Chiral quadridentate ligands derived from amino acids and some zinc complexes thereof

Article abstract of DOI:10.1002/1099-0682(200008)2000:8<1723::aid-ejic1723>3.0.co;2-n

A series of three new quadridentate ligands was synthesized by reaction of the haloacetylated amino acid esters L-BrAc-Phe-OMe (4a), L-BrAc-Lys(Z)- OMe (4b), and ClAc-Gly-OEt (4c), respectively, with bis(picolyl)amine (bpa, 5). The obtained products L-bpaAc-Phe-OMe (3a), L-bpaAc-Lys(Z)-OMe (3b), and bpaAc-Gly-OEt (3c) were treated with Zn(OTf)₂ (OTf = CF₃SO₃^-) to yield the trigonal-bipyramidal complexes [(L-bpaAc-Phe-OMe)ZnOTf](OTf) (6a), [(L- bpaAc-Lys(Z)-OMe)ZnOTf](OTf) (6b), and [(bpaAc-Gly-OEt)ZnOTf](OTf) (6c). Crystal structures of 6c and the hydrolysis product [(L-bpaAc-Phe-OMe)- (H₂O)ZnOTf](OTf)₂ (7a) are reported. The results suggest the formation of a chiral pocket at the metal center provided by the benzyl substituent in the L-phenylalanine derivative 7a. This observation is further supported by ¹H- NMR and circular dichroism spectroscopic data. These methods indicate a significant ordering effect within the ligands upon metal coordination as well as interactions between the first coordination spheres and their chiral environments provided by the L-phenylalanine and L-lysine moieties of 3a and 3b, respectively. Our results are discussed with respect to the development of chiral building blocks for transition metal catalysts and biomimetic assemblies.

Full text of DOI:10.1002/1099-0682(200008)2000:8<1723::aid-ejic1723>3.0.co;2-n

FULL PAPER
Chiral Quadridentate Ligands Derived from Amino Acids and Some Zinc
Complexes Thereof
Nicole Niklas,[a] Olaf Walter,[b] and Ralf Alsfasser*[a]
Dedicated to Prof. Dr. Heinrich Vahrenkamp on the occasion of his 60th birthday
Keywords: Bioinorganic chemistry / Zinc / Amino acids / Chiral ligands / Tripodal ligands
A series of three new quadridentate ligands was synthesized
by reaction of the haloacetylated amino acid esters
BrAc−Phe−OMe (4a), -BrAc−Lys(Z)−OMe (4b), and This observation is further supported by H-NMR and circu-
ClAc−Gly−OEt (4c), respectively, with bis(picolyl)amine
(bpa, 5). The obtained products -bpaAc−Phe−OMe (3a),
formation of a chiral pocket at the metal center provided by
L-
the benzyl substituent in the -phenylalanine derivative 7a.
L
1
L
lar dichroism spectroscopic data. These methods indicate a
significant ordering effect within the ligands upon metal co-
ordination as well as interactions between the first coordina-
tion spheres and their chiral environments provided by the
L
L-
bpaAc−Lys(Z)−OMe (3b), and bpaAc−Gly−OEt (3c) were
treated with Zn(OTf)2 (OTf = CF3SO3−) to yield the trigonal-
bipyramidal complexes [(
(6a), [( -bpaAc−Lys(Z)−OMe)ZnOTf](OTf)
[(bpaAc−Gly−OEt)ZnOTf](OTf) (6c). Crystal structures of 6c
and the hydrolysis product [( -bpaAc−Phe−OMe)-
L
-bpaAc−Phe−OMe)ZnOTf](OTf)
L-phenylalanine and L-lysine moieties of 3a and 3b, respect-
L
(6b), and
ively. Our results are discussed with respect to the develop-
ment of chiral building blocks for transition metal catalysts
and biomimetic assemblies.
L
(H2O)ZnOTf](OTf)2 (7a) are reported. The results suggest the
Introduction
blocks for polyfunctional catalysts. They are chiral and have
a powerful potential for combinatorial catalyst scre-
ening.[16,17] However, only a few examples of suitable li-
gands have been described in the literature. Those include
bifunctional chelating reagents[18Ϫ20] developed for phar-
maceutical applications, conjugates of lysine with EDTA or
EDTA-related ligands,[21Ϫ23] as well as a bipyridine-modi-
fied alanine.[24] The only example of an acyclic tridentate
amine ligand connected to an amino acid is a terpyridine
derivative of cysteine, which has not been isolated as a
monomer.[25,26]
Work in our laboratories has focused on the development
and investigation of Werner-type coordination compounds
with synthetic amino acids carrying well-defined metal bin-
ding sites.[27Ϫ29] In this report we present ligands derived
from glycine, -phenylalanine, and -lysine. Zinc complexes
have been prepared and investigated by X-ray crystallogra-
phy, NMR, and circular dichroism spectroscopy. Characte-
ristics of the compounds are the availability of suitable cou-
pling positions for further derivatization, the interplay bet-
ween the metal center and its chiral environment, as well as
the availability of open coordination sites for metal-cente-
red reactions.
Apart from their importance in biological systems, amino
acids are versatile building blocks for a variety of fascina-
ting synthetic molecular and supramolecular assemblies
such as peptide nucleic acids (PNAs),[1] dendrimers,[2] mi-
celles,[3] or de novo designed peptides[4] and proteins.[5,6]
The scope of accessible amino acid side-chain functionali-
ties has been tremendously broadened by organic chemists
who have developed different methods for the enantioselec-
tive synthesis and processing of artificial amino acids car-
rying, for example, aromatic rings,[7] sugars,[8] or organic
cofactors such as pyridoxamine[9] and flavine.[10] The latter
two examples illustrate the potential of nonnatural amino
acids as catalytically active components for the design of
new materials.
Catalytically active amino acid derivatives are attractive
targets not only for organic chemists but also for coordina-
tion chemistry. There is a still growing interest in metal
complexes as enantioselective catalysts for organic conver-
sions such as oxidations,[11,12] carbonϪcarbon bond forma-
tions,[13] or hydrolytic cleavage reactions.[14,15] Metal com-
plexes of synthetic amino acids with covalently attached
synthetic polydentate chelators are interesting building
[a]
Results
Institute for Inorganic Chemistry,
University of Erlangen-Nürnberg,
Egerlandstraße 1, 91058 Erlangen, Germany
Fax: (internat.) ϩ 49-(0)9131/852-7387
E-mail: alsfassr@anorganik.chemie.uni-erlangen.de
Ligand Synthesis
Our initial approach involved applying carboxylate-sub-
stituted tridentate amines in standard amide coupling reac-
[b]
ITC-CPV, Forschungszentrum Karlsruhe,
Postfach 3640, 76021 Karlsruhe
Eur. J. Inorg. Chem. 2000, 1723Ϫ1731
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ1948/00/0808Ϫ1723 $ 17.50ϩ.50/0
1723

N. Niklas, O. Walter, R. Alsfasser
FULL PAPER
given. Subsequent reaction of 4a and 4b with bis(picolyl)-
amine (bpa, 5) resulted in the formation of the desired chi-
ral ligands 3a and 3b.
We have also prepared the nonchiral glycine derivative 3c
(Scheme 2) for comparative studies concerning the role of
the chiral ligand environments provided by 3a and 3b. The
starting material for this synthesis was commercially availa-
ble (chloroacetyl)glycine. It turned out that the yields of its
reaction with 5 (ca. 50%) are significantly lower than those
obtained after bromide substitution even if both steps of
the bromoacetyl bromide route are considered (overall yield
ca. 80%). All three ligands were conveniently purified by
flash column chromatography and obtained as spectrosco-
pically pure (1H NMR) yellow oils, which were further cha-
racterized by FD-MS.
Scheme 1. Azide coupling strategy for the synthesis of the ligand 3a
tions with the N-termini of amino acids (Scheme 1). The
triamine used was the bis(picolyl)glycine 1, which was pre-
pared according to a procedure described by Que et al.[30]
for the synthesis of iron complexes. Different methods were
examined for coupling 1 to the amino group of -phenylala-
nine methyl ester. Attempts to prepare the acid chloride by
reaction of bis(picolyl)glycine with thionyl chloride failed.
Formation of an amide bond by the intermediate formation
of a mixed anhydride with isobutyl chlorofomate[31] also
proved unsuccessful. The desired ligand -bpaAcϪ
PheϪOMe (3a) was finally obtained from 1 and phenylala-
nine methyl ester (2a) by the application of diphenylpho-
sphoryl azide at low temperature in THF (Scheme 1).[31]
However, purification of the product was difficult and the
method afforded only poor yields (below 10%).
Since the coupling strategies described above were not
satisfactory we changed our approach. The method em-
ployed involves bromoacetylation of an appropriate amino
acid ester followed by nucleophilic substitution (Scheme 2).
This coupling method has been shown to be very useful for
the synthesis of polyfunctional chelating ligands. Typical
examples include polyazamacrocycleϪprotein conjugates[32]
for pharmaceutical applications and a phenylalanineϪ
triazacyclononanetriamide derivative that served as a model
for peptide organization at transition-metal templates.[33]
Applications are not limited to metal-peptide derivatives, as
exemplified by the synthesis of a hexadentate open-chain
ligand by Sargeson et al.[34]
Complexes
The amino acid ligands 3aϪc readily react with nonaqu-
eous zinc triflate [Zn(OTf)2] in dry acetonitrile (Scheme 3).
Single crystals suitable for X-ray crystallographic characte-
rization were obtained for [(bpaAcϪGlyϪOEt)ZnOTf]OTf
(6c) (Figure 1). The initially formed triflate complexes 6aϪc
are extremely moisture-sensitive and hygroscopic. Their hy-
drolysis products 7aϪc are readily obtained in the presence
of moisture from solvents or air. Single crystals of the aquo
complex [(-bpaAcϪPheϪOMe)(H2O)Zn](OTf)2 (7a, Fi-
gure 2) were obtained from dichloromethane/ethyl ether so-
lutions of 6a, which were exposed to air. Accordingly, it is
difficult to obtain samples that do not show at least trace
amounts of water in their NMR spectra. C,H,N elemental
analysis data are also consistent with the presence of va-
rious amounts of water. However, the monocations
[LZnOTf]ϩ are the dominant species observed by FAB mass
spectrometry for all complexes.
It is interesting to note that the glycine derivative 6c was
found to be the least moisture-sensitive whereas we were
not able to obtain
a
dry sample of the -
Scheme 2 illustrates our synthesis of -bpaAcϪ
PheϪOMe (3a) and the analogous ligand -
bpaAcϪLys(Z)ϪOMe (Z ϭ benzyloxycarbonyl) (3b). -
PheϪOMe (2a) and -Lys(Z)ϪOMe (2b) were treated with
bromoacetyl bromide to yield the respective products -
BrAcϪPheϪOMe (4a) and -BrAcϪLys(Z)ϪOMe (4b).
The synthesis of 4a has been reported earlier in a communi-
cation by Fairlie et al.[33] but no experimental details were
bpaAcϪLys(Z)ϪOMe complex 6b. Purification of the latter
was further complicated because the compound always se-
parates as an oil regardless of the solvent applied, thereby
Scheme 3. Synthesis and structures of the zinc complexes 6aϪc
and 7aϪc
Scheme 2. Haloacetyl strategy for the synthesis of the ligands 3aϪc
1724
Eur. J. Inorg. Chem. 2000, 1723Ϫ1731

Chiral Quadridentate Ligands Derived from Amino Acids
FULL PAPER
˚
Table 1. Selected bond lengths [A] and angles [°] for the complexes
6c and 7a
6c
7a
Zn(1)ϪO(2)
2.0145(18)
2.0197(I8)
2.039(2)
1.990(3)
Zn(1)ϪO(1)
2.054(2)
Zn(1)ϪN(2)
2.046(3)
Zn(1)ϪN(3)
2.060(2)
2.057(3)
Zn(1)ϪN(1)
2.1883(19)
99.29(9)
97.06(8)
2.189(3)
O(2)ϪZn(1)ϪO(1)
O(2)ϪZn(1)ϪN(2)
O(1)ϪZn(1)ϪN(2)
O(2)ϪZn(1)ϪN(3)
O(1)ϪZn(1)ϪN(3)
N(2)ϪZn(1)ϪN(3)
O(2)ϪZn(1)ϪN(1)
O(1)ϪZn(1)ϪN(1)
N(2)ϪZn(1)ϪN(1)
N(3)ϪZn(1)ϪN(1)
92.52(12)
105.96(15)
113.12(11)
101.59(15)
113.91(11)
123.42(13)
170.40(13)
78.45(10)
80.87(11)
79.48(12)
113.13(8)
102.36(8)
116.84(8)
121.80(8)
176.93(8)
80.68(7)
80.18(8)
80.32(8)
thus ensuring a correct interpretation of the data, which are
consistent with the formulation 7b given in Scheme 3.
Solid-State Structures
The mononuclear cation of [-bpaAcϪGlyϪOEt)Zn-
Figure 1. X-ray structure of the cation [(bpaAcϪGlyϪOEt) (OTf)](OTf) (6c) is shown in Figure 1. Selected bond
(OTf)Zn]ϩ (6c, H atoms omitted for clarity)
lengths and angles are summarized in Table 1. A slightly
distorted trigonal bipyramidal coordination environment at
Zn2ϩ is observed with one triflate anion and the bridging
tertiary amine nitrogen atom occupying the axial positions
(NϪZnϪO ϭ 177°). The two pyridine N atoms and the
amide oxygen atom of the amino acid ligands are bound in
the trigonal plane. A comparison with zinc complexes of
tris(picolyl)amine[35] and bis(picolyl)glycine,[36] respectively,
confirms that the equatorial pyridine NϪZn bonds
(204Ϫ206 pm), as well as the longer axial NϪZn bond (219
pm) are typical for tripodal quadridentate ligands derived
from bis(picolyl)amine. In contrast, all ZnϪN bonds are
equal in trigonal-bipyramidal[37] and octahedral[38] zinc
complexes of the tridentate bis(picolyl)amine ligand itself.
The amide and triflate OϪZn distances in 6 (CO: 202 pm;
OTf: 201 pm) are in excellent agreement with those found
for carboxylate OϪZn bonds in bis(picolyl)glycine comple-
xes.[36]
Facile exchange of a triflate ligand is an expected pro-
perty of the complexes 6aϪc. When a sample of [(-
bpaAcϪPheϪOMe)Zn(OTf)](OTf) (6a) in CH2Cl2/Et2O
was exposed to moist air overnight, crystals of the dica-
tionic aquo complex [(-bpaAcϪPheϪOMe)(H2O)-
Zn](OTf)2 (7a, Figure 2 and Table 1) were obtained. A
slight tetragonal distortion of its trigonal bipyramidal ge-
ometry is evident from the 170° angle between the coordi-
Figure 2. X-ray structure of the cation [(bpaAcϪPheϪ
nated water molecule, Zn2ϩ, and the tertiary amine nitrogen
atom. The axial oxygen ligand is tilted towards the amide
OMe)(H2O)Zn]2ϩ (7a, H atoms omitted for clarity)
oxygen atom [7a: H2OϪZnϪO
preventing recrystallization. The oil solidified as a white N(equatorial) 102Ϫ106° compared
foam upon drying under vacuum and this was characterized OTfϪZnϪO ϭ 99° OTfϪZnϪN(equatorial) ϭ 97Ϫ102°].
by NMR, IR, and circular dichroism spectroscopy, as well As can be seen from Figure 1 and 2 the ester functions
ϭ
92°/H2OϪZnϪ
ϭ
with 6:
as by FAB-MS. The spectroscopic properties of this com- of the ligands are noncoordinating and available for further
pound compare well with those of complexes 7a and 7c derivatization. An interesting feature of the chiral phenyl-
Eur. J. Inorg. Chem. 2000, 1723Ϫ1731
1725

N. Niklas, O. Walter, R. Alsfasser
FULL PAPER
alanine ligand in 7a is the orientation of its phenyl ring. The
ring covers one side of the open coordination site between
the amide oxygen atom and one of the pyridine rings with
˚
its center located 4.5 A away from the metal center. The
possible formation of a chiral pocket is an important diffe-
rence between 3a/3b and comparable ligands developed by
Canary et al.[39,40] These authors have synthesized chiral de-
rivatives of tris(picolyl)amine by derivatization of the brid-
ging methylene groups of the ligands leading to complexes
in which the bulky substituents are always pointing away
from the metal center.
The solid-state IR spectra (KBr pellets) of our com-
pounds are consistent with the X-ray crystallographic re-
sults. Binding of the amide oxygen atom is evident from a
red shift of the amide IR vibrations in the complexes com-
pared with the free ligands [1672 (3a) Ǟ 1641 (7a); 1668
(3b) Ǟ 1637 (7b); 1674 (3c) Ǟ 1641 (7c)]. The spectra of
all complexes exhibit signals for the triflate anions between
1200 and 1300 cmϪ1. These values are typical for noncoor-
dinating CF3SO3Ϫ and are consistent with the formulations
7aϪ7c. A broad OH band at 3000 cmϪ1 was always obser-
ved.
NMR Spectra
The solid-state structure of 7a suggests that the chiral
environment provided by the phenylalanine moiety may in-
fluence the accessibility of the open coordination site of the
metal centers. It is important for reactivity studies to probe
this structural feature in solution. We selected diamagnetic
Zn2ϩ complexes as a starting point for our investigations
since they allow the application of NMR spectroscopy to
compare solution and solid-state structures. The assignment
of the 1H-NMR signals of 7aϪc (CDCl3 solutions) is based
on comparison with the free ligands, the bromoacetylated
Figure 3. 1H-NMR spectra of the zinc complexes 6c, 7a, and 7b
in CDCl3
1
compounds, and the starting materials, as well as H-1H
1
and H-13C COSY spectra.
As may be expected the pyridine proton resonances are spectra of the complexes 7a and 7b since the two pyridine
shifted to lower frequencies upon coordination of the metal rings become inequivalent.
1
ion. The two rings are equivalent in the free ligands 3aϪc,
Most interesting is the H-NMR spectrum of the pheny-
as well as in [(bpa-GlyϪOEt)(H2O)Zn](OTf)2 (7c). A diffe- lalanine derivative 7a. Six doublets are observed for the six
rent pattern is observed in the spectra of the chiral comple- methylene protons. Two of them are observed at a signifi-
xes 7a and 7b. These compounds show two inequivalent cantly higher field (δ ϭ 3.7) than expected if the other two
1
pyridine rings with partially overlapping signals as a conse- complexes 7b and 7c are considered as a reference. The H-
quence of the chiral carbon center. The observed splitting 1H COSY spectrum confirms that one of these signals can
is a clear indication of the structural rigidity induced by be assigned to the C(O)ϪCH2 group, whereas the other cor-
metal coordination.
responds to a pyridineϪmethylene bridge. We interpret the
A very sensitive probe for changes in the environment observed high-field shift as an effect of the aromatic ring
are the methylene proton resonances, which are shown in current of the phenyl ring, which is situated between one
Figure 3. Unfortunately, some of the signals overlap with pyridine ring and the amide function (Figure 2). A corre-
those of the methyl esters and α-CH groups but they are sponding high-field shift is also observed for the phenyl
unambiguously assignable based on 1H-1H and 1H-13C protons in 7a, which are observed at rather unusual values
COSY experiments as well as integration. The C(O)ϪCH2 of δ ϭ 6.62 (H4) and δ ϭ 6.92 (H3,5). The NMR spectra
groups are observed as singlets in the ligands 3aϪ3c. Their thus confirm the importance of specific interactions bet-
corresponding signals of the chiral complexes 7a and 7b ween the benzyl group of phenylalanine and the metal coor-
are split into two doublets. The pyridine-CH2 protons are dination sphere in 7a.
diastereotopic in the chiral ligands 3a and 3b and their si-
Exchange of the coordinated triflate by water from air
gnals appear as AB systems with geminal coupling con- is also evident from NMR spectroscopy. For the extremely
stants of ca. 14 Hz. These signals are further split in the hygroscopic free ligands in CDCl3 we occasionally observe
1726
Eur. J. Inorg. Chem. 2000, 1723Ϫ1731

Chiral Quadridentate Ligands Derived from Amino Acids
FULL PAPER
a signal at δ ϭ 2, which is assignable to H2O. This signal is thyl ester results in a new signal with a negative Cotton
shifted to significantly lower fields in the complexes with effect at 225 nm and a positive Cotton effect at 245 nm. A
values ranging up to δ ϭ 5.6 in the spectrum of [(-bpa- shoulder at 245 nm is also well-resolved in the correspon-
LysϪOMe)(H2O)Zn](OTf)2 (7b). The position depends on ding phenylalanine derivative. This feature disappears in the
the water content and moves towards δ ϭ 2 for higher H2O spectra of the two ligands 3a and 3b and a new band with
concentrations. This is consistent with a fast equilibrium a positive Cotton effect is observed at 260 nm. We assign
between coordinated and noncoordinated water molecules. this band to π-π* transitions of the pyridine rings in
It is interesting to note that the urethane H signals of the agreement with interpretations given by Canary et al.[40]
benzyloxycarbonyl protecting groups in 3b and 7b are sensi- Upon complexation with Zn2ϩ the sign of the pyridine si-
tive to the presence of water and shift to slightly higher gnal changes and the band is shifted to slightly longer wave-
fields if the compounds are not rigorously dry. All other lengths. It is evident from Figure 4b that the intensity of
signals, including the amide H resonance, are invariant in the 220-nm band is significantly smaller for the ligand 3a
CDCl3 under all experimental conditions relevant for this than for the other phenylalanine derivatives discussed in
work.
our study. This may be a consequence of the higher flexibi-
lity of -bpaAcϪPheϪOMe compared with either 2a, 4a,
or 7a. However, we do not have an obvious explanation for
this behavior at the present stage of our investigations.
The observed spectral changes associated with the pyri-
dine ligands indicate that the interaction of the chromo-
phore with its chiral environment is effected by complexa-
tion. This observation may be compared with the organiza-
tion of peptides by metal ions[50] and the phenomenon of
metal-induced circular dichroism.[48] It is interesting to note
that the differential extinction coefficients observed in this
work are comparable with values obtained for biomolecules
such as proteins or DNA.[51]
Circular Dichroism
Ordering phenomena of chiral molecules and supramole-
cules in solution are conveniently probed by circular di-
chroism spectroscopy.[41] [49]A particular advantage of the
Ϫ
method is its applicability where UV/Vis spectra are not
very informative. The electronic absorption spectra of the
bromoacetylated amino acids 4a and 4b, (chloroacetyl)gly-
cine, the ligands 3aϪ3c, as well as the zinc complexes
7aϪ7c in methanol, show only a broad band at 260 nm,
which is largely obscured by the slope of a strong absorp-
tion below 200 nm. In contrast, the CD spectra of [(-
bpaAcϪPheϪOMe)(H2O)Zn](OTf)2 (7a, Figure 4a) and
[(-bpaAcϪLysϪOMe)(H2O)Zn](OTf)2 (7b, Figure 4b) me-
asured in methanol (10Ϫ3 ) have very distinct features that
further support the data obtained from NMR and X-ray
crystallographic studies.
The parent amino acids -LysϪOMe and -PheϪOMe
display only one band at 210 nm (Lys) and 220 nm (Phe),
respectively. The signal observed for phenylalanine is stron-
ger and may be assigned to the π-π* transition of the phenyl
ring. Bromoacetylation of ε-(benzyloxycarbonyl)lysine me-
Discussion
The ligands 3aϪc are quadridentate and readily bind
zinc(II) to yield stable compounds that are soluble in a va-
riety of solvents ranging from methanol to chloroform. A
labile coordination site is available in the trigonal-bipyrami-
dal triflate complexes 6aϪc. This is illustrated by the facile
ligand exchange observed in the presence of moisture (air),
which results in the formation of 7aϪc. We have designed
our ligands with two features in mind. One is the availabi-
lity of a functional group for further derivatization. This
requirement is met by the presence of a noncoordinating
ester function in the complexes 6aϪc and 7aϪc. No indica-
tion was found in the solid state or in solution for an inte-
raction between this group and the metal center. Further-
more, the protected ε-amino group of lysine in bpa-
Lys(Z)ϪOMe (3b) may be useful as an additional site for
modifications.
Our second objective was to find a chiral noncoordina-
ting environment provided by the ligands. The three amino
acid derivatives used in the present study are well suited
for comparative studies concerning interactions between the
coordinated metal center and its noncoordinating environ-
ment since their side chains represent achiral and chiral, as
well as aliphatic and aromatic substituents. In the solid-
state structure of 7a the phenyl ring of -phenylalanine is
oriented towards the open coordination site at Zn2ϩ (Fi-
gure 2) covering one side of the complex between a pyridine
ring and the coordinated amide group. The NMR- and CD-
spectroscopic studies presented in this report provide evi-
Figure 4. Circular dichroism spectra (10Ϫ3  in methanol) of: (a)
the
-lysine
derivatives
Lys(Z)ϪOMe
(2b;
Ϫ
Ϫ),
BrAcϪLys(Z)ϪOMe (4b; Ϫ Ϫ), bpaAcϪLys(Z)ϪOMe (3b; Ϫ Ϫ),
and [(bpaAcϪLys(Z)ϪOMe)(H2O)Zn](OTf)2 (7b, —); (b) the -
phenylalanine
derivatives
PheϪOMe
(2a;
Ϫ
Ϫ),
BrAcϪPheϪOMe (4a; Ϫ Ϫ), bpaAcϪPheϪOMe (3a; Ϫ Ϫ), and
[(bpaAcϪPheϪOMe)(H2O)Zn](OTf)2 (7a; —)
Eur. J. Inorg. Chem. 2000, 1723Ϫ1731
1727

N. Niklas, O. Walter, R. Alsfasser
FULL PAPER
ther 30 min and the resulting solution was then allowed to warm
up to room temperature. Stirring was continued overnight, all the
solvent was removed under vacuum and the residue was treated
with 10 mL of CHCl3. Cooling to Ϫ20 °C afforded a solid, which
was filtered off and discarded. The filtrate was concentrated to dry-
ness and the solid obtained was redissolved in a minimum amount
of AcOEt. This solution was purified by flash column chromato-
graphy on silica gel. Impurities eluted with AcOEt and the product
was obtained with yields below 10% by subsequent elution with
pure methanol.
dence for a significant organization of the chiral environ-
ment upon metal complexation in 7a and 7b in solution.
This is of particular interest for applications of the ligands
and complexes in molecular recognition and reactivity stu-
dies.
Conclusions
The ligands 3aϪc are useful new building blocks for the
synthesis of polyfunctional transition-metal complexes ba-
sed on the chiral pool provided by natural amino acids.
They bind tightly and in a well-defined manner to metal
ions but offer sufficient flexibility and accessible open coor-
dination sites for metal-ion reactivity. The amino acid side
chains cover one side of the complexes such that the com-
plexes 7a and 7b are promising candidates for enantioselec-
tive molecular recognition and hydrolysis studies. Our con-
cept allows a facile and systematic modification of the pro-
perties of metal complexes by variation of the amino acid.
The lysine derivative 7b is particularly interesting for further
modifications at the ε-amino group of the ligand. We are
currently investigating this possibility in order to extend our
building-block approach.
Bromoacetylated Amino Acid Esters
BrAc؊Phe؊OMe (4a): -PheϪOMe HCl (10.00 g, 46.40 mmol)
was suspended in 200 mL of THF. Triethylamine (12.93 mL,
92.80 mmol) was added with stirring and the mixture was cooled
to Ϫ10 °C in an ice/salt bath. Bromoacetyl bromide (4.04 mL,
46.40 mmol) was dissolved in 50 mL of THF and the solution was
added dropwise to the cold suspension over a period of 2 h. The
mixture was stirred for another 2 h without further cooling. Insolu-
ble HNEt3Br was filtered off and the solvent removed in a vacuum.
The crude yellow solid obtained after removal of all THF was re-
dissolved in the minimum amount of ethyl acetate. Colorless need-
les of the product 4a (13.46 g, 44.86 mmol, 96.7%) were obtained
after addition of hexane and storage in a refrigerator (Ϫ20 °C)
overnight. The compound was collected on a sintered-glass filter,
dried under vacuum, and characterized by FAB-MS, 1H-NMR and
13C-NMR spectroscopy. Ϫ FAB-MS (nitrobenzyl alcohol); m/z: 300
1
[Mϩ], 240 [Mϩ Ϫ COOMe]. Ϫ H NMR (300 MHz, CDCl3): δ ϭ
β
3.15 (m, 2 H, CH2), 3.74 (s, 3 H, OCH3), 3.84 (s, 2 H, BrϪCH2),
Experimental Section
α
4.85 (m, 1 H, CH), 6.83 (s, br, 1 H, NH), 7.12 (m, 2 H, H2-Ph ϩ
H6-Ph), 7.28 (m, 3 H, H3-Ph ϩ H4-Ph ϩ H5-Ph). Ϫ 13C NMR
(75 MHz, CDCl3): δ ϭ 28.6 (BrϪC), 37.7 (βC), 52.5 (OCH3), 53.7
(αC), 127.3, 128.7, 129.3 (C2-Ph ϩ C3-Ph ϩ C4-Ph ϩ C5-Ph ϩ
C6-Ph), 135.9 (C1-Ph), 165.2, 171.3 [C(O)-ester ϩ C(O)-amide]. Ϫ
IR (KBr): ν˜ ϭ 1734 cmϪ1 (COOMe), 1645 (amide I), 1537 (amide
II). Ϫ Circular Dichroism (10Ϫ3  in methanol): λ, nm ([θ] ϫ 104
°cm2dmolϪ1) ϭ 219 (ϩ1.67), 244 (shoulder, ϩ0.11).
General Methods: Spectra were recorded with the following instru-
ments: UV/Vis: Cary 1G Spectrophotometer. Ϫ Circular Di-
chroism: Jasco J710 Spectropolarimeter. Ϫ IR: Mattson Polaris FT
1
IR. Ϫ H and 13C NMR: Bruker Avance DPX 300. All chemical
shifts are referenced to TMS as internal standard, with high-frequ-
ency shifts recorded as positive. Ϫ All reactions were carried out
under dry nitrogen. The following workup was performed under
ambient laboratory conditions unless stated otherwise. The bis(pi-
colyl)glycine 1[30] and bis(picolyl)amine 5[52,53] were synthesized ac-
cording to published procedures. -Lys(Z)ϪOMe HCl (2b) was
purchased from Nova Biochem, -PheϪOMe HCl (2a) from
Bachem. Absolute solvents (THF, CH2Cl2, Et2O, DMF, CH3CN)
were purchased from Fluka and stored under nitrogen. Ethyl ace-
tate and hexane were reagent grade (Roth). All solvents were used
without further purification. Silca gel Merck type 9385 (230Ϫ400
BrAc؊Lys(Z)؊OMe (4b): -Lys(Z)ϪOMe HCl (5.02 g, 15.20
mmol) was suspended in 150 mL of THF and cooled to Ϫ30 °C in
a methanol/dry ice bath. Triethylamine (4.22 mL, 30.40 mmol) was
added and the mixture stirred for 30 min. Bromoacetyl bromide
(1.32 mL, 15.20 mmol) was dissolved in 50 mL of THF and the
solution added dropwise to the cold suspension over a period of
2.5 h. The mixture was stirred for another 1.5 h at Ϫ30 °C. Insolu-
ble HNEt3Br was filtered off and the solvent removed by rotary
evaporation. The crude brown solid obtained after removal of all
THF was redissolved in 50 mL of hot ethyl acetate and the solution
left at Ϫ20 °C overnight. The product precipitated as a colorless
solid, which was filtered off and dried under vacuum. A second
crop was obtained after addition of hexane and subsequent coo-
ling. The fractions were combined (5.51 g, 13.27 mmol, 87.3%) and
˚
mesh, 60 A) from Aldrich was used for flash column chromato-
graphy. Eluents were optimized by TLC on silica gel 60 F254 sheets
(0.2 mm layer) from Riedel-de Hae¨n. All other chemicals including
ClAcϪGlyϪOEt and deuterated solvents were obtained from Al-
drich. Triethylamine was distilled under N2 prior to use.
Diphenylphosphoryl Azide (DPPA) Coupling
1
characterized by FAB-MS, H-NMR and 13C-NMR spectroscopy.
bpaAc؊Phe؊OMe (3a): Freshly distilled NEt3 (1.00 mL, Ϫ FD-MS (CDCl3); m/z: 415 [Mϩ]. Ϫ 1H NMR (300 MHz,
γ
δ
7.00 mmol) was added in one portion to a stirred suspension of 2a
ϫ HCl (166 mg, 0.77 mmol) under N2 in 10 mL of absolute THF.
CDCl3): δ ϭ 1.38 (m, 2 H, CH2), 1.52 (m, 2 H, CH2), 1.81 (m, 2
β
ε
H, CH2), 3.18 (m, 2 H, CH2), 3.75 (s, 3 H, OCH3), 3.87 (s, 2 H,
Stirring was continued for 30 min, the mixture filtered to remove BrϪCH2), 4.57 (m, 1 H, CH), 4.89 (m, 1 H, NH-Z), 5.09 (s, 2 H,
α
3
NEt3 ϫ HCl and the resulting clear solution cooled to Ϫ10 °C
using an ice/salt bath. This solution was added in one portion with
stirring to another THF (10 mL) solution containing 1 (150 mg, 0.
CH2-Z), 7.35 (m, 5 H, Ph-Z), 7.02 (d, 1 H, JHH ϭ 7.3 Hz, NH).
13C NMR (75 MHz, CDCl3): δ ϭ 22.2 (γC), 28.7 (BrϪC), 29.4
(δC), 31.7 (βC), 40.47 (εC), 52.6 (OCH3 ϩ αC), 66.7 (CH2-Z), 128.1,
Ϫ
70 mmol) at Ϫ10 °C. DPPA (0.17 mL, 0.77 mmol) was added 128.1, 128.4, 128.5 (Z-C2-Ph ϩ Z-C3-Ph ϩ Z-C4-Ph ϩ Z-C5-Ph
slowly followed by dropwise addition of NEt3 (0.11 mL, ϩ Z-C6-Ph), 136.6 (Z-C1-Ph), 156.5 [Z-C(O)], 165.6, 172.2 [C(O)-
0.77 mmol). Care was taken to keep the temperature at or below ester ϩ amide]. Ϫ IR (KBr): ν˜ ϭ 1740 cmϪ1 (COOMe), 1698 (Z-
Ϫ10 °C. The stirred reaction mixture was kept at Ϫ10 °C for ano-
urethane), 1646 (amide I), 1540 (amide II). Ϫ Circular Dichroism
1728
Eur. J. Inorg. Chem. 2000, 1723Ϫ1731

Chiral Quadridentate Ligands Derived from Amino Acids
FULL PAPER
(10Ϫ3  in methanol): λ, nm ([θ] ϫ 104 °cm2dmolϪ1) ϭ 209 (ϩ0.26),
227 (Ϫ0.17), 248 (ϩ0.09).
7.1 Hz, OCH2CH3), 2 (H2O), 3.37 [s, 2 H, C(O)ϪCH2], 3.90 (s, 4
3
H, py-CH2), 4.08 (d, 2 H, JHH
5.9 Hz, αCH2), 4.18 (q, 2 H,
ϭ
3JHH ϭ 7.1 Hz, OCH2CH3), 7.16 (dd, 2 H, H5-py), 7.35 (d, 2 H,
H3-py), 7.63 (m, 2 H, H4-py), 8.55 (d, 2 H, H6-py), 9.07 (m, 1 H,
NH). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 14.1 (OCH2CH3), 41.0
(αC), 57.9 [C(O)ϪCH2], 60.2 (py-CH2), 61.1 (OCH2CH3), 122.4
(C3-py), 123.3 (C5-py), 136.6 (C4-py), 149.2 (C6-py), 158.3 (C2-
py), 169.8, 171.8 [C(O)-ester ϩ C(O)-amide]. Ϫ IR (film on NaCl):
ν˜ ϭ 1747 cmϪ1 (COOEt), 1674 (amide I), 1525 (amide II).
Ligands
General Procedure: Equimolar amounts of bis(picolyl)amine (5),
the respective haloacetylated amino acid ester, and ethyldiiso-
propylamine (DIPEA) were dissolved in DMF. The solution was
stirred for 20 h at room temperature. All solvents were removed
by rotary evaporation. Ethyl acetate was added, resulting in the
precipitation of the ammonium halide salt, which was filtered off
and discarded. The filtrate was concentrated to dryness yielding a
brown oil, which was purified by silica gel column chromatography
using CH2Cl2/MeOH (11:1) as eluent. A small yellow fraction con-
taining some of the haloacetylated amino acid ester starting mate-
rial eluted first. The product was eluted next as a broad light yellow
(yellow in the case of 3a) fraction. A third yellow fraction, which
was well separated from the product, was usually not collected. The
solution containing the desired product was concentrated to dry-
ness by rotary evaporation and the resulting light yellow oil dried
under vacuum.
Zn Complexes
General Procedure: Solid Zn(OTf)2 was added in one portion to a
stirred solution of 1 equiv. of the respective ligand in CH3CN. Stir-
ring was continued overnight at room temp. followed by removal
of all solvent under vacuum. CH2Cl2 was added to the residue and
the resulting suspension left in a refrigerator (Ϫ20 °C) overnight.
Unchanged Zn(OTf)2 precipitated and was filtered off. In the case
of 7b the solvent was removed by rotary evaporation and the resi-
due dried under vacuum. Further purification was not possible
since the compound did not precipitate but rather separated as an
oil from common organic solvents. Accordingly, the reported yield
refers to the crude product. The two other complexes (6c and 7a)
were purified by addition of Et2O to the clear CH2Cl2 filtrate and
recrystallization at Ϫ20 °C. These complexes precipitated overnight
as colorless microcrystalline solids. Yields are reported for recry-
stallized samples. It is evident from C,H,N analysis and NMR data
that the bpaAcϪGlyϪOEt complex 6c was isolated without signifi-
cant amounts of coordinated water whereas the same workup af-
fords the corresponding aquo complex 7a for bpaAcϪPheϪOMe.
Single crystals suitable for X-ray structure analysis of 6c and 7a
were obtained by slow recrystallization of the pure complexes from
CH2Cl2/Et2O at Ϫ20 °C under dry nitrogen over a period of seve-
ral weeks.
bpaAc؊Phe؊OMe (3a): 9.00 g (29.98 mmol) of 4a, 5.91 g
(29.98 mmol) of bpa, 5.20 mL (29.98 mmol) of DIPEA, 100 mL
of DMF, 100 mL of AcOEt. Yield: 10.17 g (24.31 mmol, 81%). Ϫ
C24H26N4O3 (418.5 g/mol): FD-MS (CDCl3); m/z: 418 [Mϩ]. Ϫ H
1
NMR (300 MHz, CDCl3): δ ϭ 2.00 (H2O), 3.12Ϫ3.29 (ABX, 2 H,
βCH2), 3.26 [s, 2 H, C(O)ϪCH2], 3.69 (s, 3 H, OCH3), 3.73, 3.85
(2 ϫ d, 4 H, JHH ϭ 14.2 Hz, 2 ϫ py-CH2), 4.90 (m, 1 H, αCH),
2
7.18 (m, 9 H, 5 ϫ H-Ph ϩ H3-py ϩ H5-py), 7.56 (m, 2 H, H4-py),
3
3
8.52 (d, 2 H, JHH ϭ 4.9 Hz, H6-py), 9.05 (d, 1 H, JHH ϭ 8.0 Hz,
NH). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 37.5 (βC), 52.1 (OCH3),
53.1 (αC), 57.6 [C(O)ϪCH2], 60.1 (py-CH2), 122.3, 122.9 (C3-py ϩ
C5-py), 126.80, 128.4, 129.2 (C2-Ph ϩ C3-Ph ϩ C4-Ph ϩ C5-Ph
ϩ C6-Ph), 136.5 (3 C, 2 ϫ C4-py ϩ C1-Ph), 149.1 (C6-py), 158.2
(C2-py), 171.2, 172.1 [C(O)-ester ϩ C(O)-amide]. Ϫ IR (film on
NaCl): ν˜ ϭ 1745 cmϪ1 (COOMe), 1672 (amide I), 1513 (amide
II). Ϫ Circular Dichroism (10Ϫ3  in methanol): λ, nm ([θ] ϫ 104
°cm2dmolϪ1) ϭ 221 (ϩ1.13), 257 (ϩ0.05), 265 (ϩ0.13).
[(bpaAc؊Gly؊OEt)(OTf)Zn](OTf) (6c): 426 mg (1.24 mmol) of 5,
416 mg (1.24 mmol) of Zn(OTf)2, 10 mL of CH3CN, 10 mL of
CH2Cl2. Yield: 573 mg (0.81 mmol, 65%). Ϫ C20H22F6N4O9S2Zn
(705.9 g/mol): calcd. C 34.03, H 3.14, N 7.94; found C 33.85, H
3.25, N 7.74. Ϫ FAB-MS (nitrobenzyl alcohol); m/z: 555 (3c-
ZnOTfϩ), 407 (3c-Znϩ). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 1.21
(t, 3 H, 3JHH ϭ 7.1 Hz, OCH2CH3), 4.04 [s, 2 H, C(O)ϪCH2], 4.10
(m, 4 H, αCH2, OCH2CH3), 4.34, 4.44 (2 ϫ d, 4 H, 2JHH ϭ 5.6 Hz,
2 ϫ py-CH2), 7.63 (m, 4 H, H5-py ϩ H3-py), 8.05 (m, 2 H, H4-
py), 8.92 (d, 2 H, H6-py), 9.03 (m, 1 H, NH). Ϫ 13C NMR
bpaAc؊Lys(Z)؊OMe (3b): 1.83 g (4.41 mmol) of 4b, 877 mg
(4.41 mmol) of bpa, 0.77 mL (4.41 mmol) of DIPEA, 50 mL of
DMF, 30 mL of AcOEt. Yield: 1.67 g (3.13 mmol, 71%). Ϫ
C29H35N5O5 (533.6 g/mol): FD-MS (CDCl3); m/z: 534 (Mϩ). Ϫ 1H
γ
NMR (300 MHz, CDCl3): δ ϭ 1.39 (m, 2 H, CH2), 1.51 (m, 2 H,
δCH2), 1.85 (m, 2 H, βCH2), 3.12 (m, 2 H, εCH2), 3.35 [s, 2 H,
13.9 (OCH2CH3), 42.4 (αC), 56.2
2
(75 MHz, CDCl3):
[C(O)ϪCH2], 57.8 (py-CH2), 61.8 (OCH2CH3), 120.2 (q, JCF
δ
ϭ
C(O)ϪCH2], 3.67 (s, 3 H, OCH3), 3.78, 3.86 (2 ϫ d, 4 H, JHH
ϭ
1
9.7 Hz, 2 ϫ py-CH2), 4.60 (m, 1 H, αCH), 5.06 (s, 2 H, Z-CH2),
ϭ
301.9 Hz, OTfϪ), 125.3, 125.9 (C3-py, C5-py), 141.9 (C4-py), 149.2
(C6-py), 154.3 (C2-py), 167.5, 174.3 [C(O)-ester ϩ C(O)-amide]. Ϫ
IR (KBr): ν˜ ϭ 1747 cmϪ1 (COOEt), 1641 (amide I), 1245
(CF3SO3), 1218 (CF3SO3).
5.21 (m, 1 H, Z-NH), 7.14 (dd, 2 H, H5-py), 7.32 (m, 7 H, Z-Ph
3
ϩ H3-py), 7.60 (dd, 2 H, H4-py), 8.53 (d, 2 H, JHH ϭ 4.56 Hz,
H6-py), 9.22 (d, 1 H, JHH ϭ 7.3 Hz, NH). Ϫ 13C NMR (75 MHz,
3
CDCl3): δ ϭ 22.7 (γC), 29.3 (δC), 31.7 (βC), 40.7 (εC), 51.7, 52.0
(OCH3
ϩ
αC), 57.8 [C(O)ϪCH2], 60.5 (py-CH2), 66.4 (Z-CH2),
[(bpaAc؊Phe؊OMe)(H2O)Zn](OTf)2 (7a): 743 mg (1.77 mmol) of
3a, 643 mg (1.77 mmol) of Zn(OTf)2, 15 mL of CH3CN, 15 mL of
CH2Cl2. Yield: 964 mg (1.20 mmol, 68%). Ϫ C26H28F6N4O10S2Zn
(800.0 g/mol): calcd. C 39.03, H 3.53, N 7.00; found C 38.94, H
3.53, N 6.82. Ϫ FAB-MS (nitrobenzyl alcohol); m/z: 631 (3a-
ZnOTfϩ), 481 (3a-Znϩ). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 2.84,
122.4, 123.1 (C3-py ϩ C5-py), 128.0, 128.1, 128.3, 128.4 (Z-C2-Ph
ϩ Z-C3-Ph ϩ Z-C4-Ph ϩ Z-C5-Ph ϩ Z-C6-Ph), 136.6 (2 C, Z-C1-
Ph ϩ C4-py), 149.2 (C6-py), 156.4, 158.3 [C(O)-Z ϩ C2-py], 171.5,
172.8 [C(O)-ester ϩ C(O)-amide]. Ϫ IR (film on NaCl): ν˜ ϭ 1741
cmϪ1 (COOMe), 1718 (Z-urethane), 1668 (amide I), 1529 (amide
II). Ϫ Circular Dichroism (10Ϫ3  in methanol): λ, nm ([θ] ϫ 104
°cm2dmolϪ1) ϭ 216 (ϩ0.40), 263 (ϩ0.15).
3.23 (ABX, 2 H, βCH2), 3.66 (s, 3 H, OCH3), 3.67 [d, 1 H, 2JHH
ϭ
2
16.8 Hz, py-CH(AЈ)H(BЈ)], 3.70 [d,
C(O)ϪCH(C)H(D)], 3.98 [d,
1
H, JHH
ϭ
16.8 Hz,
16.8 Hz,
bpaAc؊Gly؊OEt (3c): 7.87 g (43.81 mmol) of ClAcϪGlyϪOEt;
8.72 g (43.81 mmol) of dpa, 7.65 mL (43.81 mmol) of DIPEA,
100 mL of DMF, 100 mL of AcOEt. Yield: 6.04 g (17.60 mmol,
3
H, 2JHH
ϭ
2
C(O)ϪCH(C)H(D) ϩ H2O], 4.08 [d, 1 H, JHH ϭ 16.8 Hz, py-
CH(A)H(B)], 4.29 [d, 1 H, 2JHH ϭ 16.8 Hz, py-CH(AЈ)H(BЈ)], 4.44
40%). Ϫ C18H22N4O3 (342.4 g/mol): FD-MS (CDCl3); m/z: 342 [d, 1 H, 2JHH ϭ 16.8 Hz, py-CH(A)H(B)], 4.99 (m, 1 H, αCH), 6.62
[Mϩ]. Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 1.24 (t, 3 H, JHH ϭ (dd, 1 H, H4-Ph), 6.98 (dd, 2 H, H3,5-Ph), 7.19 (d, 2 H, H2,6-Ph),
3
Eur. J. Inorg. Chem. 2000, 1723Ϫ1731
1729

N. Niklas, O. Walter, R. Alsfasser
FULL PAPER
Table 2. Details of crystal structure analyses
Compound
6c
7a
Empirical formula
Molecular mass
Temperature
C20H21F6N4O9S2Zn
704.90
C26H26F6N4O10S2Zn H2O
816.01
200(2) K
200(2) K
˚
Wavelength [A]
0.71073
0.71073
monoclinic
P21
Crystal system
Space group
monoclinic
P21/n
˚
a [A]
15.4015(8)
9.2332(5)
13.8284 (18)
9.4051(19)
14.290(3)
˚
b [A]
˚
c [A]
21.0333(11)
108.1050(10)
2843.0(3)
β [°]
106.426(18)
1782.7(6)
3
˚
Volume [A ]
Z
4
2
Calculated density
Absorption coefficient
F(000)
Crystal size [mm]
θ range [°]
Index ranges
1.647 Mg/m3
1.104 mmϪ1
1428
1.520 Mg/m3
0.896 mmϪ1
832
0.4 ϫ 0.2 ϫ 0.2
1.96Ϫ28.36
Ϫ20 Յ h Յ 20
Ϫ12 Յ k Յ 11
Ϫ28 Յ l Յ 27
28766/6920
based on F2
6920/0/388
1.087
0.25 ϫ 0.15 ϫ 0.15
1.54Ϫ28.30
Ϫ18 Յ h Յ 18
Ϫ12 Յ k Յ 12
Ϫ18 Յ l Յ 18
19429/8552
based on F2
8552/1/473
0.886
Reflections collected/unique
Refinement method
Data/restr./parameters
Goodness-of-fit on F2
Final R indices [I Ͼ 2σ(I)]
R1 ϭ 0.0410
wR2 ϭ 0.1135
R1 ϭ 0.0549
wR2 ϭ 0.1203
R1 ϭ 0.0423
wR2 ϭ 0.0697
Rl ϭ 0.1026
wR2 ϭ 0.0806
R indices (all data)
Ϫ3
Ϫ3
˚
˚
Largest diff. peak and hole
0.874 and Ϫ1.065 eA
0.361 and Ϫ0.411 A
7.62 (m, 4 H, H3-py ϩ H5-py), 8.01, 8.08 (2 ϫ m, 2 H, H4-py),
ϫ 104 °cm2dmolϪ1) ϭ 213 (ϩ0.37), 235 (Ϫ0.03), 264 (Ϫ0.26), 269
8.83, 8.85 (2 ϫ m, 2 H, H6-py), 9.02 (d, 1 H, 3JHH ϭ 8.6 Hz, NH). (Ϫ0.26).
Ϫ
13C NMR (75 MHz, CDCl3): δ ϭ 37.87 (βC), 52.74 (OCH3),
55.28 (αC), 56.04 [C(O)ϪCH2], 57.58, 57.68 (pyϪCH2), 120.21 (q,
1JCF ϭ 317 Hz, OTfϪ), 125.12, 125.36, 125.73 (2 ϫ C3-py ϩ 2 ϫ
C5-py), 126.42, 128.01, 129.74 (C2-Ph ϩ C3-Ph ϩ C4-Ph ϩ C5-
Ph ϩ C6-Ph), 135.76 (C1-Ph), 141.71, 141.79 (2 ϫ C4-py) 148.97,
149.04 (2 ϫ C6-py), 154.25, 154.30 (2 ϫ C2-py), 169.78, 173.46
[C(O)-ester ϩ amide]. Ϫ IR (KBr): ν˜ ϭ 1749 cmϪ1 (COOMe), 1633
(amide I), 1284 (CF3SO3), 1245 (CF3SO3). Ϫ Circular Dichroism
(10Ϫ3  in methanol): λ, nm ([θ] ϫ 104 °cm2dmolϪ1) ϭ 219 (ϩ2.05),
246 (Ϫ0.05), 265 (Ϫ0.26), 270 (Ϫ0.26).
X-ray Data Collection and Structure Refinement Details: Crystal
data and experimental conditions are listed in Table 2. The molecu-
lar structures are illustrated in Figures 1 and 2. Selected bond
lengths and bond angles with standard deviations in parentheses
are presented in Table 1. Intensity data were collected with a Sie-
mens SMART 5000 CCD-Diffractometer with graphite-monochro-
˚
mated Mo-Kα radiation (λ ϭ 0.71073 A). The exposure time was
10 s per frame collected with the ω-scan technique (∆ω ϭ 0.3°).
The collected reflections were corrected for Lorentz, polarization
and absorption effects. The structures were solved by direct me-
thods and refined by full-matrix least-squares methods on
[(bpa-Lys(Z)؊OMe)(H2O)Zn](OTf)2 (7b): 131 mg (0.25 mmol) of
3b, 91 mg (0.25 mmol) of Zn(OTf)2, 10 mL of CH3CN, 5 mL of
CH2Cl2. Yield: 161 mg (0.19 mmol, 76%). Ϫ FAB-MS (nitrobenzyl
alcohol); m/z: 746 (3b-ZnOTfϩ), 596 (3b-Znϩ). Ϫ 1H NMR
(300 MHz, CDCl3): δ ϭ 1.20 (m, 2 H, γCH2), 1.46 (m, 2 H, δCH2),
1.73 (m, 2 H, βCH2), 3.07 (m, 2 H, εCH2), 3.67 (s, 3 H, OCH3),
F2.[54] [56] Non-hydrogen atoms were refined with anisotropic ther-
Ϫ
mal parameters in both structures. The hydrogen atoms of the coor-
dinated water molecule and the amide hydrogen atom of 7a were
localized from the difference electron density map and refined with
isotropic thermal parameters. All other hydrogen atoms were fixed
in geometrically calculated positions and isotropically refined. De-
tails of the crystal structure determinations have been deposited
at the Cambridge Crystallographic Data Centre as supplementary
publication nos. CCDC-140521 (6c) and -140522 (7a). Copies of
the data can be obtained free of charge on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, U.K. [Fax: (internat.)
ϩ 44-1223/336-033; E-mail: deposit@ccdc.cam.ac.uk].
2
3.93, 4.04 [2 ϫ d, 2 H, JHH ϭ 17.4 Hz, C(O)ϪCH2], 4.38 (m, 5
α
H, 2 ϫ py-CH2 ϩ CH), 5.07 (s, 2 H, CH2-Z), 5.21 (m, 1 H, NH-
Z), 7.35 (m, 5 H, Ph-Z), 7.54 (m, 4 H, 2 ϫ H3-py ϩ 2 ϫ H5-py),
8.00 (m, 2 H, 2 ϫ H4-py), 8.80 (m, 3 H, 2 ϫ H6-py ϩ NH). Ϫ 13C
NMR (75 MHz, CDCl3): δ ϭ 22.4 (γC), 29.0 (δC), 30.5 (βC), 40.4
(εC), 52.6 (OCH3), 53.9 (αC), 56.9 [C(O)ϪCH2], 58.8 (py-CH2),
1
67.9 (Z-CH2), 120.1 (q, JCF ϭ 323 Hz, OTfϪ), 125.1, 125.6 (C3-
py ϩ C5-py), 127.8, 128.0, 128.5 (5 C, Z-C2-Ph ϩ Z-C3-Ph ϩ Z-
C4-Ph ϩ Z-C5-Ph ϩ Z-C6-Ph), 136.8 (2 C, Z-C1-Ph), 141.4 (C4-
py), 148.6 (C6-py), 154.0 (C2-py), 156.8 [C(O)-Z], 170.6, 173.3
Acknowledgments
[C(O)-ester
ϩ C(O)-amide]. Ϫ IR (KBr): ν˜ ϭ
1745 cmϪ1 The authors gratefully acknowledge financial support from the
(COOMe), 1708 (Z-urethane), 1637 (amide I), 1283 (CF3SO3), 1253
Deutsche Forschungsgemeinschaft. We thank Prof. Rudi van Eldik
who generously let us share his equipment, laboratory space, and
(CF3SO3). Ϫ Circular Dichroism (10Ϫ3  in methanol): λ, nm ([θ]
1730
Eur. J. Inorg. Chem. 2000, 1723Ϫ1731

Chiral Quadridentate Ligands Derived from Amino Acids
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