used as the alkyl group on the carbenoid ester
for the calculation.
(22) (a) Maseras, F.; Morokuma, K. J. Comput. Chem. 1995, 16, 1170–
1179. (b) Humbel, S.; Sieber, S.; Modrokuma, K. J. Chem. Phys. 1996,
105, 1959–1967. (c) Matsubara, T.; Sieber, S.; Morokuma, K. Int. J.
Quantum Chem. 1996, 60, 1101–1109.
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A R T I C L E S
Suematsu et al.
3. Conclusion
We were able to, for the first time, synthesize stable chiral
IrIII-salen complexes that carry a σ-coordinated aryl ligand like
the tolyl (2 and 3) or phenyl (4) group. The present study also
revealed that complexes 2 and 4 were unique and potent
catalysts for cis-selective asymmetric cyclopropanation. This
cyclopropanation can be applied to not only conjugated but also
nonactivated olefins and provides a useful tool for enantiose-
lective synthesis of cis-disubstituted cyclopropanes. To our
knowledge, this is the first cyclopropanation method that can
be applied to conjugated, polysubstituted olefins and nonacti-
vated olefins with both high cis- and enantioselectivity.
Figure 4. Explanation of the stereochemistry of the aryliridium-salen-
catalyzed asymmetric cyclopropanation, based on the optimized structure
of the phenyliridium-salen carbenoid intermediate.
the weakly bound methanol and gives the corresponding
carbenoid species at the apical position. Thus, we optimized
the structure of the phenyliridium-salen carbenoid intermedi-
ate21 with the two-layered ONIOM approach22 in the Gaus-
sian03W package.23 We assigned the phenyliridium-salen
carbenoid complex, except for the C3- and C3′-substituents, to
the high layer and the 2-phenylnaphthyl substituents at C3 and
C3′ to the low layer. The high layer was optimized at the B3LYP
density functional theory level.24 Core electrons of the Ir atom
were described with the effective-core pseudopotentials of Hay
and Wadt,25 and valence electrons were described with the
standard LANL2DZ basis set associated with the effective core
potential. H, C, N, and O atoms were described with the 6-31G
basis set.26 The low layer was treated by the universal force
fields method.27 This calculation suggested that the basal salen
ligand of the intermediate has a stepped conformation and that
the bond Ccarbene-Cester is directed, bisecting the two Ir-N
vectors (Figure 4). Olefin is considered to approach the
carbenoid carbon from its sterically less hindered side, and the
space over the downward naphthalene ring should be less
crowded than that over the upward one. Thus, it is likely that
olefin approaches the carbenoid carbon from the side of the
downward ring. On the other hand, two proposals for access of
the olefin, perpendicular3f,h,7,28 and parallel approaches,3a,b,10,29
have been made for the metal-mediated cyclopropanation.
Although we cannot draw a conclusion on the substrate
approach, the fact that cis-ꢀ-methylstyrene was a much better
substrate for the present reaction than trans-ꢀ-methylstyrene
agrees with the perpendicular approach.30 The oncoming olefin
should direct its substituent away from the carbenoid ester group,
and this perpendicular approach, along with the subsequent
counter-clockwise rotation, leads to the major product.7b The
clockwise rotation causes steric repulsion between the phenyl
substituent and the basal salen ligand, and it should be less
favorable than the counter-clockwise one.
4. Experimental Section
1
4.1. General. H NMR spectra were recorded at 400 MHz on
a JEOL JNM-AL-400 instrument. All signals were expressed as
ppm downfield from tetramethylsilane used as an internal standard
(δ value in CDCl3). IR spectra were obtained with a Shimadzu
FTIR-8600 instrument. Optical rotations were measured with a
JASCO P-1020 polarimeter. High-resolution fast atom bombard-
ment mass spectra (HRMS-FAB) were measured with a JEOL JMS-
SX102A instrument. High-resolution electrospray ionization mass
spectra (HRESI-MS) were measured with a Bruker Daltonics Micro
TOF-KS1 focus. Electrospray ionization mass spectra (ESI-MS)
were measured with a Perkin-Elmer SCIEX API 300 instrument.
Column chromatography was conducted on silica gel BW-820MH,
70-200 mesh ASTM, available from Fuji Silysia Chemical Ltd.
Preparative thin-layer chromatography was performed on silica gel
60 F254-coated glass plates (Merck). Enantiomeric excesses were
determined by high-performance liquid chromatographic (HPLC)
analysis using a Shimadzu LC-10AT-VP instrument, equipped with
an appropriate optically active column, as described in the footnotes
to the tables. Solvents were dried and distilled shortly before use.
Olefins and tert-butyl and ethyl R-diazoacetates were also distilled
before use. The use of a non-freshly distilled olefin or R-diazoacetate
may be detrimental to the stereoselectivity of the reaction. Reactions
were carried out under a nitrogen atmosphere.
4.2. Preparation of Salen Ligands. The salen ligands (15,31
16,32 17,33 and 1834) used for this study were prepared according
to the reported procedures.
(23) Frisch, M. J.; et al. Gaussian 03, Revision C.02; Gaussian, Inc.:
Wallingford, CT, 2004.
(24) (a) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785–789.
(b) Backe, D. J. J. Chem. Phys. 1993, 98, 5648–5652. (c) Parr, R. G.;
Yang, W.; Density-functional Theory of Atoms and Molecules; Oxford
University Press: New York, 1989.
(25) (a) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270–283. (b)
Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299–310.
(26) Hehre, W.; Ditchfield, J. R.; Pople, J. A. J. Chem. Phys. 1972, 56,
2257–2261.
(27) Rappe´, A. K.; Casewit, C. J.; Colwell, K. S.; Goddard, W. A.; Skiff,
W. M. J. Am. Chem. Soc. 1992, 114, 10024–10035.
(28) (a) Davies, H. M. L.; Stafford, D. G.; Doan, B. D.; Houser, J. H.
J. Am. Chem. Soc. 1988, 120, 3326–3331. (b) Brown, K. C.; Kodadek,
T. J. Am. Chem. Soc. 1992, 114, 8336–8338. (c) Maxwell, J. L.;
Brown, K. C.; Bartley, D.; Kodadek, T. Science 1992, 256, 1544–
1547.
4.3. Preparation of Iridium-Salen Complexes (2-6). 4.3.1.
PreparationofIridium-SalenComplex2.[Ir(cod)(toluene)]+PF6- 14,35
(595 mg, 1.11 mmol) was added to a solution of (aR,R)-salen ligand
15 (965 mg, 1.11 mmol) in toluene (50 mL) under N2. The mixture
9
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Cis-Selective Asymmetric Cyclopropanation of Olefins
A R T I C L E S
was stirred for 10 min at room temperature, then for 10 h at reflux,
and cooled to room temperature. The resultant solution was used
for the next reaction without further purification. An aliquot of the
solution was submitted to ESI-MS analysis, which showed the
formation of a new complex, 19.
4: IR (KBr) 3425.3, 3051.2, 2929.7, 2858.3, 1608.5, 1606,
1577.7, 1444.6, 1427.2, 1325.0, 819.7, 742.5, 700.1 cm-1; HRESI-
MS (m/z) [M+], calcd for [C60H44IrN2O2(C6H5)]+ 1094.3423, found
1094.3422.
4.3.4. Preparation of Iridium-Salen Complex 5. Ir-salen
complex 5 was synthesized with (aR,S)-ligand 17 by the same
procedure as described for the preparation of complex 2.
5: IR (KBr) 3427.3, 3049.2, 2935.5, 2860.2, 1606.6, 1577.7,
1427.2, 1326.9, 759.9, 700.1 cm-1; HRESI-MS (m/z) [M+], calcd
for [C60H44IrN2O2(CH3C6H4)]+ 1108.3580, found 1108.3511.
4.3.5. Preparation of Iridium-Salen Complex 6. Ir-salen
complex 6 was synthesized with (R)-ligand 18 by the same
procedure as described for the preparation of complex 2.
6: IR (KBr) 3080.0, 2952.8, 2906.5, 2866.0, 1581.5, 1517.9,
1461.9, 1419.5, 1385.7, 1357.8, 1325.0, 1255.6, 1168.8, 1149.5,
19: ESI-MS (m/z) [M+], calcd for [C60H46IrN2O2(C8H12)]+
1127.4, found 1127.1.
The solution of 19 was exposed to air for 30 min and filtered
through a pad of Celite. The filtrate was evaporated to give complex
1 (699 mg, 0.60 mmol). 1 was used for the next reaction or as the
catalyst for asymmetric cyclopropanation without further purifica-
tion. The ESI-MS of 1 was measured by using methanol as the
matrix.
1: ESI-MS (m/z) [M+ + (MeOH)2], calcd for [C60H44IrN2O2-
(2MeOH)]+ 1081.4, found 1081.1.
1124.4, 1068.5, 835.1, 781.1 cm-1
.
Anal. Calcd for
Complex 1 (699 mg, 0.60 mmol) was dissolved in toluene (50
mL) under N2 and stirred for 10 min at room temperature. The
resultant solution was heated to reflux, stirred for 1 day at that
temperature, and then cooled to room temperature and evaporated
on a rotary evaporator. The residue was chromatographed on silica
gel (CH2Cl2:THF ) 100:1) to give Ir-salen complex 2 as a red-
brown solid (405 mg, 33%).
2: IR (KBr) 3427.3, 3051.2, 2927.7, 2858.3, 1722.3, 1606.6,
1577.7, 1444.6, 1425.3, 1325.0, 817.8, 744.5, 700.1 cm-1; HRMS-
FAB (m/z) [M+], calcd for [C60H44IrN2O2(CH3C6H4)]+ 1108.3580,
found 1108.3577. Anal. Calcd for C60H44IrN2O2(CH3C6H4)(2H2O):
C, 70.32; H, 4.84; N, 2.45. Found: C, 70.11; H, 4.85; N, 2.54.
4.3.2. Preparation of Iridium-Salen Complex 3. Ir-salen
complex 3 was synthesized with (aS,R)-ligand 16 by the same
procedure as described for the preparation of complex 2.
3: IR (KBr) 3423.4, 3055.0, 2933.5, 2860.2, 1610.5, 1579.6,
1446.5, 1427.2, 1353.9, 1323.1, 1186.1, 1145.6, 1122.5, 844.8,
798.5, 777.3, 750.3 cm-1; HRESI-MS (m/z) [M + H+], calcd for
[C48H37IrN2O2(CH3C6H4)]+ 957.3030, found 957.3029.
4.3.3. Preparation of Iridium-Salen Complex 4. Complex 1
(699 mg, 0.60 mmol) was dissolved in benzene (50 mL) under N2
and stirred for 10 min at room temperature. The resultant solution
was heated to reflux, stirred for 1 day at that temperature, and then
cooled to room temperature and evaporated on a rotary evaporator.
The residue was chromatographed on silica gel (CH2Cl2:THF )
100:1) to give Ir-salen complex 4 as a red-brown solid (405 mg,
33%). A single crystal suitable for X-ray diffraction analysis was
obtained by recrystallization from dichloromethane and methanol.20
C43H59IrN2O2(THF): C, 62.70; H, 7.50; N, 3.11. Found: C, 62.89;
H, 7.36; N, 3.22.
4.4. Asymmetric Cyclopropanation of Conjugated Olefins.
4.4.1. General Procedure for Asymmetric Cyclopropanation
of Conjugated Olefins. The reaction was carried out in a Schlenk
tube (5 mL) under N2. tert-Butyl R-diazoacetate (0.1 mmol) and
1-bromonaphthalene (4.0 µL, 28 µmol) were dissolved in absolute
THF (0.24 mL). The molar ratio of tert-butyl R-diazoacetate and
1
1-bromonaphthalene was determined by H NMR analysis. After
conjugated olefin (1.0 mmol) was added to the solution, the mixture
was cooled to -78 °C and stirred for 10 min. Subsequently,
complex 2 (1.1 mg, 1.0 µmol) was added, and the whole mixture
was stirred for 1 day at -78 °C. The mixture was allowed to warm
to room temperature, passed through a pad of silica gel, and
concentrated on a rotary evaporator. The residue was submitted to
1H NMR analysis to determine the yield and the cis/trans ratio.
The CDCl3 solution was chromatographed on silica gel (hexane:
i-Pr2O 1:0 to 4:1) to yield a mixture of cis- and trans-products,
which were further submitted to preparative thin-layer chromatog-
raphy (TLC) to isolate the cis-product. The enantiomeric excess of
the product was determined by HPLC analysis.
tert-Butyl (1R,2S)-2-phenylcyclopropane-1-carboxylate (Table
1, entry 1): colorless oil, 99% ee, >99% yield, [R]2D7 ) -19.5 (c
0.95, CHCl3) [Lit.6c 98% ee, (1S,2R)-isomer, [R]2D6 ) +18.0 (c
1
0.73, CHCl3)]; H NMR (CDCl3) δ ) 7.34-7.15 (m, 5H), 2.53
(pseudo-q, J ) 9.0 Hz, 1H), 1.98 (ddd, J ) 9.5, 7.8, 5.6 Hz, 1H),
1.64 (ddd, J ) 7.3, 5.6, 5.0 Hz, 1H), 1.24 (ddd, J ) 8.5, 7.8, 5.0
Hz, 1H), 1.13 (s, 9H); 13C NMR (CDCl3) δ ) 169.9, 136.7, 129.3,
127.6, 126.3, 80.0, 27.9, 25.2, 22.9, 10.7; IR (neat) 3100, 3090,
2976, 2932, 1724, 1603, 1499, 1452, 1389, 1367, 1292, 1254, 1211,
1169, 1148, 1080, 1032, 968, 849, 795, 721, 696, 569, 527 cm-1
.
(29) (a) Fritschi, H.; Leutenegger, U.; Pfaltz, A. Angew. Chem. 1986, 98,
1028–1029. (b) Fritschi, H.; Leutenegger, U.; Pfaltz, A. HelV. Chim.
Acta 1988, 71, 1553–1565. (c) Leutenegger, U.; Umbricht, G.; Fahrni,
C.; von Matt, P.; Pfaltz, A. Tetrahedron 1992, 48, 2143–2156. (d)
Nishiyama, H.; Itoh, Y.; Sugawara, Y.; Matsumoto, H.; Aoki, K.; Itoh,
K. Bull. Chem. Soc. Jpn. 1995, 68, 1247–1262. (e) Ikeno, T.; Iwakura,
I.; Yabushita, S.; Yamada, T. Org. Lett. 2002, 4, 517–520. (f) Cornejo,
A.; Fraile, J. M.; Garc´ıa, J. I.; Gil, M. J.; Mart´ınez-Merino, V.;
Mayoral, J. A.; Salvatella, L. Organometallics 2005, 24, 3448.
(30) Based on the fact that cis-olefins are much better substrates for the
epoxidation using planar metalloporphyrin or metallosalen complexes
as catalyst than trans-olefins, a perpendicular approach (side-on
approach) has been proposed for these epoxidations that proceed via
a metal-oxo species isoelectronic to a metal-carbenoid species:
McGarrigle, E. M.; Gilheany, D. G. Chem. ReV. 2005, 105, 1563–
1602.
Anal. Calcd for C14H18O2: C, 77.03; H, 8.31. Found: C, 77.04; H,
8.38.
tert-Butyl (1R*,2S*)-2-(2-methoxyphenyl)cyclopropane-1-car-
boxylate (Table 2, entry 1): colorless oil, 99% ee, 90% yield, [R]2D3
) -121.1 (c 0.30, CHCl3); 1H NMR (CDCl3): δ ) 7.23-7.14 (m,
2H), 6.89 (t, J ) 7.5 Hz, 1H), 6.80 (d, J ) 8.5 Hz, 1H), 3.78 (s,
3H), 2.43 (pseudo-q, J ) 8.5 Hz, 1H), 2.05-1.93 (ddd, J ) 9.3,
7.8, 5.6 Hz, 1H), 1.58-1.50 (m, 1H), 1.30-1.19 (m, 1H), 1.12 (s,
9H); 13C NMR (CDCl3) δ ) 170.4, 158.7, 130.2, 127.5, 125.5,
119.8, 109.4, 79.5, 55.3, 27.9, 22.1, 21.2, 10.9; IR (neat) 3070,
2976, 2934, 1722, 1600, 1585, 1497, 1462, 1440, 1391, 1366, 1288,
1248, 1213, 1146, 1115, 1084, 1030, 752 cm-1. Anal. Calcd for:
C, 72.55; H, 8.12. Found: C, 72.61; H, 8.07.
(31) (a) Kokubo, C.; Katsuki, T. Tetrahedron 1996, 52, 13895–13900. (b)
Miyafuji, A.; Katsuki, T. Tetrahedron 1998, 54, 10339–10348.
(32) Saha, B.; Uchida, T.; Katsuki, T. Tetrahedron: Asymmetry 2003, 14,
823–836.
tert-Butyl (1R*,2S*)-2-(2-chlorophenyl)cyclopropane-1-car-
boxylate (Table 2, entry 2): colorless oil, 98% ee, 90% yield, [R]2D4
) -115.4 (c 0.29, CHCl3) [Lit.36 96% ee, [R]2D6 ) -122.5 (c 0.63,
1
CHCl3)]; H NMR (CDCl3) δ ) 7.35-7.24 (m, 2H), 7.23-7.12
(33) Sasaki, H.; Irie, R.; Hamada, T.; Suzuki, K.; Katsuki, T. Tetrahedron
1994, 50, 11827–11838.
(m, 2H), 2.49 (pseudo-q, J ) 8.5 Hz, 1H), 2.13 (ddd, J ) 9.3, 8.1,
5.6 Hz, 1H), 1.62 (m, 1H), 1.33 (ddd, J ) 8.5, 8.1, 5.1 Hz, 1H),
1.16 (s, 9H); 13C NMR (CDCl3) δ ) 169.9, 135.9, 135.1, 130.9,
(34) Jacobsen, E. N.; Zhang, W.; Muci, A. R.; Ecker, J. R.; Deng, L. J. Am.
Chem. Soc. 1991, 113, 7063–7064.
(35) This iridium complex was prepared according to the reported
procedure: Sievert, A. C.; Muetterties, E. L. Inorg. Chem. 1981, 20,
489–501.
(36) Shitama, H.; Katsuki, T. Chem. Eur. J. 2007, 13, 4849–4858.
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A R T I C L E S
Suematsu et al.
128.6, 127.7, 126.0, 80.0, 27.8, 24.2, 22.6, 11.5; IR (neat) 3075,
2976, 2930, 1722, 1479, 1443, 1391, 1366, 1148, 1036, 791, 536
cm-1. Anal. Calcd for: C, 66.53; H, 6.78. Found: C, 66.72; H,
6.67.
1159, 1119, 1070, 1016, 972, 847, 734, 611 cm-1. Anal. Calcd
for: C, 62.93; H, 5.99. Found: C, 62.89; H, 5.98.
tert-Butyl (1R*,2S*)-2-(4-methylphenyl)cyclopropane-1-car-
boxylate (Table 2, entry 9): colorless oil, 95% ee, >99% yield,
[R]2D4 ) -4.3 (c 0.38, CHCl3) [Lit.36 94% ee, [R]2D6 ) -6.8 (c
tert-Butyl (1R*,2S*)-2-(3-methoxyphenyl)cyclopropane-1-car-
boxylate (Table 2, entry 3): colorless oil, 97% ee, 88% yield, [R]2D4
) -20.9 (c 0.35, CHCl3); 1H NMR (CDCl3) δ ) 7.16 (t, J ) 8.1
Hz, 1H), 6.91-6.79 (m, 2H), 6.74 (dd, J ) 8.1, 2.5 Hz, 1H), 3.78
(s, 3H), 2.51 (pseudo-q, J ) 7.8 Hz, 1H), 1.97 (ddd, J ) 9.3, 7.8,
5.6 Hz, 1H), 1.68-1.58 (m, 1H), 1.23 (ddd, J ) 8.5, 7.8, 5.1 Hz,
1H), 1.16 (s, 9H); 13C NMR (CDCl3) δ ) 169.9, 158.9, 138.4,
128.6, 121.8, 114.9, 112.1, 80.0, 55.2, 27.9, 25.2, 22.9, 10.9; IR
(neat) 3080, 2974, 2934, 2833, 1722, 1600, 1583, 1437, 1389, 1366,
1288, 1255, 1209, 1144, 1045, 980, 853, 691, 581, 517 cm-1. Anal.
Calcd for: C, 72.55; H, 8.12. Found: C, 72.74; H, 8.12.
tert-Butyl (1R*,2S*)-2-(3-chlorophenyl)cyclopropane-1-car-
boxylate (Table 2, entry 4): colorless oil, 98% ee, 91% yield, [R]2D4
1
0.18, CHCl3)]; H NMR (CDCl3) δ ) 7.15 (d, J ) 7.8 Hz, 2H),
7.05 (d, J ) 7.8 Hz, 2H), 2.48 (pseudo-q, J ) 8.4 Hz, 1H), 1.95
(ddd, J ) 9.5, 8.6, 7.8 Hz, 1H), 1.59 (m, 1H), 1.21 (ddd, J ) 8.7,
7.8, 5.1 Hz, 1H), 1.16 (s, 9H); 13C NMR (CDCl3) δ ) 169.9, 135.8,
133.6, 129.2, 128.3, 79.9, 27.9, 24.9, 22.8, 21.2, 10.8; IR (neat)
3007, 2976, 2928, 2868, 1717, 1519, 1479, 1454, 1393, 1367, 1249,
1213, 1148, 1113, 1092, 1038, 972, 829, 769, 744, 547 cm-1. Anal.
Calcd for: C, 77.55; H, 8.68. Found: C, 77.48; H, 8.72.
tert-Butyl (1R*,2S*)-2-(2-naphthyl)cyclopropane-1-carboxy-
late (Table 2, entry 10): colorless crystal, 97% ee, 97% yield, [R]2D4
) +85.3 (c 1.0, CHCl3) [Lit.7b 97% ee, [R]D25 ) +86.4 (c 0.72,
CHCl3); 1H NMR (CDCl3) δ ) 7.85-7.63 (m, 4H), 7.50-7.32
(m, 3H), 2.67 (pseudo-q, J ) 8.5 Hz, 1H), 2.06 (ddd, J ) 9.3, 7.6,
5.6 Hz, 1H), 1.77 (ddd, J ) 7.3, 5.6, 5.1 Hz, 1H), 1.33 (ddd, J )
8.5, 7.6, 5.1 Hz, 1H), 1.06 (s, 9H); 13C NMR (CDCl3) δ ) 169.9,
134.3, 133.0, 132.2, 127.9, 127.8, 127.4, 127.3, 127.1, 125.7, 125.2,
80.1, 27.9, 25.4, 23.1, 11.0; IR (neat) 3051, 2976, 2932, 2868, 2372,
1715, 1629, 1597, 1510, 1437, 1390, 1367, 1250, 1215, 1155, 1092,
1053, 862, 829, 783, 748, 646 cm-1. Anal. Calcd for: C, 80.56; H,
7.51. Found: C, 80.59; H, 7.60.
1
) -9.8 (c 0.37, CHCl3); H NMR (CDCl3) δ ) 7.29-7.23 (m,
1H), 7.22-7.13 (m, 3H), 2.49 (pseudo-q, J ) 8.5 Hz, 1H), 1.99
(ddd, J ) 9.3, 7.8, 5.7 Hz, 1H), 1.61 (m, 1H), 1.26 (ddd, J ) 8.5,
7.5, 5.1 Hz, 1H), 1.18 (s, 9H); 13C NMR (CDCl3) δ ) 169.6, 138.9,
133.4, 129.5, 128.9, 127.6, 126.5, 80.4, 27.9, 24.7, 22.9, 10.9; IR
(neat) 3070, 3001, 2978, 2932, 2872, 1724, 1599, 1568, 1479, 1448,
1391, 1367, 1292, 1213, 1148, 1082, 1036, 999, 866, 849, 833,
745, 532 cm-1. Anal. Calcd for: C, 66.53; H, 6.78. Found: C, 66.38;
H, 6.71.
tert-Butyl (1R*,2S*)-2-methyl-2-phenylcyclopropane-1-car-
boxylate (Table 3, entry 1): colorless oil, 98% ee, 51% yield, [R]2D4
) -40.8 (c 0.07, CHCl3) [Lit.6c 96% ee, [R]D25 ) -42.1 (c 0.43,
CHCl3); 1H NMR (CDCl3) δ ) 7.19-7.16 (m, 5H), 1.80 (dd, J )
7.5, 5.5 Hz, 1H), 1.70 (dd, J ) 5.5, 4.5 Hz, 1H), 1.45 (s, 3H), 1.13
(s, 9H), 1.07 (dd, J ) 7.5, 4.5 Hz, 1H); 13C NMR (CDCl3) δ )
170.2, 141.9, 128.8, 127.9, 126.4, 79.8, 31.8, 29.7, 28.8, 27.9, 19.3;
IR (neat) 3059, 3004, 2974, 2927, 2868, 1726, 1497, 1477, 1446,
1389, 1367, 1290, 1244, 1148, 1085, 844, 700 cm-1. Anal. Calcd
for: C, 77.55; H, 8.68. Found: C, 77.42; H, 8.70.
tert-Butyl (1R*,2S*)-2-(4-methoxyphenyl)cyclopropane-1-car-
boxylate (Table 2, entry 5): colorless oil, 97% ee, >99% yield,
[R]2D4 ) +2.9 (c 0.33, CHCl3) [Lit.6c 96% ee, [R]2D6 ) +3.2 (c
1
0.85, CHCl3)]; H NMR (CDCl3) δ ) 7.19 (d, J ) 9.6 Hz, 2H),
6.80 (d, J ) 9.6 Hz, 2H), 3.78 (s, 3H), 2.46 (pseudo-q, J ) 8.6
Hz, 1H), 1.94 (ddd, J ) 9.3, 7.8, 5.6 Hz, 1H), 1.58 (m, 1H), 1.21
(ddd, J ) 8.6, 7.8, 4.9 Hz, 1H) 1.17 (s, 9H); 13C NMR (CDCl3) δ
) 170.0, 158.0, 130.3, 128.8, 113.1, 79.9, 55.3, 27.9, 24.5, 22.8,
10.9; IR (neat) 3080, 3000, 2976, 2934, 2835, 1711, 1612, 1582,
1516, 1447, 1389, 1367, 1294, 1250, 1211, 1148, 1082, 1036, 970,
833, 557 cm-1. Anal. Calcd for: C, 72.55; H, 8.12. Found: C, 72.51;
H, 8.16.
tert-Butyl (1R*,2S*,3R*)-3-methyl-2-phenylcyclopropane-1-
carboxylate (Table 3, entry 2): colorless oil, 89% ee, 26% yield,
1
[R]2D7 ) +2.8 (c 0.01, CHCl3); H NMR (CDCl3) δ ) 7.36-7.17
tert-Butyl (1R*,2S*)-2-(4-chlorophenyl)cyclopropane-1-car-
boxylate (Table 2, entry 6): colorless oil, 98% ee, >99% yield,
[R]2D4 ) +2.8 (c 0.29, CHCl3) [Lit.36 96% ee, [R]2D6 ) +4.4 (c
(m, 5H), 2.58 (pseudo-t, J ) 9.0 Hz, 1H), 1.97 (pseudo-t, J ) 8.9
Hz, 1H), 1.76-1.62 (m, 1H), 1.33 (s, 9H), 1.30 (d, J ) 1.4 Hz,
3H); 13C NMR (CDCl3) δ ) 170.2, 135.2, 130.5, 127.6, 126.1,
81.6, 28.2, 28.1, 23.9, 19.4, 9.8; IR (neat) 3010, 3000, 2976, 2932,
2883, 1726, 1499, 1479, 1448, 1392, 1367, 1309, 1258, 1144, 979,
847, 698 cm-1; Anal. Calcd for: C, 77.55; H, 8.68. Found: C, 77.43;
H, 8.67.
1
0.18, CHCl3)]; H NMR (CDCl3) δ ) 7.29-7.19 (m, 4H), 2.47
(pseudo-q, J ) 8.5 Hz, 1H), 1.99 (ddd, J ) 9.3, 7.8, 5.6 Hz, 1H),
1.59 (ddd, J ) 7.3, 5.6, 5.1 Hz, 1H), 1.25 (ddd, J ) 8.5, 7.8, 5.1
Hz, 1H), 1.18 (s, 9H); 13C NMR (CDCl3) 169.7, 135.3, 132.1,
130.7, 127.8, 80.3, 27.9, 24.6, 22.9, 10.9; IR (neat) 3080, 3001,
2978, 2932, 2872, 1726, 1599, 1495, 1448, 1391, 1367, 1292, 1254,
tert-Butyl (1S*,1aR*,6aS*)-6H-1a,6a-dihydrocyclopropa[a]in-
dene-1-carboxylate (Table 3, entry 4): colorless oil, 97% ee, 80%
yield, [R]2D7 ) +150.3 (c 1.00, CHCl3); 1H NMR (CDCl3) δ )
7.35-7.28 (m, 1H), 7.15-7.08 (m, 3H), 3.35 (dd, J ) 17.1, 0.5
Hz, 1H), 3.18 (dd, J ) 17.1, 6.8 Hz, 1H), 2.85 (ddd, J ) 8.5, 6.1,
1.5 Hz, 1H), 2.2-2.12 (m, 1H), 1.97 (pseudo-t, J ) 8.5 Hz, 1H),
1.07 (s, 9H); 13C NMR (CDCl3) δ ) 168.7, 143.9, 140.7, 126.1,
125.8, 124.7, 124.2, 80.2, 32.6, 30.8, 27.7, 26.6, 22.7; IR (neat)
3050, 2976, 2909, 2843, 1724, 1587, 1477, 1460, 1393, 1367, 1348,
1323, 1244, 1134, 1026, 1003, 941, 860, 806, 752, 528 cm-1. Anal.
Calcd for: C, 78.23; H, 7.88. Found: C, 78.14; H, 7.79.
tert-Butyl (1R*,1aR*,6aS*)-1a,6a-dihydro-6-oxacyclopro-
pa[a]indene-1-carboxylate (Table 3, entry 5): colorless oil, 99%
ee, 76% yield, [R]2D7 ) +139.6 (c 1.00, CHCl3); 1H NMR (CDCl3)
δ ) 7.36 (d, J ) 7.6 Hz, 1H), 7.16 (t, J ) 8.1 Hz, 1H), 6.92 (td,
J ) 7.6, 1.0 Hz, 1H), 6.85 (d, J ) 8.1 Hz, 1H), 4.97 ( t, J ) 5.3
Hz, 1H), 3.18 (dd, J ) 9.4, 5.3 Hz, 1H), 1.81 (dd, J ) 9.4, 5.6 Hz,
1H), 1.14 (s, 9H); 13C NMR (CDCl3) δ ) 166.0, 161.1, 127.6,
125.3, 124.9, 120.8, 109.5, 80.9, 65.3, 27.8, 27.7, 19.8; IR (neat)
3057, 3003, 2972, 2932, 2870, 1726, 1690, 1614, 1597, 1477, 1460,
1406, 1369, 1346, 1327, 1252, 1227, 1202, 1140, 1074, 999, 976,
939, 862, 802, 787, 691, 599 cm-1. Anal. Calcd for: C, 72.39; H,
6.94. Found: C, 72.38; H, 6.95.
1213, 1160, 1148, 1094, 1034, 1015, 970, 833, 756, 619, 515 cm-1
Anal. Calcd for: C, 66.53; H, 6.78. Found: C, 66.83; H, 6.82.
;
tert-Butyl (1R*,2S*)-2-(4-bromophenyl)cyclopropane-1-car-
boxylate (Table 2, entry 7): colorless oil, 93% ee, 85% yield, [R]2D4
) +9.9 (c 0.52, CHCl3); 1H NMR (CDCl3) δ ) 7.34 (m, 2H),
7.14 (d, J ) 8.3 Hz, 2H), 2.44 (pseudo-q, J ) 8.7 Hz, 1H), 1.99
(ddd, pseudo-q, J ) 9.3, 7.8, 5.6 Hz, 1H), 1.59 (m, 1H), 1.25 (m,
1H), 1.18 (s, 9H); 13C NMR (CDCl3) δ ) 169.6, 135.8, 131.0,
130.7, 120.2, 80.3, 27.9, 24.6, 22.9, 10.9; IR (neat) 3003, 2979,
2968, 2933, 1709, 1491, 1447, 1393, 1367, 1252, 1217, 1148, 1167,
1105, 1074, 1009, 833, 773, 746, 522 cm-1. Anal. Calcd for: C,
56.58; H, 5.77. Found: C, 56.74; H, 5.78.
tert-Butyl (1R*,2S*)-2-[4-(trifluoromethyl)phenyl]cyclopropane-
1-carboxylate37 (Table 2, entry 8): colorless oil, 97% ee, 73% yield,
[R]2D4 ) -14.5 (c 0.11, CHCl3); 1H NMR (CDCl3) δ ) 7.52 (d, J
) 8.2 Hz, 2H), 7.39 (d, J ) 8.2 Hz, 2H), 2.55 (pseudo-q, J ) 8.6
Hz, 1H), 2.05 (ddd, J ) 9.3, 7.8, 5.6 Hz, 1H) 1.67 (m, 1H), 1.31
(m, 1H), 1.15 (s, 9H); 13C NMR (CDCl3) δ ) 169.3, 140.7, 129.4,
124.4, 124.3, 80.2, 27.7, 24.6, 22.9, 10.8; IR (neat) 3050, 3003,
2986, 2937, 1711, 1618, 1479, 1452, 1396, 1369, 1327, 1252, 1223,
(37) Hu, W.; Timmons, D. J.; Doyle, M. P. Org. Lett. 2002, 4, 901–904.
9
10334 J. AM. CHEM. SOC. VOL. 130, NO. 31, 2008

Cis-Selective Asymmetric Cyclopropanation of Olefins
A R T I C L E S
tert-Butyl (1R*,1aR*,6aR*)-1a-methyl-6a-hydro-6-oxacyclo-
propa[a]indene-1-carboxylate (Table 3, entry 6): colorless oil,
98% ee, 42% yield, [R]2D4 ) +84.1 (c 0.21, CHCl3); 1H NMR
(CDCl3) 7.28 (dd, J ) 7.3, 1.5 Hz, 1H), 7.16 (td, J ) 7.8, 1.5 Hz,
1H), 6.95 (td, J ) 7.3, 1.0 Hz, 1H), 6.84 (d, J ) 8.0 Hz, 1H), 4.71
(d, J ) 5.7 Hz, 1H), 1.74 (d, J ) 5.7 Hz, 1H), 1.65 (s, 3H), 1.12
(s, 1H); 13C NMR (CDCl3) δ ) 166.2, 160.5, 128.8, 127.5, 123.7,
120.7, 109.5, 80.7, 70.5, 34.5, 27.8, 25.9, 18.2; IR (neat) 3060,
3040, 3004, 2972, 2932, 2870, 1720, 1614, 1595, 1479, 1448, 1414,
1392, 1366, 1339, 1277, 1248, 1190, 1146, 1092, 1061, 1016, 974,
908, 870, 853, 825, 790, 752, 692, 652 cm-1. Anal. Calcd for: C,
73.15; H, 7.37. Found: C, 73.03; H, 7.38.
Ethyl (1R*,2S*)-2-phenylethynylcyclopropane-1-carboxylate
(Table 4, entry 1): colorless oil, 95% ee, 84% yield, [R]2D7 ) +99.5
(c 1.00, CHCl3); 1H NMR (CDCl3) δ ) 7.48-7.35 (m, 2H),
7.32-7.22 (m, 3H), 4.27-4.16 (m, 2H), 2.07-1.97 (m, 2H),
1.61-1.51 (m, 1H), 1.35-1.23 (m, 1H), 1.27 (t, J ) 7.2 Hz, 3H);
13C NMR (CDCl3) δ ) 169.9, 131.6, 128.0, 127.6, 123.4, 87.2,
79.5, 60.8, 21.9, 14.7, 14.6, 10.1; IR (neat) 3050, 3010, 2980, 2973,
1730, 1597, 1491, 1443, 1402, 1381, 1354, 1279, 1186, 1113, 1026,
758, 692 cm-1; HRESI-MS (m/z) [M + Na+], calcd for
[C14H14O2Na]+ 237.0886, found 237.0873.
cis/trans ratio was calculated on the basis of the respective isolated
yields of the cis and trans isomers. The enantiomeric excess of the
cis-product was determined by HPLC analysis.
tert-Butyl (1R*,2S*)-2-(2-phenylethyl)cyclopropane-1-carbox-
ylate (Table 5, entry 2): colorless oil, 98% ee, 90% yield, [R]D26
1
) -14.6 (c 0.57, CHCl3); H NMR (CDCl3) δ ) 7.33-7.12 (m,
5H), 2.64 (dd, J ) 7.8, 7.8 Hz, 2H), 1.96-1.74 (m, 2H), 1.69-1.38
(m, 1H), 1.47 (s, 9H), 1.35-1.11 (m, 1H), 0.99-0.81 (m, 2H);
13C NMR (CDCl3) δ ) 171.9, 141.9, 128.3, 128.1, 125.6, 80.1,
36.1, 29.1, 28.4, 21.3, 19.4, 13.2; IR (neat) 3061, 3026, 3003, 2976,
2928, 2860, 1720, 1603, 1497, 1481, 1391, 1367, 1252, 1209, 1151,
872, 851, 831, 746, 698 cm-1; HRESI-MS (m/z) [M + Na+], calcd
for [C16H22O2Na]+ 269.1512, found 269.1500.
Ethyl (1R*,2S*)-2-(2-phenylethyl)cyclopropane-1-carboxylate
(Table 5, entry 3): colorless oil, 96% ee, 93% yield, [R]2D5 ) -47.5
(c 0.49, CHCl3); 1H NMR (CDCl3) δ ) 7.30-7.23 (m, 2H),
7.22-7.14 (m, 3H), 4.13 (q, J ) 7.1 Hz, 2H), 2.68-2.57 (m, 2H),
1.96-1.76 (m, 2H), 1.72-1.65 (m, 1H), 1.30-1.18 (m, 1H), 1.27
(t, J ) 7.1 Hz, 3H), 1.05-0.89 (m, 2H); 13C NMR (CDCl3) δ )
172.7, 141.8, 128.4, 128.1, 125.6, 60.3, 35.9, 29.0, 21.5, 18.4, 14.5,
13.6; IR (neat) 3061, 3024, 2979, 2926, 2858, 1724, 1603, 1585,
1549, 1495, 1450, 1402, 1381, 1354, 1273, 1173, 1130, 1092, 1034,
1007, 962, 827, 748, 700, 577, 511 cm-1; HRESI-MS (m/z) [M +
Na+], calcd for [C14H18O2Na]+ 241.1199, found 241.1165.
Ethyl (1R,2S)-cis-2-hexylcyclopropane-1-carboxylate (Table
5, entry 4): colorless oil, 98% ee, 62% yield, [R]2D6 ) -41.0 (c
1.00, CHCl3) [Lit.10 94% ee, (1S,2R)-isomer, [R]2D0 ) +41.0 (c
tert-Butyl (1R*,2S*)-2-phenylethynylcyclopropane-1-carboxy-
late (Table 4, entry 2): colorless oil, 93% ee, 90% yield, [R]D24
)
1
+105.8 (c 0.63, CHCl3); H NMR (CDCl3) δ ) 7.40-7.34 (m,
2H), 7.31-7.22 (m, 3H), 1.98-1.90 (m, 2H), 1.53-1.27 (m, 1H),
1.39 (s, 9H), 1.27-1.17 (m, 1H); 13C NMR (CDCl3) δ ) 169.0,
131.5, 127.9, 127.5, 123.4, 87.5, 80.8, 79.2, 28.3, 22.8, 14.2, 9.8;
IR (neat) 3092, 3002, 2976, 2929, 1726, 1661, 1491, 1445, 1389,
1367, 1292, 1256, 1213, 1151, 1115, 756, 692 cm-1. Anal. Calcd
for: C, 79.31; H, 7.49. Found: C, 79.28; H, 7.50.
1
0.75, CHCl3)]; H NMR (CDCl3) δ ) 4.13 (q, J ) 7.1 Hz, 2H),
1.66 (ddd, J ) 8.9, 7.9, 5.5 Hz, 1H), 1.60-1.41 (m, 1H), 1.40-1.07
(m, 10H), 1.26 (t, J ) 7.1 Hz, 3H), 1.50-0.88 (m, 2H), 0.87 (t, J
) 7.3 Hz, 3H); 13C NMR (CDCl3) δ )172.8, 60.2, 31.9, 29.7,
29.1, 27.2, 22.8, 22.0, 18.4, 14.5, 14.2, 13.5; IR (neat) 2957, 2924,
2856, 1728, 1464, 1448, 1402, 1381, 1354, 1269, 1177, 1097, 1043,
829 cm-1; HRESI-MS (m/z) [M + Na+], calcd for [C12H22O2Na]+
221.1512, found 221.1506.
Ethyl (1R*,2R*)-2-styrylcyclopropane-1-carboxylate38 (Table
4, entry 3): colorless oil, 94% ee, 99% yield, [R]2D6 ) +17.9 (c
0.16, CHCl3); 1H NMR (CDCl3) δ ) 7.38-7.25 (m, 4H),
7.22-7.16 (m, 1H), 6.58 (d, J ) 15.9 Hz, 1H), 6.23 (dd, J ) 15.9,
9.2 Hz, 1H), 4.24-4.07 (m, 2H), 2.15-1.95 (m, 2H), 1.45-1.22
(m, 2H), 1.26 (t, J ) 7.1 Hz, 3H); 13C NMR (CDCl3) δ ) 171.7,
137.2, 131.2, 128.3, 127.4, 126.9, 125.8, 60.6, 24.7, 21.6, 14.9,
14.5; IR (neat) 3024, 2980, 2959, 2928, 1724, 1599, 1583, 1446,
1404, 1381, 1354, 1184, 1150, 966, 766, 741, 694 cm-1; HRESI-
MS (m/z) [M + K+], calcd for [C14H16O2K]+ 255.0782, found
255.0944.
Ethyl (1R*,2S*)-2-[4-(benzyloxy)butyl]cyclopropane-1-car-
boxylate (Table 5, entry 5): colorless oil, 97% ee, 95% yield, [R]2D6
1
) -28.1 (c 1.06, CHCl3); H NMR (CDCl3) δ ) 7.37-7.23 (m,
5H), 4.49 (s, 2H), 4.12 (q, J ) 7.0 Hz, 2H), 3.46 (t, J ) 6.6 Hz,
2H), 1.70-1.38 (m, 7H), 1.32-1.16 (m, 1H), 1.24 (t, J ) 7.0 Hz,
3H), 1.05-0.86 (m, 2H); 13C NMR (CDCl3) δ ) 172.7, 138.5,
128.2, 127.4, 127.3, 72.9, 70.4, 60.2, 29.6, 26.9, 26.4, 21.9, 18.3,
14.5, 13.5; IR (neat) 3020, 2980, 2932, 2858, 1722, 1448, 1402,
1381, 1356, 1177, 1099, 1047, 1028, 831, 737, 698 cm-1; HRESI-
MS (m/z) [M + Na+], calcd for [C17H24O3Na]+ 299.1618, found
299.1676.
tert-Butyl (1R*,2R*)-2-styrylcyclopropane-1-carboxylate (Table
4, entry 4): colorless oil, 97% ee, >99% yield, [R]2D6 ) +48.9 (c
0.08, CHCl3); 1H NMR (CDCl3) δ ) 7.42-7.24 (m, 4H),
7.21-7.14 (m, 1H), 6.57 (d, J ) 15.7 Hz, 1H), 6.21 (dd, J ) 15.7,
9.2 Hz, 1H), 2.08-1.98 (m, 1H), 1.96-1.89 (m, 1H), 1.44 (s, 9H),
1.35-1.18 (m, 2H); 13C NMR (CDCl3) δ )170.9, 137.4, 130.9,
128.3, 127.6, 126.8, 125.7, 80.6, 28.4, 24.3, 22.8, 14.3; IR (neat)
3100, 2978, 2890, 1722, 1661, 1585, 1481, 1389, 1367, 1211, 1170,
1142, 966, 818, 748, 692 cm-1; HRESI-MS (m/z) [M + Na+],
calcd for [C16H20O2Na]+ 267.1311, found 267.1356.
4.4.2. General Procedure for Asymmetric Cyclopropanation of
Nonconjugated Olefins. Reaction was carried out in a Schlenk tube
(5 mL) under N2. Nonconjugated olefin (2.0 mmol) was dissolved
in absolute THF (0.48 mL). The mixture was cooled to -78 °C
and stirred for 10 min. Subsequently, complex 2 (2.2 mg, 2.0 µmol)
was added. After an 8.6 M THF solution of R-diazoacetate (0.2
mmol) was added over 24 h, the reaction mixture was stirred for 2
days at -78 °C. The mixture was directly chromatographed on a
short silica gel (hexane/i-Pr2O ) 1/0 to 30/1). The fractions
including the cis- and trans-products were collected and concen-
trated on a rotary evaporator to yield a mixture of the products.
Unreacted alkene was also recovered upon chromatography. The
cis- and trans-product mixture was chromatographed again on silica
gel (hexane/i-Pr2O ) 1/0 to 30/1) to obtain the cis-product. The
4-[(1S*,2R*)-2-(Ethoxycarbonyl)cyclopropyl]butyl benzoate
(Table 5, entry 6): colorless oil, 95% ee, 88% yield, [R]2D7 ) -29.6
1
(c 1.02, CHCl3); H NMR (CDCl3) δ ) 8.10-7.99 (m, 2H), 7.55
(t, J ) 7.4 Hz, 1H), 7.43 (dd, J ) 7.4, 7.3 Hz, 2H), 4.31 (t, J ) 6.7
Hz, 2H), 4.11 (q, J ) 7.2 Hz, 2H), 1.83-1.73 (m, 2H), 1.73-1.35
(m, 5H), 1.30-1.17 (m, 1H), 1.24 (t, J ) 7.2 Hz, 3H), 1.06-0.90
(m, 2H); 13C NMR (CDCl3) δ ) 172.7, 166.4, 132.6, 130.4, 129.4,
128.1, 65.0, 60.3, 28.6, 26.8, 26.3, 21.8, 18.3, 14.5, 13.5; IR (neat)
3050, 2979, 2953, 2934, 1722, 1600, 1583, 1448, 1404, 1381, 1313,
1275, 1177, 1115, 1026, 714 cm-1; HRESI-MS (m/z) [M + Na+],
calcd for [C17H22O4Na]+ 313.1410, found 313.1454.
4-[(1S*,2R*)-2-(tert-Butoxycarbonyl)cyclopropyl]butyl ben-
zoate (Table 5, entry 7): colorless oil, 99% ee, 90% yield, [R]D24
) -30.7 (c 0.25, CHCl3); 1H NMR (CDCl3) δ ) 8.04 (d, J ) 8.3
Hz, 2H), 7.55 (t, J ) 7.7 Hz, 1H), 7.43 (t, J ) 7.7 Hz, 2H), 4.31
(t, J ) 6.7 Hz, 2H), 1.85-1.73 (m, 2H), 1.69-1.38 (m, 5H), 1.44
(s, 9H), 1.29-1.13 (m, 1H), 0.98-0.91 (m, 1H), 0.90-0.81 (m,
1H); 13C NMR (CDCl3) δ ) 171.9, 166.4, 132.6, 130.4, 129.4,
128.2, 80.0, 65.1, 28.7, 28.3, 26.9, 26.4, 21.5, 19.4, 13.1; IR (neat)
3080, 2976, 2929, 2860, 1720, 1601, 1585, 1450, 1391, 1367, 1275,
1211, 1148, 1115, 1070, 1028, 851, 833, 714 cm-1; HRESI-MS
(m/z) [M + Na+], calcd for [C19H26O4Na]+ 341.1723, found
341.1733.
(38) Doyle, M. P.; Dorow, R. L.; Buhro, W. E.; Griffin, J. H.; Tamblyn,
W. H.; Trudell, M. L. Organometallics 1984, 3, 44–52.
9
J. AM. CHEM. SOC. VOL. 130, NO. 31, 2008 10335

A R T I C L E S
Suematsu et al.
(1S*,2R*)-2-(Ethoxycarbonyl)cyclopropyl benzoate (Table 5,
entry 8): colorless oil, 92% ee, 83% yield, [R]2D5 ) -4.2 (c 0.46,
3H), 1.02-0.95 (m, 1H), 0.94-0.80 (m, 1H), 0.88 (t, J ) 6.3 Hz,
3H); 13C NMR (CDCl3) δ ) 172.0, 130.5, 129.8, 60.2, 32.7, 32.3,
31.9, 29.8, 29.7, 28.9, 26.7, 22.8, 21.9, 18.4, 14.5, 14.2, 13.5; IR
(neat) 2955, 2925, 2855, 1728, 1462, 1447, 1402, 1381, 1354, 1269,
1165, 1096, 1043, 966, 860, 829 cm-1; HRESI-MS (m/z) [M +
Na+], calcd for [C17H30O2Na]+ 289.2138, found 289.2135.
1
CHCl3); H NMR (CDCl3) δ ) 8.00 (ddd, J ) 8.0, 0.7, 0.7 Hz,
2H), 7.55 (t, J ) 7.6 Hz, 1H), 7.42 (dd, J ) 8.0, 7.6 Hz, 2H), 4.52
(m, 1H), 4.12 (q, J ) 7.3 Hz, 2H), 2.11-2.09 (m, 1H), 1.78-1.69
(m, 1H), 1.41-1.27 (m, 1H), 1.19 (t, J ) 7.3 Hz, 3H); 13C NMR
(CDCl3) δ ) 169.0, 166.7, 133.0, 129.5, 129.4, 128.2, 60.9, 52.9,
20.2, 14.3, 12.4; IR (neat) 3063, 2982, 2937, 2905, 1730, 1601,
1583, 1450, 1400, 1381, 1273, 1209, 1178, 1146, 1097, 1069, 1026,
964, 712 cm-1; HRESI-MS (m/z) [M + Na+], calcd for
[C13H14O4Na]+ 257.0784, found 257.0790.
Ethyl (1R*,2S*)-2-[(Z)-undec-4-enyl]cyclopropane-1-carbox-
ylate 9b (Scheme 1): colorless oil, 98% ee, 88% yield, [R]D26
)
-27.2 (c 0.73, CHCl3); 1H NMR (CDCl3) δ ) 5.42-5.25 (m, 2H),
4.13 (q, J ) 7.1 Hz, 2H), 2.09-1.91 (m, 4H), 1.75-1.10 (m, 14H),
1.26 (t, J ) 7.1 Hz, 3H), 1.08-0.75 (m, 2H), 0.88 (t, J ) 6.6 Hz,
3H); 13C NMR (CDCl3) δ ) 172.7, 130.0, 129.4, 60.2, 31.9, 29.9,
29.8, 29.1, 27.4, 27.1, 26.9, 22.8, 21.9, 18.4, 14.5, 14.2, 13.5; IR
(neat) 3001, 2955, 2926, 2855, 1728, 1463, 1448, 1402, 1381, 1354,
1165, 1096, 1043, 829 cm-1; HRESI-MS (m/z) [M + Na+], calcd
for [C17H30O2Na]+ 289.2138, found 289.2151.
(1S*,2R*)-2-(tert-Butoxycarbonyl)cyclopropyl benzoate (Table
5, entry 9): colorless oil, 94% ee, 87% yield, [R]2D5 ) -7.6 (c
1
0.88, CHCl3); H NMR (CDCl3) δ ) 8.0 (dd, J ) 8.2, 1.0 Hz,
2H), 7.55 (tt, J ) 7.3, 1.5 Hz, 1H), 7.42 (tt, J ) 8.1, 1.5 Hz, 2H),
4.45 (ddd, J ) 7.1, 6.6, 4.6 Hz, 1H), 2.0 (ddd, J ) 8.8, 7.1, 7.0
Hz, 1H), 1.68 (ddd, J ) 7.1, 7.0, 4.6 Hz, 1H), 1.38 (s, 9H), 1.29
(J ) 8.8, 7.1, 6.6 Hz, 1H); 13C NMR (CDCl3) δ ) 167.9, 166.8,
132.9, 129.5, 129.4, 128.2, 80.9, 52.9, 28.1, 21.4, 11.8; IR (neat)
3050, 2978, 2934, 2872, 1730, 1601, 1583, 1452, 1435, 1273, 1217,
1151, 1099, 1069, 1028, 1007, 964, 839, 712, 574 cm-1. Anal.
Calcd for: C, 68.68; H, 6.92. Found: C, 68.60; H, 6.90.
4.4.3. Synthesis of Methyl 8-[(1R,2S)-2-hexylcyclopropyl]-
octanoate 14. [(1R,2S)-2-Hexylcyclopropyl]methanol 11 (Scheme
1
2): colorless oil, 99% yield, [R]2D6 ) +22.73 (c 1.00, CHCl3); H
NMR (CDCl3) δ ) 3.68-3.52 (m, 2H), 1.76-1.63 (m, 1H),
1.50-1.18 (m, 9H), 1.15-1.01 (m, 1H), 0.93-0.82 (m, 1H), 0.89
(t, J ) 6.7 Hz, 3H), 0.76-0.68 (m, 1H), -0.04 (pseudo-q, J ) 4.9
Hz, 1H); 13C NMR (CDCl3) δ ) 63.4, 31.9, 30.2, 29.3, 28.7, 22.8,
18.3, 16.3, 14.2, 9.6; IR (neat) 3352, 2991, 2955, 2924, 2855, 1464,
1448, 1425, 1409, 1379, 1032 cm-1; HRESI-MS (m/z) [M + K+
+ H2O], calcd for [C10H20OK(H2O)]+ 213.1251, found 213.1441.
Ethyl (1R*,2R*)-2-cyclohexylcyclopropane-1-carboxylate (Table
5, entry 11): colorless oil, 98% ee, 46% yield, [R]2D7 ) -41.5 (c
1
0.29, CHCl3); H NMR (CDCl3) δ ) 4.13 (q, J ) 7.1 Hz, 2H),
1.84-1.47 (m, 6H), 1.33-0.88 (m, 9H), 1.26 (t, J ) 7.1 Hz, 3H);
13C NMR (CDCl3) δ ) 172.9, 60.2, 35.9, 33.5, 33.3, 28.7, 26.6,
26.3, 26.1, 18.1, 14.5, 12.6; IR (neat) 2982, 2924, 2849, 1726, 1583,
1447, 1404, 1381, 1180, 1157, 831 cm-1; HRESI-MS (m/z) [M +
Na+], calcd for [C12H20O2Na]+ 219.1356, found 219.1351.
Ethyl (1R*,2S*)-2-methyl-2-(2-phenylethyl)cyclopropane-1-
carboxylate (Table 5, entry 12): colorless oil, 83% ee, 87% yield,
[R]2D7 ) -26.0 (c 1.00, CHCl3); 1H NMR (CDCl3) δ ) 7.30-7.21
(m, 2H), 7.20-7.12 (m, 3H), 4.12 (dq, J ) 7.2, 0.7 Hz, 2H),
2.76-2.64 (m, 1H), 2.57-2.47 (m, 1H), 1.94-1.78 (m, 2H),
1.59-1.49 (m, 1H), 1.28 (t, J ) 7.2 Hz, 3H), 1.22 (s, 3H), 1.12
(pseudo-t, J ) 4.9 Hz, 1H), 0.91-0.81 (m, 1H); 13C NMR (CDCl3)
δ ) 172.4, 142.1, 128.2, 128.1, 125.5, 60.3, 34.7, 33.6, 27.1, 26.9,
24.2, 22.1, 14.5; IR (neat) 3080, 3060, 3026, 2959, 2930, 2862,
1722, 1495, 1454, 1406, 1381, 1315, 1267, 1248, 1175, 1099, 1061,
1028, 829, 746, 700 cm-1; HRESI-MS (m/z) [M + Na+], calcd
for [C15H20O2Na]+ 255.1356, found 255.1321.
5-[{(1R,2S)-(2-Hexylcyclopropyl)}methanesulfonyl]-1-phen-
yl -1H-tetrazole 12 (Scheme 2): colorless oil, 90% yield, [R]D26
)
1
-36.90 (c 0.53, CHCl3); H NMR (CDCl3) δ ) 7.72-7.57 (m,
5H), 3.96 (dd, J ) 5.6, 14.6 Hz, 1H), 3.56 (dd, J ) 9.2, 14.6 Hz,
1H), 1.51-1.09 (m, 11H), 1.06-0.95 (m, 1H), 0.94-0.76 (m, 1H),
0.89 (t, J ) 6.5 Hz, 3H), 0.24 (pseudo-q, J ) 5.4 Hz, 1H); 13C
NMR (CDCl3) δ ) 153.6, 132.9, 131.3, 129.5, 125.1, 57.2, 31.9,
29.7, 29.2, 22.8, 16.0, 14.2, 11.5, 8.2; IR (neat) 3508, 3072, 2999,
2955, 2926, 2855, 1661, 1641, 1628, 1597, 1497, 1464, 1342, 1151,
764, 691, 627cm-1; HRESI-MS (m/z) [M + Na+], calcd for
[C17H24N4O2SNa]+ 375.1512, found 375.1505.
Methyl 8-[(1R,2S)-2-hexylcyclopropyl]oct-7-enoate 13 (E/Z )
2.3:1) (Scheme 2): colorless oil, 73% yield, [R]2D6 ) +31.6 (c 0.18,
1
CHCl3); H NMR (CDCl3) δ ) 5.54-5.44 (m, 0.7H), 5.42-5.33
(m, 0.3H), 5.22-5.13 (dd, J ) 15.1, 8.3 Hz, 0.7H), 5.08-4.98 (m,
0.3H), 3.68 (s, 3H), 2.34-2.25 (m, 2H), 2.14 (q, J ) 6.8 Hz, 0.6H),
2.00 (q, J ) 6.6 Hz, 1.4H), 1.71-1.49 (m, 2H), 1.46-1.14 (m,
15H), 0.93-0.74 (m, 2.3H), 0.88 (t, J ) 7.5 Hz, 3H), 0.14-0.04
(m, 0.7H); IR (neat) 3090, 2991, 2953, 2924, 2855, 1742, 1661,
1641, 1627, 1607, 1583, 1481, 1464, 1443, 1381, 1169; HRESI-
MS (m/z) [M + Na+], calcd for [C18H32O2Na]+ 303.2295, found
303.2280.
Ethyl (1R*,2S*)-2-hexyl-2-methylcyclopropane-1-carboxylate
(Table 5, entry 13): colorless oil, 99% ee, 65% yield, [R]D27
)
1
-66.1 (c 0.08, CHCl3); H NMR (CDCl3) δ ) 4.12 (q, J ) 6.9
Hz, 2H), 1.61-1.34 (m, 4H), 1.33-1.16 (m, 10H), 1.26 (t, J )
7.1 Hz, 3H), 1.15-1.04 (m, 1H), 0.93-0.78 (m, 1H), 0.87 (t, J )
6.9 Hz, 3H); 13C NMR (CDCl3) δ ) 172.6, 60.2, 32.4, 32.0, 29.5,
27.3, 27.1, 26.9, 24.2, 22.8, 21.9, 14.5, 14.2; IR (neat) 2957, 2926,
Methyl 8-[(1R,2S)-2-hexylcyclopropyl]octanoate17g,18a 14
(Scheme 2): colorless oil, 88% yield, [R]2D6 ) -0.09 (c 1.00, CHCl3)
[Lit.11 100% ee, (1R,2S)-isomer, [R]D20 ) -0.10 (c 5.4, CHCl3)];
1H NMR (CDCl3) δ ) 3.67 (s, 3H), 2.30 (t, J ) 7.5 Hz, 2H),
1.62-1.09 (m, 22H), 0.89 (t, J ) 7.0 Hz, 3H), 0.72-0.57 (m, 2H),
0.56 (m, 1H), -0.28 to -0.34 (m, 1H); 13C NMR (CDCl3) δ )
174.4, 51.5, 34.1, 32.0, 30.2, 30.1, 29.5, 29.4, 29.3, 29.2, 28.7, 28.6,
25.0, 22.7, 15.8, 15.7, 14.2, 10.9. Anal. Calcd for C18H34O2: C,
76.54; H, 12.13. Found: C, 76.44; H, 12.21.
4.5. Conversion of Some Cyclopropanation Products
[Products in Table 5 (entries 4, 11, and 13) and Scheme 1]
into the Corresponding Dinitrobenzoates To Be Used for
HPLC Analysis. Cyclopropanecarboxylate (0.1 mmol) was dis-
solved in THF (0.40 mL). The solution was cooled to 0 °C and
stirred for 10 min. LiAlH4 (0.2 mmol) was added to the solution
and stirred for 10 min at 0 °C. The mixture was allowed to warm
to room temperature, stirred for another 2 h, and cooled to 0 °C
again. A saturated aqueous KF solution (0.40 mL) and MgSO4 (40
mg) were added, and the resultant suspension was filtered through
a pad of Celite and concentrated on a rotary evaporator. The residue
2856, 1726, 1464, 1447, 1406, 1381, 1306, 1167, 1097, 833 cm-1
;
HRESI-MS (m/z) [M + Na+], calcd for [C13H24O2Na]+ 235.1669,
found 235.1662.
Ethyl (1R*,2S*)-2-(6-phenylhex-3-enyl)cyclopropane-1-car-
boxylate (E/Z ) 9/1) 7b (Scheme 1): colorless oil, 96% ee, 74%
yield, [R]2D7 ) -48.2 (c 0.73, CHCl3); 1H NMR (CDCl3) δ )
7.31-7.09 (m, 5H), 5.47-5.33 (m, 2H), 4.17-4.02 (m, 2H), 2.66
(pseudo-t, J ) 7.3 Hz, 2H), 2.40-2.25 (m, 2H), 2.10-1.94 (m,
2H), 1.70-1.43 (m, 3H), 1.29-1.11(m, 1H), 1.23 (t, J ) 7.3 Hz,
3H), 1.02-0.85 (m, 2H); 13C NMR (CDCl3) (for E-isomer) δ )
172.7, 141.9, 129.6, 129.1, 128.3, 128.1, 125.6, 60.2, 36.1, 29.2,
27.3, 27.1, 21.6, 18.4, 14.5, 13.5; IR (neat) 3024, 3003, 2979, 2926,
2856, 1724, 1628, 1603, 1583, 1448, 1404, 1381, 1354, 1177, 1132,
1096, 831, 746, 719, 700 cm-1; HRESI-MS (m/z) [M + Na+],
calcd for [C18H24O2Na]+ 295.1669, found 295.1662.
Ethyl (1R*,2S*)-2-[(E)-undec-4-enyl]cyclopropane-1-carbox-
ylate 8b (Scheme 1): colorless oil, 96% ee, 90% yield, [R]D26
-27.49 (c 0.38, CHCl3); H NMR (CDCl3) δ ) 5.44-5.32 (m,
2H), 4.12 (q, J ) 7.3 Hz, 2H), 2.03-1.89 (m, 4H), 1.66 (ddd, J )
8.8, 7.8, 5.3 Hz, 1H), 1.59-1.15 (m, 13H), 1.26 (t, J ) 7.3 Hz,
)
1
9
10336 J. AM. CHEM. SOC. VOL. 130, NO. 31, 2008

Cis-Selective Asymmetric Cyclopropanation of Olefins
A R T I C L E S
was submitted to preparative TLC (hexane/AcOEt ) 4/1) to yield
the corresponding alcohol.
the Global COE Program, “Science for Future Molecular Systems”,
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
The resulting alcohol (0.05 mmol) was dissolved in CH2Cl2 (0.20
mL). Triethylamine (0.15 mmol) and 4-(N,N-dimethylamino)pyri-
dine (0.5 µmol) were added to this solution. The mixture was stirred
for 10 min at room temperature, and 3,5-dinitrobenzoyl chloride
(0.10 mmol) was added. The whole mixture was stirred for 2 h
and concentrated on a rotary evaporator. The residue was submitted
to preparative TLC (hexane/AcOEt ) 4/1) to yield the correspond-
ing 3,5-dinitrobenzoate.
Supporting Information Available: X-ray crystallographic
data in CIF format for complex 4; description of the analyses
and analytical data; complete ref 23. This material is available
free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. We are grateful for a Grant-in-Aid for
Scientific Research (Specially Promoted Research 18002011) and
JA802561T
9
J. AM. CHEM. SOC. VOL. 130, NO. 31, 2008 10337