Heterogeneous asymmetric addition of diethylzinc to aromatic aldehydes catalyzed by Ti(IV)/imine bridged poly(R)-binaphthol

Article abstract of DOI:10.1016/S0957-4166(00)00190-7

Heterogeneous asymmetric addition of diethylzinc to aldehydes catalyzed by chiral polymer catalysts has been achieved. The conjugated polymers based on a BINOL skeleton were synthesized in five steps and applied to this reaction with yield and e.e. up to

Full text of DOI:10.1016/S0957-4166(00)00190-7

Tetrahedron: Asymmetry 11 (2000) 2449±2454
Heterogeneous asymmetric addition of diethylzinc to
aromatic aldehydes catalyzed by Ti(IV)/imine bridged
poly(R)-binaphthol
a
a
a
a
a,
Chune Dong, Junlong Zhang, Weizhong Zheng, Liangfu Zhang, Zuolong Yu, *
b
b
Michael C. K. Choi and Albert S. C. Chan
aChengdu Institute of Organic Chemistry, Chinese Academy of Science, Chengdu, China
bOpen Laboratory of Chirotechnology and Department of Applied Biology and Chemical Technology,
Hong Kong, China
Received 3 April 2000; accepted 10 May 2000
Abstract
Heterogeneous asymmetric addition of diethylzinc to aldehydes catalyzed by chiral polymer catalysts has
been achieved. The conjugated polymers based on a BINOL skeleton were synthesized in ®ve steps and
applied to this reaction with yield and e.e. up to 95 and 84.5%, respectively. These chiral polymers can be
easily quantitatively recovered and reused without decreasing the e.e. or catalytic activity. # 2000 Elsevier
Science Ltd. All rights reserved.
1
. Introduction
The asymmetric addition of diethylzinc to aldehydes has become a useful method for the pre-
paration of a wide variety of chiral secondary alcohols. Many types of chiral ligands were applied
1
2
to this reaction. Recently, Chan et al. discovered that (R)- or (S)-binaphthol was an excellent
chiral ligand for alkylations of aldehydes catalyzed by titanium catalysts to give alcohols with e.e.
up to 95.6%.
The study of chiral polymer catalysts has attracted very extensive attention in recent years.3
These catalysts have intrinsic advantages in that they can be separated from the products by
simple ®ltration and reused without loss of catalytic activity or enantioselectivity. Several asym-
metric syntheses using chiral polymer catalysts have been reported in the literature. Traditionally,
chiral polymer catalysts were prepared by attaching the chiral ligand to a sterically irregular
4
polymer backbone. In this system, owing to the catalytic active sites being randomly oriented
along the polymer chain, it was dicult to optimize the microenvironment of the catalytic center
*
Corresponding author. E-mail: ioczlfcn@mail.sc.cninfo.net
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00190-7

2
450
C. Dong et al. / Tetrahedron: Asymmetry 11 (2000) 2449±2454
to obtain a highly active and stereoselective catalyst. Therefore, preparation of chiral polymers
where the catalytic centers are highly organized is necessary. Pu et al.
5�7
have been working on
the synthesis of chiral binaphthyl-based conjugated polymers using Suzuki-coupling reactions for
material applications as well as for catalysis. Because of imine ligands attracting much attention
in asymmetric catalytic reactions, in this paper, we report the synthesis of chiral binaphthyl poly-
8
mers coupling with an imine bond and their application in heterogeneous asymmetric addition
of diethylzinc to aldehydes.
2
. Results and discussion
The synthetic route to chiral polymers I and II is outlined in Scheme 1. Firstly, the commercially
0
0
available (R)-1,1 -bi-2,2 -naphthol 1 was reacted with bromoethane to give 2. Selective bromination
of 2 gave 3 in good yield. Lithiated 3 was reacted with DMF to give 4. Finally, the title chiral
polymers were obtained by condensing the corresponding diamine with 5, which was obtained by
deprotection of 4.
Scheme 1. Reagents and conditions: (a) bromoethane, acetone, 95%; (b) Br , CH Cl , 92%; (c) n-BuLi, DMF, 88%;
2
2
2
(
3 2 2
d) BBr , CH Cl , 93%; (e) diamine, THF:acetic acid=1:4, 56%, 68%
0
Both I and II were the major groove polymers of 1,1 -binaphthol where the polymerization
0
occurred at 6,6 -position. Unlike traditional polymeric chiral catalysts, their active centers were
highly organized in a regular chiral polymer chain. It was possible to systematically adjust the
microenvironment of the catalytic sites to tune both catalytic activity and stereoselectivity.
The e€ectiveness of the two chiral polymer ligands was assessed in the enantioselective addition
of diethylzinc to aldehydes (Fig. 1).
Table 1 shows the results. The active catalyst was formed in situ by mixing the polymer with
titanium tetraisopropoxide in CH Cl . In this reaction, the molar ratio of substrate, titanium
2
2
tetraisopropoxide, polymer ligand and diethylzinc was the same as in the homogeneous reaction.
The result indicated that the polymer took 15 h to form a complex with titanium. From Table 1 it

C. Dong et al. / Tetrahedron: Asymmetry 11 (2000) 2449±2454
2451
Figure 1.
can be observed that the two polymer ligands showed di€erent catalytic activities. The Ti(IV)/
polymer II catalyst was more enantioselective than Ti(IV)/polymer I, to give 1-phenyl-2-propanol
in 80.0% e.e (entry 6) while the latter gave the corresponding alcohol in 63.9% e.e (entry 1). The
electronic property of substituents in substrates was an important factor in¯uencing the enantio-
selectivity under the homogeneous catalytic conditions. Aldehydes with electron-donating sub-
stituents such as methyl or methoxy groups gave higher e.e. values than substrates with electron-
withdrawing substituents (entries 2, 3, 7 and 8). At the same time ortho-substituted benzaldehydes
gave products of signi®cantly lower e.e. than para-substituted benzaldehydes (entries 3, 4, 8 and
9). The polymer can be recovered by simple ®ltration and reused under the same conditions to
give almost the same result, as shown in entries 11 and 12.
Table 1
Asymmetric addition of diethylzinc to aldehydes catalyzed by chiral polymer/Ti(IV) catalysts
3
. Conclusion
In summary, two chiral heterogeneous catalysts were prepared through a practical route and
used in asymmetric additions of diethylzinc to aldehydes to give alcohols in high yields and good
e.e. values. These catalysts can be recovered and reused for the same reaction without reducing
catalytic activities or enantioselectivities. The use of these catalysts in other transformations is in
progress.

2
452
C. Dong et al. / Tetrahedron: Asymmetry 11 (2000) 2449±2454
4
. Experimental
4
.1. Materials
0
25
9
(
R)-1,1 -Bi-2-naphthol ‰ꢀŠ =+34.4 (c=1, THF) was obtained according to the literature. All
D
aromatic aldehydes were puri®ed before use. THF was distilled under N from Na/benzophenone
2
and DMF was distilled from CaH ; CH Cl was redistilled before use.
2
2
2
4
.2. Measurements
Melting points were obtained on a Buchi-510 melting point apparatus. IR was recorded on a
1
Nicolet MX-1E spectrophotometer. The H NMR was recorded on a Varian Bruker-200A spectro-
meter in CDCl or DMSO with TMS as internal standard. Elemental analyses were obtained on a
3
Carlo Erba-1106 apparatus. Optical rotations were measured with a Perkin±Elmer 341 polari-
meter in a 1 cm cell. The e.e. values were determined by GC using a CP-CYDEX-236 (0.25 mmÂ25 m)
chiral column, or by HPLC using a Chiracel OB (0.46 cmÂ25 m) column.
0
0
4
.3. (R)-2,2 -Diethoxy-1,1 -binaphthyl 2
0
0
A mixture of 3.0 g of (R)-2,2 -dihydroxy-1,1 -binaphthyl 1 (10.5 mmol), 6.8 g of bromoethane
62.8 mmol), 5.9 g of dry potassium carbonate and a catalytic amount of NaI in 16.0 mL of dry
(
acetone was stirred magnetically and re¯uxed under anhydrous conditions for two days. After
cooling the reaction mixture was poured into water, extracted with CH Cl . The combined
organic phases were dried over MgSO . The solvent was removed in vacuo after ®ltration. The
2
2
4
ꢀ
remaining oil was recrystallized from benzene/petroleum ether (60±90 C) to give 3.4 g (95.0%) of
10
ꢀ
+
white needles. Mp: 132±134 C, ‰ꢀŠ =+82.0 (c=0.2, CHCl ); MS (m/z): 343 (MH ); IR (KBr):
D
955 (-CH CH ), 1582±1610 (-Ar), 1223 (-C±O), 825 (C±O±C); H NMR (CDCl ): 1.03 (t, 6H, -CH ),
3
1
2 3 3 3
2
4
.05 (m, 4H, -CH ), 7.11 (d, 2H, J=8 Hz, -ArH), 7.23±7.30 (dd, 4H, J=7.8 Hz, -ArH), 7.46 (d,
2
2
Found: C, 83.98; H, 6.38.
H, J=8.8 Hz, -ArH), 7.85±7.94 (m, 4H, -ArH). Anal. calcd for C H O : C, 84.21; H, 6.43.
22
24
2
0
0
0
4
.4. (R)-6,6 -Dibromo-2,2 -diethoxy-1,1 -binaphthyl 3
0
0
A 2.0 g of (R)-2,2 -diethoxy-1,1 -binaphthyl 2 (5.8 mmol) was dissolved in 20 mL of CH Cl
2
2
ꢀ
and stirred at 0 C. 0.66 mL of bromine (12.8 mmol) was added in one portion with stirring and a
stream of nitrogen bubbling through the solution to remove the evolving HBr. The reaction
mixture was stirred for 5 h while the ¯ask was allowed to warm to rt. The yellow solution
was allowed to stand overnight. 10 mL of a 10% NaHSO solution was added with vigorous
3
stirring to destroy excess bromine. The organic layer was separated, washed with water and dried
over MgSO and the solvent removed in vacuo after ®ltration. The residue was recrystallized
4
ꢀ
12
from benzene/petroleum ether (60±90 C) to give 2.67 g (92.0%) of a white solid after washing with
ꢀ
+
petroleum ether. Mp: 159±160 C, ‰ꢀŠ =+15.1 (c=0.2, CHCl ); MS (m/z) 501 (MH ); IR (KBr):
D
3
1
2
925 (-CH CH ), 1518±1605 (-ArH), 1236 (-C±O), 1070 (C±Br); H NMR (CDCl ): 1.12 (t,
2 3 3
6
H, -CH ), 4.05 (m, 4H, -CH ), 6.98 (d, 2H, -ArH), 7.24 (dd, 4H, J=2 Hz, J=9 Hz, -ArH), 7.84
3
2
(d, 2H, J=8.6 Hz, -ArH), 7.96 (d, 2H, -ArH). Anal. calcd for C H Br O : C, 57.60; Br, 32.00.
Found: C, 57.58; Br, 31.85.
24 20 2 2

C. Dong et al. / Tetrahedron: Asymmetry 11 (2000) 2449±2454
2453
0 0 0
.5. (R)-2,2 -Diethoxy-6,6 -dicarbaldehyde-1,1 -binaphthyl 4
4
0
0
0
A sample of 0.5 g (R)-6,6 -dibromo-2,2 -diethoxy-1,1 -binaphthyl 3 (1.0 mmol) was dissolved in
ꢀ
15 mL dry THF under N atmosphere. The stirred solution was cooled to ^78 C and 11 mL ether
solution of 0.4 M n-BuLi was added at such a rate as not to allow the temperature to exceed
70 C. After 5 h of stirring at this temperature 0.51 mL of dry N,N-dimethylformamide (6.6 mmol)
was added slowly so that the temperature remained below ^50 C. After stirring for 45 min at this
temperature, the reaction mixture was poured into HCl/ice under vigorous stirring. It was
allowed to reach rt overnight and extracted with CH Cl . The organic layer was washed twice
2
ꢀ
^
ꢀ
2
2
with water and dried over MgSO and the solvent was removed to give an oil. The oil was submitted
4
to chromatography on silica using CH Cl /AcOEt as eluting agent to give a white solid 0.35 g
2
2
ꢀ
10
D
+
(
1
80.0%). Mp: 148 C, ‰ꢀŠ =^95.8 (c=0.01, CHCl ); MS (m/z): 398 (M ); IR (KBr): 2992 (-CH CH ),
3
2
3
1
698 (-CHO), 1215 (-C±O); H NMR (CDCl ): 1.05 (t, 6H, -CH ), 4.11 (m, 4H, -CH ), 7.16±7.72
3 3 2
(m, 6H -ArH), 8.11 (d, 2H, J=9 Hz, -ArH), 8.42 (d, 2H, -ArH), 9.94 (s, 1H, -CHO). Anal. calcd
for C H O : C, 78.39; H, 5.53. Found: C, 79.12; H, 5.50.
26
22
4
0
0
4
.6. (R)-6,6 -Dicarbaldehyde-1,1 -bi-2-naphthol 5
0
0
0
The solution of 398.0 mg (R)-6,6 -dicarbaldehyde-2,2 -diethoxy-1,1 -binaphthyl 4 (1 mmol) in
.0 mL CH Cl was added dropwise to a 1.0 M methylene chloride solution of boron tribromide
5
2
2
at rt. The mixture was stirred overnight, treated with water for 0.5 h and the layers were separated.
The aqueous layer was extracted with methylene chloride and the combined organic layes were
treated with sodium sulfate, ®ltered and concentrated to yield a yellow solid 0.32 g (93.0%). Mp:
ꢀ
8
+
1
80 C, [ꢀ] =^87.6 (c=0.2, C H OH); MS (m/z): 342 (M ); IR (KBr): 3369 (-OH), 1675 (-CHO);
D
2
5
1
H NMR (CDCl ): 5.27 (s, 2H, -OH), 6.86±7.74 (m, 6H, -ArH), 7.82 (d, 2H, J=2.0 Hz, -CHO),
.00 (d, 2H, -ArH), 10.0 (s, 2H, -CHO). Anal. calcd for C H O : C, 77.19; H, 4.09. Found: C,
3
8
22
14
4
7
7.23; H, 3.95.
4
.7. Synthesis of chiral polymers
0
0
To a solution of 129.0 mg of (R)-6,6 -dicarbaldehyde-1,1 -bi-2-naphthol 5 (0.39 mmol) in 5 mL
of tetrahydrofuran and 20 mL of glacial acetic acid was added a warm solution of 40.5 mg (0.39
mmol) o-phenylenediamine (twice recrystallized) in 10 mL of glacial acetic acid. Then the tempera-
ture was slowly raised on a water bath, the reaction mixture was stirred for 5 min, a yellow
precipitate was formed, and the mixture was allowed to reach rt. The precipitate was ®ltered,
washed with water, alcohol, tetrahydrofuran and ether and dried to give chiral polymer I 95.0 mg
8
1
(
56%). [ꢀ] =^240 (c=0.2, CH OH); IR (KBr): 3360 (-OH), 1620 (-CˆN), 1280, 818, 751; H
D
3
NMR (DMSO): 5.32 (s, -OH), 6.56±7.08 (m, -PhH), 7.13±7.98 (m, -ArH), 8.87 (s, -CHˆN). UV±vis
(
CH OH), nm: 242, 333, 420; inherent viscosity [Z]=2.64.
3
Polymer II was prepared through the same method, the yield was 68%. IR (KBr): 3368 (-OH),
1634 (-CˆN), 1465±1598 (-Ph), 816. Because of its poor solubility, other spectra were not obtained.
4
.8. General procedure for asymmetric addition of diethylzinc to aldehyde
The literature procedure for the asymmetric addition of diethylzinc to aldehydes was followed
with modi®cation.

2
454
C. Dong et al. / Tetrahedron: Asymmetry 11 (2000) 2449±2454
Under nitrogen, a Schlenck equipped with a magnetic stirring bar was charged with polymer I
50.0 mg, 0.125 mmol, based on the repeat unit) and 0.3 mL Ti(O-i-Pr) (0.875 mmol) and 5 mL
CH Cl . The mixture was stirred at ambient temperature for 15 h, then into this solution was
(
4
2
2
added 1.875 mL of 1 M solution of diethylzinc in hexane (1.875 mmol) and the mixture was
ꢀ
stirred for another 10 min. The solution was cooled to 0 C and 0.065 mL of benzaldehyde (0.625
ꢀ
mmol) was added to the solution and the ®nal mixture was allowed to stir at 0 C for 5 h. The
reaction was stopped by addition of 3 mL 1.0 M hydrochloric acid and the polymer was ®ltrated
and washed. The ethyl acetate extract was dried over MgSO and the yield was determined by
4
GC; the e.e. value was analyzed by CP-Cyclodex-236 m (0.25 mmÂ25 m) chiral column.
Acknowledgements
We thank Hong Kong Polytechnic University for ®nancial support of this study.
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