Copper(I)-homoscorpionate catalysts for the preferential, kinetically controlled cis cyclopropanation of α-olefins with ethyl diazoacetate

Article abstract of DOI:10.1021/ja011895y

In situ prepared copper catalysts Tp^xCu (Tp^x = homoscorpionate) catalyze the olefin cyclopropanation reaction using ethyl diazoacetate as the carbene source. Very high values of both activity and diastereoselectivity toward the cis isomer have been obtained for styrene, α-methylstyrene, 1-hexene, 1-octene, vinyl acetate, n-butyl vinyl ether, 2,5-dimethyl-2,4-hexadiene, and 3,3-dimethyl-1-butene. The effect of the temperature in the diastereoselectivity was almost negligible within the range -10 to +30°C. Kinetic studies have allowed us to propose that the homoscorpionate ligand might act in a dihapto form during the catalytic process. This transformation seems to operate under kinetic control, where the formation of the cis isomer would govern the reaction rate.

Full text of DOI:10.1021/ja011895y

Published on Web 01/19/2002
Copper(I)-Homoscorpionate Catalysts for the Preferential,
Kinetically Controlled Cis Cyclopropanation of r-Olefins with
Ethyl Diazoacetate
M. Mar D´ıaz-Requejo,† Ana Caballero,† Toma´s R. Belderra´ın,† M. Carmen Nicasio,†
Swiatoslaw Trofimenko,‡ and Pedro J. Pe´rez*,†
Contribution from Departamento de Qu´ımica y Ciencia de Materiales, UniVersidad de HuelVa,
Carretera de Palos de la Frontera s/n 21819-HuelVa, Spain, and Department of Chemistry and
Biochemistry, UniVersity of Delaware, Newark, Delaware 19716
Received August 6, 2001
Abstract: In situ prepared copper catalysts TpXCu (TpX ) homoscorpionate) catalyze the olefin cyclopro-
panation reaction using ethyl diazoacetate as the carbene source. Very high values of both activity and
diastereoselectivity toward the cis isomer have been obtained for styrene, R-methylstyrene, 1-hexene,
1-octene, vinyl acetate, n-butyl vinyl ether, 2,5-dimethyl-2,4-hexadiene, and 3,3-dimethyl-1-butene. The
effect of the temperature in the diastereoselectivity was almost negligible within the range -10 to +30 °C.
Kinetic studies have allowed us to propose that the homoscorpionate ligand might act in a dihapto form
during the catalytic process. This transformation seems to operate under kinetic control, where the formation
of the cis isomer would govern the reaction rate.
Scheme 1. The Olefin Cyclopropanation Reations
Introduction
The olefin cyclopropanation reaction constitutes a nice
example to evaluate the different orientations that a metal-based
catalyst can induce.1 Since the mid 1960s this transformation
has been traditionally performed by reacting a diazo compound
reagent, which acts as the carbene precursor, and an olefin
(Scheme 1), with the intermediacy of a transition-metal com-
plex.2 A nondesired side reaction, the decomposition of the diazo
reagent, also takes place simultaneously. With monosubstituted
olefins, the former reaction leads to the formation of two
cyclopropane diastereomers, cis and trans, as a consequence of
the existence of two stereogenic centers. The variables that could
be optimized in the olefin cyclopropanation reaction are (i) the
minimization of the diazo compound decomposition reaction,
(ii) the diastereoselectivity, and (iii) the enantioselectivity. The
first one has usually been avoided by means of slow addition
devices, the diazo compound concentration being maintained
at low levels compared to that of the olefin, although this method
supposes the use of long reaction times. On the other hand,
control of the enantioselectivity has been extensively studied
and maximum levels of enantioselection have already been
achieved. The most efficient catalysts for this reaction are based
on copper or rhodium, although some others of ruthenium and
cobalt have also been reported.2 The ligands employed vary from
one metal to another. Thus, semicorrines,3 bisoxazolines,4 or
bipyridines5 have been attached to copper whereas carboxylates6
or carboxamidates6 are the ligands of choice with the rhodium-
(II) Rh2L4-type catalysts. Other ligands such as porphyrins7
(3) (a) Leutenegger, U.; Umbricht, G.; Fahrni, C.; Matt, P.; Pfaltz, A.
Tetrahedron 1992, 48, 2143-2156. (b) Fritschi, H.; Leutenegger, U.; Pfaltz,
A. HelV. Chim. Acta 1988, 71, 1553-1565.
(4) (a) Evans, D. A.; Woerpel, K. A.; Himman, M. M.; Faul, M. M. J. Am.
Chem. Soc. 1991, 113, 726-728. (b) Lowenthal, R. E.; Abiko, A.;
Masamune, S. Tetrahedron Lett. 1990, 31, 6005-6008
(5) (a) Ito, K.; Katsuki, T. Chem Lett. 1994, 1857-1860. (b) Ito, K.; Katsuki,
T. Tetrahedron Lett. 1993, 34, 2661-2664. (c) Kwong, H.-L.; Lee, W.-S.;
Ng, H.-F.; Chiu, W.-H.; Wong, W.-T. J. Chem. Soc., Dalton Trans. 1998,
1043-1046.
* Corresponding author. E-mail: perez@dqcm.uhu.es.
† Universidad de Huelva.
(6) (a) Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998, 54, 7919. (b)
Kennedy, M.; McKervey, M. A.; Maguire, A. R.; Roos, G. H. P. J. Chem.
Soc., Chem. Commun. 1990, 361-362. (c) Davies, H. M. L.; Bruzinski, P.
R.; Lake, D. H.; Kong, N.; Fall, M. J. J. Am. Chem. Soc. 1996, 118, 6897-
6907. (d) Doyle, M. P.; Zhou, Q.-L. Tetrahedron Lett. 1996, 37, 4129-
4132. (e) Doyle, M. P.; Winchester, W. R.; Hoorn, J. A. A.; Lynch, V.;
Simonsen, S. H.; Ghosh, R. J. Am. Chem. Soc. 1993, 115, 9968-9978.
(7) Maxwell, J. L.; O’Malley, S.; Brown, K. C.; Kodadek, T. Organometallics
1992, 11, 645-652.
‡ University of Delaware.
(1) Doyle, M. P. In ComprehensiVe Organometallic Chemistry II; Abel, E.
W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford, U.K.,
1995; Vol 12, p 387.
(2) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds; John Wiley & Sons: New York
1998.
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978 VOL. 124, NO. 6, 2002 J. AM. CHEM. SOC.
10.1021/ja011895y CCC: $22.00 © 2002 American Chemical Society

cis Cyclopropanation of R-Olefins
A R T I C L E S
(rhodium), pybox (ruthenium),8 or salen (cobalt,9 ruthenium9,10
have also provided noticeable enantiomeric excesses.
)
achieved both highly cis and trans diastereoselectivities with
Co-salen complexes by modifying the groups attached to the
salen ligand.14 In their preliminary communication,14a a 98:2
cis/trans ratio was reported for styrene cyclopropanation using
the bulkier tert-butyl diazoacetate as the carbene source, a Co-
(II)-salen complex as the catalyst, and N-methylimidazole as
an additive. Later, this work was extended to ethyl diazoacetate,
with similar results and conditions, and 24 h as the total reaction
time.14b Finally, Mezzetti et al.15 recently reported high cis
diastereoselectivities with the five-coordinated [RuClPNNP)]+
complexes, although yields are quite low (12% yield for a 95:5
cis/trans ratio).
In contrast to the aforementioned advance in enantioselec-
tivity, diastereocontrol of this transformation has remained
somewhat elusive. The number of catalysts reported to date that
induce a noticeable degree of diastereomeric excess (de) is
relatively small in number compared with those providing large
ee’s. This fact has been explained in terms of the small influence
of the structure of the catalyst in the diastereoselectivity due to
the existence of an early transition state (A) in which the olefin
The situation with R-olefins is somewhat simple: only a few
catalysts have induced trans diastereoselectivities and none, to
our knowledge, has been reported to promote cis diastereo-
selectivity in noticeable yield. The menthyl or the BHT diazo
derivatives have provided excesses of the trans isomer in the
1-alkene cyclopropanation reaction.16 More interesting is the
cyclopropanation of 2,5-dimethyl-2,4-hexadiene to give the
chrysanthemate ester (eq 2), due to its use in pesticide industry.
is sufficiently far from the metal center to be affected by steric
effects.2 These steric influences are not therefore decisive in
the induction of de’s, although some good results have been
obtained by means of very bulky diazo compounds, olefins, or
both. The cyclopropanation of styrene has been frequently
employed as a probe to test the catalytic potential of a transition-
metal complex toward this transformation (eq 1). The vast
With those sterically demanding diazo compounds, preferentially
trans diastereoselectivity has been already published: Masam-
une17 reported 16:84 cis/trans formation with a copper-based
catalyst and menthyl diazoacetate whereas Doyle later provided
a 6:94 cis/trans ratio when using rhodium acetate and BDA as
the carbene source.16a Only the already mentioned Mezzetti’s
catalyst [RuClPNNP)]+ has afforded excesses of the cis isomer,
but only in a 18% yield.15
The above information constitutes the starting point of this
work, part of which has already been communicated:18 the
development of a cis diastereoselective catalyst for the general
cyclopropanation reaction of styrene as well as for R-olefins.
majority of reported catalysts have provided cis/trans ratios
within the range 50:50-25:75. Beyond these limits, a catalyst
could be described as unusually diastereoselective. A few
examples are known to preferentially promote the formation of
the trans diastereomer. Complex RuCl2(Pybox-ip) provided a
9:91 cis/trans ratio.8 The porphyrin osmium complex Os(TPP)
(TPP ) tetraphenylporphyrin) enhanced the trans selectivity up
to 1:13 (cis/trans),11 whereas the iron analogue decreased that
ratio to 1:9.12 The cobalt complex Co(salen)I also favored that
isomer, leading to a 2:98 cis/trans ratio.9
On the other hand, cis diastereoselectivity is still rare1 in such
a way that the maximum values reached when we started our
work on this topic corresponded to Hossain’s iron-based catalyst,
[Cp(CO)2Fe(THF)]+,12 (84:16 cis/trans ratio, 40% yield). The
well-known copper and rhodium catalysts had not provided
better results. Only a modest 74:26, cis/trans ratio had been
reported by Brunner and co-workers using a chiral, camphor-
derived tetrakis(pyrazolyl)borate copper(I) complex.13 In a work
developed simultaneously to ours, Katsuki and co-workers
Results and Discussion
r -Olefin Cyclopropanation Reaction Catalyzed by TpX
-
Cu. We previously reported the catalytic capabilities of the
complex Tp*Cu(C2H4) or its 16-e derivative Tp*Cu (Tp* )
hydrotris(3,5-dimethylpyrazolyl)borate toward the conversion
(14) (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.
(8) Nishiyama, H.; Itoh, Y.; Matsumoto, H.; Park, S.-B.; Itoh, K. J. Am. Chem.
Soc. 1994, 116, 2223
(9) Fukuda, T.; Katsuki, T. Synlett 1995, 825-826.
(10) (a) Uchida, T.; Irie, R.; Katsuki, T. Synlett 1999, 1163-1165. (b) Uchida,
T.; Irie, R.; Katsuki, T Tetrahedron 2000, 56, 3509.
(11) Smith, D. A.; Reynolds, D. N.; Woo, L. K. J. Am. Chem. Soc. 1993, 115,
2511
(15) Bachmann, S.; Furler, M.; Mezzetti, A. Organometallics 2001, 20, 2102-
2108.
(16) (a) Doyle, M. P.; Bagheri, V.; Wandless, T. J.; Harn, N. K.; Brinker, D.
A.; Eagle, C. T.; Loh, K.-L. J. Am. Chem. Soc. 1990, 112, 1906. (b) Aratani,
T. Pure Appl. Chem. 1985, 57, 1839.
(12) Seit, W. J.; Saha, A. K.; Hossain, M. M. Organometallics 1993, 12, 2604.
(13) Brunner, H.; Singh, U. P.; Boeck, T.; Altmann, S.; Scheck, T.; Wrackmeyer,
B. J. Organomet. Chem. 1993, 443, C16-C18.
(17) Lowenthal, R. E.; Masamune, S. Tetrahedron Lett. 1991, 32, 7373.
(18) D´ıaz-Requejo, M. M.; Belderrain, T. R.; Trofimenko, S.; Pe´rez, P. J. J.
Am. Chem. Soc. 2001, 123, 3167-3168.
9
J. AM. CHEM. SOC. VOL. 124, NO. 6, 2002 979

A R T I C L E S
D´ıaz-Requejo et al.
Table 1. R-Olefin Cyclopropanation Reaction Catalyzed by TpXCua
TpPhCu
TpR-NtCu
TpPh,4-MeCu
TpMsCu
olefin
% yieldb
cis:transc
% yieldb
cis:transc
% yieldb
cis:transc
% yieldb
cis:transc
de
3,3′-dimethyl-1-butened
2,5-dimethyl, 2,4-hexadiened
1-hexene
61
99
65
69
66
93
80
91
25:75
42:58
44:56
44:56
45:55
46:54
80:20
82:18
28
80
73
72
47
93
87
92
26:74
60:40
49:51
47:53
52:48
59:41
82:18
84:16
78
99
63
66
30
92
86
87
28:72
51:49
50:50
51:49
54:46
57:43
82:18
86:14
82
97
84
80
87
97
>98
98
65:35
78:22
77:23
75:25
92:8
79:21
98:2
97:3
30
56
54
50
84
58
96
94
1-octene
vinyl acetated
n-butyl vinyl ether
styrene
R-methylstyrene
a See Experimental Section b Determined by GC after total consumption of EDA. c Percentage of cyclopropanes at the end of the reaction (diethyl
fumarate and maleate accounted for 100% of EDA). d Carried out with syringe pumps.
of olefins into cyclopropanes,19 the diastereoselectivity achieved
in the cyclopropanation of styrene being modest, but favoring
the cis isomer (55:45). These catalysts have also promoted the
conversion of olefins into aziridines19a and epoxides,20 as well
as of alkynes into cyclopropenes.21 Given the availability of a
considerable number of TpX ligands,22 we have tested their
catalytic capabilities in the cyclopropanation reaction of R-ole-
fins when coordinated to a copper center. The procedure
employed was identical in all cases. The catalyst precursor was
generated in situ upon mixing equimolar amounts of CuI and
the potassium or the thalium salt of the corresponding ligand
TpX. The resulting catalyst-containing solution was charged with
for the olefins. The 3,3-dimethyl-1-butene substrate provided,
in all cases, the lowest cis diastereoselectivity. A group formed
by 2,5-dimethyl-2,4-hexadiene, 1-hexene, 1-octene, vinyl ac-
etate, and n-butyl vinyl ether provided similar values of cis/
trans for each catalyst. This is important since 1-hexene seems
to be an excellent model for the rest of those olefins. Finally,
the styrenes gave the highest values for the cis isomer. A
possible interpretation for these data could be related to the
restriction on phenyl rotation that the ortho methyl groups induce
in the TpMs case, which would force the mesityl rings to occupy
an essential orthogonal orientation with respect to the pyrazolyl
plane. Tolman and co-workers prepared the complex TpMsCu-
(THF),23 its X-ray structure being in good accord with this
proposition. A geometry that would present this characteristic,
together with the transient noncoordinated third pyrazolyl ring
as a cap during the catalytic cycle, would provide the smallest
catalytic pocket, which may be responsible for high cis
selectivity. To our knowledge, there is no previous report on a
catalyst that induces such diastereoselection in this range of
olefins toward the cis isomer using ethyl diazoacetate. As
mentioned above,15 a recent work by Mezzetti et al. described
a ruthenium-based catalyst that, despite its high diastereoselec-
tivity, presents a very low activity (yields <20%), even with
the aid of slow-addition devices. Katsuki’s remarkable cobalt
catalyst,14 which gives both high diastereoselectivity and activity
for styrene, has not yet been reported to work with other olefins.
a 1:5 mixture of ethyl diazoacetate and the olefin (1:50:250,
[Cu]:[EDA]:[olefin]) and stirred at room temperature until no
EDA was detected by GC. The olefins studied included aromatic
or aliphatic, linear or branched, as well as O-containing
substituents. Table 1 displays the results with four different
catalysts (TpPh, TpPh,4Me, TpRNt, TpMs), the most efficient, from
a diastereoselective point of view, being with no doubt TpMsCu.
The phenyl derivative only induced cis excesses for the styrene
derivatives, whereas the trans isomer was the major product
for the other six olefins. When moving to the TpPh,4Me-containing
catalyst, only the bulky 3,3-dimethyl-1-butene olefin gave
excesses in the trans isomer. Very similar values were obtained
with the R-naphthyl derivative. The use of the mesityl derivative
gave, with no exceptions, cis diastereomeric excesses for the
array of olefins studied. The cis diastereoselectivity was clearly
An important feature of these catalysts, in addition to the
preferentially cis diastereoselectivity, is their high activity toward
the cyclopropanation reaction, with very small amounts of the
EDA decomposition products being obtained. Most of the
experiments carried out in Table 1 were run without resorting
to slow-addition devices, thus shortening the reaction times.
Particularly interesting is the result obtained in a scale-up
experiment carried out with styrene, in which a 1:500:2500 [Cu]/
[EDA]/[styrene] ratio (3 g, 25 mmol of EDA, added portionwise
due to the explosive nature of the diazo compound) was
employed. The diazo compound was consumed in 2 h, leading
to a TOF value of 250 mmol h-1. Despite the high concentration
of EDA, the yield in cyclopropanes was >98%, the cis/trans
diastereoselectivity being maintained as >98:2.
increased following the sequence TpPh< TpPh,4Me < TpRNt
<
TpMs. In addition, it is also possible to establish a similar order
(19) (a) Pe´rez, P. J.; Brookhart, M.; Templeton, J. L. Organometallics 1993,
12, 261. (b) D´ıaz-Requejo, M. M.; Pe´rez, P. J.; Brookhart, M.; Templeton,
J. L. Organometallics 1997, 16, 4399. (c) D´ıaz-Requejo, M. M.; Belderrain
T. R.; Nicasio, M. C.; Pe´rez, P. J. Organometallics 2000, 19, 285-289.
(20) D´ıaz-Requejo, M. M.; Belderrain, T. R.; Pe´rez, P. J. Chem. Commun. 2000,
1853-1854.
We have also performed catalytic competition experiments
with several olefins to establish the relative reactivity of those
substrates in our catalytic systems. Styrene, R-methylstyrene,
1-hexene, and 2,5-dimethyl-2,4-hexadiene have been reacted in
(21) D´ıaz-Requejo, M. M.; Mairena, M. A.; Belderrain, T. R.; Nicasio, M. C.;
Trofimenko, S.; Pe´rez, P. J. Chem. Commun. 2001, 1804.
(22) Trofimenko, S. Scorpionates, The Coordination Chemistry of Polypyra-
zolylborate Ligands; Imperial College Press: London, 1999.
(23) Schneider, J. L.; Carrier, S. M.; Ruggiero, C. E.; Young, V. G.; Tolman,
W. D. J. Am. Chem. Soc. 1998, 129, 11408-11418.
9
980 J. AM. CHEM. SOC. VOL. 124, NO. 6, 2002

cis Cyclopropanation of R-Olefins
A R T I C L E S
Scheme 2
Figure 1. Variation of the rate constant (kobs) vs catalyst concentration for
couples, using a 1:25:250 [Cu]/[EDA]/[olefin] ratio (125 equiv
of each olefin). The relative reactivity order obtained was 322:
154:20:1 for styrene/R-methylstyrene/1-hexene/diene, respec-
tively. These data must be taken into account in a cyclopropa-
nation experiment, since those less reactive olefins would be
better cyclopropanated by means of a syringe pump, to optimize
the overall yields.
EDA decomposition catalyzed by complexes BpXCu and TpXCu.
Scheme 3
Kinetic Studies. Mechanistic studies24 carried out recently
with the model complex BpCu (Bp ) dihydrobis(pyrazolyl)-
borate) have led us to propose that the active species that reacts
with the diazo compound to generate the metal-carbene
intermediate must accomplish a 14-electron geometry. It was
also demonstrated that the olefin inhibited the consumption of
EDA, due to the formation of copper-olefin complexes. In
addition, the presence of other N-donor ligands also induced
the same effect, i.e., a decrease in the concentration of the active
catalytic species. After these results, and given the exceptional
catalytic capabilities of the TpXCu system, we decided to
compare, from a kinetic point of view, the catalytic properties
of the complexes BpXCu and the related TpXCu (BpX dBp; Bp
) Bp*, dihydridobis(3,5-dimethylpyrazolyl)borate; TpX ) Tp,
hydrotris(pyrazolyl)borate; Tp ) Tp*). Thus, the disappearance
of EDA with time was monitored for each of those catalysts,
upon varying their concentrations, in a set of experiments carried
out in the absence of olefin (see Experimental Section). In all
cases, first-order kinetics were observed, indicating that the
formation of the metal-carbene intermediate is the rate-
determining step. Scheme 2 displays a simple reaction mech-
anism that would explain these data. It can be readily seen that
the rate of EDA consumption should be given by eq 3, and the
value of kobs should be that of eq 4:
1 would invoke the existence of a dihapto-trihapto equilibrium
in the TpX complexes, in such a way that the active catalytic
species to react with EDA would be the dihapto form. If we
assume this, then Scheme 2 would convert in Scheme 3, and
the value of kobs should now include the equilibrium constant
KL (eq 5).
2k1[Cu]totKL
kobs
)
(5)
1 + KL
Our previous studies with the model system of BpCu have
shown values of KL that indicated the 14-electron species are
less favored in the equilibrium. This would explain the observed
decrease in the kobs values when moving from BpXCu to TpXCu
as the catalysts. It seems reasonable to believe that the catalytic
active species when using the complexes TpXCu as the catalyst
precursors would be a dihapto species, with a third pyrazolyl
ring uncoordinated. This κ2-TpXCu would react with EDA to
give the corresponding carbene intermediate (B in Scheme 3).
This proposal finds support in a very recent contribution from
Straub and Hoffman,25 in which they have detected for the first
time a copper(I)-carbene complex that is active in the olefin
cyclopropanation reaction. This carbene complex (C) contains
an iminophosphanamide ligand, the LCu moiety accounting for
14 electrons and being isoelectronic to the κ2-TpXCu fragment.
-d[EDA]
) 2k1[Cu]tot[EDA]
(3)
(4)
dt
kobs ) 2k1[Cu]tot
Figure 1 shows the variation of kobs versus [Cu]tot for the
four catalysts referred to above. A significant difference
appeared between the bis- and the tris(pyrazolyl)borate deriva-
tives. Both catalysts with two N-donors showed a similar
variation in the reaction rate, the same similarity being observed
with the couple of three N-donor ligands. But a considerable
difference is established between the two and three N-donor
ligands. A possible explanation for the trend observed in Figure
(24) D´ıaz-Requejo, M. M.; Belderrain T. R.; Nicasio, M. C.; Prieto, F.; Pe´rez,
P. J.; Organometallics 1999, 18, 2601-2609.
(25) Straub, B. F.; Hofmann, P. Angew. Chem., Int. Ed. 2001, 40, 1288.
9
J. AM. CHEM. SOC. VOL. 124, NO. 6, 2002 981

A R T I C L E S
D´ıaz-Requejo et al.
Table 2. cis/trans-Cyclopropane Ratio Obtained with BpXCu and
TpXCu Complexes
1
2
3
R
R
R
BpX
TpX
H
H
H
H
H
Me
H
25:75
40:60
40:60
42:58
55:45
62:38
Me
tBu
Also, Garc´ıa and co-workers26 reported a theoretical study on
the copper-catalyzed cyclopropanation reaction, in which they
have demonstrated that the carbene moiety is attached to a 14-e
metal center prior to its interaction with the olefin. In addition,
the existence of a copper-olefin complex has also been
proposed as the resting state.
We believe that the third pyrazolyl ring in κ2-TpXCu could
not be “innocent” during the cyclopropanation process: on the
other hand, its proximity to the metal center could have a certain
influence in the induction of diastereoselectivity. We have
obtained some relevant information after comparing the values
of diastereoselectivity induced by several BpXCu and TpXCu
complexes. The results are shown in Table 2. The existence of
a third pyrazolyl ring in the TpX ligands induced the enhance-
ment of the amount of the cis isomer in the three cases. We
interpret all the above results as follows: the TpX ligand acts
in a dihapto form during the carbene-transfer reaction, but the
noncoordinated ring is responsible for a certain degree of the
preferentially cis isomer formation.
Thermodynamic and Kinetic Considerations. We per-
formed several experiments at different temperatures in order
to test the influence of this variable in the catalyst-induced
diastereoselection. In the case of styrene, a similar trend was
observed for the group of TpR-Nt-, TpPh,4Me-, TpPh,4Et-, and
TpPh,4Pr-containing catalysts: the amount of the cis isomer was
slightly enhanced (5%) along the temperature range from +50
to -10 °C. In the case of the TpMsCu catalyst, the percentage
of the cis isomer remained constant within the range of
temperature studied. We believe this is a consequence of the
existence of the already mentioned rigid geometry for the latter
and a somewhat less rigid conformation for the others, so that
rotation of the phenyl ring is diminished as the temperature
decreases. We also studied the same effect with 1-hexene, but
no detectable changes in diastereoselectivity were observed with
the above catalysts. Since 1-hexene presents a considerably less
sterically demanding geometry compared to styrene, it seems
that the observed effect of the temperature in the conformation
of the phenyl rings in the TpX ligands has no parallelism in the
1-hexene case, a fact that could be applied to the rest of olefins.
From the above results, it seems that the diastereoselectivity
induced by a given catalyst and a certain olefin shows almost
no dependence with respect to temperature. This could be
interpreted as a consequence of a small or no thermodynamic
control in this transformation, which obviously must be related
to a kinetically controlled catalytic process. We have monitored
the disappearance of ethyl diazoacetate in the cyclopropanation
of styrene using four different catalysts that also differ in the
diastereoselectivity that induces to the reaction: Tp* (16% de),
Τpâ-Nt (34% de), TpPh (60% de), and TpMs (96% de). After
total consumption of EDA, first-order kinetics were observed,
Figure 2. Plot of kobs vs percentage for the cis isomer in the styrene
cyclopropanation reaction.
from which the values of kobs were obtained. Figure 2 shows
the plot of kobs versus the percentage of cis-cyclopropane, where
a linear dependence is observed. We believe that this observation
is in accord with our proposal of a kinetically controlled process.
Therefore, the cis isomer is the kinetic isomer whereas the trans
isomer is the thermodynamically favored. We might conclude
that, in this system, the generation of the cis isomer governs
the overall reaction rate.
Conclusions
A family of catalysts of general formula TpXCu, generated
in situ, catalyzes the cyclopropanation of terminal olefins,
including aryl, alkyl with O-containing substituents, and the
industrially important 2,5-dimethyl-2,4-hexadiene substrate,
using the readily available ethyl diazoacetate as the carbene
source. The mesityl derivative, TpMsCu, provides exceptionally
high levels of diastereoselectivity toward the cis-cyclopropane
for all the olefins studied and with very high yields that are, in
some cases, almost quantitative. Kinetic studies have revealed
that the TpX ligands act in a dihapto form during the carbene-
transfer reaction, with the noncoordinated pyrazolyl ring playing
a substantial role in the induction of the diastereoselectivity.
These studies have also shown that the transformation seems
to proceed under kinetic control, in which the formation of the
kinetic isomer, the cis-cyclopropane, regulates the reaction rate.
Experimental Section
General Methods. All preparations and manipulations were carried
out under an oxygen-free nitrogen atmosphere using conventional
Schlenk techniques. The solvents employed for all preparations were
degassed before use. Olefins and ethyl diazoacetate were purchased
from Aldrich and employed without further purification. The homoscor-
pionate ligands were prepared according to literature methods22 as well
as the complexes BpXCu27 and TpXCu.28 GC data were collected with
(27) (a) Bruce, M. I.; Walsh, J. D. Aust. J. Chem. 1979, 32, 2753. (b) Houser,
R. P.; Tolman, W. B. Inorg. Chem. 1995, 34, 1632.
(28) Mealli, C.; Arcus, C. S.; Wilkinson, J. L.; Marks, T. J.; Ibers, J. A. J. Am.
Chem. Soc. 1975, 98, 711.
(26) Fraile, J. M.; Garc´ıa, J. I.; Mart´ınez-Merino, V.; Mayoral, J. A.; Salvatella,
L. J. Am. Chem. Soc. 2001, 123, 7616.
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982 J. AM. CHEM. SOC. VOL. 124, NO. 6, 2002

cis Cyclopropanation of R-Olefins
A R T I C L E S
a Varian GC-3350 instrument. NMR experiments were run in a Varian
Mercury 400-MHz spectrometer.
cyclopropane (R-methylstyrene)/cyclopropane (styrene) products was
determined by GC after total consumption of EDA. Following the same
procedure, experiments with equimolar mixtures of 1-hexene/styrene
and 1-hexene/2,5-dimethyl-2,4-hexadiene gave the respective ratio of
products 0.063 and 20.21.
Kinetic Experiments. All the kinetics experiments reported in this
contribution were carried out by following the same procedure. The
required amount of the precatalyst was dissolved in 1,2-dichloro-
methane, and then olefin, EDA, or both were added to the stirred
solution in the corresponding ratio. The consumption of EDA was
monitored at 25 °C by GC. The initial conditions, concentration versus
time tables, and corresponding plots are given in the Supporting
Information.
General Cyclopropanation Reaction of Styrene. (a) A total of 0.05
mmol of CuI and an equimolar amount of the MTp′ salt (M ) K, Tl)
were suspended in CH2Cl2, and the mixture was stirred for 2-3 h.
The salts were removed by filtration, and the filtrate was charged with
styrene (1.3 g, 12.5 mmol, 500 equiv) and 50 equiv of EDA (0.285 g,
2.5 mmol). Both reagents were added in one portion. The consumption
of EDA was monitored by GC, the reaction time ranging from 1 to 3
h. The effect of temperature in the diastereoselectivity was studied upon
performing the above transformation inside a thermostatic bath of t (
0.1 °C. (b) A scale-up experiment was carried out with the TpMsCu
catalyst, using a 1:500:2500 [Cu]/[EDA]/[styrene] ratio (3 g, 25 mmol
of EDA). In this case, EDA was added portionwise to avoid explosions.
After 2 h, no EDA was detected in the reaction mixture. The yield in
cyclopropanes was >97%, with a 98:2 cis/trans diastereoselectivity.
(c) For other olefins, the procedure was identical. For the less reactive
olefins, the yields were optimized by means of a syringe pump. In this
case, a solution of EDA in 20 mL of dichloroethane was added at a 2
mL/h rate into the olefin and catalyst-containing solution. The results
are shown in Table 2.
Acknowledgment. We thank the Direccio´n General de
Ensen˜anza Superior (Proyectos PB98-0958 and 1FD97-0919-
CO2-O2) and the Universidad de Huelva (Plan Propio de
Investigacio´n and Servicio de Resonancia Magne´tica Nuclear).
Supporting Information Available: Derivation of kinetic eqs
3-5. Concentration vs time tables and the corresponding plots
for all the kinetic data referred in the text. This material is
available free of charge via the Internet at http://pubs.acs.org.
See any current masthead page for ordering information and
Web access instructions.
Cyclopropanation Competition Experiments with Several Ole-
fins. The catalyst was generated in situ following the aforementioned
procedure. The solution containing the catalyst was charged with 250
equiv (12.5 mmol) of an equimolar mixture of styrene and R-methyl-
styrene. Ethyl diazoacetate (0.142 g, 1.25 mmol) was immediately
added, in one portion, to the above solution. A 0.48 ratio of
JA011895Y
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