Polymer-Supported BINOL Ligand for the Titanium-Catalyzed Diethylzinc Addition to Aldehydes: A Remarkable Positive Influence of the Support on the Enantioselectivity of the Catalyst

Article abstract of DOI:10.1021/jo990771p

A new polymer-supported BINOL (1,1′-Bi-2-naphthol) was synthesized by coupling of aminomethyl polystyrene resin and (S)-2,2′-dihydroxy-1,1′-binaphthyl-3,3′-dicarboxylic acid. This new ligand was found to be more enantioselective for the asymmetric addition of diethylzinc to aldehydes than its "free" analog [Ti(BINOL)ⁱPrO₂]. A range of 57-99% ee's as well as 78-97% yields was obtained, and the electronic properties of the enantioselectivity were also observed.

Full text of DOI:10.1021/jo990771p

J . Org. Chem. 2000, 65, 295-296
295
P olym er -Su p p or ted BINOL Liga n d for th e Tita n iu m -Ca ta lyzed
Dieth ylzin c Ad d ition to Ald eh yd es: A Rem a r k a ble P ositive
In flu en ce of th e Su p p or t on th e En a n tioselectivity of th e Ca ta lyst
Xiao-Wu Yang,† J ian-Heng Sheng,† Chao-Shan Da,† Heng-Shan Wang,† Wu Su,†
Rui Wang,*,† and Albert S. C. Chan*,‡
Union Laboratory of Asymmetric Synthesis and School of Life Science, Lanzhou University,
Lanzhou 730000, China, and Union Laboratory of Asymmetric Synthesis and Department of Applied
Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
Received May 10, 1999
A new polymer-supported BINOL (1,1′-Bi-2-naphthol) was synthesized by coupling of aminomethyl
polystyrene resin and (S)-2,2′-dihydroxy-1,1′-binaphthyl-3,3′-dicarboxylic acid. This new ligand was
found to be more enantioselective for the asymmetric addition of diethylzinc to aldehydes than its
“free” analog [Ti(BINOL)iPrO2]. A range of 57-99% ee’s as well as 78-97% yields was obtained,
and the electronic properties of the enantioselectivity were also observed.
The methodology of attaching a chiral ligand onto a
polymer has been widely applied to the development of
new polymer-supported catalysts for asymmetric catalytic
reactions.1 This strategy often afforded several advan-
tages over the use of homogeneous catalysts in asym-
metric synthesis: (1) the ease of separation of the catalyst
from the reaction system and (2) convenient operation
in flow reactors or flow membrane reactors for continuous
production.2 Unfortunately, previous studies often showed
significant decrease of catalytic activity and/or enanti-
oselectivity for the supported catalysts as compared to
their homogeneous counterparts3 except for a few ex-
amples.4 From both fundamental and practical stand-
points, it is of high interest to explore the potential
positive influence of the polymer support on the sup-
ported chiral catalysts. In this paper, we wish to report
a new class of polymer-supported chiral catalyst that
showed significantly higher enantioselectivity than its
homogeneous counterpart.
particularly interested in the attachment at the 3,3′-
positions. The proximity of these positions to the catalyst
center offered excellent opportunities for the study of the
influence of the polymer support on the resulting catalyst.
The 3,3′-functionalized (supported) BINOL 4 was syn-
thesized according to Scheme 1. 2,2′-Dihydroxy-1,1′-
binaphthyl-3,3′-dicarboxylic acid 36 was synthesized in
two steps in 54% yield from (S)-BINOL. This acid was
further coupled with aminomethylated polystyrene7 to
give the desired ligand 4 with a loading of 0.38 mmol/g
using DCC/HOBt (1-hydroxybenzotriazole hydrate) as
coupling reagent.8 The presence of the expected supported
BINOL anchored to two polymer links is evidenced by
the presence of -CONH- functionality at 1626 cm-1 and
the disappearance of peaks of COOH at 1660, 3058 cm-1
in the FT-IR spectra.
The polymer-supported ligand 4 was found to be highly
effective in the titanium-catalyzed alkylation of alde-
hydes with diethylzinc. A profound solvent effect was
observed in the initial study, and dichloromethane (DCM)
was found to be superior to other common organic
solvents. The enantioselectivities also varied significantly
when different levels of ligands were used. The optimum
amount of ligand is 20 mol %. The Ti-4 catalyst was also
found to be highly effective for the asymmetric addition
of diethylzinc to other aryl aldehydes. In most cases, the
polymer-supported catalyst was found to be substantially
more enantioselective than its “free” analogue [Ti(BINO-
L)(OiPr)2].9 The detailed experimental results are shown
in Table 1.
1,1′-Bi-2-naphthol (BINOL) has been extensively stud-
ied as a chiral auxiliary in asymmetric synthesis.5 While
the BINOL ligand can be attached to a solid support via
the linkage at several sites of the naphthyl rings, we are
* To whom correspondence should be addressed
† Lanzhou University.
‡ The Hong Kong Polytechnic University.
(1) For reviews, see: (a) Noyori, R. Asymmetric catalysis in organic
synthesis; J ohn Wiley & Sons: New York, 1994; Chapter 8, p 347. (b)
Pu, L. Tetrahedron: Asymmetry 1998, 9, 1457. (c) Wilson, E. K. Chem.
Eng. News 1997, 75 (Dec 8), 24. For recent publications, see: (b) Altava,
B.; Burguete, M. I.; Escuder, B.; Luis, S. V.; Salvador, R. V.; Fraile, J .
M.; Mayoral, J . A.; Royo, A. J . J . Org. Chem. 1997, 62, 3126. (c)
Bayston, D. J .; Fraser, J . L.; Ashton, M. R.; Baxter, A. D.; Polywka,
M. E. C.; Moses, E. J . Org. Chem. 1998, 63, 3137. (d) Rheiner, P. B.;
Sellner, H.; Seebach, D. Helv. Chim. Acta. 1997, 80, 2027. (e) Vidal-
Ferran, A.; Bampos, N.; Moyano, A.; Pericas, M. A.; Riera, A.; Sanders,
J . K. M. J . Org. Chem. 1998, 63, 6309. (f) Gennari, C.; Ceccarelli, S.;
Piarulli, U.; Montalbetti, C. A. G. N.; J ackson, R. F. W. J . Org. Chem.
1998, 63, 5312.
(5) (a) Chan, A. S. C.; Zhang, F. Y.; Yip, C. W. J . Am. Chem. Soc.
1997, 119, 4080. (b) Noyori, R.; Ohkuma, T.; Kitamura, M.; Takaya,
H.; Sayo, N.; Kumobayashi, H.; Akutagawa, S. J . Am. Chem. Soc. 1987,
109, 5856. (c) Kitamura, M.; Tokunaga, M.; Noyori, R. J . Org. Chem.
1992, 57, 4053.
(2) Kragl, U.; Dreisbach, C. Angew. Chem., Int. Ed. Engl. 1996, 35,
642.
(3) (a) Lasperas, M.; Bellocq, N.; Brunel, D.; Moreau, P. Tetrahedron:
Asymmetry 1998, 9, 3053. (b) Dreisbach, C.; Wischnewski, G.; Kragl,
U.; Wandrey, C. J . Chem. Soc., Perkin Trans. 1 1995, 875. (c) Liu, G.;
Ellman, J . A. J . Org. Chem. 1995, 60, 7712. (d) Soai, K.; Watanabe,
M.; Yamamoto, A. J . Org. Chem. 1990, 55, 4832.
(6) (a) Kitajima, H.; Ito, K.; Katsuki, T. Chem. Lett. 1996, 343. (b)
Kitajima, H.; Ito, K.; Aoki, Y.; Katsuki, T. Bull. Chem. Soc. J pn. 1997,
70, 207
(7) The aminomethylated polystyrene (poly(4-vinyl benzylamine, 1%
DVB, active -NH2 group: 1.0 mmol/g) with its HCl salt was purchased
from Hecheng Science & Technology Development Co., Nankai Uni-
versity, and was treated with Et3N before use.
(4) Cole, B. M.; Shimizu, K. D.; Krueger, C. A.; Harrity, J . P. A.;
Snapper, M. L.; Hoveyda, A. H. Angew. Chem., Int. Ed. Engl. 1996,
35, 1668 and references therein.
(8) The loading of 4 was determined by microanalysis, which is in
good agreement with the value calculated by mass increase of the
polymer.
10.1021/jo990771p CCC: $19.00 © 2000 American Chemical Society
Published on Web 01/05/2000

296 J . Org. Chem., Vol. 65, No. 2, 2000
Yang et al.
Sch em e 1
benzaldehyde (Hammett constant σp) -0.83 for -N(CH3)2)
(entry 10). Most of the polymer-supported amino alcohols
could only give 8-65% ee for the reaction of aliphatic
aldehydes with Et2Zn.11 This polymer-supported BINOL,
however, provided slight higher ee’s for the R-branched
aliphatic and aliphatic aldehydes (runs 17 and 18). Good
enantioselectivity was also achieved for the R,â-unsatur-
ated aliphatic aldehydes (runs 14 and 19). Compared
with the addition of aromatic aldehydes with Et2Zn, the
aliphatic aldehydes took a much longer time as well as
lower yields.
To learn more about the influence of the polymer on
the enantioselectivity, we also studied the reaction of Et2-
Zn with benzaldehyde using a homogeneous BINOL
derivative 5 having a CONHCH2C6H5 group at the 3,3′-
positions of BINOL. The Ti-5 catalyst provided a faster
reaction (12 h at 0 °C) but lower enantioselectivity (63%
ee, 87% yield) than Ti-4 (97% ee).
Ta ble 1. Rea ction of Ald eh yd es w ith Dieth ylzin c
Ca ta lyzed by Ch ir a l P olym er -Su p p or ted Ti-BINOL
Com p lexa
A Typ ica l Exp er im en ta l P r oced u r e. A suspension
of 4 (50 mg, 0.38 mmol/g) in DCM was allowed to stir
under Ar at room temperature for 12 h to swell the resin.
Ti(OiPr)4 (60 µL, 0.175 mmol) was added, followed by a
solution of Et2Zn (0.38 mL of 1 M solution in DCM, 0.38
mmol). After 20 min, benzaldehyde (10 µL, 0.096 mmol)
was added dropwise at 0 °C, and the reaction was allowed
to proceed for a period of time, at the end of which the
cool solution of NH4Cl was introduced to quench the
reaction. The polymer was removed by filtration. The
alcohol was isolated by flash chromatography (silica gel)
after extraction with an organic solvent and the ee value
was determined by HPLC with a chiral OD column.
In summary, we have synthesized a useful and highly
effective polymer-supported BINOL ligand and tested its
capability in the enantioselective addition of diethylzinc
to aldehydes. The present results showed that the
polymer-supported catalyst was substantially more enan-
tioselective than its homogeneous analogue. The key
feature of the new catalyst may be due to the increased
steric influence by the support on the catalyst. This
finding opens a new frontier of development for the
improvement of polymer-supported catalysts. A system-
atic modification of the new catalyst is in progress.
run
R/RCHO
time (h)
yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Ph
24
25
24
30
24
28
48
54
48
18
24
30
28
28
48
24
72
72
60
93
92
89
88
92
78
90
88
90
97
93
89
95
97
89
87
65
52
61
97 (91.9)d
91 (68.6)
94 (88.2)
92 (88.1)
89
92 (94.0)
83 (79.0)
99 (70.0)
96
57
95
65
95
2-ClPh
3-ClPh
4-ClPh
2-MeOPh
3-MeOPh
4-MeOPh
3-NO2Ph
4-NO2Ph
4-N(Me)2Ph
3,4-(MeO)2Ph
Piperonyl
1-Br-2-Nape
(E)-PhCHdCH
2-Nap
2-MeO-1-Nap
Isopropyl
Undecyl
93
94
99
78f
65f
CH3CHdCH
88f
Aldehyde: Ti(OiPr)4/Et2Zn/4 ) 1:1.8:4:0.2; all the reactions
a
were carried out at 0 °C. Isolated yields. c Determined by HPLC
b
d
with Daicel Chiracel OD column. Data in brackets were the
results from a study using BINOL ligand. See refs 9 and 5a. e Nap:
naphthyl. f The ee was measured by analyzing the benzoate
derivative of the alcohol by HPLC with Daicel Chiracel OD column.
Ack n ow led gm en t. We thank the National Natural
Science Foundation of China, Fok Ying Tung Education
Foundation (Hong Kong), the Ministry of Education of
China, and The Hong Kong Polytechnic University for
financial supports. We also thank Dr. D. X. Liu for his
help in the HPLC analysis.
Interestingly, with this polymer-supported catalyst,
similar results were obtained for the substrates with
identical substituents at the ortho, meta, or para position
of the aromatic aldehydes (entries 2-4, 5-7, and 8-9).
However, the 3,4-dimethoxybenzaldehyde and the struc-
turally similar piperonal gave very different results
(entries 11 and 12). It was reported that electronic
properties had a remarkable effect on the enantioselec-
tivity, and the substituents bearing electron-withdrawing
groups in the para position of aryl aldehydes afforded
higher enantioselectivity than those with electron-donat-
ing groups.10 This might explain the low enantioselec-
tivity of the diethylzinc addition to 4-(dimethylamino)-
Su p p or tin g In for m a tion Ava ila ble: Detailed experi-
mental procedures and characterizations involving 2-5 and
the resulting alcohols.
J O990771P
(10) (a) Zhang, H.; Xue, F.; Mak, T. C. W.; Chan, K. S. J . Org. Chem.
1996, 61, 8002. (b) Yang, D.; Yip, Y. C.; Chen, J .; Cheung, K. K. J .
Am. Chem. Soc. 1998, 120, 7659. (c) Corey, E. J .; Heial, C. J .
Tetrahedron Lett. 1995, 36, 9153.
(9) Zhang, F. Y.; Yip, C. W.; Cao, R.; Chan, A. S. C. Tetrahedron:
Asymmetry 1997, 8, 585.
(11) Itsuno, S.; Sakurai, Y.; Ito, K.; Maruyama, T.; Nakahama, S.;
Frechet, J . M. J . J . Org. Chem. 1990, 55, 304.