Trans effect on cobalt porphyrin catalyzed asymmetric cyclopropanation

Article abstract of DOI:10.1055/s-2006-926450

A significant trans effect of potential coordinating additives was found in asymmetric cyclopropanation catalyzed by Co(II) complexes of D ₂-symmetric chiral porphyrins [Co(1)]. Among different additives, substoichiometric amounts of DMAP resul

Full text of DOI:10.1055/s-2006-926450

SPECIAL TOPIC
1697
Trans Effect on Cobalt Porphyrin Catalyzed Asymmetric Cyclopropanation
A
symmetric Cyclo
i
propa
n
n
ation by Cob
g
alt Porphyrins Chen, X. Peter Zhang*
Department of Chemistry, University of Tennessee, Knoxville, TN 37996-1600, USA
Fax +1(865)9743454; E-mail: pzhang@utk.edu
Received 16 February 2006
Recent results from us8 and others9 have suggested that
Abstract: A significant trans effect of potential coordinating addi-
tives was found in asymmetric cyclopropanation catalyzed by
Co(II) complexes of D2-symmetric chiral porphyrins [Co(1)].
Among different additives, substoichiometric amounts of DMAP
[Co(Por)] are, in fact, highly effective catalysts for car-
bene transfer processes. More importantly, we have
shown that [Co(Por)]-based catalytic systems including
resulted in substantial increases in both diastereoselectivity and cyclopropanation can be operated effectively in one-pot
enantioselectivity. A related solvent effect on the catalytic system
fashion with alkenes as limiting regents, requiring no
slow-addition of diazo reagents.8 In addition to achieving
was also observed.
Key words: cyclopropanation, chiral porphyrins, cobalt, trans ef-
fect, asymmetric catalysis
significant asymmetric induction, Co-catalyzed cyclopro-
panation can be tailored into a trans- or cis-selective sys-
tem through employment of appropriate chiral porphyrin
ligands. Using styrene as an example (Scheme 1), it was
Transition-metal-complex-catalyzed asymmetric cyclo- demonstrated that each of the four possible stereoisomers
propanation of alkenes with diazo reagents represents a could be formed as the dominant product with the use of
fundamental transformation with practical importance Co(II) complexes of the appropriate D2-symmetric chiral
(Equation 1).1 Among the various metal complexes as cat- porphyrin [Co(1)] (Figure 1).8d During the study, we have
alysts,2 metalloporphyrins have received considerable at- revealed a significant trans effect of potential coordinat-
tention due to the unique ligand environment, metal ing additives on the [Co(Por)]-based cyclopropanation,
coordination mode, and their biological relevance to the which we wish to disclose in detail in this report.
cytochrome P-450 family of monooxygenases, which are
well known to catalyze the analogous oxo-transfer pro-
The trans effect was systematically investigated for the
cyclopropanation of styrene as the standard substrate with
ethyl diazoacetate (EDA) and tert-butyl diazoacetate (t-
BDA) as carbene sources. Three different D2-symmetric
chiral cobalt porphyrins [Co(1a)], [Co(1b)], and [Co(1c)]
were used as the catalysts (Figure 1), effectively prepared
cesses.3 Porphyrin complexes of several Group 8B metals
(Rh, Fe, Ru, and Os) represent early examples of catalysts
for cyclopropanation and related carbene transfers.4–6 De-
spite the apparent periodic relationship and low cost of Co
precursors, porphyrin complexes of Co ([Co(Por)]) had
from the same bromoporphyrin synthon via palladium-
not been previously demonstrated for catalyzing carbene
transfer reactions such as cyclopropanation.7
mediated one-pot, quadruple amidation reactions with the
corresponding chiral amide building blocks.8d Using
1 mol% catalyst loading, the cyclopropanation was typi-
cally carried out at room temperature using styrene as the
limiting reagent and 1.2 equivalents of EDA or t-BDA. As
summarized in Table 1, upon addition of 0.5 equivalent of
pyridine, both diastereoselectivity and enantioselectivity
for the EDA reaction by [Co(1a)] were significantly im-
R1
R2
CO2R
[LnM]
R1
R2
+
N2CHCO2R
+
N2m
H
Equation 1
H
H
H
H
1
1
COOR
COOR
2
2
+
cis-(1R,2S)
cis-(1S,2R)
[Co(1)]
H
H
N2CHCOOR
H
H
1
1
COOR
COOR
2
EDA: R = Et
2
+
t-BDA: R = t-Bu
trans-(1S,2S)
trans-(1R,2R)
Scheme 1 Asymmetric cyclopropanation of styrene.
SYNTHESIS 2006, No. 10, pp 1697–1700
x
x.
x
x
.
2
0
0
6
Advanced online publication: 27.04.2006
DOI: 10.1055/s-2006-926450; Art ID: C00306SS
© Georg Thieme Verlag Stuttgart · New York

1698
Y. Chen, X. P. Zhang
SPECIAL TOPIC
R*
*R
R
O
O
Me
Me
N H
H N
[Co(1a)]:
R =
R* =
N
N
N
N
S-(+)
H
Co
H N
*R
N H
O
O
R
R*
Me
Me
[Co(1)]:
[Co(1b)]: R =
R* =
S-(+)
H
R*
*R
N
O
O
H
H
N
H
H
Co
MeO
H
[Co(1c)]: R =
R* =
N
N
R-(+)
Me
O
O
*R
R*
Figure 1 Structures of D2-symmetric chiral cobalt porphyrins.
proved while retaining high yields (entries 1 and 2). The tive species. A similar situation might be responsible for
selectivities were further enhanced with N-methylimida- the observed solvent effect on the catalytic process.
zole as the additive (entry 3). The best selectivities were Though reactions run in many other solvents gave similar
obtained by adding 0.5 equivalent of 4-(dimethylami- results to those in toluene, the use of coordinating sol-
no)pyridine (DMAP) (entry 4). Although a slight increase vents, such as THF, caused a dramatic decrease in product
of enantioselectivity was detected in the case of triphen- yields (entries 14–17).
ylphosphine, no effects were observed for additives such
[Co(Por)]-catalyzed cyclopropanation is one of the few
as triphenylphosphine oxide and 2,6-lutidine (entries 5–
7), presumably due to their poorly coordinative nature.
When t-BDA was used for the reaction, the positive effect
vironment of the ligand system. As both [Co(1a)] and
of DMAP was further amplified to afford 88% ee and 98%
de for the trans isomer (entry 8). Together, these results
imply possible in situ formation of five-coordinate Co(II)
catalysts when in the presence of certain additives that are
superior catalysts in comparison with the initial four-coor-
dinate Co(II) precursors.
catalytic systems that can be either trans-selective or cis-
selective using the same metal ion while changing the en-
[Co(1b)] are trans-selective catalysts, the use of [Co(1c)],
where the chiral building block is a less compact acyclic
amide (Figure 1), afforded the cis-dominant products (en-
tries 21–27). Although no obvious effect on the cis/trans
ratio was observed for the [Co(1c)]-catalyzed cyclopropa-
nation with EDA, addition of 0.5 equivalent of DMAP
Cobalt–porphyrin complex [Co(1b)], where the two non- significantly improved the enantioselectivity of the major
chiral meso-groups are 3,5-di-tert-butylphenyl instead of cis-products but reduced the yield (entries 21 and 22). As
phenyl (Figure 1), was found to be a generally more selec- in the case of [Co(1b)] (entries 14–17), similar solvent ef-
tive catalyst for cyclopropanation (entries 1, 9, and 18). In fects were observed for the [Co(1c)]-catalyzed reactions
combination with the positive trans effect of DMAP, em- (entries 23–26).
ployment of [Co(1b)] afforded even better selectivities for
both EDA and t-BDA reactions (entries 10 and 19). These
results were further improved when the reactions were
performed at a lower temperature (entries 11 and 20). In
Co(II) porphyrins. Through the systematic study, DMAP
the case of t-BDA, 98% ee and >98% de were obtained for
the cyclopropanation of styrene (entry 20). While both
diastereoselectivity and enantioselectivity were essential-
ly unaffected, increasing the equivalent of DMAP from
ity and enantioselectivity. The study may suggest the su-
the substoichiometric to stoichiometric or excess amounts
resulted in the lower product yields (entries 12 and 13),
Co(II) complexes, which might be formed in situ and in
suggesting partial inhibition of the catalyst. Presumably,
In summary, we have revealed in detail a significant trans
effect of additives with potential coordinative capabilities
for asymmetric cyclopropanation of styrene by chiral
in substoichiometric amounts was identified to have the
largest positive effect on [Co(1)]-based catalytic systems,
resulting in substantial increases in both diastereoselectiv-
perior catalytic capability of potential five-coordinate
equilibrium with the initial four-coordinate Co(II) precur-
both active sites on the catalyst were occupied with excess
sor.
DMAP, forming a high percentage of catalytically inac-
Synthesis 2006, No. 10, 1697–1700 © Thieme Stuttgart · New York

SPECIAL TOPIC
Asymmetric Cyclopropanation by Cobalt Porphyrins
1699
Table 1 Trans Effect on Asymmetric Cyclopropanation of Styrene Catalyzed by D2-Symmetric Chiral Cobalt Porphyrins [Co(1)]a
Entry
1
[Co(1)]b
[Co(1a)]
[Co(1a)]
[Co(1a)]
[Co(1a)]
[Co(1a)]
[Co(1a)]
[Co(1a)]
[Co(1a)]
[Co(1b)]g
[Co(1b)]
[Co(1b)]
[Co(1b)]
[Co(1b)]
[Co(1b)]g
[Co(1b)]g
[Co(1b)]g
[Co(1b)]g
[Co(1b)]
[Co(1b)]
[Co(1b)]
[Co(1c)]
[Co(1c)]
[Co(1c)]
[Co(1c)]
[Co(1c)]
[Co(1c)]
[Co(1c)]j
Diazo Comp Solvent
Additive (equiv)c
none
Yield (%)d
trans/cisd
87:13
96:04
97:03
96:04
84:16
89:11
89:11
99:01
88:12
97:03
98:02
96:04
96:04
88:12
90:10
87:13
82:18
92:08
>99:01
>99:01
32:68
31:69
36:64
40:60
46:54
45:55
37:63
ee (%)e
31
55
59
67
42
34
33
88
43
78
83
77
76
32
28
46
40
67
95
98
50
92
52
61
76
72
96
Configf
EDA
EDA
EDA
EDA
EDA
EDA
EDA
t-BDA
EDA
EDA
EDA
EDA
EDA
EDA
EDA
EDA
EDA
t-BDA
t-BDA
t-BDA
EDA
EDA
EDA
EDA
EDA
EDA
t-BDA
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
PhCl
92
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1S,2R
1S,2R
1S,2R
1S,2R
1S,2R
1S,2R
1S,2R
2
pyridine (0.5)
N-methylimidazole (0.5)
DMAP (0.5)
Ph3P (0.5)
Ph3PO (0.5)
2,6-lutidine (0.5)
DMAP (0.5)
none
92
3
84
4
91
5
61
6
87
7
89
8
85
9
89
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
DMAP (0.5)
DMAP (0.5)i
DMAP (1.0)
DMAP (2.0)
none
86 (82)h
86
63
50
91
CH2Cl2
MeCN
THF
none
75
none
91
none
20
toluene
toluene
toluene
toluene
toluene
PhCl
none
22
DMAP (0.5)
DMAP (0.5)i
none
88 (84)h
84 (85)h
90
DMAP (0.5)
none
65 (59)h
99
CH2Cl2
MeCN
THF
none
91
none
73
none
25
toluene
DMAP (0.5)
78 (75)h
a Carried out at r.t. for 17–20 h under N2 using 1.0 equiv of styrene, 1.2 equiv of diazo reagent, and 1 mol% catalyst with 0.25 M of [styrene].
b See Figure 1 for structures of cobalt porphyrins.
c The equivalent was relative to styrene used.
d Determined by GC.
e Enantiomeric excess of major enantiomer determined by chiral GC.
f Absolute configuration of major enantiomer determined by optical rotation.
g Used 2 mol% catalyst with 0.13 M of [styrene].
h Yields in parentheses represent isolated yields.
i Carried out at –20 °C for 8 h.
j Used 5 mol% catalyst.
All reactions were carried out under N2 in oven-dried glassware fol-
lowing standard Schlenk techniques. THF and toluene were dis-
tilled under N2 from sodium benzophenone ketyl. Other anhyd
spectra were recorded on a Varian Mercury 300 spectrometer and
referenced with respect to internal TMS standard or residual sol-
vent. GC-MS analysis was performed on a Hewlett-Packard G
1
solvents were purchased from Aldrich. H NMR and 13C NMR
Synthesis 2006, No. 10, 1697–1700 © Thieme Stuttgart · New York

1700
Y. Chen, X. P. Zhang
SPECIAL TOPIC
1800B GCD system equipped with a CP-Chirasil-Dex CB or a B-
DM column.
References
(1) (a) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B.
Chem. Rev. 2003, 103, 977. (b) Davies, H. M. L.;
Antoulinakis, E. Org. React. 2001, 57, 1. (c) Doyle, M. P.;
Forbes, D. C. Chem. Rev. 1998, 98, 911.
Cyclopropanation of Styrene; General Procedure
Catalyst [Co(1)] (1 mol%) was placed in an oven-dried, resealable
Schlenk tube. The tube was capped with a Teflon screw cap, evac-
uated, and backfilled with N2. The screw cap was replaced with a
rubber septum, and styrene (0.25 mmol, 1 equiv) was added via sy-
ringe, followed by solvent (0.5 mL), the appropriate diazo com-
pound (1.2 equiv), and again solvent (0.5 mL). The tube was purged
with N2 for 1 min and then the septum was replaced with the Teflon
screw cap. The tube was sealed and its contents were stirred at con-
stant temperature. After completion of the reaction, n-tridecane was
added as an internal standard and the crude product was analyzed by
GC-MS. The cyclopropanes were purified by flash chromatography
on silica gel and their structures confirmed by NMR spectroscopy.
(2) For selected examples on asymmetric cyclopropanation,
see: (a) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul,
M. F. J. Am. Chem. Soc. 1991, 113, 726. (b) Doyle, M. P.;
Winchester, W. R.; Hoorn, J. A. A.; Lynch, V.; Simonsen, S.
H.; Ghosh, R. J. Am. Chem. Soc. 1993, 115, 9968.
(c) Nishiyama, H.; Itoh, Y.; Matsumoto, H.; Park, S.-B.;
Itoh, K. J. Am. Chem. Soc. 1994, 116, 2223. (d) Davies, H.
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Am. Chem. Soc. 1996, 118, 6897. (e) Lo, M. M.-C.; Fu, G.
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(3) The Porphyrin Handbook; Kadish, K. M.; Smith, K. M.;
Guilard, R., Eds.; Academic Press: San Diego, 2000-2003,
Vols. 1-20.
Ethyl 2-Phenylcyclopropane-1-carboxylate7,8
trans-Isomer
1H NMR (300 MHz, CDC13): d = 7.09–7.31 (m, 5 H), 4.17 (q,
J = 7.2 Hz, 2 H), 2.52 (ddd, J = 9.3, 6.6, 4.2 Hz, 1 H), 1.90 (ddd,
J = 8.7, 5.4, 4.5 Hz, 1 H), 1.60 (ddd, J = 9.0, 5.1, 4.2 Hz, 1 H), 1.30
(ddd, J = 8.4, 6.6, 4.8 Hz, 1 H), 1.28 (t, J = 7.2 Hz, 3 H).
(4) For the first report, see: Callot, H. J.; Piechocki, C.
Tetrahedron Lett. 1980, 21, 3489.
(5) For a recent review, see: Simonneaux, G.; Le Maux, P. P. In
The Porphyrin Handbook; Kadish, K. M.; Smith, K. M.;
Guilard, R., Eds.; Academic Press: San Diego, 2003, Vol.
11, 133–159.
13C NMR (75 MHz, CDC13): d = 173.4, 140.1, 128.4, 126.4, 126.1,
60.7, 26.2, 24.2, 17.1, 14.3.
(6) For selected examples on metalloporphyrin-based
asymmetric cyclopropanation, see: (a) Ferrand, Y.; Le
Maux, P.; Simonneaux, G. Org. Lett. 2004, 6, 3211.
(b) Berkessel, A.; Kaiser, P.; Lex, J. Chem. Eur. J. 2003, 9,
4746. (c) Teng, P.-F.; Lai, T.-S.; Kwong, H.-L.; Che, C. M.
Tetrahedron: Asymmetry 2003, 14, 837. (d) Che, C. M.;
Huang, J.-S.; Lee, F.-W.; Li, Y.; Lai, T.-S.; Kwong, H.-L.;
Teng, P.-F.; Lee, W.-S.; Lo, W.-C.; Peng, S.-M.; Zhou, Z.-
Y. J. Am. Chem. Soc. 2001, 123, 4119. (e) Gross, Z.; Galili,
N.; Simkhovich, L. Tetrahedron Lett. 1999, 40, 1571.
(f) Maxwell, J. L.; O’Malley, S.; Brown, K. C.; Kodadek, T.
Organometallics 1992, 11, 645.
(7) For non-porphyrin Co-based cyclopropanation systems,
see: (a) Niimi, T.; Uchida, T.; Irie, R.; Katsuki, T. Adv.
Synth. Catal. 2001, 343, 79. (b) Ikeno, T.; Sato, M.; Sekino,
H.; Nishizuka, A.; Yamada, T. Bull. Chem. Soc. Jpn. 2001,
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Otsuka, S. J. Am. Chem. Soc. 1978, 100, 3443.
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cis-Isomer
1H NMR (300 MHz, CDC13): d = 7.18–7.28 (m, 5 H), 3.88 (q,
J = 7.2 Hz, 2 H), 2.59 (m, 1 H), 2.08 (ddd, J = 9.0, 7.8, 5.6 Hz, 1 H),
1.72 (ddd, J = 6.3, 4.9, 4.4 Hz, 1 H), 1.32 (ddd, J = 8.9, 7.9, 5.0 Hz,
1 H), 0.97 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDC13): d = 170.9, 136.5, 129.2, 127.8, 126.6,
60.1, 25.4, 21.7, 14.0, 11.1.
tert-Butyl 2-Phenylcyclopropane-1-carboxylate7,8
trans-Isomer
1H NMR (300 MHz, CDC13): d = 7.07–7.29 (m, 5 H), 2.44 (m, 1 H),
1.82 (m, 1 H), 1.53 (m, 1 H), 1.46 (s, 9 H), 1.21 (m, 1 H).
13C NMR (75 MHz, CDC13): d = 172.5, 140.5, 128.4, 126.3, 126.0,
80.5, 28.1, 26.0, 25.3, 17.0.
cis-Isomer
1H NMR (300 MHz, CDC13): d = 7.17–7.27 (m, 5 H), 2.52 (m, 1 H),
1.99 (m, 1 H), 1.65 (m, 1 H), 1.24 (m, 1 H), 1.13 (s, 9 H).
13C NMR (75 MHz, CDC13): d = 170.1, 136.8, 129.5, 127.8, 126.5,
80.0, 27.7, 25.0, 22.7, 10.5.
Acknowledgment
We are grateful for financial support for this work from the Univer-
sity of Tennessee for Startup Funds, Oak Ridge Associated Univer-
sities (ORAU) for a Powe Junior Faculty Award, ACS-PRF for an
AC grant, and NSF for a CAREER Award.
Synthesis 2006, No. 10, 1697–1700 © Thieme Stuttgart · New York