Chiral primary amine catalyzed asymmetric epoxidation of α-substituted acroleins

Article abstract of DOI:10.1002/ejoc.201001117

1,1-Disubstituted terminal alkenes remain challenging substrates in asymmetric epoxidation reactions. In this study, chiral primary amines are shown to catalyze the asymmetric epoxidation of α-substituted acroleins, a versatile type of 1,1-disubstituted t

Full text of DOI:10.1002/ejoc.201001117

FULL PAPER
DOI: 10.1002/ejoc.201001117
Chiral Primary Amine Catalyzed Asymmetric Epoxidation of α-Substituted
Acroleins
Jiuyuan Li,[a] Niankai Fu,[a] Long Zhang,[a] Pengxin Zhou,[b] Sanzhong Luo,*[a] and
Jin-Pei Cheng[b]
Keywords: Asymmetric catalysis / Epoxidation / Amines / Chirality
1,1-Disubstituted terminal alkenes remain challenging sub-
strates in asymmetric epoxidation reactions. In this study,
chiral primary amines are shown to catalyze the asymmetric
epoxidation of α-substituted acroleins, a versatile type of 1,1-
disubstituted terminal alkene. Among various chiral primary
amines explored, the chiral primary-tertiary vicinal diamine
derived from trans-1,2-diphenylethane-1,2-diamine is iden-
tified as the optimal catalyst, which, in combination with 5-
sulfosalicyclic acid (5-SSA), exhibits good catalytic activity
(up to 95% yield) and enantioselectivity (up to 88% ee).
Aqueous 2
M sodium chloride was found to be the optimal
reaction media.
tive Diels–Alder reactions,[5] [2+2] cycloaddition reac-
tions,[6] and epoxidation[3f] or peroxidation reactions.[3g,3h]
We also established chiral primary-tertiary diamines as ef-
fective catalysts for enamine activation of both ketones and
aldehydes,[7] and this catalysis has now been further ex-
panded to include iminium activation of α-acyloxy acrole-
ins.[5f] More recently, Pihko and co-workers reported that
achiral, bulky anilines could catalyze the epoxidation of α-
branched acroleins with tert-butyl hydroperoxide (TBHP)
as the oxidant.[8] Upon the submission of this manuscript,
List and co-workers reported a catalytic system that com-
bined chiral primary amines and chiral phosphoric acids
for the asymmetric epoxidation of α-substituted enals with
excellent enantioselectivity.[9] Nevertheless, a simple, asym-
metric catalytic system is still highly desirable. Herein, we
wish to report an asymmetric epoxidation of α-substituted
acroleins catalyzed by simple chiral primary-tertiary di-
amines.
Introduction
1,1-Disubstituted terminal alkenes have been regarded as
challenging substrates in asymmetric epoxidation reac-
tions.[1] In particular, catalytic asymmetric epoxidation of
α-substituted acroleins has not been achieved so far. One
conceivable way to address this type of substrate is the well-
utilized imminium catalysis.[2] Unfortunately, typical sec-
ondary amine based iminium catalysis has been much less
effective with α-substituted enones and enals, a result that
is mainly ascribed to the sterically demanding nature of α-
substituents in the iminium intermediates. Accordingly, im-
inium-catalyzed epoxidation reactions have been largely
limited to α-unsubstituted enones and enals.[3] Catalytic
enantioselective reaction with α-substituted enones and en-
als still represents an elusive target in iminium chemistry.
In this regard, α-substituted acroleins are particularly chal-
lenging substrates when the difficulties in stereocontrol with
β-unsubstituted enals are considered in the context of imin-
ium-enamine catalysis.[2a]
On the other hand, chiral primary amines have recently
appeared as efficient aminocatalysts that enable transfor-
mations with sterically congested substrates beyond the
reach of secondary amines.[4] The use of chiral primary
amines has made possible the iminium activation of α-acyl-
oxy acroleins or α-substituted enones toward enantioselec-
Results and Discussions
Initial Trials with Primary Amine Catalysts
Following Pihko’s report,[8] we first tested a series of chi-
ral anilines in the epoxidation of 2-benzylacrylaldehyde (1a)
with TBHP. Aniline-oxazoles such as 3a–c were readily syn-
thesized according to the published procedures.[10] Catalysis
by the chiral aniline-oxazoles gave moderate activity, but
rather poor enantioselectivity (Scheme 1). Extensive explor-
ations with the aniline derivatives did not lead to satisfac-
tory improvement, and the best enantioselectivity (34% ee)
was obtained only when a chiral counteranion strategy was
applied (catalyst 4, Scheme 1).[11]
[a] Beijing National Laboratory for Molecular Sciences (BNLMS),
CAS Key Laboratory of Molecular Recognition and Function,
Institute of Chemistry, Chinese Academy of Sciences,
Beijing 100190, P. R. of China
Fax: +86-10-62554449
E-mail: luosz@iccas.ac.cn
[b] Department of Chemistry and State Key Laboratory of
Elemento-organic Chemistry, Nankai University,
Tianjin 300071, P. R. of China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001117.
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Asymmetric Epoxidation of α-Substituted Acroleins
Table 1. Initial optimization of the epoxidation of 2-benzylacrylal-
dehyde catalyzed by 9a.
Entry[a] Acid[b]
Solvent
Yield [%][c]
ee [%][d]
1
2
3
4
5
6
7
8
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
2,4-DNBS
DBSA
pTSA
TFA
CH3CO2H
mNO2C6H4CO2H H2O
H3PW12O40
Zn(OAc)2
–
toluene
n-hexane
THF
MeOH
CH3CN
CH2Cl2
H2O
H2O
H2O
H2O
H2O
59
53
27
75
41
62
73
59
57
52
61
10
15
32
trace
trace
43
46
37
41
39
45
47
37
32
28
10
Ͻ5
10
9
Scheme 1. Chiral aniline catalyzed asymmetric epoxidation reaction
of 2-benzylacrylaldehyde.
9
10
11
12
13
14
15
16
Other types of chiral primary amines were then screened.
To our delight, the chiral primary-tertiary diamine
Brønsted acid conjugate catalyst 9a in combination with
trifluoromethanesulfonic acid (TfOH), previously devel-
oped in our group,[7a] was found to be the optimal primary
amino catalyst for the epoxidation reactions. With 20 mol-
% of 9a/TfOH, the reaction afforded 62% yield and 45%
ee. In contrast, other chiral pimary amine catalysts, such as
H2O
H2O
H2O
H2O
–
–
[a] Reagents and conditions: 2-benzylacrylaldehyde (73 mg,
0.5 mmol), TBHP (0.8 mmol), solvent (0.5 mL), catalyst (20 mol-%),
r.t. [b] 2,4-DNBS: 2,4-dinitrobenzenesulfonic acid; DBSA: 4-dodecyl-
amino acids, amino alcohol 5, amino sulfamide 6, and benzenesulfonic acid. [c] Isolated yield. [d] Determined by HPLC af-
ter reduction by NaBH4.
amino amide 7, were nearly inactive for the reaction
(Scheme 2).
Bearing in mind the dramatic effect of acidic additives in
the catalysis of 9a,[7] we next examined a range of acidic
additives to further improve the activity and stereoselec-
tivity. Not unexpectedly, the reaction barely occurred in the
absence of any acidic additives (Table 1, entry 16). In gene-
ral, the use of stronger acids led to better results (Table 1,
entries 7–13), and optimal results were obtained with the
most acidic additive TfOH (Table 1, entry 7). The unexpec-
ted low yield and stereoselectivity exhibited in the presence
of H3PW12O40 may be ascribed to its poor solubility in
water (Table 1, entry 14). A Lewis acid, Zn(OAc)2, was also
tested, but the reaction did not occur (Table 1, entry 15).
Screening of Primary-Tertiary Diamine Catalysts
Under the initial optimized conditions (in H2O, TfOH),
a series of chiral primary-tertiary diamines bearing different
Scheme 2. Screening of different chiral primary amines.
skeletons and substituents were synthesized (see the Sup-
porting Information for details) and assessed in the model
reaction (Figure 1). As revealed in Table 2, several general
observations can be summarized: (a) Vicinal primary-terti-
ary diamine is the optimal bifunctional catalytic motif for
this reaction. The use of other diamines such as primary-
Initial Optimization of the Epoxidation Reaction Catalyzed
by 9a
With 9a/TfOH conjugate as catalyst, the essential reac- secondary diamines 9c, 10a, or 11h (Table 2, entries 3, 6
tion conditions were first determined. As shown in Table 1, and 18), gave inferior results or was inactive in the case of
the reaction proceeded smoothly in nearly all the organic primary-primary diamine 9b (Table 2, entry 2); (b) Among
solvents examined with moderate yield and enantio- the diamine skeletons examined (9–13), those based on
selectivity (Table 1, entries 1–6). Gratifying, the catalytic ac- trans-1,2-diphenylethane-1,2-diamine stand out with gen-
tivity could be significantly improved (Table 1, entry 7, 73% erally better activity and stereoselectivity (Table 2, entries
yield, 47% ee) with water as solvent, which was then se- 11–18); (c) Side chains of the tertiary amine moieties have
lected as the optimal solvent for subsequent studies.
a significant impact on both activity and enantioselectivity.
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In an extreme case, simply switching of the acyclic dialkyl-
ated group (e.g., 11c) to a cyclic pyrrolidinyl group (11g)
makes the catalyst almost inactive (Table 2, entry 17). Fi-
nally, trans-1,2-diphenylethane-1,2-diamine derived pri-
mary-tertiary diamine 11c was identified as the optimal cat-
alyst in this round of screening. The reaction in the presence
of 10 mol-% 11c/TfOH gave 87% yield and 58% ee
(Table 2, entry 13); hence, this system was chosen for fur-
ther optimization.
Further Optimization
With 11c/TfOH established as the optimal catalyst, the
reaction was further optimized by examining different oxi-
dants, aqueous salt effects, acidic additives, and electronic
effects.
Oxidant: A range of oxidants, mostly peroxides, have
been examined (Scheme 3). All the hydroperoxides tested
could react with 2-benzylacrylaldehyde (1a) to afford the
desired epoxide product 2a, and the use of cumene hydro-
peroxide (CMHP) as the oxidant was found to give a signif-
icantly improved enantioselectivity (67% ee) albeit with a
slightly lower yield (Scheme 3). No further improvement on
enantioselectivity could be attained with either more bulky
hydroperoxides such as 14 and 15, or chiral hyroperoxides
such as 16. With a balance of activity and stereoselectivity,
CMHP was chosen as the oxidant for further optimization.
Figure 1. Selected primary-tertiary diamines.
Table 2. Screening of chiral primary-tertiary diamines.
Entry[a]
Amine
X
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9a
9b
20
20
20
20
20
20
20
20
20
20
10
10
10
10
10
10
10
10
10
10
73
Ͻ10
63
77
87
54
60
62
64
59
83
83
87
80
61
79
47
–
9c
45
46
15
56
57
59
53
45
43
49
58
53
30
37
–
9d
9e
10a
10b
10c
10d
10e
11a
11b
11c
11d
11e
11f
11g
11h
12
Scheme 3. Screening of oxidants.
9
Aqueous Salt Effect: Salt additives are well-known to
have a dramatic effect on the reactivity and stereoselectivity
for reactions in aqueous media.[12] Interestingly, the reac-
tions were accelerated considerably, along with a modest
increase of enantioselectivity, when conducted in salt solu-
tion, and the use of 2 m NaCl solution was found to give
the best improvement. In this medium, the reaction pro-
ceeded to 94% conversion with 71% ee in 16 h in the pres-
ence of 10 mol-% catalyst (Table 3, entry 5). Other aqueous
solutions were also examined and were found to exhibit
mixed salt effects. For example, in aqueous LiCl solution,
which is a typical salting-out salt like NaCl, the activity was
seriously diminished (Table 3, entry 7), suggesting that the
10
11
12
13
14
15
16
17
18
19
20
Ͻ10
49
77
31
25
5
13
60
[a] Reagents and conditions: 2-benzylacrylaldehyde (73 mg,
0.5 mmol), TBHP (0.8 mmol), water (0.5 mL), X mol-% catalyst, r.t.
[b] Isolated yield. [c] Determined by HPLC after reduction by
NaBH4.
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Asymmetric Epoxidation of α-Substituted Acroleins
salting-out effect is not the only working factor in this sys- chromatography grade, 200–400 mesh) exhibited a modest
tem. In a control experiment under neat conditions, the re- but reproducible increase in enantioselectivity (Table 4, en-
action proceeded much faster but, unfortunately, with re- try 4, 73% ee). During this study, we also noticed that
duced enantioselectivity (Table 3, entry 10), highlighting the Brønsted acids bearing bi/multi acidic moieties, such as sal-
beneficial nature of aqueous media for stereocontrol in this icyclic acid, were also an applicable type of acidic additive
case.
in addition to TfOH. By tuning the acidity of salicyclic
acid, we were able to identify an optimal Brønsted acid, 5-
sulfosalicyclic acid (5-SSA) (Table 4, entries 5–7), which
gave a slightly better enantioselectivity than that obtained
with TfOH (Table 4, entry 7 vs. entry 1). The silica gel effect
also worked with 5-SSA (Table 4, entry 8). With a 11c/5-
SSA/silica gel combination, we could obtain 96% conver-
sion and 79% ee, which is the best enantioselectivity so far
achieved at temperatures in the range of 0 °C to room tem-
perature (Table 4, entry 9). Further lowering the reaction
temperature only led to seriously reduced activity without
any noticeable improvement in enantioselectivity.
Electronic Tuning of Catalyst 11: With the established op-
timal conditions in hand, we then focused on electronic tun-
ing of diamine catalyst 11 with the aim of achieving better
stereocontrol. It is known that electronic tuning is a viable
approach for catalyst development because it can be ad-
justed without significantly perturbing the structure, and
dramatic electronic effects have also been reported in a
number of organocatalytic systems.[13] Unfortunately, no
improvement of the enantioselectivity was obtained in the
present reaction with catalyst 11 bearing either electron-do-
nating groups (11i–k, Table 5, entries 1–3) or electron-with-
drawing groups (11l–o, Table 5, entries 4–7). However, no-
table electronic effects on the activity have been observed in
this study, wherein catalyst 11l–o with electron-withdrawing
groups generally exhibited a higher activity than those (11i–
k) with electron-donating groups. Overall, the parent di-
amine 11c remained the optimal catalyst.
Table 3. Salt effect in 11c/TfOH catalyzed epoxidation of 1a.
Entry[a] Solvent
Time [h]
Conv. [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9
10
H2O
16 (36)
16 (36)
16 (36)
16 (24)
16
16
24
16
16
5
39 (83)[d]
45 (91)[d]
60 (95)[d]
84 (97)[d]
94
67
68
70
70
71
71
–
69
66
55
NaCl (0.5 m)
NaCl (1 m)
NaCl (1.5 m)
NaCl (2
brine
LiCl (2 m)
NaF (2 m)
KBr (2 m)
neat
M)
91
10
96
78
95
[a] Reagents and conditions: 2-benzylacrylaldehyde (73 mg,
0.5 mmol), CMHP (0.8 mmol), H2O (0.5 mL), catalyst (10 mol-%),
r.t. [b] Determined by GC, Ͼ90% selectivity for the desired epoxide
product. [c] Determined by HPLC after reduction by NaBH4. [d]
Conversion after the time given in parentheses in the time column.
Reidentification of Optimal Acidic Additives: Previously,
we have observed that the addition of a second weak acid
could significantly improve the catalysis of pimary-tertiary
diamines such as 9a/TfOH.[7] Considering this, we also ex-
amined the effect of a second weak acid in the current reac-
tion (10 mol-% 11c in 2 m NaCl) to further improve the
enantioselectivity. Although the activity was decreased with
an added weak acid such as 1,1Ј-bi-2-naphthol (BINOL), it
is interesting to note that the addition of silica gel (column
Table 5. Electronic effect of trans-1,2-diarylethane-1,2-diamines 11.
Table 4. Screening of acidic additives under aqueous conditions.
Entry[a]
Amine
Time [h]
Conv. [%][b]
ee [%][c]
1
2
3
4
5
6
7
11i
11j
11k
11l
11m
11n
11o
48
48
48
24
24
24
24
83
75
43
90
91
95
89
68
63
39
59
70
66
55
Entry[a]
Acid combination[b]
Time [h] Conv. [%][c] ee[%][d]
1
2
3
4
5
6
7
TfOH
16
16
16
16
36
24
24
18
24
94
44
56
95
80
94
94
92
96
71
70
70
73
53
72
75
76
79
TfOH/(R)-BINOL
TfOH/(S)-BINOL
TfOH, silica gel (20 mg)
salicyclic acid
2-SBA
5-SSA
[a] Reagents and conditions: 2-benzylacrolein (0.5 mmol), CMHP
(0.8 mmol), aqueous NaCl (2 m, 0.5 mL), catalyst (10 mol-%), silica
gel (20 mg), 0 °C (6 h), then r.t. [b] Determined by GC, Ͼ90%
selectivity for the desired epoxide product. [c] Determined by
HPLC after reduction by NaBH4.
8
5-SSA, silica gel (20 mg)
5-SSA, silica gel (20 mg)
9[e]
[a] Reagents and conditions: 2-benzylacrylaldehyde (73 mg,
0.5 mmol), CMHP (0.8 mmol), solvent (0.5 mL), catalyst (10 mol-
%), r.t. [b] 2-SBA: 2-sulfobenzoic acid; 5-SSA: 5-sulfosalicyclic
acid. [c] Determined by GC, Ͼ90% selectivity for the desired epox-
ide product. [d] Determined by HPLC after reduction by NaBH4.
[e] The reaction was first performed at 0 °C for 6 h and then
warmed to r.t. for 18 h.
Substrate Scope
Under the optimal conditions (10 mol-% of 11c/5-SSA/
silica gel in 2 m NaCl, with CMHP and at 0 °C to r.t.), we
next probed the scope of the epoxidation reaction for a vari-
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S. Luo et al.
FULL PAPER
Scheme 4. Transformation of epoxide products.
ety of α-branched acroleins. All the α-alkyl-substituted Synthetic Transformations of Epoxidation Products
acroleins reacted smoothly to generate the desired epoxides
The epoxide aldehyde obtained from the reaction mix-
ture could be readily transformed into chiral α,β-unsatu-
rated ester 17 by a standard olefination reaction without
further purification [Scheme 4, Equation (1)]. The chiral ep-
oxides could also be elaborated into 1,2-diols containing a
chiral quaternary center such as 18, which is an important
building block in many natural products and bioactive syn-
thetic molecules,[15] by reduction with LiAlH4 [Scheme 4,
Equation (2)]. In both reactions, the stereocenters of the
chiral epoxide products were maintained.
in good yields (79–95%) and enantioselectivities (32–88%
ee, Table 6). The aromatic substituents of the α-benzylacro-
leins have some effect on the enantioselectivity, and the best
enantiomeric excess (88% ee) was obtained with 2-OMe
substituted benzylacroleins such as 1g and 1j (Table 6, en-
tries 7 and 10). A reasonable enantioselectivity (75% ee)
was also obtained with non-benzylic substituted acrolein 1l
(Table 6, entry 12). The reaction works smoothly with al-
lylic alcohol type acrolein 1k to give the desired epoxide 2k
in high yield (95% yield), but low enantioselectivity (32%
ee, Table 6, entry 11). α-Alkoxyl and acryloxyl-substituted
acroleins such as 1m and 1n were found to be inert sub-
strates for the current reactions. Finally, the epoxidation re-
action of α,β-disubstituted enals, such as (E)-2-methyl-3-
phenylacrylaldehyde, was tried under the current system,
however, the reaction did not proceed at all. The absolute
configuration of products (e.g., 2a) was determined to be R
by comparison of their optical rotation values with those
of known compounds.[14]
Proposed Transition State
A catalytic cycle is proposed based on experimental ob-
servations and preliminary analysis. The reaction occurs
through iminium-activated oxa-Michael addition followed
by an enamine-mediated intramolecular α-oxidation, which
is the stereo-determining step. The hydrolysis of the imin-
ium intermediate then releases the product and completes
the cycle. In this catalytic scenario, the N–H···O hydrogen
bonding between the protonated tertiary amine and hydro-
peroxide is critical for stereocontrol (Scheme 5).
Table 6. Substrate scope of 11c/5-SSA-catalyzed epoxidation reac-
tions.
Entry[a]
1
R
Time [h]
2
Yield [%][b] ee [%][c]
1
2
3
4
5
6
7
8
1a Bn
24
36
36
24
24
24
24
24
24
24
24
36
48
48
2a 90 (96)
2b 85 (94)
2c 87 (95)
2d 88 (96)
2e 91 (97)
2f 88 (96)
2g 89 (94)
2h 89 (97)
2i 79
2j 94
2k 95
2l 85 (96)
2m no reaction
2n no reaction
79
78
82
76
79
81
88
75
78
88
32
75
–
1b 4-MeC6H4CH2
1c 4-ClC6H4CH2
1d 4-MeOC6H4CH2
1e 1-NaphCH2
1f 2-ClC6H4CH2
1g 2-MeOC6H4CH2
1h 3-MeOC6H4CH2
1i 2,4-Cl2 C6H3CH2
1j 2,4-(MeO)2C6H3CH2
1k BnOCH2
9
10
11
12
13
14
1l Bn(CH2)3
1m BnO
1n PhCOO
–
[a] Reagents and conditions: α-branched acrolein (0.5 mmol), cu-
mene hydroperoxide (0.8 mmol), aqueous NaCl (2 m, 0.5 mL), cata-
lyst (10 mol-%), silica gel (20 mg), 0 °C (6 h) then r.t. [b] Isolated
yield. Conversion determined by GC is given in parenthesis. [c]
Determined by HPLC after reduction by NaBH4.
Scheme 5. Proposed catalytic cycle.
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Asymmetric Epoxidation of α-Substituted Acroleins
33.8, 66.9, 76.4, 109.2, 115.6, 115.9, 129.6, 131.9, 148.7, 163.5 ppm.
HRMS: calcd. for C13H18N2O: 218.1419; found 218.1417.
Conclusions
We have developed a chiral primary amine 11c/5-sulfosal-
icyclic acid catalyzed enantioselective epoxidation of α-sub-
stituted acroleins with up to 95% yield and 88% ee in aque-
ous salt solution (2 m NaCl). The current study provides the
simple chiral primary-tertiary diamine 11c as a promising
lead for further developments along these lines.
Synthesis of Catalyst 11c. General Procedure: The mono acetyl pro-
tected diamine was synthesized according to the published pro-
cedure.[16] To a solution of N-[(1R,2R)-2-amino-1,2-diphenylethyl]-
acetamide (1.27 g, 5 mmol) in H2O (1 mL) and CH3CN (50 mL),
was added propionaldehyde (2 mL, 30 mmol). After stirring for
20 min at r.t., NaCNBH3 (630 mg, 10 mmol) was added and the
resulting solution was stirred for another 20 min. Acetic acid
(1 mL) was added and, after 2 h, the solvent was removed under
reduced pressure. Aqueous NaOH (1 m, 50 mL) was added and the
product was extracted with CH2Cl2 (3 ϫ 50 mL). The organic lay-
ers were combined, washed with brine (20 mL), dried with anhy-
drous Na2SO4 and concentrated. The residue was purified by flash
column chromatography and directly used for the next step.
Experimental Section
General Information: Commercial reagents were used as received,
unless otherwise indicated. 1H and 13C NMR spectra were recorded
with a 300 MHz instrument, as noted, and were internally refer-
enced to the residual protic solvent signals. Chemical shifts are re-
ported in ppm from tetramethylsilane with the solvent resonance
as the internal standard. The following abbreviations were used to
designate chemical mutiplicities: s = singlet, d = doublet, t = triplet,
q = quartet, h = heptet, m = multiplet, br = broad. All first-order
splitting patterns were assigned on the basis of the appearance of
the multiplet. Splitting patterns that could not be easily interpreted
are designated as multiplet (m) or broad (br). HPLC analysis was
performed using Chiralcel columns. Catalysts 4–10 and 13 are
known compounds.[4,7]
To the product obtained above was added aqueous HCl (4 m,
50 mL) and the solution was heated to reflux for 24 h. CH2Cl2
(60 mL) and H2O (30 mL) were added and K2CO3 was added until
pH 12 was reached. The organic phase was separated and the aque-
ous phase was extracted with CH2Cl2 (20 mL). The organic layers
were combined, dried with anhydrous Na2SO4 and concentrated.
The residue was purified by flash chromatography to afford catalyst
11c as a colorless oil (1.26 g, 85% yield). [α]2D0 = –21.9 (c = 0.5,
MeOH). 1H NMR (300 MHz, CDCl3): δ = 0.94–0.99 (t, J = 7.5 Hz,
6 H, Me), 1.53–1.62 (m, 4 H, CH2), 2.04 (br., 2 H, NH2), 2.08–
2.14 (m, 2 H, CH2), 2.57–2.61 (m, 2 H, CH2), 3.77–3.81 (d, J =
10.5 Hz, 1 H, CH), 4.41–4.45 (d, J = 10.5 Hz, 1 H, CH), 6.99–7.20
(m, 10 H, PhH) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.0, 21.8,
51.9, 55.9, 71.0, 126.6, 126.7, 127.4, 127.9, 128.1, 129.7, 136.0,
143.6 ppm. HRMS: calcd. for C20H28N2 296.2252; found 296.2254.
Synthesis of 3b. General Procedure: Synthesized according to the
published procedure.[9] To a 100 mL flask, under Argon, was added
anhydrous ZnCl2 (133 mg, 1 mmol), chlorobenzene (30 mL), 2-
aminobenzonitrile (1.18 g, 10 mmol), and (S)-2-amino-3-phen-
ylpropan-1-ol (1.51 g, 10 mmol), and the mixture was heated to
reflux for 3 d. After cooling to r.t., H2O (50 mL) was added and
the aqueous phase was extracted with CH2Cl2 (20 mL). The or-
ganic layers were combined, dried with anhydrous Na2SO4 and
concentrated. The residue was purified by flash column chromatog-
raphy to afford 3b (1.64 g, 65% yield) as a white solid. [α]2D0 = +47.8
Catalysts 11a, 11b, and 11d–j were synthesized according to same
procedure.
(1R,2R)-N1,N1-Dimethyl-1,2-diphenylethane-1,2-diamine (11a): The
catalyst was synthesized according to the general procedure as a
pale-yellow solid in 40% overall yield. [α]2D0 = –43.2 (c = 0.5,
CDCl3). 1H NMR (300 MHz, CDCl3): δ = 2.08–2.16 (br., 2 H,
NH2), 2.20 (s, 6 H, Me), 3.58–3.66 (d, J = 10.6 Hz, 1 H, CH), 4.37–
4.46 (d, J = 10.6 Hz, 1 H, CH), 6.93–7.04 (m, 3 H, ArH), 7.04–
7.18 (m, 5 H, ArH), 7.18–7.25 (d, J = 7.9 Hz, 2 H, ArH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 41.0, 55.7, 75.4, 126.8, 126.9, 127.3,
128.0, 128.1, 129.8, 134.0, 143.4 ppm. HRMS: calcd. for C16H20N2
240.1626; found 240.1628.
1
(c = 0.5, MeOH). H NMR (300 MHz, CDCl3): δ = 2.62–2.69 (m,
1 H, PhCH2), 2.99–3.06 (m, 1 H, PhCH2), 3.89–3.94 (t, J = 4.5 Hz,
1 H, OCH2), 4.13–4.19 (t, J = 9.0 Hz, 1 H, OCH2), 4.45–4.55 (m,
1 H, NCH), 5.99 (br., 2 H, NH2), 6.55–6.59 (m, 2 H, ArH), 7.07–
7.21 (m, 6 H, PhH, ArH), 7.57–7.60 (d, J = 8.1 Hz, 1 H, ArH) ppm.
13C NMR (75 MHz, CDCl3): δ = 42.3, 68.2, 70.3, 109.0, 115.7,
116.0, 126.5, 128.6, 129.3, 129.7, 132.1, 138.4, 148.7, 164.1 ppm.
HRMS: calcd. for C16H16N2O: 252.1263; found 252.1262.
(1R,2R)-N1,N1-Diethyl-1,2-diphenylethane-1,2-diamine (11b): The
needle-like catalyst was synthesized according to the general pro-
cedure in 55% overall yield. [α]2D0 = –20.8 (c = 0.5, EtOH). 1H
NMR (300 MHz, CDCl3): δ = 1.05–1.10 (t, J = 7.1 Hz, 6 H, Me),
2.03–2.14 (m, 2 H, CH2), 2.36 (br., 2 H, NH2), 2.67–2.78 (m, 2 H,
CH2), 3.76–3.79 (d, J = 10.6 Hz, 1 H, CH), 4.35–4.38 (d, J =
10.5 Hz, 1 H, CH), 6.92–7.17 (m, 10 H, PhH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.4, 43.5, 55.8, 70.4, 126.7, 126.8, 127.4,
128.0, 128.1, 129.6, 136.1, 143.3 ppm. HRMS: calcd. for C18H24N2
268.1939; found 268.1943.
Catalysts 3a and 3c were synthesized following the same procedure.
(S)-2-(4-Methyl-4,5-dihydrooxazol-2-yl)aniline (3a): Synthesized
from (S)-2-aminopropan-1-ol and 2-aminobenzonitrile in 64%
yield as a colorless oil. [α]2D0 = +14.4 (c = 1.0, MeOH). H NMR
1
(300 MHz, CDCl3): δ = 1.33–1.35 (d, J = 6.3 Hz, 3 H, Me), 3.82–
3.88 (m, 1 H, NCH), 4.37–4.43 (m, 2 H, OCH2), 6.08 (br., 2 H,
NH2), 6.63–6.70 (m, 2 H, ArH), 7.17–7.22 (m, 1 H, ArH), 7.68–
7.71 (dd, J = 7.8, 1.2 Hz, 1 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 21.7, 62.1, 72.3, 109.2, 115.6, 116.0, 129.6, 131.9,
148.6, 163.5 ppm. HRMS: calcd. for C10H12N2O: 176.0950; found
176.0951.
(1R,2R)-N1,N1-Dibutyl-1,2-diphenylethane-1,2-diamine (11d): The
catalyst was synthesized according to the standard procedure in
45% overall yield. [α]2D0 = –45.6 (c = 0.5, EtOH). 1H NMR
(300 MHz, CDCl3): δ = 0.96–0.99 (t, J = 7.2 Hz, 6 H, Me), 1.30–
1.57 (m, 8 H, CH2), 2.03–2.13 (m, 4 H, CH2 and NH2), 2.61–2.68
(S)-2-(4-tert-Butyl-4,5-dihydrooxazol-2-yl)aniline (3c): Synthesized
form (S)-2-amino-3,3-dimethylbutan-1-ol and 2-aminobenzonitrile
in 67% yield as a white solid. [α]2D0 = +29.2 (c = 0.5, MeOH). H
1
NMR (300 MHz, CDCl3): δ = 0.94 (s, 9 H, tBu), 4.08–4.14 (m, 2 (m, 2 H, CH2), 3.78–3.82 (d, J = 10.8 Hz, 1 H, CH), 4.41–4.45 (d,
H, OCH2), 4.20–4.24 (m, 1 H, NCH), 6.14 (br., 2 H, NH2), 6.62– J = 10.8 Hz, 1 H, CH), 7.00–7.07 (m, 3 H, ArH), 7.09–7.16 (m, 5
6.71 (m, 2 H, ArH), 7.16–7.22 (m, 1 H, ArH), 7.65–7.68 (dd, J =
H, ArH), 7.21–7.26 (m, 2 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 14.3, 20.8, 31.1, 49.7, 55.8, 70.7, 126.7, 126.8, 127.4,
8.1, 1.5 Hz, 1 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 25.9,
Eur. J. Org. Chem. 2010, 6840–6849
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6845

S. Luo et al.
128.0, 129.7, 135.8, 143.6 ppm. HRMS: calcd. for C22H32N2 [M + 7.09–7.15 (m, 2 H, ArH), 7.21–7.24 (m, 2 H, ArH) ppm. 13C NMR
FULL PAPER
H] 325.2644; found 325.2651.
(75 MHz, CDCl3): δ = 55.2, 55.5, 110.3, 120.3, 127.6, 128.1, 132.1,
156.9 ppm. HRMS: calcd. for C16H20N2O2 272.1525; found
272.1521. The optical purity of the (1S, 2S)-1,2-bis(2-methoxyphenyl)
ethane-1,2-diamine was determined as Ͼ99% ee by HPLC with chiral
column after acetylation. 11j was synthesized according to the stan-
dard procedure in 57% overall yield. [α]2D0 = +73.2 (c = 0.5, MeOH).
1H NMR (300 MHz, CDCl3): δ = 0.93–0.98 (t, J = 7.2 Hz, 6 H, Me),
1.53–1.63 (m, 4 H, CH2), 2.04–2.10 (m, 2 H, CH2), 2.18 (br., 2 H,
NH2), 2.54–2.63 (m, 2 H, CH2), 3.67 (s, 3 H, OMe), 3.76 (s, 3 H,
OMe), 4.75 (s, 2 H, CH), 6.63–6.74 (m, 4 H, ArH), 6.70–7.02 (m, 2
H, ArH), 7.15–7.21 (dd, J = 4.2, 10.5 Hz, 2 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 12.1, 21.8, 52.0, 55.2, 55.3, 110.2, 119.2, 120.4,
126.3, 127.3, 127.5, 128.6, 129.6, 131.4, 157.2, 158.0 ppm. HRMS:
calcd. for C22H32N2O2 356.2464; found 356.2468.
(1R,2R)-N1,N1-Dihexyl-1,2-diphenylethane-1,2-diamine (11e): The
catalyst was synthesized according to the standard procedure in
72% overall yield. [α]2D0 = –39.6 (c = 0.5, MeOH). 1H NMR
(300 MHz, CDCl3): δ = 0.89–0.95 (t, J = 7.2 Hz, Me), 1.34 (m, 12
H, CH2), 1.54 (m, 4 H, CH2), 2.05–2.11 (m, 2 H, CH2), 2.21 (br.,
2 H, NH2), 2.62–2.69 (m, 2 H, CH2), 3.77–3.81 (d, J = 10.8 Hz, 1
H, CH), 4.40–4.44 (d, J = 10.8 Hz, 1 H, CH), 6.99–7.16 (m, 8 H,
ArH), 7.21–7.25 (m, 2 H, ArH) ppm. 13C NMR (75 MHz, CDCl3):
δ = 14.1, 22.7, 27.3, 28.8, 31.9, 50.1, 55.9, 70.9, 126.6, 126.7, 127.4,
127.9, 128.1, 129.7, 136.0, 143.7 ppm. HRMS: calcd. for C26H40N2
380.3191; found 380.3193.
(1R,2R)-1,2-Diphenyl-N1,N1-bis(3-phenylpropyl)ethane-1,2-diamine
(11f): The needle-like catalyst was synthesized according to the
standard procedure in 60% overall yield. [α]2D0 = +19.8 (c = 0.5,
EtOH). 1H NMR (300 MHz, CDCl3): δ = 1.84–1.92 (m, 4 H, CH2),
2.03 (br., 2 H, NH2), 2.14–2.22 (m, 2 H, CH2), 2.57–2.82 (m, 6 H,
CH2), 3.77–3.81 (d, J = 10.5 Hz, 1 H, CH), 4.37–4.40 (d, J =
10.5 Hz, 1 H, CH), 6.90–6.93 (m, 2 H, ArH), 7.03–7.13 (m, 6 H,
ArH), 7.18–7.33 (m, 12 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 30.6, 33.8, 49.6, 55.8, 71.0, 125.8, 126.7, 126.8, 127.5,
128.0, 128.4, 128.5, 129.7, 135.6, 142.4, 143.4 ppm. HRMS: calcd.
for C32H37N2 [M + H] 449.2957; found 449.2958.
2,2Ј-[(1S,2S)-1-Amino-2-(dipropylamino)ethane-1,2-diyl]diphenol
(11k): The catalyst was synthesized by treatment of 11j with BBr3 in
90 % yield. 1H NMR (300 MHz, CDCl3): δ = 0.90–0.96 (t, J =
7.2 Hz, 6 H, Me), 1.51–1.63 (m, 4 H, CH2), 2.24–2.32 (m, 2 H, CH2),
2.76–2.95 (m, 4 H, CH2 and NH2), 4.17–4.26 (m, 2 H, CH), 6.75–
6.95 (m, 6 H, ArH), 7.18–7.26 (m, 2 H, ArH), 13.40 (br., 2 H,
OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 11.9, 20.1, 54.5, 61.6,
70.4, 77.2, 118.3, 118.7, 119.4, 119.5, 121.3, 128.7, 129.6, 129.8, 133.2,
156.1, 157.6 ppm. HRMS: calcd. for C20H28N2O2 328.2151; found
328.2154.
(1R,2R)-1,2-Diphenyl-2-(piperidin-1-yl)ethanamine (11g): The cata-
lyst was synthesized according to the standard procedure in 90%
overall yield as a white solid. [α]2D0 = –29.2 (c = 0.5, EtOH). 1H
NMR (300 MHz, CDCl3): δ = 1.37–1.39 (m, 2 H, CH2), 1.54–1.58
(m, 2 H, CH2), 1.87–1.99 (m, 2 H, NH2), 2.13–2.16 (d, J = 7.8 Hz,
1 H, CH2), 2.39 (br., 1 H, CH2), 2.73–2.77 (d, J = 11.1 Hz, CH2),
3.17–3.20 (d, J = 7.8 Hz, 1 H, CH), 3.24–3.27 (m, 1 H, CH2), 4.12–
4.14 (d, J = 7.8 Hz, 1 H, CH), 7.19–7.29 (m, 10 H, PhH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 23.6, 25.3, 31.1, 49.0, 68.6, 78.2, 79.9,
126.7, 126.8, 127.4, 128.0, 128.3, 128.4, 140.3, 144.0 ppm. HRMS:
calcd. for C19H24N2 280.1939; found 280.1944.
(1S,2S)-1,2-Bis(4-chlorophenyl)-N1,N1-dipropylethane-1,2-diamine
(11l): (1S,2S)-1,2-Bis(4-chlorophenyl)ethane-1,2-diamine was synthe-
sized according to the published procedure.[18] [α]2D0 = +33.8 (c = 0.5,
1
MeOH). H NMR (300 MHz, D2O): δ = 3.22 (br., 4 H, NH2), 4.94
(s, 2 H, CH), 7.09 (d, J = 8.4 Hz, 4 H, ArH), 7.29 (d, J = 8.4 Hz, 4
H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 56.3, 129.3, 129.4,
129.6, 135.4. 11l was synthesized by the same method used to gener-
ate 11c in 60% overall yield. [α]2D0 = –15.6 (c = 0.5, EtOH). 1H NMR
(300 MHz, CDCl3): δ = 0.93–0.98 (t, J = 7.5 Hz, 6 H, Me), 1.51–
1.60 (m, 4 H, CH2), 2.02–2.08 (m, 2 H, CH2), 2.10 (br., 2 H, NH2),
2.50–2.60 (m, 2 H, CH2), 3.68–3.72 (d, J = 10.5 Hz, 1 H, CH), 4.36–
4.40 (d, J = 10.5 Hz, 1 H, CH), 6.91–6.94 (m, 2 H, ArH), 7.07–7.15
(m, 6 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.0, 21.7,
51.8, 55.3, 70.3, 127.8, 128.2, 129.4, 130.8, 132.5, 132.6, 134.1,
142.0 ppm. HRMS: calcd. for C20H27Cl2N2 [M + H] 365.1551; found
365.1556.
(1R,2R)-N1-Butyl-1,2-diphenylethane-1,2-diamine (11h): The nee-
dle-like catalyst was synthesized according to the standard pro-
cedure in 45% overall yield. [α]2D0 = +69.3 (c = 0.5, MeOH). 1H
NMR (300 MHz, CDCl3): δ = 0.81–0.85 (t, J = 7.2 Hz, Me), 1.21–
1.44 (m, 4 H, CH2), 1.73 (br., 3 H, NH2 and NH), 2.29–2.46 (m, 2
H, CH2), 3.69–3.72 (d, J = 7.2 Hz, 1 H, CH), 3.96–3.99 (d, J =
7.2 Hz, 1 H, CH), 7.11–7.25 (m, 10 H, PhH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.0, 20.4, 32.4, 47.5, 61.9, 69.9, 126.9,
127.0, 127.8, 128.0, 128.1, 141.7, 143.6 ppm. HRMS: calcd. for
C18H24N2 268.1939; found 268.1936.
(1S,2S)-1,2-Bis(3,4-dichlorophenyl)-N1,N1-dipropylethane-1,2-diamine
(11m): (1S,2S)-1,2-Bis(3,4-dichlorophenyl)ethane-1,2-diamine was
synthesized according to the published procedure.[18] 1H NMR
(300 MHz, CDCl3): δ = 1.52 (br., 4 H, NH2), 4.01 (s, 2 H, CH), 7.04–
7.08 (m, 2 H, ArH), 7.34–7.37 (d, J = 8.1 Hz, 2 H, ArH), 7.42 (d, J
= 2.1 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 60.9,
126.4, 128.9, 130.3, 131.3, 132.6, 143.3 ppm. The needle-like catalyst
11m was synthesized according to the standard procedure in 55%
overall yield. [α]2D0 = –28.4 (c = 0.5, EtOH). 1H NMR (300 MHz,
CDCl3): δ = 0.94–0.98 (t, J = 7.2 Hz, 6 H, Me), 1.53–1.60 (m, 4 H,
CH2), 2.03–2.08 (m, 2 H, CH2), 2.10 (br., 2 H, NH2), 2.49–2.56 (m,
2 H, CH2), 3.63–3.66 (d, J = 10.5 Hz, 1 H, CH), 4.34–4.38 (d, J =
10.5 Hz, 1 H, CH), 6.83–6.86 (dd, J = 8.1, 1.8 Hz, 2 H, ArH), 6.96–
6.70 (dd, J = 8.4, 2.1 Hz, 1 H, ArH), 7.10 (s, 1 H, ArH), 7.17–7.24
(m, 2 H, ArH), 7.40 (s, 1 H, ArH) ppm. 13C NMR (75 MHz, CDCl3):
δ = 12.0, 21.7, 51.78, 54.9, 69.9, 127.6, 128.7, 129.7, 129.9, 130.0,
130.9, 131.1, 131.2, 131.9, 132.3, 135.6, 143.6 ppm. HRMS: calcd.
for C20H24Cl4N2 [M + H] 433.0772; found 433.0767.
(1R,2R)-1,2-Bis(4-methoxyphenyl)-N1,N1-dipropylethane-1,2-diamine
(11i): The needle-like catalyst was synthesized according to the stan-
dard procedure in 49% overall yield. [α]2D0 = –14.4 (c = 0.5, MeOH).
1H NMR (300 MHz, CDCl3): δ = 0.93–0.99 (m, 6 H, Me), 1.54–1.59
(m, 4 H, CH2), 2.01–2.20 (m, 2 H, CH2), 2.28 (br., 2 H, NH2), 2.53–
2.58 (m, 2 H, CH2), 3.68–3.72 (m, 7 H, OMe and CH), 4.33–4.36 (d,
J = 10.6 Hz, 1 H, CH), 6.64–6.69 (m, 4 H, ArH), 6.91–6.94 (m, 2 H,
ArH), 7.11–7.14 (m, 2 H, ArH) ppm. 13C NMR (75 MHz, CDCl3):
δ = 12.0, 21.8, 51.9, 55.0, 55.1, 55.3, 70.3, 76.6, 112.8, 113.4, 128.3,
129.0, 130.6, 135.9, 158.1, 158.2 ppm. HRMS: calcd. for C22H32N2O2
356.2464; found 356.2469.
(1S,2S)-1,2-Bis(2-methoxyphenyl)-N1,N1-dipropylethane-1,2-diamine
(11j): (1S,2S)-1,2-Bis(2-methoxyphenyl)ethane-1,2-diamine was syn-
thesized according to the published procedure.[17] [α]2D0 = +79.0 (c =
0.5, MeOH). 1H NMR (300 MHz, CDCl3): δ = 1.95 (br., 4 H, NH2),
3.79 (s, 6 H, OMe), 4.46 (s, 2 H, CH), 6.75–6.85 (m, 4 H, ArH),
(1S,2S)-N1,N1-Dipropyl-1,2-bis[4-(trifluoromethyl)phenyl]ethane-1,2-di-
amine (11n): The catalyst was synthesized according to the standard
1
procedure in 61% overall yield. [α]2D0 = +17.4 (c = 0.5, EtOH). H
6846
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6840–6849

Asymmetric Epoxidation of α-Substituted Acroleins
NMR (300 MHz, CDCl3): δ = 0.95–1.00 (t, J = 7.5 Hz, 6 H, Me),
1.51–1.63 (m, 4 H, CH2), 2.03–2.12 (m, 2 H, CH2), 2.16 (br., 2 H,
NH2), 2.54–2.64 (m, 2 H, CH2), 3.81–3.85 (d, J = 10.5 Hz, 1 H, CH),
4.51–4.55 (d, J = 10.5 Hz, 1 H, CH), 7.10–7.13 (d, J = 7.8 Hz, 2 H,
ArH), 7.32–7.44 (m, 6 H, ArH) ppm. 13C NMR (75 MHz, CDCl3):
δ = 12.0, 21.7, 51.8, 55.4, 70.4, 124.5, 124.6, 125.0, 125.1, 128.4,
129.7 ppm. HRMS: calcd. for C22H27F6N2 [M + H] 433.2078; found
433.2071.
Other epoxidation products are new compounds.
(R)-[2-(4-Methylbenzyl)oxiran-2-yl]methanol (2b): Colorless oil. 78%
ee. [α]2D0 = +19.2 (c = 0.5, EtOH). 1H NMR (300 MHz, CDCl3): δ =
1.73 (br., 1 H, OH), 2.32 (s, 3 H, Me), 2.65–2.66 (d, J = 4.5 Hz, 1
H, PhCH2), 2.80–3.06 (m, 3 H, PhCH2 and CH2), 3.55–3.62 (m, 1
H, CH2), 3.70–3.76 (m, 1 H, CH2), 7.10–7.17 (m, 4 H, ArH) ppm.
13C NMR (75 MHz, CDCl3): δ = 21.2, 37.9, 49.6, 60.0, 62.8, 129.2,
129.4, 132.9, 136.4 ppm. HRMS: calcd. for C11H14O2 178.0994;
found 178.0996.
(1S,2S)-1,2-Bis[3,5-bis(trifluoromethyl)phenyl]-N1,N1-dipropylethane-
1,2-diamine (11o): The catalyst was synthesized according to the stan-
dard procedure as a white solid in 55% overall yield. [α]2D0 = +9.6 (c
(R)-[2-(4-Chlorobenzyl)oxiran-2-yl]methanol (2c): Colorless oil. 82%
1
ee. [α]2D0 = 13.4 (c = 0.5, EtOH). H NMR (300 MHz, CDCl3): δ =
1
= 0.5, EtOH). H NMR (300 MHz, CDCl3): δ = 0.90–0.94 (t, J =
1.65 (br., 1 H, OH), 2.66–2.67 (d, J = 4.9 Hz, 1 H, PhCH2), 2.85–
2.90 (m, 2 H, PhCH2 and CH2), 3.05–3.10 (m, 1 H, CH2), 3.58–3.62
(m, 1 H, CH2), 3.72–3.76 (m, 1 H, CH2), 7.21–7.33 (m, 4 H,
ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 38.3, 49.6, 59.9, 62.8,
126.8, 128.5, 129.6, 136.0 ppm. HRMS: calcd. for C10H11ClO2
198.0448; found 198.0447.
7.2 Hz, 6 H, Me), 1.47–1.57 (m, 4 H, CH2), 2.03–2.10 (m, 2 H, CH2),
2.15 (br., 2 H, NH2), 2.53–2.63 (m, 2 H, CH2), 3.73–3.76 (d, J =
10.2 Hz, 1 H, CH), 4.58–4.62 (d, J = 10.2 Hz, 1 H, CH), 7.32 (s, 2
H, ArH), 7.51 (s, 1 H, ArH), 7.58 (s, 3 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 11.9, 21.6, 51.8, 55.6, 71.2, 121.3, 124.9, 128.3,
129.2, 130.6, 130.7, 131.0, 131.2, 131.5, 131.6, 138.1, 145.6 ppm.
HRMS: calcd. for C24H25F12N2 [M + H] 569.1826; found 569.1819.
(R)-[2-(4-Methoxybenzyl)oxiran-2-yl]methanol (2d): Colorless oil.
76% ee. [α]2D0 = +8.4 (c = 0.5, EtOH). 1H NMR (300 MHz, CDCl3):
δ = 1.70–1.74 (m, 1 H, OH), 2.64–2.65 (d, J = 4.9 Hz, 1 H, PhCH2),
2.79–3.04 (m, 3 H, CH2 and PhCH2), 3.55–3.62 (m, 1 H, CH2), 3.70–
3.75 (m, 1 H, CH2), 3.79 (s, 3 H, OMe), 6.82–6.86 (m, 2 H, ArH),
7.12–7.14 (d, J = 11.2 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 37.4, 49.6, 55.2, 60.0, 62.8, 113.9, 128.0, 130.5,
158.5 ppm. HRMS: calcd. for C11H14O3 194.0943; found 194.0945.
Synthesis of Catalyst 12: The chiral primary-primary diamine was
synthesized according to the published procedure.[19] 1H NMR
(300 MHz, CDCl3): δ = 1.31 (br., 4 H, NH2), 2.66 (t, J = 1.5 Hz, 2
H, CH), 4.03 (s, 2 H, CH), 7.13–7.16 (m, 4 H, ArH), 7.28–7.33 (m,
4 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 53.6, 62.3, 124.1,
126.1, 126.3, 126.4, 138.9, 142.1 ppm. The optical purity of the pri-
mary-primary diamine was determined as 98.5% ee by HPLC with
a chiral column after acetylation. Catalyst 12 was synthesized follow-
ing the same method used for 11c in 73% overall yield from the
(R)-[2-(Naphthalen-1-ylmethyl)oxiran-2-yl]methanol (2e): Colorless
oil. 78% ee. [α]D20 = 14.6 (c = 0.5, EtOH). 1H NMR (300 MHz,
CDCl3): δ = 1.86–1.89 (t, J = 2.4 Hz, 1 H, OH), 2.53–2.55 (d, J =
4.8 Hz, 1 H, PhCH2), 2.85–2.87 (d, J = 4.8 Hz, 1 H, PhCH2), 3.36–
3.68 (m, 2 H, CH2), 3.71–3.81 (m, 2 H, PhCH2), 7.34–7.43 (m, 2 H,
ArH), 7.48–7.56 (m, 2 H, ArH), 7.78 (d, J = 5.4 Hz, 1 H, ArH), 7.85
primary-primary diamine. [α]2D0 = –83.2 (c = 0.5, MeOH). H NMR
1
(300 MHz, CDCl3): δ = 0.72–0.76 (t, J = 7.4 Hz, 6 H, Me), 1.27–
1.36 (m, 6 H, NH2 and CH2), 2.18–2.20 (m, 2 H, CH2), 2.29–2.33
(m, 2 H, CH2), 2.47–2.49 (m, 1 H, CH), 2.93–2.95 (m, 1 H, CH),
4.04 (d, J = 7.2 Hz, 1 H, CH), 4.37 (d, J = 5.1 Hz, 1 H, CH), 7.06–
7.11 (m, 4 H, ArH), 7.23–7.32 (m, 4 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 11.6, 21.4, 47.0, 53.3, 53.5, 54.8, 72.6, 123.2,
123.8, 125.4, 125.7, 125.8, 126.0, 126.2, 140.1, 141.1, 142.4,
144.0 ppm. HRMS: calcd. for C22H28N2 320.2252; found 320.2251.
(d, J = 5.4 Hz, 1 H, ArH), 8.08 (d, J = 5.7 Hz, 1 H, ArH) ppm. 13
NMR (75 MHz, CDCl3): δ = 34.5, 49.9, 59.9, 63.5, 124.0, 125.4,
125.7, 126.2, 127.7, 128.1, 128.8, 132.2, 132.6, 133.8 ppm. HRMS:
calcd. for C14H14O2 214.0994; found 214.0996.
C
(R)-[2-(2-Chlorobenzyl)oxiran-2-yl]methanol (2f): Colorless oil. 81%
ee. [α]2D0 = +43.2 (c = 0.5, EtOH). 1H NMR (300 MHz, CDCl3): δ =
1.97 (br., 1 H, OH), 2.57–2.58 (d, J = 4.3 Hz, 1 H, PhCH2), 2.86–
2.88 (d, J = 5.4 Hz, 1 H, PhCH2), 3.06–3.27 (m, 2 H, CH2), 3.63–
3.82 (m, 2 H, CH2), 7.16–7.37 (m, 4 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 34.9, 49.5, 59.4, 63.2, 126.8, 128.4, 129.5,
132.0, 133.8, 134.6 ppm. HRMS: calcd. for C10H11ClO2 198.0448;
found 198.0450.
Typical Experimental Procedure for 11c/5-SSA-Catalyzed Epoxid-
ation: Catalyst 11c (14.8 mg, 0.05 mmol), 5-sulfosalicycic acid di-
hydrate (12.7 mg, 0.05 mmol), and silica gel (20 mg) were mixed in
aqueous NaCl (2 m, 0.5 mL) and stirred for 15 min at 0 °C. 2-Benz-
ylacrylaldehyde[20] (73 mg, 0.5 mmol) and cumene hydroperoxide
(0.8 mmol) were added and the mixture was stirred at 0 °C for 6 h,
then at r.t. for 18 h. GC monitoring indicated that the conversion of
2-benzylacrylaldehyde was 96%. The mixture was diluted with
CH2Cl2/MeOH (20 mL, 4:1, v/v), and NaBH4 (57 mg, 1.5 mmol) was
added. The solution was stirred for 15 min, then aqueous NaHCO3
(3%, 20 mL) was added. After 15 min, the organic phase was sepa-
rated and the aqueous phase was extracted with CH2Cl2 (10 mL).
The organic layers were combined, dried with anhydrous Na2SO4
and concentrated. The residue was purified by careful flash column
chromatography to afford the desired product 2a as a colorless oil
(74 mg, 90% yield). [α]2D0 = +16.8 (c = 0.5, MeOH). 1H NMR
(300 MHz, CDCl3): δ = 1.86 (br., 1 H, OH), 2.65–2.67 (d, J = 4.2 Hz,
1 H, PhCH2), 2.84–2.89 (m, 2 H, PhCH2 and CH2), 3.05–3.10 (m, 1
H, CH2), 3.56–3.61 (m, 1 H, CH2), 3.71–3.75 (m, 1 H, CH2), 7.20–
7.33 (m, 5 H, PhH) ppm. 13C NMR (75 MHz, CDCl3): δ = 38.3,
49.6, 59.9, 62.9, 126.8, 128.5, 129.6, 136.1 ppm. HRMS: calcd. for
(R)-[2-(2-Methoxybenzyl)oxiran-2-yl]methanol (2g): Colorless oil.
88% ee. [α]2D0 = +35.8 (c = 0.5, EtOH). 1H NMR (300 MHz, CDCl3):
δ = 2.12–2.17 (m, 1 H, OH), 2.67–2.69 (d, J = 4.8 Hz, 1 H, PhCH2),
2.80–2.87 (m, 2 H, CH2 and PhCH2), 3.06–3.10 (d, J = 14.1 Hz, 1
H, CH2), 3.48–3.55 (m, 1 H, CH2), 3.64–3.70 (m, 1 H, CH2), 3.81
(m, 3 H, OMe), 6.83–6.91 (m, 2 H, ArH), 7.14–7.24 (m, 2 H,
ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 30.9, 49.0, 54.0, 58.6,
61.7, 109.0, 119.3, 123.1, 126.8, 130.1, 156.0 ppm. HRMS: calcd. for
C11H15O3 [M + H] 195.1021; found 195.1029.
(R)-[2-(3-Methoxybenzyl)oxiran-2-yl]methanol (2h): Colorless oil.
75% ee. [α]2D0 = +8.8 (c = 0.5, EtOH). 1H NMR (300 MHz, CDCl3):
δ = 1.99–2.03 (m, 1 H, OH), 2.68 (d, J = 4.5 Hz, 1 H, PhCH2), 2.87
(m, 2 H, CH2 and PhCH2), 3.04 (d, J = 14.4 Hz, 1 H, CH2), 3.55
C10H12O2 164.0837; found 164.0839. The enantioselectivity was de- (m, 1 H, CH2), 3.72 (m, 1 H, CH2), 3.82 (s, 3 H, OMe), 6.75–6.82
termined by HPLC with an AD-H chiral column (iPrOH/n-hexane,
3:97; 1.0 mL/min; 210 nm; 25 °C), tR = 17.7 min (minor), tR
(m, 3 H, ArH), 7.11–7.22 (m, 1 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 38.3, 49.8, 55.2, 60.0, 62.7, 112.1, 115.4, 121.9, 129.5,
=
19.3 min (major), 79% ee. The absolute configuration was deter- 137.6, 159.6 ppm. HRMS: calcd. for C11H14O3 194.0943; found
mined as R by comparison with the known compound.[13]
194.0941.
Eur. J. Org. Chem. 2010, 6840–6849
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6847

S. Luo et al.
FULL PAPER
(R)-[2-(2,4-Dichlorobenzyl)oxiran-2-yl]methanol (2i): Colorless oil.
78% ee. [α]2D0 = +11.0 (c = 0.5, EtOH). 1H NMR (300 MHz, CDCl3):
δ = 1.83 (br., 1 H, OH), 2.52–2.54 (d, J = 4.5 Hz, 1 H, PhCH2), 2.86–
2.87 (d, J = 4.5 Hz, 1 H, PhCH2), 3.66–3.22 (m, 2 H, CH2), 3.63–
3.80 (m, 2 H, CH2), 7.17–7.24 (m, 2 H, ArH), 7.38–7.39 (d, J =
1.5 Hz, 1 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 34.2, 49.4,
59.1, 63.3, 127.1, 129.2, 132.3, 132.8, 133.5, 135.3 ppm. HRMS:
calcd. for C10H10Cl2O2 232.0058; found 232.0053.
Supporting Information (see also the footnote on the first page of this
article): NMR spectra for the catalysts and epoxide products, and
HPLC traces for the epoxide products.
Acknowledgments
This project was supported by the National Natural Science Founda-
tion of China (NSFC) (20702052 and 20972163), the Chinese Minis-
try of Science and Technology (2009ZX09501-018), and the Chinese
Academy of Sciences.
(R)-[2-(2,4-Dimethoxybenzyl)oxiran-2-yl]methanol (2j): Colorless oil.
88% ee. [α]2D0 = +36.6 (c = 0.5, EtOH). 1H NMR (300 MHz, CDCl3):
δ = 2.12–2.18 (m, 1 H, OH), 2.66–2.69 (d, J = 7.8 Hz, 1 H, PhCH2),
2.78–2.83 (m, 2 H, CH2 and PhCH2), 3.01–3.05 (m, 1 H, CH2), 3.51–
3.58 (m, 1 H, CH2), 3.66–3.72 (m, 1 H, CH2), 3.80 (s, 3 H, OMe),
3.81 (s, 3 H, OMe), 6.43–6.46 (m, 2 H, ArH), 7.06–7.08 (d, J =
8.0 Hz, 1 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 31.6, 50.3,
55.3, 60.2, 63.1, 98.5, 104.3, 116.8, 131.8, 158.3, 159.9 ppm. HRMS:
calcd. for C12H16O4 224.1049; found 224.1050.
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(R)-[2-(Benzyloxymethyl)oxiran-2-yl]methanol (2k): Colorless oil.
1
32% ee. H NMR (300 MHz, CDCl3): δ = 2.09–2.13 (t, J = 2.4 Hz,
1 H, OH), 2.75–2.77 (d, J = 4.8 Hz, 1 H, PhCH2), 2.88–2.90 (d, J =
4.8 Hz, 1 H, PhCH2), 3.60–3.67 (m, 2 H, CH2), 3.70–3.92 (m, 2 H,
CH2), 4.51–4.61 (m, 2 H, CH2), 7.27–7.38 (m, 5 H, PhH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 48.8, 58.6, 62.2, 70.8, 73.5, 127.8, 127.9,
128.5, 137.6 ppm. HRMS: calcd. for C14H14O2Na [M + Na]
237.0891; found 237.0901.
(R)-[2-(3-Phenylpropyl)oxiran-2-yl]methanol (2l): Colorless oil. 75%
ee. [α]2D0 = +15.0 (c = 0.5, EtOH). 1H NMR (300 MHz, CDCl3): δ =
1.56–1.83 (m, 5 H, OH and CH2), 2.60–2.67 (m, 3 H, CH2 and
PhCH2), 2.87 (d, J = 4.5 Hz, 1 H, PhCH2), 3.59–3.66 (m, 1 H, CH2),
3.74–3.80 (m, 1 H, CH2), 7.15–7.18 (m, 3 H, ArH), 7.26–7.31 (m, 2
H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 26.4, 31.4, 35.9,
49.7, 59.6, 62.8, 126.0, 128.3, 128.4, 141.8 ppm. HRMS: calcd. for
C12H16O2 192.1150; found 192.1149.
(R,E)-Ethyl 3-(2-Benzyloxiran-2-yl)acrylate (17): A reaction mixture
of the model reaction (0.5 mmol scale) was poured into H2O (5 mL)
and extracted with CH2Cl2 (3ϫ5 mL). After drying with Na2SO4,
the solvent was concentrated to about 5 mL and freshly prepared
Wittig reagent Ph3P=CH2CO2Et (1 mmol) was added. After 4 h, the
mixture was concentrated and purified by flash chromatography on
silica gel to afford the desired product 17 as a colorless oil (86 mg,
74% yield). The enantioselectivity was determined to be 76% ee by
HPLC. [α]D20 = –25.4 (c = 0.5, EtOH). 1H NMR (300 MHz, CDCl3):
δ = 1.13–1.19 (m, 3 H, Me), 2.72–2.88 (m, 2 H, PhCH2), 3.37 (s, 2
H, CH2), 4.20 (m, 2 H, OCH2), 6.28 (d, J = 15 Hz, 1 H, CH), 6.90
(d, J = 15 Hz, 1 H, CH), 7.18–7.38 (m, 5 H, PhH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.2, 39.3, 55.0, 57.6, 60.6, 122.4, 126.9, 128.5,
129.6, 135.5, 146.4, 166.0 ppm. HRMS: calcd. for C14H16O3
232.1099; found 232.1097.
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(R)-2-Methyl-3-phenylpropane-1,2-diol (18): A mixture of epoxide
alcohol 2a (0.5 mmol, 76% ee) and LiAlH4 (1 mmol) in THF
(10 mL) was heated to reflux for 2 h. After cooling to r.t., the reaction
was quenched with sat. aqueous Na2SO4. The solid was filtered and
washed with Et2O (3ϫ). The filtrates were concentrated and purified
by flash column chromatography to afford product 18 as a white
solid (67 mg, 85% yield based on epoxide aldehyde). [α]2D0 = +6.4 (c
= 1.0, MeOH). 1H NMR (300 MHz, CDCl3): δ = 1.14 (s, 3 H, Me),
1.95 (s, 1 H, OH), 2.07 (d, J = 6.0 Hz, 1 H, OH), 2.75–2.88 (q, J =
13.2 Hz, 2 H, PhCH2), 3.39–3.50 (m, 2 H, CH2), 7.21–7.30 (m, 5 H,
PhH) ppm. 13C NMR (75 MHz, CDCl3): δ = 23.5, 44.7, 69.2, 73.0,
126.6, 128.3, 130.5, 137.0 ppm. HRMS: calcd. for C10H14O2
166.0994; found 166.0997.
6848
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Eur. J. Org. Chem. 2010, 6840–6849

Asymmetric Epoxidation of α-Substituted Acroleins
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Received: August 9, 2010
Published Online: October 27, 2010
Eur. J. Org. Chem. 2010, 6840–6849
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6849