Supramolecular double helical Cu(I) complexes for asymmetric cyclopropanation

Article abstract of DOI:10.1039/b713010d

Chiral double-stranded helicates, formed between Cu(I) ion and C ₂-symmetric oligopyridines, were used for catalytic asymmetric cyclopropanation of alkenes; low catalyst loadings (0.2 mol%), high TONs (up to 404) and short reaction times (30-60

Full text of DOI:10.1039/b713010d

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Supramolecular double helical Cu(I) complexes for asymmetric
cyclopropanation{
Chi-Tung Yeung,a Ho-Lun Yeung,a Chui-Shan Tsang,a Wai-Yeung Wongb and Hoi-Lun Kwong*a
Received (in Cambridge, UK) 24th August 2007, Accepted 1st October 2007
First published as an Advance Article on the web 12th October 2007
DOI: 10.1039/b713010d
Chiral double-stranded helicates, formed between Cu(I) ion and
C2-symmetric oligopyridines, were used for catalytic asym-
metric cyclopropanation of alkenes; low catalyst loadings
(0.2 mol%), high TONs (up to 404) and short reaction times
(30–60 min) were achieved with [Cu2L2]OTf2 (L 5 chiral
C2-symmetric terpyridine).
Double-stranded helicates, a paradigmatic branch of supramole-
cular structures exhibiting helical topology, have received great
Scheme 1 Syntheses of L4–5.
attention over the past two decades and numerous examples have
appeared.1 Much research has been devoted to the understanding
of the self-assembly process.2 Potential applications in areas as
Using more bulky methyl or n-butyl groups dramatically enhanced
varied as anticancer drugs,3 DNA binding,4 liquid crystalline
the selectivities to 89% and 95% de, respectively. The trinuclear
materials,5 supramolecular functional devices,6 and host–guest
interactions7 have appeared. Although helicates are chiral, para-
doxically, their use in asymmetric catalysis has not been explored.
Copper(I) ions form air-stable double-stranded dinuclear
helicates with quaterpyridines8,9 and terpyridines (tpy)10–12 in
various coordination modes. Stereoselective synthesis of Cu
helicates could be achieved with the use of chiral ligands.10,13
Trinuclear Cu(I) helicates of quinquepyridine have also been
reported but are much less studied.9a,14 Cu(I) complexes are well-
known active catalysts in a number of important asymmetric
reactions,15 and herein we report several air-stable chiral double-
stranded Cu(I) helicates with C2-symmetric terpyridines L1–3 and
quinquepyridines L4–5, and their application in asymmetric
cyclopropanation.
helicates [Cu3L42]3+ showed 79% de, but [Cu2L52]2+ gave 30% de
only. Since the enantiopurities of chiral helicates are important in
preparing a chiral catalyst, all complexes were purified as a single
diastereomer (¢95%) upon repeated recrystallization. The helical
structures of the Cu(I) helicates were further examined in solution
by CD experiments. For example, the Cu(I) helicates of L1, L4 and
L5 showed strong absorption (Cotton effect) in the region of 280–
380 nm, indicating that the integrity is retained in solution (Fig. 1).
The crystal structure of double helical [Cu2L32]2+, together with
a space-filling representation, is shown in Fig. 2.{ The Cu(I) center
adopts a distorted trigonal planar geometry and the complex
exhibits almost a D2-symmetry with a rare {3 + 3} coordination.
…
˚
The Cu Cu distance is 2.536(1) A, which is the shortest among
10–12
In the case of [Cu2L52]2+
˚
reported tpy systems (2.57–2.63 A).
New ligands L4–5 were synthesized by Pd-catalyzed Stille cross-
coupling reactions (Scheme 1). Helicate formations with ligands
L1–316 and L4–5 were investigated with different Cu(I)X salts
(X 5 PF62, OTf2 and ClO42).{ The combination of elemental
analysis and ESI-MS confirmed bimetallic complexes, of formula
[Cu2L2]X2, with L1–3; and trimetallic complexes, of formula
[Cu3L2]X3, with L4; although attempted isolation of trinuclear
Cu(I) with L5 only led to corresponding binuclear Cu helicate
[Cu2L52]2+. All double-stranded helicates are stable red solids
which did not oxidize to Cu(II) even after prolonged storage in air.
NMR studies of crude [Cu2L12]2+ showed two sets of
resonances, which corresponded to P/M diastereomers of 29% de.
(Fig. 3),{ the geometries of the Cu(I) centers were perturbed by
weak interactions of terminal pyridines at the axial positions,
causing its structural parameters to be more like a pentacoordinate
Cu(I) complex with pseudo-trigonal bipyramidal geometry. The
…
Cu Cu distance is 3.482(2) A. The two methyl substituted groups
˚
…
of sterically demanding L5 are in close proximity (C C contacts:
˚
3.81(1)–3.83(1) A), which may render the coordination environ-
ment for the formation of trimetallic complexes unfavorable. The
solid state structures of [Cu2L32]2+ and [Cu2L52]2+ both revealed
stereoselective formation of P-helix.
The Cu(I) complexes were tested in the asymmetric cyclo-
propanation of styrene with ethyl diazoacetate (EDA). Helicate
[Cu2L22](OTf)2 showed unusual reactivities in air (Table 1,
entry 1), but a better result was achieved under nitrogen.
Consistent with a previous report, the use of OTf2 salt gave the
best yields and enantioselectivities.17 By employing a more con-
ventional slow addition method,17 the reaction completed in 4 h
and afforded a 92% isolated yield of cyclopropane (Table 1,
entry 3). The trinuclear double helix is also active; under the same
conditions, [Cu3L42](OTf)3 gave good yield but required longer
aDepartment of Biology and Chemistry, City University of Hong Kong,
Tat Chee Avenue, Kowloon, Hong Kong SAR, China.
E-mail: bhhoik@cityu.edu.hk; Fax: +852 2788 4706; Tel: +852 2788 7304
bDepartment of Chemistry, Hong Kong Baptist University, Waterloo
Road, Hong Kong SAR, China
{ Electronic supplementary information (ESI) available: Characterizations
of [Cu2L52](PF6)2 and [Cu2L32](ClO4)2 and general procedure of catalytic
cyclopropanation. See DOI: 10.1039/b713010d
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Chem. Commun., 2007, 5203–5205 | 5203

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Table 1 Double helical Cu(I) helicates for asymmetric cyclopropanation
% eed
Yielda
(%)
Chemo-
selectivityb cis : transc cis trans
Entry Helicate
1e,f
2f
[Cu2L22]2+ 53
[Cu2L22]2+ 66
3.1 : 1
3.6 : 1
5.1 : 1
12.1 : 1
2.0 : 1
1.8 : 1
5.8 : 1
43 : 57
43 : 57
39 : 61
43 : 57
28 : 72
45 : 55
34 : 66
b
65 63
73 71
84 74
83 76
15 30
23 52
14 31
3g
4h
5h
6h
7g,i
a
[Cu2L22]2+ 92
[Cu2L22]2+ 93
[Cu2L12]2+ 67
[Cu2L32]2+ 45
[Cu3L42]3+ 96
Isolated yields based on the expected products. Cyclopropanes :
c
coupling products. Determined by GC-FID. Determined by chiral
d
HPLC: cis-cyclopropane was (1R,2S), trans-cyclopropane was
(1R,2R). Result obtained in air. One pot addition of EDA. Slow
e
f
g
h
addition of EDA for 4 h into the catalytic mixture. Slow addition
of EDA–styrene (1
Required 16 h for complete reaction.
:
4) for 0.5
h into the catalytic mixture.
i
reaction time for completion (Table 1, entry 7). [Cu2L52](OTf)2
afforded less than 5% yield of cyclopropanes.18
Since [Cu2L22](OTf)2 gave the best result, conditions were
modified to explore its catalytic behavior. In contrast to the
prolonged EDA addition time (4 h) generally required to reduce
the formation of coupling products in cyclopropanation, we found
the helical complex to be very active: a loading of 0.2 mol%
complex and one pot addition of EDA completely consumed all
EDA and afforded cyclopropane/coupling product in 20 min. By
adding EDA–styrene in a ratio of 1 : 4 to the solution of Cu
helicates for 30 min, the coupling product was suppressed to 7%
and the yield of cyclopropane improved to 93% (Table 1, entry 4).
The turnover number (TON) reached 404 and good enantioselec-
tivities for both cis- (83%) and trans-cyclopropanes (76%) were
observed. Longer EDA addition time and higher EDA/styrene
ratio yielded no further improvement. Dramatically, Cu(I)
helicates of L1 and L3 gave much lower % yield and % ee
(Table 1, entries 5 and 6).
Fig. 1 CD spectra of [Cu2(L1)2](ClO4)2 (1.92
6
1024 M) (---),
[Cu3(L4)2](ClO4)3 (1.22 6 1025 M) (—) and [Cu2(L5)2](PF6)2 (1.27 6
1024 M) (-?-) in CH2Cl2.
Under optimum conditions, several alkenes were employed to
determine the substrate scope of [Cu2L22](OTf)2 (Table 2). At a
catalyst : EDA : alkene ratio of 1 : 500 : 2000, the complex
catalyzed a wide range of substrates with high TON and good
enantioselectivities under nitrogen. Steric hindrance at the b-posi-
tion of the styrene greatly affected the reactivities: both cis- and
trans-b-methyl styrenes gave lower reaction yields, albeit that high
levels of enantioselectivities were maintained. Most reactions
finished in 30 min. Although generally less reactive towards
cyclopropanation, with difficult substrates, such as 1-hexene and
dienes, the catalytic reactions were completed within 1 h with high
TON and moderate to good enantioselectivities.
Fig. 2 Crystal structure and space-filling model of cationic double
helicate [Cu2L32]2+
.
Although the mechanism of the catalytic cyclopropanation
is still unclear at this stage, however, preliminary experiments
looking at the reaction of [Cu2L22](OTf)2 with cyclohexyl
isocyanides gave a solid that showed positive ions at m/z 1282
([Cu2L22(CNC6H11)OTf]1+) in ESI-MS and strong absorptions
in its CD spectrum. Similar results were also found for
[Cu3L42](OTf)3. These observations suggest that these Cu(I)
helicates contained at least one vacant site for catalysis.
Fig. 3 Crystal structure and space-filling model of cationic double
helicate [Cu2L52]2+
.
5204 | Chem. Commun., 2007, 5203–5205
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Rint 5 0.0782, R1 5 0.0535 (Io . 2s(Io)) and 0.0819 (for all data),
wR2 5 0.1354 (Io . 2s(Io)) and 0.1535 (for all data). Flack
parameter 5 20.002(12). CCDC 651265. For crystallographic data in
CIF or other electronic format see DOI: 10.1039/b713010d
a
Table 2 Asymmetric cyclopropanation of alkenes by [Cu2L22](OTf)2
% eee
% Yield Chemo-
(TON)b selectivityc cis : transd cis trans
Entry Alkene
1
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93 (404) 12.1 : 1
91 (406) 16 : 1
93 (365) 6.8 : 1
43 : 57
38 : 62
36 : 64
83 76
78 76
77 80
2
3
4f
5f
86 (240) 2.2 : 1
73 (130) 0.8 : 1
18 : 82
29 : 71
83 57
83 19
6
7
86 (394) 9.3 : 1
87 (365) 9.3 : 1
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—
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9f
83 (212) 1.7 : 1
86 (316) 4.7 : 1
47 : 53
49 : 51
68 19
68 33
10f
72 (172) 1.3 : 1
39 : 61
66 31
a
Conditions: 0.2 mol% cat (6.25 mM) in CH2Cl2 at rt, slow
addition of 1 : 4 of EDA and olefin mixture over 30 min. Isolated
cyclopropanes based on expected products.
coupling products. Determined by GC-FID. Determined by chiral
HPLC:19 for entries 1–3 and 6, cis-cyclopropanes were (1R,2S),
trans-cyclopropanes were (1R,2R); entry 7, the absolute configura-
tion was (1R). Others were not determined. Required 60 min for
complete reaction.
b
c
Cyclopropanes :
d
e
f
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In conclusion, we have prepared several new double-helical
Cu(I) helicates with chiral oligopyridines L1–5 and applied some of
them in asymmetric cyclopropanation. This represents the first
application of double-stranded helicate in asymmetric catalysis.
The nature of the active intermediates and the utilities of helical
systems in other asymmetric reactions are under active investiga-
tion in our group.
Financial support for this research project from the Hong Kong
research grants council CERG grant (CityU 101104) and the City
University of Hong Kong SRG grant (7001980) is gratefully
acknowledged.
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Notes and references
{ Crystal data: (Cu2L32)(ClO4)2(H2O): C74H96Cl2Cu2N6O9, M 5 1411.55,
˚
monoclinic, space group P21, a 5 14.961(9) A, b 5 14.001(9) A,
˚
3
˚
˚
c 5 18.179(11) A, b 5 95.0730(10)u, V 5 3793.07(40) A , Z 5 2,
Dcalc 5 1.236 g cm23, m(MoKa) 5 0.687 cm21. 18953 reflections measured,
12119 unique, Rint 5 0.1380, R1 5 0.0654 (Io . 2s(Io)) and 0.1456 (for all
data), wR2 5 0.1432 (Io . 2s(Io)) and 0.1760 (for all data). Flack
parameter 5 0.007(18). CCDC 651264. Crystal data: (Cu2L52)(PF6)2:
C82H82Cu2F12N10P2, M 5 1624.60, monoclinic, space group P1211,
18 Analogous dinuclear double helical quaterpyridine copper complexes
also gave similar results.
19 The absolute configurations of cyclopropanes were determined via
literature methods: (a) H. Nishiyama, Y. Itoh, Y. Sugawara,
H. Matsumoto, Y. Aoki and K. Itoh, Bull. Chem. Soc. Jpn., 1995, 68,
1247; (b) H. Fritschi, U. Leutenegger and A. Pfaltz, Helv. Chim. Acta,
1988, 71, 1553; (c) J. E. Baldwin and C. G. Carter, J. Am. Chem. Soc.,
1982, 104, 1362.
˚
˚
˚
a 5 15.5877(8) A, b 5 13.2827(7) A, c 5 19.0425(10) A, b 5
101.6540(10)u, V 5 3861.41(30) A , Z 5 2, Dcalc 5 1.397 g cm23,
3
˚
m(MoKa) 5 0.673 cm21. 19386 reflections measured, 13289 unique,
This journal is ß The Royal Society of Chemistry 2007
Chem. Commun., 2007, 5203–5205 | 5205