A highly general catalyst for the enantioselective reaction of aldehydes with diethylzinc

Full text of DOI:10.1021/jo971985e

1364
J . Org. Chem. 1998, 63, 1364-1365
Communications
Sch em e 1. Syn th esis of (R)-2
A High ly Gen er a l Ca ta lyst for th e
En a n tioselective Rea ction of Ald eh yd es w ith
Dieth ylzin c
Wei-Sheng Huang, Qiao-Sheng Hu, and Lin Pu*
Department of Chemistry, University of Virginia,
Charlottesville, Virginia 22901
discovery that (R)-2 is not only a highly enantioselective
catalyst for the reaction of aldehydes with diethylzinc but
also the most general one for different types of aldehydes.
Received October 29, 1997
The asymmetric reaction of alkylzinc complexes with
aldehydes has been demonstrated as a very useful method
for the synthesis of optically active alcohols.1 Since the first
report of a highly enantioselective amino alcohol catalyst
by Noyori et al. in 1986,2 extensive studies have been carried
out in this area and many good catalysts have been
developed.1-18 However, the general applicability of these
catalysts is still limited because each of these catalysts is
good for certain types of aldehyde substrates only. Different
catalysts are usually required for the preparation of different
chiral alcohols by using this method. Therefore, the search
for the ultimate catalyst in this system continues.
Recently, we have reported a highly enantioselective
polymeric chiral catalyst (R)-1 for the addition of diethylzinc
to certain aldehydes.19 This polymer catalyzes the reaction
of aromatic aldehydes in up to 94% enantiomeric excess (ee)
and the reaction of aliphatic aldehydes in up to 83% ee. To
further investigate the catalytic activity and stereoselectivity
of this novel rigid and sterically regular polymeric chiral
catalyst, we have synthesized (R)-2 as the monomeric model
compound of (R)-1. In this paper, we report our exciting
(1) For reviews, see: (a) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833. (b)
Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991, 30, 49.
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(3) (a) Soai, K.; Ookawa, A.; Kaba, T.; Ogawa, K. J . Am. Chem. Soc. 1987,
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Chem. Commun. 1987, 1690. (b) Soai, K.; Yokoyama, S.; Hayasaka, T. J .
Org. Chem. 1991, 56, 4264.
A binaphthyl molecule (R)-3 is synthesized in two steps
from the optically pure (R)-1,1′-bi-2-naphthol20 by protection
of the hydroxyls with methoxymethyl groups21 and then
iodonation at the 3,3′-positions.22 The Suzuki coupling of
(R)-3 with an arylboronic acid 4 followed by hydrolysis gives
(R)-2 (Scheme 1). The specific optical rotation of (R)-2 is
[R]D ) 95.0 (c ) 0.962, THF).
(5) Watanabe, M.; Araki, S.; Butsugan, Y.; Uemura, M. J . Org. Chem.
1991, 56, 2218.
When this molecule is used to catalyze the reaction of
benzaldehyde with diethylzinc, the corresponding alcohol is
produced in over 99% ee. We have therefore explored the
generality of this catalyst. We are very pleased to discover
that (R)-2 exhibits high enantioselectivity for many different
substrates including para-, ortho-, or meta-substituted
aromatic aldehydes, linear or branched aliphatic aldehydes,
and aryl or alkyl substituted R,â-unsaturated aldehydes.
These results are summarized in Table 1. All of the
reactions are carried out in toluene solution at 0 °C using 5
mol % (R)-2 unless otherwise indicated. The racemic alcohol
products are also prepared and their HPLC or GC data are
compared with those of the optically active alcohol products
in order to determine the enantioselectivity of (R)-2. The
absolute configuration of all of the products is R as deter-
mined by comparing their optical rotation values or GC data
with the literature results.1-19 (R)-2 can be recovered by
column chromatography on silica gel with no change of the
structure or activity.
(6) J oshi, N. N.; Srebnik, M.; Brown, H. C. Tetrahedron Lett. 1989, 30,
5551.
(7) (a) Ishizaki, M.; Fujita, K.-i.; Shimamoto, M.; Hoshino, O. Tetrahe-
dron: Asymmetry 1994, 5, 411. (b) Bolm, C.; Schlingloff, G.; Hayms, K.
Chem. Ber. 1992, 125, 1191.
(8) (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.
(9) J in, M.-J .; Ahn, S.-J .; Lee, K.-S. Tetrahedron Lett. 1996, 37, 8767.
(10) Kang, J .; Lee, J . W.; Kim, J . I. J . Chem. Soc. Chem. Commun. 1994,
2009.
(11) Kang, J .; Kim, D. S.; Kim, J . I. Synlett 1994, 842.
(12) Prasad, K. R. K.; J oshi, N. N. J . Org. Chem. 1997, 62, 3770.
(13) Chelucci, G.; Conti, S.; Falorni, M.; Giacomelli, G. Tetrahedron 1991,
47, 8251.
(14) Wirth, T.; Kulicke, K. J .; Fragale, G. Helv. Chim. Acta 1996, 79,
1957.
(15) Rijnberg, E.; Hovestad, N. J .; Kleij, A. W.; J astrzebski, J . T. B. H.;
Boersma, J .; J anssen, M. D.; Spek, A. L.; van Koten, G. Organometallics
1997, 16, 2847.
(16) (a) Yoshioka, M.; Kawakita, T.; Ohno, M. Tetrahedron Lett. 1989,
30, 1657. (b) Takahashi, H.; Kawakita, T.; Yoshioka, M.; Kobayashi, S.;
Ohno, M. Tetrahedron Lett. 1989, 30, 7095.
(17) (a) Schmidt, B.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1991, 30,
99. (b) Seebach, D.; Beck, A. K.; Schmidt, B.; Wang, Y. M. Tetrahedron
1994, 50, 4363.
(18) Qiu, J .; Guo, C.; Zhang, X. J . Org. Chem. 1997, 62, 2665.
(19) (a) Huang, W.-S.; Hu, Q.-S.; Zheng, X.-F.; Anderson, J .; Pu, L. J .
Am. Chem. Soc. 1997, 119, 4313. (b) Hu, Q.-S.; Huang, W.-S.; Pu, L. J . Am.
Chem. Soc. 1997, 119, 12454.
(20) Hu, Q.-S.; Vitharana, D.; Pu, L. Tetrahedron: Asymmetry 1995, 6,
2123.
(21) Kitajima, H.; Aoki, Y.; Ito, K.; Katsuki, T. Chem. Lett. 1995, 1113.
(22) Cox, P. J .; Wang, W.; Snieckus, V. Tetrahedron Lett. 1992, 17, 2253.
S0022-3263(97)01985-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/14/1998

Communications
J . Org. Chem., Vol. 63, No. 5, 1998 1365
Ta ble 1. Rea ction of Ald eh yd es w ith Dieth ylzin c
give (R)-1-phenylpropanol as a colorless liquid (129 mg,
95%). HPLC analysis on Chiracel-OD column (eluent:
2-propanol/hexane ) 1/9; 1 mL/min) showed an ee of over
99%. When 0.5 mol % of (R)-2 was used, although the high
enantioselectivity was maintained, the reaction became
much slower.
Ca ta lyzed by (R)-2
The previously reported catalysts that have shown good
results for the asymmetric reaction of certain aldehydes with
diethylzinc are cited in refs 2-18. Most of these catalysts
are good for aromatic aldehydes and few are good for
aliphatic aldehydes. Although the addition to R,â-unsatur-
ated aldehydes is particularly useful since the resulting
chiral allylic alcohols are important precursors to many
organic compounds, it is very rare to find an enantioselective
catalyst for the reaction of alkyl-substituted R,â-unsaturated
aldehydes. Catalysts prepared by Katsuki et al.8 are also
made of the chiral binaphthyl structure. Although these
catalysts show good enantioselectivity for the reaction of
aromatic aldehydes, their catalytic properties for simple
aliphatic aldehydes and alkyl-substituted R,â-unsaturated
aldehydes have not been studied. Among all of the previ-
ously reported catalysts, the chiral titanium complexes
developed by Seebach et al.17 represent the most enantiose-
lective catalyst system. However, the use of these catalysts
normally requires the addition of a stoichiometric amount
of Ti(OiPr)4. In the work we report here, a catalytic amount
of (R)-2 can carry out the highly enantioselective reaction
of different types of substrates including aromatic, aliphatic,
and R,â-unsaturated aldehydes with diethylzinc. This un-
usually general enantioselectivity makes (R)-2 superior to
all of the currently known catalysts for this reaction.
The study of (R)-2 not only provides a highly enantiose-
lective and practical catalyst but also sheds new light on
improving the enantioselectivity of the polymeric catalyst
(R)-1. The work described here demonstrates that (R)-2 has
greater enantioselectivity as well as catalytic activity than
the polymer (R)-1 especially for the reaction of ortho-
substituted benzaldehydes and aliphatic aldehydes. We
attribute the differences in the catalytic properties between
the monomer and the polymer to their differences in
structure. In (R)-1, the dialkoxy phenylene linker can serve
as a dual ligand for both of the adjacent binaphthyl units,
which makes this polymeric catalyst structurally different
from the monomer (R)-2. On the basis of this analysis, we
have modified the structure of the polymeric catalyst and
have greatly improved its catalytic properties. These results
will be reported shortly.
a
b
Determined by HPLC-Chiracel OD column. Determined by
chiral GC (â-Dex capillary column). c Determined by HPLC-
Chiracel AD column. Determined by analyzing the acetate
d
derivative of the product on the GC-â-Dex capillary column.
e Determined by analyzing the benzoate derivative of the product
on the GC-â-Dex capillary column. f Et2O was used as the solvent.
g
h
At -40 °C. 0.3 equiv of catalyst was used. 0.2 equiv of catalyst
was used. The reaction was carried out in THF at -10 °C, and
the aldehyde was distilled before use.
Ack n ow led gm en t . This work was supported by the
Department of Chemistry at North Dakota State Univer-
sity and then by the Department of Chemistry at Univer-
sity of Virginia. Partial support from the National Science
Foundation (DMR-9529805), and the US Air Force (F49620-
96-1-0360) is also gratefully acknowledged.
A typical experimental procedure for these reactions is
described below. Under nitrogen, to a Schlenk flask con-
taining toluene (10 mL, dried with Na) were added (R)-2
(42 mg, 0.05 mmol) and diethylzinc (0.21 mL, 2.0 mmol) at
room temperature. After the colorless solution was stirred
for ca. 15 min, the flask was cooled to 0 °C and benzaldehyde
(0.1 mL, 1.0 mmol) was added dropwise. The solution turned
yellow, which then faded in 4 h, indicating the completion
of the reaction. HCl (1N) was added to quench the reaction
at 0 °C, and the aqueous layer was extracted with ether.
The combined organic layer was washed with brine until
pH ) 7 and then dried over anhydrous Na2SO4. After
removal of the solvent, the residue was purified by column
chromatography on silica gel with EtOAc/hexanes (1:5) to
Su p p or tin g In for m a tion Ava ila ble: Detailed experimental
procedures and characterizations involving (R)-2 and 4 in the
catalytic reaction and the HPLC and GC analysis results of the
chiral alcohol products (4 pages).
J O971985E