Electronically tuned chiral ruthenium porphyrins: Extremely stable and selective catalysts for asymmetric epoxidation and cyclopropanation

Article abstract of DOI:10.1002/chem.200305045

We report the use of three enantiomerically pure and electronically tuned ruthenium carbonyl porphyrin catalysts for the asymmetric cyclopropanation and epoxidation of a variety of olefinic substrates. The D₄-symmetric ligands carry a methoxy, a methyl or a trifluoromethyl group at the 10-position of each of the 9-[anti-(1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethanoanthracene)]-substituents at the meso-positions of the porphyrin. Introduction of a CF ₃-substituent in this remote position resulted in greatly improved catalyst stability, and turnover numbers of up to 7500 were achieved for cyclopropanation, and up to 14200 for epoxidation, with ee values typically >90% and ≈80%, respectively. In one example, the axial CO ligand at the ruthenium was exchanged for PF₃, resulting in the first chiral ruthenium porphyrin with a PF₃ ligand reported to date. In cyclopropanations with ethyl diazoacetate, the latter catalyst performed exceedingly well, and gave a 95% ee in the case of 1,1-diphenylethylene as substrate.

Full text of DOI:10.1002/chem.200305045

FULL PAPER
Electronically Tuned Chiral Ruthenium Porphyrins: Extremely Stable and
Selective Catalysts for Asymmetric Epoxidation and Cyclopropanation
[a]
Albrecht Berkessel,*Patrick Kaiser, and Johann Lex
Dedicated to Prof. Dr. Drs. h.c. Helmut Schwarz on the occasion of his 60th birthday
Abstract: We report the use of three
enantiomerically pure and electronically
tuned ruthenium carbonyl porphyrin
catalysts for the asymmetric cyclopropa-
nation and epoxidation of a variety of
olefinic substrates. The D4-symmetric
ligands carry a methoxy, a methyl or a
trifluoromethyl group at the 10-position
of each of the 9-[anti-(1,2,3,4,5,6,7,8-
octahydro-1,4:5,8-dimethanoanthra-
tions of the porphyrin. Introduction of
a CF3-substituent in this remote position
resulted in greatly improved catalyst
stability, and turnover numbers of up
to 7500 were achieved for cyclopropa-
nation, and up to 14200 for epoxidation,
with ee values typically >90% and
ꢀ80%, respectively. In one example,
the axial CO ligand at the ruthenium
was exchanged for PF3, resulting in the
first chiral ruthenium porphyrin with a
PF3 ligand reported to date. In cyclo-
propanations with ethyl diazoacetate,
the latter catalyst performed exceed-
ingly well, and gave a 95% ee in the case
of 1,1-diphenylethylene as substrate.
Keywords: asymmetric catalysis
cyclopropanation epoxidation
porphyrins ¥ ruthenium
¥
¥
¥
cene)]-substituents at the meso-posi-
Introduction
In organic synthesis, asymmetric epoxidation and cyclopro-
ˆ
panation are very useful transformations of the C C double
bond, and a number of highly efficient and selective catalyst
3]
systems have been developed for both reaction types.[1 In
recent years, the potential of ruthenium porphyrins in these
fields has become evident: For example, in 1996 Gross et al.
reported the first application of the chiral, tartaric acid-
derived ruthenium porphyrin 1a in asymmetric olefin epox-
idation, 58% ee were achieved with styrene as substrate.[4, 5]
This ruthenium porphyrin 1a was also tested in the asym-
metric cyclopropanation of styrene with ethyl diazoacetate by
Simonneaux et al. in 1998, and ee values up to 52% were
reported.[6, 7] Recently, further improvement resulted from
using the phenyl- (1b) and in particular the 3-chlorophenyl-
substituted catalyst 1c: Enantiomeric excesses up to 83%
were achieved in the epoxidation of 4-chlorostyrene, and total
turnover numbers reached up to ꢀ500 (epoxidation of trans-
b-methylstyrene).[8] In 1997, both we[9, 10] and the group of
Che[11] reported the synthesis of the chiral ruthenium carbonyl
porphyrin 2a, starting from the corresponding D4-symmetric
porphyrin first described by Halterman et al.[12] The latter
ruthenium porphyrin 2a turned out to be an extremely active
and selective catalyst for the asymmetric cyclopropanation of
styrenes with ethyl diazoacetate: For example, in our hands,
styrene (3) gave a quantitative yield of the corresponding
cyclopropanes with a trans/cis ratio of 96:4, and with an ee of
the trans-product 4a of 91% (at 08C; 87% ee at 258C;
Scheme 1).[10] More than 1000 catalyst turnovers could easily
be achieved.[9, 10] In catalytic epoxidation, the ruthenium
porphyrin 2a allowed the conversion of for example 1,2-
[a] Prof. A. Berkessel, Dr. P. Kaiser, Dr. J. Lex
Institut f¸r Organische Chemie der Universit‰t zu Kˆln
Greinstrasse 4, 50939 Kˆln (Germany)
Fax : (‡49)-221-470-5102
dihydronaphthalene (5) to its epoxide
6 in 77% ee
(Scheme 1).[10] Again, catalyst loadings were in the range of
0.1 mol%.
E-mail: berkessel@uni-koeln.de
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DOI: 10.1002/chem.200305045
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4746 4756
We reasoned that electronic fine-tuning of the porphyrin
ligand of 2a might allow a further increase in catalyst stability,
that is total turnover numbers, and also in selectivity.[13] We
herein report the synthesis of a new generation of chiral
ruthenium porphyrins 2b d that carry either a methoxy, a
methyl or a trifluoromethyl group in the 10-position of the
9-[anti-(1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethanoanthracene)]-
meso-substituents (X in 2b d), together with the catalytic
performance of these materials. As it turned out, in particular
the CF3 substitution improved the catalyst stability tremen-
dously, and total turnover numbers of up to 7500 were
achieved for cyclopropanation, and up to 14200 for epox-
idation, with ee values typically in the range ꢁ90% and
ꢀ80%, respectively. These catalyst stabilities are the best
reported ever in homogeneous cyclopropanation, especially
in epoxidation. Furthermore, the X-ray crystal structure and
remarkable catalytic activity of the first chiral Ru porphyrin
carrying an axial PF3-group instead of CO (2e) is also
reported.
Scheme 2. Preparation of the chiral ruthenium porphyrins 2a d from the
aldehydes 7a d.
Scheme 1. Asymmetric epoxidation and cyclopropanation with the chiral
ruthenium porphyrin 2a as catalyst. DCPNO: 2,6-dichloropyridine-N-
oxide.
Scheme 3. Conversion of the unsubstituted aldehyde rac-7a to the
methoxylated and methylated aldehydes rac-7b and rac-7c. *): racemic
mixture.
(R,R)-hydrobenzoin,[18] fractional crystallization and hydrol-
ysis proved successful. By this method, aldehyde 7a was
obtained in 60% overall yield from the racemic mixture.[19, 20]
Similarly, this method provided methoxy aldehyde ent-7b in
28% yield, methylated aldehyde 7c (22%) and its enantiomer
ent-7c (52%).[20] The enantiomeric purities of the aldehyde
products were generally ꢁ99% (GC, HPLC). Furthermore,
the absolute configurations of aldehydes 7a, ent-7b, ent-7c
and 7d were established unambiguously by X-ray structural
analyses of the intermediate crystalline (R,R)-hydrobenzoin
acetals.[16] In the case of trifluoromethylated aldehyde 7d, a
number of unsuccessful attempts were made to introduce the
CF3 substituent at the aldehyde stage, or to formylate a
trifluoromethylated precursor. Finally, the sequence shown in
Scheme 4 proved to be the most efficient one: First, the meso-
precursor 10[12] was iodinated to rac-11, followed by a
Rieche formylation to afford the iodo aldehyde rac-12 in
56% overall yield. When treated with (R,R)-hydrobenzoin in
the presence of PPTS, this material afforded 98% of the
diastereomeric acetals 13a and 13b. The copper-catalyzed
Results and Discussion
Synthesis of the ruthenium porphyrin catalysts: As shown in
Scheme 2, we prepared the chiral Ru porphyrins 2a d by
ruthenium insertion into the porphyrin ligands 8a d by using
[Ru3(CO)12] as the metal source and refluxing phenol as the
solvent, a method described by us before.[9] The porphyrins
8a d were prepared from the aldehydes 7a d by the Lindsey
method.[15]
Consequently, the synthetic approach as a whole hinges on
the availability of the aldehydes 7a d in enantiomerically
pure form. First, for the preparation of the methoxy- and
methyl-substituted aldehydes 7b and 7c in racemic form, the
benzaldehyde derivative rac-7a served as the starting material
(Scheme 3).[12] Dakin oxidation/methylation or catalytic hy-
drogenation afforded the anisol and toluene derivatives rac-
9b and rac-9c, respectively.[16] The formylation of the
intermediates rac-9b,c was performed according to Rieche,
using Cl2CH-OCH3 in the presence of SnCl4.[17] For the
separation of the enantiomers of rac-7a c, acetalization with
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A. Berkessel et al.
FULL PAPER
trifluoromethylation of 13a,b with CF3-TMS[21] proceeded
smoothly and with an excellent yield of 14a,b (96%). Finally,
the separation of 14a by crystallization and hydrolysis
afforded the enantiomerically pure (ꢁ99%) aldehyde 7d.
Again, the absolute configuration of the aldehyde 7d was
established by X-ray crystallography of the acetal 14a.[16] As
summarized in Scheme 2, both the porphyrin synthesis and
the ruthenium insertion proceeded smoothly.
Figure 1. X-ray crystal structure of the ruthenium porphyrin a) 2d and
b) chiral ruthenium-PF3-porphyrin 2e. a) The upper axial coordination site
is occupied by a CO molecule, whereas the lower one carries a methanol
molecule. b) The upper axial coordination site is occupied by a PF3 mo-
lecule, whereas the lower one carries an acetonitrile molecule.
Scheme 4. Preparation of the trifluoromethylated aldehyde 7d from the
octahydro-bis-methano-anthracene 10. *): racemic mixture; a) PhI(OAc)2,
I2; b) SnCl4, Cl2CHOCH3; c) (R,R)-hydrobenzoin, PPTS; d) CF3-TMS,
CuI, KF; e) aq. HCl, (CH2O)n.
substrate, trans/cis ratios are generally better than 95:5, and
enantiomeric excesses of the trans-product reached up to
93%. The latter result (Table 1, entry 7) was achieved with the
tetrakis-CF3-substituted catalyst 2d and represents the best ee
value achieved so far in the Ru porphyrin catalyzed asym-
metric cyclopropanation of styrene.[8, 22] The determination of
the total turnover numbers of the Ru porphyrins ent-2c and
2d revealed that these catalysts perform 5500 and 7200
cyclopropanation cycles, respectively. Overall, the tetrakis-
CF3-substituted Ru porphyrin 2d performs best (Table 1,
entries 6,7).
With a-methylstyrene as substrate, the trans-selectivity of
the Ru porphyrins 2a e is somewhat less pronounced.
Nevertheless, enantiomeric excesses of the trans-products
were generally ꢁ90%. Again, the tetrakis-CF3-substituted
Ru porphyrin 2d showed the best catalytic activity, with
basically quantitative conversion of the substrate olefin within
5 h at 258C (Table 1, entry 12). As expected, a further increase
in enantioselectivity (up to 94%) was achieved by lowering
the reaction temperature (À188C; Table 1, entry 14).
The X-ray crystal structure of the enantiomerically pure
tetrakis-trifluoromethylated ruthenium porphyrin 2d is
shown in Figure 1a. As expected from other crystal structures
of Ru porphyrins,[11] a CO molecule occupies one of the
(homotopic) axial positions of the Ru porphyrin, whereas a
molecule of the solvent methanol is coordinated to the other.
Furthermore, Figure 1a nicely demonstrates the ™chiral rim∫
on both perimeters of the porphyrin, composed of the
methano and ethano bridges of the meso-substituents.
For the generation of the ruthenium PF3 porphyrin 2e,
treatment of CO porphyrin 2a with PF3 at atmospheric
pressure resulted in quantitative conversion. The X-ray
crystal structure of this novel chiral Ru porphyrin is shown
in Figure 1b. Again, one of the axial positions at the
ruthenium ion is occupied by the PF3 ligand, whereas the
other one is occupied by a solvent molecule, in this case
acetonitrile.
In the case of styrene as substrate, the absolute config-
urations of the product cyclopropanes could readily be
assigned based on literature data.[25] However, no such data
appeared to be available for the cyclopropanation products of
a-methylstyrene. We therefore analyzed the corresponding
cyclopropane configurations as follows. First, the mixture of
stereoisomers obtained from a [Cu(acac)2]-catalyzed cyclo-
propanation of a-methylstyrene with ethyl diazoacetate was
separated into the racemic mixtures of the trans- and cis-
isomers by preparative HPLC on silica gel. The individual
enantiomers were then obtained by preparative HPLC on
Chiralpak AD, and all four stereoisomeric cyclopropane
esters were converted to the (S)-phenethylamides. One of the
Catalytic asymmetric cyclopropanation: A screening of
various types of olefins (i.e., terminal, E- and Z-di- and
trisubstituted, etc.) revealed that terminal olefins are the
substrates of choice for the ruthenium porphyrin catalysts
presented here. Our results obtained in the asymmetric
cyclopropanation of various terminal olefins with ethyl
diazoacetate in the presence of the catalysts 2a d and 2e
are summarized in Table 1. Generally, 0.1 mol% of catalyst
(relative to olefin) were employed, and a slight excess of the
diazoacetate (1.1 equiv). We generally found that the trans-
cyclopropanes are formed preferentially. With styrene (3) as
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Chiral Ruthenium Porphyrins
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diastereomeric phenethylamides of both the trans-and the cis-
cyclopropanes was analyzed by X-ray crystallography. By this
procedure, two X-ray crystal structures allowed the assign-
ment of all four of the cyclopropane absolute configurations
(see Experimental Section).
Our results obtained with 1,1-diphenylethylene as substrate
are summarized in entries 15 20 of Table 1. Among the
carbonyl complexes 2a d, again the tetrakis-CF3-substituted
Ru porphyrin 2d performed best, both in terms of rate and
enantioselectivity. However, it is interesting to note that the
ruthenium PF3 porphyrin 2e (Table 1, entries 19, 20) shows
characteristics significantly different from its CO counterpart
(Table 1, entry 15): Whereas the reaction rate of the PF3-
complex 2e is about one half of that of the CO-complex 2a,
the enantioselectivity of the former catalyst is significantly
higher (94 vs 77%: Table 1, entries 15, 19). In the case of the
2a, we could show both by NMR- and in situ IR spectroscopy
that addition of diazo acetate resulted in rapid loss of the
CO ligand and formation of the carbene complex.[23] We
therefore assume that in the case of 2e, the phosphine ligand
does not dissociate, and that a pseudo-octahedral ruthenium
species acts as a carbene carrier (as opposed to a five-
coordinated Ru complex in the case of 2a).[10, 23] This assump-
tion is in accord with the known higher stability of other
(achiral) Ru porphyrin complexes of PF3 compared with
their CO analogues.[24]
Table 1. Catalytic cyclopropanation of olefins with ethyl diazoacetate.[a]
Olefin
Catalyst
T [8C]
Conversion of
olefin [%][c]
trans/cis (% de)[c]
ee trans [%][c]
87 (1S,2S)
ee cis [%][c]
14 ( S,2R)
1
2a
25
80
96:4 (92)
1
[b]
2
3
4
5
6
7
8
ent-2a
ent-2b
ent-2c
ent-2c
2d
0
25
25
0
25
0
95:5 (90)
96:4 (92)
96:4 (92)
98:2 (96)
97:3 (94)
96:4 (92)
96:4 (92)
91 (1R,2R)
90 (1R,2R)
89 (1R,2R)
92 (1R,2R)
89 (1S,2S)
93 (1S,2S)
87 (1S,2S)
27 ( R,2S)
31 ( R,2S)
11 ( R,2S)
19 ( R,2S)
< 1
7 ( S,2R)
1
81
83
72
94
70
81
1
1
1
2d
2e
1
25
14 ( S,2R)
1
9
2a
25
79
66:34 (32)
90 (1S,2S)
38 ( S,2R)
1
10
11
12
13
14
ent-2b
ent-2c
2d
2e
2e
25
25
25
25
À 18[d]
76
81
> 98
78
73
68:32 (36)
67:33 (34)
69:31 (38)
66:34 (32)
73:28 (45)
91 (1R,2R)
91 (1R,2R)
91 (1S,2S)
90 (1S,2S)
94 (1S,2S)
43 ( R,2S)
46 ( R,2S)
36 ( S,2R)
38 ( S,2R)
53 ( S,2R)
1
1
1
1
1
15
2a
25
91
77 (S)
16
17
18
19
20
ent-2b
2c
2d
2e
2e
25
25
25
25
À 18[d]
76
86
98
56
18
77 (R)
76 (S)
82 (S)
94 (S)
95 (S)
21
2a
25
20
86:14 (72)
46 (1S,2S)
9[e]
22
23
24
25
ent-2b
ent-2c
2d
25
25
25
25
15
20
30
42
85:15 (70)
82:18 (64)
85:15 (70)
99.5:0.5 (99)
40 (1R,2R)
39 (1R,2R)
46 (1S,2S)
82 (1S,2S)
< 2[e]
< 2[e]
4[e]
2e
6[e]
26
2e
25
98
70:30 (40)
83[e]
43[e]
27
2e
À 18[d]
85
62:38 (24)
76[e]
20[e]
[a] Typical reaction conditions: substrate olefin/DAE/catalyst 1000:1100:1 in 1,2-dichloroethane; DAE was added over a period of 5 h by means of a syringe
pump. [b] Styrene/DAE/catalyst 1000:660:1; DAE was added over a period of 2 h by means of a syringe pump; olefin conversion based on DAE consumed
was quantitative. [c] Conversions and ratios of stereoisomers were determined by capillary GC as described in the Supplement. Relative and absolute
configurations were determined as described in the text. [d] Catalyst loading was 0.2 mol% relative to olefin. [e] Absolute configuration not determined.
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Table 2. Cyclopropanation of styrene and a-methylstyrene with phenyl
diazomethane, using the ruthenium porphyrin 2e as catalyst.[a]
Entries 21 27 of Table 1 summarize our evaluation of the
catalysts 2a e in the asymmetric cyclopropanation of non-
conjugated terminal olefins (1-octene, entries 21 25) and
enol ethers (a-trimethylsiloxystyrene, entries 6, 27). Whereas
all CO-complexes (2a d) afforded trans/cis ratios in the
range of 85:15 and only moderate ee values (39 46%) in the
case of 1-octene, almost perfect diastereoselectivity (trans/cis
99.5:0.5) resulted from the use of the PF3 porphyrin 2e, with
an ee of the trans-cyclopronane of 82% (Table 1, entry 25).
This result again indicates that the carbene carriers generated
from the porphyrins 2a (axial CO) and 2e (axial PF3) are not
identical, that is the PF3 ligand remains bound to the
ruthenium ion. Finally, in the case of a-trimethylsiloxystyrene,
the Ru PF3 catalyst afforded a trans/cis-ratio of about 2:1,
and moderate ee values of ꢀ80% (Table 1, entries 26, 27).
Please note that with this particular substrate, the diastereo-
and enantioselectivities decrease when the reaction temper-
ature is lowered from 25 to À188C.
Olefin
Conversion
of olefin [%][b]
trans/cis
(% de)[b]
ee trans
[%][b]
ee cis
[%][b]
1
2
6
51:49 (2)
72 (1R,2R)
45
83:17 (66)
96 (n.d.)
34 (n.d.)
[a] Typical reaction conditions: substrate olefin/phenyl diazomethane/
catalyst 500:800:1 in 1,2-dichloroethane at 258C. [b] See footnote [c] of
Table 1.
exposed to a mixture of 30000 equiv styrene and 33000 equiv
2,6-DCPNO in benzene at room temperature. Again, the CF3-
substituted catalyst 2d proved best: The epoxidation finally
stalled at 47.3% conversion of olefin to epoxide, that is 14200
catalyst turnovers had occurred. We attribute the outstanding
stability of the catalyst 2d to the electron withdrawing effect
of the four CF3 substituents. In other words, the general
competition of oxygen transfer versus oxidative destruction of
the catalyst is shifted in favor of the former. By the same
token, the higher electrophilicity of the oxygen donor (i.e.,
Ru-oxo species) results in higher turnover rates. With 1,2-
dihydronaphthalene as substrate (Table 1, entries 4 8), up to
83% ee were observed. In the case of the non-conjugated
olefin 1-octene (Table 1, entries 9 12), the turnover frequen-
cy became fairly low (ca. 2hÀ1), and the enantiomeric excesses
of the product epoxides dropped to less than 40%. Obviously,
Our results obtained with phenyl diazomethane as the
carbene source and with styrene (entry 1) and a-methylstyr-
ene (entry 2) as substrates are summarized in Table 2.
Whereas the trans/cis selectivities are only moderately in
favor of the trans-diastereomers in both cases, the trans-
cyclopropane from a-methylstyrene was formed with excel-
lent enantioselectivity (96% ee).
Finally, for the determination of the total turnover number
(TTN), one equivalent of the ruthenium porphyrin catalysts
ent-2c and 2d was exposed to a mixture of 10000 equiv
styrene and 16250 equiv ethyl diazoacetate in 1,2-dichloro-
ethane at room temperature. Again, the CF3-substituted
catalyst 2d proved best: After 72 h, 75.2% of the olefin were
converted to cyclopropane(s), that is 7520 catalyst turnovers
had occurred.
Catalytic asymmetric epoxida-
Table 3. Catalytic asymmetric epoxidation of olefins using 2,6-dichloropyridine N-oxide (2,6-DCPNO) as oxygen
tion: Our results obtained in
epoxidation catalysis are sum-
marized in Table 3. We em-
ployed the so-called Hirobe -
conditions, that is 2,6-dichloro-
donor.[a]
Olefin
Catalyst
Reaction
time [h]
Yield of
epoxide [%][b]
Turnover
frequency [hÀ1
ee of
epoxide [%][c]
]
1
ent-2b
2.5
82[d]
328
76 (R)
pyridine
N-oxide
(2,6-
DCPNO) as the oxygen donor
(1.1 equiv relative to olefin) in
benzene at room tempera-
ture.[26] Typically, catalyst load-
ings of 0.1 mol% (relative to
olefin) were used. We were
delighted to see that styrene
(3) was epoxidized at a turn-
over rate of almost 400hÀ1, and
with ꢀ80% enantiomeric ex-
cess. These results were ach-
ieved with the trifluoromethy-
lated catalyst 2d (Table 3, en-
try 3).
2
3
ent-2c
2d
2.5
2.5
78[d]
97[d]
312
388
76 (R)
79 (S)
4
2a[e]
48
85
71 (1R,2S)
5
6
7
8
ent-2b
2c
ent-2c
2d
7.5
7.5
7.5
7.5
66[f]
63[f]
70[f]
89[f]
88
85
94
80 (1S,2R)
77 (1R,2S)
78 (1S,2R)
83 (1R,2S)
118
9
2a
45
10
2
21 (R)
10
11
12
ent-2b
2c
2d
45
45
45
8
9
16
2
2
4
36 (S)
22 (R)
18 (R)
[a] Typical reaction conditions: substrate olefin/2,6-DCPNO/catalyst 1000:1100:1 in benzene, room temperature.
[b] Yield of epoxide determined by capillary GC, using bromobenzene or 1,2-dibromobenzene as internal
standard. [c] ee determined by capillary GC as described in the Experimental Section. [d] After 20 h, an epoxide
yield ˆ 98% was observed. [e] Chromatographically purified material. [f] After 70 h, an epoxide yield ˆ 98% was
observed.
For the determination of the
total turnover number (TTN),
one equivalent of the rutheni-
um porphyrin catalyst 2d was
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Chiral Ruthenium Porphyrins
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Series FT-IR and a Perkin Elmer 1000 Paragon FT-IR instrument with
Spectrum V. 1.5 software, the intensity of the absorptions are reported as
follows: w (weak), m (medium), s (strong). Elemental analysis was
performed using an Elementar CHN-Analysator Vario EL instrument.
X-ray structures were obtained using a Nonius Kappa CCD instrument
with Denzo software. The structural calculations were performed with
ShelXS86 and refined with ShelXL93 software. Melting points were
obtained in open capillary tubes and are corrected.
electron-rich olefins are the substrates of choice for our
ruthenium porphyrin catalysts.
We routinely purified our ruthenium porphyrins by re-
crystallization prior to use as catalysts. In one case (Table 3,
entry 4), we employed the catalyst 2a without recrystallisa-
tion, that is chromatographically pure material. As shown in
Table 3, this catalyst required about six-fold longer reaction
times. The time course of this reaction showed the typical lag
phase, also reported by Groves et al. (data not shown).[27] It
has been proposed that the lag phase is due to oxidative
catalyst activation. On the other hand, our observation
suggests that oxidative removal of some inhibitory impuri-
ty–which is no longer present in recrystallized material–
may as well account for the induction period.
Solvents and reagents for the catalytic studies were purchased from Fluka
AG and used as received. Solvents for the analytical HPLC were purchased
from Rathburn Chemicals or Acros Chemicals, and used as received.
Solvents for flash chromatography or preparative HPLC were dried and
distilled according to standard procedures. a-Trimethylsiloxystyrene[28] and
phenyldiazomethane[29] were prepared according to the literature proce-
dures.
General procedure a) for the catalytic cyclopropanation of olefins with
ethyl diazoacetate and the ruthenium porphyrin catalysts 2a e at 258C
(08C): A 15 mL Schlenk tube was charged with the catalyst (315 nmol,
1 equiv, see Table 4), the olefin (315 mmol, 1000 equiv) and dry 1,2-
dichloroethane (2 mL) under an argon atmosphere. A solution of ethyl
diazoacetate (36 mL, 40 mg, 347 mmol, 1100 equiv) in dry 1,2-dichloro-
ethane (2 mL) was added continuously while stirring at 258C ( 08C) within
5 h by means of a syringe pump. After the addition was complete,
bromobenzene or 1,2-dibromobenzene (internal standard, 315 mmol,
1000 equiv) was added and a small sample of the crude product was
analyzed by GC or HPLC.
Conclusion
In summary, we have synthesized a new and electronically
tuned generation of ruthenium porphyrin catalysts and have
shown their outstanding performance in cyclopropanation
and epoxidation. Clearly, fourfold introduction of the electron
withdrawing CF3 substituent provides the most reactive (i.e.,
electrophilic) catalyst. Besides impressive enantioselectivities,
the latter ruthenium porphyrin 2d is unmatched with respect
to catalyst stability, that is total turnover numbers achieved.
Table 4. Catalyst loadings used for the cyclopropanation reactions.
Catalyst
2a
2b
2c
2d
2e
mass [mg]
(315 nmol)
400
438
418
486
420
Experimental Section
General procedure b) for the catalytic cyclopropanation of olefins with
ethyl diazoacetate and the ruthenium porphyrin catalyst 2e at À188C: A
15 mL Schlenk tube was charged with the catalyst 2e (840 mg, 630 nmol,
1 equiv), the olefin (315 mmol, 500 equiv) and dry 1,2-dichloroethane
(2 mL) under an argon atmosphere. A solution of ethyl diazoacetate
(36 mL, 40 mg, 347 mmol, 550 equiv) in dry 1,2-dichloroethane (2 mL) was
added continuously while stirring at À188C within 5 h by means of a
syringe pump. After the addition was complete, bromobenzene or 1,2-
dibromobenzene (internal standard, 315 mmol, 500 equiv) was added and a
small sample of the crude product was analyzed by GC or HPLC.
General: Optical rotations were measured at 589 nm using a Propol
polarimeter (Dr. W. Kernchen) from Optik-Elektronik-Automation, or a
Perkin Elmer polarimeter 343plus. In HPLC analysis, the sense of optical
rotation was determined using the Chiralizer instrument from IBZ
Messtechnik GmbH. Analytic HPLC data were obtained using a Merck
Hitachi L-6200A intelligent pump with Merck L-7000 interface, L-7250
autosampler, L-7300 column oven, L-7100 pump, L-4500 diode array
detector and D7000 HSM software V3.1. The following columns have been
used for analytical HPLC separation: LiChroSpher Si60 (Merck, 5 mm,
250 Â 4 mm); Chiralpak AD (Daicel, 5 mm, 250 Â 4.6 mm); Supersphere 60
RP-Select B (Merck, 5 mm, 125 Â 4 mm); Chiralcel OJ-R (Daicel, 5 mm,
150 Â 4.6 mm). Preparative HPLC separations were performed using a
Merck NovaPrep 200 pump with L-7400 UV detector and TurboPrep
software V2.41. The following columns have been used for preparative
HPLC separation: LiChroSorb Si60 (Merck, 12 mm, 25 Â 5 cm); Chiralpak
AD (Daicel, 20 mm, 50 Â 5 cm). Analytical and preparative HPLC separa-
tions were carried out at 258C. Capillary GC data were obtained using a
Hewlett-Packard HP 6890 Series GC System with flame ionization detector
and HP-ChemStation software revised version A.05.01. The following
columns have been used for analytical GLC separation: HP-1, Hewlett-
Packard, crosslinked methyl silicon gum, 25 m, nitrogen as carrier gas; b-
CD1, Macherey-Nagel, heptakis-(2,6-di-O-methyl-3-O-pentyl)-b-cyclodex-
trin, 25 m, He as carrier gas; CB1, Chrompak, Chirasil-Dex CB, 25 m, He as
carrier gas. GC analysis with a mass sensitive detector was performed using
a Hewlett Packard HP 6890 Series GC System with a HP 5973 detector,
HP-ChemStation software G1701 AA V3.0 and a Hewlett Packard HP-5
crosslinked silicon gum column, 25 m, He as carrier gas. High resolution
mass spectroscopy (HR-MS) was carried out on a Finnigan MAT 900S
instrument with ES ion source and PEG as reference substances. Nuclear
magnetic resonance spectra were recorded on Bruker AC250, AC300,
DPX300 or DRX500 instruments. The chemical shift d (ppm) is referenced
against the solvent signal, the multiplicity is recorded as follows: brs (broad
singlet), s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet),
coupling constants in Hz. The assignment of the signals is based on 2-D
experiments. Infrared spectra (IR) were obtained on a Perkin Elmer 1600
General procedure c) for the determination of the total turnover number of
the catalytic cyclopropanation of styrene with ethyl diazoacetate and the
ruthenium porphyrin catalysts: A 25 mL Schlenk flask was charged with
the catalyst (666 nmol, 1 equiv), styrene (759 mL, 687 mg, 6.66 mmol,
10000 equiv) and dry 1,2-dichloroethane (5 mL) under an argon atmos-
phere. A solution of ethyl diazoacetate (1.138 mL, 1.235 g, 10.82 mmol,
16250 equiv) in dry 1,2-dichloroethane (15 mL) was added continuously
while stirring at 258C within 3 d by means of a syringe pump. After the
addition was complete, bromobenzene (internal standard, 300 mL, 447 mg,
2.85 mmol, 4278 equiv) was added and a small sample of the crude product
was analyzed by GC.
General procedure d) for the catalytic cyclopropanation of olefins with
phenyl diazomethane and catalyst 2e: A 15 mL Schlenk tube was charged
with catalyst 2e (0.82 mg, 630 nmol, 1 equiv), the olefin (315 mmol,
500 equiv) and dry 1,2-dichloroethane (2 mL) under an argon atmosphere.
A solution of phenyl diazomethane (60 mg, 504 mmol, 800 equiv) in dry 1,2-
dichloroethane (2 mL) was added continuously while stirring at 258C
within 5 h by means of a syringe pump. After the addition was complete,
dibromobenzene or dibenzyl ether (internal standard, 315 mmol, 500 equiv)
was added and a small sample of the crude product was analyzed by GC.
General procedure e) for the catalytic cyclopropanation of olefins with
[Cu(acac)2] as catalyst: A Schlenk tube was charged with the olefin,
[Cu(acac)2] (5.2 mg per mmol olefin, 4 mol%) and dry 1,2-dichloroethane
(1 mL per mmol olefin) under an argon atmosphere. A solution of the diazo
compound (1.1 equiv) in dry 1,2-dichloroethane (5 mL) was added
Chem. Eur. J. 2003, 9, 4746 4756
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4751

A. Berkessel et al.
FULL PAPER
continuously while stirring at 258C within 15 h by means of a syringe pump.
After the addition was complete, the solvent was removed by rotary
evaporation, and the crude products were purified by Kugelrohr distillation
under reduced pressure.
(1R,2R)-ethyl 2-methyl-2-phenylcyclopropanecarboxylate tR ˆ 37.6 min
Cyclopropanation of 1,1-diphenylethylene with ethyl diazoacetate: GC-
column CB1, helium 1.2 mLminÀ1 (constant flow modus), injector 2508C
(pulsed split modus), detector (FID) 2508C, oven: 808C; 58CminÀ1 1158C
(10 min), 58CminÀ1 1258C (10 min), 208CminÀ1 1408C (5 min), 208CminÀ1
1608C (5 min):
General procedure f) for the amidation of the ethyl cyclopropanecarbox-
ylates with (S)-(À)-1-phenylethylamine:
A 50 mL Schlenk tube was
1,2-dibromobenzene
1,1-diphenylethylene
tR ˆ 10.4 min
tR ˆ 30.3 min
charged with a solution of (S)-(À)-1-phenylethylamine (496 mg, 3.9 mmol,
5.0 equiv) in absolute n-hexane (10 mL) under an argon atmosphere. To the
stirred solution, 1.6n n-butyllithium (2.2 mL, 3.5 mmol, 4.5 equiv) in
absolute n-hexane (5 mL) was added dropwise at À788C. After 30 min, a
solution of the ethyl cyclopropanecarboxylate (0.78 mmol, 1.0 equiv) in dry
n-hexane (10 mL) was added, and the stirred suspension was allowed to
reach room temperature overnight. Saturated aqueous ammonium chloride
solution (10 mL) was added. The organic layer was separated, and the
aqueous layer was extracted with n-hexane (2 Â 10 mL). The combined
organic phases were washed with saturated sodium bicarbonate solution
(2 Â 10 mL), water (10 mL), and dried over Na2SO4. After filtration, the
solution was concentrated to a volume of a few mL. The desired amides
crystallized within a few days at 48C. The purity of the product was checked
by analytical HPLC.
(1R)/(1S)-ethyl 2,2-diphenylcyclopropanecarboxylate tR ˆ 40.0 min.
analytical HPLC-column Chiralcel OJ-R, isopropanol/acetonitrile/water
75:10:15 (0.4 mLminÀ1), UV/Vis array detector and optical rotation
detector (Chiralyser), tR based on Chiralyser detection:
(À)-(1R)-ethyl 2,2-diphenylcyclopropanecarboxylate tR ˆ 15.8 min
(‡)-(1S)-ethyl 2,2-diphenylcyclopropanecarboxylate tR ˆ 24.6 min
Cyclopropanation of 1-octene with ethyl diazoacetate: GC-column CB1,
helium 1.2 mLminÀ1 (constant flow modus), injector 2508C (pulsed split
modus), detector (FID) 2508C, oven: 808C, 58CminÀ1 958C (55 min),
58CminÀ1 1208C (5 min), 208CminÀ1 1608C (2 min):
1-octene
tR ˆ 1.7 min
General procedure g) for the catalytic epoxidation of olefins with 2,6-
dichloropyridine-N-oxide and the ruthenium porphyrin catalysts 2a d: A
15 mL Schlenk flask was charged with the catalyst (315 nmol, 1 equiv, see
Table 5), the olefin (315 mmol, 1000 equiv), 1,2-dibromobenzene (internal
standard, 74 mg, 38 mL, 315 mmol, 1000 equiv) and dry benzene (2 mL)
under an argon atmosphere. 2,6-Dichloropyridine-N-oxide (55 mg,
347 mmol, 1100 equiv) was added. The solution was stirred at 258C, until
no further conversion of the olefin could be observed by GC analysis.
1,2-dibromobenzene
tR ˆ 18.1 min
cis-ethyl 2-(n-hexyl)-cyclopropanecarboxylate tR ˆ 51.3 min
(cis major enantiomer obtained in catalysis with (1S)-configurated Ru
porphyrins)
cis-ethyl 2-(n-hexyl)-cyclopropanecarboxylate tR ˆ 54.0 min
(cis major enantiomer obtained in catalysis with (1R)-configurated Ru
porphyrins)
(1R,2R) ethyl 2-(n-hexyl)-cyclopropanecarboxylate tR ˆ 57.6 min
(1S,2S) ethyl 2-(n-hexyl)-cyclopropanecarboxylate
tR ˆ 58.7 min
Table 5. Catalyst loadings used for the epoxidation reactions.
Cyclopropanation of a-trimethylsiloxystyrene with ethyl diazoacetate: GC-
column b-CD1, helium 100 kPa (constant pressure modus), injector 2008C
(split modus), detector (FID) 2008C, oven: 768C:
Catalyst
2a
2b
2c
2d
mass [mg]
a-trimethylsiloxystyrene
tR ˆ 11.3 min
tR ˆ 17.7 min
(315 nmol)
400
438
418
486
1,2-dibromobenzene
(À)-cis-ethyl 2-trimethylsiloxy-cyclopropanecarboxylate tR ˆ 332.1 min
(cis major enantiomer obtained in catalysis with (1R)-configurated
Ru porphyrins)
General procedure h) for the determination of the total turnover number
of the catalytic epoxidation of styrene with 2,6-dichloropyridine-N-oxide
and the ruthenium porphyrin catalysts: A 5 mL Schlenk flask was charged
with the catalyst (314.4 nmol, 1 equiv), styrene (982 mg, 1.084 mL,
9.432 mmol, 30000 equiv), 1,2-dibromobenzene (internal standard,
743 mg, 380 mL, 3.151 mmol, 10022 equiv) and dry benzene (2 mL) under
Ar. 2,6-Dichloropyridine-N-oxide (1.701 g, 10.375 mmol, 33000 equiv) was
added. The mixture was stirred at 258C, until no further conversion of the
olefin could be observed by GC analysis.
(‡)-cis-ethyl 2-trimethylsiloxy-cyclopropanecarboxylate tR ˆ 362.8 min
(cis major enantiomer obtained in catalysis with (1S)-configurated
Ru porphyrins)
(À)-trans-ethyl 2-trimethylsiloxy-cyclopropanecarboxylate tR ˆ 430.9 min
(trans major enantiomer obtained in catalysis with (1R)-configurated
Ru porphyrins)
(‡)-trans-ethyl 2-trimethylsiloxy-cyclopropanecarboxylate tR ˆ 441.7 min
(trans major enantiomer obtained in catalysis with (1S)-configurated
Asymmetric cyclopropanation, GC- and HPLC analysis
Cyclopropanation of styrene with ethyl diazoacetate: GC-column CB1,
helium 1.2 mLminÀ1 (constant flow modus), injector 2508C (pulsed split
modus), detector (FI 2508C, oven: 808C; 58CminÀ1 1148C (40 min),
58CminÀ1 1208C (1 min), 208CminÀ1 1608C (2 min):
Ru porphyrins)
Cyclopropanation of styrene with phenyl diazomethane: GC-column CB1,
helium 1.4 mLminÀ1 (constant flow modus), injector 2508C (pulsed split
modus), detector (FID) 2508C, oven: 808C (3 min), 108CminÀ1 1238C
(73 min), 108CminÀ1 1508C (5 min), 208CminÀ1 2008C (2 min):
styrene
tR ˆ 3.4 min
tR ˆ 10.5 min
1,2-dibromobenzene
styrene
tR ˆ 4.0 min
(1S,2R)-ethyl 2-phenylcyclopropanecarboxylate tR ˆ 35.3 min
(1R,2S)-ethyl 2-phenylcyclopropanecarboxylate tR ˆ 38.5 min
(1R,2R)-ethyl 2-phenylcyclopropanecarboxylate tR ˆ 39.7 min
(1S,2S)-ethyl 2-phenylcyclopropanecarboxylate tR ˆ 41.0 min
Cyclopropanation of a-methylstyrene with ethyl diazoacetate: GC-column
CB1, helium 1.3 mLminÀ1 (constant flow modus), injector 2508C (pulsed
split modus), detector (FID) 2508C, oven: 808C; 58CminÀ1 1108C
(30 min), 58CminÀ1 1208C (5 min), 208CminÀ1 1608C (2 min):
cis-1,2-diphenylcyclopropane
tR ˆ 45.0 min
tR ˆ 60.6 min
tR ˆ 74.7 min
dibenzyl ether
(1S,2S)-1,2-diphenylcyclopropane
(1R,2R)-1,2-diphenylcyclopropane tR ˆ 75.9 min
Analytical HPLC-column Chiralpak AD, UV/Vis-array-detector and
optical rotation detector (Chiralyser); before each run, the column was
flushed with n-hexane/isopropanol 9:1 (0.7 mLminÀ1); 7 min before sample
injection, the solvent was switched to pure n-hexane (0.7 mLminÀ1),
retention times are based on Chiralyser detection:
a-methylstyrene
tR ˆ 3.4 min
tR ˆ 10.5 min
1,2-dibromobenzene
(‡)-(1R,2R)-1,2-diphenylcyclopropane tR ˆ 7.4 min
(À)-(1S,2S)-1,2-diphenylcyclopropane tR ˆ 9.8 min
Cyclopropanation of a-methylstyrene with phenyl diazomethane: GC-
column b-CD1, helium 100 kPa (constant pressure modus), injector 2008C
(1R,2S)-ethyl 2-methyl-2-phenylcyclopropanecarboxylate tR ˆ 29.2 min
(1S,2R)-ethyl 2-methyl-2-phenylcyclopropanecarboxylate tR ˆ 31.3 min
(1S,2S)-ethyl 2-methyl-2-phenylcyclopropanecarboxylate tR ˆ 36.6 min
4752
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 4746 4756

Chiral Ruthenium Porphyrins
4746 4756
(split modus), detector (FID) 2008C, oven: 808C (5 min), 208CminÀ1
1088C
trans-Enantiomers: 1H NMR (300 MHz, CDCl3): d ˆ7.41 7.14 (m, 5H,
3
3
aryl-H), 4.24 4.11 (m, 2H, CH2CH3), 1.95 (dd, Jcis ˆ 8.3 Hz, Jtrans
ˆ
6.1 Hz, 1H, HC), 1.51 (s, 3H, q-C-CH3), 1.44 1.38 (m, 2H, H2C), 1.29 (t,
a-methylstyrene
tR ˆ 2.3 min
tR ˆ 8.5 min
3J ˆ 7.1 Hz, 3H, CH2CH3); 13C NMR (75 MHz, CDCl3):
d
ˆ172.2
1,2-dibromobenzene
(carboxyl-C), 145.9 (aryl-C), 128.4 (aryl-C), 127.3 (aryl-C), 126.4 (aryl-C),
60.5 (OCH2), 30.6 (benzyl-C), 27.8 (CH), 20.8 (CH2), 19.9 (q-C-CH3), 14.4
(OCH2-CH3); (1S,2S)-isomer: elemental analysis calcd (%) for C13H16O2
(À)-cis-1-methyl-1,2-diphenylcyclopropane tR ˆ 36.1 min
(cis major enantiomer obtained in catalysis with (1R)-configurated
Ru porphyrins)
(204.26): C 76.44, H 7.90; found: C 76.16, H 7.83; (1S,2S)-isomer: [a]D20
‡2868 (CHCl3, c ˆ 0.328).
ˆ
(‡)-cis-1-methyl-1,2-diphenylcyclopropane tR ˆ 40.4 min
(cis major enantiomer obtained in catalysis with (1S)-configurated
Ru porphyrins)
cis-Enantiomers: 1H NMR (300 MHz, CDCl3): d ˆ7.41 7.14 (m, 5H, aryl-
H), 3.88 3.63 (m, 2H, CH2CH3), 1.88 (dd, 3J ˆ 7.7, 3J ˆ 5.4 Hz, 1H, HC),
3
2
1.76 (dd, J ˆ 7.7 Hz, J ˆ 4.6 Hz, 1H, CHH'cis), 1.45 (s, 3H, q-C-CH3), 1.13
(dd, 3J ˆ 5.4, 2J ˆ 4.6 Hz, 1H, CHH'trans), 0.92 (t, 3J ˆ 7.1 Hz, 3H, CH2CH3);
13C NMR (75 MHz, CDCl3): d ˆ171.2 (carboxyl-C), 141.9 (aryl-C), 128.7
(aryl-C), 128.1 (aryl-C), 126.6 (aryl-C), 60.0 (OCH2), 32.0 (benzyl-C), 28.5
(CH), 28.5 (q-C-CH3), 19.4 (CH2), 13.9 (CH2-CH3); (1S,2R)-isomer:
elemental analysis calcd (%) for C13H16O2 (204.26 gmolÀ1): C 76.44, H
7.90; found: C 76.15, H 7.81; (1S,2R)-isomer: [a]2D0 ˆ ‡618 (c ˆ 0.614,
CHCl3); (1R,2S)-isomer: elemental analysis calcd (%) for C13H16O2
(204.26 gmolÀ1): C 76.44, H 7.90; found: C 76.14, H 7.84.
(À)-trans-1-methyl-1,2-diphenylcyclopropane tR ˆ 66.6 min
(trans major enantiomer obtained in catalysis with (1R)-configurated
Ru porphyrins)
(‡)-trans-1-methyl-1,2-diphenylcyclopropane tR ˆ 67.2 min
(trans major enantiomer obtained in catalysis with (1S)-configurated
Ru-porphyrins)
Asymmetric epoxidation, GC-analysis
Epoxidation of styrene: GC-column CB1, helium 1.1 mLminÀ1 (constant
flow modus), injector 2008C (pulsed split modus), detector (FID) 2508C,
oven: 768C (33 min), 108CminÀ1 1158C (3 min), 208CminÀ1 1808C:
Preparation of trans-(1S,2S)-2-methyl-2-phenylcyclopropane-(1S')-(1-phe-
nylethyl)-carboxamide: ( 1S,2S)-Ethyl 2-methyl-2-phenylcyclopropanecar-
boxylate (80 mg, 392 mmol, 1 equiv) was amidated with (S)-(À)-1-phenyl-
ethylamine (237 mg, 252 mL, 1.96 mmol, 5 equiv) according to procedure
e). The amide was obtained as colorless crystals (39 mg, 140 mmol, 36%).
M.p. 1238C (n-hexane); analytical HPLC Supersphere 60 RP-Select B,
methanol/water 70:30 (0.3 mLminÀ1), tR ˆ 13.7 min; 1H NMR (300 MHz,
CDCl3): d ˆ 7.48 7.14 (m; 10H, aryl-H), 5.89* (brs; 1H, NH), 5.25 5.10
(m; 1H, CH-NH), 1.67 (dd, 3Jcis ˆ 8.3, 3Jtrans ˆ 5.8 Hz; 1H, CH-CONH), 1.53
(s; 3H, q-C-CH3), 1.50 (d, 3J ˆ 7.0 Hz; 3H, CH-CH3), 1.49 (dd, 3J ˆ 5.8 ,
2J ˆ 4.8 Hz; 1H, CHH'cis), 1.33 (dd, 3J ˆ 8.3, 2J ˆ 4.8 Hz; 1H, CHH'trans);
13C NMR (75 MHz, CDCl3): d ˆ169.4 (s; amide-C), 146.2 (aryl-C), 143.3
(aryl-C), 128.6 (aryl-C), 128.4 (aryl-C), 127.3 (aryl-C), 126.5 (aryl-C), 126.2
(aryl-C), 126.2 (aryl-C), 49.1 (NH-C), 30.9 (CH-CO), 28.7 (q-C-CH3), 22.0
(CH-CH3), 19.6 (CH2), 18.8 (q-C-CH3); IR (neat): nÄ ˆˆ 3277 (m), 3056 (w),
3024 (w), 2971 (w), 2925 (w), 2869 (w), 1635 (s), 1600 (w), 1539 (s), 1493 (s),
1444 (m), 1433 (m), 1397 (m), 1375 (w), 1301 (w), 1232 (m), 1116 (w), 1083
(w), 1068 (w), 1027 (w), 970 (w), 950 (w), 920 (w), 903 (w), 843 (w), 761 (m),
696 cmÀ1 (s); HR-MS (ESI, Dm ˆ 0.005): m/z: calcd for: 302.152; found:
styrene
tR ˆ 6.3 min
tR ˆ 28.8 min
tR ˆ 31.2 min
tR ˆ 37.8 min
(S)-styrene oxide
(R)-styrene oxide
1,2-dibromobenzene
Epoxidation of 1,2-dihydronaphthalene: GC-column CB1, helium
1.4 mLminÀ1 (constant flow modus), injector 2508C (pulsed split modus),
detector (FID) 2508C, oven: 1108C (30 min), 208CminÀ1 1508C (5 min),
208CminÀ1 2008C (2 min):
1,2-dihydronaphthalene
1,2-dibromobenzene
tR ˆ 6.5 min
tR ˆ 7.2 min
(1S,2R)-1,2-epoxy-1,2,3,4-tetrahydronaphthalene
tR ˆ 21.3 min
tR ˆ 23.6 min
(1R,2S)-1,2-epoxy-1,2,3,4-tetrahydronaphthalene
Epoxidation of 1-octene: GC-column CB1, helium 1.5 mLminÀ1 (constant
flow modus), injector 2008C (pulsed split modus), detector (FID) 2508C,
oven: 688C (17 min), 108CminÀ1 1208C (4 min), 308CminÀ1 2008C:
‡
302.152 [M‡Na] . The chemical shift of the amide N-H resonance strongly
depends on the water content of the CDCl3. Due to the hindered rotation
around the amide bond, more than one amide proton signal may be
detected.
1-octene
tR ˆ 2.7 min
tR ˆ 14.8 min
tR ˆ 15.1 min
tR ˆ 23.3 min
(R)-1,2-epoxyoctane
(S)-1,2-epoxyoctane
1,2-dibromobenzene
Preparation of trans-(1R,2R)-2-methyl-2-phenylcyclopropane-(1S')-(1-
phenylethyl)-carboxamide: ( R1,2R)-Ethyl 2-methyl-2-phenylcyclopropa-
necarboxylate (160 mg, 783 mmol, 1 equiv) was amidated with (S)-(À)-1-
phenylethylamine (474 mg, 504 mL, 3.92 mmol, 5 equiv) according to
procedure e). The amide was obtained as colorless crystals (90 mg,
322 mmol, 41%), the purity of the amide was confirmed by HPLC analysis.
The relative configuration of the product was determined by X-ray analysis.
M.p. 1248C (n-hexane); analytical HPLC Supersphere 60 RP-Select B,
methanol/water 70:30 (0.3 mLminÀ1), tR ˆ 13.3 min; NMR and IR data are
indistinguishable from the data of the trans-(1S,2S)-isomer; HR-MS (ESI,
Determination of the relative and absolute configurations of the cyclo-
propanes obtained from the reaction of a-methylstyrene and ethyl
diazoacetate
Cyclopropanation of a-methylstyrene with [Cu(acac)2] and ethyl diazo-
acetate: a-Methylstyrene (7.4 g, 8.2 mL, 63.0 mmol) was cyclopropanated
according to the GP d) with ethyl diazoacetate (7.9 g, 7.3 mL, 69.3 mmol,
1.1 equiv) and [Cu(acac)2] (660 mg, 2.52 mmol, 0.04 equiv). After workup,
the mixture of the stereoisomers was obtained as a colorless liquid (8.4 g,
41.0 mmol, 65%). The diastereomers were separated via preparative
HPLC on a LiChroSorb Si60 column. The two pairs of enantiomers were
then separated via preparative HPLC on a Chiralpak AD column. All four
cyclopropanes could be obtained in pure form (GC).
‡
Dm ˆ 0.005): m/z: calcd for: 302.152; found: 302.152 [M‡Na] .
Preparation of cis-(1S,2R)-2-methyl-2-phenylcyclopropane-(1S')-(1-phe-
nylethyl)-carboxamide: ( 1S,2R)-Ethyl 2-methyl-2-phenylcyclopropanecar-
boxylate (50 mg, 245 mmol, 1 equiv) was amidated with (S)-(À)-1-phenyl-
ethylamine (148 mg, 158 mL, 1.22 mmol, 5 equiv) according to procedur-
e e). The amide was obtained as colorless crystals (33 mg (118 mmol, 48%).
M.p. 1498C (n-hexane); analytical HPLC Supersphere 60 RP-Select B,
methanol/water 70:30 (0.25 mLminÀ1), tR ˆ 17.5 min; 1H NMR (300 MHz,
CDCl3): d ˆ 7.39 7.18 (m; 8H, aryl-H), 7.11 7.04 (m; 2H, aryl-H), 5.42*
Mixture of all four stereoisomers: b.p. 738C (0.4 mbar); GC-MS column
HP-5, He 1.0 mLminÀ1 (constant flow modus), Injector 2508C (split
modus), oven: 1008C (5 min), 208CminÀ1 2008C (15 min), 208CminÀ1
2808C (10 min), tR ˆ 8.7 min (cis, m/z: 204, 175, 159, 147, 131, 115, 103,
91, 77), tR ˆ 9.1 min (trans, m/z: 204, 175, 159, 147, 131, 115, 103, 91, 77);
analytical HPLC LiChroSpher Si 60, n-hexane/dichloromethane 70:30
(0.5 mLminÀ1), tR ˆ 22.0 min (trans), tR ˆ 37.2 min (cis); preparative
HPLC LiChroSorb Si 60, n-hexane/dichloromethane 70:30 (60 mLminÀ1),
tR ˆ 12.2 min (trans), tR ˆ 16.2 min (cis); analytical HPLC Chiralpak AD,
n-hexane (0.5 mLminÀ1), tR ˆ 12.2 min [(‡)-trans-(1S,2S)], tR ˆ 14.2 min
[(À)-trans-(1R,2R)], tR ˆ 27.3 min [(‡)-cis-(1S,2R)], tR ˆ 29.2 min [(À)-cis-
(1R,2S)]; preparative HPLC Chiralpak AD, n-hexane (60 mLminÀ1), tR ˆ
19.2 min [(‡)-cis-(1S,2R)], tR ˆ 27.5 min [(À)-trans-(1R,2R)], tR ˆ 30.7 min
[(‡)-cis-(1S,2R)], tR ˆ 33.1 min [(À)-cis-(1R,2S)].
3
3
(brs; 1H, NH), 4.95 4.81 (m; 1H, CH-NH), 1.86 (dd, Jcis ˆ 8.2, Jtrans
ˆ
5.6 Hz; 1H, CH-CONH), 1.65 (dd, 3J ˆ 5.6 Hz, 2J ˆ 5.0 Hz; 1H, CHH'cis),
1.44 (s; 3H, q-C-CH3), 1.29 (d, 3J ˆ 6.8 Hz; 3H, CH-CH3), 1.33 (dd, 3J ˆ
8.2 Hz, J ˆ 5.0 Hz; 1H, CHH'trans); 13C NMR (75 MHz, CDCl3): d ˆ170.0
2
(s; amide-C), 142.8.2 (aryl-C), 141.3 (aryl-C), 128.9 (aryl-C), 128.5 (aryl-C),
128.5 (aryl-C), 127.3 (aryl-C), 126.9 (aryl-C), 126.2 (aryl-C), 48.7 (NH-C),
31.2 (q-C-CH3), 30.2 (CH-CO), 28.6 (q-C-CH3), 20.8 (CH-CH3), 18.9
(CH2); IR (neat): nÄ ˆ 3271 (m), 3056 (w), 3024 (w), 2966 (w), 2922 (w), 2865
(w), 1640 (s), 1601 (w), 1539 (s), 1494 (s), 1444 (m), 1395 (w), 1376 (w), 1257
Chem. Eur. J. 2003, 9, 4746 4756
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4753

A. Berkessel et al.
FULL PAPER
3
3
(m), 1212 (m), 1131 (w), 1114 (w), 1087 (w), 1068 (w), 1026 (w), 981 (w), 896
10H, aryl-H), 4.00 3.85 (m, 2H, CH2CH3), 2.54 (dd, Jcis ˆ 8.1, Jtrans ˆ
(w), 862 (w), 844 (w), 757 (m), 696 cmÀ1 (s); HR-MS (ESI, Dm ˆ 0.005):
5.9 Hz; 1H, CH), 2.17 (dd, Jtrans ˆ 5.9, J ˆ 4.9 Hz; 1H, CHH'cis), 1.58 (dd,
3Jcis ˆ 8.1 Hz, 2J ˆ 4.9 Hz; 1H, CHH'trans), 1.00 (t, 3J ˆ 7.1 Hz ; 3 H, CH2CH3);
13C NMR (75 MHz, CDCl3): d ˆ 170.6 (carboxyl-C), 144.8 (aryl-C), 140.2
(aryl-C), 129.7 (aryl-C), 128.4 (aryl-C), 128.2 (aryl-C), 127.6 (aryl-C), 126.9
(aryl-C), 126.5 (aryl-C), 60.4 (CH2CH3), 39.8 (benzyl-C), 29.0 (CH), 20.1
(CH2), 14.0 (CH2CH3); (1S)-enantiomer: elemental analysis calcd (%) for
C13H16O2 (266.13 gmolÀ1): (1S)-enantiomer: C 81.17, H 6.81; found: C
80.81, H 6.72; (1S)-isomer: [a]2D0 ˆ ‡1808 (c ˆ 0.512, CHCl3).
3
2
‡
m/z: calcd for 302.152; found: 302.152 [M‡Na] . *) see previous para-
graph.
Preparation of cis-(1R,2S)-2-methyl-2-phenylcyclopropane-(1S')-(1-phe-
nylethyl)-carboxamide: ( 1R,2S)-Ethyl 2-methyl-2-phenylcyclopropanecar-
boxylate (50 mg, 245 mmol, 1 equiv) was amidated with (S)-(À)-1-phenyl-
ethylamine (148 mg, 158 mL, 1.22 mmol, 5 equiv) according to (e). The
amide was obtained as colorless crystals (24 mg, 86 mmol, 35%), the purity
of the amide was confirmed by HPLC analysis. The relative configuration
of the product was determined by X-ray analysis. M.p. 1928C (n-hexane);
analytical HPLC Supersphere 60 RP-Select B, methanol/water 70:30
(0.25 mLminÀ1), tR ˆ 16.4 min; NMR and IR data are undistinguishable
from the data of the cis-(1S,2R)-isomer; HR-MS (ESI, Dm ˆ 0.005): m/z:
Determination of the absolute configurations of the cyclopropanes
obtained from the reaction of 1,1-diphenylethylene with ethyl diazoacetate
Preparation of (1S)-2,2-diphenylcyclopropane carboxylic acid: A 50 mL
flask was charged with (1S)-ethyl 2,2-diphenylcyclopropanecarboxylate
(220 mg, 827 mmol), potassium hydroxide (0.5 g, 10.6 mmol), water (5 mL)
and methanol (35 mL). The mixture was stirred at room temperature for
12 h. Conc. HCl (2 mL) and water (10 mL) were added and the mixture was
extracted three times with a total of 150 mL dichloromethane. The
collected extracts were washed twice with water (20 mL) and dried over
magnesium sulfate. Evaporation of the solvent afforded the free acid as a
colorless solid (173 mg, 726 mmol, 88%). The absolute configuration of the
acid was determined by correlation of the optical rotation with literature
‡
calcd for 302.152; found: 302.153 [M‡Na] .
Determination of the relative configurations of the cyclopropanes obtained
from the reaction of a-trimethylsiloxy styrene with ethyl diazoacetate
a-Trimethylsiloxy styrene (3.0 g, 15.6 mmol, 1.0 equiv) was cyclopropanat-
ed according to the general procedure d) with ethyl diazoacetate (2.0 g,
1.8 mL, 17.2 mmol, 1.1 equiv) and [Cu(acac)2] (164 mg, 624 mmol,
0.04 equiv). After workup, the mixture of the stereoisomers was obtained
as a colorless liquid (1.4 g, 5.0 mmol, 32%). The stereoisomers were
separated or enriched, respectively, via preparative HPLC on a Chiralpak
AD column. The amidation following GP e) afforded the ring opened g-
keto amide exclusively. An assignment of the absolute configuration of the
cyclopropanes was thus not possible. The relative configuration was
assigned by NMR experiments. GC-MS column HP-5, helium 1.0 mLminÀ1
(constant flow modus), Injector 2508C (split modus), oven: 1008C (5 min),
208CminÀ1 2008C (15 min), 208CminÀ1 2808C (10 min), tR ˆ 10.4 min
(trans, m/z: 278, 249, 205, 159, 131, 105, 73), tR ˆ 10.7 min (cis, m/z: 278, 249,
205, 159, 131, 105, 73); analytical HPLC LiChroSpher Si 60, n-hexane/
dichloromethane 70:30 (1.0 mLminÀ1), tR ˆ 29.8 min (trans), tR ˆ 33.2 min
data.[30] M.p. 1418C (dichloromethane); H NMR (300 MHz, CDCl3): d ˆ
1
3
3
7.35 7.12 (m; 10H, aryl-H), 2.57 (dd, Jcis ˆ 8.0, Jtrans ˆ 5.9 Hz; 1H, CH),
2.17 (dd, Jtrans ˆ 5.9, 2J ˆ 4.8 Hz; 1H, CHH'cis), 1.58 (dd, Jcis ˆ 8.0, 2J ˆ
4.8 Hz; 1H, CHH'trans); 13C NMR (75 MHz, CDCl3): d ˆ 176.5 (carboxyl-
C), 144.5 (aryl-C), 129.6 (aryl-C), 128.5 (aryl-C), 128.4 (aryl-C), 127.6 (aryl-
C), 127.1 (aryl-C), 126.7 (aryl-C), 41.0 (benzyl-C), 28.5 (CH), 20.7 (CH2);
elemental analysis calcd (%) for C16H14O2 (238.28 gmolÀ1): C 80.65, H 5.92;
C 80.15, H 6.01, [a]D20 ˆ ‡ 2218 (c ˆ 0.329, CHCl3).
3
3
Determination of the relative and absolute configurations of the cyclo-
propanes obtained from the reaction of 1-octene with ethyl diazoacetate
Preparation of enantiomerically enriched (1S,2S)-2-(n-hexyl)-cyclopro-
pane carboxylic acid: A catalytic cyclopropanation of 1-octene was carried
out with catalyst 2e, and the reaction product was purified by Kugelrohr
distillation (b.p. 1108C at 2 mbar) and chromatography on silica gel (n-
hexane) [purity > 97%, >99% de, 82% ee (GC), sense of optical rotation
(‡)]. A 50 mL flask was charged with this enantiomerically enriched
(1S,2S)-2-(n-hexyl)-diphenylcyclopropane carboxylic ethyl ester (50 mg,
252 mmol), potassium hydroxide (0.2 g, 4.25 mmol), water (5 mL) and
methanol (15 mL). The mixture was stirred at room temperature for 12 h.
Concentrated hydrochloric acid (1 mL) and water (20 mL) were added and
the mixture was extracted three times with a total of 60 mL dichloro-
methane. The collected extracts were washed twice with water (10 mL) and
dried over magnesium sulfate. Evaporation of the solvent afforded the free
acid as a colorless oil (38 mg, 223 mmol, 89%). The trans-configuration of
the major product was assigned by NMR experiments, and correlation of
the data with those of a pure sample of the trans-enantiomers, obtained by
palladium catalyzed cyclopropanation of trans-ethyl non-2-enoate with
CH2N2. The absolute configuration of the acid was determined by
correlation of the sense of optical rotation with literature data.[31]
1H NMR (300 MHz, CDCl3): d ˆ 1.44 1.16 (m; 13H, cyclopropyl-CHH'cis,
cyclopropyl-CH, n-alkyl-H), 0.90 0.82 (m; 3H, CH3), 0.78 0.72 (m; 1H,
cyclopropyl-CHH'trans) [chemical shifts from 2D-data for the trans-acid:
1.42, 1.33, 1.32, 1.29, 1.28, 1.26, 1.21, 0.87, 0.76; for the cis-acid: 1.66, 1.55,
1.32, 1.30, 1.29, 1.28, 1.26, 1.06, 0.94, 0.87 ]; 13C NMR (75 MHz, CDCl3): d ˆ
180.9 (carboxyl-C), 33.0 (n-alkyl-CH2), 31.8 (n-alkyl-CH2); 29.0 (n-alkyl-
CH2), 28.9 (n-alkyl-CH2), 24.1 (C6H13-CH), 22.6 (n-alkyl-CH2), 20.0 (CH-
COOH), 16.4 (cyclopropyl-CH2), 14.1 (CH3) [chemical shifts for the cis-
acid: d ˆ 179.5 (carboxyl-C), 33.0 (n-alkyl-CH2), 31.8 (n-alkyl-CH2); 29.5
(n-alkyl-CH2), 26.9 (n-alkyl-CH2), 23.2 (C6H13-CH), 22.6 (n-alkyl-CH2),
18.0 (CH-COOH), 14.4 (cyclopropyl-CH2), 14.1 (CH3); (1S,2S)-isomer:
[a]2D0 ˆ ‡168 [c ˆ 0.369, CHCl3 (effective concentration of pure (1S,2S)-
enantiomer, the real concentration of the enantiomeric mixture (82% ee,
>99% de) was 450 mg per 100 mL)].
(cis); analytical HPLC Chiralpak AD, n-hexane (0.6 mLminÀ1), tR
ˆ
13.1 min [(‡)-trans], tR ˆ 15.4 min [(‡)-cis], tR ˆ 19.5 min [(À)-cis], tR ˆ
20.4 min [(À)-trans]; preparative HPLC Chiralpak, n-hexane
(60 mLminÀ1), tR ˆ 27.1 min [(‡)-trans], tR ˆ 30.2 min [(‡)-cis], tR
31.5 min [(À)-trans], tR ˆ 33.7 min [(À)-cis].
ˆ
trans-Enantiomers: 1H NMR (300 MHz, CDCl3): d ˆ 7.46 7.19 (m; 5H,
3
3
aryl-H), 3.87 3.76 (m; 2H, CH2CH3); 2.25 (dd, Jcis ˆ 9.1, Jtrans ˆ 7.0 Hz ;
1H, CH), 1.94 (dd, 3Jtrans ˆ 7.0, 2J ˆ 5.9 Hz; 1H, CHH'cis), 1.48 (dd, 3Jcis ˆ 9.1,
2J ˆ 5.9 Hz; 1H, CHH'trans), 0.93 (t, 3J ˆ 7.0 Hz ; 3 H, CH2CH3), À0.08 (s;
9H, Si(CH3)3); 13C NMR (75 MHz, CDCl3): d ˆ 173.9 (carboxyl-C), 136.6
(aryl-C), 129.0 125.0 (aryl-C; an assignment of the 13C NMR signals of the
aryl carbon atoms was not possible due to their low intensity; their
approximate chemical shifts were obtained from 2D-experiments), 65.4
(benzyl-C), 60.2 (OCH2), 30.4 (CH), 19.3 (CH2), 14.2 (OCH2-CH3), 0.7
(Si(CH3)3).
cis-Enantiomers: 1H NMR (300 MHz, CDCl3): d ˆ 7.51 7.20 (m; 5H, aryl-
H), 4.16 (q; 3J ˆ 7.2 Hz ; 2 H, CH2CH3), 1.99 1.87 (m; 2H, CH, CHH'cis),
3
1.64 (dd, Jcis ˆ 8.1, 2J ˆ 5.3 Hz; 1H, CHH'trans), 1.23 (t, 3J ˆ 7.2 Hz ; 3 H,
CH2CH3), 0.04 (s; 9H, Si(CH3)3; 13C NMR (75 MHz, CDCl3): d ˆ 169.1
(carboxyl-C), 142.8 (aryl-C), 129.0 125.0 (aryl-C, an assignment of the
13C NMR signals of the aryl carbon atoms was not possible due to their low
intensity. Their approximate chemical shifts were obtained from 2D-
experiments.), 63.5 (benzyl-C), 60.6 (OCH2), 31.1 (CH), 20.2 (CH2), 14.4
(OCH2-CH3), 0.8 (Si(CH3)3).
Cyclopropanation of 1,1-diphenylethylene with [Cu(acac)2] and ethyl
diazoacetate: 1,1-Diphenylethylene (3.1 g, 3.0 mL, 17.0 mmol, 1.0 equiv)
was cyclopropanated according to the general procedure (d) with ethyl
diazoacetate (2.1 g, 2.0 mL, 18.7 mmol, 1.1 equiv) and [Cu(acac)2] (178 mg,
680 mmol, 0.04 equiv). After workup, the product was obtained as a
colorless liquid (2.5 g, 9.3 mmol, 55%). The enantiomers were separated
via preparative HPLC on a Chiralpak AD column. Racemic mixture: b.p.
958C (0.4 mbar); GC-MS column HP-5, helium 1.0 mLminÀ1 (constant
flow modus), Injector 2508C (split modus), oven: 1008C (5 min),
208CminÀ1 2008C (15 min), 208CminÀ1 2808C (10 min), tR ˆ 14.7 min
(m/z: 266, 237, 192, 178, 165, 115, 91); analytical HPLC Chiralpak AD, n-
hexane (0.5 mLminÀ1), tR ˆ 31.0 min [(‡)-S], tR ˆ 32.6 min [(À)-R]; prep-
arative HPLC Chiralpak AD, n-hexane (70 mLminÀ1), tR ˆ 22.1 min [(‡)-
S], tR ˆ 29.4 min [(À)-R]; 1H NMR (300 MHz, CDCl3): d ˆ 7.40 7.15 (m,
Determination of the relative and absolute configurations of the cyclo-
propanes obtained from the reaction of styrene with phenyl diazomethane
Styrene (1.0 g, 1.1 mL, 9.6 mmol, 1.0 equiv) was cyclopropanated according
to the GP d) with phenyl diazomethane (1.3 g, 10.6 mmol, 1.1 equiv) and
[Cu(acac)2] (124 mg, 384 mmol, 0.04 equiv). After workup, the mixture of
the stereoisomers was obtained as a colorless liquid (0.65 g, 3.4 mmol,
4754
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 4746 4756

Chiral Ruthenium Porphyrins
4746 4756
35%). The stereoisomers were then separated or enriched, respectively, via
preparative HPLC on a Chiralpak AD column. The relative configurations
of the cyclopropanes were assigned by NMR-experiments. The absolute
configuration of the trans-products was assigned by correlation of the sense
of optical rotation with literature data.[32] GC-MS column HP-5, helium
1.0 mLminÀ1 (constant flow modus), Injector 2508C (split modus), oven:
1008C (5 min), 208CminÀ1 2008C (15 min), 208CminÀ1 2808C (10 min),
tR ˆ 10.0 min (cis, m/z: 194, 179, 165, 115), tR ˆ 10.8 min (trans, m/z: 194,
179, 165, 115), analytical HPLC Chiralpak AD, n-hexane (0.6 mLminÀ1),
tR ˆ 14.2 min [(‡)-(1R,2R)], tR ˆ 14.5 min [(À)-(1S,2S)], tR ˆ 18.7 min cis-
needles from n-hexane, 0.20  0.15  0.15 mm, monoclinic, a ˆ 10.782(1),
b ˆ 5.244(1), c ˆ 14.916(1) ä, b ˆ 109.45(1)8, Vˆ 795.23(18) ä3, space
group P21, Z ˆ 2, 1calcd ˆ 1.167 gcmÀ3, m ˆ 0.071mmÀ1, q range 1.45 to
31.118, 3568 measured reflections, 2088 independent reflections, refinement
method: full-matrix least-squares on F2, 275 parameter, goodness-of-fit on
F2 ˆ 1.193, final residuals R1 ˆ 0.0560 and wR2 ˆ 0.1053 for 1319 observed
reflections with I > 2s(I).
Crystal data for cis-(1R,2S)-2-methyl-2-phenylcyclopropane-(1S')-(1-phe-
nylethyl)-carboxamide (16): C19H21NO, M ˆ 279.38 gmolÀ1, colorless nee-
dles from n-hexane, 0.20  0.15  0.12 mm, tetragonal, a ˆ 13.586(1), c ˆ
meso; preparative HPLC Chiralpak AD, n-hexane (70 mLminÀ1), tR
ˆ
18.236(1) ä, Vˆ 3366.0(4) ä3, space group I41, Z ˆ 8, 1calcd ˆ 1.103 gcmÀ3
,
m ˆ 0.067mmÀ1, q range 1.87 to 26.988, 11662 measured reflections, 3223
independent reflections, refinement method: full-matrix least-squares on
F2, 276 parameter, goodness-of-fit on F2 ˆ 1.103, final residuals R1 ˆ 0.0469
and wR2 ˆ 0.0629 for 1794 observed reflections with I > 2s(I).
16.8 min [(‡)-(1R,2R)], tR ˆ 19.2 min [(À)-(1S,2S)], tR ˆ 24.5 min [cis-
meso].
trans-Enantiomers: 1H NMR (300 MHz, CDCl3): d ˆ7.39 7.29 (m; 4H,
aryl-H), 7.29 7.17 (m; 6H, aryl-H), 2.23 (t, 3J ˆ 7.0 Hz; 2H, CH), 1.51 (t,
3J ˆ 7.0 Hz ; 2 H, CH2; 13C NMR (75 MHz, CDCl3): d ˆ 142.4 (aryl-C), 128.3
(aryl-C), 125.7 (aryl-C), 125.6 (aryl-C), 27.9 (CH), 18.1 (CH2).
Crystal data for (1S)-diphenylcyclopropane carboxylic acid (17): C16H14O2,
M ˆ 238.28 gmolÀ1, colorless needles from dichloromethane, 0.20  0.15 Â
0.15 mm, monoclinic, a ˆ 11.959(1), b ˆ 9.803(1), c ˆ 11.931(1), b ˆ
cis-Enantiomers: 1H NMR (300 MHz, CDCl3): d ˆ 7.18 7.14 (m; 4H, aryl-
113.01(1)8, Vˆ 1287.4(2) ä3, space group P21/c, Z ˆ 4, 1calcd ˆ 1.229 gcmÀ3
,
H), 7.14 7.09 (m; 2H, aryl-H), 7.03 6.98 (m; 4H, aryl-H), 2.54 (dd, 3Jcis
ˆ
m ˆ 0.080mmÀ1, q range 1.85 to 27.008, 3073 measured reflections, 1626
independent reflections, refinement method: full-matrix least-squares on
F2, 219 parameter, goodness-of-fit on F2 ˆ 1.063, final residuals R1 ˆ 0.0480
and wR2 ˆ 0.1154 for 1182 observed reflections with I > 2s(I).
3
8.5 Hz, Jtrans ˆ 6.5 Hz; 2H, CH), 1.52 1.33 (m; 2H, CH2); 13C NMR
(75 MHz, CDCl3): d ˆ 138.3 (aryl-C), 128.9 (aryl-C), 127.5 (aryl-C), 125.5
(aryl-C), 24.1 (CH), 11.3 (CH2).
Determination of the relative configurations of the cyclopropanes obtained
All data were collected on a Nonius KappaCCD diffractometer (MoKa
radiation l ˆ 0.71073 ä at 293(2) K, graphite monochromator l/w scans).
The structures were solved using direct methods (SHELXS-97, G. M.
Sheldrick, Program for the Solution of Crystal Structures, University of
Gˆttingen (Germany), 1997), followed by full-matrix least squares refine-
ment with anisotropic thermal parameters for Ru, Ph, F, C and O and
isotropic parameters for H, (SHELXL-97, G. M. Sheldrick, Program for the
Refinement of Crystal Structures, University of Gˆttingen (Germany),
1997).
from the reaction of a-methylstyrene with phenyl diazomethane
a-Methylstyrene (10.0 g, 11.1 mL, 85.0 mmol, 1.0 equiv) was cyclopropa-
nated according to the general procedure (d) with phenyl diazomethane
(11.1 g, 93.5 mmol, 1.1 equiv) and [Cu(acac)2] (898 mg, 3.4 mmol,
0.04 equiv). After workup, the mixture of the stereoisomers was obtained
as a colorless liquid (4.7 g, 23 mmol, 27%). The relative configurations
were assigned by NMR experiments. GC-MS column HP-5, helium
1.0 mLminÀ1 (constant flow modus), Injector 2508C (split modus), oven:
1008C (5 min), 208CminÀ1 2008C (15 min), 208CminÀ1 2808C (10 min),
tR ˆ 10.3 min (cis, m/z: 208, 193, 178, 130, 115, 91), tR ˆ 11.2 min, (trans,
m/z: 208, 193, 178, 130, 115, 91); analytical HPLC Chiralpak AD, n-hexane
CCDC-210099 (2d), -210100 (2e), -210101 (trans-(1R,2R)-2-methyl-2-
phenylcyclopropane-(1S')-(1-phenylethyl)-carboxamide) (15), -210102
(cis-(1R,2S)-2-methyl-2-phenylcyclopropane-(1S')-(1-phenyl-ethyl)-car-
boxamide) (16), -210103 ((1S)-diphenylcyclopropane carboxylic acid) (17)
contain the supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrie-
ving.html (or from the Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB21EZ, UK; (fax: (‡44)1223-336-033; or e-mail:
deposit@ccdc.cam.ac.uk).
(0.3 mLminÀ1), tR ˆ 13.3 min [(À)-cis], tR ˆ 13.9 min [(‡)-cis], tR
ˆ
15.0 min [(À)-trans], tR ˆ 16.1 min [(‡)-trans].
trans-Enantiomers: 1H NMR (300 MHz, CDCl3): d ˆ 7.43 7.18 (m; 10H,
3
3
3
aryl-H), 2.40 (dd, Jcis ˆ 8.7, Jtrans ˆ 6.2 Hz; 1H, CH), 1.44 (dd, Jcis ˆ 8.7,
2J ˆ 5.1 Hz; 1H, CHH'cis), 1.23 (dd, 3Jtrans ˆ 6.2, 2J ˆ 5.1 Hz; 1H, CHH'trans),
1.11 (s; 3H, CH3); 13C NMR (75 MHz, CDCl3): d ˆ147.8 (aryl-C), 139.1
(aryl-C), 129.1 (aryl-C), 128.3 (aryl-C), 128.1 (aryl-C), 126.9 (aryl-C), 126.0
(aryl-C), 125.7 (aryl-C), 31.4 (CH), 26.9 (q-cyclopropyl-C), 21.0 (CH3), 18.6
(CH2).
Acknowledgement
cis-Enantiomers: 1H NMR (300 MHz, CDCl3): d ˆ 7.19 6.96 (m; 8H, aryl-
3
3
H), 6.76 6.71 (m; 2H, aryl-H), 2.21 (dd, Jcis ˆ 8.6, Jtrans ˆ 5.8 Hz; 1H,
CH), 1.53 (s; 3H, CH3), 1.49 (dd, 3Jtrans ˆ 5.8, 2J ˆ 5.8 Hz; 1H, CHH'cis), 1.25
(dd, 3Jcis ˆ 8.6, 2J ˆ 5.8 Hz; 1H, CHH'trans); 13C NMR (75 MHz, CDCl3): d ˆ
142.3 (aryl-C), 139.8 (aryl-C), 129.9 (aryl-C), 127.9 (aryl-C), 127.5 (aryl-C),
127.4 (aryl-C), 125.8 (aryl-C), 125.0 (aryl-C), 31.1 (q-cyclopropyl-C), 31.1
(CH), 29.6 (CH3), 19.7 (CH2).
This work was supported by the Fonds der Chemischen Industrie and by the
BASF AG, Ludwigshafen.
[1] a) E. N. Jacobsen, M. H. Wu, in Comprehensive Asymmetric Catalysis
(Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Berlin,
1999, pp. 649 677; b) E. N. Jacobsen, M. H. Wu, in Comprehensive
Asymmetric Catalysis (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto),
Springer, Berlin, 1999, pp. 1309 1326.
Details of the X-ray crystal structure analyses
Crystal data for 2d: C89H72F12N4ORu ¥ CH3OH ¥ 1.5 H2O, M ˆ
1601.64 gmolÀ1
,
red crystals from chloroform/methanol, 0.25 Â 0.20 Â
0.10 mm, orthorhombic, a ˆ 17.021(1), b ˆ 28.006(1), c ˆ 15.840(1) ä, Vˆ
[2] Catalytic Asymmetric Synthesis (Ed.: I. Ojima), Wiley-VCH, Wein-
7550.8(7) ä3, space group P21212, Z ˆ 4, 1calcd ˆ 1.409 gcmÀ3
,
m ˆ
heim, 2000.
0.293mmÀ1, qrange 1.29 to 25.008, 13204 measured reflections, 13204
independent reflections, refinement method: full-matrix least-squares on
F2, 1000 parameter, goodness-of-fit on F2 ˆ 1.046, final residuals R1 ˆ
0.0945 and wR2 ˆ 0.2069 for 9792 observed reflections with I > 2s(I).
À
[3] H. U. Reissig, ™Formation of C C Bonds by [2‡1] Cycloadditions∫ in
Houben-Weyl, Methods of Organic Chemistry, E 21 Stereoselective
Synthesis, Vol. 5 (Eds.: G. Helmchen, R. W. Hoffmann, J. Mulzer, E.
Schaumann), Thieme, Stuttgart, New York, 1996, pp. 3179 3270.
[4] Z. Gross, S. Ini, M. Kapon, S. Cohen, Tetrahedron Lett. 1996, 40,
7325 7328.
Crystal data for 2e: C84H76F3N4PRu ¥ CH3CN ¥ C6H6, M ˆ 1449.69 gmolÀ1
,
red crystals from benzene/acetonitrile, 0.20 Â 0.15 Â 0.15 mm, monoclinic,
a ˆ 9.727(1), b ˆ 27.357(1), c ˆ 14.753(1) ä, b ˆ 107.057(10)8, Vˆ
[5] S. Ini, M. Kapon, S. Cohen, Z. Gross, Tetrahedron: Asymmetry 1996, 7,
659 662.
3753.1(5) ä3, space group P21, Z ˆ 2, 1calcd ˆ 1.283 gcmÀ3, m ˆ 0.288mmÀ1
,
q range 1.44 to 25.008, 230644 measured reflections, 12873 independent
reflections, refinement method: full-matrix least-squares on F2, 910
parameter, goodness-of-fit on F2 ˆ 1.021, final residuals R1 ˆ 0.0667 and
wR2 ˆ 0.1590 for 9842 observed reflections with I > 2s(I).
¬
[6] a) E. Galardon, S. Roue, P. Le Maux, G. Simonneaux, Tetrahedron
Lett. 1998, 39, 2333 2334; b) see ref. [7] for another early example of
chiral Ru-porphyrin catalyzed asymmetric cyclopropanation (32%
ee).
Crystal data for trans-(1R,2R)-2-methyl-2-phenylcyclopropane-(1S')-(1-
phenylethyl)-carboxamide (15): C19H21NO, M ˆ 279.38 gmolÀ1, colorless
[7] E. Galardon, P. Le Maux, G. Simonneaux, Chem. Commun. 1997,
927 928.
Chem. Eur. J. 2003, 9, 4746 4756
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4755

A. Berkessel et al.
FULL PAPER
[8] Z. Gross, S. Ini, Org. Lett. 1999, 1, 2077 2080.
[9] A. Berkessel, M. Frauenkron, J. Chem. Soc. Perkin Trans. 1 1997,
2265 2266.
[20] The non-crystallizing diastereomeric acetals can be isolated by
preparative HPLC.
[21] H. Urata, T. Fuchikami, Tetrahedron Lett. 1991, 32, 91 94.
[22] R. Zhang, W.-Y. Yu, K.-Y. Wong, C.-M. Che, J. Org. Chem. 2001, 66,
8145 8153.
[23] C.-M. Che, J.-S. Huang, F.-W. Lee, Y. Li, T.-S. Lai, H.-L. Kwong, P.-F.
Teng, W.-S. Lee, W.-C. Lo, S.-M. Peng, Z.-Y. Zhou, J. Am. Chem. Soc.
2001, 123, 4119 4129.
[24] K. M. Kadish, Y. Hu, P. Tagliatesta, T. Boschi, J. Chem. Soc. Dalton
Trans. 1993, 1167 1172.
[25] D. A. Evans, K. A. Woerpel, M. M. Hinman, M. M. Faul, J. Am. Chem.
Soc. 1991, 113, 726 728.
[26] T. Higushi, H. Ohtake, M. Hirobe, Tetrahedron Lett. 1989, 30, 6545
6548.
[27] J. T. Groves, M. Bonchio, K. V. Shalyaev, T. Carofiglio, J. Am. Chem.
Soc. 1996, 118, 8961 8962.
[10] M. Frauenkron, A. Berkessel, Tetrahedron Lett. 1997, 38, 7175 7176.
[11] W.-C. Lo, C.-M. Che, K.-F. Cheng, T. C. W. Mak, Chem. Commun.
1997, 1205 1206.
[12] R. L. Halterman, S.-T. Jan, J. Org. Chem. 1991, 56, 5253 5254.
[13] For modifications of the steric properties of the porphyrin meso-
substituents, see refs. [14a,b]. See ref. [14c] for a study of the effects of
electronic ligand tuning on the performance of manganese salen
complex in asymmetric epoxidation.
[14] a) R. L. Halterman, X. Mei, Tetrahedron Lett. 1996, 37, 6291 6294;
b) R. L. Halterman, S.-T. Jan, A. H. Abdulwali, D. J. Standlee,
Tetrahedron 1997, 53, 11277 11296; c) M. Palucki, N. S. Finney, P. J.
Pospisil, M. L. G¸ler, T. Ishida, E. N. Jacobsen, J. Am. Chem. Soc.
1998, 120, 948 954.
[15] a) J. S. Lindsey, I. C. Schreiman, H. C. Hsu, P. C. Kearney, A. M.
Marguerettaz, J. Org. Chem. 1987, 52, 827 836; b) F. Li, K. Yang, J. S.
Tyhonas, K. A. MacCrum, J. S. Lindsey, Tetrahedron 1997, 53, 12339
12360.
[16] The details of the syntheses, including the X-ray structural analyses
mentioned in this communication, will be published elsewhere.
[17] A. Rieche, H. Gross, E. Hˆft, Chem. Ber. 1960, 93, 88 98.
[18] K. B. Sharpless, Z.-M. Wang, J. Org. Chem. 1994, 59, 8302 8303.
[19] Halterman et al. reported 80% yield of the enantiomerically aldehyde
7a and 53% yield for its enantiomer ent-7a (ref. [12]).
[28] O. Takashi, S. Toshihiro, S. Koji, E. Shoji, J. Org. Chem. 1993, 58,
5163 5166.
[29] C. Xavier, J. Am. Chem. Soc. 1980, 102, 1611 1618.
[30] H. M. Walborsky, C. G. Pitt, J. Am. Chem. Soc. 1962, 84, 4831 4838.
[31] T. Aratani, Pure Appl. Chem. 1985, 57, 1839 1854.
[32] Y. Kaida, Y. Okamoto, Bull. Chem. Soc. Jpn. 1993, 66, 2225 2232.
Received: April 15, 2003 [F5045]
4756
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chem. Eur. J. 2003, 9, 4746 4756