Enantioselective iminium-catalyzed epoxidation of hindered trisubstituted allylic alcohols

Article abstract of DOI:10.1016/j.tetasy.2010.06.002

The reactivity of diastereomeric biaryl iminium cations made of a (Ra)-5,5′,6,6′,7,7′,8,8′-octahydrobinaphthyl core and exocyclic appendages derived from (S)- or (R)-3,3-dimethylbutyl-2-amine was investigated with hindered trisubstituted allylic alcohols

Full text of DOI:10.1016/j.tetasy.2010.06.002

Tetrahedron: Asymmetry 21 (2010) 1611–1618
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective iminium-catalyzed epoxidation of hindered trisubstituted
allylic alcohols
*
Roman Novikov, Jérôme Lacour
Département de Chimie Organique, Université de Genève, quai Ernest Ansermet 30, CH-1211 Genève-4, Switzerland
a r t i c l e i n f o
a b s t r a c t
The reactivity of diastereomeric biaryl iminium cations made of a (Ra)-5,50,6,60,7,70,8,80-octahydrobinaph-
thyl core and exocyclic appendages derived from (S)- or (R)-3,3-dimethylbutyl-2-amine was investigated
with hindered trisubstituted allylic alcohols—a class of alkenes which had not been previously studied in
detail in epoxidation reactions with cyclic iminium catalysts (ee up to 98%). Surprisingly, generally strong
matched/mismatched effects are observed not only in terms of reactivity but also on the enantioselectiv-
Article history:
Received 10 March 2010
Revised 26 May 2010
Accepted 3 June 2010
Available online 3 July 2010
ity of the reaction (Dee up to 16%). Also, for the most hindered substrates, two sets of reaction conditions
Dedicated to Professor Henri Kagan on the
occasion of his 80th birthday
were tested in a preliminary study and little advantage was found in running reactions in MeCN/water
instead of CH2Cl2/water/18-C-6. In any case, the presence of the hydroxyl group did not reveal any anchi-
meric effect.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
Recently, several successful enantioselective variants of the imin-
ium-catalyzed epoxidation of alkenes have been reported,14–17 and
Non-racemic epoxides are useful precursors and building blocks
in synthetic organic chemistry. Quite a few effective systems have
been developed for their preparation,1 and catalytic asymmetric
epoxidation of olefins has proven to be one of the most powerful ap-
proaches. Most strategies are based on transition metal catalysis
such as the Katsuki–Sharpless epoxidation of allylic alcohols with
chiral titanium catalysts,2 vanadium-catalyzed epoxidation of
allylic3 and homoallylic alcohols4 mainly developed by Yamamoto,
and the Katsuki–Jacobsen protocol with Mn(salen) catalysts for
unfunctionalized olefins.5 During the last decade, much effort has
been devoted to the development of organocatalytic processes that
afford metal-free procedures,6,7 such as asymmetric epoxidation
catalyzed by chiral ketones,7,8 iminium salts,9 peptides,10 and
phase-transfer catalysts.11
many of them are based on configurationally stable biarylazepinium
skeletons.18–20 In this family, it was recently shown that axially chiral
5,50,6,60,7,70,8,80-octahydrobinaphthyl-derived iminium salts 1a
and 1b (Fig. 1), prepared from enantiopure (R)-BINOL and (R)-/(S)-
3,3-dimethylbutyl-2-amine, are probably the most selective
catalysts of this type for enantioselective epoxidations of simple
prochiral olefins.21 These epimeric molecules provide non-racemic
epoxides with the same absolute configuration and often with virtu-
ally the same enantiomeric purity (up to 98% ee) despite their diaste-
reomeric relationship. This unusual behavior was explained by the
existence of stereospecific atropisomers around the N(sp2)–C(sp3)
bond that links the azepinium core to the chiral appendage of 1a
In this field, oxaziridinium ions are effective oxygen transfer re-
agents toward nucleophilic substrates12 and electron-rich unfunc-
tionalized olefins in particular. Moreover, the propensity of
iminium ions to react with OxoneÒ to generate the oxaziridinium
species renders the development of catalytic processes possible
(Eq. 1).13
t-Bu
H
Me
N
N
t-Bu
Me
SbF6
H
SbF6
(Ra,R)-[1a][SbF6]
(Ra,S)-[1b][SbF6]
R1
H
O
iminium catalyst
R1
R2
H
R3
NaHCO3, Oxone®
CH3CN / water 3:2 or
ð1Þ
R2
R3
S1
CH2Cl2 / Water 3:2 / 18-C-6 (2.5 mol%)
Figure 1. Diastereomeric 5,50,6,60,7,70,8,80-octahydrobinaphthyl-derived iminium
catalysts 1 and hindered unfunctionalized olefin S1. The most selective (Ra,R)-1a
and most reactive (Ra,S)-1b derived from (R)- and (S)-3,3-dimethylbutyl-2-amine
respectively. Compounds 1a and 1b have predominantly anti- and syn-periplanar
conformations
* Corresponding author. Fax: +41 22 379 3215.
E-mail address: jerome.lacour@unige.ch (J. Lacour).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.06.002

1612
R. Novikov, J. Lacour / Tetrahedron: Asymmetry 21 (2010) 1611–1618
and 1b.22 It ensures that the same prochiral Re face of the iminium
ions 1a and 1b is accessible to OxoneÒ and to the olefin irrelevant
of the configuration of the chiral side chain.
structurally similar to that of S2, were prepared. They contain an
alkylated hydroxyl group in the form of a methoxy residue and
two electron-donating methyl groups in para-position of phenyl
rings, respectively. As expected, both modifications favored the
reaction. The increased lipophilicity and nucleophilicity of the dou-
ble bond in these two substrates accelerated the rate of the epox-
idation process. A shorter reaction time was possible with S3. With
S4, less catalyst [1a][SbF6] (10 mol % for S4 vs 20 mol % for S2,
respectively) was required to get full conversion in also reduced
amount of time (Table 1, entries 1 and 3). For this latter example,
the reaction was clean as judged by GC–MS and 1H NMR of crude
reaction mixture, but unfortunately we were not able to isolate
the epoxide in analytically pure form due to its very acid-sensitive
nature. Despite this fact, the enantioselectivity of the ‘crude’ prod-
uct was determined to be 88% ee. It shows, in comparison with the
reaction of S2, that the asymmetric induction is essentially insen-
sitive to electronic effects. A similar enantiomeric purity was
obtained for the reaction with S3 (87% ee). Then, a range of com-
pounds containing different alkyl groups (S5–S11) was studied
(see Fig. 2) to test the steric influence of the group R on both
enantioselectivity and reactivity.
However, if little differences were seen on the selectivity of the
reaction with 1a and 1b, large matched/mismatched effects were
observed in terms of reactivity. In fact, salts [1a][SbF6] and
[1b][SbF6] catalyzed the reaction with rather different rates. With
hindered substrates such as olefin S1 (Fig. 1), diminished conver-
sions and yields were obtained with the more selective salt
[1a][SbF6]. This forced us to use higher amounts of catalyst (up
to 20 mol %) and longer reaction times (up to 4 days) to drive the
reaction to completion. The only reported solution to this reactivity
problem was the use of the more reactive salt [1b][SbF6] that led,
with S1, to a moderately lower enantioselectivity value (ee 93%
with 1b instead of 98% with 1a).
We wondered about the generality of this observation and
decided to study the reactivity of a similar yet different class of ole-
fin—that of allylic alcohols which had not been previously studied
in details in epoxidation reactions with cyclic iminium catalysts.
Herein we report that surprisingly,19 generally strong matched/
mismatched effects are observed with the diastereomeric catalysts
not only in terms of reactivity but also on the enantioselectivity of
the reaction (Dee up to 16%). We wondered if the selected reaction
CH2OH
S5 to S11
conditions were having an influence with these polar substrates.
We decided to briefly check, for the most hindered substrates, if
the more traditional CH3CN/water conditions would not be better
than our strictly biphasic CH2Cl2/water conditions. However, preli-
minary data indicate that little difference can be observed for the
two solvent systems.
Ar
R
Alkyl group (Me to cyclohexyl)
Figure 2. Hindered trisubstituted allylic alcohols.
Unexpected and disappointing results were obtained with allylic
alcohol S5 containing a methyl group as substituent R (Table 1, entry
4). In this particular case, the reaction was very capricious. If only
10 mol % of [1a][SbF6] was needed to obtain full conversion of the
substrate, it was not possible to isolate the desired epoxide detected
in the 1H NMR spectrum of the crude mixture and no measure of the
enantiomeric excess of the epoxide could be made.
2. Results and discussion
2.1. Enantioselective epoxidation of hindered trisubstituted
allylic alcohols using [1a][SbF6] iminium salt as catalyst
Diastereomeric iminium salts (Ra,R)-1a and (Ra,S)-1b are effec-
tive asymmetric epoxidation catalysts with lipophilic hindered
alkenes that present (i) little differences in terms of the enantiose-
lectivity but (ii) large matched/mismatched effects in terms of
reactivity.21 We wondered about the generality of this observation
and decided to investigate the reactivity of these catalysts with an-
other class of olefins.
Moving to more hindered substrates S6 (R = Et) and S7 (R = i-Bu),
better results were obtained. Full and clean conversions of starting
materials to their corresponding epoxides were observed. The prod-
ucts were isolated in pure form in good yields and enantioselectivi-
ties. A higher asymmetric induction in the case of S7 compared to S6
(90% ee vs 87% ee) was noticed whichwas explained by a larger steric
influence of the isobutyl group relative to the ethyl. In this spirit,
moving to bulkier substrates S8 (R = i-Pr) and S10 (R = cyclohexyl),
the enantioselectivity values were higher (95% and 98% ee, respec-
tively, entries 7 and 9). Clearly the trend is conserved; the bulkier
the alkyl group R, the better the enantioselectivity.
Globally, the reactions were clean. No post-decomposition or
racemization of the products was observed under the reaction con-
ditions. For example, increasing the reaction time in the epoxida-
tion reaction of S6 from 24 h to 48 h (full conversion is obtained
in 24 h) did not yield any variation in the enantiomeric excess of
the desired epoxide which was isolated in similar yield. However,
whereas enantioselectivity levels increased moving from non-hin-
dered substrates to bulky compounds, reactivity significantly
dropped. Only 80% conversion of S8 was obtained under CH2Cl2/
water reaction conditions in 24 h. Increasing the reaction time
from 24 h to 48 h or longer did not have any effect; the conversion
remaining the same.
A range of hindered trisubstituted allylic alcohols S2–S11 was
synthesized usually by Horner–Wadsworth–Emmons olefination
of ketones and subsequent reduction with DIBAL-H, and studied
in the asymmetric epoxidation reaction (Eq. 1). For all substrates,
the reaction was studied under biphasic CH2Cl2/water. In fact, for
iminium-catalyzed epoxidation reactions, we have previously
introduced the use of strict biphasic CH2Cl2/water/18-C-6 condi-
tions. With catalytic iminium salts associated with a lipophilic
TRISPHAT counterion,23,24 an enhancement of the selectivity was
observed using these conditions in which the oxidation occurs in
the organic CH2Cl2 phase only.15 A similar observation was re-
ported by Page et al. who developed strict anhydrous conditions
using pure CH2Cl2 as a solvent and tetraphenylphosphonium
monoperoxybisulfate (TPPP) as a stoichiometric oxidant.16,20,25
First, 3,3-diphenylprop-2-en-1-ol S2 was successfully trans-
formed into the corresponding epoxide in good yield and enanti-
oselectivity using [1a][SbF6] salt as the catalyst (Table 1, entry 1).
However, the reaction was quite slow and required 20 mol % of
iminium salt. This lack of reactivity was somewhat surprising
and two possible factors were considered to explain this result:
(i) an unfavorable partition of the allylic alcohol in the biphasic
CH2Cl2/water mixture and (ii) an effect of the electron-withdraw-
ing hydroxyl group that renders the double bound less nucleo-
philic. To test these hypotheses, compounds S3 and S4,
2.2. Enantioselective epoxidation of hindered trisubstituted
allylic alcohols using [1b][SbF6] iminium salt as catalyst
This lack of reactivity was disappointing. We felt that the more
reactive catalyst [1b][SbF6] should be tried with the more trouble-
some substrates—if only to tabulate the reactivity of 1b with 1a.

R. Novikov, J. Lacour / Tetrahedron: Asymmetry 21 (2010) 1611–1618
1613
Table 1
Asymmetric epoxidation of various allylic alcohols mediated by catalyst [1a][SbF6] (most selective catalyst) in CH2Cl2/H2O conditions
Entry
Substrate
Solvent
Catalyst (mol %)
Time (h)
Yielda (conv.b %)
eec (%)
88
Config.
Ph
OH
d
1
S2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
20
48
80 (>97)
(ꢀ)-(S)e
Ph
Ph
OMe
d
d
2
3
S3
20
10
10
20
20
20
20
20
20
24
24
24
24
24
24
24
24
24
76 (93)
(>99)
87
(ꢀ)
—
Ph
p-MeC6H4
OH
S4
88
p-MeC6H4
Me
OH
OH
OH
OH
d
d
d
d
4
S5
(>99)
n.d.
87
—
Ph
Et
5
S6
84 (>99)
69 (>99)
65 (80)
63 (85)
65 (75)
37 (75)
(+)
(+)
(+)
(+)
Ph
i-Bu
6
S7
90
Ph
i-Pr
7
S8
95
Ph
OH
i-Pr
d
d
d
8
S9
95
p-MeC6H4
Cy
OH
9
S10
S11
98 (>99f)
95
(+)-(2S,3S)e
Ph
Cy
OH
10
(+)
p-BrC6H4
a
b
c
d
e
f
Isolated yields of pure epoxides.
Determined by GC–MS or 1H NMR analysis of the crude reaction mixture.
Determined by CSP-HPLC (see the Experimental).
Conditions: substrate (0.2 mmol), catalyst (x mol %), 2.5 mol % of 18-C-6, 1.1 equiv OxoneÒ, 4.0 equiv NaHCO3, CH2Cl2/H2O (3:2), 0 °C.
The absolute configuration of the major enantiomers was determined by comparison of the optical rotation with that reported in the literature.
After single recrystallization from n-hexane/i-PrOH.
The results are presented in Table 2. They are in line with our
expectations. Quite lower amounts of catalyst are necessary
(5–10 with 1b vs 20–30 mol % with 1a) to reach full conversions.26
However, in terms of selectivity, initial tests with challenging sub-
strate S10 (Table 2, entry 1 and Table 1, entry 9) indicated a very
strong matched/mismatched behavior between diastereomeric
catalyst [1b][SbF6] and [1a][SbF6]. Much lower enantiomeric ex-
cess values were obtained with the more reactive catalyst 1b (ee
85% in CH2Cl2). The drop in enantiomeric excess (ꢀ13%) compared
to that of 1a is consequent. It can be perceived even more by con-
sidering enantiomeric ratios instead of enantiomeric excesses. The
reaction of S10 with [1b][SbF6] in CH2Cl2 yields the scalemic epox-
ide in 13:1 ratio, whereas under the same conditions [1a][SbF6] af-
fords the product in 104:1 ratio.27 It is the first time that such a
difference of selectivity is observed with diastereomeric biaryl
azepinium catalysts.
The trend was confirmed in all other experiments. Alkenes S7,
S8, S9, and S11 also yielded the corresponding epoxides with major
losses of enantiomeric purity (ꢀ10%, –10%, –12%, and even –16% ee,
respectively). The reason(s) for these general losses in enantio-
meric purity is (are) still under evaluation.
Yet, despite this major shortcoming, catalyst [1b][SbF6] has the
advantage of providing reproducible results that can be readily
scaled-up. The selectivity issue can be offset if an effective enant-
ioenrichment protocol can be coupled to the oxidation. For
instance, the epoxidation reaction of S10 can be readily performed
with 1.0 g of substrate (4.63 mmol) and the desired epoxide was
isolated with the same enantiomeric purity (86% ee) and slightly
better yield (87%) than in the test reaction.28 After a single recrys-
tallization from n-hexane/i-PrOH (25:1), the product was obtained
in enantiopure form (>99% ee) (Scheme 1).
2.3. Acetonitrile/water versus dichloromethane/water
conditions. Preliminary results
Traditionally, epoxidation reactions with iminium catalysts are
not performed in CH2Cl2 but instead in mixtures of CH3CN and
water.29 Both lipophilic alkenes and polar BF4 or PF6 iminium
salts display usually a good solubility in CH3CN. In some instances,
the epoxidation reactions can proceed faster in the acetonitrile/
water system than in the dichloromethane/water mixture.30 We
thus wondered if acetonitrile/water conditions might not be an an-
swer to our reactivity problem with salt [1a][SbF6] and hindered
alcohols S7–S11. We reasoned that the higher polarity of the ace-
tonitrile/water mixture could help the solubilization and reactivity
of these polar substrates. Results are reported in Table 3 (entries
1–5) and can be compared with that in CH2Cl2 (Table 1).
ꢀ
ꢀ
First, the absolute configuration of the resulting epoxides re-
mains the same under the two sets of reaction conditions. The
enantioselectivity values are virtually identical (ee 1% in CH2Cl2
and CH3CN). This result is interesting as stronger differences could
have been expected.30 It should be noted that the acetonitrile/
water (3:2) system is not monophasic but triphasic. Two liquid
layers and one inorganic precipitate can be seen from the start to

1614
R. Novikov, J. Lacour / Tetrahedron: Asymmetry 21 (2010) 1611–1618
Table 2
Asymmetric epoxidation of a selection of allylic alcohols mediated by catalyst [1b][SbF6] (most reactive catalyst) in CH2Cl2/H2O conditionsa
Entry
1
Substrate
Solvent
Catalyst (mol %)
Time (h)
Yieldb (conv.c %)
eed (%)
eed (%) with [1a][SbF6]
OH
Cy
e
S10
S7
CH2Cl2
10
24
81 (>99)
85 (96f)
98 (>99f)
Ph
OH
i-Bu
e
2
3
4
CH2Cl2
10
10
5
24
24
24
61 (>99)
86 (>99)
86 (>99)
80
85
88
90
95
95
Ph
OH
i-Pr
e
S8
CH2Cl2
Ph
OH
i-Pr
e
S9
CH2Cl2
p-MeC6H4
Cy
OH
e
5
S11
CH2Cl2
10
24
82 (>99)
79
95
p-BrC6H4
a
b
c
d
e
f
All epoxide products from the reaction of S7–S11 are dextrorotatory irrespective of the use of catalyst [1b][SbF6] or [1a][SbF6].
Isolated yields of pure epoxides.
Determined by GC–MS analysis of crude reaction mixture.
Determined by CSP-HPLC (see the Experimental).
Conditions: substrate (0.2 mmol), catalyst (x mol %), 2.5 mol % of 18-C-6, 1.1 equiv OxoneÒ, 4.0 equiv NaHCO3, CH2Cl2/H2O (3:2), 0 °C.
After single recrystallization from n-hexane/i-PrOH.
allowing yet to increase the catalyst loading due to the better sol-
ubility of [1a][SbF6] in CH3CN.31 Nevertheless, these MeCN/water
conditions are clearly not a general answer to the reactivity prob-
lem spotted with these substrates.
Finally, in the MeCN/water medium, substrate S10 was treated
with catalyst [1b][SbF6]. Again, as for reactions in CH2Cl2/water, a
very strong matched/mismatched behavior between diastereo-
meric catalysts. A much lower enantiomeric excess value was ob-
tained with the more reactive 1b (ee 84% in CH3CN, see the
Experimental). The drop is again important in enantiomeric excess
(ꢀ12%) or in enantiomeric ratios (11:1 vs 71:1) with [1b][SbF6] in-
stead of [1a][SbF6].
OH
Ph
(E)
1.0 g
(Ra,S)-[1b][SbF6] (5 mol%)
Oxone, NaHCO3
18-C-6 (2.5 mol%)
CH2Cl2 / water 3 / 2
24h, 0 °C
OH
O
Ph
2.4. Absolute sense of stereoinduction
(+)-(2S,3S)
We have recently proposed that any trisubstituted alkene of
type 2 with the substitution pattern displayed in Figure 3 should
lead to high enantiomeric excesses in an enantioselective epoxida-
tion reaction catalyzed by salt [1a][SbF6]. Clearly, this proposition
is a working model with allylic alcohols S2–S11. All epoxide prod-
ucts displayed rather high level of enantiomeric purity in reactions
performed in CH2Cl2/water or in CH3CN/water conditions.
It was also shown that the major enantiomer comes usually
from the addition of the O-atom on the top face of the alkene in
the geometrical disposition provided in Figure 3. With the novel
alcohols, this could be verified only in the case of S10 which is
the only novel substrate for which the absolute configuration of
the epoxide is known. In this case, the (+)-(2S,3S)-trans-3-cyclo-
hexyl-3-phenyloxiranemethanol was obtained and this product
comes indeed from a Re face oxidation of the alkene. Most proba-
bly, the same approach takes place for the others substrates.
86% ee, 87% yield (0.93 g)
single recrystallization from
n-hexane / i-PrOH (25:1, 60 mL)
>99% ee, 56% yield (0.60 g)
Scheme 1. Enantioselective epoxidation of S10 performed on 1.0 g of substrate.
the end of the reaction. It is then not clear in which liquid phase(s)
the epoxidation reaction actually proceeds. Possibly, the epoxida-
tion process takes place at an interface but this is short of an expla-
nation to account for the minimal difference in selectivity between
the two solvent systems. It should also be mentioned that 18-C-6,
which is absolutely necessary for the phase transfer of KHSO5 in
the biphasic CH2Cl2/water conditions,15,17 is not required anymore
in the ternary MeCN/water system.
3. Conclusion
Specifically, for S9, the reaction proceeded faster but 20 mol % of
catalyst was still needed (entry 3). For substrates S8, S10, and S11,
full conversion to their corresponding epoxides was now achieved.
Nevertheless, with these substrates, no measurable increase in
reactivity was seen in the polar CH3CN/water conditions. It was
actually necessary to use a higher amount of catalyst (25–30
mol %) to reach full conversion—the CH3CN/water combination
The reactivity of diastereomeric biaryl iminium cations made of
a (Ra)-5,50,6,60,7,70,8,80-octahydrobinaphthyl core and exocyclic
appendages derived from (S)- or (R)-3,3-dimethylbutyl-2-amine
was investigated with hindered trisubstituted allylic alcohols—a
class of alkenes which had not been previously studied in detail
in epoxidation reactions with such cyclic iminium catalysts.
Surprisingly strong matched/mismatched effects are observed not

R. Novikov, J. Lacour / Tetrahedron: Asymmetry 21 (2010) 1611–1618
1615
Table 3
Asymmetric epoxidation of various allylic alcohols mediated by catalyst [1a][SbF6] (most selective catalyst) in MeCN/H2O conditions
b
Entry
Substrate
Solvent
Catalyst (mol %)
Time (h)
Yielda (conv. %)
eec (%)
91
Config.d
(+)
OH
OH
i-Bu
1
S7
MeCNe
20
24
73 (>99)
79 (98)
84 (>99)
80 (>99)
77 (98)
Ph
i-Pr
2
3
4
5
S8
MeCNe
MeCNe
MeCNe
MeCNe
25
20
30
30
24
24
24
24
95
(+)
(+)
Ph
OH
i-Pr
S9
95
p-MeC6H4
Cy
OH
S10
S11
96 (>99f)
94
(+)-(2S,3S)
Ph
Cy
OH
(+)
p-BrC6H4
a
b
c
d
e
f
Isolated yields of pure epoxides.
Determined by GC–MS or 1H NMR analysis of the crude reaction mixture.
Determined by CSP-HPLC (see the Experimental).
The absolute configuration of the major enantiomers was determined by comparison of the optical rotation with that reported in the literature.
Conditions: substrate (0.2 mmol), catalyst (x mol %), 1.1 equiv OxoneÒ, 4.0 equiv NaHCO3, MeCN/H2O (3:2), 0 °C.
After single recrystallization from n-hexane/i-PrOH (25:1).
experiments. IR spectra were recorded using a diamond ATR Gold-
en Gate sampling. Melting points (mp) were measured in open
capillary tubes and were uncorrected. MS-EI spectra were obtained
with ionizing voltage 70 eV and 40 eV; m/z (intensity in%) by the
Department of Mass Spectroscopy of the University of Geneva.
Optical rotations were measured in a thermostated 10.0 cm long
microcell with high pressure lamp of sodium and are reported as
Small alkyl group
clean
top
R'
β
approach
Ar
Any alkyl or aryl group
R
α
2
eg
follows: ½a tD
ꢁ
(c (g/1000 mL), solvent). HPLC analyses were per-
Re
Ph
(S)
OH
formed using Chiralcel OD-H, OJ and OJ-H (0.46 ꢂ 25 cm) columns.
Chiral stationary phase (CSP) chromatography was performed
using a Hydrodex-b column (25 m ꢂ 0.25 mm, H2, 40 Psi). GC–MS
analysis was performed using a HP-5MS column (30 m ꢂ 0.25 mm,
He 1.0 mL/min).
OH
O
Ph
(S)
ee 98%
Re
S10
(+)-(2S,3S)
Figure 3. Proposed model type of alkenes giving epoxides with high enantiomeric
excesses. Facial selectivity of the epoxide formation (Re face in case of allylic
alcohols).
4.1. Typical enantioselective epoxidation procedure under
CH2Cl2/water (3:2) conditions
only on the reactivity but also on the enantioselectivity of the reac-
tion (Dee up to 16%). For the most hindered substrates, two sets of
conditions (CH2Cl2/water/18-C-6 or MeCN/water) were tested but
little difference was noticed for the two systems.
Finally, if one compares the results obtained herein with hin-
dered allylic alcohols and that previously reported with the corre-
sponding alkenes (for instance S2 and 1,1-diphenylpropene),21
very similar results are obtained in term of yields and enantiomeric
excesses. It seems to indicate that the hydroxyl group has no (or
very little) interaction with the catalysts at play and anchimeric ef-
fects do not need to be considered.
All reactions were performed in a standard test tube equipped
with a magnetic stirring bar. NaHCO3 (67 mg, 0.80 mmol, 4.0
equiv) was dissolved in 800 l
L of water. OxoneÒ (132 mg, 0.21
mmol, 1.1 equiv) was then added as a solid in one portion and
the solution was stirred for few minutes until effervescence sub-
sided. Five-hundred microliters of a 0.4 mol/L solution of an al-
kene (0.20 mmol, 1.0 equiv) in CH2Cl2 was added and the
resulting biphasic mixture was cooled to 0 °C with a cryostat
bath. A catalyst was added in CH2Cl2 (500
by a solution of 18-C-6 (1.0 mg, 5.0 mol, 2.5 mol %) in CH2Cl2
(200 L) and the resulting mixture was then vigorously stirred
lL) in one pot followed
l
l
(very important!) at 0 °C. After the indicated amount of time,
the reaction mixture was diluted with dichloromethane (10 mL)
and water (10 mL), and the layers were separated. The aqueous
phase was extracted with CH2Cl2 (2 ꢂ 10 mL). The combined or-
ganic layers were dried (Na2SO4), filtered, concentrated under
vacuum, and purified.
4. Experimental
NMR spectra were recorded on 300, 400, and 500 MHz spec-
trometers at room temperature (25 °C) unless otherwise stated.
1H NMR: chemical shifts are given in parts per million (ppm) rela-
tive to Me4Si with the solvent resonance used as the internal stan-
dard (CDCl3 d 7.26 ppm; CD2Cl2 d 5.32 ppm; DMSO-d6 d 2.50 ppm).
13C-NMR (75, 100, 125 MHz): chemical shifts were given in ppm
relative to Me4Si, with the solvent resonance used as the internal
standard (CDCl3 d 77.16 ppm; CD2Cl2 d 54.0 ppm). Assignments
may have been achieved using COSY, DEPT-135, HSQC, and NOESY
4.2. Typical enantioselective epoxidation procedure under
MeCN/water (3:2) conditions
The reaction procedure is similar to the CH2Cl2/water protocol
with small modifications. All reactions were performed in a

1616
R. Novikov, J. Lacour / Tetrahedron: Asymmetry 21 (2010) 1611–1618
standard test tube equipped with a magnetic stirring bar. NaHCO3
(67 mg, 0.80 mmol, 4.0 equiv) was dissolved in 800 L of water.
(37), 55(23). HRMS-EI: calcd for C13H18O [M]+ 190.1355, found
190.1358.
l
OxoneÒ (132 mg, 0.21 mmol, 1.1 equiv) was then added as a solid
in one portion and the solution was stirred for few minutes until
effervescence subsided. Five-hundred microliters of a 0.4 mol/L
solution of an alkene (0.20 mmol, 1.0 equiv) in MeCN was added
(after the addition was done the mixture became triphasic: precip-
itation of inorganic material was observed and the liquid layer sep-
4.8. (E)-4-Methyl-3-phenylpent-2-en-1-ol S835
Colorless oil. 1H NMR (CDCl3, 300 MHz): d = 1.03 (d, 6H,
2 ꢂ CH3, J = 7.0 Hz), 1.29 (br m, 1H, OH), 3.01 (sept, 1H, CH,
J = 7.0 Hz), 4.34 (dd, 2H, CH2, J = 6.5 Hz, 5.3 Hz), 5.46 (t, 1H, CH vi-
nyl, J = 6.8 Hz), 7.11–7.31 (m, 5H, CarH) ppm.
arated in two phases) with the aid of MeCN (200 lL) which was
used to rinse the walls of the flask, and the resulting mixture
was cooled to 0 °C with a cryostat bath. A catalyst was added as
4.9. (E)-4-Methyl-3-(4-methylphenyl)pent-2-en-1-ol S935
a solution in MeCN (500 lL) in one pot. After few minutes without
any stirring the resulting triphasic mixture was then vigorously
stirred (very important!) at 0 °C. After the indicated amount of
time, the reaction mixture was diluted with dichloromethane
(20 mL), water (10 mL), and the layers were separated. The aque-
ous phase was extracted with CH2Cl2 (2 ꢂ 10 mL). The combined
organic layers were dried (Na2SO4), filtered, concentrated under
vacuum, and purified.
Colorless oil. 1H NMR (CDCl3, 300 MHz): d = 1.05 (d, 6H,
2 ꢂ CH3, J = 7.1 Hz), 1.30 (t, 1H, OH, J = 5.4 Hz), 2.35 (s, 3H, CH3),
3.02 (sept., 1H, CH, J = 7.1 Hz), 4.35 (dd, 2H, CH2, J = 6.6 Hz,
5.4 Hz), 5.47 (t, 1H, CH vinyl, J = 6.6 Hz), 7.03–7.14 (m, 4H, CarH)
ppm.
4.10. (E)-3-Cyclohexyl-3-phenylprop-2-en-1-ol S1032
4.3. 3,3-Diphenylprop-2-en-1-ol S232
Colorless viscous oil.1H NMR (CDCl3, 400 MHz): d = 1.19–1.39
(m, 6H), 1.56–1.80 (m, 5H), 2.55–2.68 (m, 1H), 4.36 (dd, 2H,
CH2–OH, J = 6.3 Hz, 5.3 Hz), 5.46 (t, 1H, CH vinyl, J = 6.8 Hz),
7.12–7.18 (m, 2H, CarH), 7.22–7.32 (m, 3H, CarH) ppm.
White solid. Mp = 62.8–63.5 °C (lit. 53–56 °C32). 1H NMR (CDCl3,
300 MHz): d = 1.57 (br s, 1H, OH), 4.33 (d, 2H, CH2, J = 6.8 Hz), 6.36
(t, 1H, CH vinyl, J = 6.8 Hz), 7.24–7.53 (m, 10H, CarH) ppm.
4.11. (E)-3-(4-Bromophehyl)-3-cyclohexylprop-2-en-1-ol S11
4.4. 1,1-Diphenyl-3-methoxyprop-1-ene S3
White solid. Mp = 69.6–70.2 °C. 1H NMR (CDCl3, 500 MHz):
d = 0.98–1.11 (m, 1H), 1.15–1.36 (m, 4H), 1.42 (s, 1H, OH), 1.56–
1.78 (m, 5H), 2.53–2.65 (m, 1H, CH of Cy), 4.34 (dd, 2H, CH2–OH,
J = 6.3 Hz, 3.3 Hz), 5.44 (t, 1H, CH vinyl, J = 6.7 Hz), 7.02 (d, 2H,
CH2, J = 8.5 Hz), 7.40 (d, 2H, CH2, J = 8.2 Hz) ppm. 13C NMR (CDCl3,
125 MHz): d = 26.0 (CH2), 26.7 (CH2), 32.2 (CH2), 40.8 (CH of Cy),
59.0 (CH2–OH), 120.8 (C quat.), 128.1 (CH vinyl), 130.2 (CH),
130.8 (CH), 141.8 (C quat.), 148.6 (C quat.) ppm. IR (neat): 3307
(br, w), 2925 (m), 2851 (m), 1646 (w), 1586 (w), 1485 (m), 1448
(w), 1009 (m), 823 (m) cmꢀ1. MS-EI m/z (rel intensity): 296 [M]+
(11), 294 [M]+ (16), 252 (19), 213 (85), 169 (40), 141 (62), 115
(96), 83 (77), 55 (100). HRMS-EI: calcd for C15H17OBr [Mꢀ2H]+
292.0463, found 292.0463.
Pale yellow oil. 1H NMR (CD2Cl2, 500 MHz): d = 3.28 (s, 3H, CH3),
3.96 (d, 2H, CH2, J = 6.6 Hz), 6.19 (t, 1H, CH vinyl, J = 6.6 Hz), 7.14–
7.19 (m, 2H, CarH), 7.22–7.42 (m, 8H, CarH) ppm. 13C NMR (CD2Cl2,
125 MHz): d = 58.3 (CH3), 70.7 (CH2), 126.5 (CH vinyl), 128.01 (CH),
128.03 (CH), 128.1 (CH), 128.7 (CH), 128.72 (CH), 130.3 (CH), 139.9
(C quat.), 142.6 (C quat.), 145.0 (C quat.) ppm. IR (neat): 3056 (w),
3027 (w), 2981 (w), 2923 (w), 2818 (w), 1599 (w), 1576 (w), 1493
(w), 1444 (w), 1378 (w), 1114 (m), 1086 (m), 757 (m), 695 (s)
cmꢀ1. MS-EI m/z (rel intensity): 224 [M]+ (42), 193 (40), 192
(100), 165 (34), 115 (61), 77 (26). HRMS-EI calcd for C16H16
O
[M]+ 224.1193, found 224.1201.
4.5. 3,3-Di(4-methylphenyl)prop-2-en-1-ol S433
4.12. (ꢀ)-(S)-3,3-Diphenyloxiranemethanol, epoxide of S221
Purification—preparative TLC on silica gel, eluent n-hexane/
White solid. Mp = 68ꢀ69.5 °C (lit. 69–70 °C33). 1H NMR (CDCl3,
400 MHz): d = 1.36 (t, 1H, OH, J = 5.5 Hz), 2.34 (s, 3H, CH3), 2.38
(s, 3H, CH3), 4.22 (dd, 2H, CH2–OH, J = 6.8 Hz, 5.5 Hz), 6.18 (t, 1H,
CH vinyl, J = 6.8 Hz), 7.02–7.21 (m, 8H, CarH) ppm.
EtOAc 3:2. ½a 2D5
ꢁ
¼ ꢀ16:6 (c 0.5, CHCl3) 88% ee [lit.36
½
a 2D5
ꢁ
¼ þ33:8
(c 0.42, CHCl3) for 94% ee epoxide with absolute configuration
(R)]. 1H NMR (CD2Cl2, 300 MHz): d = 1.96 (br s, 1H, OH), 3.3–3.42
(m, 1H), 3.55–3.72 (m, 2H), 7.25–7.45 (m, 10H, CarH) ppm. 13C
NMR (CD2Cl2, 75 MHz): d = 62.6 (CH2), 66.2 (CH), 66.5 (C quat.),
127.4 (CH), 128.3 (CH), 128.4 (CH), 128.5 (CH), 128.8 (CH), 128.9
(CH), 137.6 (C quat.), 141.0 (C quat.) ppm. CSP-HPLC separation:
Chiracel OD-H column, n-hexane/i-PrOH 95:5, 0.5 mL/min, 23 °C,
k = 210 nm); tR (major) = 35.09 min, tR (minor) = 40.47 min.
4.6. (E)-3-Phenylpent-2-en-1-ol S634
Colorless oil. 1H NMR (CDCl3, 300 MHz): d = 0.93 (t, 3H, CH3,
J = 7.5 Hz), 1.27 (br s, 1H, OH), 2.48 (q, 2H, CH2, J = 7.5 Hz), 4.29
(dd, 2H, CH2–OH, J = 6.3 Hz, 4.3 Hz), 5.77 (t, 1H, CH vinyl,
J = 6.8 Hz), 7.14–7.36 (m, 5H, CarH) ppm.
4.7. (E)-5-Methyl-3-phenylhex-2-en-1-ol S7
4.13. (ꢀ)-1,1-Diphenyl-3-methoxyprop-2-ene oxide, epoxide of
S3
Clean colorless oil. 1H NMR (CD2Cl2, 500 MHz): d = 0.84 (d, 6H,
2 ꢂ CH3, J = 6.6 Hz), 1.43 (br s, 1H, OH), 1.49–1.59 (m, 1H, CH of
i-Pr), 2.42 (d, 2H, CH2, J = 7.2 Hz), 4.31 (d, 2H, CH2–OH, J = 6.6 Hz),
5.86 (t, 1H, CH vinyl, J = 6.8 Hz), 7.22–7.39 (m, 5H, CarH) ppm. 13C
NMR (CD2Cl2, 125 MHz): d = 22.6 (CH3), 27.7 (CH of i-Pr), 39.3
(CH2), 60.3 (CH2–OH), 127.1 (CH), 127.6 (CH), 128.8 (CH), 129.0
(CH), 142.8 (C quat.), 143.3 (C quat.) ppm. IR (neat): 3315 (br, w),
2953 (w), 2867 (w), 1643 (w), 1599 (w), 1493 (w), 1463 (w),
1444 (w), 1366 (w), 1010 (m), 764 (m), 696 (m) cmꢀ1. MS-EI m/z
(rel intensity): 190 [M]+ (25), 133 (100), 115 (40), 91 (50), 77
Purification—preparative TLC on silica gel, eluent n-hexane/
EtOAc/Et3N 80:20:1. Rf = 0.57. Pale yellow oil. ½a D25
¼ ꢀ28:6 (c 1.0,
ꢁ
CHCl3) 87% ee. 1H NMR (CDCl3, 300 MHz): d = 3.16 (dd, 1H, –
CHH–OMe, J = 11.1 Hz, 6.2 Hz), 3.33 (s, 3H, CH3), 3.45 (dd, 1H, –
CHH–OMe, J = 11.1 Hz, 4.2 Hz), 3.61 (dd, 1H, CH–O, J = 5.8 Hz,
4.6 Hz), 7.20–7.50 (m, 10H, CarH) ppm. 13C NMR (CDCl3, 75 MHz):
d = 59.3 (CH3), 64.3 (CH), 65.2 (C quat.), 71.8 (CH2), 127.0 (CH),
128.0 (CH), 128.1 (CH), 128.4 (CH), 128.5 (CH), 137.0 (C quat.),
140.4 (C quat.) ppm. IR (neat): 3061 (w), 3029 (w), 2984 (w),

R. Novikov, J. Lacour / Tetrahedron: Asymmetry 21 (2010) 1611–1618
1617
2928 (w), 2821 (w), 1495 (w), 1448 (m), 1122 (m), 1088 (m), 764
(m), 753 (m), 696 (s) cmꢀ1. MS-EI m/z (rel intensity): 240 [M]+ (4),
208 (37), 195 (11), 165 (100), 105 (28), 77 (24). HRMS-EI: calcd for
192.1150, found 192.1129. CSP-HPLC separation: Chiracel OD-H
column, n-hexane/i-PrOH 90:10, 0.8 mL/min, 23 °C, k = 210 nm);
tR (major) = 9.84 min, tR (minor) = 16.92 min.
C
16H16O2 [M]+ 240.1150, found 240.1141. CSP-HPLC separation:
Chiracel OD-H column, n-hexane/i-PrOH 99:1, 0.5 mL/min, 23 °C,
k = 210 nm); tR (minor) = 16.04 min, tR (major) = 17.43 min.
4.17. (+)-trans-3-Isopropyl-3-(4-methylphenyl)oxiranemeth-
anol epoxide of S9
4.14. (+)-trans-3-Ethyl-3-phenyloxiranemethanol, epoxide of S6
Purification—preparative TLC on silica gel, eluent n-hexane/
EtOAc/Et3N 60:40:1. Rf = 0.53 (silica gel, n-hexane/EtOAc 3:2). Pale
Purification—preparative TLC on silica gel, eluent n-hexane/
yellow viscous oil. ½a D25
ꢁ
¼ þ25:9 (c 1.0, CHCl3) 95% ee. 1H NMR
EtOAc 3:2. Rf = 0.45. Pale yellow oil. ½a D25
ꢁ
¼ þ5:3 (c 1.0, CHCl3)
(CDCl3, 500 MHz): d = 0.93 (d, 3H, CH3, J = 6.6 Hz), 0.99 (d, 3H,
CH3, J = 7.3 Hz), 1.82 (sept., 1H, CH, J = 7.0 Hz), 1.91 (br s, 1H,
OH), 2.34 (s, 3H, CH3), 3.17 (dd, 1H, CH–O, J = 6.6 Hz, 4.4 Hz),
3.89 (dd, 1H, –CHH–, J = 12.1 Hz, 7.0 Hz), 4.03 (dd, 1H, –CHH–,
J = 12.1 Hz, 4.6 Hz), 7.12 (d, 2H, CarH, J = 7.9 Hz), 7.20 (d, 2H, CarH,
J = 7.9 Hz) ppm. 13C NMR (CDCl3, 125 MHz): d = 18.2 (CH3 of i-Pr),
19.7 (CH3 of i-Pr), 21.3 (CH3), 31.5 (CH of i-Pr), 60.8 (CH2), 64.7
(CH–O), 69.8 (C quat.), 128.1 (CH), 128.4 (CH), 135.0 (C quat.),
137.3 (C quat.) ppm. IR (neat): 3416 (br, w), 2966 (w), 2874 (w),
1516 (w), 1459 (w), 1385 (w), 1365 (w), 1031 (m), 905 (w), 815
(m) cmꢀ1. MS-EI m/z (rel intensity, 40 eV): 205 [MꢀH]+ (10), 191
(31), 163 (15), 145 (66), 131 (100), 105 (80), 91 (69). HRMS-EI:
calcd for C13H18O2 [MꢀH]+ 205.1226, found 205.1229. CSP-HPLC
separation: Chiracel OJ column, n-hexane/i-PrOH 90:10, 1.0 mL/
min, 23 °C, k = 210 nm); tR (major) = 8.59 min, tR (minor) = 13.27
min.
87% ee. 1H NMR (CDCl3, 500 MHz): d = 0.94 (t, 3H, CH3,
J = 7.4 Hz), 1.74–1.84 (m, 1H, –CHH–CH3), 1.87 (dd, 1H, OH,
J = 6.9 Hz, 5.0 Hz), 2.08–2.18 (m, 1H, –CHH–CH3), 3.12 (dd, 1H,
CH–O, J = 6.4 Hz, 4.2 Hz), 3.80–3.90 (m, 1H, –CHH–OH), 3.94–4.04
(m, 1H, –CHH–OH), 7.26–7.37 (m, 5H, CarH) ppm. 13C NMR (CDCl3,
125 MHz): d = 9.6 (CH3), 24.7 (–CH2–CH3), 61.2 (–CH2–OH), 65.9 (C
quat.), 66.0 (CH–O), 126.1 (CH), 127.6 (CH), 128.5 (CH), 140.3 (C
quat.) ppm. IR (neat): 3399 (br, w), 2975 (w), 2938 (w), 2878
(w), 1496 (w), 1449 (w), 1379 (w), 1303 (w), 1030 (m), 888 (w),
761 (m), 698 (m) cmꢀ1. MS-EI m/z (rel intensity, 40 eV): 177
[MꢀH]+ (9), 160 (9), 147 (14), 131 (50), 117 (100), 105 (39), 91
(83), 77 (50). HRMS-EI: calcd for C11H13O2 [MꢀH]+ 117.0917, found
117.0916. CSP-HPLC separation: Chiracel OJ column, n-hexane/i-
PrOH 90:10, 1.0 mL/min, 23 °C, k = 210 nm); tR (major) = 7.51 min,
tR (minor) = 9.23 min.
4.15. (+)-trans-3-Isobutyl-3-phenyloxiranemethanol, epoxide of
S7
4.18. (+)-(2S,3S)-trans-3-Cyclohexyl-3-phenyloxiranemethanol,
epoxide of S1037
Purification—preparative TLC on silica gel, eluent n-hexane/
Purification—preparative TLC on silica gel, eluent n-hexane/
EtOAc/Et3N 60:40:1. Rf = 0.53 (silica gel, n-hexane/EtOAc 3:2).
White solid, mp = 153.8–155 °C (recrystallized from n-hexane/i-
EtOAc/Et3N 60:40:1. Rf = 0.65. Pale yellow oil. ½a D25
¼ þ20:4 (c 1.0,
ꢁ
CHCl3) 92% ee. 1H NMR (CDCl3, 300 MHz): d = 0.87 (d, 3H, CH3,
J = 6.0 Hz), 0.89 (d, 3H, CH3, J = 6.0 Hz), 1.45–1.73 (m, 3H), 2.18
(dd, 1H, i-Pr-CHH–, J = 13.9 Hz, 5.2 Hz), 2.98 (dd, 1H, CH–O,
J = 6.6 Hz, 4.3 Hz), 3.77–3.89 (m, 1H, –CHH–OH), 3.92–4.04 (m,
1H, –CHH–OH), 7.22–7.40 (m, 5H, CarH) ppm. 13C NMR (CD2Cl2,
125 MHz): d = 22.5 (CH3), 23.7 (CH3), 25.9 (CH of i-Pr), 40.2 (i-Pr-
CH2–), 61.6 (–CH2–OH), 64.7 (C quat.), 65.1 (CH–O), 126.4 (CH),
127.8 (CH), 128.8 (CH), 141.7 (C quat.) ppm. MS-EI m/z (rel inten-
sity): 205 [MꢀH]+ (16), 176 (9), 163 (12), 147 (36), 131 (100), 105
(78), 91 (95), 77 (76). IR (neat): 3398 (w), 2955 (w), 2870 (w), 1496
(w), 1465 (w), 1450 (w), 1368 (w), 1294 (w), 1033 (m), 761 (w),
698 (m) cmꢀ1. HRMS-EI: calcd for C13H18O2 [M]+ 206.1307, found
206.1293. CSP-HPLC separation: Chiracel OJ-H column, n-hexane/
i-PrOH 90:10, 1.0 mL/min, 23 °C, k = 210 nm); tR (major) = 8.09 -
min, tR (minor) = 9.34 min.
PrOH, 96% ee). ½a D25
ꢁ
¼ þ42:0 (c 1.0, CHCl3, 96% ee). [lit.37
½
a 2D0
ꢁ
¼
þ42:0 (c 1.0, CHCl3) for 97% epoxide with absolute configuration
(2S,3S)). 1H NMR (CDCl3, 500 MHz): d = 0.83–1.03 (m, 2H), 1.07–
1.30 (m, 3H), 1.49 (tt, 1H, CH of Cy ring, J = 12.3 Hz, 3.1 Hz),
1.55–1.63 (m, 1H), 1.65–1.79 (m, 3H), 1.84–1.93 (m, 1H), 2.0 (br
m, 1H, OH), 3.17 (dd, 1H, CH–O, J = 6.6 Hz, 4.4 Hz), 3.91 (dd, 1H,
–CHH–OH, J = 12.1 Hz, 6.8 Hz), 4.03 (dd, 1H, –CHH–OH, J =
12.1 Hz, 4.4 Hz), 7.26–7.34 (m, 5H, CarH) ppm. 13C NMR (CDCl3,
125 MHz): d = 26.0 (CH2), 26.1 (CH2), 26.4 (CH2), 28.7 (CH2), 30.1
(CH2), 42.0 (CH of Cy), 60.8 (CH2–OH), 64.3 (CH–O), 69.4 (C quat.),
127.6 (CH), 127.7 (CH), 128.0 (CH), 138.9 (C quat.) ppm. IR (neat):
3427 (m), 2928 (m), 2855 (w), 1495 (w), 1460 (w), 1446 (w), 1297
(w), 1279 (w), 1029 (m), 885 (w), 770 (m), 722 (w), 707 (m), 653
(w) cmꢀ1. MS-EI m/z (rel intensity, 40 eV): 231 [M-H]+ (36), 187
(17), 131 (100), 105 (79), 91 (89), 55 (41). HRMS-EI: calcd for
4.16. (+)-trans-3-Isopropyl-3-phenyloxiranemethanol, epoxide
C
15O20O2 [M]+ 232.1446, found 232.1463. CSP-HPLC separation:
of S8
Chiracel OJ column, n-hexane/i-PrOH 90:10, 1.0 mL/min, 23 °C,
k = 210 nm); tR (major) = 6.10 min, tR (minor) = 11.14 min.
Purification—preparative TLC on silica gel, eluent n-hexane/
EtOAc/Et3N 60:40:1. Rf = 0.53 (silica gel, n-hexane/EtOAc 3:2). Col-
4.19. (+)-trans-3-(4-Bromophenyl)-3-cyclohexyloxiranemeth-
anol epoxide of S11
orless viscous oil. ½a D25
ꢁ
¼ þ33:0 (c 1.0, CHCl3) 95% ee. 1H NMR
(CD2Cl2, 500 MHz): d = 0.91 (d, 3H, CH3, J = 6.6 Hz), 0.99 (d, 3H,
CH3, J = 7.0 Hz), 1.83 (sept. 1H, CH, J = 7.0 Hz), 2.50 (br s, 1H, OH),
3.12 (dd, 1H, CH–O, J = 6.6 Hz, 4.4 Hz), 3.85 (dd, 1H, –CHH–,
J = 12.0 Hz, 6.6 Hz), 4.02 (dd, 1H, –CHH–, J = 12.0 Hz, 4.4 Hz),
7.26–7.35 (m, 5H, CarH) ppm. 13C NMR (CD2Cl2, 125 MHz):
d = 18.4 (CH3), 19.8 (CH3), 31.9 (CH of i-Pr), 61.1 (CH2), 65.2 (CH–
O), 69.9 (C quat.), 127.9 (CH), 128.0 (CH), 128.7 (CH), 138.7 (C
quat.) ppm. IR (neat): 3415 (br, w), 2967 (w), 2934 (w), 2875
(w), 1497 (w), 1462 (w), 1447 (w), 1386 (w), 1365 (w), 1030 (m),
905 (w), 760 (m), 701 (m) cmꢀ1. MS-EI m/z (rel intensity, 40 eV):
191 [MꢀH]+ (12), 161 (7), 149 (12), 131 (76), 117 (100), 105
Purification—preparative TLC on silica gel, eluent n-hexane/
EtOAc/Et3N 60:40:1. Rf = 0.4 (silica gel, n-hexane/EtOAc 3:2). Pale
yellow tar. ½a 2D5
ꢁ
¼ þ26:1 (c 1.0, CHCl3) 79% ee. 1H NMR (CDCl3,
500 MHz): d = 0.75–1.38 (m, 6H), 1.47 (tt, 1H, CH of Cy,
J = 12.3 Hz, 2.8 Hz), 1.53–1.93 (m, 7H), 3.11 (dd, 1H, CH–O,
J = 6.6 Hz, 4.7 Hz), 3.8–4.08 (m, 2H, –CH2–OH), 7.17 (d, 2H, CarH,
J = 8.2 Hz), 7.44 (d, 2H, CarH, J = 8.5 Hz) ppm. 13C NMR (CDCl3,
125 MHz): d = 26.0 (CH2), 26.1 (CH2), 26.4 (CH2), 28.6 (CH2), 30.1
(CH2), 41.8 (CH of Cy), 60.6 (CH2–OH), 64.2 (CH–O), 68.8 (C quat.),
121.7 (C quat.), 129.7 (CH), 130.9 (CH), 137.9 (C quat.) ppm. IR
(neat): 3405 (br, w), 2927 (m), 2853 (m), 1592 (w), 1490 (w),
(45), 91 (68), 77 (41). HRMS-EI: calcd for
C
12H16O2 [M]+

1618
R. Novikov, J. Lacour / Tetrahedron: Asymmetry 21 (2010) 1611–1618
1451 (w), 1027 (w), 1011 (m), 884 (w), 825 (m) cmꢀ1. MS-EI m/z
(rel intensity): 312 [M]+ (13), 310 [M]+ (13), 253 (28), 251 (33),
211 (76), 209 (70), 169 (97), 141 (36), 129 (72), 81 (96), 55
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(100). HRMS-EI: calcd for
C
15H19O2Br [M]+ 310.0568, found
310.0552. CSP-HPLC separation: Chiracel OJ-H column, n-hexane/
i-PrOH 95:5, 1.0 mL/min, 23 °C, k = 210 nm); tR (major) = 7.76 min,
tR (minor) = 10.75 min.
Acknowledgments
We are grateful for financial support of this work by the Swiss
National Science Foundation and the University of Geneva. We
thank Dr. Klaus Ditrich (BASF) for the generous gift of (R)- and
(S)-3,3-dimethylbutyl-2-amine.
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2004, 69, 3595.
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Chem. 2005, 70, 5903.
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