Dinuclear titanium(IV) complex of p-tert-butylthiacalix[4]arene as a novel bidentate Lewis acid catalyst

Article abstract of DOI:10.1016/S0040-4039(02)01833-6

Treatment of p-tert-butylthiacalix[4]arene (H₄L, 2) with TiCl₄ in dichloromethane gave two novel dinuclear titanium(IV) complexes formulated as [Ti₂LCl₄]. One of the complexes was subjected to X-ray crystallogra

Full text of DOI:10.1016/S0040-4039(02)01833-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7769–7772
Dinuclear titanium(IV) complex of p-tert-butylthiacalix[4]arene
as a novel bidentate Lewis acid catalyst
a, ,†
a
a
b
Naoya Morohashi, * Tetsutaro Hattori, Katsuya Yokomakura, Chizuko Kabuto and
a,
Sotaro Miyano *
a
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Aramaki-Aoba 07, Aoba-ku,
Sendai 980-8579, Japan
b
Instrumental Analysis Center for Chemistry, Graduate School of Science, Tohoku University, Aoba, Aoba-ku, Sendai 980-8578,
Japan
Received 24 July 2002; revised 19 August 2002; accepted 23 August 2002
Abstract—Treatment of p-tert-butylthiacalix[4]arene (H L, 2) with TiCl in dichloromethane gave two novel dinuclear titaniu-
4
4
m(IV) complexes formulated as [Ti LCl ]. One of the complexes was subjected to X-ray crystallographic analysis to show that the
2
4
4−
calixarene ligand (L ) adopted a cone conformation, forcing the two metal centers to reside in close vicinity with syn arrangement
with respect to the mean plane defined by the macrocycle (3). The other one was assigned to be an anti titanium(IV) complex (4)
1
based on H NMR spectroscopy. The syn complex showed high catalytic activity in the Mukaiyama–aldol reaction of aromatic
aldehydes with silyl enol ethers, indicating the double-activation ability of the bidentate Lewis acid toward the aldehydes. © 2002
Elsevier Science Ltd. All rights reserved.
Polynuclear metal complexes have attracted much inter-
1
est in the field of metal catalysis. The metal centers
located close in such complexes may activate substrate
molecule(s) cooperatively or simultaneously, and/or
migrate the substrate between the metal centers, which
cannot be realized by mononuclear metal complexes.
Therefore, polynuclear complexes are expected to show
special catalysis or high performance in catalytic activ-
ity. Recently, we have introduced new members of
calix[4]arenes, in which the four methylene bridges of
calix[4]arene (e.g. 1) are replaced by epithio (e.g. 2),
2
,3
sulfinyl or sulfonyl linkages. They show marked abil-
ity to form metal complexes without the need to modify
the upper and/or lower rim, as is the case for the
Furthermore, the sulfur-based calix[4]arenes can form
not only mono- but also polynuclear metal complexes
by virtue of the heterogeneous coordination sites.
4
6,7
conventional calix[4]arenes. This is attributed to the
ligation of the sulfur-based functionalities to a metal
center in cooperation with the phenoxy oxygens, as
Therefore, our attention has been focused on designing
polynuclear metal complexes of the sulfur-based
calix[4]arenes, which should be suitable for metal cata-
5
revealed by solvent extraction studies and X-ray crys-
6
8
tallographic analyses.
lysts. As a part of such efforts, we report, herein, the
synthesis of dinuclear titanium(IV) complexes (3,4) of
p-tert-butylthiacalix[4]arene (2) and the application of
the former as a bidentate Lewis acid catalyst for the
Keywords: calixarene; titanium complex; aldol reaction; X-ray crystal-
lographic analysis.
9,10
Mukaiyama–aldol reaction.
*
Corresponding authors. Tel./fax: +81-22-217-7262; e-mail:
miyano@orgsynth.che.tohoku.ac.jp
Present address: Department of Materials Science and Engineering,
Faculty of Engineering, Yamagata University, 3-16, Jonan,
Yonezawa, Yamagata 992-8510, Japan.
Reaction of thiacalixarene 2 with an excess of TiCl in
4
†
dichloromethane led to the formation of two complexes
3 and 4, the latter being essentially insoluble in the
11
solvent (Scheme 1). Fortunately, diffusion of hexane
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01833-6

7
770
N. Morohashi et al. / Tetrahedron Letters 43 (2002) 7769–7772
Scheme 1.
to a solution of complex 3 in dichloromethane under
nitrogen gave single crystals, one of which was sub-
12
jected to X-ray crystallographic analysis (Fig. 1). The
complex consisted of two titanium ions, a tetraanion of
4
−
thiacalixarene (L ), four chlorine ions and an aqua
ligand to form [Ti LCl (H O)]. Although the operation
2
4
2
proceeded under nitrogen, the water molecule seemed
to have been introduced to the complex during recrys-
tallization, showing the high oxophilicity of complex 3
4
−
(
vide infra). The L ligand adopted a cone conforma-
1
Figure 2. Partial H NMR spectra of thiacalixarene 2 in
tion and coordinated to each metal ion in a tridentate
fashion via the two phenoxy oxygens and an epithio
function. Therefore, the two titanium ions occupied syn
positions with respect to the mean plane defined by the
macrocycle. The metal centers had a distorted octahe-
dral environment bridged by the water molecule, a C2
symmetry axis passing through the center of the cavity
CD Cl on progressive addition of TiCl . (a) R=[TiCl ]/[2]=
2
2
4
4
−3
4, (b) R=2, (c) R=1, (d) R=0, where [2]=6.3 mmol dm .
13
conformation,
as long as the complexes are
monomeric. Complex 4 was, therefore, assumed to
adopt a 1,2-alternate conformation with an anti
arrangement of the two titanium ions based on the
titration study and the stereochemistry of complex 3.
4
−
of the L ligand.
In order to gain insight into the complexation behavior,
1
a H NMR titration experiment was carried out. In the
absence of TiCl , the spectrum of thiacalixarene 2 in
The highly oxophilic nature of complex 3 was
attributed to simultaneous coordination of the oxygen
atom of a water molecule to the two titanium centers
exquisitely held by a thiacalixarene ligand, which
tempted us to examine the double-activation ability of
the complex toward carbonyl compounds in the
4
dichloromethane-d showed three singlets correspond-
2
ing to tert-butyl, aromatic and hydroxy protons (Fig.
2
d). As 2 mol equiv. of TiCl was added portionwise to
4
the solution of thiacalixarene 2, new signals, including
those assigned to complex 3, appeared (Fig. 2c). During
the time course, complex 4 was precipitated. On reach-
14
Mukaiyama–aldol reaction (Table 1). To our plea-
sure, the reaction of benzaldehyde with silyl enol ether
ing the molar ratio of TiCl : 2 to 2:1, all the signals of
4
free ligand 2 disappeared and only the signals of com-
plex 3 were observed (Fig. 2b). Further increase in the
molar ratio did not cause any spectral change (Fig. 2a).
These observations may indicate that complexes 3 and
5
in the presence of 5 mol% of complex 3 proceeded
smoothly at −78°C to give b-hydroxy ketone 7 quanti-
tatively in 15 min (entry 1), while a control reaction
using complex 4 as a catalyst gave the product in only
4
+
4
have a stoichiometry of Ti :2=2:1. Both complexes
2
% yield (entry 2). The catalytic activity of complex 3
1
showed the same pattern of H NMR peaks in THF-d ,
8
was clearly superior even to that of TiCl (entry 3).
4
that is, one singlet assigned to tert-butyl and two
These observations will indicate that complex 3 acts as
a bidentate Lewis acid, which strongly enhances the
reactivity of the aldehyde toward ether 5 via the double
electrophilic activation of the carbonyl moiety as
depicted in Fig. 3b, whereas TiCl and complex 4 act
11
doublets to aromatic protons, which indicates that the
thiacalixarene ligand adopts a cone or 1,2-alternate
9
4
as monodentate Lewis acid catalysts (Fig. 3a). Ether 5
was hydrolyzed in the presence of complex 3 at an
elevated temperature (0°C), which significantly reduced
the product yield (entry 4). Addition of powdered
molecular sieves (4 A) (MS4A) was crucial for obtain-
,
ing good results (entry 5), suggesting that the catalyst is
incompatible with a trace amount of incidental water in
the reaction system. Reaction of several other aromatic
aldehydes was conducted under the standard conditions
to give the corresponding hydroxy ketones 7 in yields
depending on the substituents on the aromatic ring
(entries 6–8, 10, 11 and 13). The steric bulk of the ortho
Figure 1. ORTEP drawing and schematic view of
[
Ti LCl (H O)] obtained by recrystallization of complex 3.
2 4 2
Hydrogen atoms are omitted for clarity.

N. Morohashi et al. / Tetrahedron Letters 43 (2002) 7769–7772
Table 1. Reaction of aldehydes with silyl enol ethers
7771
Entry
Aldehyde
Silyl enol ether
Lewis acid (mol%)
Yield (%)a
1
2
3
Benzaldehyde
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
6
6
6
6
6
3 (5.0)
4 (5.0)
TiCl4 (10)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
3 (5.0)
93
2
36
6
b
4
5
c
61
85
88
57
77
30
50
87
91
87
0
95
93
97
95
92
6
7
8
4-Chlorobenzaldehyde
4-Methylbenzaldehyde
2-Methylbenzaldehyde
d
9
10
11
12
13
14
15
16
17
18
19
20
2,6-Dimethylbenzaldehyde
1-Naphthaldehyde
d
2-Naphthaldehyde
Cinnamaldehyde
3-Phenylpropanal
Benzaldehyde
4-Chlorobenzaldehyde
4-Methylbenzaldehyde
1-Naphthaldehyde
2-Naphthaldehyde
a
b
c
Isolated yield.
The reaction was conducted at 0°C for 2 h.
MS4A was not added.
d
The reaction was conducted at −78°C for 2 h.
In conclusion, we have shown here that p-tert-butylthi-
acalix[4]arene can be used as an efficient scaffold for
the construction of a dinuclear titanium(IV) complex,
in which two metal centers are located so closely as to
activate aldehydes doubly as a bidentate Lewis acid.
Further studies on the synthesis and catalytic applica-
tion of polynuclear metal complexes based on p-tert-
butylthiacalix[4]arene and its analogues are in progress.
Figure 3. Single (a) and double (b) electrophilic activation of
aldehyde by titanium Lewis acids.
substituent significantly affected the reactivity of the
aldehyde (compare entry 8 with 1, entry 10 with 8 and
entry 11 with 13), while the electronic effect of the para
substituent is negligible (compare entry 6 with 7).
Molecular model inspections suggested that the benzene
ring of benzaldehyde, when the aldehyde coordinates to
complex 3, will be oriented perpendicular to the car-
bonyl plane to avoid the steric repulsion between itself
and the chlorine atoms. As a result, the ortho sub-
stituent resides on a side of the carbonyl plane, which
will prevent enol ether 5 from attacking the carbonyl
group. An aldol adduct was also obtained by the
reaction of 3-phenylpropenal (cinnamaldehyde) (entry
Acknowledgements
This work was supported by the JSPS Research for the
Future Program.
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8
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3
mmol) in dichloromethane–benzene (3:1, 80 cm ) was
−3
added TiCl (1.0 mol dm in dichloromethane; 800 ml,
4
8
00 mmol) and the mixture was stirred for 1 h. The
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5
1
t
H NMR (400 MHz, THF-d ) l 1.27 (36H, s, Bu ×3),
8
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1
2. Crystal data for [Ti LCl (H O)]·H O·2CH Cl : C H -
2
4
2
2
2
2
44 52
7
559–7562; (c) Morohashi, N.; Iki, N.; Sugawara, A.;
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8
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4
2
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0.055(4), c=14.491(3) A
,
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6
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A
,
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1
(
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3
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Rint=0.033), final R=0.051, R =0.061 for 3747
w
observed reflections (I >5|(I )), GOF=1.83. Selected
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bond distances (A
.639; TiꢀCl, 2.251 and 2.256; TiꢀOaqua, 1.813.
,
): TiꢀOphenoxy, 2.040 and 2.042; TiꢀS,
2
1
1
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2
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002, 41, 2076–2078.
4. Typical procedure for the aldol reaction: A mixture of an
aldehyde (500 mmol), a catalyst, MS4A (200 mg) and
2
7
8
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Chem. Lett. 2001, 66–67.
3
dichloromethane (4.0 cm ) was stirred at room tempera-
ture for 10 min and then cooled to −78°C. To the
solution was added dropwise a solution of ether 5 or 6
3
(
2
1
600 mmol) in dichloromethane (1.0 cm ) over a period of
. Recently, methylene-bridged calixarenes have been uti-
lized as ligands for transition-metal catalysts: (a) Ozerov,
O. V.; Patrick, B. O.; Ladipo, F. T. J. Am. Chem. Soc.
min and the resulting solution was stirred for a further
5 min. The mixture was quenched with 2 mol dm HCl
−
3
and extracted with chloroform. After the solvents were
evaporated, the residue was treated with a mixture of
2
000, 122, 6423–6431; (b) Massa, A.; D’Ambrosi, A.;
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. For a review of leading studies on bidentate Lewis acid
catalysts, see: Maruoka, K. Catal. Today 2001, 66, 33–45.
3
−3
3
THF (12 cm ) and 2 mol dm HCl (6.0 cm ) at room
temperature for 30 min. The resulting mixture was
extracted with chloroform and worked up as usual. The
crude product was purified by TLC to give the corre-
sponding aldol adduct.
9
1
1
0. Mukaiyama, T. Org. React. 1982, 28, 203–331.
1. Synthesis of complex 3: To a solution of thiacalixarene 2