Structures, spectroscopy and modeling of a rare set of isomeric copper(II) complexes

Article abstract of DOI:10.1016/j.ica.2011.02.047

The structures and spectroscopic properties of various conformations of two diasteromeric pairs of enantiomers of pentacoordinate Cu^II bispidine complexes with chiral tetradentate ligands are reported. With one of the ligands an interesting type of distortional isomerism was observed experimentally, and this was studied in detail on the basis of the experimental structural and spectroscopic data (UV-Vis-NIR, EPR) and a DFT-, MM- and ligand-field-theory-based analysis.

Full text of DOI:10.1016/j.ica.2011.02.047

Inorganica Chimica Acta 374 (2011) 422–428
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Inorganica Chimica Acta
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Structures, spectroscopy and modeling of a rare set of isomeric copper(II) complexes
⇑
Peter Comba , Shanthi Pandian, Hubert Wadepohl, Sebastian Wiesner
Universität Heidelberg, Anorganisch-Chemisches Institut, INF 270, D-69120 Heidelberg, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 27 February 2011
The structures and spectroscopic properties of various conformations of two diasteromeric pairs of enan-
tiomers of pentacoordinate CuII bispidine complexes with chiral tetradentate ligands are reported. With
one of the ligands an interesting type of distortional isomerism was observed experimentally, and this
was studied in detail on the basis of the experimental structural and spectroscopic data (UV–Vis–NIR,
EPR) and a DFT-, MM- and ligand-field-theory-based analysis.
Dedicated to Prof. W. Kaim
Keywords:
Ó 2011 Elsevier B.V. All rights reserved.
Distortional isomerism
Density functional theory
Ligand field
Diastereo isomer
Copper bispidine
Axial and rhombic
1. Introduction
tial applications, since the near degenerate minima on the PES may
have strikingly different structures and therefore may significantly
CuII bispidine complexes find a wide range of applications in
biomimetic chemistry and catalysis (see Scheme 1 for the chiral
tetradentate bispidines L discussed here) [1–7]. This is mainly
due to the rigid 3,7-diazabicyclo[3.3.1]nonane (bispidine) back-
bone of the tetra-, penta- and hexadentate ligands, which enforces
specifically distorted square pyramidal or cis-octahedral geome-
tries, which are in particular highly complementary for the Jahn–
Teller active CuII ions [8–12]. The shape and rigidity of the
bispidine ligands leads to relatively flat potential energy surfaces
(PES) with steep boundaries and various shallow minima in the flat
area, i.e., a rigid ligand cavity and elastic coordination geometries
[13,14]. This is of interest because the isomeric structures are close
to degenerate and have significantly different structures and prop-
erties [5–7,11,15].
Bond-stretch or distortional isomers are molecules which differ
only in the length of one or several bonds – much like conformers,
they are species on a single potential energy surface with two or
more minima, and there is a long and controversial history of dis-
tortional isomerism [16–20]. Complexes of the rigid bispidine li-
gands with flat PES and various nearly degenerate minima are
potential candidates for distortional isomerism, and a number of
examples have been discussed in detail.1 This has interesting poten-
differ in various molecular properties [22].
2. Results and discussion
The bispidine ligand L has two stereo centers when R – H (car-
bon atoms 4 and 8 in Scheme 1), leading to two diastereomeric
pairs of enantiomers of the corresponding pentacoordinate
[CuII(L)(Cl)]+ complexes. In each of the four configurations the
methyl substituent at C8 may be axial (ax) or equatorial (eq),
depending on the conformation of the corresponding six-mem-
bered chelate ring involving Npy1. The 4-(R)-8-(R)- and 4-(R)-8-
(S) isomers of L2 were isolated and their CuII complexes prepared
and fully characterized (see Section 3). The synthesis of the ligands
is based on a known method for the preparation of the chiral pip-
eridone precursor [7,23], followed by a Mannich condensation
with CH2O and the corresponding amine fragment, i.e., optically
pure (R)-a-Me- or (R)-a
-Phe-picolylamine. Complexation to CuII
was followed by chromatographic separation of the two diastereo-
meric forms.
The CD spectra of the pure diastereomers of the CuII complexes
4-(R)-8-(R)-[(L2)CuII(Cl)]+ and 4-(R)-8-(S)-[(L2)CuII(Cl)]+ (see Sup-
plementary information) are, as expected, close to mirror images
with positive
De values in the CT and dd range of the spectra for
4-(R)-8-(R)-[(L2)CuII(Cl)]+ and negative values for 4-(R)-8-(S)-
[(L2)CuII(Cl)]+ (see computed structures and their discussion,
Fig. 1); the dd transitions for the former complex are at slightly
lower energy than for the latter. This also emerges from the
⇑
Corresponding author. Fax: +49 6221 546617.
E-mail address: peter.comba@aci.uni-heidelberg.de (P. Comba).
Not all examples from the area of bispidine complexes published so far are bond-
1
stretch isomers in a purist sense [2,9,12,13,21].
0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2011.02.047

P. Comba et al. / Inorganica Chimica Acta 374 (2011) 422–428
423
therefore allow predicting the two minimum structures of the
4-(R)-8-(R)-(L2)-based complex, for which no experimental struc-
tural data are available. The DFT- and the MM-based computed CuII
structures of this diastereomer are reasonably similar to each
other, with the exception of the N7–Cu–Cl angle of the conformer
with an equatorial 8-Me substituent, and this leads to some ambi-
guity with respect to the
s value and also to some deviation in the
predicted Cu–Npy2 distance.
The generally observed accuracy of the structural data (X-ray
versus DFT versus MM)2 allows to make valid estimates of the rel-
ative stabilities of various isomers of [(L2)Cu(Cl)]+. Listed in Table 1
are the DFT-computed relative free energies and the MM-derived
strain energy differences for all relevant structures.3 The DFT-com-
puted and LFMM-derived energy differences between ax- and
eq-4-(R)-8-(S)-[(L2)Cu(Cl)]+ are 8.2 and 10.9 kJ/mol, respectively, in
favor of the ax isomer, and those between ax- and eq-4-(R)-8-(R)-
[(L2)Cu(Cl)]+ are 3.7 and 9.6 kJ/mol, with the eq isomer lower in en-
ergy.4 It is interesting to note that similar energy differences were
reported for the axial and rhombic structures of blue copper proteins,
which exhibit a similar type of distortional isomerism [28].
Scheme 1. Chemical structure of the chiral tetradentate bispidine ligands L; L1:
R = H, L2: R = CH3, L3: R = C6H5.
solution electronic spectra (see Supplementary information for the
spectra and below for the discussion of the transition energies).
X-band EPR spectra of 4-(R)-8-(R)- and 4-(R)-8-(S)-[(L2)CuII(Cl)]+
(see Supplementary information) indicate that the CuII centers
have axial symmetry with a dx2–y2 ground state. The spin Hamilto-
nian parameters are, as expected, slightly different for the two
structures (see below).
A DFT-based relaxed PES scan for the 4-(R)-8-(S)-[(L2)Cu(Cl)]+
diastereoisomer was performed along various internal coordinates
connecting the two conformers with ax versus eq 8-Me groups and
elongations along Cu–N3 versus Cu–Npy2. Scans along the Cu–N3
and Cu–Npy2 modes alone did not interconvert the ax to eq geom-
etries and vice versa but lead to distorted geometries with a 2.8 kJ/
mol energy difference to the eq-4-(R)-8-(S)-[(L2)Cu(Cl)]+ minimum
on the PES (11.0 kJ/mol to the ax-4-(R)-8-(S)-[(L2)Cu(Cl)]+ struc-
ture); the corresponding energies for the eq- and ax-4-(R)-8-(R)-
[(L2)Cu(Cl)]+ isomers are 3.4 and 7.1 kJ/mol. Fig. 2 shows an overlay
plot of the DFT-optimized structures of ax- and eq-4-(R)-8-(S)-
[(L2)Cu(Cl)]+ together with the corresponding double-minimum
PES and the computed transition structure.5
Angular overlap model (AOM) calculations (coordinates from
the X-ray, DFT and MM derived structures) were used to compute
the electronic dd transition energies and the g tensor parameters of
all four isomers (see Table 2) [30–34]. The calculated g-values are
in acceptable agreement with the simulated values except for gII of
ax-4-(R)-8-(S)-[(L2)Cu(Cl)]+.6 The calculated dd transition energies
indicate that the ligand field spectra of the four isomers are very
similar, and this is what was observed experimentally (see Table 2
and Supplementary information). Clearly, the agreement between
computed and observed transition energies is lower than one would
hope (and lower than in other published examples [32,33], and this
is partially due to deficiencies related to the computed structures but
also due to the fact that ligand field parameters are not transferable
[32]. However, the focus in this report is on the relatively small dif-
ferences of the spectroscopic properties. Moreover, the small barrier
Single crystal structural analyses of the ligands L1, 4-(R)-8-(R)-
L2, 4-(R)-8-(S)-L2, 4-(R)-8-(R)-L3 and 4-(R)-8-(S)-L3, as well as of
the CuII complex of L1, [(L1)CuII(Cl)]+ [7], and two conformers of
the L2-based CuII complex with axial and equatorial orientation
of the 8-Me substituent, ax-4-(R)-8-(S)-[(L2)CuII(Cl)]+ and eq-4-
(R)-8-(S)-[(L2)CuII(Cl)]+ are available (Fig. 1, Table 1; in all CuII
structures, the ligands have, in contrast to the metal-free ligands
and as usual [7], a hydrolyzed bridge-head keto group). All me-
tal-free ligands have chair-boat conformations of the bispidine
backbone with a well preorganized N3–py2 coordination pocket.
Interestingly, the unit cell of 4-(R)-8-(S)-[(L2)Cu(Cl)]+ includes
two independent complex cations with strikingly different struc-
tures. The eq-4-(R)-8-(S)-[(L2)Cu(Cl)]+ complex, similar to that of
the parent compound with the unsubstituted ligand L1, has a dis-
torted square pyramidal geometry (
= 0.0 for square pyramidal, 1.0 for trigonal bipyramidal [24])
s
= 0.27 (L2) versus 0.18 (L1);
s
and the pseudo-Jahn–Teller axis along the Cu–Npy2 bond. The api-
cal Cu–Npy2 bond distance for eq-4-(R)-8-(S)-[(L2)Cu(Cl)]+ is 2.25
versus 1.98–2.10 Å for the other N-donor groups. The second struc-
ture, ax-4-(R)-8-(S)-[(L2)Cu(Cl)]+ has a geometry which is more dis-
torted towards trigonal bipyramidal (s = 0.34) and has a tertiary
amine as the (pseudo)apical ligand (N3) with a Cu–N3 distance
of 2.22 versus 2.10 Å. An ORTEP plot, based on the X-ray crystal
structure analysis, of the two diastereomeric forms and of the par-
ent L1-based complex is shown in Fig. 1, the corresponding struc-
tural parameters are given in Table 1. Since these two isomers of
4-(R)-8-(S)-[(L2)Cu(Cl)]+ have very different geometries and appear
in the same crystal lattice, they must be close to degenerate and
therefore are typical examples for distortional isomerism.
2
The root mean square deviation (RMSD) between the DFT and X-ray structures is
0.07 Å for distances and 6.4° (ax isomer), 5.8° (eq isomer) for angles; the RMSD
between the experimental and LFMM calculated structures is 0.07 Å for distances,
4.9° (ax isomer) and 2.4° (eq isomer) for angles.
For the L2-based CuII complexes, the structural variation was
therefore also studied with computational methods: the structures
and relative stabilities of the four possible geometries (two confor-
mations each [ax and eq] for the two diastereoisomeric forms of the
coordinated ligand (4-(R)-8-(S)- and 4-(R)-8-(R)-(L2)) as well as the
electronic and spectroscopic properties and the energy barriers be-
tween the conformations were studied by density functional the-
ory (DFT) as well as with empirical force field calculations with
the ligand field molecular mechanics approach (LFMM)
[12,25,26], and with ligand field theory (angular overlap model,
AOM) calculations. The DFT- as well as the MM-optimized struc-
tures of the two conformers of the 4-(R)-8-(S)-(L2)-based com-
plexes are in very good agreement with the experimental
structures (except for the Cu–Npy2 bond in the axial conformer,
which is computed approx. 0.1 Å too long, see Table 1) and
3
Note that no solvation corrections were adopted for the MM-derived relative
energies; with crystal-structure-based force fields, averaged secondary interactions
are believed to included [27].
4
Note that DFT predicts ax-4-(R)-8-(S)-[(L2)Cu(Cl)]+ to be lowest in energy, while
the absolute minimum structure predicted by MM is eq-4-(R)-8-(R)-[(L2)Cu(Cl)]+. This
deviation may be due to the structural inaccuracies described above but this should
not be overinterpreted because energy differences below 10 kJ/mol should be
interpreted cautiously, specifically when very different methods have been used.
5
Note that this obviously is not an optimized transition state structure but the
indication is that there is a very low energy pathway for the structural interconver-
sion; such a low activation barrier indicates that the distortional isomers may not
easily be trapped and observed experimentally (e.g., not by X-band EPR spectroscopy;
high-field (95 GHz) ESE-detected EPR was used to characterize the two electronic
ground states of azurin mutants) [29].
6
Model calculations indicate that this is not due to possible ligand exchange, i.e.,
the corresponding aqua complex leads to similar g-parameters.

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P. Comba et al. / Inorganica Chimica Acta 374 (2011) 422–428
Fig. 1. Plots of the molecular structures of (a) X-ray structures of the ligands 1: L1, 2: 4-(R)-8-(R)-L2, 3: 4-(R)-8-(S)-L2, 4: 4-(R)-8-(R)-L3, 5: 4-(R)-8-(S)-L3; (b) X-ray crystal
structures of [(L1)Cu(Cl)]+ and of both conformers (eq and ax) of 4-(R)-8-(S)-[(L2)Cu(Cl)]+; and (c) DFT optimized structures of eq-4-(R)-8-(S)-[(L2)CuII(Cl)]+, ax-4-(R)-8-(S)-
[(L2)CuII(Cl)]+, eq-4-(R)-8-(R)-[(L2)CuII(Cl)]+ and ax-4-(R)-8-(R)-[(L2)CuII(Cl)]+.
between the various isomers leads to fast dynamics, i.e., the ob-
served spectra are obviously mixtures between different forms
(see above).
was used to show that eq-4-(R)-8-(S)-[(L2)Cu(Cl)]+ is best described
as distorted square pyramidal, while the corresponding ax-isomer
is distorted trigonal bipyramidal. The computed structures are in
good agreement with experiment and allow to predicting a similar
isomerism in the complexes with the 4-(R)-8-(R)-L2-based com-
plexes. This structural variation leads to subtle but small differ-
ences in the spectroscopic properties. However, the fact that the
various isomers are close to degenerate and the shallow minima
In conclusion, the tetradentate chiral bispidine ligand L2 with its
two diastereoisomers leads to four isomeric pentacoordinate CuII
complexes eq- and ax-4-(R)-8-(S)-[(L2)Cu(Cl)]+ and eq- and ax-4-
(R)-8-(R)-[(L2)Cu(Cl)]+. Interestingly, there are striking differences
in terms of the coordination geometries, and X-ray crystallography

P. Comba et al. / Inorganica Chimica Acta 374 (2011) 422–428
425
Table 1
Comparison of experimentally determined, DFT (italics, in parentheses) and LFMM optimized (italics, in square brackets) structural parameters of the CuII complexes (distances in
Å; angles in °; relative free energies in kJ/mol).
[(L1)Cu(Cl)]+ [7]
eq-4-(R)-8-(S)-[(L2)CuII(Cl)]+
ax-4-(R)-8-(S)-[(L2)CuII(Cl)]+
eq-4-(R)-8-(R)-[(L2)CuII(Cl)]+
ax-4-(R)-8-(R)-[(L2)CuII(Cl)]+
Cu–N3
Cu–N7
2.084(2)
2.053(2)
2.077(2)
2.250(2)
2.280(2)
163.1(1)
93.015(1)
78.009(1)
152.1(1)
0.18
2.099(4) (2.11) [2.17]
2.036(5) (2.09) [2.08]
1.983(5) (2.03) [2.06]
2.259(5) (2.35) [2.25]
2.244(2) (2.27) [2.25]
161.7(2) (165.3) [162.5]
90.1(2) (94.2) [93.1]
77.8(2) (77.0) [75.8]
145.4(2) (153.7) [143.4]
0.27 (0.18) [0.25]
2.220(5) (2.29) [2.24]
2.067(5) (2.08) [2.08]
2.017(5) (2.06) [2.09]
2.088(6) (2.18) [2.19]
2.269(2) (2.26) [2.25]
128.9(2) (137.8) [134.4]
150.8(2) (144.9) [147.9]
78.2(2) (75.6) [75.9]
171.2(2) (172.8) [166.6]
0.34 (0.47) [0.31]
(2.04) [2.09]
(2.18) [2.22]
(1.99) [2.02]
(2.27) [2.12]
(2.28) [2.24]
(167.9) [164.8]
(94.7)[93.8]
(78.6)[79.9]
(136.5) [114.1]
(0.52) [0.83]
(2.96) [2.94]
(8.0) [0.0]
(2.19) [2.19]
(2.11) [2.11]
(2.05) [2.09]
(2.27) [2.18]
(2.26) [2.23]
(143.4) [134.4]
(137.8) [146.7]
(76.1) [77.1]
(173.1) [170.0]
(0.50) [0.60]
(2.95) [2.91]
(11.7) [9.6]
Cu–Npy1
Cu–Npy2
Cu–Cl
Npy1–Cu–N3
Npy1–Cu–Npy2
Npy2–Cu–N3
N7–Cu–Cl
s
N3Á Á ÁN7
2.807(2)
2.832(2) (2.92) [2.93]
(8.2) [19.7]
2.825(2) (2.92) [2.92]
(0.0) [8.8]
Relative free energies
Fig. 2. (a) Overlay of ax-4-(R)-8-(S)-[(L2)Cu(Cl)]+ (light) and eq-4-(R)-8-(S)-[(L2)Cu(Cl)]+ (dark); and (b) PES of the interconversion of the two isomeric structures together with
the distorted transition structure.
Table 2
Experimentally determined and calculated (AOM) transition energies and g-tensors for all four isomers, in comparison with the experimental data from ax-4-(R)-8-(S)-
[(L2)CuII(Cl)]+ and eq-4-(R)-8-(R)-[(L2)CuII(Cl)]+.
Complex
Method
E(xy) (cmÀ1
)
E(yz) (cmÀ1
)
E(xz) (cmÀ1
)
E(z2) (cmÀ1
)
g1
g2
g3
ax-4-(R)-8-(S)-[(L2)CuII(Cl)]+
X-ray
15 680
14 510
14 220
14 290
14 790
13 220
14 270
14 150
14 850
14 030
15 600
16 600
13 200
12 380
12 100
10 710
12 950
10 330
12 300
12 080
12 330
11 310
14 230
13 340
12 870
12 410
13 800
11 990
13 300
12 910
13 570
12 500
14 700
13 600
8560
8780
8010
5420
10 240
7760
8590
7560
9590
7630
10 500
10 500
2.04
2.04
2.04
2.06
2.04
2.05
2.04
2.03
2.01
2.02
2.05
2.06
2.07
2.09
2.09
2.06
2.07
2.08
2.09
2.10
2.11
2.10
2.05
2.06
2.23
2.24
2.25
2.25
2.23
2.26
2.24
2.25
2.21
2.24
2.35
2.25
DFT-AOM
MM-AOM
X-ray
DFT-AOM
MM-AOM
DFT-AOM
MM-AOM
DFT-AOM
MM-AOM
exp
eq-4-(R)-8-(S)-[(L2)CuII(Cl)]+
ax-4-(R)-8-(R)-[(L2)CuII(Cl)]+
eq-4-(R)-8-(R)-[(L2)CuII(Cl)]+
ax-4-(R)-8-(S)-[(L2)CuII(Cl)]+
eq-4-(R)-8-(R)-[(L2)CuII(Cl)]+
exp
on the potential energy surfaces are connected with low energy
barriers, leads to fast dynamics and prevents to trap and spectro-
scopically characterize the various structures.
Hamiltonian parameters were obtained by simulation with X-
Sophe [35]. NMR spectra were recorded at 200.13 MHz (1H) and
50.33 MHz (13C) on a Bruker AS-200 or a Bruker DRX-200 instru-
ment with the solvent signals used as reference. IR spectra were re-
corded with a Perkin–Elmer Spectrum 100 FT-IR spectrometer
instrument from KBr pellets. Mass spectra were obtained with a
JEOL JMS-700 or Finnigan TSQ 700/Bruker ApexQe hybrid 9.4 FT-
ICR instrument. For optical rotations a Jasco DIP 370 polarimeter
and for CD spectra a Jasco J 710 spectropolarimeter were used.
3. Experimental
3.1. General
Chemicals (Aldrich, Fluka) and solvents were of highest possible
grade and used as purchased. Elemental analyses were performed
by the analytical laboratories of the chemical institutes of the Uni-
versity of Heidelberg.
3.2. Syntheses
Electronic spectra were measured with a Tidas II J&M or a Jasco V-
570 UV–Vis–NIR-spectrophotometer. EPR (X-band, 9.5 GHz) spectra
at liquid N2 temperature were recorded on a Bruker Biospin ELXSYS
E500 spectrometer with a rectangular TE102 cavity mode. The spin
3.2.1. Piperidone precursor pL (6,8-dimethyl-7-oxo-5-(pyridinyl-
2yl)octahydroindolizin-6,8-dicarboxylate)
c-Aminobutyraldehydediethylacetal (18.4 g, 11.4 mmol) was
heated (65 °C) in HCl (1.5 M in MeOH, 200 ml). At ambient temper-

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P. Comba et al. / Inorganica Chimica Acta 374 (2011) 422–428
ature, pyridin-2-aldehyd (12.2 g, 11.4 mmol) and acetondicarboxy-
late–dimethylester (19.8 g, 11.4 mmol) were added and the pH
was adjusted to 4 by Na2CO3. After stirring at ambient conditions
for 1 week, the pH was adjusted to 9 (Na2CO3), and the solution
was extracted with CH2Cl2 (five times). The combined CH2Cl2 frac-
tion was dried over MgSO4 and evaporated to dryness. The oily res-
idue was washed with diethylether and dissolved in MeOH
(80 ml); H2O (10 ml) was added under stirring. At 4 °C, a white so-
lid crystallized and was removed by filtration, washed with EtOH/
H2O 1:1 and dried in vacuum. Yield: 3.3 g (1 mmol; 9%), white so-
lid. Anal. Calc. for C17H20N2O5: C, 61.44; H, 6.07; N, 8.43. Found: C,
61.37; H, 6.04; N, 8.42%. 1H NMR (200 MHz, CDCl3): d = 1.94 (m,
3H, CH–CH2–CH2); 2.30 (m, 2H, N–CH2–CH2); 2.81 (td,
3J = 2.72 Hz, 3J = 8.6 Hz, 1H, N–CH–CH2); 3.18 (m, 1H, N–CH2–
CH2); 3.74 (s, 3H, O–CH3); 3.86 (d, 3J = 11.2 Hz, 1H, CO–CH–CO);
3.97 (s, 3H, O–CH3); 4.19 (d, 3J = 10.7 Hz, 1H, CO–CH–CO); 4.50
(d, 3J = 11.04 Hz, 1H, N–CH–Py); 7.45 (m, 2H, HAr); 7.86 (td,
3J = 7.6 Hz, 4J = 1.77 Hz, 1H, HAr); 8.86 (d, 3J = 5.53 Hz, 1H, HAr).
13C NMR (50 MHz, CDCl3): d = 21.75 (1C, N–CH2–CH2À); 30.15
(1C, CH–CH2–CH2À); 51.13 (1C, N–CH2–CH2À); 52.41 (1C, O–CH3);
52.54 (1C, O–CH3); 61.51 (1C, CO–CH–CO); 62.68 (1C, N–CH–Py);
67.10 (1C, CO–CH–CO); 69.10 (1C, N–CH–CH2); 123.67, 124.53,
137.09, 150.63, 157.67 (5C, C-arom.); 170.5 (1C, COOCH3); 171.80
(1C, COOCH3); 199.82 (1C, C@O). MS: FAB C17H20N2O5,
[M+H]+ = 333.1.
1.55–2.15 (m, 10H, CH2); 2.91 (q, 3J = 8.2 Hz, 2H); 3.10 (m, 2H);
3.43 (t, 3J = 10.9 Hz, 2H); 3.59 (dd, 4J = 2.7 Hz, 3J = 11.0 Hz, 2H);
3.69 (s, 3H, –OCH3); 3.71 (s, 3H, –OCH3); 3.75 (s, 3H, –OCH3);
3.78 (s, 3H, –OCH3); 4.04 (d, 3J = 11.5 Hz, 2H); 4.10 (d,
3J = 11.7 Hz, 2H); 4.19 (d, 3J = 4.1 Hz, 2H); 7.15–7.70 (m, 12H,
HAr); 8.50–8.60 (m, 4H, HAr). 13C NMR (50 MHz, CDCl3): d = 17.42,
17.50, 21.37, 25.90, 30.90, 50.50, 50.57, 51.15, 51.79, 52.22,
52.30, 52.34, 52.45, 53.78, 54.46, 62.52, 62.68, 63.19, 64.77,
64.82, 68.63, 68.78, 72.01, 72.05, 121.90, 121.94, 122.34, 122.50,
122.93, 122.97, 124.59, 124.68, 136.04, 136.11, 136.22, 148.35,
149.32, 149.34, 156.81, 156.83, 163.47, 163.50, 169.67, 169.88,
170.20, 170.26, 202.59, 202.63, 206.92. MS: FAB C26H30N4O5
D
[M+H]+ = 479.3. [
a]
20 = 36.3° (R, rac) (c = 1 in CHCl3).
3.2.4. L3 (S,rac)-9-Oxo-2-(pyridin2-yl)-7-(phenyl(pyridin-2yl)-
methyl)-3,7-diazatricyclo[3.3.33,4.1]-dodecan-1,5-
dicarbonsäuredimethylester
7-Oxo-5-(pyridinyl-2yl)octahydroindolizine-6,8-dicarboxylate-
dimethylester (900 mg, 2.7 mmol), suspended in EtOH (10 ml) was
cooled to 0 °C. (S)-phenyl(pyridin-2-yl)methylamine (500 mg,
2.7 mmol) were added dropwise, stirred for 30 min and formalde-
hyde (0.5 ml, 6 mmol, 37% in H2O) were added. After 24 h at ambi-
ent temperature, the solvent was removed in vacuum, the residue
dissolved in little CH2Cl2 and dried over MgSO4. The solution was
evaporated to dryness and the residue crystallized from EtOH/
Et2O. Yield: 660 mg (1.2 mmol, 32%), white solid (1:1 mixture of
[S,S], [S,R] diastereomers). X-ray structure (co_SEW 20). Anal. Calc.
for C31H32N4O5: C, 65.87; H, 5.97; N, 10.36. Found: C, 65.32; H,
6.00; N, 10.14%. 1H NMR (200 MHz, CDCl3): d = 1.40–2.10 (m,
10H, CH2); 2.82 (m, 2H); 3.02 (m, 2H); 3.23 (d, 3J = 10.9 Hz, 1H);
3.35 (d, 3J = 11.1 Hz, 1H); 3.45–3.60 (m, 2H); 3.63, 3.64, 3.72,
3.73 (s, 12H, –OCH3); 3.99 (d, 3J = 10.8 Hz, 2H); 4.10 (d,
3J = 8.9 Hz, 2H); 4.65 (s, 2H, py–CH–N); 7.75–7.95 (m, 22H, HAr);
8.30–8.50 (m, 4H, HAr). 13C NMR (50 MHz, CDCl3): d = 21.42,
25.94, 50.34, 52.20, 52.34, 53.68, 54.19, 54.61, 62.72, 63.46,
68.97, 71.87, 122.18, 122.98, 124.75, 125.10, 127.56, 128.32,
3.2.2. L1 (9-Oxo-2-(pyridin2-yl)-7-(pyridin-2yl-methyl)-3,7-
diazatricyclo[3.3.33,4.1]dodecan-1,5-dicarbonsäuredimethylester)
7-Oxo-5-(pyridinyl-2yl)octahydroindolizine-6,8-dicarboxylate-
dimethylester (4.6 g, 13.8 mmol) were suspended in EtOH (35 ml)
and cooled to 0 °C. 2-Aminomethylpyridin (1.6 g, 14.7 mmol) were
added dropwise, and the solution was left stirring for 30 min be-
fore formaldehyde (2.7 ml, 32.4 mmol, 37% in H2O) was added.
After 24 h stirring at ambient temperature, the solution was evap-
orated to dryness in vacuum, dissolved in (CH2Cl2, 50 ml) and dried
over MgSO4. This solution was evaporated to dryness and the res-
idue was recrystallized from EtOH/Et2O. Yield: 2.8 g (6.0 mmol,
43.5%), white solid. X-ray structure of the racemic ligand (co_SEW
4a). Anal. Calc. for C25H28N4O5: C, 64.64; H, 6.08; N, 12.06. Found: C,
64.22; H, 6.08; N, 11.89%. 1H NMR (200 MHz, CDCl3): d = 1.70–2.35
(m, 4H, CH–CH2–CH2); 3.18 (td, 2J = 15.2 Hz, 3J = 8.4 Hz, 2H, N–
CH2); 3.60–3.85 (m, 3H); 3.88 (s, 3H, OCH3); 3.97 (s, 3H, OCH3);
4.04 (s, 2H, Py–CH2); 4.36 (s, 1H, Py–CH–N); 7.25–7.90 (m, 6H,
128.45, 136.09, 136.58, 140.89, 148.69, 149.40, 156.66, 169.74,
D
170.27. MS: FAB C31H32N4O5 [M+H]+ = 541.4. [
(c = 1 in CHCl3).
a]
20 = 5.4° (S,rac)
3.2.5. (rac)-[(L1)Cu(OTf)]OTfÃH2O
L1 (400 mg, 0.86 mmol) und Cu(OTf)2 (312 mg, 0.86 mmol) in
MeCN (water-free, 10 ml) were stirred under Ar for 6 h. The blue
solution was reduced to approx. 5 ml (vacuum), and Et2O (10 ml)
was slowly diffused into this solution. The resulting blue solid
was collected and crystallized from MeCN/Et2O. Yield: 350 mg
(0.4 mmol, 47%), blue solid. Anal. Calc. for C27H30CuF6N4O12S2: C,
38.41; H, 3.58; N, 6.64. Found: C, 38.27; H, 3.69; N, 6.72%. MS:
FAB C27H30CuF6N4O12S2, [(L7)Cu(OTf)]+ = 677.1 (calc.: 677.1).
H
Ar); 8.69 (d, 3J = 4.8 Hz, HAr); 8.74 (d, 3J = 4.8 Hz, HAr). 13C NMR
(50 MHz, CDCl3): d = 21.37 (1C, N–CH2–CH2À); 25.86 (1C, CH–
CH2–CH2À); 50.47 (1C, N–CH2–CH2À); 52.41, 52.24 (2C, O–CH3);
55.24, 56.00 (2C, N–CH–Cq); 62.43, 63.06 (2C, Cq); 62.74 (1C, N–
CH2–Py); 121.90, 122.74, 122.91, 124.61, 136.03, 136.27, 148.62,
149.25, 156.70, 158.72 (10C, CAr); 169.55, 170.00 (2C, –OCH3);
202.59 (1C, C@O). MS: FAB C25H28N4O5 [M+H]+ = 465.2.
3.2.6. (R,rac)-[(L2)Cu(OTf)]OTfÃH2OÃMeOH
3.2.3. L2 (R,rac)-9-oxo-2-(pyridin2-yl)-7-(1-(pyridin-2yl)-ethyl)-3,7-
diazatricyclo[3.3.33,4.1]dodecan-1,5-dicarbonsäuredimethylester
7-Oxo-5-(pyridinyl-2yl)octahydroindolizin-6,8-dicarboxylate-
dimethylester (2.5 g, 7.5 mmol), suspended in MeOH (60 ml) was
cooled to 0 °C. (R)-1-(pyridinyl-2yl)ethylamine (0.92 g, 7.5 mmol)
was added dropwise and stirred for 30 min. Formaldehyde
(1.8 ml, 15 mmol, 37% in H2O) was added and, after stirring at
ambient temperature for 24 h, the solution was evaporated to dry-
ness in vacuum, dissolved with the minimum amount of CH2Cl2
and dried over MgSO4. The solution was evaporated to dryness
and the residue crystallized from EtOH/Et2O. Yield: 1.8 g
(3.7 mmol, 50%), white solid (1:1 mixture of [R,S], [R,R] diastereo-
mers). X-ray structure (co_SEW 17a). Anal. Calc. for C26H30N4O5: C,
65.26; H, 6.32; N, 11.71. Found: C, 65.28; H, 6.35; N, 11.68%. 1H
NMR (400 MHz, CDCl3): d = 1.47 (t, 3J = 6.7 Hz, 6H, CH–CH3);
(R,rac)-L2 (200 mg, 0.4 mmol) and Cu(OTf)2 (137 mg, 0.4 mmol)
in MeOH (water-free, 5 ml) were stirred under Ar at ambient tem-
perature for 6 h. The blue solution was reduced to approx. 2 ml
(vacuum), and Et2O (5 ml) was slowly diffused into this solution.
The resulting blue solid was collected and crystallized from
MeOH/Et2O. Yield: 170 mg (0.19 mmol, 48%), green solid. Anal.
Calc. for C29H36CuF6N4O13S2: C, 39.12; H, 4.08; N, 6.29. Found: C,
39.54; H, 4.32; N, 6.36%. MS: FAB
C29H36CuF6N4O13S2,
[(L7)Cu(OTf)]+ = 691.2 (calc.: 691.2); [(L7)Cu(OTf)](H2O)+ = 709.3
(calc.: 709.2); [(L7)Cu(OTf)](MeOH)+ = 723.2 (calc.: 723.2).
3.2.7. (S,rac)-[(L3)Cu(OTf)]OTfÃH2OÃMeOH
(S,rac)-L3 (200 mg, 0.37 mmol) and Cu(OTf)2 (127 mg, 0.37 mmol)
in MeOH (water-free, 5 ml) were stirred under Ar at ambient tem-
perature for 6 h. The blue solution was reduced to approx. 2 ml

P. Comba et al. / Inorganica Chimica Acta 374 (2011) 422–428
427
(vacuum), and Et2O (5 ml) was slowly diffused into this solution.
The resulting blue solid was collected and crystallized from
MeOH/Et2O. Yield: 144 mg (0.15 mmol, 40%), blue solid. Anal. Calc.
for C34H38CuF6N4O13S2: C, 42.88; H, 4.02; N, 5.88. Found: C, 42.68;
H, 4.14; N, 5.90%. MS: FAB C29H36CuF6N4O13S2, [(L9)Cu(OTf)]+ =
753.2 (calc.: 753.2); [(L9)Cu(OTf)](H2O)+ = 771.2 (calc.: 771.2);
[(L9)Cu(OTf)](MeOH)+ = 785.3 (calc.: 785.3).
present study [12]. The angular overlap model (AOM) calculations
were carried out using CAMMAG, a ligand field program [48]. The
electronic parameters (e , eds, spin–orbit coupling) used in the
r
AOM calculations were similar to those described previously (see
Supplementary information for the ligand field parameters)
[32,49–52].
Acknowledgment
3.2.8. (R,R)-[(L2)Cu(OH2)](BF4)2/(R,S)-[(L2)Cu(OH2)](BF4)2
(R,rac)-L2 (200 mg, 0.4 mmol) and Cu(OTf)2 (137 mg, 0.4 mmol)
in MeOH (water-free, 10 ml) were stirred under Ar at ambient tem-
perature for 6 h. The blue solution was added to H2O (500 ml) and
sorbed onto a ion exchange column (Sephadex CM25, 200 eq, 80 g).
The complex was eluted with sodium (L)-tartrate (0.1 M) until two
fully separated bands were visible. The column was then washed
with H2O (1500 ml), and the two isomers were then eluted with
NaBF4. These solutions were reduced in volume on a rotavap, and
the NaBF4 salt was reduced by addition of EtOH/cooling/filtration.
The solids (1st band: R,S-, 2nd band: R,R-isomer) were then crys-
tallized from MeOH/Et2O. Single crystals for an X-ray crystal struc-
Generous financial support by the German Science Foundation
(DFG) is gratefully acknowledged.
Appendix A. Supplementary material
CCDC 809607–809610 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. Supplementary data associ-
ated with this article can be found, in the online version, at
doi:10.1016/j.ica.2011.02.047.
ture analysis were obtained from the 1st fraction, eluted with
632.5
0.1 M NaCl (chloro complex). [
a
]
20 = À53.3° (R,S) (c = 1 in
References
632.5
CHCl3),
26H32B2CuF8N4O6: C, 42.56; H, 4.40; N, 7.64. Found: C, 42.86; H,
4.39; N, 7.62%.
[
a]
20 = 1.9° (R,R) (c = 1 in CHCl3). Anal. Calc. for
C
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