Syntheses of zinc complexes with multidentate nitrogen ligands: New catalysts for aldol reactions

Article abstract of DOI:10.1002/1099-0682(200212)2002:12<3284::AID-EJIC3284>3.0.CO;2-6

The ligands 2,6-bis{[(pyrid-2-ylmethyl)amino]methyl}-pyridine with an N₅ pattern and (6-{[(pyrid-2-ylmethyl)amino]methyl}pyrid-2-yl)methanol with an N₃O pattern were synthesized. Zn^II complexes of the two ligands could be obtained, and the single-crystal X-ray structure of (2,6-bis{[(pyrid-2-ylmethyl)amino]methyl}pyridine)zinc chloride showed Zn coordination to all five nitrogen atoms. The strong complexation of 2,6-bis{[(pyrid-2-ylmethyl)-amino]methyl}pyridine and (6-{[(pyrid-2-ylmethyl)amino]-methyl}pyrid-2-yl)methanol with Zn^II were demonstrated by ¹H NMR spectroscopic studies and electrospray mass spectrometry. The coupling of 2-hydroxyacetophenone and benzaldehyde was studied in the presence of the prepared Zn complexes, and it was shown that the coupling product was obtained at room temperature in up to 60% yield with 7.5 mol% of the zinc catalyst. The present complexes mimic the active site of the zinc-dependent class II aldolases, where Zn^II is coordinated to three nitrogen atoms. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0682(200212)2002:12<3284::AID-EJIC3284>3.0.CO;2-6

FULL PAPER
Syntheses of Zinc Complexes with Multidentate Nitrogen Ligands:
New Catalysts for Aldol Reactions
Tamis Darbre,*[a] Christian Dubs,[a] Eduard Rusanov,[b] and Helen Stoeckli-Evans[b]
Keywords: Aldol reaction / Catalysis / N ligands / N,O ligands / Zinc
The ligands 2,6-bis{[(pyrid-2-ylmethyl)amino]methyl}-
pyridine with an N5 pattern and (6-{[(pyrid-2-
ylmethyl)amino]methyl}pyrid-2-yl)methanol with an N3O
pattern were synthesized. ZnII complexes of the two ligands
could be obtained, and the single-crystal X-ray structure
1H NMR spectroscopic studies and electrospray mass spec-
trometry. The coupling of 2-hydroxyacetophenone and
benzaldehyde was studied in the presence of the prepared
Zn complexes, and it was shown that the coupling product
was obtained at room temperature in up to 60% yield with
7.5 mol % of the zinc catalyst. The present complexes mimic
the active site of the zinc-dependent class II aldolases, where
ZnII is coordinated to three nitrogen atoms.
of
(2,6-bis{[(pyrid-2-ylmethyl)amino]methyl}pyridine)zinc
chloride showed Zn coordination to all five nitrogen atoms.
The strong complexation of 2,6-bis{[(pyrid-2-ylmethyl)-
amino]methyl}pyridine and (6-{[(pyrid-2-ylmethyl)amino]-
methyl}pyrid-2-yl)methanol with ZnII were demonstrated by
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Introduction
fuculose 1-phosphate aldolase produced by E. coli.[6] Upon
substrate binding, the carboxylate group dissociates from
the ZnII reaction center and moves away, providing space
for the hydroxy ketone to bind to the ZnII ion and at the
same time deprotonating the carbon atom in the α-position
to the carbonyl group. The resulting enediolate is proposed
to be stabilized through binding to the zinc ion and to act
as a nucleophile (Figure 1).[6]
The aldol reaction is of central importance for construc-
tion of CϪC bonds in organic chemistry.[1] It is therefore
not surprising that several catalysts and reagents have been
developed in order to achieve efficient condensation with
high diastereomeric and enantiomeric selectivity.[2] Further-
more, due to its importance for organic synthesis, the asym-
metric aldol reaction has become, without doubt, one of
the most important topics in modern catalytic synthesis.
From the several methods available for the aldol reaction,
the direct condensation of an aldehyde with a ketone[3] is a
most attractive approach since it does not require the isola-
tion of preformed enolates.[4] Therefore, the development
of new catalysts for the direct condensation is a field of
considerable importance.
In nature, aldol reactions also constitute an important
reaction class that is mediated by aldolases, ubiquitous en-
zymes that catalyze among other reactions, the reversible
aldol cleavage of fructose-1,6-bis(phosphate) (FBP) in gly-
colysis. Aldolases are divided into two distinct classes ac-
cording to their enzymatic mechanism. Whereas the class I
aldolases form a Schiff base intermediate between the e-
amino group of a lysine residue and the carbonyl carbon
atom of the substrate, class II aldolases are zinc-depend-
ent.[5] Three histidine side chains and a carboxylate group
of a glutamic acid are coordinated to the ZnII ion in class II
Figure 1. Proposed mechanism for the aldol reaction catalyzed by
type II aldolase[6]
Although it has been demonstrated that ZnII salts cata-
lyze the aldol condensation,[7] Zn complexes with nitrogen
ligands have not been explored much as catalysts for aldol
reactions. In a structural model for aldolases, a modified
tris(pyrazolyl)borate ligand[8] was used to mimic the three
nitrogen atoms in the enzyme’s active site. A model with
four nitrogen atoms and a carbonyl group bound to the
zinc ion has also been developed.[9] Proline has been used
as an asymmetric catalyst,[10,11] and some early work has
shown that the ZnII ion coordinated to pyridine and bi- and
ter(pyridine)s can catalyze the reaction of aldehydes and ke-
tones to give unsaturated ketones.[12]
[a]
Department of Chemistry and Biochemistry, University of
Bern,
Freiestrasse 3, 3012, Switzerland
Chiral dinuclear Zn complexes with chiral binol as ligand
as well as other oxygen-containing ligands have been re-
[b]
ˆ
Institute of Chemistry, University of Neuchatel,
Avenue de Bellevaux 51, 2007 Neuchatel, Switzerland
3284  2002 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ1948/02/1212Ϫ3284 $ 20.00ϩ.50/0 Eur. J. Inorg. Chem. 2002, 3284Ϫ3291

Syntheses of Zinc Complexes with Multidentate Nitrogen Ligands
FULL PAPER
cently
reactions.[13Ϫ18]
Inspired by the ZnII coordination site in the active site of
reported
to
catalyze
asymmetric
aldol yield. The latter was deprotected in the same way as 5 to
give 9 in 76% yield (Scheme 1).
The ligands 6 and 9 became readily available in a few
the class II aldolases, we have prepared ligands containing steps and high yields by the syntheses developed here.
nitrogen-binding sites in order to develop novel catalysts for
Complexation of 6 and 9 with Zn Salts
the aldol reaction.
Here we report on the efficient synthesis of ligands con-
taining nitrogen as binding sites (N5 and N3O), the syn-
thesis of new ZnII complexes where the zinc center is coord-
inated to nitrogen atoms, and our first results on the activity
of the new zinc complexes as catalysts for the condensation
of benzaldehyde and 2-hydroxyacetophenone.
Having the two ligands 6 and 9 at hand, we have pre-
pared a series of ZnII complexes to test their ability to act
as catalysts for aldol reactions. Thus, ligand 6 was refluxed
with ZnCl2, Zn(CH3COO)2·2H2O or Zn(ClO4)2·6H2O in a
1:1 ration in MeOH to give the corresponding complexes
1a, 1b and 1c in 64%, 82% and 81% yield, respectively. All
three complexes could be identified by their 1H and 13C
NMR spectra, and ESI-MS. The 1H NMR spectrum in
CD3OD of 1a, 1b, 1c showed shifts of the signals for the
pyridine hydrogen atoms as well as for the two methylene
Results and Discussion
The syntheses of the ligands with N5 and N3O coordina- groups [the signals of the pyCH2N methylene groups ap-
tion sites (6 and 9) are shown in Scheme 1. Synthesis of pear at δ ϭ 3.97 ppm (8 H) for the ligand 6 and at δ ϭ
tosylamine 3 was achieved by treatment of 2-(aminomethyl)- 4.28 ppm (4 H) and δ ϭ 4.39 ppm (4 H) for the acetate
pyridine with NaOH and tosyl choride in a two-phase sys- complex 1b]. The ESI-MS data showed for the three com-
tem (H2O/diethyl ether) in 89% yield.[19] Coupling of 3 with plexes, 1a, 1b and 1c, peaks at m/z ϭ 382, 384, 386, that
2,6-bis(bromomethyl)pyridine (4), also in a two-phase sys- can be assigned to [6 Ϫ Hϩ ϩ ZnII], with relative intensities
tem and nBu4NBr as a phase-transfer catalyst, gave product of 100:59:41 for 1a, 100:61:38 for 1b and 100:59:41 for 1c,
5, which could be isolated after chromatography in 86% in good agreement with the calculated intensities of
yield. The tosyl group was removed by heating the tosylate 100:60:42 for the three zinc isotopes. Furthermore, the
5 with concentrated sulfuric acid to yield the ligand 6 in peaks for [6 ϩ ZnII ϩ ClϪ] at m/z ϭ 418, 420 and 422 are
94% yield. The three-step synthesis gives 6 in an overall also observed for 1a, as well as the peaks for the [6 ϩ ZnII
yield of 72%. There are two reports in the literature of com- ϩ CH3COOϪ] at m/z ϭ 442,444 and 446 and for the [6 ϩ
pounds related to 6; in the first the tetraammonium salt of ZnII ϩ ClO4Ϫ] at m/z ϭ 482, 484 and 486 for 1b and 1c,
6 is prepared by a different procedure,[20] and in the second respectively. The free ligand 6, however, could not be de-
G. Newkome et al.[19] report the synthesis of 6 in 28% yield. tected in the ESI-MS.
The latter authors describe the product obtained as an un-
Insight into the geometry of the complexes and the bind-
stable oil whereas we isolated 6 as a brownish, stable solid. ing mode of the zinc atom with the ligand 6 was obtained
For the synthesis of the new ligand 9, the tosylamine 3 by single-crystal X-ray analysis. The reaction of 6 with
was alkylated with [6-(bromomethyl)pyrid-2-yl]methanol ZnCl2 gave two pseudo-polymorphs, 1a·CH3OH solvate
(7) in the presence of K2CO3 in acetonitrile to give 8 in 74% and 1a·2H2O. Here the ZnII ion is coordinated to the five
Scheme 1
Eur. J. Inorg. Chem. 2002, 3284Ϫ3291
3285

T. Darbre, C. Dubs, E. Rusanov, H. Stoeckli-Evans
FULL PAPER
nitrogen atoms of the ligand and to a chloride anion, pro-
ducing complexes with pseudo-C2 symmetry (for example,
see Figure 2). The zinc atoms and the pyridine rings of the
side chain are almost co-planar. The amine N atoms, N2
and N4, are displaced above this plane towards the central
pyridine ring. The reaction of 6 with Zn(ClO4)2 gave 1c, in
which the metal ion is pentacoordinate, with all five nitro-
gen atoms coordinated to the metal (Figure 3). Due to the
lack of a sixth ligand, the two pyridine rings are bent down-
wards, but the complex retains the pseudo-C2 symmetry.
The bond angles N1ϪZnϪN3 and N3ϪZnϪN5 have an
average value of 128.3° relative to 89.3° for the two hexaco-
ordinate 1a complexes. The zincϪN bond lengths in 1c are
notably shorter than those observed in complexes
1a·CH3OH and 1a·2H2O. These differences are particularly
important for the central ZnϪN(pyridine) distance (ca. 0.1
˚
˚
A) and the outer ZnϪN(pyridine) distances (ca. 0.15 A).
Selected bond lengths and angles for the three structures
are given in Table 1.
Figure 3. Perspective view of cation 1c, showing the crystallo-
graphic numbering scheme, and thermal ellipsoids at 50% probabil-
Ϫ
ity; the ClO4 anions have been omitted for clarity
˚
Table 1. Selected bond lengths [A] and angles [°] for complexes
1a·CH3OH solvate, 1a·2H2O and 1c
1a·CH3OH
1a·2H2O
1c
ZnϪN1
ZnϪN2
ZnϪN3
ZnϪN4
ZnϪN5
ZnϪCl1
N1ϪZnϪN2
N1ϪZnϪN3
N1ϪZnϪN4
N1ϪZnϪN5
N2ϪZnϪN3
N2ϪZnϪN4
N2ϪZnϪN5
N3ϪZnϪN4
N3ϪZnϪN5
N4ϪZnϪN5
Cl1ϪZnϪN1
Cl1ϪZnϪN2
Cl1ϪZnϪN3
Cl1ϪZnϪN4
Cl1ϪZnϪN5
2.199(3)
2.221(3)
2.12183)
2.200(3)
2.190(3)
2.376(1)
77.71(10)
86.73(11)
101.02(11)
176.87(11)
77.18(12)
154.44(12)
101.44(10)
77.26(11)
90.14(11)
78.41(11)
91.18(8)
2.214(2)
2.200(2)
2.121(2)
2.212(2)
2.154(2)
2.383(1)
77.81(7)
88.26(6)
101.38(7)
179.36(7)
77.74(7)
155.26(7)
102.82(7)
77.52(7)
91.87(6)
78.03(7)
89.08(5)
101.73(5)
177.34(5)
102.99(5)
90.79(5)
2.051(2)
2.174(2)
2.029(2)
2.179(2)
2.027(2)
81.07(10)
128.98(9)
114.16(9)
103.44(10)
78.64(9)
157.32(01)
111.89(10)
78.69(10)
127.55(9)
81.95(10)
Figure 2. Perspective view of cation 1a·CH3OH solvate, showing
the crystallographic numbering scheme, and thermal ellipsoids at
50% probability; the ClϪ anion and the CH3OH solvent molecule
have been omitted for clarity
101.32(9)
177.64(8)
104.24(9)
91.95(8)
Complexes 2a, 2b and 2c were obtained by refluxing the
zinc salts and 9 in a 1:1 ratio in methanol. Partial evapora-
tion of the solvent and addition of diethyl ether gave [(6-
{[(pyrid-2-ylmethyl)amino]methyl}pyrid-2-yl)methanol]zinc
dichloride (2a), [(6-{[(pyrid-2-ylmethyl)amino]methyl}-
pyrid-2-yl)methanol]zinc diacetate (2b) and [(6-{[(pyrid-2-
ylmethyl)amino]methyl}pyrid-2-yl)methanol]zinc
chlorate (2c) as white solids (Scheme 1), in 41, 62 and 66% singlets (δ ϭ 3.95 and 3.96 ppm) corresponding to four pro-
yields, respectively. tons (2 H1Ј and 2 H1ЈЈ). After complexation, five signals
diper- can be seen; a singlet at δ ϭ 4.72 ppm (2 H1), and two close
1
The complexes 2a, 2b, 2c were characterized by H and appeared for the same six hydrogen atoms and the two H1,
1
13C NMR spectroscopy, and ESI-MS. The H NMR spec- two H1Ј and two H1ЈЈ atoms, became nonequivalent. We
trum in [D4]methanol of 9, 2b and 2c are shown in Figure 4. observe two broad signal at δ ϭ 5.05 and 4.97 ppm for the
In general, we can see that for the three methylene groups two H1 atoms, a broad signal at δ ϭ 4.54 ppm for two
a strong downfield shift is observed upon complexation, hydrogen atoms (1 H1Ј and 1 H1ЈЈ) and two broad doublets
whereas the aromatic protons are less influenced by the Zn at δ ϭ 4.16 and 3.82 ppm for the remaining two hydrogen
coordination. For ligand 9, three signals for the 6 H atoms atoms (1 H1Ј and 1 H1ЈЈ). For 2c the signals are well de-
in the positions 1, 1Ј and 1ЈЈ (see numbering in Scheme 1) fined.
3286
Eur. J. Inorg. Chem. 2002, 3284Ϫ3291

Syntheses of Zinc Complexes with Multidentate Nitrogen Ligands
FULL PAPER
fore, the preliminary reactivity studies described below were
conducted with the acetates.
Reactivity Studies
In order to explore the ability of the new zinc complexes
to act as catalysts for aldol reactions, the zinc-catalyzed re-
action of benzaldehyde (10) with 2-hydroxyacetophenone
(11) to give 1,3-diphenylpropan-1-one (12) was investig-
ated (Scheme 2).
Scheme 2
The results are summarized in Tables 2Ϫ4. The aldol
product 12 was formed when a mixture of 1.0 equiv. of
benzaldehyde (10) and 1.5 equiv. of 2-hydroxyacetophenone
(11) reacted in the presence of 7.5 mol % of either 6 or 9
and 7.5 mol % of zinc acetate.[21] The reaction took place in
THF but also in a protic solvent, methanol, and the yields
improved with addition of 0.5 equiv. of triethylamine. The
ligand 9 was the more efficient of the two ligands studied,
giving the addition product in 53% in methanol and 56%
in THF. The conversion was higher when diethylzinc was
added to 9 (62%, Entry 7, Table 3). The preformed com-
plexes 1b and 2b could also catalyze the aldol reaction; 2b
gave the higher yield (59%) of 12. We have also observed
that an excess of benzaldehyde or 2-hydroxyacetophenone
can lead to better yields (51Ϫ52%) when 1b is the catalyst
(Entries 4 and 7 in Table 4). The syn/anti ratio of 12, deter-
1
1
Figure 4. Top: H NMR in CD3OD of ligand 9; center: H NMR
1
spectrum, in CD3OD, of complex 2b; bottom: H NMR spectrum
in CD3OD of complex 2c; the aromatic region and the methylene
groups are shown (in ppm)
1
mined by H NMR spectroscopy for the reactions shown
in the tables, was 1:1 for all the experiments with exception
of Entry 4 inTable 3 (1.5:1 syn/anti ratio) and Entry 5 in
Table 3 (3:1 syn/anti ratio).
1
The assignment of the hydrogen signals in the H NMR
spectrum of complex 2b was determined by a 1H-1H
COSY measurement.
The electrospray mass spectra of 2a, 2b and 2c show the
peaks corresponding to [9 Ϫ Hϩ ϩ ZnII] at m/z ϭ 292, 294
and 296 in the expected relative intensities, consistent with
the structure shown in Scheme 1. The peaks corresponding Table 2. Aldol reaction using the ligands 6 and 9 and zinc salts as
to [9 Ϫ Hϩ ϩ ZnII ϩ ClϪ] for 2a and [9 Ϫ Hϩ ϩ ZnII
ϩ
catalysts in MeOH (in all experiments, 0.5 mmol of benzaldehyde,
0.75 mmol of 2-hydroxyacetophenone and 0.05 mmol of catalyst
were used; 12 was obtained as a 1:1 syn/anti mixture and the yields
and diastereomeric ratios were determined by 1H NMR spectro-
scopy; Py: pyridine; Im: imidazole; Et3N: triethylamine)
CH3COOϪ] for 2b are also present. Similar to the com-
plexes of 6, the peak corresponding to the free ligand 9 is
not observed in the ESI-MS.
The structures for the complexes 2a, 2b, 2c in Scheme 1
indicate a protonated hydroxy group, although depro-
tonation cannot be excluded. The presence of a hydroxy
Entry Catalyst (7.5 mol %) Additives
Yield of 12 (%)
1
2
3
4
5
6
7
8
9
6
0
37
1
group was inferred by the fact that the H NMR spectrum
6, Zn(Ac)2
of the acetate complex 2b showed six protons for two acet-
ate anions, indicating the presence of two counter-anions
in 2b.
The acetates 1b and 2b proved to be soluble in a variety
of organic solvents, an important property for efficient cata-
lysis of organic reactions. The acetate anion can also act as
a base to deprotonate a ketone in the aldol reaction. There-
6, Zn(CH3COO)2
6, Zn(CH3COO)2
6, Zn(CH3COO)2
9
0.25 mmol Et3N 45
0.25 mmol py
0.25 mmol Im
24
17
0
9, Zn(CH3COO)2
9, Zn(CH3COO)2
9, Zn(CH3COO)2
38
0.25 mmol Et3N 53
Na2SO4 35
Eur. J. Inorg. Chem. 2002, 3284Ϫ3291
3287

T. Darbre, C. Dubs, E. Rusanov, H. Stoeckli-Evans
FULL PAPER
were distilled prior to use. Chemicals were purchased from com-
mercial suppliers (FLUKA and Aldrich) and, unless otherwise
stated, used without further purification. Acetonitrile was refluxed
under nitrogen for 2 h in the presence of CaH2, distilled and kept
over molecular sieves. Column chromatography (CC): silica gel 60
from FLUKA; thin layer chromatography (TLC): silica gel plates
Alugram Sil G/UV254; visualization was made with a UV lamp
(λ ϭ 254 nm) or with 10% ninhydrin solution in 90% ethanol.
Table 3. Aldol reaction using the ligands 6 and 9 and zinc salts as
catalysts in THF (in all experiments, 0.5 mmol of benzaldehyde,
0.75 mmol of 2-hydroxyacetophenone and 0.05 mmol of catalyst
were used; 12 was obtained as a 1:1 syn/anti ratio and the yields
and diastereomeric ratios were determined by 1H NMR spectro-
scopy; Py: pyridine; Et3N: triethylamine; MS: molecular sieves
Entry Catalyst (7.5 mol %) Additives
Yield of 12 (%)
1
NMR spectra: Bruker AC-300 spectrometer, 300 MHz for H and
1
2
3
4
5
6
7
6, Zn(CH3COO)2
6, Zn(CH3COO)2
6, Zn(CH3COO)2
6, Zn(CH3COO)2
9,Zn(CH3COO)2
9,Zn(CH3COO)2
9, Zn(Et)2
40
40
75 MHz for 13C. Chemical shifts δ are given in ppm and were calib-
rated against the deuterated solvent. The multiplicity of the 13C
NMR peaks were determined by 13C NMR DEPT spectra and the
expected chemical shifts; the J values are in Hz. Mass spectra were
provided by the Service of Mass Spectrometry of the Department
of Chemistry and Biochemistry in Bern. Infrared spectroscopy was
performed with a Perkin-Elmer 1600 series FTIR spectrometer.
Frequencies ν˜ are given in cmϪ1 (s strong, m medium, w weak).
MS
0.25 mmol Et3N, MS 50
0.25 mmol py, MS
MS
48
38
0.25 mmol Et3N, MS 56
62
Table 4. Aldol reaction using the complexes 1b and 2b as catalysts
(Entries 1Ϫ9 in THF; Entries 10, 11 in MeOH)
Caution: Perchlorates are potentially explosive and should be
handled with the necessary precautions.[22]
2-[(Tosylamino)methyl]pyridine (3): Prepared as described.[19] Tosyl
chloride (14.12 g, 74 mmol) in diethyl ether (14 mL) was added to
a mixture of 2-(aminomethyl)pyridine (8 g, 74 mmol) and NaOH
(4.4 g, 110 mmol) in water (20 mL). The two-phase reaction mix-
ture was stirred in a closed flask for 18 h. The ether was then evap-
orated and the pH of the aqueous phase adjusted to 7 with 1 
HCl solution. The precipitated white solid was filtered, dried and
dissolved in ethanol. The ethanol was evaporated to yield 3 as a
Entry Catalyst (7.5 mol %) Additives
1[a]
Yield of 12 (%)
1b
MS
40
2[a] 1b
3[a]] 1b
4[b] 1b
5[b] 1b
6[e] 1b
7[e] 1b
8[a] 2b
9[a] 2b
10[a] 2b
11[a] 2b
0.25 mmol Et3N, MS 48
0.25 mmol py, MS
MS
38
51[c]
0.25 mmol Et3N, MS 39[d]
MS
0.25 mmol Et3N, MS 52
MS 41
0.25 mmol Et3N, MS 59
29
45
1
white solid (17.36 g, 89% yield). H NMR (CDCl3): δ ϭ 2.39 (s, 3
H, CH3Ts), 4.24 (d, J ϭ 5.49, 2 H, NCH2Py), 5.90 (br. t, 1 H,
NH), 7.14Ϫ7.19 (m, 2 H, 3-pyH and 5-pyH), 7.23Ϫ7.26 (m, 2 H,
3-phH), 7.61 (ddd, 1 H, 4-pyH), 7.74 (d, J ϭ 7.7, 12 H, 2-phH),
8.45 (d, J ϭ 4.77, 1 H, 6-pyH) ppm. 13C NMR (CDCl3): δ ϭ 22.17
(q), 48.05 (t), 122.65 (d), 123.29 (d), 127.91 (d), 130.8 (d), 137.52
(d), 144.04 (q), 149.57 (d), 155.47 (q) ppm.
Na2SO4
23
[a]
[b]
0.5 mmol benzaldehyde, 0.75 mmol 2-hydroxyacetophenone.
[c]
1 mmol benzaldehyde, 0.25 mmol 2-hydroxyacetophenone. 1.5:1
[d]
syn/anti.
3:1 syn/anti. The yields and diastereomeric ratios were
determined by 1H NMR spectroscopy. MS: molecular sieves. Py:
pyridine; Et3N: triethylamine.
2,6-Bis(bromomethyl)pyridine (4) and [6-(Bromomethyl)pyrid-2-yl]-
methanol (7): 2,6-bis(hydroxymethyl)pyridine (2 g,14.4 mmol) was
heated for 15 h in 48% HBr solution (20 mL). The solution was
cooled with an ice bath and 10  NaOH was added until pH ϭ 12
was reached. After extraction with ether (3 ϫ 60 mL), the ether
phase was dried with MgSO4, filtered and the ether evaporated to
give a white solid. The products were separated by column chroma-
tography (diethyl ether/hexane, 3:7) to give two fractions. Fraction
A: 4 (1.94 g, yield 51%) as white needle-like crystals. Rf ϭ 0.4 (di-
ethyl ether/hexane, 3:7). 1H NMR (CDCl3): δ ϭ 4.55 (s, 4 H,
CH2Py), 7.39 (d, J ϭ 7.74 Hz, 2 H, 3-pyH), 7.72 (ap. t, J ϭ 7.73 Hz,
1 H, 4-pyH) ppm. 13C NMR (CDCl3): δ ϭ 33.45 (t), 122.79 (d),
138.11 (d), 156.73 (s) ppm. Fraction B: 7 (720 mg, yield 24%) as
[e]
0.25 mmol benzaldehyde,
0.75 mmol 2-hydroxyacetophenone. In all experiments 0.05 mmol
of catalyst was used. 12 was obtained as a 1:1 syn/anti ratio with
[c]
[d]
the exception of footnotes and
.
Further studies of the catalytic system developed with
other substrates and screening for reaction conditions that
will lead to improved yields are now under way.
Conclusions
In a search for new ZnII complexes that can act as cata-
lysts for aldol reactions, we have prepared novel zinc com-
1
white needle-like crystals. Rf ϭ 0.05 (diethyl ether/hexane, 3:7). H
NMR (CDCl3): δ ϭ3.66 (br. s, 1 H, OH), 4.56 (s, 2 H, OCH2py),
plexes with N5 and N3O coordination. For that, the ligands 4.77 (s, 2 H, BrCH2py), 7.18 (d, J ϭ 7.7 Hz, 1 H,), 7.36 (d, J ϭ
7.5 Hz, 2 H), 7.61 (app t, J ϭ 7.7 Hz, 1 H, 4-pyH) ppm. By adding
more HBr after 15 h and refluxing for a longer time, the yield of 4
could be increased to 69%. By stopping the reaction immediately
after all the 2,6-bis(hydroxymethyl)pyridine had disappeared on the
TLC the yield of 7 could be increased to 37%.
6 and 9 were synthesized in a few steps with high yields.
The complexes prepared catalyze the reaction of hydroxya-
cetophenone and benzaldehyde to give 2,3-diphenylpropan-
1-one in yields of 60% when 9 plus diethylzinc or the pre-
formed zinc complex 2b were the catalysts.
2,6-Bis{[(pyrid-2-ylmethyl)(tosyl)amino]methyl}pyridine
(5):
nBu4NBr (6.48 g) and KOH (80 g) in water (240 mL) was added to
2-[(tosylamino)methyl]pyridine (3) (8 g, 30.4 mmol) in dichlorome-
thane (800 mL). The reaction mixture was heated to reflux and 2,6-
bis(bromomethyl)pyridine (4) (4 g, 15.2 mmol) in dichloromethane
was added at once. The reaction mixture was refluxed for 14 h. The
Experimental Section
General Remarks: All reactions were carried out, unless mentioned,
in open flasks, without exclusion of O2 or H2O. Technical solvents
3288
Eur. J. Inorg. Chem. 2002, 3284Ϫ3291

Syntheses of Zinc Complexes with Multidentate Nitrogen Ligands
FULL PAPER
two phases were separated and the dichloromethane was evapor-
ated to leave a brown oil. Column chromatography (hexane/ethyl
7.14Ϫ7.18 (m, 1 H, 5-pyH), 7.23 (d, J ϭ 7.71 Hz, 1 H, 3-pyH),
7.33 (d, J ϭ 7.7 Hz, 1 H, 5-pyH), 7.59Ϫ7.66 (m, 2 H, 4-pyH), 8.55
(d, J ϭ 4.05 Hz, 1 H, 6-pyH) ppm. H NMR(CD3OD): δ ϭ 3.91
1
acetate, 1:1 with 1% triethylamine) yielded 5 as a brown viscous oil
1
(8.25 g, yield 86%). Rf ϭ 0.1 (hexane/ethyl acetate, 1:1). H NMR and 3.93 (2 s, 4 H), 4.69 (s, 2 H), 7.25Ϫ7.34 (m, 2 H), 7.40 (d, J ϭ
(CDCl3): δ ϭ 2.39 (s, 3 H, TsCH3), 4.36 (s, 4 H, pyCH2), 4.49 (s, 7.74 Hz, 1 H), 7.50 (d, J ϭ 7.71 Hz, 1 H), 7.72Ϫ7.85 (m, 2 H),
4 H, pyCH2), 7.05Ϫ7.09 (m, 4 H,3,5-pyH), 7.23 (d, J ϭ 8.1 Hz, 4 8.49 (d, J ϭ 4.02 Hz, 1 H) ppm. 13C NMR (CDCl3): δ ϭ 54.97 (t),
H, phH), 7.31 (d, J ϭ 7.92 Hz, 2 H, 3,5-pyH), 7.36 (ap. t, J ϭ 55.24 (t), 64.68 (t), 119.34 (d), 121.44 (d), 122.74 (d), 123.08 (d),
7.71 Hz, 1 H, 4-pyH), 7.53 (ddd, J ϭ 7.63, J ϭ 1.6 Hz, 2 H, 4-
pyH), 7.65 (d, J ϭ 8.2 Hz, 4 H, phH), 8.34 (d, J ϭ 4.2 Hz, 2 H, 6- ppm. IR (CHCl3): ν˜ ϭ 3016 w, 1595 m, 1576 m, 1216 s, 754 s, 668
pyH) ppm. 13C NMR (CDCl3): δ ϭ 22.16 (q), 54.31 (t), 54.56 (t), m cmϪ1. FAB-NBA: m/z ϭ 230 [M ϩ 1]. High resolution ESI-
137.23 (d), 137.81 (d), 149.98 (d), 159.02 (s), 159.37 (s), 159.99 (s)
121.83 (d), 123.02 (d), 123.36 (d), 128.06 (d), 130.24 (d), 137.26 (d), TOF-MS: calculated for C13H16N3O: 230.1293; found 230.1288.
137.61 (d), 144.03 (s), 149.44 (d), 156.42 (s), 157.14 (s) ppm.
(2,6-Bis{[(pyrid-2-ylmethyl)amino]methyl}pyridine)zinc Dichloride
2,6-Bis{[(pyrid-2-ylmethyl)amino]methyl}pyridine (6):
5
(7.6 g, (1a):
2,6-bis{[(pyrid-2-ylmethyl)amino]methyl}pyridine
(6)
12.1 mmol) was dissolved in 98% H2SO4 (10 mL) and heated to
120 °C for 3 h. The liquid turned black. The solution was poured
into a brine/NaOH solution (20 mL) and the pH of the solution
was adjusted to 12 with an NaOH solution The aqueous solution
(200 mg, 0.63 mmol) and ZnCl2 (85 mg, 0.63 mmol) were dissolved
in methanol (15 mL) and chloroform (3 mL). The solution was
refluxed for 3 h. The methanol was reduced to 3 mL, and complex
1a could be obtained as crystals (183 mg; yield 64%) by gradually
was extracted with dichloromethane (4 ϫ 100 mL). The organic adding (day by day 0.3Ϫ0.5 mL) diethyl ether. 13C NMR (CDCl3):
phase was dried with MgSO4, filtered and the dichloromethane
evaporated to give 6 as a brown solid (3.65 g, yield 94%). 1H NMR (d), 142.64 (d) 148.83 (d), 155.32 (s), 157.87 (s) ppm. IR: ν˜ ϭ 3462
(CDCl3): δ ϭ 2.32 (s, 2 H, NH), 3.96 and 3.98 (2s, 8 H, CH2py), s, 3196 s, 1653 w, 1627 w, 1603 s, 1586 m, 1434 s, 1097 m, 915 m,
7.13Ϫ7.15 (m, 2 H, pyH), 7.21 (d, J ϭ 7.71, 2 H, pyH), 7.35 (d, 781 m, 771 s, 760 s cmϪ1. ESI-MS: m/z (%) ϭ 382 (86) [6-Hϩ
J ϭ 7.71 Hz, 2 H, 3,5-pyH), 7.57Ϫ7.66 (m, 3 H, 4-pyH), 8.54 (d,
64Zn], 384 (51) [6-Hϩ 66Zn], 386 (35) [6-Hϩ 68Zn], 418 (100)
J ϭ 4.8 Hz, 2 H, 6-pyH) ppm. 13C NMR (CDCl3): δ ϭ 55.31 (t) [6 ϩ 64Zn ϩ 35C] , 420 (92) [6 ϩ 64Znϩ 37Cl, 6 ϩ 66Znϩ 35Cl], 422
55.44 (t), 121.15 (d), 122.63 (d), 123.01 (d), 137.15 (d), 137.59 (d),
(65) [6 ϩ 66Zn ϩ 37Cl, 6 ϩ 68Zn ϩ 35Cl]. High resolution ESI-TOF-
149.96 (d), 159.70 (s), 160.31 (s) ppm. IR (CHCl3): ν˜ ϭ 3425 s, MS: C19H20N5Zn calcd. 382.1010, found 382.1005; C19H20ClN5Zn
δ ϭ 52.29 (t), 54.28 (t), 123.32 (d), 125.49 (d), 125.97 (d), 142.01
ϩ
ϩ
ϩ
1604 m, 1215 s, 742 s, 668 s cmϪ1. MS: m/z (%) ϭ 319 (1.6) [Mϩ],
241 (2.6), 227 (3.0), 213 (71), 107 (88), 93 (100). FAB (DTT/DTE):
m/z ϭ 320 [M ϩ 1]. HRMS: calculated for C19H21N5 319.179696,
found 319.179690.
calcd. 418.0776; found 418.0742. For X-ray structure see X-ray sec-
tion.
(2,6-Bis{[(pyrid-2-ylmethyl)amino]methyl}pyridine)zinc
Diacetate
(1b): 6 (150 mg, 0.5 mmol) and Zn(CH3COO)2 (108 mg, 0.5 mmol)
[6-{[(Pyrid-2-ylmethyl)(tosyl)amino]methyl}pyrid-2-yl]methanol (8): were dissolved in methanol (5 mL). After refluxing for 3 h, the
A mixture of 3 (1.9 g, 7.2 mmol), 7 (1.5 g, 7.2 mmol) and K2CO3 methanol was evaporated to leave the 1b complex as a brown vis-
(2.7 g) in acetonitrile (140 mL) was refluxed for 6 h. The precipitate
was collected by vacuum filtration and washed with acetonitrile.
The acetonitrile was evaporated to give an orange oil. Chromato-
cous oil (200 mg, yield 82%). The complex was soluble in various
organic solvents (THF, acetonitrile, dichloromethane and meth-
anol). H NMR (MeOD): δ ϭ 1.83 (s, COOCH3, 6 H), 4.28 and
1
graphy using
a
gradient (ethyl acetate/hexane/triethylamine,
4.39 (2 br. s, 8 H, CH2py), 7.34Ϫ7.43 (m, 4 H, pyH), 7.54 (d, J ϭ
1000:100:1 to ethyl acetate/methanol/triethylamine, 1000:100:1) 7.71 Hz, 2 H, pyH), 7.87Ϫ7.99 (m, 3 H, pyH), 8.49 (d, J ϭ 3.66 Hz,
gave 8 as a colorless viscous oil (2.05 g, yield 74%). Rf ϭ 0.62 (ethyl
2 H, 6-pyH) ppm. 13C NMR (CD3OD): δ ϭ 23.46 (q), 52.54 (t),
acetate/methanol, 25:2). 1H NMR (CDCl3): δ ϭ2.42 (s, 3 H, 54.14 (t), 122.91 (d), 124.95 (d), 125.30 (d), 140.95 (d), 141.81 (d),
CH3Ts), 4.54Ϫ4.56 (3 s, 6 H, CH2py), 6.98 (d, J ϭ 7.8 Hz, 1 H, 3-
pyH), 7.06Ϫ7.10 (m, 1 H, 5-pyH), 7.16 (d, J ϭ 7.35 Hz, 1 H, 5-
pyH), 7.27 (d, J ϭ 7.71 Hz, 2 H, phH), 7.35 (d, J ϭ 8.1 Hz, 1 H,
148.87 (d), 155.68 (s), 157.62 (s) ppm. IR: ν˜ ϭ 3447 s, 1653 m, 1560
s, 1419 m, 1215 w, 770 s cmϪ1. FAB MS (matrix: 3-NBA): m/z
(%) ϭ 382 (100) [6-Hϩ
ϩ ϩ
64Zn], 384 (61) [6-Hϩ 66Zn], 386 (38)
3,5-pyH), 7.48- 7.58 (m, 2 H, 4-pyH), 7.70 (d, J ϭ 8.34 Hz, 2 H, [6-Hϩ
ϩ
68Zn], 442 (34) [6 ϩ 64Zn ϩ CH3COOϪ], 444 (19) [6 ϩ
phH), 8.33 (d, J ϭ 4.77 Hz, 1 H, 6-pyH) ppm. 13C NMR (CDCl3): 66Zn ϩ CH3COOϪ], 446 (12) [6 ϩ 68Zn ϩ CH3COOϪ]. HR ESI-
δ ϭ 22.17 (q), 54.01 (t), 54.61 (t), 64.40 (t), 119.65 (d), 122.03 (d), TOF-MS: C19H20N5Zn calcd. 382.1010, found 382.1027;
123.04 (d), 123.44 (d), 127.98 (d), 130.30 (d), 137.20 (d), 137.31 (s), C21H24N5O2Zn calcd. 442.1221, found 442.1226.
137.79 (d), 144.15 (s), 149.57 (d), 155.70 (s), 157.12 (s), 159.99 (s)
(2,6-Bis{[(pyrid-2-ylmethyl)amino]methyl}pyridine)zinc Diperchlor-
ppm. IR (CHCl3): ν˜ ϭ 3018 m, 1597 s, 1576 s, 1339 s, 1159 s, 1091
m, 756 s, 668 m cmϪ1. MS: m/z (%) ϭ 207 (11), 162 (27), 155 (30),
134 (33), 105 (30), 91 (52), 69 (69), 57 (100). FAB-NBA: m/z ϭ
384 [M ϩ 1]. High resolution LSIMS: calculated for C20H22N3O3S
384.138189; found 384.13812.
ate (1c): 6 (150 mg, 0.5 mmol) and Zn(ClO4)2 (175 mg, 0.5 mmol)
were dissolved in methanol (4 mL) The solution was refluxed for
3 h. By addition of the Zn(ClO4)2 a white solid immediately precip-
itated. The methanol was evaporated to leave 1c as a white solid
(235 mg, yield 81%). The solid was dissolved in acetonitrile and
[6-{[(Pyrid-2-ylmethyl)amino]methyl}pyrid-2-yl]methanol (9): The upon slow evaporation crystals were obtained. 1H NMR (DMSO):
tosylate 8 (2.0 g, 5.2 mmol) was dissolved in 98% H2SO4 (10 mL)
and heated to 120 °C for 3 h. The liquid turned black. The solution
was poured into a brine/NaOH solution (20 mL), and the pH was
adjusted to 12 with NaOH solution. The water phase was extracted
with dichloromethane (4 ϫ 100 mL). The organic phase was dried
with MgSO4, filtered and the dichloromethane evaporated to give
δ ϭ 4.10 (br. s, 4 H, CH2py), 4.57 (br. d, 4 H, CH2py), 5.77 (br. t,
NϪH, 2 H), 7.43 (d, J ϭ 7.71 Hz, 2 H, 5-pyH), 7.58 (t, J ϭ
6.26 Hz, 2 H, 3-pyH), 7.66 (d, J ϭ 7.71 Hz, 2 H, 3,5-pyH), 7.97 (t,
J ϭ 7.73 Hz, 1 H, 4-pyH), 8.10 (dd, J ϭ 7.71, J ϭ 1.47 Hz, 2 H,
6-pyH) ppm. 13C NMR (CD3OD): δ ϭ60.84 (t), 62.47 (t), 131.26
(d), 133.70 (d), 133.94 (d), 150.27 (d), 150.55 (d), 157.00 (d), 163.09
(s), 165.96 (s) ppm. IR (CHCl3): ν˜ ϭ 3500 s, 1610 s, 1450 s, 1100
1
9 as an oil with a slight orange color (0.91 g, yield 76%). H NMR
(CDCl3): δ ϭ 3.15 (br. s, 2 H, OH ϩ NH), 3.95 and 3.96 (2 s, 4 H,
s, 770 s, 620 s cmϪ1. ESI-MS: m/z (%) ϭ 382 (22) [6-Hϩ 64Zn],
ϩ
CH2py), 4.72 (s, 2 H, pyCH2O), 7.10 (d, J ϭ 7.71 Hz, 1 H, 3-pyH), 384 (13) [6-Hϩ
ϩ
66Zn], 386 (9) [6-Hϩ
ϩ
68Zn], 482 (100) [6 ϩ
Eur. J. Inorg. Chem. 2002, 3284Ϫ3291
3289

T. Darbre, C. Dubs, E. Rusanov, H. Stoeckli-Evans
66Zn], 296 (33) [9-Hϩ 68Zn]. HR ESI-MS-TOF:
FULL PAPER
64Znϩ 35ClO4], 484 (95) [6 ϩ 64Zn ϩ 37ClO4, 6 ϩ 66Zn ϩ 35ClO4, (55) [9-Hϩ
ϩ
ϩ
486 (63) [6 ϩ 66Zn ϩ 37ClO4, 6 ϩ 68Zn ϩ 35ClO4]. HR ESI-TOF-
MS: C19H21N5O4ClZn calcd. 482.0573, found 482.0586;
C19H20N5Zn calcd. 382.1010, found 382.1035.
C13H14N3OZn calcd. 292.0428, found 292.0438.
[(6-{[(Pyrid-2-ylmethyl)amino]methyl}pyrid-2-yl)methanol]zinc Per-
chlorate (2c): 9 (400 mg, 1.74 mmol) and Zn(ClO4)2·6H2O (650 mg,
1.74 mmol) in methanol (25 mL) were refluxed for 1 h. The meth-
anol was reduced to 3Ϫ4 mL and the complex precipitated by addi-
tion of diethyl ether to give 2b as a white amorphous solid (565 mg,
66% yield). 1H NMR (CD3OD): δ ϭ 4.04Ϫ4.17 (2 d, 2 H, CH2py),
4.50Ϫ4.70 (2 d, 2 H, CH2py), 5.00Ϫ5.16 (2 d, 2 H, pyCH2O),
7.40Ϫ7.53 (m, 4 H, 3,5-pyH), 7.92Ϫ8.00 (m, 2 H, 4-pyH), 8.51 (d,
1 H, 6-pyH) ppm. 13C NMR (CD3OD): δ ϭ 53.99 (t), 54.70 (t),
61.40 (t), 121.78 (d), 123.28 (d), 125.23 (d), 125.85 (d), 141.60 (d),
142.04 (d), 148.04 (d), 154.49 (s), 155.18 (s), 156.70 (s) ppm. IR:
ν˜ ϭ 3331 s, 2739 s, 2330 w, 2023 w, 1615 s, 1486 s, 1109 s, 658 s
cmϪ1. ESI-MS: m/z (%) ϭ 292 (100) [9-Hϩ ϩ 64Zn], 294 (58) [9-Hϩ
(6-{[(Pyrid-2-ylmethyl)amino]methyl}pyrid-2-yl]methanol)zinc
Chloride (2a):
9 (150 mg, 0.66 mmol) and Zn(Cl)2 (89 mg,
0.66 mmol) were dissolved in methanol (15 mL) and refluxed for
1 h. The methanol was reduced to 3Ϫ4 mL and by addition of
diethyl ether 2a precipitated as a white amorphous solid (98 mg,
41%). Recrystallization from ethanol/dichloromethane gave crys-
tals that were too small to perform X-ray analysis. 1H NMR
(CD3OD): δ ϭ 3.77 (br. d, 1 H, CH2py), 4.23 (br. d, 1 H, CH2py),
4.45Ϫ4.66 (br. m, 2 H, CH2py), 5.05 (br. d, 2 H, pyCH2O),
7.51Ϫ7.66 (m, 4 H, 3,5-pyH), 8.09 (dd, J ϭ 7.80, J ϭ 5.31 Hz, 2
H, 4-pyH), 8.61 (d, J ϭ 5.3 Hz, 1 H, 6-pyH) ppm. 13C NMR
(CD3OD): δ ϭ 51.69 (t), 52.85 (t), 61.86 (t), 122.28 (d), 123.86 (d),
124.94 (d), 126.04 (d), 142.34 (d), 142.60 (d), 148.79 (d), 155.81 (s),
157.69 (s), 158.10 (s) ppm. IR (CHCl3): ν˜ ϭ 3414 s, 3223 s, 2908
m, 1604 s, 1575 m, 1465 m, 1452 m, 1444 m, 1285 w, 1063 s, 1012
s, 802 m, 767 s, 644 w cmϪ1. ESI-MS: m/z (%) ϭ 292 (100) [9-Hϩ
ϩ
66Zn], 296 (37) [9-Hϩ ϩ 68Zn]. HR ESI-TOF-MS: C13H14N3OZn
calcd. 292.0428, found 292.0418.
X-ray Crystallography: Intensity data for crystals of 1a·CH3OH
solvate (0.25 ϫ 0.15 ϫ 0.15mm), 1a·2H2O (0.25 ϫ 0.18 ϫ 0.15
mm), and 1c (0.40 ϫ 0.35 ϫ 0.35 mm), were collected at 153 K with
a Stoe Image Plate Diffraction System[23] using Mo-Kα graphite-
monochromated radiation. Image plate distance 70 mm, ϕ oscilla-
tion scans 0Ϫ180° or 0Ϫ200°, step ∆ϕ ϭ 1.2°, 1.5° and 2°, respect-
ϩ
64Zn], 294 (57) [9-Hϩ 66Zn], 296 (38) [9-Hϩ 68Zn], 328 (24)
ϩ ϩ
[9 ϩ 64Zn ϩ 35ClϪ], 330 (21) [9 ϩ 64Znϩ 37ClϪ, 9 ϩ 66Znϩ 35ClϪ],
332 (14) [9 ϩ 66Znϩ 37ClϪ, 9 ϩ 68Znϩ 35ClϪ]. HR ESI-TOF-MS:
C13H14N3OZn calcd. 292.0428, found 292.0429; C13H15ClN3OZn
calcd. 328.0195, found 328.0214.
˚
ively. 2θ range 3.27Ϫ52.1°, dmax.Ϫdmin. ϭ 12.45Ϫ0.81 A. The struc-
[(6-{[(Pyrid-2-ylmethyl)amino]methyl}pyrid-2-yl)methanol)]zinc tures were solved by direct methods using the program SHELXS-
Acetate (2b): 9 (150 mg, 0.66 mmol) and Zn(CH3COO)2 (143 mg, 97.[24] Refinement and all further calculations were carried out us-
0.66 mmol) in methanol (15 mL) were refluxed for 1 h. The meth-
anol was reduced to 3Ϫ4 mL and the complex precipitated by addi-
tion of diethyl ether to give 2b as a white amorphous solid (168 mg,
62% yield). H NMR (MeOD): δ ϭ 1.93 (s, COOCH3, 6 H), 3.82
(br. d, 1 H, CH2py), 4.16 (br. d, 1 H, CH2py), 4.47Ϫ4.60 (br. m, 2
H, CH2py), 5.01 (br. d, 2 H, pyCH2O), 7.43Ϫ7.58 (m, 4 H, 3,5-
ing SHELXL-97.[25] The H atoms were located from difference
maps and refined isotropically. In 1a·CH3OH, the solvent H atoms
were included in calculated positions and treated as riding atoms
using SHELXL default parameters. The non-H atoms were refined
anisotropically, using weighted full-matrix least squares on F2. The
molecular structure and crystallographic numbering schemes are
1
pyH), 7.97Ϫ8.06 (m, 2 H, 4-pyH), 8.64 (d, J ϭ 4.77, 1 H, 6-pyH) illustrated in the PLATON[26] figures. Further crystallographic data
ppm. 13C NMR (MeOD): δ ϭ 22.98 (q), 52.09 (t), 52.78 (t), 62.64 are summarized in Table 5. CCDC-183956 (1a·CH3OH), -183957
(t), 121.87 (d), 123.20 (d), 124.56 (d), 125.63 (d), 141.78 (d), 142.00
(d), 148.97 (d), 155.68 (s), 157.97 (s), 159.03 (s), 180.89 (s) ppm.
IR (CHCl3): ν˜ ϭ 3406 m, 2924 w, 1606 s, 1385 s, 1080 m, 1014 m,
(1a·2H2O) and -183958 (1c) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html or from the
668 w cmϪ1. ESI-MS: m/z (%) ϭ 292 (100) [9-Hϩ
ϩ
64Zn], 294 Cambridge Crystallographic Data Centre, 12, Union Road, Cam-
Table 5. Crystallographic data for complexes 1a·CH3OH, 1a·2H2O, and 1c
1a·CH3OH
1a·2H2O
1c
Empirical formula
C19H20Cl2N5Zn·CH3OH
C19H20Cl2N5Zn·2H2O
491.71
9.0366(7)
16.1489(14)
15.2881(11)
90
97.34(10)
90
2212.7(3)
4
C19H21N5Zn·(ClO4)2
583.68
13.4064(13)
14.3351(14)
12.2712(11)
90
102.01(1)
90
2306.7(4)
4
Formula mass [g molϪ1
]
487.72
8.9211(6)
9.2475(6)
26.2005(14)
90
95.58(1)
90
˚
a [A]
˚
b [A]
˚
c [A]
α [°]
β [°]
γ [°]
3
˚
V [A ]
Z
2154.6(2)
4
Space group
T [K]
P21/c
153(2)
1.504
0.71073
1.409
0.0381
0.0764
P21/c
153(2)
1.476
0.71073
1.376
0.0261
0.0537
P21/c
153(2)
1.681
0.71073
1.354
0.0329
0.0761
ρcalcd. [g cmϪ1
]
˚
λ [A]
µ [mmϪ1
]
R1[a] (obsd. data)
wR2[b] (obsd. data)
[a]
[b]
2
2
4 1/2
R1 ϭ Σ||Fo| Ϫ |Fc||/Σ|Fo|. wR2 ϭ [Σw(|Fo | Ϫ |Fc |)2/ΣwFo ]
.
3290
Eur. J. Inorg. Chem. 2002, 3284Ϫ3291

Syntheses of Zinc Complexes with Multidentate Nitrogen Ligands
FULL PAPER
D. Veot, J. G. Veot, Biochemistry, John Wiley & Sons, Inc.,
[5]
bridge CB2 1EZ, UK [Fax: (internat.) ϩ 44-1223/336-033; E-mail:
deposit@ccdc.cam.ac.uk].
Weinheim, 1990.
[6] [6a]
[6b]
G. Schulz, M. Dreyer, J. Mol. Biol. 1996, 259, 458Ϫ466.
Reactivity Tests: All reactivity tests were performed using the 12
place Carousel Reaction Station with Reflux Heads from Radleys
Discovery Technologies (RR98030) or the Cooled Carousel Reac-
tion Station from Radleys Discovery Technologies (RR99900). All
the reactions were performed under nitrogen at room temperature
in 5 mL of solvent. For more details refer to the result section. The
benzaldehyde was distilled prior to use and 2-hydroxyacetophenone
was purified on a silica gel column (hexane/ethyl acetate, 1:1). Pro-
cedure A (Entry 7, Table 2): diethylzinc (46 µL, 1.1 ) in toluene
was added to ligand 9 (11.5 mg, 0.0.05 mmol) in dry THF (5 mL).
After 10 min, benzaldehyde (53 mg, 0.5 mmol), and hydroxyaceto-
phenone (90 mg, 0.66 mmol) were added, and the reaction mixture
was stirred under N2 for 48 h. The solvent was evaporated and the
products analyzed by 1H NMR spectroscopy. The coupling product
12 was formed in 62% yield. The 1H NMR spectroscopic yields
were determined by the ratio of the areas of the following peaks:
benzaldehyde (δ ϭ 10.03 ppm, 1 H), 2-hydroxyacetophenone (δ ϭ
4.90 ppm, 2 H) and the four doublets corresponding to the two
diastereomers of 12 (anti: δ ϭ 5.41 ppm, 1 H and δ ϭ 5.08 ppm,
1 H; syn: δ ϭ 5.24 ppm, 1 H and δ ϭ 4.95 ppm, 1 H).[27] Procedure
B: Benzaldehyde (53 mg, 0.5 mmol), 2-hydroxyacetophenone
(90 mg, 0.66 mmol), 2b (20.1 mg, 0.049 mmol) and 35 µL of triethy-
lamine in dry methanol (5 mL) were stirred at room temperature
under N2 for 48 h. The reaction mixture was analyzed as described
above to give 59% of product 12.
B. S. Szwergold, K. Ugurbil, T. R. Brown, Arch. Biochem.
[6c]
´
N. S. Blom, S. Tetreault, R.
Biophys. 1995, 317, 244Ϫ252.
Coulombe, J. Sygusch, Nat. Struct. Biol. 1996, 3, 856Ϫ862.
[7] [7a]
L. Liu, S.H. Chen, Y. L Wang, Z. X. Yang, Chin. Chem.
[7b]
Lett. 2000, 6, 485Ϫ488.
1974, 959Ϫ960.
19, 1291Ϫ1296.
M. Iwata, S. Emoto, Chem. Lett.
Y. Zhang, W. Xu, Synth. Commun. 1989,
[7c]
[8]
[9]
H. Vahrenkamp, I. Brasack, K. Weis, M. Ruf, Inorg. Chim.
Acta 1996, 250, 271Ϫ281.
E. Kimura, T. Gotoh, T. Koike, M. Shiro, J. Am. Chem. Soc.
1999, 121, 1267Ϫ1274.
B. List, R. A. Lerner, C. F. Barbas, III, J. Am. Chem. Soc.
2000, 122, 2395Ϫ2396.
W. Notz, B. List, J. Am. Chem. Soc. 2000, 122, 7386Ϫ7387.
K. Watanabe, K. Irie, Bull. Chem. Soc. Jpn. 1980, 53,
1366Ϫ1371; K. Watanabe, Y. Yamada, K. Goto, Bull. Chem.
Soc. Jpn. 1985, 58, 1401Ϫ1406.
M. Shibasaki, T. Suzui, T. Ohshima, G. Moll, S. Matsunaga,
N. Kumagai, N. Yoshikawa, J. Am. Chem. Soc. 2001, 123,
2466Ϫ2467.
M. Shibasaki, T. Ohshima, N. Yoshikawa, S. Matsunaga, N.
Kumagai, Org. Lett. 2001, 3, 1539Ϫ1542.
M. Shibasaki, N. Yoshikawa, Tetrahedron 2001, 57,
[10]
[11]
[12]
[13]
[14]
[15]
2569Ϫ2579.
[16]
[17]
B. Trost, H. Ito, J. Am. Chem. Soc. 2000, 122, 12003Ϫ12004.
B. Trost, H. Ito, E. Silcoff, J. Am. Chem. Soc. 2001, 123,
3367Ϫ2268.
B. Trost, H. Ito, E. Silcoff, Org. Lett. 2001, 3, 2497Ϫ2500.
G. R. Newkome, V. K. Gupta, F. R. Fronczek, S. Pappalardo,
Inorg. Chem. 1984, 23, 2400Ϫ2408.
D. W. Gruenwedel, Inorg. Chem. 1968, 7, 495Ϫ501.
The condensation is also catalyzed by Zn(OAc)2 and other zinc
salts under the conditions described. The yields were, however,
lower than the ones obtained in the presence of the ligands.
W. C. J. Wolsey, J. Chem. Educ. 1973, 50, A335ϪA336.
Stoe & Cie, IPDS Software, Stoe & Cie GmbH, Darmstadt,
Germany, 2000.
SHELXS-97, Program for Crystal Structure Determination: G.
M. Sheldrick, Acta Crystallogr., Sect. A 1990, 46, 467Ϫ473.
G. Sheldrick, SHELXL-97, Universität Göttingen, Göttingen,
Germany, 1999.
[18]
[19]
[1]
Comprehensive Organic Synthesis, vol. 2 (Eds.: B. M. Trost, I.
[20]
[21]
Fleming, C. H. Heathcock), Pergamon, Oxford, 1991.
[2]
[2a]
For review articles and references:
C.-H. Wong, T. Ma-
chajewski, Angew. Chem. 2000, 112, 1406 Ϫ1430; Angew.
[2b]
Chem. Int. Ed. 2000, 39, 1352Ϫ1374.
C. Palomo, M. Oiar-
bide, J. M. Garcia, Chem. Eur. J. 2002, 8, 36Ϫ34. [2c] S. Takay-
ama, G. McGarvey, C.-H. Wong, Chem. Soc. Rev. 1997, 26,
407Ϫ414.
[22]
[23]
[3] [3a]
[24]
[25]
[26]
[27]
Y. M. A. Yamada, N. Yoshikawa, H. Sasai, M. Shibasaki,
Angew. Chem. Int. Ed. Engl. 1997, 36, 1871Ϫ1873; Angew.
Chem. 1997, 109, 1942Ϫ1944. [3b] Y. M. A. Yamada, A. Shiba-
saki, Tetrahedron Lett. 1998, 39, 5561Ϫ5564. [3c] N. Yoshikawa,
Y. M. A. Yamada, J. Das, H. Sasai, M. Shibasaki, J. Am. Chem.
Soc. 1999, 121, 4168Ϫ4178.
PLATON/PLUTON (version 1999): A. L. Spek, Acta Crys-
tallogr., Sect. A 1990, 46, C-34.
[4] [4a]
S. E. Denmark, R. A. Stavenger, J. Org. Chem. 1998, 63,
For the 1H NMR characterization of 12, see: O. Porta, A.
Clerici, J. Org. Chem. 1989, 54, 3872Ϫ3878.
Received April 25, 2002
[4b]
9524Ϫ9527.
Res. 2000, 33, 432Ϫ440.
J. Am. Chem. Soc. 2000, 122, 8837Ϫ8847.
S. E. Denmark, R. A. Stavenger, Acc. Chem.
[4c]
S. E. Denmark, R. A. Stavenger,
[I02226]
Eur. J. Inorg. Chem. 2002, 3284Ϫ3291
3291