Chiral dirhodium(II) catalysts with ortho-metalated arylphosphine ligands: Synthesis and application to the enantioselective cyclopropanation of α-diazo ketones

Article abstract of DOI:10.1021/om0110437

Chiral dirhodium(II) compounds, Rh₂(O₂CR)₂(pc)₂ (pc = ortho-metalated arylphosphine), with a head-to-tail arrangement (1-21) are used in the cyclopropanation of α-diazo ketones. The influence of catalyst ligands and substrate structure on enantioselectivity is studied. Temperature and solvent dependence assays are performed, the best ee values being obtained in refluxing pentane. Results compare favorably with those reported in the literature using Ru, Cu, and other Rh(II) catalysts.

Full text of DOI:10.1021/om0110437

Organometallics 2002, 21, 1667-1673
1667
Ch ir a l Dir h od iu m (II) Ca ta lysts w ith Or th o-Meta la ted
Ar ylp h osp h in e Liga n d s: Syn th esis a n d Ap p lica tion to
th e En a n tioselective Cyclop r op a n a tion of r-Dia zo
Keton es
Mario Barberis and J ulia Pe´rez-Prieto*
Departamento de Quı´mica Orga´nica/ Instituto de Ciencia Molecular, Facultad de Farmacia,
Universidad de Valencia, Vice´nt Andre´s Estelle´s s/ n, Burjassot, 46100 Valencia, Spain
Konrad Herbst and Pascual Lahuerta*
Departamento de Quı´mica Inorga´nica, Facultad de Qu´ımicas, Universidad de Valencia,
Vice´nt Andre´s Estelle´s s/ n, Burjassot, 46100 Valencia, Spain
Received December 6, 2001
Chiral dirhodium(II) compounds, Rh2(O2CR)2(pc)2 (pc ) ortho-metalated arylphosphine),
with a head-to-tail arrangement (1-21) are used in the cyclopropanation of R-diazo ketones.
The influence of catalyst ligands and substrate structure on enantioselectivity is studied.
Temperature and solvent dependence assays are performed, the best ee values being obtained
in refluxing pentane. Results compare favorably with those reported in the literature using
Ru, Cu, and other Rh(II) catalysts.
In tr od u ction
structure. Achievements in asymmetric catalytic metal
carbene transformations are impressive, but they are
by no means complete. Although chiral dirhodium(II)
carboxamide catalysts have proven to be the most
selective catalysts for intramolecular cyclopropanation
reactions of diazoacetates and diazoacetamidates,5 they
have failed to induce even moderate levels of enanti-
oselectivities with diazo ketones.6 However, diazo ke-
tones have found a large number of successful applica-
tions in racemic synthesis.7 In 1995, Pfaltz et al.8
achieved cyclopropanation of diazo ketones with a
moderate yield (less than 60%) using chiral semicorrin-
copper catalysts. Later, new chiral catalysts were
unsuccessfully sought for improving the enantioselec-
tivity in the intramolecular cyclopropanation of diazo
ketones. Thus, Ru(II) with chiral (diphenylphosphino)-
(oxazolinyl)quinoline ligands provided high yields in the
cyclization, although with less enantiocontrol compared
to Pfaltz’s catalysts (Tables 1 and 4).9 Chiral biferrocene-
based bis(oxazoline) Cu(I) compounds showed low re-
activity and low to moderate enantiocontrol (Table 1,
entry 23; Table 4, entry 9; Table 5, entry 8).10 As a
result, until now, Pfaltz’s catalysts were the most
efficient compounds for inducing enantiocontrol in the
cyclization of the above-mentioned substrates. However,
their enantioselectivities (14-95%) strongly depended
on the substitution pattern of the C-C double bond (see
Tables 1 and 3-5).
The cyclopropyl moiety is increasingly regarded and
used as a functional group involved in reactions of
preparative importance, due to the ring strain.1 Also, a
large number of natural and synthetic cyclopropanes
display interesting biological activities.2 Consequently,
a great deal of effort is presently being devoted to the
development of methods which make the construction
of cyclopropanes with high enantioselectivities pos-
sible.2,3
The metal-catalyzed cyclopropanation of olefins with
diazo compounds is a general strategy for the obtention
of three-membered carbocycles;3 the utility of this
approach is directly related to the level of selectivity of
the process. There is indirect evidence that these
reactions take place via metal carbenes as intermedi-
ates;4 consistently, the selectivity of the process strongly
depends on the nature of the metal and the catalyst
* To whom correspondence should be addressed. J .P.-P.: fax, 34-
6-3864939; e-mail, jperez@uv.es. P.L.: fax, 34-6-386 4322; e-mail,
pascual.lahuerta@uv.es.
(1) (a) Wong, H. C. N.; Hon, M. Y.; Tse, C. W.; Yip, Y. C.; Tanko, J .;
Hudlicky, T. Chem. Rev. 1989, 89, 165. (b) Reissig, H. U. In The
Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: Chich-
ester, U.K., 1987; Chapter 8, p 375.
(2) Liu, H. W.; Walsh, C. T. In The Chemistry of the Cyclopropyl
Group; Rappoport, Z., Ed.; Wiley: Chichester, U.K., 1987; Chapter 16,
p 959.
(3) (a) Pfaltz, A. In Comprehensive Asymmetric Catalysis; J acobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York, 1999; Vol.
II, Chapter 16.1, p 513. (b) Lydon, K. M.; McKervey, M. A. In
Comprehensive Asymmetric Catalysis; J acobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: New York, 1999; Vol. II, Chapter 16.2,
p 539. (c) Charette, A. B.; Lebel, H. In Comprehensive Asymmetric
Catalysis; J acobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
New York, 1999; Vol. II, Chapter 16.3, p 581. (d) Aratani, T. In
Comprehensive Asymmetric Catalysis; J acobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: New York, 1999; Vol. III, Chapter 41.3,
p 1451.
(5) (a) Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998, 7919.
(b) Doyle, M. P.; Forbes, D. C. Chem. Rev. 1998, 98, 911.
(6) Doyle, M. P.; Eismont, M. Y.; Zhou, Q. L. Russ. Chem. Bull. (Engl.
Transl.) 1997, 46, 955.
(7) (a) Taber, D. F.; Stiriba, S. E. Chem. Eur. J . 1998, 4, 990. (b)
Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091.
(8) Pique´, C.; Fa¨hndrich, B.; Pfaltz, A. Synlett 1995, 491.
(9) Park, S. W.; Son, J . H.; Kim, S. G.; Ahn, K. H. Tetrahedron:
Asymmetry 1999, 10, 1903.
(4) Doyle, M. P. Chem. Rev. 1986, 86, 919.
(10) Kim, S. G.; Cho, C. W.; Ahn, K. H. Tetrahedron 1999, 55, 10079.
10.1021/om0110437 CCC: $22.00 © 2002 American Chemical Society
Publication on Web 03/21/2002

1668 Organometallics, Vol. 21, No. 8, 2002
Barberis et al.
Ta ble 1. Ca ta lyst-Dep en d en t Ster eocon tr ol in th e
Cycliza tion of 22
Ta ble 3. Cyclop r op a n a tion of Dia zo Keton e 24
25
23a-c
entry
catalyst
solvent
yield (%)
ee (%)
entry
catalyst
yield (%)
ee (%)
1
2
3
4
5
6
(M)-2
(M)-7
(M)-7
(M)-8
(M)-8
(M)-13
Cu(I)a
Cu(I)b
Rh(II)c
CH2Cl2
n-C5H12
CH2Cl2
n-C5H12
CH2Cl2
CH2Cl2
93
96
85
90
92
97
84
90
87
95
89
79
1S,6R
1S,6R
1S,6R
1S,6R
1S,6R
1S,6R
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
(M)-1
(M)-2
(M)-3
(M)-4
(M)-5
(M)-6
(M)-7
(M)-8
83
98
99
88
95
92
96
98
92
96
98
98
99
89
97
83
82
85
84
80
82
47
56
34
27
24
60
65
64
60
65
35
46
57
17
27
40
34
38
18
17
14
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1S,5R
1R,5S
1S,5R
1R,5S
1S,5R
1R,5S
1S,5R
1R,5S
7
8
9
(ClCH2)2
C6H6
CH2Cl2
57
72
58
95
22
6
1S,6R
1S,6R
(M)-9
Copper semicorrin complexes.8 b Chiral salicylaldimine copper
a
(M)-10
(M)-11
(M)-12
(M)-13
(P )-14
(M)-15
(P )-16
(M)-17
(P )-18
(M)-19
(P )-20
(M)-21
complexes.20 c Rh2(5S-MEPY)4.6
Ta ble 4. Cyclop r op a n a tion of Dia zo Keton e 26
27
22
23
24
25
26
Cu(I)d
Cu(I)e
Cu(I)f
Rh(II)g
Ru(II)h
50
75
25
77
23
5
1S,5R
1R,5S
1R,5S
entry
catalyst
solvent
yield (%)
ee (%)
1
2
3
4
5
6
7
(M)-2
(M)-2
(M)-7
(M)-7
(M)-8
(M)-8
(M)-12
Cu(I)a
Cu(I)b
Rh(II)c
Ru(II)d
n-C5H12
CH2Cl2
n-C5H12
CH2Cl2
n-C5H12
CH2Cl2
CH2Cl2
99
99
99
99
99
99
99
76
68
80
52
70
58
46
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
1R,5S
54
85
84
a
b
Cyclopropanation yield based on the diazo ketone. ee values
calculated in this report were based on GC analysis with a 2,3-
di-O-acetyl-6-O-(tert-butyldimethylsilyl)-beta-CDX column. c Re-
actions with Rh(II) catalysts with ortho-metalated arylphosphines
8
9
10
11
(ClCH2)2
(ClCH2)2
CH2Cl2
CHCl3
58
51
80
91
85
63
27
75
1S,5R
d
were performed in refluxing dichloromethane for 1 h. Copper
semicorrin complexes, in (ClCH2)2 as solvent.8 e Biferrocene-based
bis(oxazoline) copper complex, in dichoromethane as solvent.10
f Chiral salicylaldimine copper complexes, in benzene as solvent.20
1R,5S
Rh2(4S-IPOX)4, in dichloromethane as solvent.6 Ru(II) with
g
h
a
b
Copper semicorrin complexes.8 Biferrocene-based bis(oxazo-
line) copper complex.10 c Rh2(4S-MEOX)4.6 Ru(II) with chiral
d
chiral (diphenylphosphino)(oxazolinyl)quinoline ligands, in chlo-
roform as solvent.9
(diphenylphosphino)(oxazolinyl)quinoline ligands.9
Ta ble 2. Solven t a n d Tem p er a tu r e Effects on
En a n tioselectivities in th e Rh (II)-Ca ta lyzed
Cyclop r op a n a tion of 22
pounds have backbone chirality, and they have been
obtained as pure enantiomers by conventional resolution
methods.13 They are the first examples of dirhodium-
(II) chiral catalysts without chiral ligands, and they
induce moderate asymmetry in the C-H insertion of
diazo ketones.13a Recently, we have demonstrated that
chiral dirhodium(II) complexes Rh2(O2CCF3)2(pc)2 (pc )
(p-CH3C6H4)2P(p-CH3C6H3) (m-CH3C6H4)2P(m-CH3C6H3))
provide a high yield and a good level of enantiocontrol
in the cyclopropanation of diazo ketones.14 In this work
we wish to report in full our results on the influence of
catalyst ligands, substrate structure, solvent, and tem-
perature on the process enantioselectivity.
23
entry Rh T (°C) time (h)
solvent
yield (%) ee (%)
1
2
3
4
5
6
7
8
9
2
2
7
7
7
7
7
7
7
7
40a
83a
1
1
1
1
1
72
4
1
1
1
CH2Cl2
(CH2Cl2)2
CH2Cl2
n-C5H12
n-C5H12
98
94
96
91
90
77d
40
59
74
94
56
49
65
68
74
41
55
67
66
62
40a
25b
36a
-15b
25b
50b
74b
98a
n-C7H14
n-C7H14
n-C7H14
n-C7H14
c
c
c
c
c
10
n-C7H14
a
b
d
Refluxing solvent. Bath temperature. c 0.02% water. 22%
(11) Chakravarty, A. R.; Cotton, F. A.; Tocher, D. A.; Tocher, J . H.
Organometallics 1985, 4, 8.
diazo compound recovered.
(12) (a) Estevan, F.; Lahuerta, P.; Pe´rez-Prieto, J .; Pereira, I.;
Stiriba, S. E. Organometallics 1998, 17, 3442. (b) Estevan, F.;
Lahuerta, P.; Pe´rez-Prieto, J .; Sanau´, M.; Stiriba, S. E.; Ubeda, M. A.
Organometallics 1997, 16, 880.
(13) (a) Estevan, F.; Herbst, K.; Lahuerta, P.; Barberis, M.; Pe´rez-
Prieto, J . Organometallics 2001, 20, 950. (b) Taber, D. F.; Malcolm, S.
C.; Bieger, S. K.; Lahuerta, P.; Stiriba, S. E.; Pe´rez-Prieto, J .; Sanau´,
M.; Monge, M. A. J . Am. Chem. Soc. 1999, 121, 860.
(14) Barberis, M.; Pe´rez-Prieto, J .; Stiriba, S. E.; Lahuerta, P. Org.
Lett. 2001, 3, 3317.
Dirhodium(II) complexes derived from ortho-meta-
lated arylphosphines, Rh2(O2CR)2(pc)2 (pc ) ortho-
metalated arylphosphine, with head-to-tail arrange-
ment), are readily prepared by the thermal reaction of
Rh2(O2CCH3)4 and arylphosphines.11 They were shown
to be regio- and chemoselective catalysts in the trans-
formation of R-diazo ketones.12 These rhodium com-

Dirhodium(II) Catalysts with Arylphosphine Ligands
Organometallics, Vol. 21, No. 8, 2002 1669
Ta ble 5. Cyclop r op a n a tion of Dia zo Keton e 28
catalyst ligands on the enantiocontrol of the process. All
the tested catalysts Rh2(O2CR)2(pc)2 (1-21) afforded
ketone 23 in high yield (80-99%) (see Table 1). The
highest ee values (ca. 65%) were obtained with catalysts
possessing trifluoroacetate as the carboxylate ligands
(catalysts 7, 8, and 10). Comparison of the catalysts 2,
7, 8, and 10-13 with the same carboxylate, trifluoro-
acetate, but different phosphines revealed the low
influence of the electronic and steric nature of the
phosphine, except in the case of catalyst 11 with tris-
(p-tert-butylphenyl)phosphine. Catalysts with carboxy-
lates bulkier than trifluoroacetate or acetate, such as
pivalate and triphenylacetate, led to a low enantiocon-
trol (27% ee for 4, 24% ee for 5). On the other hand,
enantiomerically pure Rh2(protos)2(pc)2 compounds 14-
21 were also tested in this reaction, but they provided
low ee values (<40%). Both P series of dirhodium
catalysts 1-13 and prolinate derivatives yielded the
compound (1S,5R)-23 as the predominant enantiomer.
To optimize the conditions for enantioselective cyclo-
propanation, we explored the effect of temperature and
solvent, polar and nonpolar, on the enantiocontrol using
the cyclization of diazo compound 22 as the pattern
reaction. The temperature had a low influence (entries
6-10, Table 2). A high yield of cyclopropanation with
the best asymmetry induction was obtained in refluxing
dry pentane (entry 5, Table 2); lower temperatures did
not improve the enantiocontrol.16
Therefore, trifluoroacetate-derived dirhodium(II) cata-
lysts, which were shown to be the most selective for the
cyclopropanation of diazo compound 22, were further
used to study the influence of the substrate structure
on enantioselectivity. Reactions were performed in both
refluxing dichloromethane and pentane. Again, pentane
led to cyclization with the highest enantiocontrol (Tables
3 and 4).
In the cyclization of diazo ketone 28, two products
were obtained: the cyclopropanation product with a six-
membered ring, 29, and the allylic insertion product
with a five-membered ring, 30 (Table 5). Cyclopropa-
nation was the predominant reaction, mainly in pen-
tane. Interestingly, while solvents affected the asym-
metry induction in the cyclopropanation reaction, the
C-H insertion product was obtained with high ee values
in both dichloromethane and pentane. Several authors17
have observed solvent-dependent enantiocontrol in the
Rh(II)-catalyzed cyclization of diazo compounds. De-
pending on the Rh(II) complex, the increasing solvent
polarity improved or decreased the asymmetry induction
level.18 However, it appeared that, for the Rh(II) cata-
lysts with ortho-metalated arylphosphines as ligands,
29
yield ee
(%) (%)
30
yield
yield ee
(%) (%)
entry catalyst (%)
solvent
1
2
3
4
5
6
(M)-2
(M)-2
(M)-7
(M)-7
(M)-8
(M)-8
99
99
87
74
92
93
n-C5H12
CH2Cl2
n-C5H12
CH2Cl2
n-C5H12
CH2Cl2
91
50
93
67
69
51
55 1S,6R
9
50
7
33
31
49
83
80
91
93
94
92
20 1S,6R
80 1S,6R
63 1S,6R
80 1S,6R
63 1S,6R
7
8
9
Cu(I)a
Cu(I)b
Rh(II)c
50
12
67
(ClCH2)2 50
(ClCH2)2 12
14
64
17
CH2Cl2
76
24
1
a
b
Copper semicorrin complexes.8 Biferrocene-based bis(oxazo-
line) copper complex.10 c Rh2(5S-MEPY)4.6
Resu lts
Syn th esis of Dir h od iu m (II) Com p lexes. Rh(II)
complexes of the general formula Rh2(O2CR)2(pc)2 (1-
13) were prepared by a modified method first published
by Cotton et al.11 These compounds are inherently chiral
and are obtained as a racemic mixture of the P and M
enantiomers (Figure 1). The racemic mixture of the
Rh2(O2CCH3)2(pc)2 compounds was transformed into two
diastereoisomers by replacement of the acetate groups
for the chiral carboxylate protons (protosH ) N-((4-
methylphenyl)sulfonyl)-L-proline). Both proline deriva-
tives were separated by column chromatography, and
the pure enantiomers of compounds 1-13 were obtained
via ligand exchange with the corresponding carboxylic
acid (Scheme 1). The enantiomer arising from the first
eluted diastereoisomer was the dextrorotatory isomer
in all the compounds, and it was assigned the M
configuration by correlation of the sign of the rotation
of polarized light with the known structure of (M)-1.
Not only these compounds but also some proline deriva-
tives (14-21; Figure 1) were used in the following
catalytic studies.
Asym m et r ic Ca t a lysis. The diazo compounds 22,
24, 26, and 28 were prepared from the corresponding
acid by reaction with methyl chloroformate, followed by
treatment with freshly prepared diazomethane.15
Catalytic reactions were performed by addition of a
solution containing the diazo species to a solution of the
dirhodium(II) complex in the same solvent (diazo:Rh )
100:1, the reaction time and temperature are indicated
in the tables). The solution was filtered through a short
plug silica gel to remove the catalyst, the solvent was
evaporated under reduced pressure, and the crude
product was analyzed by 1H and 13C NMR. The products
were separated by HPLC chromatography, and the ee
values were based on GC analysis with a 2,3-di-O-acetyl-
6-O-(tert-butyldimethylsilyl)-beta-CDX column.
The cyclization of the diazo compound 22 in refluxing
dichloromethane was used as the pattern reaction to
study the influence of the phosphine and carboxylate
(16) Usually, the enantioselectivity increases by lowering the reac-
tion temperature: (a) Davies, H. M. L.; Hansen, T. J . Am. Chem. Soc.
1997, 119, 9075. (b) Watanabe, N.; Ohtake, Y.; Hashimoto, S.; Shiro,
M.; Ikegami, S. Tetrahedron Lett. 1995, 36, 1491. (c) Nishiyama, H.;
Itoh, Y.; Sugawara, Y.; Matsumoto, H.; Aoki, K.; Itoh, K. Bull. Chem.
Soc. J pn. 1995, 68, 1247.
(17) (a) Wynne, D. C.; Olmstead, M. M.; J essop, P. G. J . Am. Chem.
Soc. 2000, 122, 7638. (b) Doyle, M. P.; Davies, S. B.; Hu, W. Org. Lett.
2000, 2, 1145. (c) Davies, H. M. L.; Panaro, S. A. Tetrahedron Lett.
1999, 40, 5287. (d) Davies, H. M. L.; Kong, N. Tetrahedron Lett. 1997,
38, 4203. (e) Kitagaki, S.; Matsuda, H.; Watanabe, N.; Hashimoto, S.
Synlett 1997, 1171. (f) Doyle, M. P.; Zhou, Q. L.; Charnsangavej, C.;
Longoria, M. A.; McKervey, M. A.; Garc´ıa, C. F. Tetrahedron Lett. 1996,
37, 4129.
(18) It has been suggested that solvent can influence the alignment
of the ligands on chiral Rh(II) complexes and affect the enantioselec-
tivity; thus, rigid chiral Rh(II) carboxamides can prevent similar
solvent effects.17f
(15) Boer, Th.; Backer, H. J . In Organic Synthesis; Rabjohn, N., Ed.;
Wiley: New York, 1963; Vol. IV, p 250.

1670 Organometallics, Vol. 21, No. 8, 2002
Barberis et al.
F igu r e 1. List of Rh(II) catalysts with ortho-metalated arylphosphine ligands.
the ability of the solvent to influence the enantiocontrol
depended on the type of reaction performed. We have
previously described the intermolecular cyclopropana-
tion of styrenes with ethyl diazoacetate catalyzed by
these types of compounds.19 Due to the above results,
we decided to investigate the influence of solvents on
the enantiocontrol of the cyclopropanation of styrene.
The results obtained, shown in Table 6, demonstrated
that both the yield of cyclopropanation and the asym-
metry induction improved in pentane, the less polar
solvent.
Furthermore, enantioselectivity values obtained in
the intramolecular cyclopropanation of the tested diazo
ketones with our Rh(II) complexes compared favorably
with those reported for other chiral catalysts (see Tables
1-5), and access to both enantiomers of 23, 25, 27, 29,
and 30 can be achieved with the use of the P or M forms
of the catalyst. For the same type of catalysts (either P
or M series) cyclopentanones 23 and 27 were obtained
with an absolute configuration opposite that of their
homologous cyclohexanones 25 and 29, respectively.
Discu ssion
The high ee values and the sense of asymmetric
induction we observed can be tentatively rationalized
on the basis of the model previously used to explain the
results in intramolecular C-H insertions promoted by
this type of catalyst.13a Compound (P )-1, viewed down
the rhodium-rhodium axis, reveals that the four quad-
rants around the metal atom have different steric
congestion. In particular, two quadrants are more
sterically hindered due the to aryl groups attached to
P which protrude into the region where the carbene
transfer takes place (Scheme 2). Thus, the ketone chain
(19) Barberis, M.; Lahuerta, P.; Pe´rez-Prieto, J .; Sanau´, M. Chem.
Commun. 2001, 439.

Dirhodium(II) Catalysts with Arylphosphine Ligands
Organometallics, Vol. 21, No. 8, 2002 1671
Sch em e 1
Sch em e 2
Ta ble 6. Asym m etr ic Cyclop r op a n a tion of Styr en e
Ca ta lyzed by th e (M)-Rh (II) En a n tiom er
Results obtained with our catalysts demonstrated
that, for the same catalyst, there is a reversal in the
preferred configuration of the five-membered-ring and
six-membered-ring ketones, 23 and 25, respectively
(entry 2, Table 1 vs entry 1, Table 3). From the
transition state A, the observed sense of induction for
the cyclopropanation is consistent with the alkenes
approaching as depicted in I and II (Scheme 2). In these
representations the carbon-carbon double bond ap-
proaches the carbene by the more nucleophilic terminal
carbon, with the hydrogen substituents oriented toward
the catalyst. The different ring sizes might originate
conformational differences in both transition states,
which could explain the reversal of configuration.
Dauben et al.20 have published similar findings in the
asymmetry induction of diazo compounds 22 and 24
promoted by chiral Cu catalysts (entry 24 in Table 1 vs
entry 8 in Table 3).
ee (%)
Rh
yield (%)c
solvent
32/33a
32b
33b
2
2
7
7
8
8
55
62
40
57
36
60
CH2Cl2
n-C5H12
CH2Cl2
n-C5H12
CH2Cl2
n-C5H12
48/52
42/58
61/39
57/43
51/49
44/56
91
93
87
95
88
95
87
94
75
84
81
92
a
b
Determined by GC analysis. ee values were based on GC
analysis with a 2,3-di-O-acetyl-6-O-(tert-butyldimethylsilyl)-beta-
CDX colum. c Cyclopropanation yield based on ethyl diazoacetate.
occupies one of the two open quadrants with the
carbonyl group “syn” to the metal carbene bond (A and
B, Scheme 2). We have previously suggested that the
repulsive interaction between the keto group and the
metaled aryl group might be the origin of the lower
stability of transition state B, leaving transition state
A as the preferred one.
Furthermore, in the case of the cyclopropanation of
the substituted analogues 26 and 28 with our catalysts,
(20) Dauben, W. G.; Hendricks, R. T.; Luzzio, M. J .; Howard, P. N.
Tetrahedron Lett. 1990, 31, 6969.

1672 Organometallics, Vol. 21, No. 8, 2002
Barberis et al.
mixtures are volume/volume mixtures. Organic chemicals were
purchased from Aldrich Chemical Co. All reactions were
carried out in flame-dried glassware under an argon atmo-
sphere. CH2Cl2 was distilled from CaH2 under argon im-
mediately before use. Optical rotations were measured on a
Perkin-Elmer 241 polarimeter at the Na D line in 10 cm quartz
cuvettes. The ee values were based on GC analysis with a 2,3-
di-O-acetyl-6-O-(tert-butyldimethylsilyl)-beta-CDX column us-
ing hydrogen as the gas carrier.
the same reversal in their absolute configuration is
observed (compare entries 1 in Tables 4 and 5). The
sense of induction for the cyclopropanation is consistent
with the transition states depicted in III and IV
(Scheme 2). In this representation the CdC double bond
approaches the carbene by the less substituted (more
nucleophilic) carbon, with the methyl groups pointing
away from the catalyst. This behavior of substituted and
nonsubstituted olefins has precedents. Thus, Park et al.9
also reported the formation of cyclopentanones 23 and
27 with the same absolute configuration by using chiral
Ru catalysts in the cyclopropanation of 22 and 26; they
reported that in this case the olefin approach to the
carbene carbon for both types of olefins must be different
as well.21
Gen er a l P r oced u r e for th e Syn th esis of En a n tiom er i-
ca lly P u r e R h (II) Com p lexes w it h Or t h o-Met a la t ed
Ar ylp h osp h in es. To a solution of racemic Rh2(O2CCH3)2(pc)2‚
2HO2CCH3 (pc ) ortho-metalated arylphosphine) was added
N-((4-methylphenyl)sulfonyl)-L-proline (protosH; 8 equiv), and
the mixture was refluxed for 2 h using a Soxhlet apparatus
with a sodium carbonate trap. The crude product was dissolved
in acetone with sodium carbonate to eliminate the excess of
protosH, and the two diastereoisomers were separated using
standard conditions.13a Then, the corresponding carboxylic acid
(10 equiv) was added to a dichloromethane (30 mL) solution
of each diastereisomer, and the mixture was stirred for 1/2 h.
The solution was concentrated, transferred to a column, and
eluted with dichloromethane/hexane (10/10) and 1% of the
carboxylic acid to afford a complete exchange of the protos
groups.
Finally, increasing the bulk of the carboxylate ligands
(pivalate, triphenylacetate, protos) or the bulk of the Y
substituent on the metaled aryl group should cause a
greater hindrance in the preferred area for the carbene
transfer and a decreased enantiocontrol of the process.
Con clu sion
A family of chiral dirhodium(II) catalysts with ortho-
metalated arylphosphine ligands has been synthesized,
and its use in the enantioselective cyclopropanation of
R-diazo ketones has been explored. M and P forms of
each catalyst induced identical enantiocontrol in the
cyclization of R-diazo ketones, but with opposite sense.
The highest enantiocontrol was obtained using pentane
as solvent. Most of the dirhodium catalysts tested in this
paper gave higher enantioselectivities than dirhodium-
(II) catalysts with chiral carboxamidate or carboxylate
ligands. Until now, dirhodium(II) complexes with ortho-
metalated arylphosphine ligands have proven to be the
most effective catalysts in the enantioselective cyclo-
propanation of R-diazo ketones.
(M)-Rh 2[(C6H4)P (C6H5)2]2(O2CCH3)2 ((M)-1). Yield: 85%.
[R]20 ) -75 (c 0.05, CHCl3).
D
(M)-Rh 2[(C6H4)P (C6H5)2]2(O2CC3F 7)2 ((M)-3). Yield: 95%.
[R]20 ) -120 (c 0.05, CHCl3).
D
(P )-Rh 2[(C6H4)P (C6H5)2]2[O2CC(CH3)3]2 ((P )-4). Yield: 87%.
[R]20 ) +25 (c 0.05, CHCl3).
D
(P )-Rh 2[(C6H4)P (C6H5)2]2[O2CC(C6H5)3]2 ((P )-5). Yield:
1
90%. 31P{1H} NMR: δ 14.7. H NMR: δ 6.39 (m, 2 H), 6.60-
7.20 (aromatic signals, 54 H), 7.93 (m, 2 H). 13C{1H} NMR: δ
121.7-138.9 (aromatic signals), 145.1, 163.0 (m), 182.9. [R]20
D
) +60 (c 0.05, CHCl3).
(M)-Rh 2[(p-CH3C6H3)P (p-CH3C6H4)2]2(O2CCH3)2 ((M)-6).
Yield: 80%. [R]20 ) -48 (c 0.05, CHCl3).
D
(P )-Rh 2[(C6H4)P (m-xylyl)2]2(O2CCH3)2 ((P )-9). Yield: 75%.
[R]20 ) +43 (c 0.05, CHCl3).
D
Exp er im en ta l Section
In t r a m olecu la r Cyclop r op a n a t ion . All the catalytic
reactions were performed by dissolving the catalyst in dry
solvent (30 mL) under an argon atmosphere and adding a
solution of the corresponding diazo compound (35 mg, [sub-
strate]/[Rh(II) complex] ) 100). The mixture was stirred until
complete transformation of the diazo compound (the reaction
was monitored by TLC). The solvent was trap-to-trap evapo-
rated, and the crude product was filtered in a short chroma-
tography column to eliminate the catalyst. The yield of the
reaction was calculated by proton NMR, the cyclization product
was purified by HPLC, and the enantiomeric excesses were
calculated by chiral gas chromatography.
Bicyclo[3.1.0]h exa n -2-on e (23)26 was purified by HPLC
using a hexane/ethyl acetate mixture (10/1) as eluent: flow
rate 4 mL/min, tR ) 12.0 min. The enantiopurity of the product
was determined by chiral GC analysis (oven temperature 100
°C for 2 min, then 5 °C/min to 180 °C). tR: 1R,5S, 6.92 min;
1S,5R, 8.18 min.
Commercially available Rh2(O2CCH3)4‚2MeOH was pur-
chased from Pressure Chemical Co. The synthesis of the
following Rh(II) catalysts has been previously described:
racemic, 1,12 3,12 4,12 6,12 9;13a enantiomerically pure, 2,13a 7,13a
8,13a 10,13a 11,13a 12,13a 13,13a (P )-14,13a (M)-15,13a (P )-16,13a
(M)-17,13a (P )-18,13a (M)-19,13a (P )-20,13a (M)-21.13a The diazo
compounds 1-diazo-5-hexen-2-one,22 1-diazo-6-hepten-2-one,20
1-diazo-6-methyl-5-hepten-2-one,23 and 1-diazo-7-methyl-6-
octen-2-one24 were prepared according to literature procedures,
and the analytical data were coincident with those previously
1
reported. H, 19F, 13C, and 31P NMR spectra were recorded on
a Bruker AC-300 FT spectrometer as solutions in CDCl3 unless
specified otherwise. Chemical shifts are reported in ppm. The
coupling constants (J ) are in Hertz (Hz). All Rh(II) compounds
show 31P NMR spectra corresponding to an AA′XX′ system.
The Centro Microana´lisis Elemental, Universidad Com-
plutense de Madrid, provided analysis. Column chromatogra-
phy was performed on silica gel (70-230 mesh). Solvent
Bicyclo[4.1.0]h ep ta n -2-on e (25)26 was purified by HPLC
using a hexane/ethyl acetate mixture (10/1) as eluent, flow rate
4 mL/min, tR ) 13.0 min. The enantiopurity of the product
was determined by chiral GC analysis (oven temperature 100
°C for 2 min, then 5 °C/min to 180 °C). tR: 1R,6S, 11.71 min;
1S,6R, 12.73 min.
(21) It should be noted that cyclopentanones 23 and 27, obtained
from the same rhodium enantiomer, have different spatial configura-
tions. However, the absolute configurations assigned to them are the
same, due to the priority rules of the groups around the stereo-
centers: (a) Cahn, R. S.; Ingold, C. K.; Prelog, V. Angew. Chem., Int.
Ed. Engl. 1966, 5, 385. (b) Prelog, V.; Helmchen, G. Angew. Chem.,
Int. Ed. Engl. 1982, 21, 567.
(22) Christensen, B. G.; Cama, L. D.; Guthikonda, R. N. J . Am.
Chem. Soc. 1974, 96, 7584.
(23) J ulia, S.; Linstrumelle, G. Bull. Soc. Chim. Fr. 1966, 11, 3490.
(24) Mori, K.; Matsui, M. Tetrahedron 1969, 25, 5013.
(25) Lahuerta, P.; Pereira, I.; Pe´rez-Prieto, J .; Sanau´, M.; Stiriba,
S.-E.; Taber, D. F. J . Organomet. Chem. 2000, 612, 36.
(26) Mash, E. A.; Nelson, K. A. Tetrahedron 1987, 43, 679.

Dirhodium(II) Catalysts with Arylphosphine Ligands
Organometallics, Vol. 21, No. 8, 2002 1673
6,6-Dim eth ylbicyclo[3.1.0]h exa n -2-on e (27)24,27b was pu-
rified by HPLC using a hexane/ethyl acetate (10/1) mixture
as eluent: flow rate 4 mL/min, tR ) 8.27 min. The enantiopu-
rity of the product was determined by chiral GC analysis (oven
temperature 90 °C for 2 min, then 5 °C/min to 180 °C). tR:
1R,5S, 9.41 min; 1S,5R, 9.63 min.
In ter m olecu la r Cyclop r op a n a tion . A solution of ethyl
diazoacetate (17 mg, 0.15 mol) in pentane or dichloromethane
(5 mL) was added, via a syringe pump (1 mL/h), to a refluxing
solution of the catalyst (1.5 mg) and styrene (156 mg, 1.5 mol)
in the corresponding solvent (30 mL). After complete addition,
the reaction mixture was stirred at reflux for an additional 4
h and cooled to room temperature. The solvent was evaporated
and the crude product filtered in a short chromatography
column to eliminate the catalyst. The yield of the reaction was
calculated by proton NMR28 and the enantiopurities of the
products were calculated by chiral gas chromatography (oven
temperature 70 °C for 10 min, then 1 °C/min to 130 °C). tR:
cis-1S,2R, 58.13 min; cis-1R,2S, 58.71 min; trans-1S,2S, 68.89
min; trans-1R,2R, 69.34 min.
7,7-Dim eth ylbicyclo[4.1.0]h ep ta n -2-on e (29)24,27 was pu-
rified by HPLC using a hexane/ethyl acetate mixture (10/1)
as eluent: flow rate 4 mL/min, tR ) 13.93 min. The enan-
tiopurity of the product was determined by chiral GC analysis
(oven temperature 100 °C for 2 min, then 5 °C/min to 180 °C).
tR: 1S,6R, 6.76 min; 1R,6S, 7.16 min.
3-(2-Meth yl-1-p r op en yl)cyclop en ta n on e (30)6 was puri-
fied by HPLC using a hexane/ethyl acetate mixture (10/1) as
eluent: flow rate 4 mL/min, tR ) 9.51 min. The enantiopurity
of the product was determined by chiral GC analysis (oven
temperature 80 °C for 2 min, then 1 °C/min to 180 °C). tR:
26.11 and 26.36 min. 13C{1H} NMR: δ 17.0, 24.6, 29.3, 35.0,
37.5, 44.5, 126.4, 131.8, 218.7. HRMS (m/z): calcd for C9H14O,
138.1045; found, 138.1044.
Ack n ow led gm en t. We thank the Direccio´n General
de Investigacio´n Cient´ıfica y Te´cnica (DGICYT) (Project
PB98-1437) and the EC (Project TMR Network ERBFM-
RXCT 60091).
OM0110437
(27) (a) Yamada, S. I.; Takamura, N.; Mizoguchi, T. Chem. Pharm.
Bull. 1975, 23, 2539. (b) Lightner, D. A.; J ackman, D. E. Tetrahedron
Lett. 1975, 3051.
(28) (a) Fritschi, H.; Leutenegger, U.; Pfaltz, A. Helv. Chim. Acta
1988, 71, 1553A. (b) Nakamura, A.; Konishi, A.; Tsujitani, R.; Kudo,
M.; Otsuka, S. J . Am. Chem. Soc. 1978, 100, 3449.