Rhodium(II)-catalyzed inter- and intramolecular cyclopropanations with diazo compounds and phenyliodonium ylides: Synthesis and chiral analysis

Article abstract of DOI:10.1002/hlca.200590003

Different classes of cyclopropanes derived from Meldrum's acid (=2,2-dimethyl-1,3-dioxane-4,6-dione; 4), dimethyl malonate (5), 2-diazo-3-(silyloxy)but-3-enoate 16, 2-diazo-3,3,3-trifluoropropanoate 18, diazo(triethylsilyl)acetate 24a, and diazo(dimethylphenylsilyl)acetate 24b were prepared via dirhodium(II)-catalyzed intermolecular cyclopropanation of a set of olefins 3 (Schemes 1 and 4-6). The reactions proceeded with either diazo-free phenyliodonium ylides or diazo compounds affording the desired cyclopropane derivatives in either racemic or enantiomer-enriched forms. The intramolecular cyclopropanation, of allyl diazo(triethylsilyl)acetates 28, 30, and 33 were carried out in the presence of the chiral dirhodium(II) catalyst [Rh ₂{(S)-nttl)₄}] (9) in toluene to afford the corresponding cyclopropane derivatives 29, 31 and 34 with up to 37% ee (Scheme 7). An efficient enantioselective chiral separation method based on enantioselective GC and HPLC was developed. The method provides information about the chemical yields of the cyclopropane derivatives, enantioselectivity, substrate specifity, and catalytic activity of the chiral catalysts used in the inter- and intramolecular cyclopropanation reactions and avoids time-consuming workup procedures.

Full text of DOI:10.1002/hlca.200590003

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Helvetica Chimica Acta ± Vol. 88 (2005)
Rhodium(II)-Catalyzed Inter- and Intramolecular Cyclopropanations
with Diazo Compounds and Phenyliodonium Ylides: Synthesis and Chiral
Analysis
by Ashraf Ghanem*a)1), Fabienne Lacrampeb), and Volker Schurigc)
a) Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, CH-1211 Geneva 4
(e-mail: ashraf.ghanem@chiorg.unige.ch)
b) Natural Product Discovery, MtGravatt Research Park, Brisbane, Queensland 4111, Australia
c) Institute of Organic Chemistry, University of Tübingen, Auf der Morgenstelle 18, D-72076 Tübingen
Dedicated to Professor Paul Müller on the occasion of his 65th birthday and retirement from the University of
Geneva
Different classes of cyclopropanes derived from Meldrumꢀs acid (ˆ2,2-dimethyl-1,3-dioxane-4,6-dione; 4),
dimethyl malonate (5), 2-diazo-3-(silyloxy)but-3-enoate 16, 2-diazo-3,3,3-trifluoropropanoate 18, diazo(tri-
ethylsilyl)acetate 24a, and diazo(dimethylphenylsilyl)acetate 24b were prepared via dirhodium(II)-catalyzed
intermolecular cyclopropanation of a set of olefins 3 (Schemes 1 and 4 ± 6). The reactions proceeded with either
diazo-free phenyliodonium ylides or diazo compounds affording the desired cyclopropane derivatives in either
racemic or enantiomer-enriched forms. The intramolecular cyclopropanation of allyl diazo(triethylsilyl)acetates
28, 30, and 33 were carried out in the presence of the chiral dirhodium(II) catalyst [Rh2{(S)-nttl)4}] (9) in
toluene to afford the corresponding cyclopropane derivatives 29, 31 and 34 with up to 37% ee (Scheme 7). An
efficient enantioselective chiral separation method based on enantioselective GC and HPLC was developed.
The method provides information about the chemical yields of the cyclopropane derivatives, enantioselectivity,
substrate specifity, and catalytic activity of the chiral catalysts used in the inter- and intramolecular
cyclopropanation reactions and avoids time-consuming workup procedures.
1. Introduction. ± Due to its unusual bonding and large inherent ring strain, the
cyclopropane moiety is unique among cyclic hydrocarbons in its properties, synthesis,
and reactions. Naturally occurring and synthetic cyclopropanes bearing simple or
complex functionalities are endowed with a large spectrum of biological properties
ranging from enzyme inhibitions to insecticidal, antifungal, herbicidal, antimicrobial,
antibiotic, antibacterial, antitumor, and antiviral activities [1]. Thus, they constitute a
common structural motif in pyrethroids [2], the antidepressant tranylcyclopromine [3],
papain and cystein protease inhibitors [4], potentially antipsychotic substances [5],
anti-HIV agents [6], and marine lactones [7]. Accordingly, a great deal of effort has
been developed over the last two decades to make the stereochemically controlled
synthesis of substituted cyclopropanes more appealing to organic chemists [8]. Besides
the resolution of their racemates [9], a number of synthetic methodologies, including
the asymmetric SimmonsÀSmith reaction and metal-catalyzed reaction of diazo
1
)
Current address: Department of Biological & Medicinal Research (MBC 03-95), King Faisal
Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia (e-mail:
ghanem@kfshrc.edu.sa).
ꢁ 2005 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta ± Vol. 88 (2005)
217
compounds with olefins, have been developed to access to the enantiomerically pure or
enriched cyclopropanes [10].
The latter proceeds via an asymmetric carbene-transfer reaction. Thus, the
transition-metal-catalyzed decomposition of the diazo precursor affords a metal-
locarbene (ˆ metal-carbene complex; see Fig. 1) as reactive intermediate, which then
transfers the carbene moiety to an appropriate substrate. The enantioselectivity of the
reaction may be controlled by chiral ligands surrounding the metal. Recently,
phenyliodonium ylides were used as potential substitutes to diazo compounds; the
utility of the ylide approaches is directly related to the level of selectivity of the process,
which is believed to proceed also via metallocarbenes as intermediates [11].
Fig. 1. MetalÀcarbene complex
The ways in which efficiency and practicality of these procedures are defined is
depending on a large number of factors. Among these factors are suitable catalyst,
scale, reagent costs, time allotted and required, and suitable equipments and reliable
methods used in the determination of the enantiomer excess (ee) of the resulting
cyclopropanes. The development of accurate non chiroptic methods for the determi-
nation of enantiomer purity has been critical for the development of enantioselective
catalysis. Thus, a prerequisite in the metal-catalyzed asymmetric synthesis is a precise
and reliable assessment of the enantiomer purity of the resulting products [12]. Among
these methods are: polarimetric methods, gas-chromatographic methods, liquid-
chromatographic methods, and NMR spectroscopy. The modern and most sensitive
methods used in the determination of enantiomer purity of the outcome of metal-
catalyzed reactions, allowing a detection as little as 0.1% of one enantiomer in the
presence of another, are chiral-GC and -HPLC methods [13 ± 17]. Here, we report on
the synthesis of cyclopropane derivatives via inter- and intramolecular cyclopropana-
tions and their chiral analysis on either Chirasil-b-Dex as chiral stationary phase in GC
or Chiralcel OD (cellulose tris(3,5-dimethylphenylcarbamate)) coated on 10-mm silica
gel as chiral stationary phase in HPLC.
2. Results and Discussion. ± 2.1. Intermolecular Cyclopropanation. 2.1.1. Diazo-Free
One-Pot Procedure. The conventional ylide approach used to prepare cyclopropanes
consisted of the intermolecular cyclopropanation of olefins with isolated phenyl-
iodonium ylides 1 or 2 (cf. Fig. 2). The efficiency of this method is depending on how
convenient is the ylide to be handled and isolated in pure form.
Fig. 2. Phenyliodonium ylids 1 and 2 generated in situ from Meldrumꢀs acid (4) and dimethyl malonate (5)

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To avoid the difficulty in isolating sensitive ylides, a method was developed to
generate the phenyliodonium ylides 1 and 2 in situ. Thus, a set of cyclopropanes derived
from Meldrumꢀs acid (ˆ2,2-dimethyl-1,3-dioxane-4,6-dione; 4) and dimethyl malonate
(ˆdimethyl propanedioate; 5) were prepared by a user-friendly diazo-free one-pot
procedure. The intermolecular cyclopropanation of olefins 3a ± f) was carried out with
either 4 or 5 and bis(acetato-kO)phenyliodine (ˆdiacetoxyiodobenzene; PhI(OAc)2;
6) or iodosylbenzene PhI ˆ O; 7) in the presence of 5 mol-% of rhodium(II) catalyst
[Rh2(OAc)4] (8) to afford the racemic cyclopropane derivates 11 and 12, respectively,
with high yield (up to 85%) (Scheme 1).
Scheme 1. One-Pot Synthesis of Cyclopropane Derivatives 11 and 12 from Meldrumꢀs Acid (4) or Dimethyl
Malonate (5), Respectively, and PhI(OAc)2 (6) or PhIˆO (7), in Presence of the Achiral Rhodium(II) Catalyst 8
(L ˆ AcO) or the Chiral Rhodium(II) Catalyst 9 (L ˆ (S)-nttl) or 10 (L ˆ 4-Cl-(S)-nttl)
The ylides 1 and 2 were generated and decomposed by the appropriate rhodium
catalyst in situ to afford the cyclopropanes upon reaction with olefins [11]. Attempts to
use a chiral rhodium(II) catalyst, i.e., [Rh2, {(S)-nttl}4] (9; below, Scheme 2), instead of
[Rh2(OAc)4] (8) afforded the enantiomer-enriched cyclopropanes 11a ± f derived from
Meldrumꢀs acid with 57, 51, 70, 33, and 30% ee, respectively. The cyclopropanation of
styrene (3a) with dimethyl malonate (5) and iodosylbenzene (7) furnished the
cyclopropane 12a with only 37% ee, while 12b ± f were obtained with low ee (<20%)
(cf. Figs. 3 ± 6).

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Fig. 3. Analysis of 11a: a) HPLC and b) GC. Cyclopropanation conditions: 4 ‡ 3a, ylide precursor 6, catalyst
10. * ˆ By-products (see Chap. 2.3).
The situation improved markedly when a Cl-substituent was introduced into the 4-
position of the naphthalene ring of the catalyst ligand 9 to form [Rh2{4-Cl-(S)-nttl}]
(10). In the presence of 10, the asymmetric cyclopropanation of styrene (3a) with
Meldrumꢀs acid (4) and bis(acetato-kO)phenyliodine (6) in CH2Cl2 gave 11a with 70%
ee (81% yield) (cf. Fig. 3), while the cyclopropanation of styrene (3a) with dimethyl
malonate (5) and iodosylbenzene (7) in CH2Cl2 afforded 12a with 66% ee (77% yield).
Similarly, cyclopropane derivative 12e was obtained with 56% ee (cf. Fig. 7).

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Fig. 4. Analysis of 11b: a) HPLC and b) GC. * ˆ By-products (see Chapt. 2.3).
The catalysts [Rh2{S)-nttl}4] (9) and [Rh2{4-Cl-(S)-nttl}] (10) were prepared via
condensation of the appropriate 1,8-naphthalic anhydride 13a or 13b and the amino
acid l-tert-leucine (ˆ(2S)-2-amino-3,3-dimethylbutanoic acid; 14) in DMF under
reflux, which afforded the ligands 15a,b easily and in high yield (Scheme 2). Ligand
exchange was carried out by refluxing [Rh2(OAc)4] (8) with a tenfold excess of ligand
15a or 15b in chlorobenzene (see Exper. Part), furnishing the desired chiral
dirhodium(II) catalyst 9 or 10 in 80± 90% chemical yield.

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Fig. 5. Analysis of 11d: a) HPLC and b) GC. * ˆ By-products (see Chapt. 2.3).
2.1.2. Cyclopropanation with Isolated Diazo Compounds. The intermolecular
cyclopropanations of styrene were carried out with either 2-diazo-3-(silyloxy)but-3-enoate
16 (Scheme 3) or 2-diazo-3,3,3-trifluoropropanoate 18 (Scheme 4) and achiral rhodium
catalyst [Rh2(OAc)4] (8) affording trans-17 and a mixture of cis- and trans-19 in 60and
70% yield, respectively. Reduction of cis/trans-19 gave the alcohols cis/trans-20, while
hydrolysis afforded the acids cis/trans-21. Esterification of trans-20 with either 3,5-
dinitrobenzoic acid or 4-nitrobenzoic acid yielded trans-22 and -23, respectively (cf. Fig. 8).

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Fig. 6. Analysis of 11e: a) HPLC and b) GC. * ˆ By-products (see Chapt. 2.3).
In the presence of the chiral rhodium(II) catalyst [Rh2{(S)-pttl}4] or [Rh2{(S)-
bpttl}4], and [Rh2{(S)-nttl}4] in refluxing toluene, the intermolecular cyclopropanations
of styrene with diazo(triethylsilyl)- and diazo(dimethylphenylsilyl)acetate 24a and 24b
provided the silylated 2-phenylcyclopropane-1-carboxylates cis/trans-25a and cis/trans-
25b, respectively, with similar diastereoisomer ratio (trans/cis 82 :18) (Scheme 5; cf.
below, Fig. 9,a).

Helvetica Chimica Acta ± Vol. 88 (2005)
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Fig. 7. Analysis of 12e: a) HPLC and b) GC. Cyclopropanation conditions: 5 ‡ 3e, ylide precursor 7, catalyst 10.
* ˆ By-products (see Chapt. 2.3).

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Scheme 2. Synthesis of Chiral Rhodium(II) Catalysts
Scheme 3. Intermolecular Cyclopropanation of Styrene with 2-Diazo-3-(silyloxy)but-3-enoate 16
The preference for the formation of trans-25 where the phenyl and ethoxycarbonyl
groups are cis-positioned (see Scheme 5) is of some interest since, in the cyclo-
propanation with ethyl diazoacetate, the trans-isomer usually predominates. However,
upon protiodesilylation of cis/trans-25a 18 :82 with Bu4NF, epimerization occurred and
the desilylated cyclopropanecarboxylates cis/trans-26 were isolated in an equal
entantiomer ratio of 48 :48 (cf. Scheme 6 and Fig. 9,b ± d), even when the reaction
was carried out at À 788. The enantioselective GC separation of the enantiomers of the
silylated cyclopropanecarboxylates cis/trans-25a failed but could be achieved upon
their reduction with LiAlH4 to a diastereoisomer mixture cis/trans-27. The relative
configurations of the diastereoisomeric alcohols cis/trans-27 were verified by compar-
ison of the NMR signals of the CH2OH group with those reported for the trimethylsilyl

Helvetica Chimica Acta ± Vol. 88 (2005)
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Scheme 4. Intermolecular Cyclopropanation of Styrene with 2-Diazo-3,3,3-trifluoropropanoate 18
analogues [18]. The latter failed to undergo protiodesilylation upon exposure to Bu4NF,
even upon prolonged reaction times (cf. Fig. 10).
2.2. Intramolecular Cyclopropanation. The intramolecular cyclopropanation of allyl
diazo(triethylsilyl)acetates 28, 30, and 33 were carried out in the presence of chiral
rhodium(II) catalyst [Rh2{(S)-nttl}4] (9) in toluene affording the corresponding
cyclopropanes 29, 31, and 34 with 37, 8 and 32% ee, respectively (Scheme 7 and Fig. 11).
The diazo decomposition of 28 generated by-products whose structure could not be
established. However, a b-lactone may be implicated (see below). The diazo
decomposition of 2-methyl substituted diazoacetate 30, in turn, proceeded to 31 in
mediocre yield of ca. 20% with up to 8% ee, and was accompanied by the formation of
the b-lactone 32 (15 ± 18% yield). In contrast, the reaction proceeded well with the
(2Z)-pent-2-enyl diazoester 33 resulting in yields of ca. 70% of cyclopropane 34 with
32% ee. The structure of 34 was confirmed via protiodesilylation with Bu4NF in THF to

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Fig. 8. HPLC Analysis of esters trans-22 and trans-23, obtained by cyclopropanation of styrene with
diazopropanoate 18 and further transformations (see Scheme 4)

Helvetica Chimica Acta ± Vol. 88 (2005)
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Scheme 5. Intermolecular Cyclopropanation of Styrene with Diazo(triethylsilyl)acetate 24a and Diazo(di-
methylphenylsilyl)acetate 24b
Scheme 6. Desilylation and Reduction of cis/trans-2-Phenyl-1-(triethylsilyl)cyclopropanecarboxylates cis/trans-
25a
the known 35 with 22% ee, which was used for the determination of the ee. The
absolute configuration of 34 was determined according to [18].
2.3. Enantioselective Separation of Cyclopropane Derivatives: Enantioselective
Analysis (GC vs. HPLC). For efficient monitoring of the reaction progress,
enantioselective gas chromatography (GC) was first used for the determination of
the enantiomer excess of the resulting cyclopropane derivatives. The enantiomer
separation of the cyclopropane derivatives is demonstrated by using Chirasil-b-Dex as a
chiral stationary phase for enantioselective gas chromatography. The reactions were
monitored qualitatively and quantitatively with GC/MS and dodecane as internal
standard. Thus, after a simple filtration and a single GC run, information regarding the
yield of the resulting cyclopropane derivatives and the selectivity of the catalyst is
provided without further workup.

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Fig. 9. GC Separation a) of the diastereoisomers cis/trans-25b, b) of the diastereoisomers cis/trans-26, c) of the
enantiomers of cis-26, and d) of the enantiomers of trans-26. The silylated cis/trans-25a were obtained by
cyclopropanation (see Scheme 5) and the desilylated cis- and trans-26 by subsequent desilylation (Scheme 6).
Note the effect of the silyl moiety on the separation: enantiomers of silylated cis/trans-25a were not separated,
while those of cis- and trans-26 were baseline-separated (Fig. 9,b ± d).
Despite the baseline GC separation, some of the cyclopropane derivatives 11 and 12
from Meldrumꢀs acid (4) and dimethyl malonate (5) underwent a thermal decom-
position on GC affording as by-products the cyclopropanedicarboxylic acid derivatives
(cf. Fig. 3 ± 7) in ca. 16% yield. The latter were identified qualitatively and
quantitatively by GC/MS. The enantiomeric cyclopropanedicarboxylic acid derivatives
resulting from the thermal decomposition on GC were baseline-separated in some
cases (e.g., by-products of 11a, b, d, e and 12e, f) while others were not (cf. Fig. 3 ± 7).

Helvetica Chimica Acta ± Vol. 88 (2005)
229
Fig. 9 (cont.)
In addition, some compounds, i.e., trans-22 and trans-23, were not separated at all by
GC. The effect of the silyl moiety on the chiral separation was noticed in case of the
silylated cyclopropane derivatives 25 and the corresponding desilylated 26 (cf.
Schemes 5 and 6 and Fig. 9). Only the silylated diastereomeric cis/trans-25 could be
separated but not their enantiomers (Fig. 9,a). The four enantiomers of the
corresponding desilylated cis/trans-26 were baseline separated (cf. Fig. 9,b ± d). Other
cyclopropane derivatives containing an alcohol moiety were successfully resolved with
reasonable resolution and separation factor (cf. Fig. 10). Among the different classes of
cyclopropane derivatives separated by GC, 12a, 17, and trans-20 were the fastest eluted
enantiomers with resolutions (Rs) of 4.29, 1.80, and 3.37 and separation factors (a) of
1.10, 1.04, and 1.08, respectively. The latter can be used in the high-throughput
screening to discover the enantioselective catalyst in a combinatorial approach. The

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Fig. 10. GC Separationa) of the enatiomers of cis-27 and b) of the enantiomersof trans-27. The silylated cis- and
trans-27 were obtained by cycloproparation ( ! cis/trans-25a, Scheme 5) followed by reduction (Scheme 6).
chromatographic parameters including the separation factor (a) and the resolution
(Rs) of the GC enantiomer separation of the prepared cyclopropane derivatives are
summarized in Table 1.
To avoid the thermal decomposition by GC and to achieve a base-line separation of
all cyclopropane derivatives concomitant with the determination of the sign of their
optical rotations, we used a HPLC workstation equipped with a sensitive optical-
rotation detector for the monitoring of the optical activity of racemic and enantiomer-
enriched cyclopropane derivatives resulting from the RhII-catalyzed asymmetric
carbene-transfer reactions. The polysaccharide chiral stationary phase was Chiralcel-
OD (ˆcellulose tris(3,5-dimethylphenylcarbamate) and the mobile phase was hexane/
iPrOH 90:10( v/v) for all 11 and 12 and 99 :1 (v/v) for 17, 22, and 23 (see Exper. Part).
The chromatographic parameters of the HPLC separation of cyclopropane derivatives
are summarized in Table 2. The absolute configurations of 11, 12, and 17 were

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Scheme 7. Rhodium(II)-Catalyzed Intramolecular Cyclopropanation of Allyl Diazo(triethylsilyl)acetates
Table 1. GC Separation of Racemic Cyclopropane Derivatives on Chirasil-b-Dex: Oven Temperature (T),
Retentiom Time (tR ), Resolution (Rs), and Separation Factor (a)
Ta)
tR (S)
tR (R)
Rs
a
11a
11b
11c
11d
11e
12a
12b
12c
1308
1408
1008
858
1308
1308
1208
808
37.2
33.035.1
14.8
28.7
21.9
8.7
22.6
13.7
25.9
48.5
22.4
23.2
4.8
38.8
26.84
15.7
29.9
23.1
9.6
24.1
15.9
27.2
50.2
23.8
25.7
5.2
17.7
1.89
1.0
2.33
1.63
2.22
4.29
2.65
1.14
1.93
1.45
2.601.0
4.89
3.37
1.04
1.05
1.04
1.26
1.10
1.06
1.02
1.05
1.03
12d
12e
12f
758
1158
1408
1308
1208
1508
n.s.b)
n.s.b)
1258
1508
1008
1308
1308
6
trans-17
trans-20
cis-21
trans-22
trans-23
cis/trans-25a
cis/trans-25b
trans-26
cis-27
trans-27
1.10
1.08
1.14
n.s.b)
n.s.b)
1.03
1.04
1.08
15.4
5.46
n.s.b)
n.s.b)
37.4 (trans)
29.4 (trans)
19.7
n.s.b)
n.s.b)
38.6 (cis)
30.7 (cis)
21.3
n.s.b)
n.s.b)
1.05
1.77
3.28
3.801.10
3.71
42.4
41.6
46.7
45.6
1.09
a) Head pressure 150KPa, injector temperature 200 8, and FID temperature 2508. b) n.s. ˆ not separated by GC.

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Fig. 11. GC Separation of the enantiomers of a) 29, b) 31, c) 34, and d) 35. The silylated 29, 31, and 34 were
obtained by cyclopropanation and 35 by subsequent desilylation (Scheme 7). Note the effect of the silyl moiety
on the separation Fig. 11, c vs. d.
determined by previously reported procedures; however, those of 22 and 23 are not yet
known.
3. Conclusion. ± A set of cyclopropane derivatives were prepared via inter- and
intramolecular cyclopropanation catalyzed by achiral and chiral rhodium(II) catalysts.
Both the diazo and ylide approach were utilized to access the cyclopropanes. The
advantages of the liquid-chromatographic separation of cyclopropane enantiomers
over the gas-chromatographic analysis of the same compounds were demonstrated. The
results revealed that HPLC equipped with a chiralyzer might be a useful tool in the

Helvetica Chimica Acta ± Vol. 88 (2005)
233
Fig. 11 (cont.)
determination of the enantiomer excess as well as in identifying the absolute
configuration of cyclopropanes prepared via metal-catalyzed carbene-transfer reaction.
This work was supported by the Swiss National Science Foundation (Project No. 20-52581.97 and
2027048156) and by the European Commission for Science, Research and Development (COSTAction D12). We
also thank the Swiss Chemical Society, Analytical Division, for a travel grant awarded to A. G.
Experimental Part
1. General. All olefins were commercially available and distilled prior to use. Meldrumꢀs acid (4), dimethyl
malonoate (5), bis(acetato-kO)phenyliodine ([PhI(OAc)2]; 6), 1,8-naphthalic anhydride (ˆ1H,3H-naph-
tho[1,8-cd]pyran-1,3-dione; 13a) and its 4-Cl-substituted derivative 13b were purchased from Acros Organics
(Geel, Belgium). Iodosylbenzene (PhI ˆ O; 7), [Rh2{(S)-nttl}4] (9) and [Rh2{4-Cl-(S)-nttl}4] (10) were
prepared as described below. [Rh2(OAc)4] (8) was purchased from Pressure Chemical (Pittsburgh, USA).
Solvents were dried prior use. HPLC-Grade hexane and propan-2-ol were purchased from Fluka (Buchs,

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Table 2. HPLC Separation of Racemic Cyclopropane Derivatives on Chiralcel OD at Room Temperature:
Retentiom Time (tR ), Resolution (Rs) and the Separation Factor (a)a)
tR (S)-(À)
18.4
16.9
27.1
10.9
19.7
18.7
24.3
±
±
21.9
25.3
23.2 (1R,2S)
38.4 (n.d.)
24.4 (n.d.)
tR (R)-(‡)
22.1
19.9
29.2
11.1
24.1
19.6
25.9
±
±
24.5
26.7
25.7 (1S,2R)
46.8 (n.d.)
29.1 (n.d.)
Rs
a
11ab)
3.19
2.57
2.61
1.03
3.24
3.201.11
2.62
±
1.21
1.19
1.20
1.01
1.23
11bb)
11cb)
11db)
11eb)
12ab)
12bb)
1.02
±
±
12cb)
12db)
±
12eb)
1.801.12
2.64
2.96
2.19
3.11
12fb)
1.05
1.22
1.22
1.20
trans-17c)
trans-22c)
trans-23c)
b
a) n.d. ˆ Absolute configuration not determined. ) Mobile phase: iPrOH/hexane 10: 90( v/v), flow rate 0.3 ml/
min. c) Mobile phase: hexane 1 : 99 (v/v), flow rate 0.3 ml/min.
Switzerland). Diazo compounds were synthesized as described below [18 ± 20]. CC ˆ column chromatography;
FC ˆ flash chromatography. IR Spectra: Shimadzu FT-IR-9100 spectrometer. 1H- and 13C-NMR Spectra:
Bruker (400 MHz) spectrometer; d(H) in ppm rel. to the internal standard SiMe4 (ˆ0ppm), J in Hz. HPLC:
Waters binary pump, model 1525 (Milford, MA, USA), equipped with a dual l absorbance detector model 2487,
an autosampler model 717plus, and an optical-rotation detector (Chiralyzer, IBZ Messtechnik GmbH,
Hannover, Germany) operating at r.t.; UV detector set at 245 nm; Chiralcel OD column (4.6 Â 250mm coated
on 10-mm silica gel) from Daicel Chemical Industries Ltd. (Tokyo, Japan), data collection with Breeze software
from Waters; the mobile phase was filtered through a Millipore membrane filter (0.2 mm) from Nihon Millipore
(Yonezawa, Japan) and degassed before use; the buffer was adjusted with a pH meter from Orion Research
(model 611; Orion Research Inc., USA); flow 0.3 ml/min. GC: Hewlett-Packard 580 (Waldbronn, Germany)
equipped with a flame-ionization detector (FID); the chiral stationary phase, permethylated pent-5-enyl-b-
cyclodextrin (20% (w/w)), was dissolved in dimethylpolysiloxane containing 5% SiÀH groups (Gelest, ABCR
GmbH & Co., Karlsruhe, Germany) and coated on a 20m  0.25 mm fused-silica capillary column (0.25-mm film
thickness) according to [12], injector temp. 2008, FID temp. 2508, oven temp. varying depending on the structure
of the cyclopropane; H2 as carrier gas (150KPa column-head pressure).
2. Catalyst [Rh2{(S)-nttl}4] (10). (aS)-6-Chloro-a-(1,1-dimethylethyl)-2,3-dihydro-1,3-dioxo-1H-naph-
tho[1,8-cd]pyridine-2-acetic Acid (15b). A mixture of l-tert-leucine (14; 1.01 g, 7.72 mmol) and 4-chloro-1,8-
naphthalic anhydride (2.0g, 8.6 mmol; 13b) in DMF (25 ml) was heated to reflux for 1.0h under N 2. The DMF
was removed by distillation, and the solid residue was purified by FC (SiO2, AcOEt/MeOH 99 :1): 2.56 g (86%)
24
D
of 15b. Colorless solid. M.p. 1228. ‰aŠ ˆ À53 (c ˆ 0.1, CHCl3). IR (KBr): 3088w, 2956w, 2912w, 2862w, 1736m,
1703m, 1660s, 1585m, 1569m, 1366s, 1341s, 1234s. 1H-NMR (400 MHz, CDCl3): 1.11 (s, 9 H); 5.48 (s, 1 H); 7.69
(d, J ˆ 8, 1 H); 7.74 (t, J ˆ 8, 1 H); 8.40± 8.45, ( m, 1 H); 8.44 (d, J ˆ 8, 1 H); 8.55 ± 8.65 (m, 1 H). 13C-NMR
(100 MHz, CDCl3): 28.5 (q); 36.1 (s); 59.8 (d); 124.2 (s); 124.9 (s); 128.9 (s); 129.1 (d); 130.7 (d); 130.8 (d); 131.7
‡
‡
(s); 131.8 (d); 132.3 (d); 132.7 (s); 163.8 (s); 164.1 (s); 173.6 (s). MS: 345, 347 (0, M ), 289 (26, [M À C4H8] ),
273 (21), 272 (10), 271 (62), 245 (10), 241 (12), 216 (29), 214 (10), 190 (11), 188 (34), 160 (15), 126 (12), 73
(100), 57 (40). HR-MS: 289.0168 (C14H835ClNO4 ; calc. 289.0142), 291.0139 (C14H835ClNO4 ; calc. 291.0112).
Tetrakis{m-[aS)-6-chloro-a-(1,1-dimethylethyl)-2,3-dihydro-1H-naphtho[1,8-cd]pyridine-2-acetato-kO:
kO']dirhodium(RhÀRh) ([Rh2{(S)-4-Cl-nttl}4]; 10). Dirhodium(II) acetate ([Rh2(OAc)4]; 110mg, 0.25 mol),
15b (0.82 g, 2.4 mmol), and chlorobenzene (40 ml) were heated under reflux and N2 in a Soxhlet apparatus fitted
‡
‡
with a thimble containing dried Na2CO3 and sand in a 1:1 ratio (removal of AcOH). After 24 h, the solvent was
24
D
evaporated, and the gummy residue was purified by FC (basic alumina, MeOH): 10 (85%). Green solid. ‰aŠ
ˆ
1
‡166 (c ˆ 0.1, CHCl3). IR (KBr): 2956w, 1709s, 1667s, 1608m, 1591m, 1575m, 1399m, 1366m, 1344s. H-NMR

Helvetica Chimica Acta ± Vol. 88 (2005)
235
(400 MHz, CDCl3): 1.31 (s, 9 H); 5.79 (s, 1 H); 8.28 ± 8.30( m, 2 H); 8.32 (d, J ˆ 8, 1 H); 8.43 (d, J ˆ 8, 1 H);
8.51 ± 8.60( m, 1 H). 13C-NMR (100 MHz, CDCl3): 28.8 (q); 29.4 (q); 29.7 (q), 36.2 (s); 62.1 (d); 121.8 (s), 123.2
(s); 123.3 (s); 127.4 (d); 127.8 (d); 128.4 (d); 128.9 (s); 131.8 (d); 132.2 (d); 138.5 (s); 162.4 (s); 162.7 (s); 186.8
‡
(s). MALDI-MS: 1605.0680 (C72H3605Cl4N4NaO16Rh2 ; calc. 1605.0768).
3. Intermolecular Cyclopropanation of Olefins with Meldrumꢀs Acid (4): General Procedure: CH2Cl2
(10ml) was added by syringe to a mixture of 4 (2.10mmol, 1 equiv.), 6 (1.4 equiv.), [Rh2(OAc)4] or [Rh2{(S)-
nttl}4] (5 mol-%), Al2O3 (2.3 equiv.), and 4-Š molecular sieves (250mg), followed by the addition of the olefin
(10equiv.). The mixture was thermostatted in an oil bath to 30 8 and stirred under Ar. Then 100-ml samples were
taken after several time intervals. The samples were filtered by using a syringe filter holder (0.2-mm pore size),
and the org. phase was diluted with CH2Cl2 (100 ml) and analyzed by GC. The reaction progress was monitored
qualitatively and quantitatively by GC/MS (dodecane as internal standard). When maximum conversion was
reached, the reaction was terminated by filtration through Celite. The residue on the Celite was washed twice
with CH2Cl2. Evaporation of the combined filtrates followed by CC (silica gel, pentane/AcOEt 2 :1 afforded the
desired cyclopropane derivatives 11a ± d.
Data of 11a ± f: In agreement with those reported in [11].
4. Iodosylbenzene (PhI ˆ O; 7). To finely powdered 6 (32.2 g, 0.10 mol) was added 3n NaOH (150ml)
within 5 min under vigorous stirring, and the lumps of solid which formed where crushed with a spatula. The
mixture was stirred for 45 min and then diluted with H2O (100 ml). The crude yellow solid was collected by
filtration, washed with H2O (3 Â 100 ml), and dried under vacuum. It was suspended in CHCl3 (75 ml),
macerated, and separated by filtration. The crude 6 was air-dried and used without further purification.
5. Intermolecular Cyclopropanation of Olefins with Dimethyl Malonate (5): General Procedure. To a
mixture of 7 (1.4 equiv.), olefin (10equiv.), MgO (2.3 equiv.), rhodium(II) catalyst (5 mol-%), and 4-Š
molecular sieves (250mg) in CH 2Cl2 (10ml), 5 (0.01 mol) was added. The mixture was stirred under Ar for 24 h.
Then, 100-ml samples were taken after several time intervals and analyzed as described in Exper. 3. Workup as
described in Exper. 3 and CC (silica gel, heptane/AcOEt 5 :1) afforded the desired cyclopropane derivatives
12a ± f.
Dimethyl 2-Phenylcyclopropane-1,1-dicarboxylate (12a): 1H-NMR (400 MHz, CDCl3): 1.71 (dd, J ˆ 4, 4,
1 H); 2.18 (dd, J ˆ 4, 4, 1 H); 3.21 (t, J ˆ 8, 1 H); 3.34 (s, 3 H); 3.76 (s, 3 H); 7.19 ± 7.28 (m, 5 H). 13C-NMR
(100 MHz, CDCl3): 19.1 (t); 32.6 (d); 37.2 (s); 52.2 (q); 52.6 (q); 127.4 (d); 128.2 (d); 128.4 (d); 134.5 (s); 164.8
‡
(s); 169.4(s). HR-MS: 234.0897 (C13H14O4 ; calc. 234.0892).
Dimethyl 2-(4-Methylphenyl)cyclopropane-1,1-dicarboxylate (12b): 1H-NMR (400 MHz, CDCl3): 1.79
(dd, J ˆ 4, 4, 1 H); 2.18 (dd, J ˆ 8, 8, 1 H); 2.20( s, 3 H); 3.21 (t, J ˆ 12, 1 H); 3.42 (s, 3 H); 3.81 (s, 3 H); 7.15
(s, 4 H). 13C-NMR (100 MHz, CDCl3): 19.0( t); 20.9 (q); 32.3 (d); 37.0( s); 52.0( q); 52.6 (q); 128.1 (d); 128.7 (d);
‡
131.3 (s); 136.9 (s); 166.9 (s); 170.1 (s). HR-MS: 248.10530 (C14H16O4 ; calc. 248.10491). Anal. calc. for C14H16O4
(248.28): C 67.73, H 6.50; found: C 67.50, H 6.58.
1
Dimethyl 2-Propylcyclopropane-1,1-dicarboxylate (12c): H-NMR (400 MHz, CDCl3): 0.90 (t, J ˆ 7, 3 H ) ;
1.09 ± 1.19 (m, 1 H); 1.37 ± 1.52 (m, 5 H); 3.34 (s, 3 H); 3.76 (s, 3 H). 13C-NMR (100 MHz, CDCl3): 13.7 (q); 21.5
(t); 22.2 (t); 28.2 (d); 30.6 (t); 33.9 (s); 52.2 (q); 52.4 (q); 168.8 (s); 171.4(s).
Data of 12d: In agreement with those reported in [10].
Dimethyl 2-(4-Chlorophenyl)cyclopropane-1,1-dicarboxylate (12e): 1H-NMR (400 MHz, CDCl3): 1.72
(dd, J ˆ 4, 4, 1 H); 2.13 (dd, J ˆ 8, 1 H); 3.16 (t, J ˆ 8, 1 H); 3.40( s, 3 H); 3.79 (s, 3 H); 7.12 (d, J ˆ 8, 2 H); 7.23
(d, J ˆ 8, 2 H). 13C-NMR (100 MHz, CDCl3); 18.1 (t); 30.7 (d); 36.2 (s); 51.9 (q); 52.4 (q); 127.6 (d); 129.0( d);
‡
132.1 (s), 132.3 (s); 165.8 (s); 168.9 (s). HR-MS: 268.0492 (C13H3135ClO4 ; calc. 268.0502). Anal. calc. for
C13H13ClO4 (268.70): C 58.11, H 4.88; found: C 58.0, H 4.70.
Dimethyl 2-(4-Bromophenyl)cyclopropane-1,1-dicarboxylate (12f): 1H-NMR (400 MHz, CDCl3): 1.75
(dd, J ˆ 4, 4, 1 H); 2.15 (dd, J ˆ 8, 8, 1 H); 3.21 (t, J ˆ 8, 1 H); 3.42 (s, 3 H); 3.81 (s, 3 H); 7.0 8 (d, J ˆ 4, 2 H); 7.40
(d, J ˆ 8, 2 H). 13C-NMR (100 MHz, CDCl3): 19.1 (t); 32.6 (d); 37.2 (s); 52.2 (q); 52.6 (q); 120.4 (s); 129.1 (d);
‡
‡
129.9 (d); 132.6 (s); 165.8 (s); 168.9 (s). MS: 314 (14, M ), 312 (14, M ), 282 (82), 280(28), 250(20), 148 (19),
202 (19), 201 (100), 199 (69), 195 (26), 193 (26), 173 (20), 170 (27), 145 (27), 129 (13), 115 (62), 114 (23), 113
‡
(10), 103 (12), 102 (10), 89 (16), 77 (14), 63 (17), 59 (45), 51 (10). HR-MS: 312.0010 (C13H7139BrO4 ; calc.
‡
311.9997), 313.9998 (C13H8131BrO4 ; calc. 313.9977). Anal. calc. for C13H13BrO4 (311.9): C 50.86, H 4.16; found: C
50.64, H 4.10.
6. Intermolecular Cyclopropanation of Styrene with Methyl 2-Diazo-3-[(triisopropylsilyl)oxy]but-3-enoate
(16): Methyl 2-Phenyl-1-{1-[(triisopropylsilyl)oxy]ethenyl}cyclopropanecarboxylate (trans-17). The rhodium
catalyst (0.008 mmol) was activated by heating in vacuo, and dissolved in toluene (3 ml). After addition of
styrene (730mg, 7 mmol), the mixture was cooled to 0 8, and 16 (208 mg, 0.70 mmol) in toluene (2 ml) was added

236
Helvetica Chimica Acta ± Vol. 88 (2005)
dropwise. After the addition, stirring was continued for 1 h. The solvent was evaporated and the residue purified
by FC (SiO2, Et2O/pentane 5 :95): trans-17 (60%). IR (KBr): 2955w, 2868w, 1747s, 1608s, 1451w, 1475w, 1349s,
1266s, 1214s. 1188s. 1H-NMR (400 MHz, CDCl3): 0.84 (d, J ˆ 7.2, 9 H); 0.94 (d, J ˆ 7.2, 9 H); 0.96 ± 1.04
(m, 3 H); 1.67 (dd, J ˆ 4.9, 9.15, 1 H); 1.74 (dd, J ˆ 5.1, 7.4, 1 H); 3.04 (t, J ˆ 8.5, 1 H); 3.74 (s, 3 H); 4.25 (s, 1 H);
4.23 (s, 1 H); 7.51 ± 7.60( m, 5 H). 13C-NMR (100 MHz, CDCl3): 12.8 (d); 17.8 (q); 17.9 (q); 19.7 (t), 31.5 (d); 38.6
‡
(s); 52.1 (q); 93.6 (t); 127.3 (s); 127.7 (d); 128.8 (d); 136.4 (s); 154.9 (s); 173.8 (s). MS 359 (2, M ), 332 (26), 331
(100), 141 (10), 117 (19), 115 (13), 103 (10), 91 (12), 89 (28), 75 (37), 61 (10), 59 (27). HR-MS: 359.2054
‡
(C21H31O3Si ; calc. 359.2043). Data in agreement with those reported in [19].
7. RhII-Catalyzed Carbene Transfer with Ethyl 2-Diazo-3,3,3-trifluoropropanoate (18): Ethyl cis/trans-2-
Phenyl-1-(trifluoromethyl)cyclopropanecarboxylate (cis/trans-19). At r.t., 18 (92 mg, 0.50 mmol) in CH2Cl2
(5 ml) was added within 8 h to the olefin (5 mmol) in CH2Cl2 (5 ml) containing the appropriate catalyst (5 mol-
%). After completion of the reaction, the mixture was passed through a short plug of silica gel, which was
subsequently washed with CH2Cl2 (20ml). The solvent was evaporated and the crude product purified by FC:
cis- and trans-19.
Data of cis-19. IR (film): 3034w, 2980w, 1725s, 1386m, 1298s, 1225s, 1158s. 1H-NMR (CDCl3, 400 MHz):
1.32 ± 1.34 (t, J ˆ 7.3, 3 H); 1.90± 1.98 ( m, 2 H); 3.02 ± 3.05 (t, J ˆ 9, 1 H); 4.21 ± 4.27 (m, 2 H); 7.16 ± 7.32
(m, 5 H). 13C-NMR (CDCl3, 100 MHz): 14 (q); 16.2 (t); 32.4 (d); 35 (q); 62.4 (t); 128.0( d); 129.2 (d); 129.6 (q);
129.8 (d); 133.5 (s); 168.5 (s). MS: 258 (41), 238 (27), 213 (13), 210(18), 193 (43), 192 (26), 190(42), 185 (63),
184 (16), 183 (21), 181 (10), 173 (15), 170 (47), 166 (20), 165 (87), 164 (34), 147 (14), 146 (77), 145 (26), 135
(25), 134 (11), 133 (23), 116 (30), 115 (100), 107 (28), 105 (16), 104 (17), 91 (29), 89 (20), 79 (13), 78 (13), 77
‡
(21), 65 (19), 63 (18), 51 (22). HR-MS: 258.0869 (C13H13O2F3 ; calc. 258.0868).
Data of trans-19. IR (film): 3014w, 2984w, 1735s, 1456w, 1386m, 1225s, 1149s, 1158s. 1H-NMR (CDCl3,
400 MHz): 0.82 ± 0.84 (t, J ˆ 7.4, 3 H); 1.80± 1.88 ( m, 1 H); 2.03 ± 2.06 (m, 1 H); 3.01 ± 3.04 (t, J ˆ 9, 1 H); 4.01 ±
4.07 (m, 2 H); 7.12 ± 7.32 (m, 5 H). 13C-NMR (CDCl3, 100 MHz): 13.9 (q); 15.2 (t); 30.4 (d); 34 (q); 61.4 (t);
124.0( q); 128.2 (d); 129.2 (d); 133.4 (s); 167.5 (s). MS: 258 (41), 238 (30), 213 (13), 210 (22), 193 (43), 210 (22),
193 (43), 192 (30), 190 (45), 186 (10), 185 (76), 184 (16), 183 (23), 181 (12), 173 (16), 171 (10), 170 (49), 166
(23), 165 (95), 164 (34), 147 (13), 146 (71), 145 (25), 135 (33), 134 (10), 133 (21), 127 (20), 123 (10), 116 (31),
115 (100), 107 (36), 105 (16), 104 (17), 91 (23), 89 (22), 79 (15), 78 (13), 77 (22), 65 (15), 63 (19), 51 (24). HR-
‡
MS: 258.0864 (C13H13O2F3 ; calc. 258.0868).
7. Hydrolysis of cis/trans-19: cis/trans-2-Phenyl-1-(trifluoromethyl)cyclopropanecarboxylic Acid (cis/trans-
21). See [20]: cis- or trans-19 (34 mg, 0.13 mmol) was hydrolyzed with KOH (15 mg, 0.27 mmol) in MeOH
(1.5 ml) at r.t. overnight. The solvent was evaporated, and the residue was treated with 1n HCl and extracted
twice with CH2Cl2. Recrystallization from CH2Cl2/pentane afforded cis- or trans-21 in 65 ± 75% yield.
Data of cis-21: IR (film): 3034w, 2880w, 1705s, 1440s, 1386m, 1298s, 1125s, 1155s. 1H-NMR (CDCl3,
400 MHz): 2.04 ± 2.06 (m, 2 H); 3.12 ± 3.15 (m, 1 H); 7.36 ± 7.38 (m, 5 H). 13C-NMR (CDCl3, 100 MHz): 17 (t);
‡
32.8 (q); 34 (d); 124.0( q); 128.2 (d); 128.6 (d); 129.8 (d); 133.2 (s); 176.5 (s). MS: 230(38, M ), 210(20), 190
(19), 185 (53), 176 (12), 173 (12), 170(12), 166 (14), 165 (58), 164 (26), 147 (13), 146 (60), 145 (16), 117 (50),
116 (29), 115 (100), 114 (12), 107 (68), 105 (13), 91 (25), 90 (10), 89 (27), 79 (20), 78 (11), 77 (25), 75 (10), 65
‡
(14), 63 (26), 51 (32). HR-MS: 230.0559 (C11H9O2F3 ; calc. 230.0555).
Data of trans-21: IR (film): 3036w, 2920m, 1705s, 1460m, 1436m, 1393m, 1318s, 1125s, 1145s, 1078s.
1H-NMR (CDCl3, 400 MHz): 2.04 ± 2.06 (m, 2 H); 3.12 ± 3.15 (m, 1 H); 7.36 ± 7.38 (m, 5 H). 13C-NMR (CDCl3,
100 MHz): 16 (t); 30.8 (d); 34 (q); 124.0( q); 127.2 (d); 128.4 (d); 129.3 (d); 132.2 (s); 169.5 (s). MS: 230(37,
‡
M ), 210(21), 190(19), 185 (53), 176 (12), 170(11), 166 (13), 165 (58), 164 (26), 147 (14), 146 (61), 145 (16),
137 (10), 133 (17), 117 (14), 116 (29), 115 (100), 114 (13), 107 (78), 91 (24), 90 (12), 89 (28), 79 (25), 78 (13), 76
‡
(10), 75 (11), 65 (18), 63 (32), 62 (11), 51 (41), 50 (16). HR-MS: 230.0557 (C11H9O2F3 ; calc. 230.0555).
8. Reduction of cis/trans-19: cis/trans-2-Phenyl-1-(trifluoromethyl)cyclopropanemethanol (cis/trans-20).
See [20]: At 08, cis- or trans-19 (72 mg, 0.28 mmol) in THF (2 ml) was added within 30 min by syringe to LiAlH4
(19 mg, 0.5 mmol) in THF. After the addition, the mixture was heated to reflux for 4 h. AcOEt was added to
decompose the remaining LiAlH4, followed by H2O. After extraction with Et2O, the org. layer was filtered
through a plug of silica gel, which was washed with AcOEt (20ml). The solvent was evaporated and the crude
product purified by FC (SiO2, CH2Cl2/pentane 60:40): cis- or trans-20.
Data of cis-20. IR (film): 3632w, 1387w, 1211m, 1215m, 1223s, 1138m. 1H-NMR (500 MHz, CDCl3): 1.23 ±
1.35 (m, 1 H); 1.64 ± 1.67 (m, 1 H); 2.58 ± 2.59 (t, J ˆ 7.7, 1 H); 3.75 (d, J ˆ 13, 1 H); 4.02 (d, J ˆ 13, 1 H); 7.23 ±
7.25 (m, 5 H). 13C-NMR (125 MHz, CDCl3): 11.5 (t); 26.4 (d); 31.4 (q); 64.5 (t); 125 (q); 126.4 (d); 129.1 (d);
‡
134.6 (s). MS: 216 (14, M ), 198 (22), 186 (18), 185 (16), 166 (16), 165 (25), 164 (11), 130(11), 129 (100), 128

Helvetica Chimica Acta ± Vol. 88 (2005)
237
(16), 117 (21), 116 (10), 115 (24), 107 (15), 104 (14), 91 (26), 89 (10), 78 (13), 77 (14), 63 (10), 51 (15). HR-MS:
‡
216.0784 (C11H11OF3 ; calc. 216.0762).
Data of trans-20. IR (film): 3032w, 2923w, 1698s, 1432m, 1395m, 1311s, 1239m, 1223m, 1149m, 1135s, 1075s.
1H-NMR (500 MHz, CDCl3): 1.33 ± 1.37 (m, 1 H); 1.47 ± 1.52 (m, 1 H); 2.76 ± 2.79 (t, J ˆ 9.0, 1 H); 3.65 (d, J ˆ
13, 1 H); 3.62 (d, J ˆ 13, 1 H); 7.13 ± 7.21 (m, 5 H). 13C-NMR (125 MHz, CDCl3): 11.3 (t); 25.4 (d); 30.8 (q); 61.5
‡
(t); 126 (q); 127.8 (q); 128.4 (d); 128.9 (d); 134.9 (s). MS: 216 (15, M ), 198 (26), 186 (21), 185 (19), 166 (19),
165 (25), 164 (10), 130 (12), 129 (100), 128 (16), 117 (21), 116 (11), 115 (24), 107 (16), 104 (15), 91 (18), 89 (10),
‡
78 (14), 77 (15), 63 (10), 51 (16). HR-MS: 216.0771 (C11H11OF3 ; calc. 216.0762).
9. Esterification of trans-20: General Procedure. Under anhydrous conditions, a mixture of trans-20
(0.1 mmol) and 3,5-dinitrobenzoic acid or 4-nitrobenzoic acid (0.12 mmol) in pyridine (10 ml) was slowly heated
to reflux temp. and maintained under gentle reflux for 2 h and then cooled. H2O was added, the mixture
extracted with AcOEt, the org. layer washed with 1n HCl and H2O, dried (Na2SO4), and evaporated, and the
residue purified by FC (SiO2, Et2O/pentane 20:80).
3,5-Dinitrobenzoic Acid [trans-2-Phenyl-1-(trifluoromethyl)cyclopropyl]methyl Ester (trans-22): IR (film):
1
3052w, 2923w, 1708s, 1532m, 1498m, 1318s, 1249m, 1263m, 1169m, 1175s, 1085s. H-NMR (400 MHz, CDCl3):
1.15 ± 1.23 (m, 1 H); 1.53 ± 1.57 (m, 1 H); 2.38 ± 2.39 (t, J ˆ 7.7, 1 H); 4.07 (s, 2 H); 7.21 ± 7.24 (m, 5 H); 9.12 ± 9.16
(m, 3 H). 13C-NMR (100 MHz, CDCl3): 11.1 (t); 24.9 (d); 30.7 (q); 59.5 (t); 125.1 (q); 127.5 (d); 128.9 (d); 134.8
‡
(s); 123 (d); 130.9 (d); 149.2 (s); 132.1 (s); 168.4 (s). HR-MS: 410.3029 (C18H13F3N2O6 ; calc. 410.3027).
4-Nitrobenzoic Acid [trans-2-Phenyl-1-(trifluoromethyl)cyclopropyl]methyl Ester (trans-23): IR (film):
3152w, 2980w, 1710s, 1562m, 1488m, 1330s, 1260m, 1278m, 1178m, 1180s, 1095s. 1H-MR (400 MHz, CDCl3):
1.14 ± 1.22 (m, 1 H); 1.53 ± 1.57 (m, 1 H); 2.38 ± 2.39 (t, J ˆ 7.7, 1 H); 4.05 (s, 2 H); 7.23 ± 7.25 (m, 5 H); 8.23 ± 8.30
(m, 4 H). 13C-NMR (100 MHz, CDCl3): 11.0( t); 24.6 (d); 30.5 (q); 59.3 (t); 125.0( q); 127.3 (d); 128.4 (d); 128.9
‡
(d); 136.0( s); 123 (d); 130.4 (d); 136.5 (s); 152.4 (s); 168.9 (s). HR-MS: 356.3049 (C18H14F3NO4 ; calc.
365.3056).
10. RhII-Catalyzed Intermolecular Cyclopropanation of Styrene with Silylated Diazoacetate 24a,b: General
Procedure. To the RhII catalyst (2 mol-%) was added styrene (920 ml, 8.0mmol) under Ar and the silylated
diazoacetate 24a or 24b (0.85 mmol). The mixture was heated until the decomposition of the diazoacetate was
completed (ca. 2 h). The solvent was evaporated, and the crude product was purified by FC according to [18].
Ethyl cis/trans-2-Phenyl-1-(triethylsilyl)cyclopropanecarboxylate (cis/trans-25a): IR (film): 2958w, 2878w,
‡
1714s, 1461m, 1208m, 1004m, 698s. MS: 30 4 (7,M ), 275 (15), 231 (19), 135 (19), 131 (100), 115 (40), 87 (70), 75
‡
(35), 59 (37). HR-MS : 304.1849 (C18H28O2Si , calc. 304.1858). NMR Data were obtained from diastereoisomer
mixtures. trans-25a: 1H-NMR (300 MHz, CDCl3): 0.68 ± 0.76 (m, 6 H); 1.0 8 (t, J ˆ 7.7, 9 H); 1.20± 1.26 ( m, 1 H);
1.36 (t, J ˆ 7.0, 3 H); 1.96 (dd, J ˆ 6.4, 4.9, 1 H); 2.46 (t, J ˆ 7.2, 1 H); 3.80( dd, J ˆ 7.2, 0.8, 2 H); 7.20 ± 7.32
(m, 5 H). 13C-NMR (75 MHz, CDCl3) : 2.8 (t); 7.6 (q); 13.5 (t); 13.9 (q); 27.5 (d); 60.1 (t); 126.4 (d); 126.9 (d);
1
128.5 (d); 137.5 (s); 172.3 (s). cis-25a: H-NMR (300 MHz, CDCl3): 0.25 ± 0.48 (m, 6 H); 0.85 (t, J ˆ 7.9, 9 H);
0.92 (t, J ˆ 7.1, 3 H); 1.44 ± 1.48 (m, 1 H); 1.80( dd, J ˆ 8.8, 4.0, 2 H); 2.76 (dd, J ˆ 7.0, 8.8, 1 H); 4.22 (qd, J ˆ 7.1,
0.8, 2 H); 7.20 ± 7.32 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 3.8 (t); 7.7 (q); 14.3 (q); 16.0( t); 31.6 (d); 60.7 (t);
127.9 (d); 128.0( d); 130.0 (d); 138.3(s); 172.3 (s).
Ethyl cis/trans-1-(Dimethylphenylsilyl)-2-phenylcyclopropane-1-carboxylate (cis/trans-25b): IR (film):
‡
2971w, 1716s, 1427m, 1275s, 1108s. MS: 324 (9, M ), 246 (9), 144 (12), 136 (14), 135 (100), 107 (14), 103
‡
(21), 75 (11). HR-MS: 324.1545 (C20H24O2Si , calc. 324.1546). NMR Data were obtained from diastereoisomer
1
mixtures. trans-25b: H-NMR (300 MHz, CDCl3): 0.52 (s, 3 H); 0.55 (s, 3 H); 0.89 (t, J ˆ 7.17, 3 H); 1.15 ± 1.20
(m, 1 H); 2.02 (m, 1 H); 2.45 (t, J ˆ 8.3, 1 H); 3.77 (dd, J ˆ 1.1, 7.17, 2 H); 7.20± 7.30 ( m, 5 H); 7.42 ± 7.44
(m, 5 H); 7.64 ± 7.67 (m, 2 H). 13C-NMR (75 MHz, CDCl3): À 3.6 (q); À 2.1 (q); 13.9 (t); 14.4 (t); 22.6 (s); 28.2
(d); 60.2 (t); 126.4 (d); 127.7 (d); 127.8 (d); 128.7 (d); 129.3 (d); 134.2 (d); 136.7 (s); 137.0( s); 172.0( s). cis-25b:
1H-NMR (300 MHz, CDCl3): 0.52 (s, 3 H); 0.55 (s, 3 H); 0.89 (t, J ˆ 7.2, 3 H); 1.61 (dd, J ˆ 4.0, 6.8, 1 H); 1.88
(dd, J ˆ 4.0, 8.9, 1 H); 2.89 (dd, J ˆ 6.8, 8.7, 1 H); 4.14 (q, J ˆ 7.2, 2 H); 7.20± 7.30( m, 5 H); 7.42 ± 7.44 (m, 5 H);
7.64 ± 7.67 (m, 2 H). 13C-NMR (75 MHz, CDCl3): À 2.6 (q); À 2.1 (q); 13.9 (t); 16.1 (t); 19.8 (s); 32.5 (d); 60.2
(t); 126.8 (d); 127.3 (d); 127.9 (d); 128.5 (d); 130.0 (d); 133.9 (d); 136.7 (s); 137.0( s); 172.0( s).
11. Desilylation of cis/trans-25a: Ethyl cis/trans-2-Phenylcyclopropanecarboxylate (cis/trans-26). To trans-
25a (48% ee)/cis-25a (30% ee) 82 :18 (142 mg, 0.56 mmol) in THF (3.0 ml) was added 1m Bu4NF (1.0ml) in
THF at À 788. The temp. was allowed to reach r.t. After stirring for 2 ± 4 h, the mixture was quenched with H2O
(2 ml) and extracted with CH2Cl2. The org. layer was dried (MgSO4) and evaporated, and the residue was
purified by FC (SiO2, pentane/AcOEt 97:3): cis/trans-26 70:30, (1 S,2S)-trans-26 (48% ee), and (1R,2S)-cis-26
(48% ee) in 81% yield (cf. Fig. 9,c and d).

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Helvetica Chimica Acta ± Vol. 88 (2005)
Similarily, starting from trans-25a (54% ee)/cis-25a (27% ee) 82 :18, trans-26 (51% ee)/cis-26 (49% ee)
were obtained.
The same procedure was applied to trans/cis-25b 88 : 12 (100.5 mg, 0.31 mmol; from reaction with [Rh2{(S)-
pptl}4]), which afforded (1S,2S)-trans-26 (31%; 15% ee) and (1R,2S)-cis-26 (18%; 13% ee).
Data of trans-26: IR (film): 2982w, 1725s, 1185s, 755m, 698m. 1H-NMR (300 MHz, CDCl3): 1.26 (t, J ˆ 7.2,
3 H); 1.56 ± 1.68 (m, 1 H); 1.86 ± 1.92 (m, 1 H); 2.48 ± 2.54 (m, 1 H); 4.16 (q, J ˆ 7.2, 2 H); 7.07 ± 7.30 (m, 5 H).
13C-NMR (75 MHz, CDCl3): 14.3 (q); 17.0( t); 24.1 (d); 26.1 (d); 60.6 (t); 126.1 (d); 126.4 (d);128.4 (d); 140.1 (s);
‡
‡
173.4 (s). MS: 190(33, M ), 145 (23), 117 (100), 115 (50), 91 (21). HR-MS: 190.0981 (C12H14O2 ; calc.
190.0994).
1
Data of cis-26: IR (film): 3009w, 1721s, 1186s, 1081w, 864w. H-NMR (300 MHz, CDCl3): 0.93 (t, J ˆ 7.2,
3 H); 1.27 ± 1.35 (m, 2 H); 1.70± 1.76 ( m, 1 H); 2.05 ± 2.13 (m, 1 H); 2.59 (m, 1 H); 3.88 (q, J ˆ 7.2, 2 H); 7.20±
7.28 (m, 5 H). 13C-NMR (75 MHz, CDCl3): 11.0( t); 13.9 (q); 21.8 (d); 25.4 (d); 60.1 (t); 126.6 (d); 127.8 (d);129.3
‡
‡
(d); 136.6 (s); 170.9 (s). MS: 190(32, M ), 145 (20), 117 (100), 115 (53), 91 (23). HR-MS: 190.1003 (C12H14O2 ;
calc. 190.0994).
12. Reduction of cis/trans-25a: cis/trans-2-Phenyl-1-(triethylsilyl)cyclopropanemethanol (cis/trans-27). To
LiAlH4 (2 equiv.) in THF (2.0ml) was added, under Ar, cis/trans-25a (0.80 mmol) in THF (4.0 ml). The mixture
was stirred overnight at r.t. The excess of LiAlH4 was decomposed by the addition of ethane-1,2-diamine (2 ml),
followed by 8% NaOH soln. (2.0ml) and H 2O. The crude product was extracted with Et2O (10ml), dried
(Na2SO4), filtered, and evaporated. The diastereoisomers were separated by FC (SiO2, CH2Cl2/pentane 80:20):
cis- and trans-27.
Data of trans-27a: Yield 45%. Colorless oil. IR (film): 2945m, 2871m, 1458w, 1239w, 1003s, 726s. 1H-NMR
(300 MHz, CDCl3): 0.68 (q, J ˆ 7.9, 6 H); 0.87 ± 0.99 (m, 2 H); 1.0 5 (t, J ˆ 7.9, 9 H); 2.24 (t, J ˆ 6.7, 1 H); 3.22
(d, J ˆ 11.8, 1 H); 3.53 (d, J ˆ 11.8, 1 H); 7.24 ± 7.30( m, 5 H). 13C-NMR (75 MHz, CDCl3): 2.6 (t); 7.6 (q); 11.7
‡
(t); 15.9 (s); 24.3 (d); 65.7 (t); 126.2 (d); 128.3 (d); 128.9 (d); 138.4 (s). MS: 233 (12, [M À C2H5] ), 215 (27), 130
‡
(36), 115 (43), 103 (100), 87 (65), 75 (80). HR-MS: 233.1386 (C14H21OSi ; calc. 233.1362).
1
Data of cis-27a: Yield 13%. Colorless oil. IR (film): 2951m, 2874m, 1455w, 1238w, 1005s, 726s. H-NMR
(300 MHz, CDCl3): 0.24 ± 0.40 (m, 6 H); 0.85 (t, J ˆ 7.7, 9 H); 1.20( t, J ˆ 5.6, 1 H); 1.47 (s, 1 H); 2.10± 2.20
(m, 2 H); 3.27 (d, J ˆ 11.0, 1 H); 3.87 (d, J ˆ 11.0, 1 H); 7.20 ± 7.30 (m, 5 H). 13C-NMR (75 MHz, CDCl3): 3.3 (t);
‡
7.6 (q); 12.0( t); 17,6 (s); 27.0( d); 71.5 (t); 126.2 (d); 127.9 (d); 129.7 (d); 139.7 (s). MS: 233 (8, [M À C2H5] ), 215
‡
(21), 171 (12), 130 (39), 115 (39), 103 (100), 87 (60), 75 (85). HR-MS: 233.1372 (C14H21OSi ; calc. 233.1361).
13. Intramolecular Cyclopropanation of Allyl Diazo(triethylsilyl)acetates 28, 30, and 33: General Procedure.
To the RhII catalyst (2 mol-% with respect to the allyl diazo(triethylsilyl)acetates) was added the
diazosilylacetate 28, 30, or 33 (0.40 mmol) under Ar within 5 min. The mixture was stirred for 2 h at r.t. The
soln. was evaporated and the residue purified by FC to afford the desired cyclopropane derivatives according to
[18].
(1S,5R)-1-(Triethylsilyl)-3-oxabicyclo[3.1.0]hexan-2-one (29): FC (SiO2, pentane/AcOEt 97:3) afforded
20
D
29. For yields, see Table 2. Colorless oil. ‰aŠ ˆ ‡7.2 (c ˆ 1.00, EtOH; for 30% ee). IR (film): 2954m, 2876m,
1753s, 1248m, 994s. 1H-NMR (300 MHz, CDCl3): 0.59 ± 0.67 (m, 6 H); 0.96 (t, J ˆ 8.1, 9 H); 1.17 (dd, J ˆ 7.0, 4.5,
1 H); 2.04 ± 2.06 (m, 1 H); 4.24 (m, 2 H). 13C-NMR (MHz, CDCl3): 2.0( t); 7.2 (q); 13.3 (s); 15.6 (t); 21.9 (t); 68.2
‡
(t); 178.8 (s). MS: 183 (85, [M À C2H5] ), 139 (30), 111 (100), 83 (42), 59 (27), 53 (36). HR-MS: 183.0850
‡
(C9H15O2Si ; calc. 183.0841).
cis-(1S,5R)-5-Methyl-1-(triethylsilyl)-3-oxabicyclo[3.1.0]hexan-2-one (31): FC (SiO2, pentane/AcOEt
97:3) afforded 31 (20%; with [Rh2{(S)-nttl}4]). Colorless oil. IR: 2954m, 2879m, 1750s, 1188s, 1056s, 1006s.
1H-NMR (300 MHz, CDCl3): 0.68 ± 0.76 (m, 6 H); 0.99 (t, J ˆ 7.5, 9 H); 1.09 (d, J ˆ 4.2, 1 H); 1.16 (d, J ˆ 3.9,
1 H); 1.36 (s, 3 H); 3.94 (d, J ˆ 8.8, 1 H); 4.20( d, J ˆ 8.8, 1 H). 13C-NMR (75 MHz, CDCl3): 2.5 (t); 7.3 (q); 16.8
‡
(q); 22.9 (t); 30.0 (s); 72.2 (t); 113.9 (s); 179.4 (s). MS: 197 (100, [M À C2H5] ), 125 (92), 115 (36), 103 (24), 97
‡
(54), 87 (52). HR-MS: 197.1004 (C12H22O2Si ; calc. 197.0998).
cis-4-Isopropenyl-3-(triethylsilyl)oxetan-2-one (32): FC (SiO2, pentane/AcOEt 97:3) afforded 32 (18%;
with [Rh2{(S)-nttl}4]). IR (film): 2956m, 2874m, 1807s, 1255w, 1111s, 1008s. 1H-NMR (300 MHz, CDCl3): 0.67 ±
0.76 (m, 6 H); 0.98 (t, J ˆ 8.1, 9 H); 1.79 (s, 3 H); 3.55 (dd, J ˆ 6.4, 2.5, 1 H); 4.88 (d, J ˆ 6.4, 1 H); 5.08 (s, 1 H);
5.26 (s, 1 H). 13C-NMR (75 MHz, CDCl3): 3.5 (t); 7.2 (q); 19.1 (d); 44.6 (q); 73.3 (d); 113.0( t); 140.2 (s); 170.0
‡
‡
(s). MS: 226 (3, M ), 198 (17), 197 (100), 125 (54), 103 (38), 75 (54). HR-MS: 226.138750 (C12H22O2Si ; calc.
226.1389).
(1S,5R,6R)-6-Ethyl-1-(triethylsilyl)-3-oxabicyclo[3.1.0]hexan-2-one (34). FC (SiO2, pentane/AcOEt 97:3)
gave 34 (76%; [Rh2{(S)-nttl}4]; 38% ee as determined after desilylation to 35). Colorless oil. IR (film): 2952m,
2873m, 1745s, 1197w, 1070m, 1000m. 1H-NMR (500 MHz, CDCl3): 0.64 (q, J ˆ 7.7, 6 H); 0.96 (t, J ˆ 7.7, 9 H ) ; 1.04

Helvetica Chimica Acta ± Vol. 88 (2005)
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(t, J ˆ 7.2, 3 H); 1.26 ± 1.55 (m, 3 H); 2.08 (t, J ˆ 5.6, 1 H); 4.13 (d, J ˆ 9.6, 1 H); 4.29 (dd, J ˆ 9.6, J ˆ 5.5, 1 H).
13C-NMR (MHz, CDCl3): 2.1 (t); 7.2 (q); 13.3 (q); 17.0( t); 19.4 (s); 27.1 (d); 27.3 (d); 65.1 (t); 177.1 (s). MS: 211
‡
‡
(100 [M À C2H5] ), 115 (16), 109 (15), 103 (69), 81 (25), 75 (46). HR-MS: 211.1158 (C11H19O2Si ; calc.
211.1154).
14. Desilylation of 34: (1R,5S,6R)-6-Ethyl-3-oxabicyclo[3.1.0]hexan-2-one (35). At r.t., 1m Bu4NF in THF
(1 ml) was added dropwise to 34 (0.56 mmol). After stirring for 2 ± 4 h, H2O (2 ml) was added, and the mixture
was extracted with CH2Cl2. The org. layer was dried (MgSO4) and evaporated and the residue purified by FC
20
(SiO2, pentane/AcOEt 96 :4): 12 mg (37%) of 35. Colorless oil. ‰aŠ ˆ 26.3 (c ˆ 0.24, EtOH; for 28% ee). IR
D
1
(film): 2965m, 2876w, 1756s, 1173w, 1058s, 979s. H-NMR (300 MHz, CDCl3): 1.07 (t, J ˆ 6.8, 3 H); 1.40± 1.43
(m, 3 H); 2.18 ± 2.29 (m, 2 H); 4.15 (d, J ˆ 9.9, 1 H); 4.41 (dd, J ˆ 9.8, 5.3, 1 H). 13C-NMR (75 MHz, CDCl3):
‡
13.3 (q); 16.3 (t); 22.5 (d); 22.7 (d); 23.9 (d); 66.0( t); 175.1 (s). MS: 126 (3, M ), 111 (9), 97 (15), 85 (100), 67
‡
(84), 55 (46). HR-MS: 126.0688 (C7H10O2 ; calc. 126.0680).
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Received September 19, 2004