Highly cis -selective Rh(I)-catalyzed cyclopropanation reactions

Article abstract of DOI:10.1021/jo102140z

The performance of recently reported highly cis-diastereoselective Rh(I) cyclopropanation catalysts has been significantly improved by a systematic study of different reaction parameters (catalyst activation, solvent, temperature, stoichiometry). The cata

Full text of DOI:10.1021/jo102140z

ARTICLE
pubs.acs.org/joc
Highly cis-Selective Rh(I)-Catalyzed Cyclopropanation Reactions
Marianne Lenes Rosenberg,† Klꢀara Vlaꢁsanꢀa,§,† Nalinava Sen Gupta,† David Wragg,† and Mats Tilset*,‡
†Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, N-0315 Oslo, Norway
‡Centre of Theoretical and Computational Chemistry (CTCC), Department of Chemistry, P.O. Box 1033 Blindern, N-0315 Oslo,
Norway
S Supporting Information
b
ABSTRACT: The performance of recently reported highly cis-diastereoselective
Rh(I) cyclopropanation catalysts has been significantly improved by a systematic
study of different reaction parameters (catalyst activation, solvent, temperature,
stoichiometry). The catalyst efficiency and diastereoselectivity were enhanced by
changing the activating agent from AgOTf to NaBArf. With this new system, the
Rh(I) catalyst was shown to be a highly efficient and cis-diastereoselective
cyclopropanation catalyst in reactions between R-diazoacetates and a range of
different alkenes and substituted derivatives. Particularly noteworthy is the
remarkable reactivity and cis-diastereoselectivity displayed in the reactions between
ethyl diazoacetate and cyclopentene, 2,5-dihydrofuran, and benzofuran, with yields
up to 99% and cis-selectivities greater than 99%.
Scheme 1. Highly cis-Selective Cyclopropanation Reaction
’ INTRODUCTION
with Rh(I) Catalyst 128
Cyclopropanes are highly interesting compounds, from both a
biological and synthetic point of view. They are versatile molecules
with numerous potential applications in organic synthesis.1-3 Cyclo-
propanes are important substructures in many synthetic and naturally
occurring biologically active compounds.4-6 Reported biological acti-
vities include enzyme inhibition, antimicrobial, antibiotic, antitumor,
and antiviral activities.5 The most common catalytic method for gene-
rating cyclopropanes involves transfer of a carbene moiety from a
diazocarbonyl compound to an olefin. In such a reaction, up to three
new stereocenters can be formed. A challenge in intermolecular
cyclopropanation reactions can be to achieve good diastereoselectiv-
ities, and preferably with simple, readily available diazo compounds
such as ethyl diazoacetate (EDA). Consequently, great effort has been
invested in developing methods and catalysts that are highly diaster-
eoselective. There are quite a few reports on catalysts that are very
efficient and highly selective for the formation of the thermodynami-
cally favored trans isomer.7-9 On the other hand, high diastereo-
selectivity and good yields in the formation of the unfavored cis isomer
remain a greater challenge. There are few reports on highly
cis-selective cyclopropanations.9-14 Among the reported cis-selective
catalysts is a Cu(I) homoscorpionate catalyst that gives very good
yields and high cis-selectivities in the cyclopropanation reaction
between EDA and styrene.15 Mezzetti and co-workers have shown
that some Ru-salen16-20 complexes display very high cis-selectivities
with EDA. Co-salen complexes have also been reported to give high
cis-selectivitites using EDA21 and tert-butyl diazoacetate,10 and Ir-
salen22,23 complexes give high reactivity and cis-selectivities using tert-
butyl diazoacetate.
more substituted diazo compounds, there are not many examples
of good diastereoselectivities using EDA as the diazo compound.
There are only a few examples of highly trans-selective catalysts, and
we have encountered only a couple of examples of Rh(II)
carboxylate based catalysts that give good cis-selectivities in the
cyclopropanation of styrene,9,25-27 the best selectivity being 90:10.
We recently reported the preparation of Rh(I) catalyst 1 with a
chelating imine-functionalized N-heterocyclic carbene (NHC)
ligand. Following activation with silver triflate (AgOTf), this
catalyst was reported to display a remarkable high reactivity and
cis-selectivity in the cyclopropanation reaction between EDA and
styrene (Scheme 1).28 These are among the highest cis-selectivities
reported in this reaction andthe highest cis-selectivity ever reported
with a Rh catalyst. We here report a more detailed study of recent
developments of this very promising catalytic system. The effects of
changing different experimental parameters (catalyst activation,
Rh(II) carboxylates constitute one of the most extensively used
classes of catalysts in cyclopropanation reactions.8,9,24 While they
are known to give excellent diastereoselectivities with bulkier or
Received: October 28, 2010
Published: March 17, 2011
r
2011 American Chemical Society
2465
dx.doi.org/10.1021/jo102140z J. Org. Chem. 2011, 76, 2465–2470
|

The Journal of Organic Chemistry
ARTICLE
Table 1. Cyclopropanation Reaction between Styrene and EDA Catalyzed by 1 with AgOTf as the Activating Agenta
entry
catalyst loading (mol %) rel to EDA
equiv of styrene rel to EDA
AgOTf (mol %)
reaction time (h)
yieldb (%)
cis:transc
1
2
3
4
5
5
5
2
3
98
89
50
47
>99:1
94:6
92:8
95:5
2.5
1
5
2.5
1
5
48
24
5
2.5
5
a Reaction conditions: 1.00 mmol of EDA and given quantities of 1, AgOTf, and styrene in 20 mL of CH2Cl2 at 0 °C. b Isolated yield based on EDA
limiting reagent. c cis:trans ratio determined by 1H NMR and GC.
Table 2. Cyclopropanation Reaction between Styrene and EDA Catalyzed by 1 Using NaBArf As the Activating Agenta
entry
catalyst loading (mol %) rel to EDA
equiv styrene rel to EDA
NaBArf (mol %)
reaction time (h)
yieldb (%)
cis:transc
1
2
3
4
5
5
5
5
1
2
98
98
49
98
70
>99:1
>99:1
96:4
2.5
1
5
2.5
1
5
24
2
2.5
2.5
2.5
99:1
2.5
1
2.5
2
99:1
a Reaction conditions: 1.00 mmol of EDA and given quantities of 1, NaBArf, and styrene in 20 mL of CH2Cl2 at 0 °C. b Isolated yield based on EDA
limiting reagent. c cis:trans ratio determined by 1H NMR and GC.
catalyst loading, solvent, temperature, stoichiometry) in the cata-
lytic system have been investigated in order to improve the catalytic
performance. Several new alkenes and substituted derivatives as
well as diazo compounds as carbenoid sources have also been tested
in order to broaden and explore the scope of the catalytic process.
1 mol % catalyst loading the yield and selectivity were significantly
reduced (entry 3). It is not known whether these changes in yields and
selectivities are due to catalyst destruction, deactivation, or modifica-
tion facilitated by the prolonged reaction times that are needed for the
reaction to proceed at lower catalyst loadings. Importantly, the new
catalyst activation procedure made it possible to reduce the amounts of
styrene to 2.5 and even 1 equiv relative to EDA while the high
diastereoselectivities and good yields were still obtained (entries 4 and
5). This makes the catalyst more attractive for use in synthesis where it
is not desirable to use an excess of the alkene. The fact that using the
sodium salt NaBArf as the activating agent gave better results than salt
AgOTf also rules out the involvement of Ag species in these
cyclopropanation reactions, and supports the notion that the mode
of activation is a straightforward chloride abstraction.
Attempted Preparation of an Activation-Free Cationic Rh
Catalyst. A new cationic Rh(I) complex (6) was also synthesized,
in which the CO and chloride ligands in 1 are replaced by the
bidentate norbornadiene (nbd) ligand. It was envisioned that
complex 6 might be a better catalyst for the cyclopropanation,
without need for prior catalyst activation, provided that the nbd
ligand would be sufficiently labile to provide a coordination site at
Rh. The synthesis of complex 6 is depicted in Scheme 2.
The imidazolium salt 4 was reacted with in situ generated
[Rh(Ot-Bu)(nbd)]2 to furnish the 5-coordinated Rh complex
5,33 which was directly used in the next step. The stable cationic
complex 6 was obtained by chloride removal from 5 with NaBArf, a
well-established procedure for chloride abstraction in organometal-
lic chemistry.32 The driving force for chloride removal is the
formation of NaCl, poorly soluble in CH2Cl2; this is quite analogous
to the formation of AgCl when AgOTf is the activating agent. The
13C NMR spectrum of 6 exhibited a characteristic doublet for the
carbene carbon at δ 177.8 with J(103Rh-13C) = 61 Hz. The IR
νCdN absorption of the imine was lowered by 51 cm-1 compared to
that of the imidazolium salt 4, strongly indicating that the imino-
carbene ligand had formed the expected κ2(C,N) chelate at Rh. An
X-ray crystal structure of complex 6 is presented in Figure 1. The
X-ray structure analysis confirmed that the iminocarbene ligand had
formed a κ2(C,N) chelate at Rh and the expected square planar
geometry was assumed for the d8 ML4 complex. The Rh-C(nbd)
bond distances are considerably longer for the part of the diene that
’ RESULTS AND DISSCUSSION
Catalyst Activation: Necessity To Form a Rh Cation. In our
recent communication on the performance of catalyst 1,28 it was
demonstrated that in order to obtain catalytic activity, the catalyst
had to be activated. The activating agent of choice in the first study
was AgOTf, the role of which was presumed to be abstraction of the
chloride ligand to create a vacant (or loosely solvated) coordination
site. Activation of 1 with AgOTf for 20 min, followed by addition of
styrene andEDAat0°C, furnished the cis and trans cyclopropanes 2
and 3, respectively, in 98% isolated yield and with a better than 99:1
cis-diastereoselectivity (Scheme 1). The diazo compound could be
added in one portion without any sign of formal carbene dimeriza-
tion, a rather desirable and unusual feature of this catalyst. These
results where obtained with a catalyst loading of 5 mol % of 1, 5 mol
% of AgOTf, and a 5-fold excess of styrene, all measured relative to
EDA (Table 1, entry 1). When the catalyst loading (entries 2 and 3)
or the amount of styrene (entry 4) were reduced, yields and
diastereoselectivities both dropped. Under reaction conditions
that led to reduced yields, formal carbene dimerization (as observed
by formation of diethyl maleate and diethyl fumarate) was observed to
be a major side reaction but the mechanistic implications are unclear.
There were no signs of side products arising from the known24 formal
dipolar cycloadditions of EDA to maleate or fumarate.
It was obviously desirable to modify the reaction conditions in order
to obtain a more efficient and versatile process. Triflate is a fairly small
and slightly coordinating anion.29,30 Previous reports have demon-
strated that replacement of the triflate anion with the larger, more
weakly coordinating31 BArf- anion (BArf-=B[3,5-(CF3)2C6H3)]4 )
-
can significantly increase the reactivity in Rh(II)-catalyzed cyclopro-
panations.32 Indeed, enhanced reactivity was seen also in our system.
WiththeuseofNaBArfastheactivatingagent,itwaspossibletoreduce
the catalyst loading from 5 to 2.5 mol % without detrimental effects on
the reactivity or selectivity (Table 2, entries 1 and 2). However, with
2466
dx.doi.org/10.1021/jo102140z |J. Org. Chem. 2011, 76, 2465–2470

The Journal of Organic Chemistry
ARTICLE
Scheme 2. Synthesis of the Cationic Rh(I) Complex 6
Table 3. Testing of Solvent Effectsa
entry
solvent
yieldb (%)
cis:transc
1
2
3
4
5
6
7
8
9
dichloromethane
trifluorotoluene
trifluoroethanol
toluene
98
65
70
63
94
56
>99:1
>99:1
98:2
98:2
fluorobenzene
nitromethane
ethanol
95:5
97:3
THF
acetonitrile
a Reaction conditions: 1.00 mmol of EDA, 5 equiv of styrene, 2.5 mol %
of 1, 2.5 mol % of NaBArf in 20 mL of the given solvent at 0 °C. b Isolated
yield based on EDA limiting reagent. c cis:trans ratio determined by 1H
NMR and GC.
polarities and donor strengths have now been tested in order to
examine the solvent effects on the catalytic system (Table 3).
As can be seen in Table 3, the initially chosen solvent dichloro-
methane proved to be the best for yields and selectivities (entry 1). In
trifluorotoluene (entry 2), which is similar in polarity and promoted as
a “greener” alternative36 to dichloromethane, the same excellent
selectivity was observed but the yield was considerably lower. Good
selectivities were also observed by using trifluoroethanol and toluene
(entries 3 and 4), but the yields were moderate and products from
formal carbene dimerization were observed in the 1H NMR spectra of
the crude product mixture. No product from formal carbene insertion
into the solvent O-H bond24 was found with trifluoroethanol, but
with ethanol (entry 7) the cyclopropanes (2 and 3) were not formed
and instead the only products observed were those from O-H
insertion and formal carbene dimerization. In fluorobenzene the yield
was high, but the cis:trans selectivity dropped to 95:5 (entry 5). In
nitromethane, the cyclopropanes were formed with good selectivity
and moderate yields (entry 6). In the better donor solvents THF and
acetonitrile the only products observed where those from formal
carbene dimerization (entries 8 and 9). These solvents are presumably
inefficient for cyclopropanation because of the donor properties, but it
is not clear mechanistically how this leads to carbene dimerization.
Scope of Reactants: Diazo Compounds. As discussed above,
Rh(I) catalyst 1 gives excellent results with commercially avail-
able EDA as the diazo compound. tert-Butyl diazoacetate was also
tested under the conditions found to be best for EDA. As shown
in Scheme 3 (top), similarly high yield and cis-selectivity were
observed in the synthesis of cyclopropanes 7 and 8.
Figure 1. ORTEP drawing of 6 (hydrogen atoms and the BArf-
counteranion have been removed for clarity, ellipsoids at 30% propability).
Selected bond distances (Å) and angles (deg): Rh-N(1) 2.069(11),
Rh-C(1) 1.991(12), Rh-C(8) 2.096(11), Rh-C(5) 2.184(11),
Rh-C(1)-N(2), 118.7(8), Rh-C(1)-N(3) 140.3(10), N(1)-
Rh-C(1) 76.1(5).
Ethyl phenyl diazoacetate was also tested as a carbenoid precursor,
Scheme 3 (bottom). The phenyl diazoacetates are known to have a
high preference for formation of the E isomer.37,38 Indeed, with Rh(I)
catalyst 1, the E isomer was the favored isomer with a selectivity of
26:74. With ethyl phenyl diazoacetate, the reaction temperature had
to be raised from 0 °C to ambient and a catalyst loading of 10 mol %
was necessary in order to furnish a reasonable 48% yield of the
cyclopropanes 9 and 10. A diastereomeric ratio of >99:1 in favor of
the E isomer has been reported using a Cu catalyst in the same
reaction.39 Thus, catalyst 1 shows an enhanced cis-selectivity in its
formal carbene additions when compared to other catalysts in the
reactions between styrene and three different diazoacetate reagents.
Scope of Reactants: Alkenes. Cyclopropanations with cata-
lyst 1 and EDA were previously tested on a range of different
alkenes.28 Some of these alkenes were now tested again with the
new and more efficient system using NaBArf as the activating
is trans to the NHC (2.19(1) Å) than for the part that is cis
(2.10(1)) to the NHC ligand, as expected from the greater trans
influence of the NHC ligand compared to the imine.34,35
Complex 6 was then tested in the cyclopropanation reaction
between EDA and styrene by using 5 mol % of 6 and 5 equiv of
styrene under the reaction conditions reported in Table 2. Unfortu-
nately, the new catalyst gave rather low yields (39%) of the
cyclopropanes 2 and 3 and only a slight excess of the cis isomer
(cis:trans 66:44). Probably, the nbd ligand is not sufficiently labile to
effectively create the necessary vacant coordination site. A more
labile ligand than nbd is then obviously needed to furnish a more
efficient and selective catalyst than the original catalyst 1.
Solvent Effects. Dichloromethane, one of the most commonly
used solvents in cyclopropanation reactions, was the solvent used in
the initial study of 1. A range of different solvents of highly variable
2467
dx.doi.org/10.1021/jo102140z |J. Org. Chem. 2011, 76, 2465–2470

The Journal of Organic Chemistry
ARTICLE
Scheme 3. Cyclopropanation of Styrene with tert-Butyl Diazoacetate and Ethyl Phenyldiazoacetate
Table 4. Cyclopropanation of Different Alkenes with EDAa
Table 5. Cyclopropanation of 5-Ring Oxygen-Heterocyclic
Alkenes with EDAa
entry
alkene
yieldb,c (%)
cis:transc,d
1
2
3
4
5
styrene
98 (98)
99 (98)
99 (98)
95 (60)
80 (38)
>99:1 (>99:1)
>99:1 (98:2)
99:1 (99:1)
indene
cyclopentene
1-octene
75:25 (78:22)
75:25 (66:44)
R-methylstyrene
a Reaction conditions: 1.00 mmol of EDA, 5 equiv of alkene, 2.5 mol % of
1, 2.5 mol % of NaBArf in 20 mL of CH2Cl2 at 0 °C. b Isolated yield
based on EDA limiting reagent. c Numbers in parentheses refer to yields
and selectivities reported with AgOTf activation.11 d cis:trans ratio
determined by 1H NMR and GC.
agent, and the results are presented in Table 4 (previously
reported results shown in parentheses for comparison).
With NaBArf as the activating agent, the yields improved slightly
for indene and cyclopentene (entries 2 and 3), and for indene the
selectivity improved from 98:2 to >99:1. For both 1-octene and
R-methylstyrene (entries 4 and 5) the yields improved significantly
but the selectivities were still moderate. Thus, Rh(I) catalyst 1
displays very high reactivity and cis-selectivity in the reactions with
indene and cyclopentene; for cyclopentene this is the highest yield
and by far the highest cis-selectivity that has been reported in reactions
with EDA. This unusual reactivity prompted us to investigate the
reactivity toward a number of O-heterocyclic analogues, the furan
derivatives in Table 5. The corresponding cyclopropanation products
formed from these substrates can be important intermediates40-42 or
substructures in biologically active compounds, as for example in
nucleoside derivatives which have been reported to have antiviral
activity.5 Cyclopropanated carbohydrates are also of particular
interest.3 The selected substrates and the results from their reactions
with EDA using 1as the catalyst with NaBArf activation are presented
in Table 5.
a Reaction conditions: 1.00 mmol of EDA, 5 equiv of alkene, 5 mol % of
1, 5 mol % of NaBArf in 20 mL of CH2Cl2 at 0 °C. b Isolated yield based
on EDA limiting reagent. c cis:trans ratio determined by 1H NMR
e
1
and GC. d No trans product detected. Yield determined by H NMR
by use of benzaldehyde as internal standard.
observed. In these reactions a catalyst loading of 5 mol % of 1hadtobe
used in order to obtain good yields. No products arising from
insertions into substrate C-H bonds24 were observed in these
reactions. This is in accord with our previously reported results28
which also showed that catalyst 1 is a highly selective catalyst for
cyclopropanation reactions vs C-H insertion. The selectivities
observed in the reactions of 2,5-dihydrofuran and benzofuran open
up the possibility of highly selective syntheses of interesting building
blocks and potentially biologically active compounds.
An excellent yield and a selectivity of >99:1 in favor of the cis isomer
was achieved with 2,5-dihydrofuran (entry 1). With benzofuran, the
selectivity was also >99:1 in favor of the cis isomer, and a good yield
was obtained (entry 2). No trans isomer was detected by 1H NMR or
GC analysis in these experiments. For 2,3-dihydrofuran, yield and
selectivity were moderate but still with a considerable cis-selectivity. In
the reaction with furan, only traces of the cyclopropane products were
’ CONCLUSION
The efficiency and the scope of our recently developed highly cis-
selective Rh(I) catalyst 1 has been improved through tuning of
different experimental parameters in its cyclopropanation reactions.
By changing the activating agent from AgOTf to NaBArf, the catalyst
loading could be reduced and the yields and selectivities were
2468
dx.doi.org/10.1021/jo102140z |J. Org. Chem. 2011, 76, 2465–2470

The Journal of Organic Chemistry
ARTICLE
improved for several of the tested alkenes compared to the previously
reported results. A screening of different solvents showed that the best
results were obtained with CH2Cl2 as solvent. Bulkier substituents on
the ester group in the diazo compound were found to have little effect
on the high yields and selectivities, potentially broadening the
synthetic utility of cyclopropanations catalyzed by catalyst 1. Catalyst
1is a very efficient and highly cis-selective catalyst in cyclopropanation
reactions between EDA and sterically unhindered electron-rich
alkenes. The high reactivity and selectivities observed in the reactions
between EDA and the cyclic substrates cyclopentene, 2,5-dihydrofur-
an, and benzofuran are especially interesting, as these results suggest
the possibility of highly selective syntheses of biologically interesting
compounds. These are, to the best of our knowledge, the highest cis-
selectivities and yields observed in cyclopropanation reactions with
these substrates using EDA as the diazo compound.
Rh(I) Iminocarbene Complex 6. The method is an adaption of a
published method for making related Rh(I) oxazolinylcarbene complexes.33
KOt-Bu (0.0570 g, 0.508 mmol, 2.2 equiv) and [RhCl(nbd)]2 (0.107 g,
0.231 mmol, 1.0 equiv) were mixed in the drybox. Dry degassed THF
(7.5 mL) was added and the reaction mixture was stirred at ambient
temperature for 30 min. The mixture was added dropwise to a solution of
imidazolium salt 4 (0.150 g, 0.461 mmol, 2.0 equiv) in THF (15 mL) at
-78 °C, and the reaction mixture was slowly heated to ambient tempera-
ture overnight. The reaction mixture was centrifuged, the resulting orange
supernatant was separated, and the solvent was removed in vacuo. The
crude product was recrystallized from CH2Cl2/Et2O and this gave 5 as an
orange solid. The product was used directly in the following synthesis of 6.
1H NMR of 5 (CD2Cl2, 200 MHz) δ 7.48-7.32 (m, 5H, Ph-H), 7.14 (br s,
1H, NCHCHN), 6.97-6.90 (m, 3H, Dmp-H), 6.86 (d, 1H, J = 2.2 Hz,
NCHCHN), 3.72 (s, 3H, N-CH3), 3.70-3.63 (m, 4H, nbd-H), 3.60-3.53
(m, 2H, nbd-H), 2.32 (s, 6H, Dmp-CH3), 1.11-1.09 (m, 2H, nbd-H).33
A mixtureof5(0.040 g, 0.080 mmol, 1.0 equiv) and NaBArf (0.042 g, 0.16
mmol, 2.0 equiv) was dissolved in CH2Cl2 (5.0 mL) and the reaction mixture
was stirred at ambient temperature for 3 h under argon. The reaction mixture
was centrifuged and the solvent was removed in vacuo. The product was
recrystallized from CH2Cl2/Et2O. This gave 6 as a purple solid (0.0862 g,
80%). 1H NMR (CD2Cl2, 600 MHz) δ 7.74-7.71 (m, 8H, BArf-Ar-Ho),
7.57-7.55 (m, 4H, BArf-Ar-Hp),7.54-7.52 (m, 1H, Ph-Hp),7.43-7.38 (m,
2H, Ph-H), 7.23-7.19 (m, 2H, Ph-H), 7.01-7.0 (m, 3H, Dmp-H), 6.85 (d,
1H, J = 2.3 Hz, NCHCHNCH3), 6.80 (d, 1H, J = 2.3 Hz, NCHCHNCH3),
4.98 (dd, 2H, J = 4.8, 2.6 Hz, nbd-H), 4.21 (dd, 2H, J = 4.5, 1.8 Hz, nbd-H),
4.09-4.05 (m, 2H, nbd-H), 3.46 (s, 3H, NCH3), 2.27 (s, 6H, Dmp-CH3),
1.62 (dt, 1H, J = 1.6, 8.8 Hz, nbd-H), 1.37 (dt, 1H, J = 1.6, 8.8 Hz, nbd-H);
Rh(I) catalyst 1 has been demonstrated to be an efficient, highly
cis-selective cyclopropanation catalyst in reactions between simple
commercially available diazo compounds and a range of different
alkenes. The catalytic system is under continuing investigation in
our laboratories.
’ EXPERIMENTAL SECTION
General Procedures. All reactions involving organometallic com-
pounds were carried out with use of drybox and inert atmosphere
techniques unless otherwise noted. Solvents for reactions were dried
according to standard procedures. THF, CH2Cl2, Et2O, and CH3CN were
dried using a MB SPS-800 solvent purifying system. NMR spectra were
recorded at 25 °C. The assignments of 1H and 13C signals for complex 6
were aided by COSY 45, HMQC, and HMBC spectroscopy. For brevity,
the following abbreviations are used for the assignment: Ph = phenyl, Dmp
=2,6-dimethylphenyl; Ar = 3,5-bis(trifluoro)phenyl: Ho/m/p and Ci/o/m/p
denote the ipso/ortho/meta/para atoms relative to the point of attachment
to the imine nitrogen. Imidazolium salt 4 was synthesized according to
previously reported procedures.28,34 Where CH2Cl2 was found in the
elemental analysis, this was also observed in the 1H NMR spectra.
General Procedure for Cyclopropanation. The procedure is an
adaption of the one used in our recent communication.28 Rh complex 1
(0.0114 g, 0.025 mmol, 2.5 mol %) and NaBArf (0.0221 g, 0.025 mmol, 2.5
mol %) were stirred in dry CH2Cl2 (13.0 mL) at ambient temperature for 1 h
under an argon atmosphere. The reaction mixture was cooled to 0 °C andthe
substrate was added. Ethyl diazoacetate (0.12 mL, 1.00 mmol, 1.0 equiv) in
dry CH2Cl2 (7.0 mL) was then added in one portion. The reaction mixture
was stirred at 0 °C. CH2Cl2 was removed in vacuo and the crude product was
purified by flash chromatography (ethyl acetate:hexane) to afford the
cyclopropanes. The cis:trans ratio and characterization of the cyclopropanes
were determined by GC analysis and by comparison of 1HNMRspectrawith
literature data.
1
13C NMR (CD2Cl2, 126 MHz) δ 177.8 (d, J(103Rh-13C) = 60.8 Hz,
NHC-C), 163.1 (CdN), 162.1(q,J=49.9 Hz, BArf-Ar-C), 140.9 (Dmp-C),
135.2 (br s, BArf-Ar-Co), 133.6 (Ph-CH), 129.6 (Ph-CH), 129.4 (Dmp-
CH), 129.1 (br s, BArf-Ar-C), 128.4 (Ph-CH), 127.5 (Dmp-C), 126.0 (Ph-
C), 123.9 (NCHCHNCH3), 124.8 (q, J = 304.5 Hz, BArf-CF3), 119.0
(NCHCHNCH3), 117.9 (m, BArf-Ar-Cp), 88.8, 88.7 (nbd-CH), 67.5, 67.4
(nbd-CH), 66.7, 66.6 (nbd-CH), 55.1, 55.0 (nbd-CH), 36.7 (NCH3), 18.8
(Dmp-CH3); ESI-MS (CH3CN) m/z 474 (Rh cation - nbd þ2 ꢀ
CH3CN). Anal. Calcd for C58H39F24BRhN3 0.3CH2Cl2: C, 50.9; H, 2.9;
3
N, 3.1. Found: C, 51.0; H, 3.1; N, 3.1.
’ ASSOCIATED CONTENT
1
S
Supporting Information. Characterization data and H
b
NMR of cyclopropanes, 1H NMR and 13C NMR spectra of Rh
complex 6, crystal data for 6, and structural data in CIF format.
This material is available free of charge via the Internet at http://
pubs.acs.org.
’ AUTHOR INFORMATION
Most of the cyclopropanation reactions described have exceptionally good
isolated yields of pure products. We attribute this to the fact that when these
reactions work well, only a simple and quick flash chromatography procedure
is required to separate excess alkene from the cyclopropane products. We
note that there are numerous reports in the literature of cyclopropanation
reactions giving yields of 98% to “quantitative”.7,15,22,23,39,43
Corresponding Author
*E-mail: mats.tilset@kjemi.uio.no.
Present Addresses
§Present address: Department of Organic and Nuclear Chem-
istry, Charles University in Prague, Hlavova 8, 128 43 Praha 2,
Czech Republic.
Ethyl cis-2-phenylcyclopropane-1-carboxylate (2):44. 1H
NMR (CDCl3, 300 MHz) δ 7.25 (m, 4H, Ph-H), 7.18 (m, 1H, Ph-H),
3.87 (q, 2H, J = 7.1 Hz, OCH2CH3), 2.67-2.52 (m, 1H, cyclopropane-H),
2.06 (ddd, 1H, J = 9.3, 7.9, 5.7 Hz, cyclopropane-H), 1.70 (ddd, 1H, J = 9.3,
7.4, 5.3 Hz, cyclopropane-H), 1.40-1.23 (m, 1H, cyclopropane-H), 0.95
(t, 3H, J = 7.1 Hz, OCH2CH3); 13C NMR (CDCl3, 75 MHz) δ 170.8
(CdO), 136.5 (Ph-C), 129.2 (Ph-CH), 127.7 (Ph-CH), 126.5 (Ph-CH),
60.0 (OCH2CH3), 25.3 (cyclopropane-CH), 21.7 (cyclopropane-CH),
13.9 (OCH2CH3), 11.0 (cyclopropane-CH2); EI-MS m/z (%) 190 (Mþ,
42), 162 (7), 145 (20), 117 (100), 91 (24).
’ ACKNOWLEDGMENT
We acknowledge generous financial support from the Norwe-
gian Research Council, NFR (stipend to M.L.R. through grant
no. 177325/V30). We thank Senior engineer Dirk Petersen for
assistance with obtaining NMR data.
2469
dx.doi.org/10.1021/jo102140z |J. Org. Chem. 2011, 76, 2465–2470

The Journal of Organic Chemistry
ARTICLE
’ REFERENCES
(41) Matlin, S. A.; Chan, L.; Catherwood, B. J. Chem. Soc., Perkin
Trans. 1 1990, 89–96.
(42) Temme, O.; Taj, S.-A.; Andersson, P. G. J. Org. Chem. 1998,
63, 6007–6015.
(43) Bonge, H. T.; Pintea, B.; Hansen, T. Org. Biomol. Chem. 2008,
6, 3670–3672.
(44) Lou, Y.; Horikawa, M.; Kloster, R. A.; Hawryluk, N. A.; Corey,
(1) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. Rev. 2007,
107, 3117–3179.
(2) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.; Tanko, J.;
Hudlicky, T. Chem. Rev. 1989, 89, 165–198.
(3) Cousins, G. S.; Hoberg, J. O. Chem. Soc. Rev. 2000, 29, 165–174.
(4) Donaldson, W. A. Tetrahedron 2001, 57, 8589–8627.
(5) Sala€un, J. Top. Curr. Chem. 2000, 207, 1–67.
E. J. J. Am. Chem. Soc. 2004, 126, 8916–8918.
(6) Halton, B. Chem. N. Z. 2007, 71, 53–60.
(7) Doyle, M. P. Angew. Chem., Int. Ed. 2009, 48, 850–852.
(8) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem.
Rev. 2003, 103, 977–1050.
(9) Caballero, A.; Prieto, A.; Díaz-Requejo, M. M.; Pꢀerez, P. J. Eur. J.
Inorg. Chem. 2009, 1137–1144.
(10) Shitama, H.; Katsuki, T. Chem.—Eur. J. 2007, 13, 4849–4858.
(11) L€uning, U.; Fahrenkrug, F. Eur. J. Org. Chem. 2006, 916–923.
(12) Alexander, K.; Cook, S.; Gibson, C. L. Tetrahedron Lett. 2000,
41, 7135–7138.
(13) Uchida, T.; Irie, R.; Katsuki, T. Synlett 1999, 1793–1795.
(14) Casey, C. P.; Polichnowski, S. W.; Shusterman, A. J.; Jones,
C. R. J. Am. Chem. Soc. 1979, 101, 7282–7292.
(15) Díaz-Requejo, M. M.; Caballero, A.; Belderrain, T. R.; Nicasio,
M. C.; Trofimenko, S.; Pꢀerez, P. J. J. Am. Chem. Soc. 2002, 124, 978–983.
(16) Bonaccorsi, C.; Santoro, F.; Gischig, S.; Mezzetti, A. Organo-
metallics 2006, 25, 2002–2010.
(17) Bonaccorsi, C.; Mezzetti, A. Organometallics 2005, 24, 4953–4960.
(18) Bonaccorsi, C.; Bachmann, S.; Mezzetti, A. Tetrahedron: Asym-
metry 2003, 14, 845–854.
(19) Bachmann, S.; Furler, M.; Mezzetti, A. Organometallics 2001,
20, 2102–2108.
(20) Bachmann, S.; Mezzetti, A. Helv. Chim. Acta 2001, 84, 3063–3074.
(21) Uchida, T.; Katsuki, T. Synthesis 2006, 1715–1723.
(22) Suematsu, H.; Kanchiku, S.; Uchida, T.; Katsuki, T. J. Am.
Chem. Soc. 2008, 130, 10327–10337.
(23) Kanchiku, S.; Suematsu, H.; Matsumoto, K.; Uchida, T.;
Katsuki, T. Angew. Chem., Int. Ed. 2007, 46, 3889–3891.
(24) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds: From Cyclopro-
panes to Ylides; Wiley: New York, 1998.
ꢀ
(25) Estevan, F.; Lloret, J.; Sanaꢀu, M.; Ubeda, M. A. Organometallics
2006, 25, 4977–4984.
(26) Estevan, F.; Lahuerta, P.; Lloret, J.; Sanaꢀu, M.; Ubeda, M. A.;
Vila, J. Chem. Commun 2004, 2408–2409.
(27) Doyle, M. P.;Davies, S. B.;Hu, W.Chem. Commun. 2000, 867–868.
(28) Rosenberg, M. L.; Krivokapic, A.; Tilset, M. Org. Lett. 2009,
11, 547–550.
(29) Beck, W.; S€unkel, K. Chem. Rev. 1988, 88, 1405–1421.
(30) Strauss, S. H. Chem. Rev. 1993, 93, 927–942.
(31) Krossing, I.; Raabe, I. Angew. Chem., Int. Ed. 2004, 43, 2066–2090.
(32) Krumper, J. R.; Gerisch, M.; Suh, J. M.; Bergman, R. G.; Tilley,
T. D. J. Org. Chem. 2003, 68, 9705–9710.
(33) Cꢀesar, V.; Bellemin-Laponnaz, S.; Gade, L. H. Eur. J. Inorg.
Chem. 2004, 3436–3444.
(34) Netland, K. A.; Krivokapic, A.; Schr€oder, M.; Boldt, K.;
Lundvall, F.; Tilset, M. J. Organomet. Chem. 2008, 693, 3703–3710.
(35) Frøseth, M.; Netland, K. A.; Rømming, C.; Tilset, M. J.
Organomet. Chem. 2005, 690, 6125–6132.
(36) Green Reaction Media in Organic Synthesis; Mikami, K., Ed.;
Wiley-Blackwell: Oxford, UK, 2005.
(37) Davies, H. M. L.; Bruzinski, P. R.; Fall, M. J. Tetrahedron Lett.
1996, 37, 4133–4136.
(38) Davies, H. M. L.; Rusiniak, L. Tetrahedron Lett. 1998,
39, 8811–8812.
(39) Xu, Z.-H.; Zhu, S.-N.; Sun, X.-L.; Tang, Y.; Dai, L.-X. Chem.
Commun 2007, 1960–1962.
(40) Kim, C.; Brady, T.; Kim, S. H.; Theodorakis, E. A. Synth.
Commun. 2004, 34, 1951–1965.
2470
dx.doi.org/10.1021/jo102140z |J. Org. Chem. 2011, 76, 2465–2470