Asymmetric epoxidation catalyzed by novel azacrown ether-type chiral quaternary ammonium salts under phase-transfer catalytic conditions

Article abstract of DOI:10.1016/j.tetlet.2006.02.142

Asymmetric epoxidation of (E)-chalcone with alkaline hydrogen peroxide by novel chiral phase-transfer catalysts (chiral PTCs) with quaternary ammonium salts of azacrown ether proceeded in high yield and good enantioselectivity. Remarkably, this reaction d

Full text of DOI:10.1016/j.tetlet.2006.02.142

Tetrahedron Letters 47 (2006) 3115–3118
Asymmetric epoxidation catalyzed by novel azacrown
ether-type chiral quaternary ammonium salts under
phase-transfer catalytic conditions
Kazushige Hori,* Mina Tamura, Keita Tani, Nagatoshi Nishiwaki,
Masahiro Ariga and Yasuo Tohda
Division of Natural Science, Osaka Kyoiku University, 4-698-1 Asahigaoka, Kashiwara, Osaka 582-8582, Japan
Received 28 September 2005; revised 24 February 2006; accepted 27 February 2006
Available online 13 March 2006
Abstract—Asymmetric epoxidation of (E)-chalcone with alkaline hydrogen peroxide by novel chiral phase-transfer catalysts (chiral
PTCs) with quaternary ammonium salts of azacrown ether proceeded in high yield and good enantioselectivity. Remarkably, this
reaction depended on the length of the carbon chain on the nitrogen atom with the chiral PTCs and on the bulk of the base.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Chiral phase-transfer catalyst (chiral PTC) reaction has
been increasingly useful for asymmetric synthesis, where
there is no necessity to perform it under strict reaction
conditions such as inert gas or dehydrated circumstance.
In particular, quaternary ammonium salts derived from
cinchona alkaloids have been more widely used in chiral
PTC,1 although there are many restrictions in the cata-
lyst design. Therefore, some developments of novel chi-
ral PTCs have been reported for asymmetric alkylation
of glycine imine esters recently,2 and the progress of
new chiral PTCs is a challenging theme in asymmetric
synthesis. For example, in asymmetric epoxidation of
electron-deficient olefins under PTC conditions,3 it has
been reported by Maruoka and co-workers that spiro-
type quaternary ammonium salts, prepared via multi-
steps from BINOL, have been effective in this reaction.4
Since we thought it would be interesting to devise a com-
pound which functions not only as a surfactant but also
a chiral recognition molecule, we constructed the C2-
symmetry chiral PTC 5n with long-alkyl chains (n de-
notes the carbon number of two alkyl chains on their
nitrogen), in which quaternary ammonium salts of chiral
azacrown ether worked as a molecular recognition site
and were easier to prepare. In this letter, we wish to de-
scribe the synthesis of novel PTC (S,S)-5n derived from
(S)-BINOL and its application to asymmetric epoxida-
tion of chalcones under PTC conditions (Fig. 1, Scheme 1).
The chiral quaternary ammonium salts (S,S)-5n were
readily prepared via four steps (Scheme 2). The ether
(S,S)-1, which was obtained from two (S)-BINOLs,5 re-
acted with N-protected diethanolamine ester 2 to give
the azacrown ether precursor (S,S)-3 in 52% yield.
Deprotection of the p-nitrobenzenesulfonyl group in
(S,S)-3 by p-toluenethiol6 afforded the azacrown ether
Chiral PTC has been generally classified into two sys-
tems: one is chiral onium salts which function as surfac-
tant in liquid–liquid phase (aqueous solution/less polar
organic solvent), and the another is chiral crown ethers
which have high ability of molecular recognition in
solid–liquid phase (inorganic salt/less polar organic
solvent).1
CnH2n+1
CnH2n+1
N
I
O
O
O
O
Keywords: Chiral phase-transfer catalyst; Azacrown ether; Asymmetric
epoxidation.
O
*
Corresponding author. Tel.: +81 729 78 3648; fax: +81 729 78
3647; e-mail: kzhori@cc.osaka-kyoiku.ac.jp
Figure 1. Structure of (S,S)-5n (n = 1 and 6–10).
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.02.142

3116
Ph
K. Hori et al. / Tetrahedron Letters 47 (2006) 3115–3118
catalyst only in 7% yield, which showed the effectiveness
of (S,S)-51 for the epoxidation, though enantioselectiv-
ity was low (Table 1, run 1). At 0 ꢁC, the reaction cata-
lyzed by (S,S)-58, of which two carbon chains on the
quaternary nitrogen atom were longer than those of
(S,S)-51, improved the enantioselectivity to 46% ee
(run 3).
PTC: (S,S)-5n 10 mol%
Ph
Ph
Ph
O
base, oxidant, 24 h
O
O
(E)-chalcone
6
Scheme 1. Asymmetric epoxidation of (E)-chalcone.
(S,S)-4 in 78% yield. The desired chiral quaternary
ammonium salts (S,S)-5n were prepared by treatment
of (S,S)-4 with alkyl iodides and potassium carbonate
in high yield (ca. 80%).
Interestingly, it was found that the kind of base was
important in this reaction (runs 5–8). There was a ten-
dency that the use of the hydroxide having a large cation
such as K+, Cs+, and tetramethylammonium ion gave
good enantioselectivity. To examine the interaction be-
tween 5n and the counter cation of the base, (S,S)-7, in
which the aliphatic ether oxygen atom of (S,S)-58 was
converted to a methylene group (Fig. 2), was applied
to this reaction. The lower enantioselectivity in run 9
indicates complexation ability of the azacrown ether
ring of 58 with the counter cation would be necessary.
In a preliminary investigation on the potentiality of
(S,S)-5n as chiral PTC, we applied it to asymmetric
epoxidation of (E)-chalcone. Typical results are summa-
rized in Table 1. The epoxidation using an aqueous solu-
tion of NaOH as a base and hydrogen peroxide in the
presence of (S,S)-51 gave the corresponding epoxy com-
pound 6 in quantitative yield, while in the absence of
OH
O
HO
O
(S)-BINOL
i)
+
O
TsO
OTs
O
(S,S)-1
R
N
R
N
RO
OR
O
O
O
O
iv)
2 (R = p-NO2PhSO2)
(S,S)-5n
ii)
O
(S,S)-3: R = p-NO2PhSO2
(S,S)-4: R = H
iii)
Scheme 2. Synthesis of (S,S)-5n. Reagents and conditions: (i) NaH, THF, reflux 24 h; (ii) K2CO3, methyl ethyl ketone, reflux 24 h; (iii) p-MePhSH,
K2CO3, DMF, rt 24 h; (iv) CnH2n+1I, K2CO3, MeCN, reflux 24 h.
a
Table 1. Asymmetric epoxidation of (E)-chalcone catalyzed by PTC (S,S)-5n
Run
PTC
Solvent
Oxidant
Base
Temperature
Yieldb (%)
% ee
1
2
3
4
5
6
7
8
9
10
11
12
13
(S,S)-51
(S,S)-51
(S,S)-58
(S,S)-58
(S,S)-58
(S,S)-58
(S,S)-58
(S,S)-58
(S,S)-7
(S,S)-58
(S,S)-58
(S,S)-58
(S,S)-58
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
CH2Cl2
nBu2O
30% aq H2O2
30% aq H2O2
30% aq H2O2
10% aq NaClO
30% aq H2O2
30% aq H2O2
30% aq H2O2
30% aq H2O2
30% aq H2O2
30% aq H2O2
30% aq H2O2
30% aq H2O2
30% aq H2O2
2 M aq NaOH
2 M aq NaOH
2 M aq NaOH
—
rt
100
13
53
73
43
85
38
86
61
72
79
70
69
6
3
46
2
43
70
65
71
4
0 ꢁC
0 ꢁC
0 ꢁC
0 ꢁC
0 ꢁC
0 ꢁC
0 ꢁC
0 ꢁC
0 ꢁC
0 ꢁC
0 ꢁC
0 ꢁC
LiOHÆH2Oc
2 M aq KOH
2 M aq CsOH
2 M aq Me4NOH
2 M aq KOH
2 M aq KOH
2 M aq KOH
2 M aq KOH
2 M aq KOH
0
14
44
3
Et2O
EtOH
a Reaction conditions: 2 M aqueous solution of base (1.25 mmol) was added to a solution of (E)-chalcone (0.5 mmol) and PTC (0.05 mmol) in solvent
(1.5 mL) at room temperature. After stirring for 20 min, aqueous solution of oxidant (4.93 mmol) was added to the above mixture at appropriate
temperature, and then the mixture was stirred for 24 h.
b The yield was determined by 1H NMR.
c Solid LiOHÆH2O was used.

K. Hori et al. / Tetrahedron Letters 47 (2006) 3115–3118
3117
Table 3. Asymmetric epoxidation of chalcones in the presence of
(S,S)-5n
C8H17
C8H17
a
N
I
Run
Substrate
PTC
Yieldb (%)
% ee
O
O
O
O
1
2
3
4
5
6
7
8
9
7
(S,S)-57
(S,S)-58
(S,S)-59
(S,S)-57
(S,S)-58
(S,S)-59
(S,S)-57
(S,S)-58
(S,S)-59
(S,S)-58
(S,S)-58
91
95
90
96
70
68
85
72
69
72
75
83
32
41
22
71
32
66
—
—
8
9
Figure 2. Structure of (S,S)-7.
In addition, use of toluene gave the best result in 85%
yield and 70% ee among the several solvents (runs 6
and 10–13).7,8
c
10
11
10
11
—
d
—
a The reaction condition is given in Table 1, run 6.
b The yield was determined by 1H NMR.
c The complex mixture was obtained.
d No reaction.
Based on the results of (S,S)-51 and (S,S)-58 (Table 1,
runs 2 and 3), the length of two carbon chains on the
nitrogen of 5n was investigated in this epoxidation with
aqueous KOH and H2O2 in toluene (Table 2). It was
noted that the octyl group ((S,S)-58) was the best length;
in other words, longer or shorter alkyl groups caused
reduction of the catalytic ability. These results may be
ascribed to the distribution rate of 5n for toluene and
the aqueous phase was important. Furthermore, appli-
cations of (S,S)-5n to the epoxidation in an aqueous
phase (without organic solvent) were examined (runs
6–8 in Table 2), which indicated that (S,S)-512 func-
tioned as both a surfactant and PTC.
R1
R2
R1
R2
PTC: (S,S)-5n 10 mol%
O
2M aq. KOH, 30% aq. H2O2
toluene
O
O
Cl
Ph
Ph
O
O
With the optimized conditions, the scope of the epoxida-
tion catalyzed by (S,S)-57–59 was explored (Table 3).
The product from chalcone 7 was obtained in 90% yield
with 83% ee when (S,S)-59 was used, and for the reac-
tion of 40-chlorochalcone 9, (S,S)-57 was suitable (runs
1–3 and 7–9). It should be noted that the optimized
length of 5n varied with chalcones. However, that of 4-
chlorochalcone 8 decreased the enantioselectivity (runs
4–6) and electron-rich chalcones such as 10 and flava-
none 11 were ineffective (runs 10 and 11) (Scheme 3).
7
8
Cl
OMe
Ph
Ph
O
O
10
9
O
Ph
O
In conclusion, we have synthesized a new type chiral
PTC 5n and have applied it to asymmetric epoxidation
of chalcones to give the corresponding epoxy compound
in excellent yield and good enantioselectivity. This study
shows that the application of 5n would be able to achieve
asymmetric PTC reactions by control of the length of
the carbon chains in the quaternary ammonium salts.
Further studies of related PTC-catalyzed chemistry are
currently in progress.
11
Scheme 3. Asymmetric epoxidation of various chalcones.
Acknowledgements
We thank Professor Tetsuo Ohta and Koji Kano (Doshi-
sha University) for HRMS measurements of (S,S)-51–
512 and many interesting discussions.
a
Table 2. Effect of functional group with nitrogen atom on (S,S)-5n
Supplementary data
Run
PTC
n
Yieldb (%)
% ee
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.02.142.
1
2
3
4
(S,S)-56
(S,S)-57
(S,S)-58
(S,S)-59
(S,S)-510
(S,S)-58
(S,S)-510
(S,S)-512
6
7
8
9
10
8
11
75
85
42
11
Trace
18
1
54
70
32
32
ND
5
5
6c
7c
8c
References and notes
10
12
57
11
1. For recent reviews on the asymmetric PTC reaction, see: (a)
Oehme, G. In Comprehensive Asymmetric Catalysis; Jac-
obsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
New York, 1999; Vol. 3, Chapter 38.2; (a) Nelson, A.
a The reaction condition is given in Table 1, run 6.
b The yield was determined by 1H NMR.
c These reactions performed without toluene.

3118
K. Hori et al. / Tetrahedron Letters 47 (2006) 3115–3118
Angew. Chem., Int. Ed. Engl. 1999, 38, 1583; (b) O’Donnell,
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6. Xu, M.-H.; Lin, J.; Hu, Q.-S.; Pu, L. J. Am. Chem. Soc.
2002, 124, 14239, and references cited therein.
7. Representative asymmetric epoxidation of (E)-chalcone
M. J., In Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I.,
Ed.; Wiley-VCH: New York, 2000; Chapter 10; (c) Shioiri,
T.; Arai, S. In Stimulating Concepts in Chemistry; Vogtle,
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(d) Ohshima, T.; Shibuguchi, T.; Fukuta, Y.; Shibasaki,
M. Tetrahedron 2004, 60, 7743, and references cited
therein.
3. For recent publications relating to the use of chiral PTC in
the asymmetric epoxidation of enones, see: (a) Adam, W.;
Rao, P. B.; Degen, H.-G.; Saha-Mo¨ller, C. R. Tetrahedron:
Asymmetry 2001, 12, 121; (b) Arai, S.; Tsuge, H.; Oku, M.;
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Adam, W.; Rao, P. B.; Degen, H.-G.; Levai, A.; Patonay,
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procedure. To a solution of (E)-chalcone (104.1 mg,
0.50 mmol) and (S,S)-58 (53.2 mg, 0.050 mmol) in toluene
(1.5 mL) was added 2 M aq KOH (0.63 mL, 1.25 mmol),
and then the resultant mixture was stirred vigorously at
0 ꢁC for 20 min. After the mixture was added 30% aq H2O2
(0.50 mL, 4.93 mmol) and was stirred vigorously at 0 ꢁC for
24 h, the reaction mixture was quenched by addition of 10%
aq NaHSO3 (20 mL) and extracted with dichloromethane
(3 · 20 mL). The combined organic extracts were washed
with brine (25 mL), dried over anhydrous magnesium
sulfate, and concentrated in vacuo to afford a crude
product. The yield was determined by 1H NMR spectro-
scopy of the mixture of the crude product and anthracene
(17.8 mg, 0.1 mmol) as internal standard, which used the
ratio of the integral value between the signal of 6 (d 4.08 (d,
J = 1.7 Hz, 1H)) and of anthracene (d 8.43 (s, 2H)). The
enantiomeric excess was determined by HPLC analysis
(n-hexane/2-propanol = 98:2), flow rate; 0.5 mL/min,
retention time; 32.4 and 34.3 min.
8. The absolute configuration of 6 was (aR,bS), which was
determined by comparison of HPLC data with the
reference.4