Enantioselective epoxidation of olefins catalyzed by new sterically hindered salen-Mn(III) complexes

Article abstract of DOI:10.1016/S0040-4039(01)00195-2

New, sterically hindered chiral salen-Mn(III) complexes, 5 and 6, were prepared from an aldehyde derived from BINOL. These substances catalyze efficient, enantioselective NaOCl-promoted epoxidations of olefins and enantioselectivities as high as 96-99% ee

Full text of DOI:10.1016/S0040-4039(01)00195-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2485–2488
Enantioselective epoxidation of olefins catalyzed by new
sterically hindered salen–Mn(III) complexes
Kwang-Hyun Ahn,a,* Sang Wook Park,a Soojin Choi,a Hyun-Ju Kimb and Chi Jang Moonb
aCollege of Environments and Applied Chemistry, Kyung Hee University, Yongin City 449-701, South Korea
bChoongwae Pharma Corporation, Hwasung-Goon, Kyunggi-Do 445-970, South Korea
Received 22 January 2001; revised 30 January 2001; accepted 1 February 2001
Abstract—New, sterically hindered chiral salen–Mn(III) complexes, 5 and 6, were prepared from an aldehyde derived from
BINOL. These substances catalyze efficient, enantioselective NaOCl-promoted epoxidations of olefins and enantioselectivities as
high as 96–99% ee are observed in epoxidations of cis-b-methylstyrene and 2,2-dimethylchromene. © 2001 Elsevier Science Ltd.
All rights reserved.
Optically active epoxides are important starting materi-
als in the synthesis of a wide variety of biologically and
pharmaceutically important compounds.1 Epoxidations
of unfunctionalized olefins, catalyzed by chiral salen–
Mn(III) complexes (e.g. 1–3), initially developed by
Jacobsen2 and Katsuki,3 have emerged as practical
methods for the synthesis of optically active epoxides.
In addition, various epoxidation strategies utilizing
homogeneous4,5 and supported6,7 salen–Mn(III) com-
plexes and a host of oxidants,8,9 including the economi-
cal NaOCl,10 have been developed to improve the
enantioselectivities of these reactions. Epoxidations
promoted by the Katsuki catalyst 3, which contains two
additional (compared to the Jacobsen catalysts) stereo-
genic axes at the C3 and C3% positions of the salen
ligand,11 are noteworthy owing to the exceptionally
high levels of enantioselectivity observed with a variety
of alkenes.
recent investigations in which we developed a new
method for efficient resolution of BINOL.12 We
believed that salen–Mn(III) complexes related to 5
would be worthy targets of our continuing efforts since
these complexes might be more easily prepared than the
Katsuki catalyst 3. Furthermore, we felt that the pres-
ence of polar ester groups at R2 in 5 would enhance the
rate of transfer of the oxidant between the phases in the
aqueous/alkene biphasic reaction system and, as a
result, increase turn over frequencies in the epoxidation
reactions would be expected. Below, we describe the
preparation of the new salen–Mn(III) complexes 5 and
6 and their use as efficient catalysts for enantioselective
epoxidations of unfunctionalized olefins.
The chiral aldehyde 11 serves as the key intermediate in
synthetic routes to 5 and 6. This substance is prepared
from bis-MOM-protected BINOL 9 by a sequence
(Scheme 1) involving mono-formylation and deprotec-
tion (“10, 65%) and sterically controlled mono-esterifi-
cation with pivaloyl chloride (89%).13a Reaction of 11
Our interest in preparing novel ligands for transition
metal catalyzed asymmetric reactions grew out of
R
N
O
R
N
O
R
N
O
R
N
O
Mn
Cl
Mn
Cl
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
(R)-1 R = Ph
(S)-1 R = Ph
(R)-2 R = -(CH2)4-
(S)-2 R = -(CH2)4-
* Corresponding author. Tel.: +82+31-201-2447; fax: +82+31-202-7337; e-mail: khahn@khu.ac.kr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00195-2

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K.-H. Ahn et al. / Tetrahedron Letters 42 (2001) 2485–2488
R1
N
R1
N
R1
N
R1
N
Mn
Cl
Mn
Cl
R2 R2
1'
2'
1
2
3
O
O
O
O
3'
R2
R2
3
R1 = Ph
(R,S)-5 R1 = Ph
(R,S)-6 R1 = -(CH2)4- R2 = -OOC-t-Bu
R2 = Ar
R2 = -OOC-t-Bu
4
R1 = H
(R,R)-5 R1 = Ph
(R,R)-6 R1 = -(CH2)4- R2 = -OOC-t-Bu
R2 = -OOC-t-Bu
R2 = -OOC-t-Bu
(R,R)-7 R1 = Ph
(R,R)-8 R1 = Ph
R2 = -OOCCH3
R2 = -OSiPh2(t-Bu)
both catalysts give low levels of enantioselectivity
(entries 7 and 8).
with ethylenediamines gives salen ligands, which are
metallated with Mn(OAc)2 and LiCl to yield the salen–
Mn(III) complexes 4–6.13
Epoxidations of cis- and trans-b-methylstyrenes,
indene, 2,3-dihydronaphthalene, 2,2-dimethylchromene
and 6-cyano-2,2-dimethylchromene, catalyzed by 5 and
6, occur with exceptionally high enantioselectivities (up
to 99% ee). Especially noteworthy is the (R,S)-5 cata-
lyzed epoxidation of cis-b-methylstyrene, which pro-
ceeds with 96% ee and yields a cis/trans epoxide ratio
of 15 (entry 11) that is higher than that obtained in any
other NaOCl promoted reaction at 0°C. The absolute
configuration of the epoxides obtained in these pro-
cesses is again governed by the chirality of the diamine
group in the salen ligand (entries 10 and 11). However,
the % ee is strongly influenced by the chirality at C3
and C3%. For example, epoxidations of sterically hin-
dered acyclic and cyclic alkenes such as cis-b-methyl-
styrene, 2,2-dimethylchromene and 6-cyano-2,2-dimeth-
ylchromene catalyzed by (R,S)-5 uniformly give higher
levels of enantioselectivity as compared to those pro-
moted by (R,R)-5. In contrast, (R,R)-5 was found to
give higher selectivities in epoxidations of trans-b-
methylstyrene,16 indene and 2,3-dihydronaphthalene.
The catalytic activities of 4–6, along with those of the
Jacobsen catalysts 1–2, for epoxidation of alkenes were
determined by using Jacobsen’s conditions and NaOCl
as the oxidant.14 The results, summarized in Table 1,
show that 4–6 efficiently catalyze the epoxidation of
styrene (entries 3–6, Table 1). However, the levels of
enantioselectivity (25–62% ee) are similar to those
obtained by using the Jacobsen catalysts (entries 1–2).
The high epoxidation yields observed with 4–6 may be
due to the predicted high transfer rates of oxidant
between the aqueous and organic phases.15 The two
layers are well-mixed in reactions with 4–6 as compared
to those employing 1–2. The comparatively low 25% ee
(entry 3) associated with reactions employing catalyst 4,
which contains stereogenic centers at only C3 and C3%
of the salen ligand, suggests that chirality in the
diamine moiety is a requirement for high levels of
enantioselectivity. Also, as seen by comparing the
results of epoxidations catalyzed by (R,R)-5 and (R,S)-
5 (entries 4 and 5), the absolute configuration of the
styrene oxide product is determined by chirality in the
diamine bridge and not by the absolute configuration at
C3 and C3% in the BINOL unit. To evaluate the steric
effects of the salen R2-substituent on these reactions,
salen–Mn(III) complexes 7 and 8 were prepared and
tested as styrene epoxidation catalysts. Although active,
In summary, we have synthesized new chiral salen–
Mn(III) complexes, 5–6 and shown that they serve as
efficient catalysts for NaOCl-induced epoxidations of
olefins. Moreover, epoxidation reactions, catalyzed by
these substances, yield chiral epoxides with exception-
ally high levels of enantioselectivity.
CHO
CHO
OMOM
OMOM
a, b
d, e, f
OH
OH
OH
O
c
4-6
65%
89%
85-95%
O
9
1
0
11
Scheme 1. (a) t-BuLi, DMF, THF, −78°C; (b) HCl, EtOH; (c) NaH, pivaloyl chloride, THF; (d) diamine, EtOH, reflux; (e)
Mn(OAc)2, EtOH, reflux, O2; (f) LiCl, EtOH.

K.-H. Ahn et al. / Tetrahedron Letters 42 (2001) 2485–2488
Table 1. Salen–Mn(III) complex catalyzed NaOCl epoxidations of olefins
2487
Entry
Alkene
Styrene
Catalyst
Yielda
% Eeb
Config.c
1
2
(R)-1
(R)-2
53
76
65
46
R
R
3
4
97
25
R
4
5
6
7
8
9
(R,R)-5
(R,S)-5
(R,R)-6
(R,R)-7
(R,R)-8
(S)-1
(R,R)-5
(R,S)-5
(R)-1
87
95
\99
97
25
62
55
41
52
R
S
R
R
43
R
cis-b-Methylstyrene
90
85(17)d
(S,R)
(R,S)
(S,R)
(S,S)
(S,S)
(S,S)
(R,R)
(S,S)
(R,S)
(R,S)
(S,R)
(R,S)
(R,S)
(R,S)
(S,R)
(R,S)
(3R,4R)
(3R,4R)
(3S,4S)
(3R,4R)
(3R,4R)
(3R,4R)
(3S,4S)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
62
87(8)d
87(16)e
96(90e, 15d)
trans-b-Methylstyrene
59
75
38
95
35
80
57
28
23
57
30
63
84
94
(R)-2
(R,R)-5
(R,S)-5
(R,R)-6
(R)-1
(R,R)-5
(R,S)-5
(R,R)-6
(R)-1
(R,R)-5
(R,S)-5
(R,R)-6
(R)-1
(R,R)-5
(R,S)-5
(R,R)-6
(R)-2
Indene
55(55)e
63
88(98)e
90
2,3-Dihydronaphthalene
2,2-Dimethylchromene
6-Cyano-2,2-dimethylchromene
62
65
77
95
60(78)e
62
87(98)e
95
85
60
99
85
80(75)e
62
99(99)e
98
92
77
87
96
78
92
(R,R)-5
(R,S)-5
a GC yield (entries 1–16) or isolated yield (entries 17–31).
b Determined by GC with either Supelco chiral b-dex 325 (30 m×0.25 mm×0.25 mm, entries 1–16) or b-dex 120 (30 m×0.25 mm×0.25 mm, entries
21–24) column and HPLC with either Whelk-O1 (5 mm, 4.5×250 mm with CN guard, entries 17–20) or Daicel Chiralcel OJ column (entries
25–31).
c Absolute configuration was assigned according to the literature procedure.2,3,9–11
d The cis/trans ratio.
e Results obtained with Katsuki’s catalyst.11b
Acknowledgements
5. (a) Katsuki, T. Coord. Chem. Rev. 1995, 140, 189; (b)
Ito, Y. N.; Katsuki, T. Bull. Chem. Soc. Jpn. 1999, 72,
603.
6. Canali, L.; Sherrington, D. C. Chem. Soc. Rev. 1999, 28,
85.
This work was supported by a grant from the Korea
Science and Engineering Foundation (98-0501-04-01-3).
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Yao, X.; Chen, H.; Lu¨, W.; Pan, G.; Hu, X.; Zheng, Z.
Tetrahedron Lett. 2000, 41, 10267; (e) Reger, T. S.; Janda,
K. D. J. Am. Chem. Soc. 2000, 122, 6929.
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Adam, W.; Jeko, J.; Levai, A.; Nemes, C.; Patonay, T.;
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Chemistry II; Abel, E. W.; Stone, F. G. A.; Wilkinson,
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10. (a) Zhang, W.; Jacobsen, E. N. J. Org. Chem. 1991, 56,
2296; (b) Jacobsen, E. N.; Zhang, W.; Muci, A. R.;
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11. (a) Hosoya, N.; Hatayama, A.; Irie, R.; Sasaki, H.;
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Irie, R.; Hamada, T.; Suzuki, K.; Katsuki, T. Tetra-
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R.; Katsuki, T. Synlett 1995, 827.
The mixture was heated to reflux for an additional 2 h
and cooled to room temperature. Saturated aqueous LiCl
was added. The product was extracted with ethyl acetate,
and the organic phase was dried over MgSO4 and con-
centrated. Flash chromatography (MeOH/CH2Cl2=1/9)
provided (R,R)-5 (93 mg, 85%): IR (KBr) w 2968, 2928,
1745, 1608, 1584, 1556; HRMS (FAB), m/z calcd
C66H55N2O6Mn (M−Cl+H)+ 1026.3441, found 1026.3439;
(c) Analytical data for (R,R)-6: HRMS (FAB), m/z calcd
C58H53N2O6Mn (M−Cl+H)+ 928.3284, found 928.3278.
14. The general procedure used for the epoxidation reactions
is as follows: To a stirred solution of olefin (0.5 mmol) in
CH2Cl2 (2.5 mL), catalyst (0.02 mmol) and 4-
phenylpyridine-N-oxide (4-PPNO, 0.1 mmol) at 0°C is
added pre-cooled buffered bleach (2.5 mmol, buffered to
pH 11.3 with Na2HPO4). The mixture is stirred for either
4 h (entries 1–16) or 8 h (entries 17–31). The organic
phase is separated, dried (MgSO4) and concentrated in
vacuo giving a residue which is subjected to silica gel
chromatography.
15. (a) A referee suggested the ligand acceleration observed
by Katsuki15b as an another possible explanation for the
high yield; (b) Nishikori, H.; Katsuki, T. Tetrahedron
Lett. 1996, 37, 9245.
16. (a) High enantioselective epoxidation of trans-b-methyl-
styrene using metal–salen catalysts has been reported
recently;16b–c (b) Bousquet, C.; Gilheany, D. G. Tetra-
hedron Lett. 1995, 36, 7739; (c) Nishikori, H.; Ohta, C.;
Katsuki, T. Synlett 2000, 1557.
12. Kim, H. C.; Choi, S.; Kim, H.; Ahn, K.-H.; Koh, J. H.;
Park, J. Tetrahedron Lett. 1997, 38, 3959.
13. (a) To a mixture of 10 (120 mg, 0.38 mmol) and NaH (23
mg, 0.96 mmol) in THF (7 mL) at 0°C was added
pivaloyl chloride (46 mg, 0.38 mmol). After 2 h at room
temperature, water was added. Product was extracted
with ethyl acetate, and the organic phase was dried over
MgSO4 and concentrated. Flash chromatography (hex-
ane/ethyl acetate=4/1) provided 11 (134 mg, 89%). 1H
NMR (CDCl3, 300 MHz) l 0.79 (s, 9H), 7.22–8.01 (m,
9H), 8.05 (d, J=8.90 Hz, 1H), 8.33 (s, 1H), 10.21 (s, 1H),
10.48 (s, 1H); 13C NMR (CDCl3) l 26.42, 38.61, 117.01,
121.75, 122.06, 123.06, 124.47, 125.45, 125.58, 125.62,
126.73, 127.29, 128.35, 129.51, 129.61, 130.54, 131.76,
133.19, 137.47, 138.06, 147.18, 153.48, 176.31, 196.57;
HRMS (EI) m/z calcd C26H22O4 (M+) 398.1518, found
398.1521; (b) A solution of 11 (100 mg, 0.25 mmol) and
(1R,2R)-1,2-diphenylethylenediamine (28 mg, 0.13 mmol)
in EtOH (4 mL) was heated to reflux for 2 h before the
addition of manganese(II) acetate (42 mg, 0.24 mmol).
.
.