Direct organocatalytic asymmetric epoxidation of α,β-unsaturated aldehydes

Article abstract of DOI:10.1016/j.tetlet.2005.10.128

The organocatalytic asymmetric epoxidation of α,β-unsaturated aldehydes with peroxides or sodium percarbonate is presented. Chiral pyrrolidine derivatives, proline and amino acid derived imidazolidinones mediate the asymmetric epoxidation of α,β-unsaturat

Full text of DOI:10.1016/j.tetlet.2005.10.128

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 99–103
Direct organocatalytic asymmetric epoxidation
of a,b-unsaturated aldehydes
*
´
´
Henrik Sunden, Ismail Ibrahem and Armando Cordova
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden
Received 3 August 2005; revised 21 October 2005; accepted 26 October 2005
Available online 16 November 2005
Abstract—The organocatalytic asymmetric epoxidation of a,b-unsaturated aldehydes with peroxides or sodium percarbonate is
presented. Chiral pyrrolidine derivatives, proline and amino acid derived imidazolidinones mediate the asymmetric epoxidation
of a,b-unsaturated aldehydes. For example, commercially available protected a,a-diphenyl-2-prolinol catalyzes the asymmetric
formation of 2-epoxy-aldehydes in 81–95% conversion with up to 96:4 dr and 98% ee. The use of non-toxic catalysts, aqueous
solvents and hydrogen peroxide or sodium percarbonate as the oxygen sources makes the reaction environmentally benign.
Ó 2005 Elsevier Ltd. All rights reserved.
Catalytic asymmetric epoxidation is a fundamental reac-
tion in organic synthesis.1 The pioneering work of Kat-
suki and Sharpless resulted in the discovery of titanium–
tartrate complexes as asymmetric epoxidation catalysts
of allylic alcohols.2 Following this seminal work Jacob-
sen and Katsuki independently demonstrated that chiral
manganese–salen complexes were excellent catalysts for
the asymmetric epoxidation of unfunctionalized olefins.3
Catalytic asymmetric epoxidation reactions are also
mediated by organic catalysts.4 For example, epoxida-
tions of a,b-enones are mediated by polypeptides5 and
cinchona alkaloids.6 Moreover, Shi and Aggarwal have
developed elegant methods for the epoxidations of
unfunctionalized olefins catalyzed by chiral ketones7
and pyrrolidines,8 respectively. Furthermore, Shibasaki
and co-workers have developed several chiral Lewis
acid-catalyzed epoxidations of a,b-unsaturated carbonyl
compounds.9
tion.11 It is known that chiral amines can activate a,b-
unsaturated aldehydes and ketones towards nucleophilic
attack by forming iminium ions.13 However, the direct
asymmetric epoxidation of a,b-unsaturated aldehydes
is a new frontier in asymmetric catalysis.14 Based on
our research program on the development of environ-
mentally benign enantioselective oxidations,11,12 we
became interested in whether hydrogen peroxide and
sodium percarbonate15 (SPC) could be used as nucleo-
philic oxidants in organocatalytic asymmetric epoxida-
tions of a,b-unsaturated aldehydes. Herein, we show
that proline, several chiral pyrrolidine derivatives and
imidazolidinone 11 catalyze the asymmetric epoxidation
of a,b-unsaturated aldehydes with hydrogen peroxide or
solid SPC as the oxidants.
In an initial catalyst screen, we tested different organo-
catalysts (10–30 mol %) for their ability to mediate the
asymmetric epoxidation of cinnamic aldehyde 1a
(0.25 mmol) with hydrogen peroxide (50 wt %, aqueous
solution, 1.2–7 equiv) in CHCl3 (2 mL) (Table 1).
The direct organocatalytic asymmetric a-oxidation of
aldehydes and ketones is performed with electrophilic
oxidants such as nitrosobenzene,10 iodosobenzene,11
oxaziridines,11 and singlet molecular oxygen.12 In stark
contrast, tert-butyl hydroperoxide, m-CPBA and hydro-
gen peroxide failed as oxidants for this transforma-
We found that organocatalysts 3–6 and 8–11 mediated
the direct asymmetric epoxidation of 1a. Notably, addi-
tion of 0.8 equiv of TEA enabled the use of proline and
tetrazole 4 as catalysts (entries 2 and 3). For example,
proline catalyzed the formation of ent-2a with 79% con-
version and 36% ee.16 Moreover, chiral proline-derived
diamines such as 5 and 6 catalyzed the asymmetric epox-
idation of 1a with poor to good enantioselectivity.17 For
instance, catalyst 5 exhibited the highest asymmetric
Keywords: Asymmetric catalysis; Proline derivatives; a,b-Unsaturated
aldehydes; Epoxides.
*
Corresponding author. Tel.: +46 8 162479; fax: +46 8 154908; e-mail
addresses: acordovala@netscape.net; acordova@organ.su.se
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.128

100
H. Sunde´n et al. / Tetrahedron Letters 47 (2006) 99–103
Table 1. Catalyst screen for the direct catalytic asymmetric epoxidation of 1a with hydrogen peroxidea
O
O
Catalyst
O
HOOH
+
H2O
+
H
H
(10-30 mol%)
(1.2-7 equiv)
1a
2a
O
H2N
N
H
N
H
N
N
N
OH
N
N
N
N
H
H
N
N
N
HN
HN
N
N
N
O
3
4
5
6
7
O
O
N
COOEt
N
H
N
H
N
HCl
N
H
N
OH
OTMS
H
O
8
9
10
11
12
Entry
Catalyst
Time (h)
Conversion (%)b
drc
ee (%)c
1
2
3
4
5
6
7
8
3d
24
16
16
22
19
24
14
16
2
<1
79
82
60
41
<1
85
43
91 (81)g
28
n.d.
60:40
74:26
53:47
45:54
n.d.
79:21
5:95
93:7
n.d.
ꢀ36
ꢀ15
66
7
n.d.
24
22
97
12
12
3d,e
4d,e
5d
6d
7d
8d
9d
9
10f
11f,h
11f,i
12d
10
11
12
3
18
16
48:52
96:4
n.d.
55
<1
n.d.
a To a stirred solution of catalyst (10-30 mol %) in CHCl3 (1 mL) was added aldehyde 1a (0.25 mmol) and H2O2 (0.3–1.75 mmol, 50% aqueous
solution). The reaction was vigorously stirred at room temperature and monitored by chiral-phase GC analyses.
b Amount of formed product as determined by chiral-phase GC analyses.
c The dr (trans/cis) and ee were determined by chiral-phase GC analyses.
d 30 mol % catalyst.
e 0.8 equiv TEA added.
f 10 mol % catalyst and 1.2 equiv H2O2.
g Isolated yield of pure 2a after silica gel column chromatography.
h Reaction run in H2O/EtOH 1:1.
i Reaction run in dioxane.
induction and catalyzed the enantioselective epoxidation
of 1a with good conversion (60%) to furnish 2a in a
53:47 dr (trans/cis) and with 66% ee. Moreover, we
investigated diphenyl-2-pyrrolidinemethanol (9, diphen-
ylprolinol), which has been developed by Corey and co-
workers,18 as a catalyst. Diphenylprolinol 9 (20 mol %)
catalyzed the stereoselective epoxidation of 1a with
excellent diastereoselectivity (5:95) and low enantiose-
lectivity (22%). The exchange of the hydroxy group in
9 to a siloxy group had a remarkable effect on the reac-
tivity and enantioselectivity of the asymmetric epoxida-
tion.19 That is, the chiral pyrrolidine 10 (10 mol %)
catalyzed the asymmetric epoxidation of 1a within 2 h
(91% conv.) and furnished epoxide 2a in 81% yield in
a 93:7 dr and 97% ee. Moreover, TMS protection of
diphenylprolinol 9 switched the diastereoselectivity of
the reaction. MacMillanÕs imidazolidinones such as 11
also catalyzed the direct asymmetric epoxidation of
a,b-unsaturated aldehydes with high diastereoselectivity
and modest enantioselectivity under our reaction condi-
tions.20 Encouraged by our initial results, we decided to
investigate the utilization of different oxidants and reac-
tion conditions for the direct asymmetric epoxidation of
1a mediated by catalysts 5 and 10 (Table 2).
The proline-derived diamine 5 catalyzed the enantio-
selective epoxidation of 1a with the highest asymmetric
induction in CHCl3. Unfortunately, decreasing the
reaction temperature to ꢀ20 °C and increasing the cat-
alyst loading did not improve the enantioselectivity
(entries 2 and 3). Moreover, chiral amine 10 catalyzed
the asymmetric epoxidation of a,b-unsaturated alde-
hyde 1a with hydrogen peroxide, solid SPC and tert-
butyl hydrogen peroxide as the oxidants to form 2a
with high diastereoselectivities (82:18–95:5) and excel-
lent enantioselectivities (>95% ee). The highest diaste-
reo and enantioselectivity for the catalyst 10-mediated
asymmetric epoxidation of 1a was achieved at 4 °C
and room temperature in CHCl3 using H2O2 and
SPC, respectively, as the oxidants. In addition, chiral

H. Sunde´n et al. / Tetrahedron Letters 47 (2006) 99–103
101
Table 2. The catalyst 5- and 10-mediated direct asymmetric epoxidation of 1a mediated by catalysts 5 and 10 under different reaction conditionsa
5 ( 30 mol%) or 10 (10 mol%)
O
O
O
H2O
+
+
oxidant
H
H
Solvent
(1.2 equiv)
1a
Oxidant
2a
Entry
Cat.
Solvent
Temp (°C)
Time (h)
Conv. (%)b
drb
ee (%)b
1
2
3
4
5
6
7
8
5
5c
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
SPC
t-BuOOH
m-CPBA
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
CHCl3
CHCl3
CH2Cl2
TBME
THF
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
Toluene
THF
EtOH
H2O/tert-BuOH (1:1)
H2O/EtOH (1:1)
4
22
19
19
48
48
2
7
6
3
16
2
60
94
97
53
53:47
81:19
82:18
58:42
56:44
93:7
66
60
50
31
52
97
98
>95
>95
51
96
97
90
92
94
90
ꢀ20
5c
ꢀ20
4
5
5
4
rt
4
7
10
10
10
10
10
10
10
10
10
10
10
91 (81)d
88
75
84
95:5
rt
rt
rt
rt
rt
rt
rt
rt
rt
84:16
82:18
96:4
90:10
91:9
9
10
11
12
13
14
15
16
<10
88
94
17
94
84
67
2
2
2
2
95:5
87:13
87:13
87:13
2
a To a stirred solution of catalyst 5 (30 mol %) or 10 (10 mol %) in organic solvent (2 mL) was added aldehyde 1a (0.25 mmol) and oxidant (0.3 mmol,
1.2 equiv). The reaction was vigorously stirred at the temperature shown in the table and monitored by chiral-phase GC analyses.
b Determined by chiral-phase GC analyses.
c 60 mol % catalyst. and 7 equiv H2O2.
d Isolated yield of pure 2a after silica gel column chromatography.
amine 10 catalyzed the direct asymmetric epoxidation
of 1a in CH2Cl2, toluene, THF and ethanol with excel-
lent stereoselectivities. Notably, high enantioselectivity
was obtained in aqueous media (H2O/tert-BuOH 1:1
or H2O/EtOH 1:1) where epoxide 2a was formed with
90–94% ee. Thus, the chiral amine-catalyzed asymmet-
ric epoxidation reaction is environmentally benign.
Diamines 5 and 6 catalyzed the asymmetric epoxida-
tions of a,b-unsaturated aliphatic aldehydes 1 using
hydrogen peroxide as the oxidant with high diastere-
oselectivity and modest enantioselectivity. To our satis-
faction, TMS prolinol 10 was an excellent catalyst for
the asymmetric synthesis of aliphatic and ester func-
tionalized epoxides such as 2b–d (91:9–96:4 dr and
91–98% ee). Moreover, TMS-prolinol 10 mediated the
direct asymmetric epoxidations with excellent stereo-
selectivity in aqueous solvent utilizing H2O2 as the
oxidant.
Next, we reacted a series of different substituted a,b-
unsaturated aldehydes 1 with H2O2 and SPC as the oxi-
dants in the presence of catalysts 5, 6 and 10 (Table 3).21
Table 3. The direct asymmetric epoxidation of a,b-unsaturated aldehydes 1 with hydrogen peroxide or SPC mediated by catalysts 5, 6 and 10a
5, 6 ( 30 mol%) or 10 (10 mol%)
O
O
O
H2O
+
+
oxidant
(1.2 equiv)
R
H
R
H
CHCl3, rt
Temp (°C)
1
2
Entry
Cat.
Oxidant
R
Prod.
Time (h)
Conv. (%)b
drc
ee (%)c
1
2
3
4
5
6
7
8
9
5
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
SPC
Ph
Ph
2a
2a
2b
2b
2b
2b
2c
2d
2d
4
22
2
20
20
2
2e
1.5
2
2
60
53:47
93:7
66
97
6
14
93
>95e
91
98
98
10
6
rt
rt
rt
rt
rt
rt
rt
rt
91 (81)d
81
n-Propyl
n-Propyl
n-Propyl
n-Propyl
n-butyl
CO2Et
CO2Et
84:16
81:19
95:5
96:4e
95:5
5
70
10
10
10
10
10
>90
99e
94
>90
>90
91:9
90:10
a To a stirred solution of catalyst 5, 6 (30 mol %) or 10 (10 mol %) in CHCl3 (2 mL) was added aldehyde 1 (0.25 mmol) and oxidant (0.3 mmol,
1.2 equiv). The reaction was vigorously stirred at the temperature shown in the table and monitored by chiral-phase GC analyses.
b Amount of formed product as determined by chiral-phase GC analyses.
c Determined by chiral-phase GC analyses.
d Isolated yield of pure 2 after silica gel column chromatography.
e Reaction run in H2O/tert-BuOH 1:1.

102
H. Sunde´n et al. / Tetrahedron Letters 47 (2006) 99–103
X
+
X
N
N
R1
R1
O
O
OR
OR
H
O
H
H2O
R1
X
+
1
N
X
N
H
R1
O
O
O
R1
H
2
Scheme 1. The probable catalytic mechanism of the chiral pyrrolidine-catalyzed asymmetric epoxidation of a,b-unsaturated aldehydes.
We also attempted the catalytic asymmetric epoxidation
of a,b-unsaturated ketones with different oxidants and
10 as the organocatalyst under our reaction conditions.
However, catalyst 10 failed to furnish the desired epox-
ide. Instead, diphenylprolinol 9 mediated the asymmet-
ric epoxidation of a,b-unsaturated ketones.8c
aqueous media, hydrogen peroxide and non-toxic
metal-free catalysts makes this process environmentally
benign.
Acknowledgement
The mechanism of the direct organocatalytic asymmet-
ric epoxidation of a,b-unsaturated aldehydes starts with
iminium activation of the a,b-unsaturated aldehyde by
the chiral pyrrolidine derivative followed by stereoselec-
tive nucleophilic conjugate attack on the b-carbon
resulting in a chiral enamine derivative (Scheme 1).
Next, the chiral enamine performs a nucleophilic attack
on the electrophilic peroxygen, followed by hydrolysis of
the resulting iminium intermediate. The reverse catalytic
cycle has been observed in direct organocatalytic enan-
tioselective tandem a-aminoxylation/Michael reac-
tions10i,k,l and aza-Diels–Alder reactions22 with a,
b-unsaturated ketones, which further supports the
proposed mechanism. The remarkable change of the
reactivity by TMS protection of the diphenylprolinol 9
was explained by prevention of plausible aminal forma-
tion and increased hydrophobicity of the catalyst, which
improves the rate of iminium formation with aldehydes
1. In addition, the high enantioselectivity observed for
the asymmetric epoxidations with catalyst 10 is plausi-
bly due to stabilization of the configuration of the imin-
ium ion intermediate as well as efficient shielding of the
Si-face of the chiral iminium and enamine intermediates
by the bulky aryl groups.
A.C. thanks the Swedish Research Council and Wenner-
Gren Foundation for financial support.
References and notes
1. (a) Comprehensive Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Heidel-
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2. Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102,
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3. (a) Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E.
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1990, 31, 7345, Review see: Katsuki, T. in Ref. 1c, pp.
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4. For selected reviews see: (a) Dalko, P. I.; Moisan, L.
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Armstrong, A. Angew. Chem., Int. Ed. 2004, 43, 1460, and
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5. (a) Julıa, S.; Masana, J.; Vega, J. C. Angew. Chem., Int.
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J. Chem. Soc., Perkin, Trans. 1 1982, 1317.
In summary, we have shown that proline, proline-de-
rived chiral amines and imidazolidinone 11 catalyze
the asymmetric epoxidation of a,b-unsaturated alde-
hydes with hydrogen peroxide or SPC. In particular,
organocatalyst 10, derived in one-step from the com-
mercially available diphenylprolinol 9, catalyzed the
asymmetric epoxidation with excellent stereoselectivity
and furnished the desired products in high efficiency
with up to 96:4 dr and 98% ee. Moreover, the use of
6. For selected examples see: (a) Helder, T.; Hummelen, J.
C.; Laane, R. W. P. M.; Wiering, J. S.; Wynberg, H.
Tetrahedron Lett. 1976, 21, 1831; (b) Corey, E. J.; Zhang,
F.-Y. Org. Lett. 1999, 1, 1287; (c) Lygo, B.; Wainwright,
P. G. Tetrahedron Lett. 1998, 38, 1599; (d) Jew, S.-S.; Lee,
J.-H.; Jeong, B.-S.; Yoo, M.-S.; Kim, M.-J.; Lee, Y.-J.;
Lee, J.; Choi, S.-H.; Lee, K.; Lah, M.-S.; Park, H.-G.
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H. Sunde´n et al. / Tetrahedron Letters 47 (2006) 99–103
103
7. Shi, Y. Acc. Chem. Res. 2004, 37, 488, and references cited
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analyses. The formation and enantiomeric excess of 2a
was determined on a Chromasil CP-Chirasil-Dex CB-
column. Temperature program: 70–160 °C, rate; 10 °C/
min, hold 1 min, 160–200 °C, rate; 80 °C/min, hold 5 min.
tR (min) = major enantiomer 8.04 min, minor enantiomer
8.12 min.
8. (a) Bohe, L.; Hanquet, M.; Lusinchi, M.; Lusinchi, X.
Tetrahedron Lett. 1993, 34, 7271; (b) Adamo, M. F. A.;
Aggarwal, V. K.; Sage, M. A. J. Am. Chem. Soc. 2000,
122, 8317; For a very recent chiral pyrrolidine-catalyzed
epoxidation of a,b-enones see: (c) Lattanzi, A. Org. Lett.
2005, 7, 2579.
17. Typical catalyst 5, 6, 9 and 10 catalyzed asymmetric
epoxidation: To a stirred solution of 4, 5 (30 mol %), 9
(20 mol %) or 10 (10 mol %) in CHCl3 (2 mL) was added
aldehyde 1a (0.25 mmol) and H2O2 (0.3 mmol, 50%
aqueous solution). The reaction was vigorously stirred at
room temperature and monitored by chiral-phase GC
analyses. The formation and enantiomeric excess of 2a
was determined on a Chromasil CP-Chirasil-Dex CB-
column. Temperature program: 70–160 °C, rate; 10 °C/
min, hold 1 min, 160–200 °C, rate; 80 °C/min, hold 5 min.
tR (min) = major enantiomer 8.04 min, minor enantiomer
8.12 min. Isolation of 2a derived by diphenylprolinol 10
catalysis by silica gel column chromatography (pentane/
EtOAc 3:1) furnished (2S,3R)-3-phenyloxirane-2-carbal-
9. Nemoto, T.; Ohshima, T.; Shibasaki, M. J. Am. Chem.
Soc. 2001, 123, 9474, and references cited therein.
´
´
10. (a) Bøgevig, A.; Sunden, H.; Cordova, A. Angew. Chem.,
´
´
Int. Ed. 2004, 43, 1109; (b) Cordova, A.; Sunden, H.;
Bøgevig, A.; Johansson, M.; Himo, F. Chem. Eur. J. 2004,
10, 3673; (c) Zhong, G. Angew. Chem., Int. Ed. 2003, 42,
4247; (d) Brown, S. P.; Brochu, M. P.; Sinz, C. J.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 10808;
(e) Hayashi, Y.; Yamaguchi, J.; Hibino, K.; Shoji, M.
Tetrahedron Lett. 2003, 44, 8293; (f) Hayashi, Y.; Yama-
guchi, J.; Hibino, K.; Shoji, M. Angew. Chem., Int. Ed.
2004, 43, 1112; (g) Hayashi, Y.; Yamaguchi, J.; Sumiya,
T.; Hibino, K.; Shoji, M. J. Org. Chem. 2004, 69, 5966; (h)
Momiyama, N.; Torii, H.; Saito, S.; Yamamoto, H. Proc.
Natl. Acad. Sci. U.S.A. 2004, 101, 5374; (i) Yamamoto,
Y.; Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc.
2004, 126, 5962; (j) Wang, W.; Wang, J.; Li, H.; Liao, L.
1
dehyde 2a (81%, 30 mg). H NMR (CDCl3, 400 MHz): d
(ppm) 9.20 (d, J = 6.1 Hz, 1H), 7.39–7.29 (m 5H), 4.17 (d,
J = 1.8 Hz, 1H), 3.46 (dd, J = 1.8, 6.1 Hz, 1H); 13C NMR
(CDCl3, 125 MHz): d (ppm): 196.7, 134.2, 129.2, 128.8
25
(2C), 125.7 (2C), 62.9, 56.6; ½aꢁD ꢀ30.1 (c = 1.6, CHCl3)
23
Tetrahedron Lett. 2004, 45, 7235; (k) Sunden, H.; Dahlin,
(Lit. ent-2a, ½aꢁD +14.3 (c = 0.48, CHCl3, 94% ee)9).
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´
N.; Ibrahem, I.; Adolfsson, H.; Cordova, A. Tetrahedron
18. Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc.
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19. The commercially available catalyst 9 (1 g, 3.95 mmol) was
readily protected with TMSOTf (1.1 g, 5.1 mmol) in the
presence of TEA (0.51 g, 5.1 mmol) in CH2Cl2 (20 mL) at
0 °C. The reaction was stirred at room temperature for
17 h and quenched with water (10 mL). The aqueous layer
was extracted with CH2Cl2 (3x15 mL). The combined
organic extracts were stirred with NaHCO3 for 15 min,
dried over anhydrous Na2SO4 and concentrated in vacuo
after filtration. Purification with silica gel column chro-
matography (EtOAc/pentane 1.7 ! 1.3) furnished 10 as a
thick oil (99%, 1.3 g). Jørgensen and co-workers have
shown that TMS protection of diarylprolinols is an
excellent strategy to achieve high stereoselectivity in
organocatalytic a-fluorinations and a-sulfenylation of
aldehydes see: (a) Marigo, M.; Wabnitz, T. C.; Fielenbach,
D.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2005, 44, 794;
(b) Marigo, M.; Fielenbach, D.; Braunton, A.; Kjaersg-
aard, A.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2005,
44, 3703; (c) Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji,
M. Angew. Chem., Int. Ed. 2005, 44, 4212.
20. Typical 11-catalyzed asymmetric epoxidation: To a stirred
solution of 11 (10 mol %) in solvent (2 mL) was added
aldehyde 1a (0.25 mmol) and H2O2 (0.3 mmol, 50%
aqueous solution). The reaction was vigorously stirred at
room temperature and monitored by chiral-phase GC
analyses. The formation and enantiomeric excess of 2a
was determined on a Chromasil CP-Chirasil-Dex CB-
column.
21. Typical 10-catalyzed asymmetric epoxidation of aldehydes
1: To a stirred solution of 10 (10 mol %) in solvent (2 mL)
was added aldehyde 1a (0.25 mmol) and H2O2 (0.3 mmol,
50% aqueous solution) or SPC (0.38 mmol + 50 lL H2O).
The reaction was vigorously stirred at room temperature
and monitored by chiral-phase GC analyses. The forma-
tion and enantiomeric excess of the desired epoxides 2
were determined on a Chromasil CP-Chirasil-Dex CB-
column.
´
´
11. Engqvist, M.; Casas, J.; Sunden, H.; Ibrahem, I.; Cordo-
va, A. Tetrahedron Lett. 2005, 46, 2053.
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12. (a) Cordova, A.; Sunden, H.; Engqvist, M.; Ibrahem, I.;
´
Casas, J. J. Am. Chem. Soc. 2004, 126, 8914; (b) Sunden,
´
H.; Engqvist, M.; Casas, J.; Ibrahem, I.; Cordova, A.
Angew. Chem., Int. Ed. 2004, 43, 6532.
13. For selected examples of MacMillan catalyst promoted
iminium activations see: (a) Ahrendt, K. A.; Borths, C. J.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 4243;
(b) Paras, N. A.; MacMillan, D. W. C. J. Am. Chem. Soc.
2001, 123, 4370; (c) Kunz, R. K.; MacMillan, D. W. C. J.
Am. Chem. Soc. 2005, 127, 3240; (d) Ouellet, S. G.; Tuttle,
J. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127,
32; (e) Yang, J. W.; Hechavarria Fonseca, M. T.; Vignola,
N.; List, B. Angew. Chem., Int. Ed. 2005, 44, 108; For
examples of Jørgensen catalyst promoted iminium activa-
tions see: (f) Halland, N.; Hazell, R.; Jørgensen, K. A.
J. Org. Chem. 2002, 67, 8331; (g) Halland, N.; Aburel, P.
S.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2003, 42, 661;
(h) Halland, N.; Hansen, T.; Jørgensen, K. A. Angew.
Chem., Int. Ed. 2003, 42, 4955; (i) Halland, N.; Aburel, P.
S.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2004, 43,
1272.
14. During our studies the following excellent paper appeared:
´
Marigo, M.; Franzen, J.; Poulsen, T. B.; Zhuang, W.;
Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 6964.
15. Sodium percarbonate (SPC) represents one of the most
powerful oxidants available. It is particularly advanta-
geous owing to its ease of handling and storage. See: (a)
McKillop, A.; Sanderson, W. R. Tetrahedron 1995, 51,
6145; (b) Muzart, J. Synthesis 1995, 1325.
16. Typical proline and tetrazole 4 catalyzed asymmetric
epoxidation: To a stirred solution of proline or 4
(30 mol %) in CHCl3 (2 mL) was added aldehyde 1a
(0.25 mmol), H2O2 (1.75 mmol, 50% aqueous solution)
and TEA (0.2 mmol). The reaction was vigorously stirred
at room temperature and monitored by chiral-phase GC
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22. Sunden, H.; Ibrahem, I.; Eriksson, L.; Cordova, A.
Angew. Chem., Int. Ed 2005, 44, 4877.