Immobilization of a BINOLate-titanium catalyst by use of aggregation phenomenon

Article abstract of DOI:10.1055/s-2005-923610

Upon treatment with titanium tetraisopropoxide, tris-BINOL with a rigid aromatic tether forms an insoluble polymeric aggregate, which shows a catalytic activity in asymmetric addition of diethylzinc to aldehydes. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-923610

LETTER
321
Immobilization of a BINOLate–Titanium Catalyst by Use of Aggregation
Phenomenon
I
mmobilization
o
of
a
BIN
O
L
s
h
um
C
atalystiro Harada,* Masashi Nakatsugawa
Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Fax +81(75)7247580; E-mail: harada@chem.kit.ac.jp
Received 26 October 2005
Ln
Abstract: Upon treatment with titanium tetraisopropoxide, tris-
BINOL with a rigid aromatic tether forms an insoluble polymeric
aggregate, which shows a catalytic activity in asymmetric addition
of diethylzinc to aldehydes.
M
M
M
Ln
a)
Ln
2
3
1
Key words: asymmetric catalysis, heterogeneous catalysis, Lewis
acids, titanium, zinc
Ln
M
M
Ln
M
M
Ln
b)
M
M
Ln
Heterogeneous catalysis offers the advantages of easy
separation of the catalyst from the reaction mixture, pos-
sible recycling, and, in many cases, enhanced stability in
comparison with the soluble analogue. The immobiliza-
tion of asymmetric homogeneous catalysts is a current
subject of intense research activity because sophisticated
and expensive chiral ligand systems might become attrac-
tive for industrial applications by their heterogenization.1
The most frequently used strategy of heterogenization is
covalent binding of the catalyst or ligand of choice to
organic or inorganic supports. Many homogeneous
asymmetric catalysts have been immobilized onto organic
polymers and inorganic supports such as silicas and zeo-
lites. However, the activity of immobilized catalysts is of-
ten reduced with respect to their soluble analogues, due to
diffusion problems or to the fact that the preferred confor-
mation of the catalytic moiety cannot be adopted. New
methods need to be developed for the heterogenization of
homogeneous asymmetric catalysts.2,3
Ln
4
5
Ln
Ln
M
M
Ln
M
M
Ln
M
M
Ln
Ln
Ln
6
Scheme 1 Immobilization of asymmetric catalysts by aggregation
focus our attention on the heterogenization of BINOLate–
Ti(Oi-Pr)2 based upon the approach presented in
Scheme 1 (b). Herein, we wish to report the preparation of
an immobilized chiral titanium complex from tris-BINOL
ligand 9 as well as its application to asymmetric addition
of diethylzinc to aldehydes.
6
It is often observed that a catalyst complex 2 prepared
from a chiral ligand 1 is in equilibrium with a dimeric
aggregate 3 in solution (Scheme 1, a). When a complex is
prepared from ligand 4 in which molecules of ligand 1 are
linked with a polyvalent tether, the resulting complex is
anticipated to form insoluble polymeric aggregate 5
(Scheme 1, b). The aggregate 5 might undergo partial dis-
sociation in a reversible manner to generate active sites
and exhibit a catalytic activity similar to that of a parent
homogeneous catalyst while maintaining its hetero-
geneous state.
Tris-BINOL 9 was synthesized in a convergent manner by
joining three BINOL units with a rigid trivalent tether 77
(Scheme 2). Treatment of a MOM-protected (R)-3-iodo-
BINOL derivative 8 (3.2 equiv) and 7 in THF and Et3N
(3:1) in the presence of Pd(PPh3)4 (10 mol%) and CuI (20
mol%) afforded the corresponding coupling product in
91% yield. Removal of the protecting groups with
Me3SiBr in the presence of molecular sieves 4 Å8 fur-
nished 9 in 92% yield.
Titanium complexes of 1,1¢-bi-2-naphthol (BINOL) and
its derivatives have been employed as enantioselective
chiral Lewis acid catalysts in a number of useful asym-
metric processes.4 They are known to form aggregates
both in solution and solid state.5 In the present study, we
Treatment of 9 with titanium tetraisopropoxide (3 equiv)
in CH2Cl2 followed by addition of toluene and distillation
of the solvents, to remove isopropyl alcohol liberated,
gave 9-[Ti(Oi-Pr)2]3 as a dark orange amorphous solid.
The solid was washed three times in toluene by centrifu-
gation. Dissolution in toluene was negligibly small in the
second and third wash. The yield of 9-[Ti(Oi-Pr)2]3 was
estimated to be 75% from the recovery of the ligand 9
after hydrolysis of the solid.
SYNLETT 2006, No. 2, pp 0321–0323
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2.
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Advanced online publication: 23.12.2005
DOI: 10.1055/s-2005-923610; Art ID: U29705ST
© Georg Thieme Verlag Stuttgart · New York

322
T. Harada, M. Nakatsugawa
LETTER
Table 2 Asymmetric Ethylation of Aldehydes Catalyzed by 9-
a
[Ti(Oi-Pr)2]3
I
OMOM
HO
Entry
Aldehyde
Time (h) Conversion (%) ee (%)b
HO
OMOM
1
2
3
4
5
p-MeC6H4CHO
m-ClC6H4CHO
19
24
>98
>98
>98
95c
74
81
79
84
79
8
HO
1) Pd(PPh3)4, CuI,
Et3N
HO
m-MeOC6H4CHO 20
2) Me3SiBr
OH
OH
7
1-NaphCHO
22
19
63%
9
PhCH2CH2CHO
>98
a Reactions were carried out under conditions similar to those of entry
1 in Table 1.
b Determined by chiral stationary phase HPLC (Chiralcel OD
=
column).
c Isolated yield.
Scheme 2 Preparation of tris-BINOL 9
(entry 3). To gain information on the catalytic activity of
9-[Ti(Oi-Pr)2]3 in its solid form, control experiments were
carried out in which a supernatant of a mixture of the tita-
nium complex, titanium tetraisopropoxide (1 equiv), and
diethylzinc (3 equiv) was used (entries 2 and 4). The reac-
tions were slower and less selective, indicating the cata-
lytic activity of the solid fraction of 9-[Ti(Oi-Pr)2]3.
The activity of 9-[Ti(Oi-Pr)2]3 as a catalyst was examined
in a prototypical diethylzinc addition to benzaldehyde
(Table 1; R = Ph).9 The solid catalyst was prepared by a
procedure similar to that described above and stored under
argon prior to use. Upon treatment of benzaldehyde with
diethylzinc (3 equiv), titanium tetraisopropoxide (1
equiv), and 3.3 mol% of the catalyst 9-[Ti(Oi-Pr)2]3
suspended in toluene and hexane (73:27) at 0 °C, the
ethylation reaction proceeded smoothly under the hetero-
geneous conditions to give (R)-1-phenylpropanol in 74%
ee (Table 1, entry 1). The solid catalyst was recovered
quantitatively by centrifugation. When twice as much
solvent (toluene–hexane = 93:7) was used, a similar level
of enantioselectivity and catalyst recovery was obtained
albeit with considerable lowering in the reaction rate
Extension of the above asymmetric alkylation reaction to
other aldehydes also gave relatively high enantioselectiv-
ity (Table 2). Of these, the reaction of 1-naphthaldehyde
exhibited the highest ee of 84% (entry 4). The catalyst was
also used successfully in the reaction of an aliphatic alde-
hyde without a decrease in enantioselectivity (entry 5).10
The reuse of the polymeric aggregate catalyst was exam-
ined in the asymmetric ethylation of aldehydes (Table 3).
The reuse experiments were carried out in a flask
Table 3 Reuse of 9-[Ti(Oi-Pr)2]3 in Asymmetric Ethylation of
Aldehydesa
Table 1 Asymmetric Ethylation of Benzaldehyde Catalyzed by
9-[Ti(Oi-Pr)2]3
Entry Aldehyde
Cycle Time (h) Conversion ee (%)b
(%)
9-[Ti(Oi-Pr)2]3 (3.3 mol%),
O
OH
Ti(Oi-Pr)4 (1 equiv)
+
Et2Zn
Ph
H
Ph
1
2
3
4
5
6
7
8
9
PhCHO
1
2
3
4
5
6
1
2
3
18
18
18
18
18
18
22
22
22
>98
>98
>98
>98
>98
>98
95c
72
75
75
75
74
74
84
80
84
0 °C, toluene, hexane
(3 equiv)
PhCHO
Entry Catalyst
Time
Conversion ee
Recovery
(%)c
(mmol/mL)a (h)
(%)
>98
83
(%)b
PhCHO
1
1.5
20
20
67
67
74
98
–
PhCHO
2d
3
1.5
58
PhCHO
0.75
0.75
>98
39
74
99
–
PhCHO
4d
40
1-NaphCHO
1-NaphCHO
1-NaphCHO
a The amount (mmol) of the catalyst suspended in 1 mL of solvents
(toluene–hexane = 73:27 for entries 1 and 2 and 93:7 for entries 3 and
4).
97c
98c
b Determined by chiral stationary phase HPLC (Chiralcel OD
column).
a Reactions were carried out as described in the text under the condi-
tions similar to that of entry 1 in Table 1.
b Determined by chiral stationary phase HPLC.
c Isolated yield.
c Recovery of the solid catalyst.
d The reaction was carried out after removing solid fraction of the
catalyst by centrifugation.
Synlett 2006, No. 2, 321–323 © Thieme Stuttgart · New York

LETTER
Immobilization of a BINOLate–Titanium Catalyst
323
(5) (a) Boyle, T. J.; Barnes, D. L.; Heppert, J. A.; Morales, L.;
Takusagawa, F. Organometallics 1992, 11, 1112.
equipped with a filter. The solid catalyst was separated
from the product by filtration and used in the subsequent
cycle. For the reaction of benzaldehyde, the catalyst
maintained its activity even after six cycles without
lowering of the enantioselectivity (entries 1–6). The recy-
cled catalyst was also used effectively for 1-naphthalde-
hyde (entries 7–9).
(b) Boyle, T. J.; Eilerts, N. W.; Heppert, J. A.; Takusagawa,
F. Organometallics 1994, 13, 2218. (c) Balsells, J.; Davis,
T. J.; Carroll, P.; Walsh, P. J. J. Am. Chem. Soc. 2002, 124,
10336. (d) Waltz, K. M.; Carroll, P.; Walsh, P. J.
Organometallics 2004, 23, 127.
(6) For a relevant work on a BINOLate–lanthanum complex,
see: (a) Inanaga, J.; Hayano, T.; Furuno, H. Shokubai 2003,
45, 285. (b) Wang, X.; Shi, L.; Li, M.; Ding, K. Angew.
Chem. Int. Ed. 2005, 44, 6362.
(7) (a) Uno, M.; Dixneuf, P. H. Angew. Chem. Int. Ed. 1998, 37,
1714. (b) McDonagh, A. M.; Powell, C. E.; Morrall, J. P.;
Cifuentes, M. P.; Humphrey, M. G. Organometallics 2003,
22, 1402.
(8) Huffman, J. W.; Zhang, X.; Wu, M.-J.; Joyner, H. H.;
Pennington, W. T. J. Org. Chem. 1991, 56, 1481.
(9) (a) Mori, M.; Nakai, T. Tetrahedron Lett. 1997, 38, 6233.
(b) Zhang, F.-Y.; Yip, C.-W.; Cao, R.; Chan, A. S.
Tetrahedron: Asymmetry 1997, 8, 585.
In summary, we have developed a new method for the
immobilization of BINOLateTi(Oi-Pr)2 by utilizing an
aggregation phenomenon. Upon treatment with titanium
tetraisopropoxide, tris-BINOL 9 formed an insoluble
polymeric aggregate, which exhibited a catalytic activity
in asymmetric ethylation of aldehydes. The catalyst toler-
ated recycled uses at least six times, suggesting the poten-
tial of the present method of immobilization based on an
aggregation phenomenon.
(10) Typical Experimental Procedure (Table 2, Entry 4).
To a solution of tris-BINOL 9 in CH2Cl2 (0.08 M) in a
Schlenk flask at r.t. under argon atmosphere was added
titanium tetraisopropoxide (3 equiv). The resulting dark
orange suspension was stirred for 1 h. After addition of
toluene, the mixture was concentrated by distillation of the
solvents under atmospheric pressure. The residue was
washed three times with toluene by centrifugation under
argon and vacuum dried to give 9-[Ti(Oi-Pr)2]3, which was
stored in an argon-filled glovebox prior to use. To a
suspension of 9-[Ti(Oi-Pr)2]3 (27 mg, 0.015 mmol) in
toluene (7.2 mL) and hexane (1.3 mL) at 0 °C under argon
atmosphere was added titanium tetraisopropoxide (0.13 g,
0.46 mmol). The resulting suspension was sonicated for 15
min at 0 °C. To this at 0 °C was added diethylzinc (1.0 M in
hexane) (1.4 mL, 1.4 mmol) and the mixture was stirred for
20 min. To the resulting mixture was added 1-naphthalde-
hyde (72 mg, 0.46 mmol). After being stirred at 0 °C for 22
h, the reaction mixture was filtered in a glovebox under
argon atmosphere. The filtrate was poured into aq 1 N HCl,
extracted three times with EtOAc, and washed with aq 5%
NaHCO3. The organic layer was dried (MgSO4) and
concentrated in vacuo. The residue was purified by flash
column chromatography (silica gel, 15% EtOAc in hexane)
to give 81 mg (95% yield) of (R)-1-naphthyl-1-propanol
(74% ee). Enantioselectivity was determined by HPLC
analysis using a Chiralcel OD column (10% i-PrOH in
hexane, 0.8 mL/min); tR = 11.8 min (minor S enantiomer),
22.5 min (major R enantiomer). The absolute structure of the
product was determined by comparing the retention time
with that of an authentic sample prepared by asymmetric
ethylation using (R)-BINOL as a ligand.9
References and Notes
(1) (a) De Vos, D. E.; Vankelecom, I. F. J.; Jacobs, P. A. Chiral
Catalyst Immobilization and Recycling; Wiley-VCH:
Weinheim, 2000. (b) Fan, Q.-H.; Li, Y.-M.; Chan, A. S. C.
Chem. Rev. 2002, 102, 3385.
(2) For soluble chiral catalysts bearing linear polymeric or
dendritic ligands, see: (a) McNamara, C. A.; Dixon, M. J.;
Bradley, M. Chem. Rev. 2002, 102, 3275. (b) Dickerson, T.
J.; Reed, N. N.; Janda, K. D. Chem. Rev. 2002, 102, 3325.
(c) Bergbreiter, D. E. Chem. Rev. 2002, 102, 3345.
(d) Leadbeater, N. E.; Marco, M. Chem. Rev. 2002, 102,
3717.
(3) For a metal-bridged polymeric catalyst, see: (a) Yamada, Y.
M. A.; Ichinohe, M.; Takahashi, H.; Ikegami, S.
Tetrahedron Lett. 2002, 43, 3431. (b) Takizawa, S.; Somei,
H.; Jayaprakash, D.; Sasai, H. Angew. Chem. Int. Ed. 2003,
42, 5711. (c) Guo, H.; Wang, X.; Ding, K. Tetrahedron Lett.
2004, 45, 2009. (d) Liang, Y.; Jing, O.; Li, X.; Shi, L.; Ding,
K. J. Am. Chem. Soc. 2005, 127, 7694. (e) Wang, X.;
Wang, X.; Guo, H.; Wang, Z.; Ding, K. Chem. Eur. J. 2005,
11, 4078.
(4) Mikami, K. In Encyclopedia of Reagents for Organic
Synthesis, Vol. 1; Paquette, L. A., Ed.; John Wiley and Sons:
New York, 1995, 403.
Synlett 2006, No. 2, 321–323 © Thieme Stuttgart · New York