Catalytic asymmetric cyclopropanation at a chiral platform

Article abstract of DOI:10.1039/b503971a

Novel chiral Robson-type macrocyclic complexes M₂-L [where M = Mn(II), Mn(III), Co(II) and Co(III) and L denotes tetra-Schiff base chiral ligands, L1 or L2] have been synthesized by metal template condensation of 2,6-diformyl-4-methyl-phenol, w

Full text of DOI:10.1039/b503971a

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A R T I C L E
Catalytic asymmetric cyclopropanation at a chiral platform†‡
a
a
b
Jian Gao,* F. Ross Woolley and Ralph A. Zingaro
a
Department of Radiology, University of Texas Health Science Center—San Antonio, San
Antonio, Texas, 78229-3900, U. S. A. E-mail: gao2@uthscsa.edu; Fax: +1-210-567-0494;
Tel: +1-210-567-0655
b
Department of Chemistry, Texas A & M University, College Station, Texas,
77843-3255, U. S. A.
Received 18th March 2005, Accepted 11th April 2005
First published as an Advance Article on the web 27th April 2005
Novel chiral Robson-type macrocyclic complexes M
denotes tetra-Schiff base chiral ligands, L1 or L2] have been synthesized by metal template condensation of
,6-diformyl-4-methyl-phenol, with 1R,2R-diaminocyclohexane (L1) or 1R,2R-diphenylethylenediamine (L2). The
2
–L [where M = Mn(II), Mn(III), Co(II) and Co(III) and L
2
dinuclear Co(II) and Co(III) complexes catalyze asymmetric cyclopropanation of styrene with diazoacetate
cooperatively and with high enantioselectivity.
Schiff base Robson-type macrocycles containing two bridging
phenol groups have been widely used to synthesize homo- and
1
heterodinuclear complexes. Detailed investigations in this area
have provided valuable insight into bioinorganic and catalytic
2
chemistry. However, chiral Robson-type macrocyclic com-
plexes, such as M
2
–L (M = Mn(II), Mn(III), Co(II) or Co(III), L =
3
L1 or L2; Scheme 1) have rarely been investigated to date. Our
interest in such complexes centers on their potential application
in metal ion-mediated asymmetric catalytic reactions.
Scheme 2
Scheme 1
Chiral Salen-complex catalysts containing 1R,2R-diamino-
cyclohexane moieties and various metals have being used in
the promotion of numerous catalytic asymmetric reactions such
4
5
Scheme 3
as the asymmetric epoxidation, aziridination, nucleophilic
6
7
8
epoxide ring opening, Michael addition, Diels–Alder reaction
9
and cyanide addition to aldehydes and imines These catalyst
molecules incorporate a single chirality and a single metal ion
to chiral induction by the chiral backbone as they approach
the complex platform. Other than the geometric interaction
occurring in multi-chiral complexes, the potential synergism
between the metal centers should improve the enantioselectivity
of the product. The chiral di- and multi-nuclear complex
(
Scheme 2). The molecular structure can be described as a 4-
coordinated metal adjacent to a chiral diaminocyclohexanal
backbone. The enantioselectivity for the formation of a given
product is governed at the metal center, as a result of the
presence of the stereogenic carbon. It is noteworthy that, in
such complexes, the effect of approaching reactants can occur,
not only in the axial direction, but also in the planar direction,
opposite to the cyclohexyl ring. Such actions are substantiated
by the observation of improved enantioselectivity when t-Bu
groups are integrated with the “Salen” ligand.
10–13
14–16
catalysts we have employed
along with other researchers
have received substantial attention due to their unique nature
and potential for developing entirely new areas of investigation
in synthetic chemistry.
A review of the literature indicates that transition metal-
catalyzed asymmetric cyclopropanation has been an area of
17
intense study for several years. Some of the most effi-
However, chiral Robson-type dinuclear complexes which are
cient catalysts include the following complexes, Cu(I)/Cu(II)–
bis(oxazoline), Ru(II), Co(II)/Co(III)–Salen and Fe(II)/
Fe(III). Despite the presence of a wide variety of mononuclear
complexes and their high enantioselectivity, there appear to be
limited publications which deal with dimetallic complexes. The
research reported herein deals with enantioselective catalysis and
is focused on the development of dinuclear complex catalysts,
which can function cooperatively within complexes having
enzyme-like active centers.
“
coupled-Salen” complexes (Scheme 3) may represent a new
18
19
20
type of effective catalysts in asymmetric synthesis. This is due to
the fact that the substrate molecules will invariably be subjected
21
(
†
This research program was supported by grants from Welch Founda-
tion A-259 and A-084.
Electronic supplementary information (ESI) available: experimental
‡
procedures. See http://www.rsc.org/suppdata/ob/b5/b503971a/
2
1 2 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 2 6 – 2 1 2 8
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5

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The dinuclear Mn(II) and Co(II) complexes of L1 and L2 were
successfully prepared by direct template condensation (refer to
the supplementary information). The molecular structures of
the Co(II) complexes of L1 and L2 were defined by electro
spray ionization (ESI) and elemental analyses. Molecular mod-
eling indicates that the energy-minimized conformations of the
complexes are basically planar (Scheme 4), providing sufficient
new information to begin a mechanistic analysis of the subject
reaction. The dimanganese (III) and dicobalt(III) complexes were
prepared by oxidation of the corresponding Mn(II) or Co(II)
complex by air in the presence of acetic acid. A tetranuclear
respectively. Solvent effects were also investigated by changing
the reaction medium, and demonstrated a corresponding yield
and selectivity (entry 9–12). The use of alcohol solvent was
found to decrease the stereoselectivity by more than 30% based
on the ee. This is likely to be the result of a subtle interaction
between the complex and the diazo reagent.
To gain a greater understanding of the underlying mecha-
nisms, three other complexes (Scheme 5) were tested. As shown
in Table 2, L4–Co(II) produces very little catalytic activity.
Catalyst L3–Co(II) affords a somewhat improved yield (48%)
and an ee of 57% for the cis enantiomer. This may be due to the
substituent effect of t-Bu groups on L3. Further improvement in
stereo- (cis : trans, 69 : 31) and enantioselectivity (cis enantiomer
ee = 80.4%) were observed for the mononuclear L1–Co(II) com-
plex, indicating the combined effects of asymmetric induction
and steric hindrance from the proximal chiral cyclohexyl moiety.
Co(III) complex [L1
2
Co
4
(III)(OH)
2
(OAc)
2
](ClO
4
)
4
·4CH
3
OH has
3
been defined by X-ray studies.
Scheme 5 Introducing of the steric barrier on the molecular plan.
Scheme 4
A probable mechanism for the transition metal complex-
catalyzed cyclopropanation may be the following: a transition
metal complex reacts with diazoacetates to generate a metal–
carbene intermediate. The intermediate then reacts with the
With the structurally defined catalysts in hand, we proceeded
to investigate the catalytic asymmetric cyclopropanation of
styrene with diazoacetic ester. Using 4.0 mmol of styrene and
◦
20a
5
.0 mol% catalyst in 10 ml of CH
2
Cl
2
at 25 C as standard con-
alkene to produce cyclopropane. In our catalysts, two carbene
ditions, the results are shown in Table 1. The product yields were
good to excellent (70–94%) for Mn(II), Mn(III), Co(II) and Co(III)
Table 2 Yields and enantioselectivities of different Co(II) complex as a
control
complexes. For the L1–Co
2
(III) complex, a trans-to-cis ratio of
7
4 : 26 was observed with an enantiomeric excess (ee) of 88.4
and 94.2% for trans and cis cyclopropane isomers, respectively.
Investigation of the dinuclear Co(II) complexes indicated that the
stereo- and enantioselectivity are similar to the corresponding
dinuclear Co(III) complexes, which implies that the underlying
mechanism is the same. However when employing the dinuclear
Mn(III) complex of L1, the stereo- and enantioselectivities were
found to be comparatively lower with trans-to-cis ratios of 68 :
b
c
Entry Catalysts Yield (%) trans : cis ee (trans, %) ee (cis, %)
1
2
3
L1–Co(II) 74
L3–Co(II) 48
L4–Co(II) 25
69 : 31
62 : 38
45 : 55
78.0
47.2
14.3
80.4
57.0
15.2
a
b
The solvent was added in preparing the reaction mixture. 1R,2R as
c
the major enantiomer; 1S,2R as the major enantiomer.
3
2 and an ee of 56.0 and 58.2% for the trans and cis isomer
Table 1 Dimetallic Mn(II), Mn(III), Co(II) and Co(III) complexes showing catalyzed cyclopropanation
a
b
Entry
Catalyst
Solvent
Yield (%)
trans : cis
ee (trans, %)
ee (cis, %)
1
2
3
4
5
6
7
8
9
L1–Mn
L1–Mn
2
(II)
(III)
(II)
(III)
(II)
(III)
(II)
(III)
(III)
(III)
(III)
(III)
CH
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
2
2
70
62
90
92
84
69
93
94
72
65
49
85
64 : 36
68 : 32
72 : 28
74 : 26
67 : 33
69 : 31
70 : 30
76 : 24
66 : 34
62 : 38
49 : 51
71 : 29
51.3
56.0
86.2
88.4
82.4
77.6
89.0
94.3
58.3
47.2
35.0
60.9
57.0
58.2
91.5
94.2
86.2
69.7
92.0
90.6
60.9
52.1
40.4
68.3
2
L1–Co
L1–Co
2
2
L2–Mn
L2–Mn
2
2
L2–Co
L2–Co
L2–Co
L2–Co
L2–Co
L2–Co
2
2
2
2
2
2
EtOH
t-BuOH
Ph–CH
1
1
1
0
1
2
2
OH
MeCN
a
b
1
R,2R as the major enantiomer. 1S,2R as the major enantiomer.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 2 6 – 2 1 2 8
2 1 2 7

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intermediates might have been held by a single complex molecule
and were subsequently re-oriented as a result of interaction
References
1
(a) N. H. Pilkington and R. Robson, Aust. J. Chem., 1970, 23, 2225;
b) R. Das and K. Nag, Inorg. Chem., 1991, 30, 2831; (c) B. Bosnich,
Inorg. Chem., 1999, 38, 2554.
2 (a) R. C. Long and D. N. Hendrickson, J. Am Chem. Soc., 1983,
05, 1513; (b) A. Atkins, D. Black, A. J. Blake, A. Marin-Becerra, S.
Persons, L. Ruiz-Ramirez and M. Schroder, Chem. Commun., 1996,
(
Scheme 6). The enantioselectivity occurring in these cyclo-
(
propanation reactions can be correlated with the orientation
of the carbene ligand and the approach of the incoming olefins.
1
4
57; (c) M. Yonemura, N. Usuki, Y. Nakamura, M. Ohba and H.
Okawa, J. Chem. Soc., Dalton Trans., 2000, 3624.
3
4
J. Gao, J. H. Reibenspies, R. A. Zingaro, F. Ross Woolley, A. E.
Martell and A. Clearfield, Inorg. Chem., 2005, 44, 232–241.
(a) S. Cheng, N. H. Lee and E. N. Jacobsen, J. Org. Chem., 1993,
5
8, 6939; (b) P. J. Pospisil, D. H. Carsten and E. N. Jacobsen,
Chem. Eur. J., 1996, 2, 974; (c) T. Flessner and S. Doye, J. Prakt.
Chem./Chem.-Ztg., 1999, 341, 436; (d) Z. Li and C. Jablonski, Chem.
Commun., 1999, 1531.
Z. Li, K. R. Conser and E. N. Jacobsen, J. Am. Chem. Soc., 1993,
115, 5326.
5
6
Scheme 6
(a) L. E. Martinez, J. A. Leighton, D. H. Carsten and E. N. Jacobsen,
J. Am. Chem. Soc., 1995, 117, 5897; (b) J. F. Larrow, S. E. Schaus and
E. N. Jacobsen, J. Am. Chem. Soc., 1996, 118, 7420; (c) M. Tokunaga,
J. F. Larrow, F. Kakiuchi and E. N. Jacobsen, Science, 1997, 277, 936.
J. K. Myers and E. N. Jacobsen, J. Am. Chem. Soc., 1999, 121, 8959.
(a) D. A. Evans, T. Lectka and S. J. Miller, Tetrahedron Lett., 1993,
34, 7027; (b) S. E. Schaus, J. Branalt and E. N. Jacobsen, J. Org.
Chem., 1998, 63, 403.
The favorable orientation of the carbene intermediates in
the L1–Co (II) catalyzed reaction is shown in Scheme 7.
2
7
8
One carbene-plane is parallel to the other, but the planes
are perpendicular to the complex platform. This arrangement
minimizes the steric interactions between the ester groups as
well as their interaction with the axial hydrogen atoms on the
sterogenic centers. As demonstrated in a prior investigation of
cyclopropanation by 8 group transition metal metalloporphyrin
carbene complexes, the approach of olefin with its C=C axis
9
(a) M. S. Sigman and E. N. Jacobsen, J. Am. Chem. Soc., 1998,
1
20, 5315; (b) V. I. Tararov, D. E. Hibbs, M. B. Hursthouse, N. S.
Ikonnikov, K. M. A. Malik, M. North, C. Orizu and Y. N. Belokon,
J. Chem. Soc., Chem. Commun., 1998, 387.
0 J. Gao, R. A. Zingaro, J. H. Reibenspies and A. E. Martell, Org.
Lett., 2004, 14, 2453.
1
21
parallel to the M=C bonds is strongly preferred. The approach
of a styrene along path a can minimize the steric interaction
of axial hydrogen atoms with the olefin phenyl group. This
produces the desired cis product with a 1S,2R configuration.
The major trans enantiomer results from an approach along
path b, which is consistent with the observed stereochemistry.
After numerous efforts to obtain a crystal structure of the bis-
carbene complexes, we remain unsuccessful with our available
equipment and techniques. Although the carbene intermediate
was difficult to isolate, this mechanistic analysis is critical and
may shed light on the future design of highly selective catalysts
in other asymmetric syntheses.
11 J. Gao, J. H. Reibenspies and A. E. Martell, Angew. Chem., Int. Ed.,
003, 42, 6008–6012.
2
1
1
1
2 J. Gao and A. E. Martell, Org. Biomol. Chem., 2003, 1, 2801.
3 J. Gao and A. E. Martell, Org. Biomol. Chem., 2003, 1, 2795.
4 (a) B. M. Trost and L. R. Terrell, J. Am. Chem. Soc., 2003, 125, 338;
(
(
b) B. M. Trost and V. S. C. Yeh, Angew. Chem., Int. Ed., 2002, 41, 5;
c) B. M. Trost, E. R. Silcoff and H. Ito, Org. Lett., 2001, 3, 2497.
15 (a) M. Shibasaki and N. Yoshikawa, Chem. Rev., 2002, 102, 2187–
2209; (b) M. Shibasaki, H. Sasai and T. Arai, Angew. Chem., Int. Ed.,
1
997, 36, 1236.
1
1
6 (a) T. P. Yoon and E. N. Jacobson, Science, 2003, 299, 1691; (b) J. M.
Ready and E. J. Jacobsen, Angew. Chem., Int. Ed., 2002, 41, 1374.
7 (a) M. P. Doyle, M. A. Mckervey and T. Ye, Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds: From Cy-
clopropanes to Ylids, John Wiley and Sons, New York, 1998; (b) T.
Ye and M. A. Mckervey, Chem. Rev., 1994, 94, 1091; (c) M. P. Doyle,
D. C., Chem. Rev., 1998, 98, 911; (d) J. Gao and S. H. Zhong, J. Mol.
Catal., 2003, 191, 23; (e) A. M. Harm, J. G. Knight and G. Stemp,
SYNLETT, 1996, 677.
1
1
8 (a) R. J. Clarke and I. J. Shannon, Chem. Commun., 2001, 1936;
(
b) M. I. Burguete, J. M. Fraile, J. I. Garcia, E. G. Verdugo, S. V.
Luis and J. A. Mayoral, Org. Lett., 2000, 24, 3905; (c) R. Boulch, A.
Scheurer, P. Mosset and R. W. Saalfrank, Tetrahedron Lett., 2001, 41,
1
023; (d) R. E. Lowenthal, A. Abiko and S. Masamune, Tetrahedron
Lett., 1990, 31, 6005; (e) D. A. Evans, K. A. Woerpel, M. M. Hinman
and M. M. Faul, J. Am. Chem. Soc., 1991, 113, 726.
9 (a) Z. Zheng, X. Yao, C. Li, H. Chen and X. Hu, Tetrahedron Lett.,
2
001, 42, 2847; (b) X. Yao, M. Qiu, W. Lu, H. Chen and Z. Zheng,
Tetrahedron: Asymmetry, 2001, 12, 197; (c) H. Nishiyama, Y. Itoh,
H. Matsumoto, S. B. Park and K. Itoh, J. Am. Chem. Soc., 1994, 116,
2
1
232; (d) S. B. Park, N. Sakata and H. Nishiyama, Chem. Eur. J.,
996, 2, 303; (e) H. Nishiyama, Y. Itoh, H. Matsumoto, S.-B. Park
and K. Itoh, J. Am. Chem. Soc., 1994, 116, 2223.
0 (a) T. Ikeno, I. Iwakura and T. Yamada, J. Am. Chem. Soc., 2002,
2
2
1
24, 15152; (b) T. Fukuda and T. Katsuki, SYNLETT, 1995, 825;
(
c) T. Niimi, T. Uchida, R. Irie and T. Katsuki, Adv. Synth. Catal.,
001, 343, 79.
2
1 (a) C. G. Hamaker, G. A. Mirafzal and L. K. Woo, Organometallics,
2001, 20, 5171; (b) G. Du, B. Andrioletti, E. Rose and L. K. Woo,
Organometallics, 2002, 21, 4490.
Scheme 7 The possible mechanism that will lead to four different
isomers (E denotes the ester groups bound with the Co(II) centers).
2
1 2 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 2 6 – 2 1 2 8