Tuning the polarity of hierarchically assembled helicates

Article abstract of DOI:10.1055/s-0029-1218684

Catechol ligands bearing ester groups in 3-position (1a,b, 2) are building blocks for the formation of triply lithium-bridged dinuclear helicate-type complexes [Li1a,b,2)i^-. Attachment of appropriate functionalities at the ester unit allows the fine tuning of the polarity of the compounds to afford solubility in highly nonpolar as well as highly polar solvents. The investigations show that the internal dinuclear core is stable in a broad variety of solvents, even in water. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0029-1218684

PAPER
953
Tuning the Polarity of Hierarchically Assembled Helicates
H
ierarchically
A
ssem
b
i
ledHe
r
licates iam Baumert,a Markus Albrecht,*a Henrik D. F. Winkler,b Christoph A. Schalleyb
a
b
Received 27 August 2009
voring the monomer as major product. This preference of
monomer versus dimer is due to the ability of the solvent
to solubilize lithium cations and to disrupt the dimer.
Herein, we extend our studies to the extremes of solvent
Abstract: Catechol ligands bearing ester groups in 3-position
(1a,b, 2) are building blocks for the formation of triply lithium-
bridged dinuclear helicate-type complexes [Li3(1a,b,2)6Ti2]–. At-
tachment of appropriate functionalities at the ester unit allows the
fine tuning of the polarity of the compounds to afford solubility in polarity. First we present complexes, which assemble and
highly nonpolar as well as highly polar solvents. The investigations
are soluble in nonpolar solvents (benzene, chloroform)
show that the internal dinuclear core is stable in a broad variety of
solvents, even in water.
and in the second part hierarchical helicate formation in
water as highly polar reaction medium is described. The
aim of this study is to test the stability of the dimeric com-
plexes of ester type ligands in the opposed solvent ex-
Key words: helicates, dinuclear complexes, esters, hierarchical
self-assembly, templates
tremes.
The hierarchical formation of highly complex structures is
a common process in nature as well as in artificial sys-
tems.1 Examples are proteins2 or the tobacco mosaic vi-
rus.3 Recently, we described the stepwise assembly of
dinuclear double-4 and triple-stranded helicate-type com-
plexes.5,6 Catechol building blocks with a carbonyl donor,
such as esters, ketones, and aldehydes in 3-position were
used to form dinuclear complexes with various coordina-
tion centers (TiIV, Mo VIO2, BIII) (Scheme 1).
Hierarchical Assembly of Highly Hydrophobic Heli-
cates
Long alkyl chains were introduced as substituents in
ligand 1b-H2 in order to generate hydrophobicity
(Scheme 2). For comparison, the methyl-substituted
ligand 1a-H2 was prepared as well.
The synthesis consists of five steps, starting with gallic
acid propyl ester (3), which couples in an SN-type reaction
with iodomethane or 1-bromotetradecane to yield 4a,b
(100% a, 69% b).7 The following step is the reduction of
the ester function with LiAlH4 to afford 5a,b, followed by
substitution of the benzylic alcohol by PBr3 leading to the
benzyl bromides 6a,b (yield over two steps: a: 69%, b:
100%).8 Compounds 6a,b react with 2,3-diacetoxybenzo-
ic acid (7) under basic conditions to yield the protected
ligands 8a,b. The ligand precursor selectively is depro-
tected by mild basic conditions resulting in the ligands
1a,b (yield over two steps: 42% a, 29% b). Finally, titani-
um(IV) complexes Li2[Ti(1a,b)3] were prepared by dis-
solving 3 equivalents of the corresponding ligand 1a,b-
H2, 1 equivalent of TiO(acac)2, and 1 equivalent of
Li2CO3 in chloroform. After stirring overnight, the sol-
vent was removed under reduced pressure to afford the
complexes in quantitative yield as red solids.
Common solvents used for study of the ‘monomer-dimer’
system were methanol, which shifts the equilibrium to-
wards the dinuclear complex and dimethyl sulfoxide fa-
RO
O
O
O
Ti
O
RO
O
RO
O
O
OR
Ti4+
LI+
Li2
OH
OH
O
O
step 1:
first recognition
event
O
step 2:
second recognition
event
O
O
O
O
Ti
O
O
RO
O
O
OR
OR
O
O
OR
Li
Li
RO
Li
Li
RO
O
O
In earlier studies we have shown that the equilibrium be-
tween the mononuclear complex and the dinuclear heli-
cate (see Scheme 1) relies on the polarity of the solvent.4,5
By dissolving crystals of the dimeric species in different
solvents, different equilibrium mixtures of monomer and
dimer occur instantaneously.
1H NMR spectrum of the complex Li[Ti2(1a)6Li3] with
methyl groups show diasteretopic splitting and – com-
pared to the free ligand – high-field shift of the benzylic
O
Ti
O
O
O
O
O
Scheme 1 Hierarchical formation of triply lithium-bridged dinu-
clear titanium(IV) helicates
SYNTHESIS 2010, No. 6, pp 0953–0958
x
x
.
x
x
.2
0
1
0
Advanced online publication: 24.02.2010
DOI: 10.1055/s-0029-1218684; Art ID: Z18109SS
© Georg Thieme Verlag Stuttgart · New York

954
M. Baumert et al.
PAPER
PrO
O
PrO
O
OH
RX
K2CO3
LiAlH4
HO
OH
RO
OR
RO
OR
OH
OR
4a: R = Me
4b: R = C14H29
OR
5a: R = Me
5b: R = C14H29
3
HO
O
OR
RO
RO
OAc
OAc
Br
PBr3
7
O
O
K2CO3
RO
OR
OAc
OAc
OR
8a: R = Me
8b: R = C14H29
6a: R = Me
6b: R = C14H29
OR
Figure 2 1H NMR spectrum of dimeric Li[Ti2(1b)6Li3] in CDCl3
RO
RO
K2CO3
MeOH, H2O
O
O
methanol). A spectroscopic probe are the diastereotopic
protons e of the benzylic group at d = 4.54 (d, J = 8.2 Hz,
6 H) and 4.00 (br, 6 H). The latter signal is observed as a
‘shoulder’ of the multiplet, which is assigned to the meth-
ylene groups of the alkyl chains connected to the ether ox-
ygen atoms at d = 3.88. The observation of diastereotopic
behavior of those protons clearly shows the presence of
the dimeric species. In the case of the monomer, fast race-
mization would take place and would result in only one
singlet. The lack of this resonance indicates that the
dimer-monomer equilibrium is strongly shifted towards
the dimer.
OH
OH
1a-H2: R = Me
1b-H2: R = C14H29
Scheme 2 Ligand synthesis 1a,b-H2
The dimer Li3[Ti2(1b)6]– is observed as a peak at m/z =
5392 in ESI FT-ICR-MS studies in THF–methanol.
The model complex Li4[Ti2(1a)6] shows good solubility
in a polar solvent like methanol revealing the presence of
the dimeric species. Adding nonpolar side chains to obtain
Li4[Ti2(1b)6] allows us to dissolve the complex even in
chloroform. In this solvent, the lithium cations cannot be
solvated and therefore the dimer is further stabilized and
seems to be the exclusive species.
Figure 1 1H NMR spectrum of dimeric Li[Ti2(1a)6Li3] in CD3OD
protons f at d = 4.31 (d, J = 8.2 Hz, 6 H) and 3.89 (d, J =
8.2 Hz, 6 H) (Figure 1), which is typical for the dimeric
species.
Hierarchical Assembly of Highly Hydrophilic Heli-
cates
In order to test the possibilities to tune the polarity of our
complexes to the extremes we prepared the carboxylic
acid substituted ligand 2-H2 (Scheme 3). The synthetic
procedure follows a simple basic ester coupling as the key
reaction with some additional protective group transfor-
mations. Initially the carboxylic acid function of 4-bro-
mobutyryl chloride (9) is reacted with benzyl alcohol.
Subsequently the protected bromide 10 is coupled in a
Williamson ether synthesis9 with 2,3-dibenzoxybenzoic
The monomer-dimer equilibrium of the nonpolar complex
Li4[Ti2(1b)6] with long alkyl-substituents was studied in
deuterochloroform. To improve the quality of the NMR
signals a minute amount of methanol was added. 1H NMR
spectroscopy revealed the presence of only one species
(Figure 2).
1
The H NMR spectrum shows all relevant signals with
some broadening due to aggregation of the complexes in
solution (this is suppressed by addition of small amount of
Synthesis 2010, No. 6, 953–958 © Thieme Stuttgart · New York

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Hierarchically Assembled Helicates
955
acid (11) under basic conditions and the resulting ligand stereotopic splitting and no significant high field shifts are
precursor 12 is deprotected by hydrogenation in the pres- detected as expected for the quickly racemizing monomer.
ence of palladium on charcoal to yield ligand 2-H2 (over- The second, dimeric species shows two diastereotopic
all: 79%).
protons at d = 3.51 and 2.88 indicating the dimer to be
configuratively stable. The high field shifts of Hd and Hd¢
are typical for helicate formation due to the location of the
CH2 ester protons close to the aromatic unit in the dimer.
As additional species traces of free ligand could be detect-
ed due to some minor hydrolysis of the complex.
O
O
BzOH
Br
Br
Cl
BzO
9
10
HO
O
1
For comparison, we measured the H NMR spectrum of
Li4[Ti2(2)6] in deuterated methanol (Figure 3b). In this
case we only detected the dimeric species, which showed
the typical high field shift and two signals for the diaste-
reotopic protons at d = 3.60 (br, 6 H) and 3.05 (br, 6 H).
OBz
OBz
BzO2C
O
O
H2, Pd/C
11
K2CO3
OBz
OBz
Negative ESI-MS investigations in H2O–MeOH show the
dimeric species [Li3Ti2(2)6]– as the only peak at m/z =
1547.
12
HO2C
O
O
Herein we have described the synthesis of highly nonpolar
1a,b-H2 and highly polar ligands 2-H2 as well as the cor-
responding complexes Li[Li3[Ti2(1a,b, 2)6]. The mono-
mer-dimer equilibrium leading to the hierarchical helicate
formation is closely connected to the reaction media. By
tuning the polarity we increased the band width of the
concept to create helicates by hierarchical self-assembly.
The combination of nonpolar reaction media with hydro-
phobic esters as carbonyl donors leads exclusively to the
formation of lithium templated dimeric helicates. By us-
ing a polar ligand and changing the solvent to water,
which is an excellent lithium solvating media, we got the
mononuclear complex as major product. Surprisingly we
still were able to observe the dimeric complex in signifi-
cant amounts. This unexpected stability of the helicate
type complex is probably due to protonation/deprotona-
tion equilibrium at the carboxylate ester substituents,
leading to an enhanced negative charge and stronger elec-
trostatic attraction of the bridging lithium cations. Also,
the multivalency effect of the three identical pockets for
lithium coordination may play a role: Once the first lithi-
um is bound, the two monomers are much better preorga-
nized for coordination of the second, which again
increases preorganization of the complex for the third lith-
ium ion. The results presented here show that we can
modify the polarity features of the complexes leading to
soluble systems in a broad variety of solvents. This might
be of interest for processing of related derivatives, which
can have some specific properties.
OH
OH
2-H2
Scheme 3 Synthesis of 2-H2
The titanium(IV) complex Li2[Ti(2)3] was prepared by
dissolving 3 equivalents of the corresponding ligand 2-H2,
1 equivalent TiO(acac)2, and 1 equivalent Li2CO3 in
methanol. After stirring overnight, the solvent was re-
moved under reduced pressure to give the complex in
quantitative yield as red solid.
The complex Li4[Ti2(2)6] is soluble in methanol and even
in water. The H NMR in D2O (Figure 3c) reveals the
presence of three different species: two coordination com-
pounds and the free ligand. For the major species no dia-
1
NMR spectra were recorded with a Varian Mercury 300 or Inova
400 spectrometer. FT-IR spectra were recorded by diffuse reflection
(KBr) on a Bruker IFS spectrometer. Mass spectra were measured
on a Finnigan SSQ 7000 or a ThermoFisher Scientific LTQ-Orbi-
trap XL. Elemental analyses were obtained with a Heraeus CHN-O-
Rapid analyzer. Melting points: Büchi B-540 (uncorrected). Chem-
icals were used as received by commercial suppliers.
Alkyl Aryl Ethers 4a,b; General Procedure
Figure 3 1H NMR spectra of a) ligand 2-H2 in CD3OD; b) dimeric
Li[Ti2(2)6Li3] in CD3OD; c) Li2[Ti(2)3]/Li[Ti2(2)6Li3] in D2O;
(M = monomer, D = dimer, L = free ligand)
Gallic acid propyl ester (3; 4.2 g, 20 mmol, 1 equiv), K2CO3 (17.4
g, 120 mmol, 6 equiv), and MeI (9.9 g, 70 mmol, 3.5 equiv) or 1-
bromotetradecane (19.4 g, 70 mmol, 3.5 equiv) were suspended in
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956
M. Baumert et al.
PAPER
acetone (150 mL) and refluxed for 48 h. Then, H2O (50 mL) was
added. Acetone was removed under reduced pressure and the aque-
ous phase was extracted with CH2Cl2 (2 × 20 mL). The combined
organic phases were dried (Na2SO4), the solvent was removed under
vacuum, and the residue dried under high vacuum.
13C NMR (75 MHz, CDCl3): d = 153.2 (C), 136.0 (C), 15.3 (CH),
69.1 (CH2), 65.7 (CH2), 32.0 (CH3), 29.9 (CH2), 29.8 (CH2), 29.7
29.9 (CH2), 29.5 (CH2), 29.4 (CH2), 26.2 (CH2), 22.8 (CH2), 14.2
(CH3).
EI-MS: m/z = 745 [M]+.
Anal. Calcd for C49H92O4: C, 78.97; H, 12.44. Found: C, 78.89; H,
11.48.
3,4,5-Trimethoxybenzoic Acid Propyl Ester (4a)
Yield: 5.1 g (quant); colorless oil.
IR (KBr): 2963, 2839, 1715, 1590, 1502, 1461, 1415, 1335, 1227,
1181, 1126, 1002, 764 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.23 (s, 2 H), 4.20 (t, J = 6.9 Hz,
2 H), 3.84 (s, 6 H), 3.82 (s, 3 H), 1.73 (m, 2H), 0.95 (t, J = 6.9 Hz,
3 H).
13C NMR (75 MHz, CDCl3): d = 165.9 (C), 152.9 (C), 142.2 (C),
124.8 (C), 108.0 (CH), 73.5 (CH2), 66.5 (CH2), 62.3 (CH3), 55.1
(CH3), 10.6 (CH3).
Bromination of the Alcohol Function; General Procedure
Compound 5 (5a: 2.0 g, 5b: 7.4 g, 10 mmol, 3 equiv) was dissolved
in Et2O (20 mL) and pyridine (2 equiv) was added. The solution was
cooled to –20 °C, PBr3 (1 equiv) was added, and the suspension was
stirred overnight. H2O (10 mL) was added, the phases were separat-
ed, the organic layer was dried (Na2SO4), and the solvent removed
under reduced pressure.
3,4,5-Trimethoxybenzyl Bromide (6a)
Yield: 2.1 g (80%); colorless solid; mp 76 °C.
EI-MS: m/z = 254 [M]+.
Anal. Calcd for C13H18O5: C, 61.41; H, 7.13. Found: C, 61.55; H,
7.28.
IR (KBr): 2940, 2837, 1589, 1506, 1463, 1424, 1329, 1244, 1207,
1125, 989, 830, 780, 664, 596, 545 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.54 (s, 2 H), 4.39 (s, 2 H), 3.80
3,4,5-Tristetradecyloxybenzoic Acid Propyl Ester (4b)
Yield: 11.1 g (69%); colorless solid; mp 31–33 °C.
(s, 6 H), 3.77 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 153.2 (C), 138.1 (C), 133.1 (C),
106.1 (CH), 60.9 (CH3), 56.2 (CH3), 34.4 (CH2).
EI-MS: m/z = 262 [M + H]+, 181 [M – Br]+.
IR (KBr): 2924, 2854, 1718, 1588, 1463, 1432, 1334, 1215, 1114,
761 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.26 (s, 2 H), 4.26 (t, J = 6.6 Hz,
2 H), 4.01 (t, J = 6.6 Hz, 6 H), 1.79 (m, 8 H), 1.46 (m, 6 H), 1.27
(br, 60 H), 1.02 (t, J = 6.6 Hz, 6 H), 0.88 (t, J = 6.6 Hz, 6 H).
Anal. Calcd for C10H13BrO3: C, 46.00; H, 5.02. Found: C, 46.48; H,
4.94.
13C NMR (75 MHz, CDCl3): d = 166.5 (C), 152.8 (C), 142.3 (C),
125.0 (C), 108.0 (CH), 73.5 (CH2), 69.2 (CH2), 66.5 (CH2), 31.9
(CH2), 29.7 (CH2), 29.6 (CH2), 29.5 (CH2,), 29.3 (CH2), 26.1 (CH2),
22.1 (CH2), 14.1 (CH3), 10.5 (CH3); some CH2 groups were not ob-
served due to overlap of the resonances.
3,4,5-Tristetradecyloxybenzyl Bromide (6b)
Yield: 8.0 g (quant); colorless solid; mp 49–50 °C.
IR (KBr): 2923, 2853, 1591, 1503, 1462, 1335, 1243, 1121, 724
cm–1.
EI-MS: m/z = 811 [M]+.
1H NMR (400 MHz, CDCl3): d = 6.50 (s, 2 H), 4.36 (s, 2 H), 3.90
(m, 6 H), 1.78 (m, 6 H), 1.37 (br, 6 H), 1.20 (br, 60 H), 0.81 (t,
J = 6.6 Hz, 9 H).
13C NMR (100 MHz, CDCl3): d = 153.1 (C), 138.3 (C), 132.5 (C),
107.5 (CH), 69.1 (CH2), 34.7 (CH2), 33.0 (CH2), 29.9 (CH2), 29.8
(CH2), 29.7 (CH2), 29.5 (CH2), 26.2 (CH2), 22.8 (CH2), 14.2 (CH3);
some groups were not observed due to overlap of the resonances.
Anal. Calcd for C52H96O5·H2O: C, 76.13; H, 12.16. Found: C, 76.43;
H, 11.67.
Reduction of the Esters 4a,b to Benzyl Alcohols 5a,b; General
Procedure
Compound 4 (4a: 2.5 g, 4b: 8.1 g, 10 mmol, 1 equiv) was dissolved
in Et2O (100 mL). LiAlH4 (1 equiv) was added slowly and stirred
for 4 h. H2O (10 mL) was added, the solution neutralized with
H2SO4 (10%), and the phases were separated. The organic layer was
washed with brine (30 mL), dried (Na2SO4), and the solvent was re-
moved under vacuum.
EI-MS: m/z = 808 [M]+.
Anal. Calcd for C49H91BrO3: C, 72.82; H, 11.35. Found: C, 71.57;
H, 10.87.
Ester Formation and Cleavage of the Protective Groups; Gen-
eral Procedure
3,4,5-Trimethoxybenzyl Alcohol (5a)
The bromide 6 (6a: 0.5 g, 6b: 1.6 g, 2 mmol, 1 equiv), K2CO3 (1.7
g, 12 mmol, 6 equiv), and 2,3-diacetoxybenzoic acid (7; 0.3 g, 2
mmol, 1 equiv) were suspended in acetone (30 mL) and refluxed for
2 h. H2O (10 mL) was added and the mixture extracted with CH2Cl2
(2 × 15 mL). The combined organic layers were dried (Na2SO4) and
the solvent was removed. The crude product was purified by flash
chromatography (8a: CH2Cl2, 8b: n-pentane–CH2Cl2, gradient 4:1
to 2:1). Compound 8 (1 equiv) and K2CO3 (1 equiv) were refluxed
for 2 h in H2O–acetone (1:10) mixture. The suspension was filtered
and the crude product was purified by flash chromatography in the
case of 1a-H2 (CH2Cl2). CH2Cl2–pentane (4:1) was used as eluent
for 1b-H2.
Yield: 1.7 g (86%); lightly yellow oil.
IR (KBr): 3401, 2942, 1594, 1505, 1460, 1424, 1331, 1237, 1128,
1058, 1009, 830 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.61 (s, 2 H), 4.57 (s, 2 H), 3.79
(s, 6 H), 3.76 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 153.1 (C), 137.0 (C), 136.9 (C),
103.6 (CH), 65.0 (CH2), 60.8 (CH3), 56.0 (CH3).
EI-MS: m/z = 198 [M]+.
3,4,5-Tristetradecyloxybenzyl Alcohol (5b)
Yield: 7.4 g (quant); colorless solid; mp 50–51 °C.
2,3-Dihydroxybenzoic Acid 3,4,5-Trimethoxybenzyl Ester (1a-
H2)
Yield: 0.3 g (42%); colorless solid; mp 136 °C.
IR (KBr): 2922, 2852, 1593, 1509, 1466, 1438, 1341, 1230, 1129,
726 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.49 (s, 2 H), 4.52 (s, 2 H), 3.89
(m, 6 H), 1.74 (m, 6 H), 1.22 (br, 66 H), 0.81 (t, J = 6.6 Hz, 9 H).
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Hierarchically Assembled Helicates
957
IR (KBr): 3430, 2942, 2840, 1737, 1669, 1595, 1509, 1464, 1425,
1333, 1307, 1238, 1129, 1007, 822, 758 cm–1.
5.08 (s, 2 H), 4.29 (t, J = 6.3 Hz, 2 H), 2.45 (t, J = 6.3 Hz, 2 H), 2.03
(ps q, J = 6.3 Hz, 2 H).
1H NMR (400 MHz, CD3OD): d = 7.21 (dd, J = 8.0, 1.7 Hz, 1 H),
6.93 (dd, J = 8.0, 1.7 Hz, 1 H), 6.70 (s, 2 H), 6.65 (t, J = 8.0 Hz, 1
H), 5.23 (s, 2 H), 3.78 (s, 6 H), 3.67 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 170.1 (C), 153.4 (C), 149.0 (C),
145.1 (C), 138.3 (C), 132.4 (C), 120.6 (CH), 120.0 (CH), 119.3
(CH), 112.4 (C), 105.7 (CH), 67.4 (CH2), 60.9 (CH3), 56.2 (CH3).
13C NMR (75 MHz, CDCl3): d = 172.7 (C), 166.2 (C), 152.8 (C),
148.3 (C), 137.5 (C), 136.6 (C), 135.9 (C), 128.6 (CH), 128.5 (CH),
128.4 (CH), 128.3 (CH), 128.2 (CH, double int.), 128.1 (CH), 127.9
(CH), 127.6 (CH), 127.0 (C), 124.0 (CH), 122.8 (CH), 118.0 (CH),
75.7 (CH2), 71.3 (CH2), 66.4 (CH2), 64.1 (CH2), 30.9 (CH2), 24.1
(CH2).
ESI-MS (+, CHCl3): m/z = 517 [M + Li]+.
EI-MS: m/z = 334 [M]+.
Anal. Calcd for C17H18O7·0.5H2O: C, 59.48; H, 5.58. Found: C,
59.88; H, 6.23.
2,3-Dihydroxybenzoic Acid 3-Carboxypropyl Ester (2-H2)
Ligand precursor 12 (0.3 g, 0.5 mmol, 1 equiv) was dissolved in
EtOAc (50 mL), 10% Pd/C catalyst (30 mg) was added, and the
mixture stirred for 12 h under H2 atmosphere (10 bar). The catalyst
was filtered off and the solvent removed under reduced pressure to
give the product as a colorless solid; yield: 120 mg (quant); mp
51 °C.
2,3-Dihydroxybenzoic Acid 3,4,5-Tristetradecyloxybenzoyl Es-
ter (1b-H2)
Yield: 0.5 g (29%); colorless solid; mp 39–44 °C.
IR (KBr): 3565, 2921, 2851, 1672, 1593, 1469, 1438, 1383, 1302,
1236, 1121, 968, 752, 723 cm–1.
IR (KBr): 3465, 3101, 3039, 2965, 2363, 2339, 1729, 1668, 1470,
1408, 1311, 1273, 1159, 1067, 994, 761, 591 cm–1.
1H NMR (400 MHz, CD3OD): d = 7.22 (dd, J = 8.0, 1.4 Hz, 1 H),
6.90 (dd, J = 8.0, 1.4 Hz, 1 H), 6.65 (t, J = 8.0 Hz, 1 H), 4.29 (t,
J = 6.3 Hz, 2 H), 2.37 (t, J = 6.3 Hz, 2 H), 1.98 (ps q, J = 6.3 Hz, 2
H).
1H NMR (400 MHz, CDCl3): d = 10.84 (s, 1 H, OH), 7.39 (dd,
J = 8.0, 1.4 Hz, 1 H), 7.10 (dd, J = 8.0, 1.4 Hz, 1 H), 6.79 (t, J = 8.0
Hz, 1 H), 6.61 (s, 2 H), 5.64 (s, 1 H, OH), 5.27 (s, 2 H), 3.97 (m, 6
H), 1.78 (m, 6 H), 1.46 (br, 6 H), 1.26 (br, 60 H), 0.88 (t, J = 8.0 Hz,
9 H).
13C NMR (75 MHz, CDCl3): d = 170.1 (C), 153.3 (C), 148.9 (C),
145.1 (C), 138.6 (C), 130.0 (C), 120.7 (CH), 119.9 (CH), 119.2
(CH), 112.5 (C), 107.2 (CH), 69.2 (CH2), 31.9 (CH2), 30.3 (CH2),
29.8 (CH2), 29.7 (CH2), 29.6 (CH2), 29.3 (CH2), 26.2 (CH2), 22.7
(CH2), 14.1 (CH3); some groups are not observed due to overlap of
the resonances.
13C NMR (100 MHz, CDCl3): d = 175.1 (C), 170.2 (C), 149.8 (C),
145.6 (C), 120.3 (CH), 119.8 (CH), 118.6 (CH), 112.4 (C), 64.4
(CH2), 30.2 (CH2), 23.9 (CH2).
EI-MS: m/z = 240 [M]+.
Anal. Calcd for C11H12O6: C, 55.00; H, 5.04. Found: C, 55.26; H,
5.24.
ESI-MS (+, MeOH): m/z = 905 [M + Na]+.
Anal. Calcd for C56H96O7·H2O: C, 74.79; H, 10.98. Found: C, 74.74;
H, 11.07.
Titanium(IV) Complexes of Ligands 1 and 2; General Proce-
dure
Catechol ligand 1a,b-H2, 2-H2 (1a-H2: 33 mg, 1b-H2: 82 mg, 2-H2:
24 mg, 0.1 mmol, 3 equiv), titanyl bis(acetylacetonate) (8.7 mg, 1
equiv), and Li2CO3 (2.5 mg, 1 equiv) were dissolved in CHCl3 or
MeOH (10 ml), and the mixture was stirred overnight. The solvent
was removed and the residue dried under vacuum to afford the
ligands as red solids in quantitative yield.
4-Bromobutyric Acid Benzyl Ester (10)
To a solution of 4-bromobutyryl chloride (9; 0.4 g, 2 mmol, 1 equiv)
in CHCl3 (10 mL) were added benzylic alcohol (0.2 g, 1 equiv) and
Et3N (0.2 g, 1 equiv), and the mixture was stirred overnight. H2O (2
mL) was added, the CHCl3 layer was dried (Na2SO4), and the sol-
vent removed under reduced pressure to give the crude product as
colorless oil; yield: 0.5 g (89%).
Li4[Ti2(1a)6]
Yield: 35 mg.
IR (KBr): 3443, 3033, 2920, 2850, 1735, 1450, 1383, 1309, 1269,
1173, 1125, 991, 746, 698 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.35 (m, 5 H), 5.13 (s, 2 H), 3.45
(t, J = 6.4 Hz, 2 H), 2.55 (t, J = 6.4 Hz, 2 H), 2.19 (ps q, J = 6.4 Hz,
2 H).
13C NMR (75 MHz, CDCl3): d = 172.4 (C), 135.8 (C), 128.6 (CH),
128.3 (CH), 128.2 (CH), 66.7 (CH2), 32.7 (CH2), 32.5 (CH2), 27.8
(CH2).
IR (KBr): 3433, 2944, 1681, 1594, 1508, 1449, 1382, 1336, 1296,
1254, 1218, 1125, 1007, 817, 748, 691, 577, 535 cm–1.
1H NMR (400 MHz; CD3OD): d = 7.09 (dd, J = 8.2, 1.7 Hz, 6 H),
6.55 (dd, J = 8.2, 1.7 Hz, 6 H), 6.47 (t, J = 8.2 Hz, 6 H), 6.41 (s, 12
H), 4.31 (d, J = 8.2 Hz, 6 H), 3.89 (d, J = 8.2 Hz, 6 H), 3.59 (s, 36
H), 3.58 (s, 18 H).
ESI-MS (–, CHCl3–MeOH): m/z = 2148 [Li4Ti2(1a)6CH3O]–.
ESI-MS (+, CHCl3–MeOH): m/z = 1065 [Li3Ti(1a)3]+.
EI-MS: m/z = 258 [M + H]+.
Anal. Calcd for C102H96Li4O42Ti2·5H2O: C, 55.48; H, 4.84. Found:
C, 55.68; H, 5.34.
2,3-Bisbenzyloxybenzoic Acid 3-Benzyloxycarbonylpropyl Es-
ter (12)
Bromide 10 (0.3 g, 1 mmol, 1 equiv), 2,3-dibenzoxybenzoic acid
(11; 0.2 g, 1 equiv), and K2CO3 (0.4 g, 3 equiv) were suspended in
acetone (10 mL) and the mixture refluxed for 3 h. The salts were fil-
tered off, the solvent removed under reduced pressure, and the
crude product purified by flash chromatography (CH2Cl2) to give
the desired product as a colorless oil; yield: 0.5 g (89%).
Li4[Ti2(1b)6]
Yield: 90 mg.
IR (KBr): 2924, 2853, 1679, 1593, 1447, 1382, 1334, 1295, 1257,
1220, 1116, 996, 820, 747, 695, 543 cm–1.
1H NMR (300 MHz, CD3OD–CDCl3, 1:2): d = 7.21 (d, J = 8.2 Hz,
6 H), 6.66 (d, J = 8.2 Hz, 6 H), 6.14 (t, J = 8.2 Hz, 6 H), 6.44 (s, 12
H), 4.54 (d, J = 8.2 Hz, 6 H), 4.00 (br, 6 H), 3.88 (m, 36 H), 1.74
(m, 36 H), 1.44 (br, 36 H), 1.28 (br, 36 H), 0.89 (m, 54 H).
IR (KBr): 3033, 2951, 1730, 1581, 1464, 1379, 1264, 1157, 1088,
1044, 979, 911, 737, 698 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.33 (m, 16 H), 7.13 (dd, J = 8.2,
1.7 Hz, 1 H), 7.96 (t, J = 8.2 Hz, 1 H), 5.13 (s, 2 H), 5.10 (s, 2 H),
ESI-MS (–, THF–MeOH): m/z = 5392 [Li3Ti2(1b)6]–.
Synthesis 2010, No. 6, 953–958 © Thieme Stuttgart · New York

958
M. Baumert et al.
PAPER
Chem. 2009, 121, 1117. (c) Pradeep, C. P.; Long, D.-L.;
Newton, G. N.; Song, Y.-F.; Cronin, L. Angew. Chem. Int.
Ed. 2008, 47, 4388; Angew. Chem. 2008, 120, 4460.
(d) Cheglakov, Z.; Weizmann, Y.; Braunschweig, A. B.;
Wilner, O. I.; Willner, I. Angew. Chem. Int. Ed. 2008, 47,
126; Angew. Chem. 2008, 120, 132. (e) Matsuura, K.;
Murasato, K.; Kimizuka, N. J. Am. Chem. Soc. 2005, 127,
10148.
Anal. Calcd for C168H282Li2O21Ti·6H2O: C, 71.86; H, 10.69. Found:
C, 71.90; H, 10.40.
Li4[Ti2(2)6]
Yield: 26 mg.
IR (KBr): 3364, 2954, 2320, 1729, 1676, 1592, 1563, 1442, 1296,
1253, 1214, 1156, 1064, 1012, 987, 806, 746, 680 cm–1.
1H NMR (300 MHz, CD3OD): d = 7.09 (m, 6 H), 6.57 (m, 12 H),
3.60 (br, 6 H), 3.05 (br, 6 H), 2.28 (t, J = 7.2 Hz, 12 H), 1.72 (ps q,
J = 7.2 Hz, 12 H).
1H NMR (300 MHz, D2O): d [dimer (minor species)] = 7.38 (d,
J = 8.1 Hz, 6 H), 7.15 (d, J = 8.1 Hz, 6 H), 6.75 (t, J = 8.1 Hz, 6 H),
3.51 (m, 6 H), 2.88 (m, 6 H), 2.15 (t, J = 7.4 Hz, 12 H), 1.82 (ps q,
J = 7.4 Hz, 12 H); d [monomer (major species)] = 7.07 (d, J = 7.9
Hz, 3 H), 6.55 (m, 6 H), 4.14 (t, J = 6.3 Hz, 6 H), 2.27 (t, J = 6.3 Hz,
6 H), 1.88 (ps q, J = 6.3 Hz, 6 H).
(3) (a) Klug, A. Angew. Chem., Int. Ed. Engl. 1983, 22, 565;
Angew. Chem. 1983, 95, 579. (b) Tan, W. S.; Lewis, C. L.;
Horelik, N. E.; Pregibon, D. C.; Doyle, P. S.; Yi, H.
Langmuir 2008, 24, 12483.
(4) (a) Albrecht, M.; Baumert, M.; Klankermayer, J.; Kogej, M.;
Schalley, C. A.; Fröhlich, R. Dalton Trans. 2006, 4395.
(b) Albrecht, M.; Fiege, M.; Baumert, M.; de Groot, M.;
Fröhlich, R.; Russo, L.; Rissanen, K. Eur. J. Inorg. Chem.
2007, 609.
(5) Albrecht, M.; Mirtschin, S.; de Groot, M.; Janser, I.;
Runsink, J.; Raabe, G.; Kogej, M.; Schalley, C. A.; Fröhlich,
R. J. Am. Chem. Soc. 2005, 127, 10371.
(6) Reviews on helicates: (a) Piguet, C.; Bernardinelli, G.;
Hopfgartner, G. Chem. Rev. 1997, 97, 2005. (b) Albrecht,
M. Chem. Rev. 2001, 101, 3457. (c) Hannon, M. J.; Childs,
L. J. Supramol. Chem. 2004, 16, 7. (d) Albrecht, M. Bull.
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(7) Terazzi, E.; Torelli, S.; Bernardenielli, G.; Rivera, J.-P.;
Benech, J.-M.; Bourgogne, C.; Donnio, B.; Guillon, D.;
Imbert, D. G.; Bünzli, J.-C.; Pinto, A.; Jeannerat, D.; Piguet,
C. J. Am. Chem. Soc. 2005, 127, 888.
ESI-MS (+, H2O–MeOH): m/z = 1547 [Li5Ti2(2)6]+.
Anal. Calcd for C33H27O18Li2Ti·3H2O: C, 47.51; H, 3.99. Found: C,
47.64; H, 4.51.
Acknowledgment
Financial support by the Deutsche Forschungsgemeinschaft (DFG)
and the Fonds der Chemischen Industrie is gratefully acknowled-
ged.
(8) Tanabe, K.; Yasuda, K.; Yoshio, M.; Kato, T. Org. Lett.
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Synthesis 2010, No. 6, 953–958 © Thieme Stuttgart · New York