Asymmetric epoxidation of α,β-unsaturated ketones catalyzed by chiral ytterbium complexes

Article abstract of DOI:10.1016/S0040-4039(01)01336-3

Several derivatives of (S)-(-)-BINOL ligands with 6,6′-substitutents were synthesized and applied as chiral ligands in the Yb(O-i-Pr)₃-catalyzed asymmetric epoxidation of α,β-unsaturated ketones. Superior results were obtained with 6,6′-diphenyl-BINOL, exemplified in the asymmetric epoxidation of (E)-1,3-diphenylprop-2-en-1-one in 91% yield and up to 97% ee.

Full text of DOI:10.1016/S0040-4039(01)01336-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6919–6921
Asymmetric epoxidation of a,b-unsaturated ketones catalyzed by
chiral ytterbium complexes
Ruifang Chen,a Changtao Qiana,* and Johannes G. de Vriesb,*
aState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China
bDSM Research, Dept. LS-2CC, PO Box 18, 6160 MD Geleen, The Netherlands
Received 7 June 2001; revised 9 July 2001; accepted 20 July 2001
Abstract—Several derivatives of (S)-(−)-BINOL ligands with 6,6%-substitutents were synthesized and applied as chiral ligands in
the Yb(O-i-Pr)3-catalyzed asymmetric epoxidation of a,b-unsaturated ketones. Superior results were obtained with 6,6%-diphenyl-
BINOL, exemplified in the asymmetric epoxidation of (E)-1,3-diphenylprop-2-en-1-one in 91% yield and up to 97% ee. © 2001
Elsevier Science Ltd. All rights reserved.
The catalytic asymmetric epoxidation of a,b-enones has
received much attention during the past few years.1,2
Recent developments include the use of molecular oxy-
gen and diethylzinc in the presence of (R,R)-N-
BINOL is a very efficient chiral ligand in the lan-
thanoid-catalyzed epoxidation of chalcone; up to 97%
ee could be achieved, which is the highest ee value for
epoxychalcone reported so far.
methylpseudoephedrine3
or
optically
active
polybinaphthyl derivatives.4 Achiral alkyl peroxides, in
conjunction with optically active (+)-diethyltartrate as a
chiral auxiliary, resulted in good enantioselectivities.5
The Shibasaki catalyst, which is generated from an
equimolar mixture of (R)-(+)-1,1%-2-naphthol (BINOL)
and La(O-i-Pr)3, can catalyze the asymmetric epoxida-
A series of 6,6%-disubstituted BINOL ligands were syn-
thesized in the following manner (Scheme 1). (S)-
BINOL 1 was brominated (Br2 in CH2Cl2, −78°C) to
give (S)-6,6%-dibromo-1,1%-bi-2-naphthol 2 in 98% yield.
After converting the hydroxyl groups into MOM-
,
tion of a range of (E)-enones in the presence of 4 A
molecular sieves.6a In this case, chalcone was epoxi-
dized in 93% chemical yield and 83% ee using cumene
hydroperoxide (CMHP) as an oxidant. Ytterbium cata-
lysts were found to give good enantioselectivities with
alkyl a,b-enones. The effect of water on the ytterbium
catalyst was also investigated;6b 96% ee was obtained
by Inanaga6c after external addition of triphenylphos-
phine oxide (15 mol%). However, this became a multi-
component catalytic system, which made the reaction
conditions more complicated.
Br
[a]
OH
OH
[b]
OH
OH
Br
(S)-1
(S)-2
Ar
Br
Br
[c]
[d]
OH
OH
OMOM
OMOM
We envision that introduction of substituents on the
6,6%-positions of BINOL might have a profound effect
on the activity and enantioselectivity as both the elec-
tronic and steric properties7–10 of the catalyst will be
influenced. We have found that (S)-6,6%-diphenyl-
Ar
(S)-3
(S)-4-8
Scheme 1. Preparation of BINOL-derived ligands. Reagents
and conditions: (a) Br2, −78°C, CH2Cl2; (b) NaH,
ClCH2OCH3, rt; (c) ArMgBr, Ni(PPh3)2Cl2, Et2O, reflux; (d)
trace HCl, MeOH.
* Corresponding authors.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01336-3

6920
R. Chen et al. / Tetrahedron Letters 42 (2001) 6919–6921
ethers, aryl groups were introduced by cross coupling
with an aryl Grignard reagent, catalyzed by
Ni(PPh3)2Cl2 in Et2O. Hydrolysis of the MOM-ethers
with HCl/MeOH completed the synthesis of (S)-4–8.
The total yields of the corresponding ligands of (S)-4–8
are listed in Table 1. The chiral ytterbium catalysts
were successfully prepared from ligands (S)-1, 2, 4–8 by
reacting them with Yb(O-i-Pr)3 in THF in the presence
BINOL ((S)-1) as the ligand, the epoxy ketone 10a was
isolated in a low ee of 44% (Table 2, entry 1). (S)-2,
which has bromine atoms on the 6,6%-positions of the
phenyl, led to a moderate ee of 62% (Table 2, entry 2),
although it exhibited a more promising optical induc-
tion in the enantioselective Strecker-type reactions of
aldimine.11 However, introduction of aryl substituents
onto the 6,6%-positions of BINOL, induced much better
enantioselectivity. Among all the ligands tested, (S)-4
showed the highest enantioselectivity, with up to 95%
ee obtained at room temperature (Table 2, entry 3). The
same major (−)-enantiomer was formed in all cases.
Comparison of the sign of the optical rotation with the
literature data12 revealed that the (−)-enantiomer of the
epoxy ketone possessed the aR,bS configuration.
,
of MS 4 A. The exact nature of the catalyst is still
under investigation. It was found that an almost 1:1
ratio of Yb(O-i-Pr)3 and ligand (S)-4 afforded the
maximum enantiomeric excesses.
Chalcone 9a was selected as the representative example
to study. The reaction of 9a with cumene hydroperox-
ide (CMHP) was carried out as described in Eq. (1) and
the results are summarized in Table 2.
In order to further improve the enantioselectivity of the
reaction, we have examined the effect of solvents and
the reaction temperature. It was found that solvents
strongly influence the degree of enantiomeric excesses,13
though the absolute configuration remains the same.
THF gave the best result at room temperature. This
may be ascribed to its ability to coordinate with the
rare earth metal. The same results were obtained when
(R)-4 was used in place of (S)-4. Ligand (S)-4 could be
recovered and reused without any loss of yield or ee.
(Table 2, entry 5). Lower reaction temperatures led to
an improvement in enantioselectivity, although at the
expense of reaction rate. That is, at 0°C the chalcone
could be epoxidized with 5 mol% Yb catalyst in 97% ee
and 91% isolated yield after 3 days (Table 2, entry 6).
In addition, the use of tert-butyl hydroperoxide
(TBHP) instead of CMHP did not improve the asym-
metric epoxidation, giving the product with 93% ee in
91% yield (Table 2, entry 7), which is in contrast to the
results reported by Shibasaki.6a Moreover, the addition
of both water and triphenylphosphine oxide to the
Yb-4 catalyst system resulted in no further improve-
ment in the ee value.
It is obvious that the 6,6%-disubstitutents on BINOL
have a remarkable effect on the enantioselectivity of the
asymmetric epoxidation reaction. Using simple (S)-
Table 1. Total yields for the ligands of (S)-4–8
Entry
Ligand (Ar)
Yield (%)
1
2
3
4
5
(S)-4 (Ph)
71
64
45
67
33
(S)-5 (p-MeC6H4)
(S)-6 (p-MeOC6H4)
(S)-7 (p-CF3C6H4)
(S)-8 (1-Naphthyl)
Table 2. Ligand optimization in Yb(O-i-Pr)3-catalyzed
asymmetric epoxidation of chalconea
O
O
O
(S)-Yb cat.
+
(1)
CMHP
Ph
Ph
Ph
Ph
βS
αR
9a
10a
The scope and the potential of the epoxidation of
a,b-unsaturated ketones catalyzed by Yb(O-i-Pr)3-(S)-
6,6%-diphenyl-BINOL was further demonstrated by
reacting a range of a,b-unsaturated ketones under opti-
mized reaction conditions. The results are summarized
in Table 3. It is clear that the nature of the substituents
R1 and R2 of the enones has a great influence on the
enantioselectivity of the epoxidation. Enones with aro-
matic substituents could be epoxidized in higher enan-
tiomeric excesses than alkyl-substituted enones, which
gave a lower ee value (Table 3, entry 6). In addition,
when o-MOMOC6H4 was used instead of Ph as the
olefinic substituent (R1), the ee value decreased to 47%.
Entry
Ligand
Yield (%)
Ee (%)b
1
2
3
4
5
6
7
8
(S)-1
(S)-2
(S)-4
(S)-4
(R)-4
(S)-4
(S)-4
(S)-5
(S)-6
(S)-7
(S)-8
95
76
91
90
90
91
91
78
86
88
84
44
62
95
95c
95d
97e
93f
70
9
10
11
83
89
63
a Reaction conditions: Yb(O-i-Pr)3 (5 mol%), Yb:ligand=1:1; CMHP
(150 mol%), t=8 h, rt, THF.
In conclusion, the ytterbium complex generated from
Yb(O-i-Pr)3 and (S)-6,6%-diphenyl-BINOL in THF was
found to be an efficient catalyst for the asymmetric
epoxidation of a,b-unsaturated enones with cumene
hydroperoxide. The best results were obtained for (E)-
1,3-diphenylprop-2,3-epoxy-1-one with up to 97% ee in
91% chemical yields.
b Determined by HPLC (chiral OD column), absolute configuration
was determined to be (aR,bS).
c Ligand recovered after one experiment.
d (R)-4 was used.
e 0°C, 36 h.
f TBHP used instead of CMHP.

R. Chen et al. / Tetrahedron Letters 42 (2001) 6919–6921
Table 3. Asymmetric epoxidation of enones with Yb(O-i-Pr)3-(S)-4a
6921
O
O
O
(S)-Yb cat.
R1
+
R2
R2
βS
R1
CMHP
αR
9a-g
10a-g
Entry
Enone
R1
R2
Ph
Epoxide
Yield (%)
Eeb (%)
1
2
3
4
5
6
7
9a
9b
9c
9d
9e
9f
Ph
Ph
Ph
Ph
Ph
Ph
10a
10b
10c
10d
10e
10f
10g
95
83
85
85
81
85
88
95
54
54
53
66
38
47
p-MeC6H4
p-MeOC6H4
p-ClC6H4
o-MeOC6H4
CH3CH2CH2
Ph
9g
o-MOMOC6H4
a Reaction conditions: Yb cat. 5 mol%, CMHP, 8 h, rt, THF.
b Determined by HPLC (chiral OD column), absolute configuration was determined to be (aR,bS).
Acknowledgements
(b) Julia, S.; Guixer, J.; Masana, J.; Rocas, J. J. Chem.
Soc., Perkin Trans. 1 1982, 1317–1324.
5. Elston, C. L.; Jackson, R. F. W.; MacDonald, S. J. F.;
Murray, P. J. Angew. Chem., Int. Ed. Engl. 1997, 36,
410–411.
Financial support from DSM Research, Platform Life
Sciences, the National Natural Sciences Foundation of
China and the State Key Project of Basic Research
6. (a) Bougauchi, M.; Watanabe, S.; Arai, T.; Sasai, H.;
Shibasaki, M. J. Am. Chem. Soc. 1997, 119, 2329–2330;
(b) Watanabe, S.; Kobayashi, Y.; Arai, T.; Sasai, H.;
Bougauchi, M.; Shibasaki, M. Tetrahedron Lett. 1998, 39,
7353–7356; (c) Daikai, K. D.; Kamaura, M.; Inanaga, J.
Tetrahedron Lett. 1998, 39, 7321–7322.
7. Sasai, H.; Tokunaga, T.; Watanabe, S.; Suzuki, T.; Itoh,
N.; Shibasaki, M. J. Org. Chem. 1995, 60, 7388–7389.
8. Terada, M.; Motoyama, Y.; Mikami, K. Tetrahedron
Lett. 1994, 36, 6693–6696.
(Project 973, No.
acknowledged.
G 2000048007) are gratefully
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