Asymmetric Epoxidation of α,β-Unsaturated Ketones Catalyzed by Chiral Polybinaphthyl Zinc Complexes: Greatly Enhanced Enantioselectivity by a Cooperation of the Catalytic Sites in a Polymer Chain

Article abstract of DOI:10.1021/jo990749w

Polybinaphthyl zinc catalysts have been developed for the asymmetric epoxidation of a,/3-unsaturated ketones in the presence of tert-butyl hydroperoxide. Up to 81% ee has been achieved for the epoxidation of α,β-unsaturated ketones containing β-aliphatic

Full text of DOI:10.1021/jo990749w

J . Org. Chem. 1999, 64, 8149-8155
8149
Asym m etr ic Ep oxid a tion of r,â-Un sa tu r a ted Keton es Ca ta lyzed by
Ch ir a l P olybin a p h th yl Zin c Com p lexes: Gr ea tly En h a n ced
En a n tioselectivity by a Coop er a tion of th e Ca ta lytic Sites in a
P olym er Ch a in
Hong-Bin Yu, Xiao-Fan Zheng, Zhi-Ming Lin, Qiao-Sheng Hu, Wei-Sheng Huang, and
Lin Pu*
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901
Received May 5, 1999
Polybinaphthyl zinc catalysts have been developed for the asymmetric epoxidation of R,â-unsaturated
ketones in the presence of tert-butyl hydroperoxide. Up to 81% ee has been achieved for the
epoxidation of R,â-unsaturated ketones containing â-aliphatic substituents by using a binaphthyl
polymer combined with diethylzinc. A very interesting positive cooperative effect of the catalytic
sites in the polymer chain is observed which leads to greatly increased enantioselectivity over the
corresponding monomer ligands.
In tr od u ction
Sch em e 1. Th e Ep oxid a tion of r,â-Un sa tu r a ted
Keton es
The asymmetric epoxidation of R,â-unsaturated ke-
tones (1) is a very important organic transformation since
the resulting chiral R,â-epoxy ketones (2) are versatile
precursors to many natural products and drug molecules
Scheme 1).1 In 1980, J ulia et al. discovered that the
-6
(
use of an excess amount of polypeptides and hydrogen
peroxide could promote the asymmetric epoxidation of
chalcone and its derivatives with both good enantiose-
lectivity and diastereoselectivity.1a However, this epoxi-
dation process is found to be mostly limited for the
reaction of aryl-substituted R,â-unsaturated ketones.1
The polypeptide reagents cannot carry out the epoxida-
tion of R,â-unsaturated ketones with â-alkyl groups other
than tert-butyl or cyclopropyl. Recently, important progress
,2
When substrates contained only aromatic substituents,
this process showed only modest enantioselectivity. Later,
J ackson and co-workers found that when (+)-diethyl
tartrate (4) was treated with dibutylmagnesium, it
catalyzed the epoxidation of aryl-substituted R,â-unsat-
urated ketones with high enantioselectivity in the pres-
ence of t-BuOOH. Recently, Shibasaki and co-workers
reported a catalytic asymmetric epoxidation of R,â-
unsaturated ketones by using hydroperoxides and cata-
has been made by Lygo,3 Taylor, and Arai
a
3b
3c,d
on using
chiral phase transfer catalysts for the asymmetric ep-
oxidation of both alkyl- and aryl-substituted R,â-unsatur-
ated ketones.
In 1996, Enders et al. reported an epoxidation of R,â-
unsaturated ketones under oxygen for substrates con-
taining alkyl substituents with good enantioselectivity.4
The reaction was conducted in the presence of a stoichio-
metric amount of a zinc complex generated from the
reaction of a chiral amino-alcohol 3 with diethylzinc.
5
lysts made from the reaction of the chiral binaphthyl
6
ligands 5 with La(O-i-Pr) and Yb(O-i-Pr) . These lan-
3
3
thanoid catalysts showed very good enantioselectivity for
substrates containing either alkyl or aryl substituents.
(
1) (a) J uli a´ , S.; Masana, J .; Vega, J . C. Angew. Chem., Int. Ed. Engl.
1
980, 19, 929. (b) Kroutil, W.; Lasterra-S a´ nchez, M. E.; Maddrell, S.
J .; Mayon, P.; Morgan, P.; Roberts, S. M.; Thornton, S. R.; Todd, C. J .;
T u¨ ter, M. J . Chem. Soc., Perkin Trans. 1 1996, 2837. (c) Itsuno, S.;
Sakakura, M.; Ito, K. J . Org. Chem. 1990, 55, 6047.
(
2) For reviews on the polypeptide-mediated epoxidation of R,
â-unsaturated ketones, see: (a) Pu, L. Tetrahedron: Asymmetry 1998,
, 1457. (b) Ebrahim, S.; Wills, M. Tetrahedron: Asymmetry 1997, 8,
9
3
163.
In our laboratory, we are interested in studying asym-
metric reactions catalyzed by chiral polymers. We have
used binaphthyl structures to construct a class of chiral
(3) (a) Lygo, B.; Wainwright, P. G. Tetrahedron 1999, 55, 6289. (b)
Macdonald, G.; Alcaraz, L.; Lewis, N. J .; Taylor, R. J . K. Tetrahedron
Lett. 1998, 39, 5433. (c) Arai, S.; Oku, M.; Miura, M.; Shioiri, T. Synlett
1
rigid polymers7 and have applied these materials to a
-9
998, 1201. (d) Arai, S.; Tsuge, H.; Shioiri, T. Tetrahedron Lett. 1998,
9, 7563.
3
9-11
number of catalytic asymmetric reactions.
Catalysts
(4) (a) Enders, D.; Zhu, J .; Raabe, G. Angew. Chem., Int. Ed. Engl.
based on these polymers have exhibited very high enan-
1
1
996, 35, 1725. (b) Enders, D.; Zhu, J .; Kramps, L. Liebigs Ann./ Recueil
997, 1101.
(
1
0
tioselectivity for the organozinc addition to aldehydes,
5) Elston, C. L.; J ackson, R. F. W.; MacDonald, S. J . F.; Murray,
P. J . Angew. Chem., Int. Ed. Engl. 1997, 36, 410.
6) Bougauchi, M.; Watanabe, S.; Arai, T.; Sasai, H.; Shibasaki, M.
J . Am. Chem. Soc. 1997, 119, 2329.
the hetero Diels-Alder reaction of ethyl glyoxylate with
(
(7) Pu, L. Chem. Rev. 1998, 98, 2405.
1
0.1021/jo990749w CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/07/1999

8
150 J . Org. Chem., Vol. 64, No. 22, 1999
Yu et al.
Ta ble 1. Ep oxid a tion of r,â-Un sa tu r a ted Keton es in th e P r esen ce of th e P olybin a p h th yl (R)-6, Dieth ylzin c, a n d Oxygen
2
-methyl-1,3-butadiene,11a and the 1,3-dipolar cycload-
ketones. Table 1 summarizes the use of (R)-6 for the
epoxidation of various substrates under various condi-
1
1b
12
dition of nitrones with vinyl ethers. Herein, we report
our discovery that the polybinaphthyls can also catalyze
the asymmetric epoxidation of R,â-unsaturated ketones.
An interesting cooperative effect of the catalytic sites in
a binaphthyl polymer chain is found to greatly enhance
the enantioselectivity over the corresponding monomer
ligands.
Resu lts a n d Discu ssion
1
. Th e Asym m etr ic Ep oxid a tion of r,â-Un sa tu r -
a ted Keton es in th e P r esen ce of Dieth ylzin c, Oxy-
gen , a n d a Stoich iom etr ic Am ou n t of a Ch ir a l
Bin a p h th yl P olym er . Previously, we have prepared a
polybinaphthyl (R)-6 from the Suzuki coupling of an
optically pure binaphthyl monomer with a phenylene
tions. As shown in entry 1, 1 equiv (based on the
binaphthyl unit) of the polymer after treated with 0.95
equiv of diethylzinc was used to oxidize chalcone (1a ) in
methylene chloride under oxygen. After 18 h at 0 °C, the
epoxy product 2a was obtained in 41% yield. Its ee was
determined to be 71% by HPLC-Chiracel OD column.
The absolute configuration of the product was 2S and 3R
by comparing its optical rotation with the literature
linker.1 Analogous to Enders’s study of 3, we have used
polymer (R)-6 combined with diethylzinc and oxygen to
carry out the asymmetric epoxidation of R,â-unsaturated
0b
4
(8) (a) Hu, Q.-S.; Vitharana, D.; Liu, G.; J ain, V.; Wagaman, M. W.;
Zhang, L.; Lee, T. R.; Pu, L. Macromolecules 1996, 29, 1082. (b) Ma,
L.; Hu, Q.-S.; Vitharana, D.; Wu, C.; Kwan, C. M. S.; Pu, L.
Macromolecules 1997, 30, 204. (c) Hu, Q.-S.; Vitharana, D.; Liu, G.;
J ain, V.; Pu, L. Macromolecules 1996, 29, 5075. (d) Ma, L.; Hu, Q.-S.;
Musick, K.; Vitharana, D.; Wu, C.; Kwan, C. M. S.; Pu, L. Macromol-
ecules 1996, 29, 5083. (e) Musick, K. Y.; Hu, Q.-S.; Pu, L. Macromol-
ecules 1998, 31, 2933.
4
data. When increasing the amount of diethylzinc, al-
though the yield became much higher, the ee was
significantly reduced (entry 2). No epoxidation was
observed when the reaction was conducted in THF (entry
6
), probably because THF reduced the reactivity of the
(
9) (a) Hu, Q.-S.; Zheng, X.-F.; Pu, L. J . Org. Chem. 1996, 61, 5200.
b) Hu, Q.-S.; Vitharana, D.; Zheng, X.-F.; Wu, C.; Kwan, C. M. S.; Pu,
L. J . Org. Chem. 1996, 61, 8370.
10) (a) Huang, W.-S.; Hu, Q.-S.; Zheng, X.-F.; Anderson, J .; Pu, L.
polybinaphthyl zinc complex, formed from the reaction
of the polymer with diethylzinc, through coordination to
the zinc center. Both the ee and yield were very low for
(
(
J . Am. Chem. Soc. 1997, 119, 4313. (b) Hu, Q.-S.; Huang, W.-S.;
Vitharana, D.; Zheng, X.-F.; Pu, L. J . Am. Chem. Soc. 1997, 119, 12454.
(
c) Huang, W.-S.; Hu, Q.-S.; Pu, L. J . Org. Chem. 1998, 63, 1364. (d)
(12) References about the R,â-unsaturated ketones: (a) See ref 4b
for 1b and 1c. (b) For 1d and 1e: Krauss, S. R.; Smith, S. G. J . Am.
Chem. Soc. 1981, 103, 141. (c) For 1f: Ross, D. R.; Waight, E. S. J .
Chem. Soc. 1965, 6710. (c) For 1g: Bowers, K. W.; Giese, R. W.;
Grimshaw, J .; House, H. O.; Kolodny, N. H.; Kronberger, K.; Roe, D.
K. J . Am. Chem. Soc. 1970, 92, 2783. (c) For 1h : Shotter, R. G.
Tetrahedron 1973, 29, 2163.
Hu, Q.-S.; Huang, W.-S.; Pu, L. J . Org. Chem. 1998, 63, 2798. (e)
Huang, W.-S.; Pu, L. J . Org. Chem.. 1999, 64, 4222. (f) Huang, W.-S.;
Hu, Q.-S.; Pu, L. J . Org. Chem. 1999, 64, 7940-7956.
(11) (a) J ohannsen, M.; J ørgensen, K. A.; Zheng, X.-F.; Hu, Q.-S.;
Pu, L. J . Org. Chem. 1999, 64, 299. (b) Simonsen, K. B.; J orgensen, K.
A.; Hu, Q.-S.; Pu, L. J . Chem. Soc., Chem. Commun. 1999, 811.

Asymmetric Epoxidation of R,â-Unsaturated Ketones
J . Org. Chem., Vol. 64, No. 22, 1999 8151
Ta ble 2. Asym m etr ic Ep oxid a tion of r,â-Un sa tu r a ted Keton es in th e P r esen ce of th e P olym er (S)-14, Dieth ylzin c, a n d
Oxygen
Sch em e 2. A P r op osed Mech a n ism for th e
P olybin a p h th yl-Med ia ted Ep oxid a tion of Ch a lcon e
Sch em e 3. Syn th esis of a Mon om eth yla ted Ch ir a l Bin a p h th ol P olym er (S)-14
the substrate containing a â-aliphatic substituent (1b)
entry 10). In all the reactions, only one diastereomer was
formed from each enone.
epoxide from the (E)-R,â-unsaturated ketone. This inter-
mediate generates (2S,3R)-2a as the major enantiomer.
We have modified the polymer by introducing a methyl
group (R′ ) Me) into the binaphthyl unit of (R)-6-(R)-8.
As shown in Scheme 3, monomethylation of 6,6′-dibromo-
(
On the basis of Enders’s study on the amino alcohol-
4
diethylzinc-mediated epoxidation, a mechanism for the
9
asymmetric epoxidation promoted by polymer (R)-6 is
proposed (Scheme 2). The reaction of (R)-6 with dieth-
ylzinc can lead to (R)-7 which can be oxidized by oxygen
to give the zinc peroxy complex (R)-8. Enders’s work
indicates that the rate-limiting step is probably the
conversion from such a zinc peroxy complex to a Michael
addition type intermediate like 9. Formation of interme-
diate 9 explains the exclusive production of the trans-
1,1′-bi-2-naphthol [(S)-10] gave (S)-11 which was then
converted to a binaphthyl acetate monomer (S)-12. The
Suzuki coupling of (S)-12 with a diboronic acid 13
followed by hydrolysis led to the formation of polymer
(S)-14 with monomethylated binaphthol units. The mo-
lecular weight of this polymer was M
) 12 800 (PDI ) 2.8) as measured by gel permeation
chromatography (GPC) relative to polystyrene standards.
w
) 36 000 and M
n

8
152 J . Org. Chem., Vol. 64, No. 22, 1999
Yu et al.
Sch em e 4. A P r op osed Mech a n ism for th e
P olybin a p h th yl-Ca ta lyzed Asym m etr ic
Ep oxid a tion of Ch a lcon e
to be catalytic may be the equilibrium between zinc
peroxide (R)-15 and zinc tert-butoxide (R)-16 in the
presence of t-BuOOH. In this step, (R)-16 reacts with
t-BuOOH to regenerate chiral zinc peroxide (R)-15 which
oxidizes 1a to 2a .
We have tested the use of two monomer ligands (R)-
0c
71 and (R)-18
10f
1
for the epoxidation of a â-propyl-
substituted enone 1c. Both (R)-17 and (R)-18 contain 3,3′-
aryl substituents on the binaphthyl units which was
expected to provide increased chiral barrier and better
steric control. However, when the epoxidation of 1c was
conducted in the presence of t-BuOOH and diethylzinc,
neither of the monomer ligands showed improvement on
the enantioselectivity. At room temperature, (R)-17
converted 1c to 2c in 75% yield and 30% ee, and (R)-18
did in 83% yield and 21% ee.
Although these monomer ligands gave very low enan-
tioselectivity, when (R)-19, a polymer containing mono-
mer ligand (R)-17 as its structural unit was used to
catalyze the epoxidation of 1c, the corresponding epoxy
product 2c was obtained in 91% yield and 76% ee (Table
3
, entry 1). Thus, from the monomer to the polymer, there
is a dramatic enhancement in enantioselectivity. Table
3
summarizes the use of polymer (R)-19 for the asym-
1
2
metric epoxidation of various R,â-unsaturated ketones.
As shown in Table 3, up to 81% ee (entry 8) was observed
for the asymmetric epoxidation of the R,â-unsaturated
ketones containing aliphatic substituents, and over 70%
ee was observed in general for the epoxidation of the R,â-
unsaturated ketones containing only aromatic substitu-
ents. In most of the reactions, 20 mol % of the polymer
Its specific optical rotation was [R]
CH Cl ). This polymer had better solubility than (R)-6
in organic solvents.
D
) -301.1 (c ) 0.5,
2
2
(based on the binaphthyl unit) was used. When a sto-
Polymer (S)-14 was used for the asymmetric epoxida-
tion of R,â-unsaturated ketones in the presence of dieth-
ylzinc and oxygen (Table 2). This polymer showed largely
improved yield for the epoxidation without using excess
diethylzinc. The diastereoselectivity also remained very
high (>99% de). However, introduction of the methyl
group to the binaphthyl unit of the polymer did not
improve the enantioselectivity.
ichiometric amount of (R)-19 was used, no improvement
on the enantioselectivity was observed (entry 6). The
configuration of the major enantiomers of the epoxy
products is 2R and 3S as determined by comparing their
optical rotations with the literature data. This is opposite
to that of the products generated in the presence of
polymer (R)-6, even though both of the polymers contain
R binaphthyl units. Factors causing this difference
remain to be investigated.
2
. Develop m en t of a Ca ta lytic Asym m etr ic Ep -
oxid a tion of r,â-Un sa tu r a ted Keton es Usin g P oly-
bin a p h th yls, Dieth ylzin c, a n d ter t-Bu tyl Hyd r op -
er oxid e. As shown above, when the epoxidation of R,â-
unsaturated ketones was carried out by using the
binaphthyl polymeric zinc complexes and oxygen, the
results were not satisfactory. Although up to 71% ee was
obtained, the conversion was low (Table 1, entry 1). On
the other hand, when high conversions were achieved,
the ee’s became small (Table 2). In all cases, the use of a
stoichiometric amount of the chiral binaphthyl polymers
was necessary.
To improve the polybinaphthyl-mediated epoxidation,
we decided to use t-BuOOH in place of oxygen as the
oxidants. This led to our discovery of a catalytic asym-
metric epoxidation of R,â-unsaturated ketones by using
the polybinaphthyl zinc complexes. In the presence of 5
mol % of polymer (R)-6 and 10 mol % of diethylzinc in
methylene chloride at 0 °C, chalcone (1a ) was oxidized
by t-BuOOH13 to the corresponding epoxide 2a in 95%
isolated yield and with >99% de and 28% ee. Scheme 4
shows a possible mechanism for this catalytic process.
The key step that enables this zinc-mediated epoxidation
To understand the origin of the greatly enhanced
enantioselectivity of polymer (R)-19 versus monomer (R)-
1
0d
1
7, we have studied the use of another polymer (R)-20
for the asymmetric epoxidation. Under the conditions of
entry 1 in Table 3, (R)-20 converted 1c to 2c with 37%
ee and 99% yield, and 1b to 2b with 55% ee and 88%
yield. Thus, the enantioselectivity of (R)-20 is very similar
to that of monomer (R)-17 and much lower than that of
polymer (R)-19. This indicates that the steric and elec-
tronic environments of the monomer catalyst are mostly
preserved in polymer (R)-20 and are quite different from
those of polymer (R)-19. The high enantioselectivity of
polymer (R)-19 over monomer (R)-17 is not merely due
to the increased size of the macromolecules.
We propose that the much better enantioselectivity of
polymer (R)-19 over monomer (R)-17 and polymer (R)-
2
0 might arise from the structure of the polymeric zinc
complex (R)-21 probably formed when (R)-19 is treated
with diethylzinc. In (R)-21, the p-dialkoxylphenylene
linker acts as a dual ligand to coordinate to the zinc
centers on the two adjacent binaphthyl units. Thus, there
is a cooperative effect between the neighboring catalytic
sites in the polymer chain which has greatly increased
the enantioselectivity of the catalyst. However, neither
monomer (R)-17 nor polymer (R)-20 could achieve such
(
13) The commercially obtained t-BuOOH was treated before use:
Hill, J . G.; Rossiter, B. E.; Sharpless, K. B. J . Org. Chem. 1983, 48,
607.
3

Asymmetric Epoxidation of R,â-Unsaturated Ketones
J . Org. Chem., Vol. 64, No. 22, 1999 8153
a site cooperation and each of their binaphthyl units
should function independently. The cooperative effect as
shown in (R)-21 might have changed the electronics as
well as the steric conformation of both the catalytic sites
and the polymer chain. Earlier, we had observed that this
cooperation of the catalytic sites led to negative effects
on the asymmetric reaction of diethylzinc with aldehydes,
effect in the binaphthyl polymer could allow the design
of new and highly enantioselective polymeric catalysts
for asymmetric synthesis.
Exp er im en ta l Section
Gen er a l Da ta . All the solvents were dried according to the
standard methods prior to use. Chalcone was purchased from
Aldrich and dried under vacuum for 10 h. t-BuOOH was
purchased from Aldrich and was treated according to litera-
i.e., both monomer (R)-17 and polymer (R)-20 had much
better enantioselectivity than (R)-19.1
0a-d
Thus, interac-
13
ture before use. Diethylzinc and palladium tetrakis(triph-
tion of the neighboring catalytic sites in the polymer
chain of (R)-21 has imposed very different effects on
different reactions.
enylphosphine) were purchased from Strem. Molecular weights
of the polymers were measured with gel permeation chroma-
tography by using THF eluent and polystyrene standards.
P r ep a r a tion a n d Ch a r a cter iza tion of (S)-11. To a
suspension of (S)-10 (7.75 g, 17.5 mmol) and K
2 3
CO (3.6 g, 26.3
3
. Su m m a r y
mmol) in acetone was added CH I (1.2 mL, 24.2 mmol) at room
3
temperature. The mixture was stirred at room temperature
for 32 h and monitored by H NMR spectroscopy. When the
dimethylated side product started to form, the reaction was
In summary, polybinaphthyl zinc catalysts have been
developed for the asymmetric epoxidation of R,â-unsatur-
ated ketones. A binaphthyl polymer has shown up to 81%
ee for the epoxidation of R,â-unsaturated ketones con-
taining â-aliphatic substituents. These substrates failed
to undergo epoxidation when using the previously re-
ported polypeptide reagents. In addition, only a catalytic
amount of the binaphthyl polymer is used in our new
epoxidation process but excess polypeptides (based on the
monomer units) were required previously. A very inter-
esting positive cooperative effect of the catalytic sites in
the polybinaphthyl chain is observed, which leads to
greatly increased enantioselectivity over the correspond-
ing monomer ligands. Understanding of this cooperative
1
stopped by pouring the mixture into H
ethyl acetate (3 × 100 mL), the combined organic layer was
SO . The
2
O. After extraction with
washed with brine (3 × 20 mL) and dried over Na
2
4
solvent was then removed in a vacuum, and the crude product
was purified by flash chromatography on silica gel (EtOAc/
hexane: 20:1) to give (S)-11 as a white crystalline solid in 40%
1
yield (3.1 g). mp 92-94 °C. [R]
D
) 113.3 (c ) 0.5, CH
, 400 MHz) δ 3.80 (s, 3H, CH
.86 (d, J ) 8.9 Hz, 1H), 6.99 (d, J ) 8.8 Hz, 1H), 7.28 (dd, J
2
Cl
2
). H
NMR (CDCl
3
3
), 4.90 (s, 1H, OH),
6
)
(
1.9, 8.9 Hz, 1H), 7.34 (m, 2H), 7.48 (d, J ) 9.1 Hz, 1H), 7.81
d, J ) 8.9 Hz, 1H), 7.95 (d, J ) 9.2 Hz, 1H), 8.01 (d, J ) 1.9
Hz, 1H), 8.05 (d, J ) 1.9 Hz, 1H). Anal. Calcd for C H O -
2
1
14
2
2
Br : C, 55.02; H, 3.06. Found: C, 55.93; H, 3.33.

8
154 J . Org. Chem., Vol. 64, No. 22, 1999
Ta ble 3. Asym m etr ic Ep oxid a tion of r,â-Un sa tu r a ted Keton es Ca ta lyzed by P olym er (R)-19a
Yu et al.
P r ep a r a tion a n d Ch a r a cter iza tion of (S)-12. To a
solution of (S)-11 (0.54 g, 1.2 mmol) and Et N (1 mL) in CH
Cl was added Ac O (0.5 mL) at 0 °C. The mixture was stirred
organic layer was then separated and combined with CH
(500 mL). After washed with brine and dried over Na SO , the
solvent was removed, and the residue was redissolved in a
minimum amount of CH Cl . Methanol was then added to
precipitate out the polymer. This process was repeated three
times to give (S)-14 as a yellow solid in 75% yield. GPC: M
) 36 000 and M ) 12 800 (PDI ) 2.8). [R] ) 301.1 (c ) 0.5,
). H NMR (CDCl , 400 MHz) δ 0.80 (s, 6H with a
2 2
Cl
3
2
-
2
4
2
2
at room temperature for 4 h, and the reaction was monitored
2
2
1
by H NMR spectroscopy. After the reaction was complete, the
mixture was poured into H
2
O and extracted with EtOAc. The
w
combined organic layer was washed with brine (5 mL), 1 N
n
D
1
HCl (2 × 10 mL), brine (5 mL), saturated sodium bicarbonate
CH
2
Cl
2
3
solution (10 mL), and brine (5 mL) and dried over Na
2
SO
4
.
shoulder at 0.92), 1.24 (m, 10H), 1.38 (m, 4H), 1.70 (m, 4H),
3.92 (m, 7H), 5.02 (br, 1H), 7.13 (s, 2H, small peaks at 6.93,
7.04), 7.19 (m, 1H), 7.32 (m, 1H), 7.40 (m, 1H), 7.58 (m, 3H),
After evaporation of the solvent, the residue was recrystallized
from EtOAc/hexanes (1:3) to give (S)-12 as a white crystalline
solid in 87% yield (0.51 g). mp 164-165 °C. [R]
D
) +85.9 (c )
7.98 (m, 1H), 8.15 (m, 3H). Anal. Calcd for (C39
81.53; H, 7.32. Found: C, 81.47; H, 7.50.
42 4 n
H O ) : C,
1
0
.5, CH Cl ). H NMR (CDCl , 400 MHz) δ 1.79 (s, 3H), 3.76
2
2
3
(
(
(
s, 3H), 6.95 (d, J ) 8.9 Hz, 1H), 7.05 (d, J ) 9.1 Hz, 1H), 7.29
dd, J ) 1.9, 9.2 Hz, 1H), 7.34 (dd, J ) 1.7, 8.9 Hz, 1H), 7.43
s, 1H), 7.45 (s, 1H), 7.88 (d, J ) 3.0 Hz, 1H), 7.90 (d, J ) 3.5
A Typ ica l P r oced u r e for th e Asym m etr ic Ep oxid a tion
in th e P r esen ce of P olym er (R)-6, Dieth ylzin c, a n d
Oxygen . Ep oxid a tion of tr a n s-Ch a lcon e (1a ). In a drybox,
diethylzinc (38 µL, 0.38 mmol, 0.95 equiv) was added to a
Hz, 1H), 8.01 (d, J ) 1.6 Hz, 1H), 8.10 (d, J ) 1.6 Hz, 1H).
Anal. Calcd for C23 Br : C, 55.20; H, 3.20. Found: C,
5.40; H, 3.12.
P r ep a r a tion a n d Ch a r a cter iza tion of Ch ir a l P olybi-
n a p h th yl (S)-14. Under nitrogen, a mixture of (S)-12 (0.50
g, 1.0 mmol), diboronic acid 13 (1.0 mmol), Pd(PPh (58 mg,
.05 mmol) in THF (5 mL)/1 N K CO (5 mL) was heated at
H
16
O
3
2
2 2
solution of (R)-6 (224 mg, 0.40 mmol, 1.0 equiv) in dry CH Cl
5
(15 mL) in a 50 mL Schlenk flask at room temperature while
stirring. After 90 min, the reaction mixture was cooled to 0
°C and was placed under a balloon filled with O . The nitrogen
2
inside the flask should not be displaced. After stirred for 2 h,
the reaction mixture was cooled to -78 °C, and trans-chalcone
(80 mg, 0.38 mmol, 0.95 equiv) was added. The reaction
mixture was stirred for 30 min at this temperature and then
3
)
4
0
2
3
reflux. After 48 h, KOH (0.56 g) was added, and the mixture
was heated at reflux for another 12 h under nitrogen. The

Asymmetric Epoxidation of R,â-Unsaturated Ketones
J . Org. Chem., Vol. 64, No. 22, 1999 8155
1
2
rapidly warmed to 0 °C while stirring. The reaction progress
was followed by thin-layer chromatography. After 18 h,
2a (R ) R ) P h ). Flow rate: 1.0 mL/min. Eluent: hexane:
i-PrOH ) 90:10. Retention time: minor 10.6 min, major 11.3
4
b
saturated aqueous NH
4
Cl (5 mL), 10% aqueous Na
2
SO
3
(5 mL),
min. ee: 73%. [R]D ) -151.1 (c ) 1.0, CH Cl ). Literature
[R]D ) -130.0 (c ) 1.1, CH Cl ).
2
2
and Et O (50 mL) were sequentially added to the reaction
2
2
2
mixture, and the organic phase was separated. The polymer
was precipitated out of the diethyl ether solution with metha-
nol and recovered. The organic solution was evaporated and
was combined with more diethyl ether extracts from the
aqueous solution. The combined organic extracts were washed
b (R1 ) P h , R2 ) i-P r ). Flow rate: 1.0 mL/min. Eluent:
hexane:i-PrOH ) 90:10. Retention time: minor 6.5 min, major
2
4
b
7
.3 min. ee: 78%. [R]
R] ) +32.0 (c ) 1.3, CH
2c (R1 ) P h , R2 ) n -P r ). Flow rate: 1.0 mL/min. Eluent:
hexane:i-PrOH ) 90:10. Retention time: minor 7.0 min, major
D
) +26.6 (c ) 0.93, CH
2 2
Cl ). Literature
[
D
2
2
Cl ).
2 4
with saturated brine and dried over Na SO . The solvent was
then removed under reduced pressure. After purification by
flash chromatography on silica gel (hexane/EtOAc: 15:1), the
chiral epoxide was obtained in 41% yield. Its ee was 71% as
determined by HPLC-Chiracel OD column. The recovered
4
b
7.4 min. ee: 76%. [R]
+0.9 (c ) 1.1, CH Cl
d (R1 ) P h , R2 ) p -CH
Eluent: hexane:i-PrOH ) 90:10. Retention time: minor 18.6
min, major 20.2 min. ee: 70%. [R] ) -171.0 (c ) 1.08, CH
) -210 (c ) 1, CH Cl ).
e (R1 ) P h , R2 ) p-ClP h ). Flow rate: 0.5 mL/min.
Eluent: hexane:i-PrOH ) 98:2. Retention time: minor 38.5
min, major 40.6 min. ee: 79%. [R] )-176.8 (c ) 0.70, CH
) -195 (c ) 1, CH Cl ).
g (R1 ) P h , R2 ) t-Bu ). Flow rate: 0.5 mL/min. Eluent:
hexane:i-PrOH ) 90:10. Retention time: minor 11.3 min,
major 13.4 min. ee: 64%. [R] ) +14 (c ) 0.36, CHCl ).
) +10 (c ) 0.53, CHCl ).
D
) +1.7 (c ) 1.0, CH
2
Cl
2
) Lit. [R] )
D
2
2
).
2
3
P h ). Flow rate: 0.5 mL/min.
polymer was redissolved into CH
10 mL) and brine, and dried over Na
removed, and the residue was redissolved in a minimum
amount of CH Cl . Methanol was added to precipitate out the
2
Cl
2
, washed with 1 N HCl
(
2
SO . The solvent was
4
D
2
-
5
Cl
2
). Literature [R]
D
2
2
2
2
2
polymer which was then dried under vacuum. This process
gave the recovered (R)-6 in 90% yield.
A Typ ica l P r oced u r e for th e Asym m etr ic Ep oxid a tion
in th e P r esen ce of P olym er (R)-19, Dieth ylzin c, a n d ter t-
Bu tyl Hyd r op er oxid e. Under nitrogen, to a diethyl ether
solution (10 mL) of polymer (R)-19 (0.1 mmol based on the
repeating unit) was added diethylzinc (18 µL, 0.18 mmol) at
room temperature. After stirring for 15 min, an R,â-unsatur-
ated ketone (0.5 mmol) and t-BuOOH (135 µL, 4.43 M in
toluene, 0.6 mmol) were added, and the resulting solution was
stirred at room temperature for the time shown in Table 3.
The reaction was quenched with 1 N HCl and extracted with
ethyl acetate. The organic layer was washed with aqueous
saturated sodium hydrogensulfite, brine, aqueous sodium
bicarbonate, and brine. After the solution was concentrated,
the polymer was precipitated out with addition of methanol.
The solution was concentrated under vacuum, and the residue
was purified by column chromatography to give the epoxida-
tion product.
D
2
-
5
Cl
2
). Literature [R]
D
2
2
2
D
3
14
Literature [R]
D
3
Ack n ow led gm en t. This work was initially sup-
ported by the Department of Chemistry at North Dakota
State University and then by the Department of Chem-
istry at University of Virginia. Partial support from the
National Science Foundation (DMR-9529805), the US
Air Force (F49620-96-1-0360), and the J effress Memo-
rial Trust is gratefully acknowledged.
J O990749W
Deter m in a tion of th e ee’s of th e Ep oxid a tion P r od u cts
2
F or m ed by Usin g P olym er (R)-19 a s th e Ca ta lyst. All
the ee’s were determined by Chiral HPLC: Chiracel OD
column with hexanes/2-propanol as eluent and 254 nm UV
detector.
(
14) Lasterra-S a´ nchez, M. E.; Felfer, U.; P. Mayon, P.; Roberts, S.
M.; S. R. Thornton, S. R.; Todd, C. J . J . Chem. Soc, Perkin Trans. 1
1996, 343.