Intramolecular epoxidation in unsaturated ketones and oxaziridines

Article abstract of DOI:10.1039/b107839a

The possibility of intramolecular epoxidation in acyclic unsaturated ketones (via dioxiranes) and oxaziridines (via oxaziridinium species) has been investigated. Treatment of several acyclic unsaturated ketones with Oxone led to low levels of regio- and stereocontrol, suggesting that background epoxidation by Oxone dominates. However, treatment of unsaturated oxaziridines with methyl trifluoromethanesulfonate led to intramolecular epoxidation. This process allowed regioselective epoxidation of a non-conjugated diene. It also proceeded with a high degree of stereocontrol consistent with a stereoelectronic preference for aspiro-transition state.

Full text of DOI:10.1039/b107839a

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Intramolecular epoxidation in unsaturated ketones and oxaziridines
Alan Armstrong*† and Alistair G. Draffan
School of Chemistry, University of Nottingham, Nottingham, UK NG7 2RD
1
Received (in Cambridge, UK) 31st August 2001, Accepted 19th September 2001
First published as an Advance Article on the web 17th October 2001
The possibility of intramolecular epoxidation in acyclic unsaturated ketones (via dioxiranes) and oxaziridines
(via oxaziridinium species) has been investigated. Treatment of several acyclic unsaturated ketones with Oxone®
led to low levels of regio- and stereocontrol, suggesting that background epoxidation by Oxone® dominates.
However, treatment of unsaturated oxaziridines with methyl trifluoromethanesulfonate led to intramolecular
epoxidation. This process allowed regioselective epoxidation of a non-conjugated diene. It also proceeded
with a high degree of stereocontrol consistent with a stereoelectronic preference for a spiro-transition state.
variables, including pH. We used this two-phase system to study
Introduction
the Oxone® epoxidation of the Z-acyclic unsaturated ketones12
3–5 which would be expected to undergo intramolecular
epoxidation with a high degree of diastereoselectivity due to the
effect of A1,3-strain.13 However, conversions were low and little
or no stereoselectivity was observed. Several pieces of evidence
led to the conclusion that the interaction of the KHSO5 and the
ketone takes place in the aqueous phase, where direct, back-
ground epoxidation of the alkene by Oxone® is rapid.12b,14 The
tetraalkylammonium salt likely plays the role of surfactant,
increasing the water solubility of the substrate, rather than
acting as phase-transfer catalyst. The complicated solubility
requirements of this two-phase solvent system meant that is
was largely superseded when Yang introduced an experi-
mentally far more convenient monophasic CH3CN–H2O
system, in the presence of NaHCO3 to effect pH control.15 We
therefore decided to investigate the possibility of intra-
molecular epoxidation of acyclic ketoalkenes 3–5 in this
monophasic system. Even at high dilution (8 mM in
ketoalkene), diastereoselectivity never exceeded 1.8 : 1. We sus-
pected that non-stereoselective background epoxidation by
Oxone® was competing with any intramolecular dioxirane
epoxidation. Indeed, the epoxidation of a simple dialkyl substi-
tuted alkene such as decene occurs over a similar time period
under the same reaction conditions in the absence of a ketone
promoter. We therefore attempted to increase the ketone
reactivity by incorporation of an α-chloro substituent, since
Yang16 and ourselves3b had shown that chloroacetone promotes
epoxidation of (E)-stilbene approximately 17 times faster than
acetone itself. Disappointingly, however, at 8 mM concen-
tration, diastereoselectivity in the epoxidation of 6–8 did not
exceed 1.4 : 1. Since it was conceivable that the A1,3-strain con-
formational preference was preventing the preferred spiro-TS
geometry17 for dioxirane epoxidation, we decided to remove
the allylic stereocentre and use regioselectivity as a probe for
intramolecular epoxidation. The non-conjugated dienyl ketone
10 and its α-chloro isomer 11 were prepared as shown in
Scheme 2, with the Z-geometry of the disubstituted alkene
being installed using Ni-catalysed ring opening of dihydro-
pyran with a Grignard reagent.18 Intramolecular epoxidation
would be expected to occur at the disubstituted olefin, closest
to the ketone. However, reaction of 10 with 1 equiv. Oxone®
under the Yang CH3CN–H2O conditions at 40 mM concen-
tration led to exclusive epoxidation at the trisubstituted alkene.
Under the same conditions, and also under the Shi higher pH
conditions,19 chloroketone 11 provided a ca. 3 : 1 ratio of
inseparable epoxides, with reaction on the trisubstituted alkene
Intramolecular reactions often proceed with significant levels
of regio- and stereocontrol. Although alkene epoxidation is one
of the most useful synthetic transformations, and the directing
effects of substituents have been widely studied,1 there are few
examples of intramolecular oxygen transfer to alkenes.2 This is
largely because of the inherent stereoelectronic constraints of
such processes. We have been interested in the catalysis of
Oxone® epoxidation of alkenes by ketones3 (via dioxiranes)4
and iminium salts5 (via oxaziridinium species).6 Most studies of
these compounds have been concerned with the development of
new chiral reagents for asymmetric alkene epoxidation,3–7 but
we were also attracted to the possibility that intramolecular
variants of these processes (Scheme 1) may proceed with a high
Scheme 1
degree of regio- and stereocontrol. Moreover, it had already
been established that the epoxycarbonyl products 2 (X = O) were
useful intermediates in the synthesis of oxygen heterocycles.8
Here we describe in full9 our studies of these intramolecular
epoxidation reactions.
Results and discussion
(a) Oxone® epoxidation of unsaturated ketones
At the outset of our studies, the generation of dioxiranes from
ketones and Oxone® (active constituent KHSO5) required
a two-phase, CH2Cl2–H2O solvent system in the presence of a
tetraalkylammonium salt, presumed to act as a phase-transfer
catalyst to take the HSO5Ϫ anion into the organic phase to react
with the ketone.10 Indeed, Curci and co-workers have reported
the epoxidation of hex-5-en-2-one under these conditions in the
absence of a separate ketone, although it was not established
whether the epoxidation was intramolecular.10 Subsequent
detailed study of this reaction system by Denmark and co-
workers11 underscored the need for careful control of several
† Present address: Department of Chemistry, Imperial College, London,
UK SW7 2AY.
DOI: 10.1039/b107839a
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This journal is © The Royal Society of Chemistry 2001
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chromatography on deactivated (Et3N) silica. A characteristic
triplet at ca. 3.90 ppm (1H NMR) and the oxaziridine carbon
signal at ca. 82 ppm (13C NMR) served to confirm structure.
With the seven novel oxaziridines in hand, attention was
focused on the intramolecular epoxidation process. The first
substrate to be subjected to N-alkylation was 14a. When a
42 mM dichloromethane solution of 14a was treated with
methyl trifluoromethanesulfonate (MeOTf ), formation of a
more polar product was observed by TLC. The presumed
intermediate epoxy iminium salt was readily hydrolysed by
addition of saturated aqueous sodium bicarbonate to the
reaction mixture. 1H NMR analysis of the crude reaction
product following extraction with dichloromethane showed
only the expected epoxyaldehyde (rac-15a) and N-methyl-
benzylamine to be present (Scheme 4). Despite repeated
Scheme 2
again predominating. This suggested that the desired intra-
molecular epoxidation may be occurring to a small extent, but
not enough to make the reaction useful. For high levels of
regio- or stereocontrol to be achieved it seems likely that the
reactivity of the olefin component towards Oxone® would have
to be substantially reduced (e.g. by aromatic substitution), as
well as having an activated ketone. The need for heavily biased
substrates would clearly limit the scope of this chemistry and
would restrict the synthetic utility of any product epoxyketones.
Efforts in this area were therefore abandoned.
Scheme 4
attempts, the epoxyaldehyde could not be isolated in yields
greater than ca. 40%. This was attributed mainly to loss during
chromatographic purification and isolation due to volatility
of the product. The low yields were not due to the presence
of trifluoromethanesulfonic (triflic) acid (from hydrolysis of
MeOTf ) since addition of the hindered base 2,6-di-tert-butyl-
pyridine (4 equiv. relative to oxaziridine) had no observable
effect on the reaction.
In order to demonstrate that this epoxidation reaction was
indeed intramolecular, we designed a crossover experiment in
which the epoxidation reaction was repeated in the presence of
a second olefin, benzyl ether 16, expected to be of comparable
reactivity. The methylation and hydrolysis of 14a was carried
out as before at the same concentration in the presence of an
equimolar amount of 16. The reaction proceeded as before with
(b) Intramolecular epoxidation of unsaturated oxaziridines
The major problem in the attempted intramolecular dioxirane
epoxidations appeared to be competing background epoxid-
ation by Oxone®. The related oxaziridinium epoxidation
system offered an attractive alternative since, as well as being
accessible by iminium oxidation, these species can be prepared
by a non-oxidative method: quaternisation of an N-alkyl-
oxaziridine.6 However, preparation of unsaturated oxaziridines
for quaternisation would still require oxidation of the corre-
sponding unsaturated imine in the presence of the alkene.
Scattered examples in the literature suggested that this would be
possible.20 For our initial studies, we opted to study aldimines to
ensure high E/Z-selectivity in imine formation. As shown in
Scheme 3 and Table 1, a range of unsaturated aldehydes 12 of
1
no evidence for the epoxidation of 16 by TLC or H NMR
analysis of the crude reaction product. The main product again
was epoxyaldehyde rac-15a (39%) and 16 was recovered in good
yield following flash column chromatography (Table 2, entry 1),
indicating that the selective epoxidation of 14a was due to an
intramolecular epoxidation process.
We wished to investigate the range of substrates for which the
sequence of oxaziridine formation and intramolecular epoxid-
ation could be applied. In particular, increasing tether length
might reduce the rate of intramolecular oxygen transfer relative
to intermolecular reaction. Directed epoxidations tend only
to be highly selective when the functional groups are close
together.1 If intramolecular selectivity were maintained for
longer tether lengths it would represent
a considerable
achievement. The chain extended homologues 14b and 14c were
subjected to identical reaction conditions (4 equiv. of MeOTf
1
over 4 hours) followed by hydrolysis. As before, TLC and H
NMR analysis showed clean transformation to the epoxyalde-
hydes but the isolated yields were moderate (38% for rac-15b
and 58% for rac-15c) following chromatography. Crossover
experiments were again conducted (Table 2, entries 2 and 3)
with the chain-extended benzyl ether 17 present in the case of
oxaziridine 14c. Pleasingly, the reaction proceeded as before in
both cases generating the epoxyaldehydes with no evidence
for intermolecular epoxidation. Benzyl ethers 16 and 17 were
recovered unchanged after purification.
Scheme 3
varying tether length and alkene substitution pattern were
reacted with achiral primary amines, and indeed provided
exclusively the E-imine product 13. Best results for selective
imine oxidation were obtained using 0.6 equiv. Oxone® (1.2
equiv. KHSO5) to prevent over-oxidation, leading to the desired
unsaturated oxaziridines 14. The crude oxaziridines required
little purification but were found to be stable to flash column
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Table 1 Preparation of unsaturated oxaziridines 14 from aldehydes 12a
Substrate 12
R1
R2
R3
R4
n
Yield for 12
14 (%)
a
b
c
d
e
f
H
H
H
nBu
H
H
H
Me
Me
Me
H
H
nBu
nBu
Me
Me
Me
H
nPr
H
Bn
Bn
Bn
Bn
Bn
Bn
nPr
1
2
3
1
1
1
1
73
60
64
72
73
45
39
g
H
a Conditions as shown in Scheme 3.
Table 2 Crossover experiments: conversion of 14a–c to 15a–c in the
presence of 16 or 17a
Entry
Substrate 14
n
14
15 (%)
Recovered alkene
1
2
3
a
b
c
1
2
3
39
41
55
16 (73%)
16 (96%)
17 (90%)
a Conditions as shown in Scheme 4, with 1 equiv. 16 or 17.
Scheme 6
Following the procedure applied to the previous series,
aldehyde 19 was reacted with benzylamine followed by imine
oxidation to provide 20 (Scheme 7). Oxaziridine 20 was then
Table 3 Conversion of 14d–g to 15d–ga
Substrate 14
R1
R2
R3
R4
14
15 (%)
d
e
f
nBu
H
H
H
H
nBu
nBu
H
nPr
H
Bn
Bn
Bn
nPr
39
56
60
48
g
H
H
a Conditions as shown in Scheme 5.
These initial studies provided an important proof of concept
for the intramolecular oxaziridinium epoxidation. Our attention
then turned to variation of the alkene substitution pattern
(Scheme 5, Table 3). The representative 1,1-disubstituted (14d)
Scheme 5
Scheme 7
and trans-(14e) and cis-(14f ) 1,2-disubstituted unsaturated
oxaziridines were again converted to the epoxyaldehydes 15
upon treatment with MeOTf followed by aqueous bicarbonate
work-up. The amine portion was also varied (14g). The pure
epoxyaldehydes, the major components of the crude reaction
mixtures, were isolated in moderate yield following chrom-
atography (Table 3). As expected, only one epoxide isomer was
observed for 15e–g, indicating that intramolecular epoxidation
is a stereospecific process. This is in agreement with previous
studies on intermolecular oxaziridinium epoxidation which
have demonstrated retention of alkene configuration,6 and
provide further evidence that oxaziridinium epoxidation is a
concerted process.
We next investigated the possibility of applying this intra-
molecular epoxidation to the regioselective epoxidation of a
polyene. The previously prepared substrate 9 containing cis-
disubstituted and trisubstituted alkenes was again chosen. It
was proposed that intermolecular epoxidation by an electro-
philic oxidant, such as peracid or an oxaziridinium salt, would
occur at the trisubstituted alkene whereas intramolecular
reaction should be directed to the cis-double bond adjacent
to the functional group. Indeed, it was found that oxidation
of 9 with MCPBA produced the 8,9-epoxide 18 (75% after
chromatography) as the sole product (Scheme 6).
subjected to methylation and hydrolysis resulting solely in
epoxidation of the disubstituted alkene. Thus, as expected,
intramolecular epoxidation via the oxaziridinium salt com-
pletely controls the site of oxidation. The yield of this process
was not optimised, but the concept of regiocontrol through
intramolecular epoxidation had clearly been demonstrated.
(c) Stereoselective intramolecular epoxidation in unsaturated
oxaziridines
Our attention next turned to the stereochemical aspects of the
intramolecular epoxidation process. At this point in our studies,
there was no information as to whether alkene epoxidation by
oxaziridinium species displayed a stereoelectronic preference
for a spiro or a planar geometry (Fig. 1). This point is important
for the rational design of chiral oxaziridinium salts for asym-
metric epoxidation. However, inspection of molecular models
indicated that for an oxaziridinium of fixed configuration at the
ring carbon, these two extreme geometries would lead to intra-
molecular epoxidation on opposite faces of the olefin (Fig. 1).
Thus, study of the stereochemistry of the intramolecular
process would provide information on the stereoelectronic
preference as well as potentially leading to epoxyaldehydes of
high enantiomeric purity. We reasoned that oxidation of an
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Fig. 1 Stereoelectronics of oxaziridinium epoxidation.
Table 4 Preparation of unsaturated oxaziridines 23 and 24 from alde-
imine derived from an enantiomerically pure chiral primary
hydes 12a
amine and an unsaturated aldehyde could yield separable
diastereomeric oxaziridines, allowing the oxygen transfer
process to be studied in each. Thus, reaction of the previously
prepared aldehydes 12a, 12e, and 12d with (S)-α-methylbenzyl-
amine in the presence of molecular sieves produced the trans-
imines 22 (Scheme 8). Oxone® oxidation of each imine
Substrate 12
R1
R2
R3
23 : 24b
23 (%)c
24 (%)c
a
e
d
H
H
nBu
Me
H
H
Me
nPr
H
3 : 1
4 : 1
3 : 1
22
21
54
14
15
15
a Conditions as shown in Scheme 8. b Estimated from the crude 1H
NMR spectrum. c Isolated yields after chromatography. Diastereomeric
excess of purified samples as indicated in Table 5.
precedent that imine oxidation will result in products with the
N-substituent trans to the substituent on the ring carbon.21,22
With regard to configuration at the ring carbon, it has been
consistently observed that the main stereoisomeric oxaziridine
formed by peracid oxidation of imines bearing an N-α-
methylbenzyl substituent has unlike relative stereochemistry
at the nitrogen and α-stereocentres (cf. 23).21 For example,
MCPBA oxidation of 25 was shown to provide a 2.3 : 1 ratio
of 26 : 27 (Scheme 9).21e We repeated this reaction under
Scheme 8
proceeded smoothly to provide a mixture of two diastereomeric
oxaziridine products 23 and 24 in good combined yield (>90%).
The diastereomeric ratio could be determined by integration of
Scheme 9
our Oxone® conditions and obtained a 3 : 1 mixture with the
same major isomer predominating. In accord with literature
precedent,21e the oxaziridine ring proton and the proton α to
nitrogen are at a higher field in 26 (δ 3.53 and 3.02 respectively)
than in the minor isomer 27 (δ 3.59 and 3.10). This correlation
was observed for all the oxaziridines 23 and 24 prepared in our
studies. For example, the major isomer 23a was characterised
by the upfield resonances of the ring proton and α-proton (3.81
and 3.04) compared with the minor isomer 24a (3.86 and 3.14,
respectively).
Attention was then turned to intramolecular epoxidation
in the purified diastereomeric oxaziridines (Scheme 10 and
Table 5). These compounds were treated with MeOTf as before;
the presence of 2,6-di-tert-butylpyridine (4 equiv.) proved to be
beneficial to prevent degradation of the starting material and
the product epoxide mediated by adventitious triflic acid. Enan-
tiomeric purity of the resulting epoxyaldehydes 15 was then
1
the H NMR spectra. However, the similar Rf values of the
diastereomers necessitated repeated column chromatography
leading to low yields of the isolated diastereomerically enriched
oxaziridines. Nevertheless, samples of suitably high diastereo-
selectivity for further studies were obtained (Table 4). One of
the minor oxaziridine ring diastereomers, 24d, contained an
1
impurity which did not correspond to 23d by H NMR, and
which was tentatively assigned as a cis oxaziridine isomer. The
1H NMR spectrum of this impurity had a triplet resonance for
the oxaziridine ring proton at 4.15 ppm (cf. 3.89 for 24d) and a
benzylic quartet at 3.62 ppm (cf. 3.14 for 24d).
The configuration of the two oxaziridine diastereomers was
assigned by comparison to secure literature precedent for the
oxidation of imines derived from α-methylbenzylamine.20a,21
The ring nitrogen is a stereocentre, and inversion does not occur
in N-alkyloxaziridines at room temperature. There is good
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Table 5 Intramolecular epoxidation of 23a,d,e and 24a,d,ea
Substrate 23/24
R1
R2
R3
23 De (%)b
28 Ee (%)c
15 Yield (%)
24 De (%)b
ent-28 Ee (%)c
ent-15 Yield (%)
a
e
d
H
H
nBu
Me
H
H
Me
nPr
H
∼83
>90
>90
81
93
>98
60
35
55
>90
>90
∼83d
94
92
84
40
47
70
1
a Conditions as shown in Scheme 10. b Estimated from the crude H NMR spectrum. c Measured by chiral HPLC. d Sample of 24d contained an
impurity (see text).
Scheme 11
Scheme 10
determined by reduction and conversion to the benzyl ethers
28, which could be resolved by chiral HPLC. The absolute con-
figuration of the major isomers was determined by preparation
of authentic samples for chiral HPLC analysis using reliable
methods of asymmetric synthesis. Thus, epoxidation using the
Shi fructose-derived ketone 2919 provided samples of 28a and
28e (Scheme 11). Sharpless epoxidation23 was the key step in the
synthesis of epoxide ent-28d (Scheme 12).
Scheme 12
Several interesting features emerge from the results in Table
5. In all cases, epoxide products were obtained with enantio-
meric excess very close to the diastereomeric excess of the
starting oxaziridine 23/24. Thus, the intramolecular epoxidation
appears to proceed with a very high level of stereocontrol. Of
particular note is the formation of a terminal epoxide, 15d/28d,
of very high enantiomeric excess, since direct asymmetric
epoxidation of “unfunctionalised” terminal alkenes is still a
difficult transformation. Importantly, epoxides of opposite
absolute configuration were obtained from the two oxaziridine
diastereomers 23 and 24, suggesting that it is the ring carbon
rather than the chiral α-methylbenzyl unit that determines the
stereochemistry of the epoxide. In all cases, the observed major
enantiomer is consistent with intramolecular attack via a spiro
transition state, and this work provided the first evidence for
such a preference. Following the communication of our results,
the first computational study of epoxidations by oxaziridinium
salts was reported by Washington and Houk.24 All calculated
transition structures (Becke3LYP/6-31G*) for epoxidations
of simple alkenes by substituted oxaziridiniums were indeed
found to have spiro geometry. Examples of stereoselective
oxaziridinium epoxidation were also modelled including the
intramolecular epoxidation of 24a to give epoxyaldehyde
ent-15a in 94% ee. Using N,N-dimethyl-3-butenyloxaziridinium
as a model it was found that the spiro transition state leading to
the observed S-epoxide was 6.6 kcal molϪ1 lower in energy than
the planar mode. It is very pleasing that this ab initio study
validates our experimental work and supports the proposed
spiro transition state for epoxidation by oxaziridinium salts.
We were interested in expanding the scope of the intra-
molecular epoxidation methodology further to different alkene
substitution patterns and longer tether lengths. (Z)-Oct-5-en-1-
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ol was oxidised to the aldehyde followed by imine formation
and oxidation under standard conditions to generate oxazir-
idines 37 and 38 in high diastereomeric excess after purification
(Scheme 13).
benzyl ethers 40 following the established protocol. Chiral
HPLC analysis of these epoxide products showed that the
epoxide ring had been installed in high and similar enantio-
meric excess, with the configuration of the major isomers
assigned assuming that
a spiro-transition state is again
preferred. However, given the high de of 37 and 38 it is evident
that complete chirality transfer has not occurred. The drop in
stereoselectivity in this series could be due to the increased alkyl
tether length reducing the difference in transition state energies
for epoxidation of opposite alkene faces. Alternatively, the
reduced enantiomeric excess could result from an increased
spiro TS energy for the Z-alkene due, for example, to a steric
clash between the alkene ethyl substituent and oxaziridine
ring hydrogen. Further experiments combined with molecular
modelling studies would help clarify this result.
Conclusions
Two different approaches towards selective intramolecular
epoxidation have been studied. The first investigated the
possibility for ketone-directed oxidation via an intermediate
dioxirane generated in situ from Oxone®. It was found that
direct, non-selective epoxidation by Oxone® competed with the
intramolecular dioxirane reaction leading to poor levels of
diastereo- and regiocontrol in a homogenous solvent system.
New methodology was developed for the synthesis and epox-
idation of a range of unsaturated oxaziridines. Treatment with
MeOTf followed by hydrolysis yielded epoxyaldehydes, pre-
sumably via the oxaziridinium salts. Crossover experiments and
the completely regioselective epoxidation of a non-conjugated
diene provided strong evidence for intramolecular reaction. The
use of α-methylbenzylamine as a chiral auxiliary allowed
diastereomeric oxaziridines to be isolated. Intramolecular
epoxidation was then observed to proceed with extremely
high stereoselectivity. The observed stereochemistry for each of
the intramolecular epoxidations was consistent with a spiro-
transition state. This represents the first experimental evidence
for the transition state geometry in epoxidation by oxazirid-
inium salts and may help in the future rational design of chiral
catalysts. The intramolecular epoxidation process would now
be improved by use of an alternative chiral amine which
leads to higher diastereoselectivity in the imine oxidation and
therefore higher yields of diastereomerically pure oxaziridine.
Scheme 13
The intramolecular epoxidation of the oxaziridine pair 37
and 38 was then undertaken. We were pleased to isolate the
product epoxyaldehydes 39 in excellent yield (Scheme 14). The
Experimental
General details
NMR spectra were recorded on a JEOL EX 270, Bruker WM
250, Bruker AM 400 or Bruker DRX 500 spectrometer using
CDCl3 with tetramethylsilane or CDCl3 (δC = 77.0) as internal
reference. Coupling constants are measured in hertz and are
quoted to the nearest 0.5 Hz. Multiplicities in 13C spectra were
determined by DEPT experiments. Infrared spectra were
recorded on a Perkin-Elmer 1605 FT-IR spectrometer from
4000 to 600 cmϪ1. Mass spectra were recorded at the University
of Nottingham or the EPSRC service at Swansea. Optical
rotations were measured using a JASCO DIP-370 digital
polarimeter. Diethyl ether (referred to throughout as ether) and
tetrahydrofuran (THF) solvents were distilled from sodium
benzophenone ketyl. Dichloromethane, acetonitrile, triethyl-
amine and pyridine were distilled from calcium hydride.
Toluene and benzene were distilled from sodium and DMF
from anhydrous magnesium sulfate. Petrol refers to light petrol-
eum ether of boiling range 40–60 ЊC which was distilled prior
to use. All commercial reagents were used without further
purification unless stated otherwise. Flash column chrom-
atography was performed using Merck Kieselgel 60 (230–400
mesh). Where appropriate the silica gel was neutralised by
flushing with a 1% solution of triethylamine. Thin layer
chromatography was performed using precoated glass-backed
Scheme 14
improved recovery compared with previous reactions with
variable yields may be due to the methylation reactions being
conducted on a larger scale so that proportionately less material
was lost on isolation and purification. The product epoxyalde-
hydes were then easily transformed into the corresponding
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plates (Merck Kieselgel 60 F254) and visualised by ultraviolet
light and/or acidic ceric ammonium molybdate or potassium
permanganate as appropriate.
acetate 10 : 1); νmax (film) 2961, 1720, 1459, 1403, 1372 and 737
cmϪ1; δH (400 MHz, CDCl ) 5.36–5.29 (1H, m, HC᎐CH), 5.09–
᎐
3
5.04 (1H, m, HC᎐CH), 4.06 (2H, s, ClCH C᎐O), 2.56 (2H, t,
᎐
᎐
2
Chiral HPLC determinations of enantiomeric excess of
28a,d,e and 40 were performed on an HP Series 1100 with diode
array detection at 254 nm; Chiracel OD column; eluent: 0.1%
isopropyl alcohol–hexane; flow rate: 0.6 ml minϪ1. Retention
times: 28a, 51.5 min; ent-28a, 55.2 min; 28e, 54.2 min; ent-28e,
58.8 min; 28d, 52.4 min; ent-28d, 57.1 min; 40, 94.3 min; ent-40,
99.1 min.
J 7.5 Hz, CH CH C᎐O), 2.46–2.40 [1H, m, CH CH(CH )],
᎐
2 2 2 3
2.06–2.00 (2H, m, CH CH᎐), 1.63–1.52 [4H, m, CH CH -
᎐
2
2
2
CH(CH3)], 1.37–1.17 (2H, m, CH2CH3), 0.96 (3H, t, J 7.5 Hz,
CH2CH3), 0.94 [3H, d, J 6.5 Hz, CH(CH3)]; δC (68 MHz,
CDCl3) 202.2 (s), 134.9 (d), 130.7 (d), 48.2 (t), 39.8 (t), 36.8 (t),
31.5 (d), 21.7 (t), 21.7 (t), 21.4 (q), 20.8 (t), 14.5 (q); m/z (CIϩ)
217 (M ϩ H), 201, 183, 167, 149, 135, 123, 110, 95.
Ketones 3–5 were prepared as previously described.12
Oxone® epoxidation of unsaturated ketones 3–8
(Z )-1-Chloro-4-methylnon-5-en-2-one 6
To a solution of ketone (0.30 mmol) stirred in acetonitrile (22.5
ml) was added an aqueous 0.4 mM Na2EDTA solution (15 ml).
To this homogeneous solution was added a mixture of Oxone®
(1.84 g, 3.0 mmol) and NaHCO3 (391 mg, 4.65 mmol) in
portions over 30 minutes. The reaction was followed to comple-
tion by TLC, poured into water (20 ml) and extracted with
dichloromethane (3 × 20 ml). The combined organic extracts
were dried (MgSO4), filtered and the solvent removed under
reduced pressure to give a yellow oil. Epoxide diastereomeric
ratios were then determined by 1H NMR integration.
To a stirred solution of diisopropylamine (0.218 ml, 1.56 mmol)
in THF (2.0 ml) at 0 ЊC under nitrogen was added n-butyl-
lithium (2.2 M in THF, 0.707 ml, 1.56 mmol) over 10 minutes.
The solution was cooled to Ϫ78 ЊC and (Z)-4-methylnon-5-en-2-
one 312 (200 mg, 1.29 mmol) added dropwise in THF (1.5 ml).
After 40 minutes, freshly distilled chlorotrimethylsilane (0.181
ml, 1.42 mmol) was added and stirring continued for 20 minutes
before the reaction was allowed to warm to room temperature
for 1 hour. The reaction was poured into half-saturated
aqueous NaHCO3 (5 ml), the mixture extracted with ethyl
acetate (3 × 5 ml) and the combined organics washed consec-
utively with aqueous NaHCO3 and saturated NaCl and
then dried (Na2SO4). Filtration and removal of solvent under
reduced pressure gave the TMS enol ether as a yellow oil. To a
mixture of N-chlorosuccinimide (260 mg, 1.94 mmol) and
sodium acetate (182 mg, 2.22 mmol) in acetone (5.9 ml) and
water (1.2 ml) at Ϫ5 ЊC was added the enol ether in acetone
(1.5 ml) over 5 minutes. After 1.5 hours 20% aqueous NaHSO3
solution (3 ml) and saturated NaCl (6 ml) were added and
the mixture extracted with dichloromethane. The combined
organic extracts were evaporated under reduced pressure,
dissolved in dichloromethane, washed with saturated aqueous
NaHCO3, dried (Na2SO4) and filtered. Removal of solvent
under reduced pressure gave a yellow oil. Flash column
chromatography (petrol–ethyl acetate 15 : 1) yielded the
α-chloroketone (140 mg, 58%) as a colourless oil, Rf 0.51
(petrol–ethyl acetate 10 : 1); νmax (film) 2959, 1732, 1456, 1402
and 735 cmϪ1; δH (400 MHz, CDCl3) 5.37–5.31 (1H, m,
HC᎐CH), 5.17–5.12 (1H, m, HC᎐CH), 4.05 (2H, s, ClCH C᎐
(Z )-9-Methyldeca-4,8-dien-1-ol 9
To a stirred suspension of magnesium (1.32 g, 54.1 mmol) in
ether (25 ml) was added 1-bromo-4-methylpent-3-ene25 (8.54 g,
52.6 mmol) dropwise under nitrogen and stirring was continued
for 2 hours. The ethereal solution was added dropwise to
(PPh3)2NiCl2 (2.07 g, 3.15 mmol) in toluene (125 ml) and the
mixture stirred for 30 minutes. Removal of ether in vacuo was
followed by slow addition of 3,4-dihydro-2H-pyran (4.08 g,
48.5 mmol) after which the mixture was stirred for 4 days. The
reaction was quenched by being poured into a vigorously
stirred saturated NH4Cl solution, the layers separated and the
aqueous layer extracted with ether (3 × 150 ml). The combined
organics were dried (MgSO4) and filtered and the solvent
removed under reduced pressure to a yellow oil. Flash column
chromatography (petrol–ethyl acetate 2 : 1) yielded the alcohol 9
(1.3 g, 16%) as a colourless oil, Rf 0.27 (petrol–ethyl acetate
2 : 1); νmax (film) 3326 (br), 2927, 1673, 1652, 1450, 1376 and
1060 cmϪ1; δH (270 MHz, CDCl ) 5.45–5.36 (2H, m, HC᎐CH),
᎐
᎐
᎐
᎐
2
3
O), 3.08–3.04 [1H, m, CH2CH(CH3)], 2.52 (2H, d, J 7.0 Hz,
CH C᎐O), 2.04–2.01 (2H, m, CH CH᎐), 1.38–1.35 (2H, m,
5.15–5.10 [1H, m, HC᎐C(CH ) ], 3.66 (2H, t, J 6.5 Hz,
᎐
3 2
CH OH), 2.21–2.02 (6H, m, 3 CH CH᎐), 1.69 (3H, s, CH ),
᎐
᎐
᎐
2
2
2
2
3
CH2CH3), 1.00 [3H, d, J 6.5 Hz, CH(CH3)], 0.90 (3H, t, J 7.5
Hz, CH2CH3); δC (68 MHz, CDCl3) 201.6 (s), 133.5 (d), 130.0
(d), 48.8 (t), 47.1 (t), 29.4 (t), 28.3 (d), 22.8 (t), 21.2 (q), 13.8 (q);
m/z (CIϩ) 189 (M ϩ H), 188, 173, 153, 145, 139, 111, 97;
observed 188.0964. C10H1735ClO (Mϩ) requires 188.0968.
1.66–1.63 (2H, m, CH2CH2CH2), 1.61 (3H, s, CH3), 1.43–1.29
(1H, m, OH); δC (68 MHz, CDCl3) 133.1 (s), 131.7 (s), 130.5 (d),
125.4 (d), 64.1 (t), 34.0 (t), 29.5 (t), 28.9 (t), 27.1 (q), 25.0 (t),
19.1 (q); m/z (EIϩ) 168 (Mϩ), 153, 125, 109, 96, 81, 69; observed
168.1513. C11H20O (Mϩ) requires 168.1514.
(Z )-1-Chloro-5-methyldec-6-en-2-one 7
(Z )-10-Methylundeca-5,9-dien-2-one 10
This was prepared from 412 using the procedure described
above to give 7 (54%) as a colourless oil, Rf 0.54 (petrol–ethyl
acetate 10 : 1); νmax (film) 2957, 1720, 1456, 1402, 1374 and 738
cmϪ1; δH (250 MHz, CDCl ) 5.38–5.31 (1H, m, HC᎐CH), 5.11–
To a solution of (Z)-9-methyldeca-4,8-dien-1-ol 9 (700 mg, 4.16
mmol) in DMF (23 ml) under nitrogen was added pyridinium
dichromate (6.26 g, 16.6 mmol) in a single portion. After 20
hours the reaction was poured into water (50 ml) and extracted
with ether (4 × 25 ml). The combined organics were washed
with brine, dried (MgSO4) and filtered and the solvents
removed under reduced pressure to afford a pale green oil.
Flash column chromatography (petrol–ethyl acetate 1 : 1)
yielded (Z)-9-methyldeca-4,8-dienoic acid as a white solid (595
mg, 79%), Rf 0.57 (petrol–ethyl acetate 1 : 1); νmax (film) 2918
(br), 1711, 1435, 1282 and 938 cmϪ1; δH (250 MHz, CDCl3)
᎐
3
5.02 (1H, m, HC᎐CH), 4.06 (2H, s, ClCH C᎐O), 2.58–2.51 (2H,
᎐
᎐
2
d, J 7.0 Hz, CH CH C᎐O), 2.47–2.40 [1H, m, CH CH(CH )],
᎐
2
2
2
3
2.04–1.93 (2H, m, CH CH᎐), 1.70–1.64 [1H, m, CHHCH-
᎐
2
(CH3)], 1.52–1.43 [1H, m, CHHCH(CH3)], 1.36 (2H, q, J 7.0
Hz, CH2CH3), 0.96 [3H, d, J 6.5 Hz, CH(CH3)], 0.90 (3H, t,
J 7.0 Hz, CH2CH3); δC (68 MHz, CDCl3) 202.6 (s), 134.9 (d),
129.7 (d), 48.2 (t), 37.9 (t), 31.1 (t), 30.8 (d), 29.5 (t), 22.9 (t),
21.4 (q), 13.8 (q); m/z (CIϩ) 203 (M ϩ H), 202, 185, 167,
153, 110, 95; observed 202.1119. C11H1935ClO (Mϩ) requires
202.1124.
5.47–5.37 (2H, m, HC᎐CH), 5.14–5.11 [1H, m, HC᎐C(CH ) ],
᎐
᎐
3
2
2.40–2.34 (4H, m, HO CCH CH CH᎐), 2.10–2.02 (4H, m,
᎐
2
2
2
᎐CHCH CH CH᎐), 1.69 (3H, s, CH ), 1.61 (3H, s, CH ); δ (68
᎐
᎐
2
2
3
3
C
MHz, CDCl3) 178.3 (s), 132.0 (s), 131.3 (d), 127.2 (d), 123.9 (d),
33.9 (t), 28.0 (t), 27.5 (t), 25.7 (q), 22.6 (t), 17.7 (q); m/z (EIϩ)
182 (Mϩ), 150, 139, 122, 69; observed 182.1307. C11H18O2 (Mϩ)
requires 182.1307.
(Z )-1-Chloro-6-methylundec-7-en-2-one 8
This was prepared from 512 using the procedure described
above to give 8 (47%) as a colourless oil, Rf 0.56 (petrol–ethyl
J. Chem. Soc., Perkin Trans. 1, 2001, 2861–2873
2867

View Article Online
To a solution of the acid (223 mg, 1.22 mmol) in THF (10 ml)
under nitrogen at 0 ЊC was added rapidly methyllithium (1 M in
THF, 4.89 ml, 4.89 mmol). After 2.5 hours, the reaction was
quenched with freshly distilled chlorotrimethylsilane (3.05 ml,
24.4 ml) and allowed to warm to room temperature. 1 M HCl
(10 ml) was then added and the solution stirred for 30 minutes.
The mixture was extracted with ether (3 × 20 ml) and the com-
bined organics washed with water, dried (MgSO4), filtered and
solvents removed under reduced pressure to a yellow oil. Flash
column chromatography (petrol–ethyl acetate 15 : 1) yielded the
ketone 10 (140 mg, 64%) as a colourless oil, Rf 0.44 (petrol–ethyl
with dichloromethane (3 × 50 ml). The combined organic
extracts were dried (MgSO4), filtered and the solvent removed
under reduced pressure to give a yellow oil. Flash column
chromatography (petrol–ethyl acetate 10 : 1 or petrol–dichloro-
methane 1 : 1) on base-washed silica yielded the oxaziridine.
2-Benzyl-3-(4Ј-methylpent-3Ј-enyl)oxaziridine 14a. Colour-
less oil (73%), Rf 0.42 (petrol–ethyl acetate 10 : 1); νmax (film)
2916, 1640, 1496 and 1453 cmϪ1; δH (270 MHz, CDCl3) 7.37–
7.29 (5H, m, Ph), 5.11–5.05 [1H, m, HC᎐C(CH ) ], 3.90 [1H, t,
᎐
3
2
J 5.0 Hz, HCN(O)], 3.83 (2H, s, PhCH2N), 2.14–2.06 [2H, m,
acetate 10 : 1); νmax (film) 2916, 1718, 1446, 1362 and 1158 cmϪ1
δH (270 MHz, CDCl ) 5.45–5.27 (2H, m, HC᎐CH), 5.12–5.09
;
CH CH᎐C(CH ) ], 1.74–1.67 [2H, m, CH CHN(O)], 1.67 (3H,
᎐
2
3
2
2
s, CH3), 1.58 (3H, s, CH3); δC (68 MHz, CDCl3) 135.5 (s), 132.7
(s), 128.8 (d), 128.6 (d), 127.8 (d), 122.7 (d), 81.8 (d), 65.6 (t),
32.3 (t), 25.6 (q), 22.7 (t), 17.6 (q); m/z (CIϩ) 218 (M ϩ H), 200,
174, 159, 146, 132, 126, 106, 91; observed: 218.1544. C14H20NO
(M ϩ H) requires 218.1545.
᎐
3
[1H, m, HC᎐C(CH ) ], 2.50–2.45 (2H, m, CH C᎐O), 2.34–2.27
᎐
᎐
2
3
2
(2H, m, CH CH᎐), 2.14 (3H, s, CH C᎐O), 2.11–2.01 (4H, m,
᎐
᎐
3
2
᎐CHCH CH CH᎐), 1.69 (3H, s, CH ), 1.60 (3H, s, CH ); δ (68
᎐
᎐
2
2
3
3
C
MHz, CDCl3) 208.6 (s), 131.5 (s), 130.8 (d), 127.9 (d), 124.0 (d),
43.6 (t), 30.0 (q), 28.1 (t), 27.5 (t), 25.7 (q), 21.7 (t), 17.7 (q); m/z
(EIϩ) 180 (Mϩ), 162, 137, 122, 111, 69; observed 180.1512.
C12H20O (Mϩ) requires 180.1514.
2-Benzyl-3-(5Ј-methylhex-4Ј-enyl)oxaziridine 14b. Colourless
oil (60%), Rf 0.45 (petrol–ethyl acetate 10 : 1) (Found C: 77.81;
H: 9.40; N: 6.10. C15H21NO requires C: 77.88; H: 9.15; N:
6.05%); νmax (film) 2925, 1644, 1496, 1456 and 1376 cmϪ1; δH
(270 MHz, CDCl3) 7.37–7.30 (5H, m, Ph), 5.09–5.03 [1H, m,
(Z )-1-Chloro-10-methylundeca-5,9-dien-2-one 11
This was prepared from 10 using the procedure described above
for the preparation of 6, to give 11 (38%) as a colourless oil, Rf
0.45 (petrol–ethyl acetate 10 : 1); νmax (film) 2926, 1718, 1456
and 1400 cmϪ1; δH (270 MHz, CDCl3) 5.45–5.27 (2H, m,
HC᎐C(CH ) ], 3.90 [1H, t, J 5.0 Hz, HCN(O)], 3.87 (1H, d,
᎐
3
2
J 13.0 Hz, PhCHHN), 3.81 (1H, d, J 13.0 Hz, PhCHHN),
2.03–1.95 [2H, m, CH2CH᎐C(CH3)2], 1.70–1.59 [5H, m, CH2-
᎐
CHN(O) and CH3], 1.57 (3H, s, CH3), 1.47–1.40 (2H, m,
CH2CH2CH2); δC (68 MHz, CDCl3) 135.6 (s), 132.5 (s), 129.1
(d), 128.8 (d), 128.1 (d), 124.0 (d), 82.3 (d), 65.8 (t), 32.0 (t), 27.8
(t), 25.9 (q), 24.4 (t), 17.9 (q); m/z (CIϩ) 232 (M ϩ H), 214, 174,
146, 132, 106, 91; observed: 232.1709. C15H22NO (M ϩ H)
requires 232.1701.
HC᎐CH), 5.12–5.09 [1H, m, HC᎐C(CH ) ], 4.07 (2H, s,
᎐
᎐
3
2
ClCH C᎐O), 2.67–2.61 (2H, m, CH CH C᎐O), 2.40–2.32 (2H,
᎐
᎐
2
2
2
m, CH CH᎐), 2.09–2.02 (4H, m, ᎐CHCH CH CH᎐), 1.69 (3H,
᎐
᎐
᎐
2
2
2
m, CH3), 1.61 (3H, s, CH3); δC (68 MHz, CDCl3) 202.3 (s), 131.7
(s), 131.4 (d), 127.2 (d), 123.9 (d), 48.2 (t), 39.7 (t), 28.0 (t), 27.4
(t), 25.7 (q), 21.5 (t), 17.7 (q); m/z (EIϩ) 214 (Mϩ), 145, 122,
107, 84, 69; observed 214.1125. C12H1935ClO (Mϩ) requires
214.1124.
2-Benzyl-3-(6Ј-methylhept-5Ј-enyl)oxaziridine 14c. Colourless
oil (64%), Rf 0.47 (petrol–ethyl acetate 10 : 1); νmax (film) 2926,
1643, 1452, 1377, 1310 and 969 cmϪ1; δH (400 MHz, CDCl3)
Oxone® epoxidation of unsaturated ketones 10 and 11
7.36–7.31 (5H, m, Ph), 5.07–5.04 [1H, m, HC᎐C(CH ) ], 3.89
᎐
3
2
To a stirred solution of ketone (0.30 mmol) in acetonitrile (4.5
ml) was added an aqueous 0.4 mM Na2EDTA solution (3.0 ml).
To this homogeneous solution was added a mixture of Oxone®
(184 mg, 0.30 mmol) and NaHCO3 (39 mg, 0.465 mmol) in
portions over 30 minutes. The reaction was followed to com-
pletion by TLC, poured into water (20 ml) and extracted with
dichloromethane (3 × 20 ml). The combined organic extracts
were dried (MgSO4), filtered and the solvent removed under
reduced pressure to give a yellow oil. Epoxide regioisomeric
ratios were determined by 1H NMR integration.
[1H, t, J 4.5 Hz, HCN(O)], 3.88 (1H, d, J 13.0 Hz, PhCHHN),
3.79 (1H, d, J 13.0 Hz, PhCHHN), 1.97–1.91 [2H, m, CH CH᎐
᎐
2
C(CH3)2], 1.67 (3H, d, J 1.0 Hz, CH3), 1.65–1.62 [2H, m,
CH2CHN(O)], 1.57 (3H, s, CH3), 1.43–1.29 (4H, m, CH2CH2-
CH2CH2); δC (68 MHz, CDCl3) 135.4 (s), 131.6 (s), 128.9 (d),
128.6 (d), 127.9 (d), 124.2 (d), 82.2 (d), 65.6 (t), 32.1 (t), 29.5 (t),
27.8 (t), 25.7 (q), 23.7 (t), 17.7 (q); m/z (EIϩ) 245 (Mϩ), 192,
149, 105, 91; observed: 245.1778. C16H23NO (Mϩ) requires
245.1780.
Unsaturated aldehydes 12a,26 12b,27 12c,28 12d,29 12e,30 12f,30
19,31 and (Z)-oct-5-enal32 were prepared according to known
procedures and gave spectroscopic data in accord with those in
the literature.
2-Benzyl-3-(3Ј-butylbut-3Ј-enyl)oxaziridine 14d. Colourless
oil (72%), Rf 0.42 (petrol–ethyl acetate 10:1) (Found C: 78.17;
H: 9.74; N: 5.66. C16H23NO requires C: 78.32; H: 9.45; N:
5.71%); νmax (film) 2929, 1644, 1496, 1454, 1422 and 890 cmϪ1
;
δH (250 MHz, CDCl3) 7.36–7.31 (5H, m, Ph), 4.72 (1H, s,
HHC᎐C), 4.69 (1H, s, HHC᎐C), 3.93 [1H, t, J 5.0 Hz,
General procedure for preparation of unsaturated imines 13
᎐
᎐
HCN(O)], 3.83 (2H, s, PhCH2N), 2.15–2.09 (2H, m, one of
CH C᎐), 2.02–1.96 (2H, m, one of CH C᎐), 1.86–1.76 [2H, m,
To a stirred solution of unsaturated aldehyde (5.0 mmol) in
dichloromethane (5.0 ml) under nitrogen was added benzyl-
amine (536 mg, 5.0 mmol) followed by powdered 4 Å molecular
sieves (500 mg). The reaction was stirred for 15 hours, filtered
and the sieves washed with dichloromethane. The solvent was
removed under reduced pressure to yield the crude imine as a
yellow oil which was carried onto the next stage without purifi-
᎐
᎐
2
2
CH2CHN(O)], 1.42–1.26 (4H, m, CH2CH2CH3), 0.89 (3H, t,
J 7.0 Hz, CH3); δC (68 MHz, CDCl3) 148.4 (s), 135.5 (s), 128.9
(d), 128.6 (d), 127.9 (d), 109.4 (t), 81.8 (d), 65.6 (t), 35.7 (t), 30.3
(t), 30.3 (t), 29.9 (t), 22.4(t), 14.0 (q); m/z (CIϩ) 246 (M ϩ H),
229, 228, 216, 202, 174, 154, 141, 91; observed: 246.1859.
C16H24NO (M ϩ H) requires 246.1858.
1
cation. In all cases H NMR showed a single imine, presumed
to be the E-isomer.
(E )-2-Benzyl-3-hept-3Ј-enyloxaziridine 14e. Colourless oil
(73%), Rf 0.52 (petrol–ethyl acetate 10 : 1); νmax (film) 2958,
1598, 1496, 1454 and 970 cmϪ1; δH (270 MHz, CDCl3) 7.37–7.31
General procedure for preparation of unsaturated oxaziridines
To a stirred solution of imine (4.0 mmol) in acetonitrile (60 ml)
was added deionised water (40 ml). To this homogeneous
solution was added a mixture of Oxone® (1.48 g, 4.8 mmol
KHSO5) and NaHCO3 (627 mg, 7.46 mmol). The reaction was
stirred for 30 minutes, poured into water (100 ml) and extracted
(5H, m, Ph), 5.44–5.32 (2H, m, HC᎐CH), 3.92 [1H, t, J 5.0 Hz,
᎐
HCN(O)], 3.87 (1H, d, J 13.0 Hz, PhCHHN), 3.79 (1H, d,
J 13.0 Hz, PhCHHN), 2.15–2.08 (2H, m, one of CH CH᎐),
᎐
2
1.97–1.90 (2H, m, one of CH CH᎐), 1.80–1.62 [2H, m, CH -
᎐
2
2
CHN(O)], 1.42–1.28 (2H, m, CH2CH3), 0.88 (3H, t, J 7.5 Hz,
2868
J. Chem. Soc., Perkin Trans. 1, 2001, 2861–2873

View Article Online
CH3); δC (68 MHz, CDCl3) 135.4 (s), 131.4 (d), 128.9 (d), 128.6
(d), 128.4 (d), 127.8 (d), 81.7 (d), 65.6 (t), 34.6 (t), 32.1 (t), 27.2
(t), 22.6 (t), 13.6 (q); m/z (FABϩ) 232 (M ϩ H), 214, 202, 188,
176, 136, 106, 91; observed: 232.1712. C15H22NO (M ϩ H)
requires 232.1701.
MHz, CDCl ) 9.83 (1H, t, 1.5 Hz, HC᎐O), 2.77 [1H, dd, J 7.5,
᎐
3
5.0 Hz, HC(O)C(CH3)2], 2.69–2.63 (2H, m, CH2CHO), 2.03–
1.90 [1H, m, CHHCH(O)C], 1.80–1.67 [1H, m, CHHCH(O)C],
1.32 (3H, s, CH3), 1.30 (3H, s, CH3); δC (68 MHz, CDCl3) 201.6
(d), 63.4 (d), 59.2 (s), 41.1 (t), 25.0 (q), 21.8 (t), 19.0 (q); m/z
(EIϩ) 129 (M ϩ H), 111, 95, 85, 71; observed: 129.0911.
C7H13O2 (M ϩ H) requires 129.0915.
(Z )-2-Benzyl-3-oct-3Ј-enyloxaziridine 14f. Colourless oil
(45%), Rf 0.58 (petrol–ethyl acetate 10 : 1); νmax (film) 2955,
1496, 1454, 1421 and 1030 cmϪ1; δH (270 MHz, CDCl3) 7.37–
4-(3Ј,3Ј-Dimethyloxiranyl)butyraldehyde rac-15b. Colourless
oil (41%), Rf 0.46 (petrol–ethyl acetate 2 : 1); νmax (film) 2960,
1723, 1458, 1378 and 1120 cmϪ1; δH (400 MHz, CDCl3) 9.80
7.30 (5H, m, Ph), 5.49–5.27 (2H, m, HC᎐CH), 3.92 [1H, t, J 5.0
᎐
Hz, HCN(O)], 3.83 (2H, s, PhCH2N), 2.20–2.12 (2H, m, one of
CH CH᎐), 2.03–1.96 (2H, m, one of CH CH᎐), 1.76–1.68 [2H,
(1H, t, J 1.5 Hz, HC᎐O), 2.72 [1H, t, 6.0 Hz, HC(O)C(CH ) ],
᎐
3
2
᎐
᎐
2
2
2.55–2.52 (2H, m, CH2CHO), 1.86–1.70 [2H, m, CH2CH(O)C],
1.67–1.50 (2H, m, CH2CH2CH2), 1.32 (3H, s, CH3), 1.26 (3H, d,
J 1.5 Hz, CH3); δC (68 MHz, CDCl3) 202.0 (d), 63.9 (d), 58.2 (s),
43.4 (t), 28.2 (t), 24.8 (q), 19.1 (t), 18.7 (q); m/z (FABϩ) 143
(M ϩ H), 141, 125, 113, 95; observed: 143.1072. C8H15O2 (M ϩ
H) requires 143.1072.
m, CH2CHN(O)], 1.34–1.29 (4H, m, CH2CH2CH3), 0.92–0.86
(3H, m, CH3); δC (68 MHz, CDCl3) 135.5 (s), 131.2 (d), 128.8
(d), 128.6 (d), 127.8 (d), 127.6 (d), 81.7 (d), 65.6 (t), 32.2 (t), 31.8
(t), 26.9 (t), 22.3 (t), 21.9 (t), 14.0 (q); m/z (FABϩ) 246 (M ϩ H),
230, 216, 202, 154, 136, 120, 107, 91; observed: 246.1853.
C16H24NO (M ϩ H) requires 246.1858.
5-(3Ј,3Ј-Dimethyloxiranyl)pentanal rac-15c. Colourless oil
(55%), Rf 0.20 (petrol–ethyl acetate 5 : 1); νmax (film) 2929, 2720,
1724, 1459, 1378 and 1118 cmϪ1; δH (400 MHz, CDCl3) 9.78
(Z )-3-Oct-3Ј-enyl-2-propyloxaziridine 14g. Colourless oil
(39%), Rf 0.49 (petrol–ethyl acetate 15 : 1) (Found C: 73.27; H:
12.06; N: 6.87. C12H23NO requires C: 73.04; H:11.75; N:
7.10%); νmax (film) 2959, 1654, 1458, 1421 and 1256 cmϪ1
;
(1H, t, J 1.5 Hz, HC᎐O), 2.71 [1H, t, 6.0 Hz, HC(O)C(CH ) ],
᎐
3
2
2.47 (2H, dt, J 7.5, 1.5 Hz, CH2CHO), 1.73–1.67 [2H, m,
CH2CH(O)C], 1.59–1.48 (4H, m, CH2CH2), 1.31 (3H, s, CH3),
1.27 (3H, s, CH3); δC (68 MHz, CDCl3) 202.4 (d), 64.1 (d), 58.2
(s), 43.8 (t), 28.6 (t), 26.1 (t), 24.9 (q), 21.9 (t), 18.7 (q); m/z
(EIϩ) 156 (Mϩ), 138, 113, 109, 98, 85; observed: 156.1155.
C9H16O2 (Mϩ) requires 156.1150.
δH (250 MHz, CDCl ) 5.46–5.36 (2H, m, HC᎐CH), 3.72 [1H, t,
J 5.0 Hz, HCN(O)], 2.79 (1H, dt, J 12.5, 7.5 Hz, CHHN),
2.52 (1H, dt, J 12.5, 7.0 Hz, CHHN), 2.26–2.17 (2H, m, one
᎐
3
of CH CH᎐), 2.08–2.00 (2H, m, one of CH CH᎐), 1.75–1.61
᎐
᎐
2
2
[4H, m, CH2CHN(O) and CH2CH2N], 1.39–1.26 (4H, m,
CH2CH2CH3), 0.99 (3H, t, J 7.5 Hz, CH3), 0.92–0.87 (3H,
m, CH3); δC (68 MHz, CDCl3) 131.2 (d), 127.8 (d), 81.8 (d),
63.6 (t), 32.3 (t), 31.8 (t), 26.9 (t), 22.3 (t), 21.9 (t), 21.3 (t),
14.0 (q), 11.8 (q); m/z (FABϩ) 198 (M ϩ H), 182, 154, 136,
91, 73, 55; observed 198.1862. C12H24NO (M ϩ H) requires
198.1858.
3-(2Ј-Butyloxiranyl)propionaldehyde rac-15d. Colourless oil
(39%), Rf 0.35 (petrol–ethyl acetate 5 : 1); νmax (film) 2932, 2722,
1724, 1458, 1389 and 1142 cmϪ1; δH (250 MHz, CDCl3) 9.77
(1H, s, HC᎐O), 2.62–2.57 [2H, m, H C(O)C], 2.48 (2H, t, J 7.5
᎐
2
Hz, CH2CHO), 2.04 [1H, dt, J 15.0, 7.5 Hz, CHHC(O)], 1.90
[1H, dt, J 15.0, 7.5 Hz, CHHC(O)], 1.69–1.60 (1H, m, CHHPr),
1.52–1.40 (1H, m, CHHPr), 1.38–1.25 (4H, m, CH2CH2CH3),
0.90 (3H, t, J 6.5 Hz, CH3); δC (68 MHz, CDCl3) 201.4 (d), 58.5
(s), 51.9 (t), 38.8 (t), 34.5 (t), 27.0 (t), 25.9 (t), 22.7 (t), 14.0 (q);
m/z (FABϩ) 157 (M ϩ H) 139, 125, 109, 83, 73, 69; observed
157.1223. C9H17O2 (M ϩ H) requires 157.1229.
(Z)-2-Benzyl-3-(8Ј-methylnona-3Ј,7Ј-dienyl)oxaziridine
20.
Colourless oil (47%), Rf 0.51 (petrol–ethyl acetate 10 : 1); νmax
(film) 2924, 1496, 1453, 1376 and 1030 cmϪ1; δH (270 MHz,
CDCl ) 7.37–7.30 (5H, m, Ph), 5.39–5.28 (2H, m, HC᎐CH),
᎐
3
5.15–5.05 [1H, m, HC᎐C(CH ) ], 3.91 [1H, t, J 5.0 Hz,
᎐
3
2
HCN(O)], 3.83 (2H, s, PhCH2N), 2.20–2.12 (2H, m, one of
CH CH᎐), 2.10–1.95 (4H, m, two of CH CH᎐), 1.76–1.71 [2H,
᎐
᎐
2
2
trans-3-(3Ј-Propyloxiranyl)propionaldehyde rac-15e. Colour-
less oil (56%), Rf 0.32 (petrol–ethyl acetate 4 : 1); νmax (film)
2961, 2725, 1724, 1458, 1242, 1048 and 906 cmϪ1; δH (250 MHz,
m, CH2CHN(O)], 1.68 (3H, s, CH3), 1.60 (3H, s, CH3);
δC (68 MHz, CDCl3) 135.5 (s), 131.9 (s), 130.8 (d), 128.8 (d),
128.6 (d), 128.0 (d), 127.8 (d), 124.0 (d), 81.7 (d), 65.6 (t), 32.2
(t), 28.0 (t), 27.4 (t), 25.7 (q), 21.9 (t), 17.7 (q); m/z (CIϩ)
272 (M ϩ H), 256, 242, 228, 214, 202, 188, 174, 159, 149, 136,
121, 106, 91; observed 272.2010. C18H26NO (M ϩ H) requires
272.2014.
CDCl ) 9.81 (1H, t, J 1.0 Hz, HC᎐O), 2.76–2.69 [2H, m,
᎐
3
HC(O)CH], 2.60 (2H, dt, J 7.0, 1.0 Hz, CH2CHO), 2.09–1.96
[1H, m, CHHCH(O)], 1.80–1.60 [1H, m, CHHCH(O)], 1.56–
1.35 (4H, m, CH2CH2CH3), 0.98–0.92 (3H, m, CH3); δC (68
MHz, CDCl3) 201.2 (d), 58.8 (d), 57.4 (d), 40.0 (t), 33.9 (t), 24.5
(t), 19.2 (t), 13.9 (q); m/z (EIϩ) 142 (Mϩ), 125, 113, 101, 99, 87,
71; observed 142.0998. C8H14O2 (Mϩ) requires 142.0994.
General procedure for methylation of oxaziridines and hydrolysis
to epoxyaldehydes
To a stirred solution of oxaziridine (0.25 mmol) in dichloro-
methane (6.0 ml) at 0 ЊC under nitrogen was added dropwise
methyl trifluoromethanesulfonate (0.056 ml, 0.50 mmol). The
reaction was followed by TLC with a further amount of methyl
trifluoromethanesulfonate (0.50 mmol) added every 90 minutes
until reaction was complete. Saturated aqueous NaHCO3
(3.0 ml) was added and the reaction stirred vigorously for 20
minutes before separation and extraction of the aqueous layer
with dichloromethane (3 × 10 ml). The combined organic
extracts were dried (MgSO4), filtered and the solvent removed
under reduced pressure to yield a yellow oil. Flash column
chromatography (petrol–ethyl acetate 5 : 1) yielded the
epoxyaldehyde.
cis-3-(3Ј-Butyloxiranyl)propionaldehyde rac-15f. Colourless
oil (60 and 48%), Rf 0.33 (petrol–ethyl acetate 4 : 1); νmax (film)
2958, 2724, 1723, 1458 and 1389 cmϪ1; δH (270 MHz, CDCl3)
9.84 (1H, t, J 1.0 Hz, HC᎐O), 2.99–2.92 [2H, m, HC(O)CH],
᎐
2.71–2.64 (2H, m, CH2CHO), 2.01–1.88 [1H, m, CHHCH(O)],
1.80–1.66 [1H, m, CHHCH(O)], 1.54–1.30 [6H, m, (CH2)3CH3],
0.93 (3H, t, J 7.0 Hz, CH3); δC (68 MHz, CDCl3) 201.2 (d), 57.6
(d), 56.0 (d), 40.9 (t), 28.6 (t), 27.4 (t), 22.6 (t), 20.6 (t), 14.0 (q);
m/z (FABϩ) 157 (M ϩ H), 139, 127, 121, 111, 99, 81, 69;
observed 157.1223. C9H17O2 (M ϩ H) requires 157.1229.
cis-3-[3Ј-(4Љ-methylpent-3Љ-enyl)oxiranyl]propionaldehyde 21.
Colourless oil (48%), Rf 0.14 (petrol–ethyl acetate 10 : 1); νmax
(film) 2966, 2724, 1724, 1450 and 1387 cmϪ1; δH (250 MHz,
3-(3Ј,3Ј-Dimethyloxiranyl)propionaldehyde rac-15a. Colour-
less oil (39%), Rf 0.51 (petrol–ethyl acetate 1 : 1); νmax (film)
2965, 2728, 1724, 1458, 1380, 1252, 1124 and 916 cmϪ1; δH (270
CDCl3) 9.83 (1H, s, HC᎐O), 5.14 [1H, t,
J
6.5 Hz,
᎐
HC᎐C(CH ) ], 2.97–2.94 [2H, m, HC(O)CH], 2.69–2.63 (2H,
᎐
3
2
m, CH CHO), 2.17–2.03 [2H, m, CH CHC᎐C(CH ) ], 2.00–
᎐
2
2
3 2
J. Chem. Soc., Perkin Trans. 1, 2001, 2861–2873
2869

View Article Online
1.87 [2H, m, one of CH2CH(O)], 1.80–1.62 [2H, m, one of
CH2CH(O)], 1.70 (3H, s, CH3), 1.62 (3H, s, CH3); δC (68 MHz,
CDCl3) 201.1 (s), 132.6 (s), 123.1 (d), 57.2 (d), 56.1 (d), 40.9 (t),
27.9 (t), 25.7 (q), 25.0 (t), 20.6 (t), 17.7 (q); m/z (EIϩ) 182 (Mϩ),
164, 138, 96, 82; observed 182.1306. C11H18O2 (Mϩ) requires
182.1307.
Preparation of oxaziridines 23, 24, 37 and 38
The diastereomeric unsaturated oxaziridines, prepared follow-
ing the general procedure described above for 14, were
separated by flash column chromatography (petrol–ethyl
acetate or petrol–dichloromethane) on base-washed silica and
gave the following data.
5-Methylhex-4-en-1-ol benzyl ether 16
(2R,3R,1ЈS)-3-(4Љ-Methylpent-3Љ-enyl)-2-(1Ј-phenylethyl)-
oxaziridine 23a. Colourless oil (22%), Rf 0.38 (petrol–
dichloromethane 1 : 1); [α]2D5 Ϫ36.5 (c 1.0, CHCl3); νmax (film)
2970, 1602, 1494, 1452, 1374 and 913 cmϪ1; δH (400 MHz,
Sodium hydride as a 60% dispersion in oil (168 mg, 4.20 mmol)
was washed with hexane, triturated and dried over a stream of
nitrogen. DMF (1.0 ml) was added and the solution cooled to
0 ЊC. To this was added dropwise 5-methylhex-4-en-1-ol33 (400
mg, 3.50 mmol) in DMF (0.50 ml) followed, after 10 minutes,
by tetrabutylammonium iodide (65 mg, 0.176 mmol) in DMF
(0.50 ml) and benzyl bromide (0.46 ml, 3.85 mmol). After 30
minutes the reaction was quenched by addition of water
followed by saturated NH4Cl before separation and extraction
of the aqueous layer with ether (3 × 10 ml). The combined
organic extracts were washed successively with 2M NaOH,
water and brine and dried (MgSO4). Filtration and removal of
solvent under reduced pressure gave a yellow oil. Flash column
chromatography (petrol–ethyl acetate 15 : 1) yielded the benzyl
ether 16 (622 mg, 87%) as a colourless oil, Rf 0.58 (10 : 1 petrol–
EtOAc); νmax (film) 2926, 1603, 1495, 1453, 1376, 1363 and 1102
cmϪ1; δH (270 MHz, CDCl3) 7.35–7.24 (5H, m, Ph), 5.14–5.08
CDCl ) 7.36–7.31 (5H, m, Ph), 4.93–4.90 [1H, m, HC᎐
᎐
3
C(CH3)2], 3.81 [1H, t, J 5.0 Hz, HCN(O)], 3.04 [1H, q, J 6.5 Hz,
PhCH(CH )N], 1.93–1.88 [2H, m, CH CH᎐C(CH ) ], 1.71–
᎐
3
2
3 2
1.53 [2H, m, CH2CHN(O)], 1.59 [3H, d, J 6.5 Hz, PhCH-
(CH3)N], 1.58 (3H, s, CH3), 1.46 (3H, s, CH3); δC (68 MHz,
CDCl3) 140.1 (s), 132.6 (s), 128.7 (d), 128.0 (d), 127.3 (d), 122.6
(d), 81.7 (d), 70.9 (d), 32.5 (t), 25.6 (q), 22.7 (t), 21.6 (q), 17.5
(q); m/z (EIϩ) 231 (Mϩ), 213, 171, 149, 119, 105, 77; observed:
231.1622. C15H21NO (Mϩ) requires 231.1623.
(2S,3S,1ЈS)-3-(4Љ-Methylpent-3Љ-enyl)-2-(1Ј-phenylethyl)-
oxaziridine 24a. Colourless oil (14%), Rf 0.46 (petrol–
dichloromethane 1 : 1); [α]2D5 Ϫ90.5 (c 1.0, CHCl3) (Found C:
77.86; H: 9.30; N: 5.73. C15H21NO requires C: 77.88; H: 9.15; N:
6.05%); νmax (film) 2922, 1495, 1447, 1374 cmϪ1; δH (400 MHz,
[1H, m, HC᎐C(CH ) ], 4.50 (2H, s, PhCH O), 3.46 (2H, t, J 6.5
᎐
3
2
2
CDCl ) 7.43–7.27 (5H, m, Ph), 5.18–5.15 [1H, m, HC᎐
᎐
3
Hz, CH OCH Ph), 2.11–2.03 (2H, m, CH CH᎐C), 1.68 (3H, d,
᎐
2
2
2
C(CH3)2], 3.86 [1H, t, J 5.0 Hz, HCN(O)], 3.14 [1H, q, J 7.0 Hz,
PhCH(CH3)N], 2.23–2.17 [2H, m, CH2CHC(CH3)2], 1.84–1.70
[2H, m, CH2CHN(O)], 1.71 (3H, s, CH3), 1.64 (3H, s, CH3),
1.44 [3H, d, J 7.0 Hz, PhCH(CH3)N]; δC (68 MHz, CDCl3)
142.1 (s), 132.8 (s), 128.5 (d), 127.5 (d), 126.8 (d), 122.9 (d), 82.0
(d), 69.7 (d), 32.6 (t), 25.7 (q), 22.9 (t), 19.4 (q), 17.8 (q); m/z
(EIϩ) 231 (Mϩ), 215, 171, 149, 119, 105, 77; observed 231.1625.
C15H21NO (Mϩ) requires 231.1623.
J 1.5 Hz, CH3), 1.65–1.58 (2H, m, CH2CH2CH2), 1.60 (3H, s,
CH3); δC (68 MHz, CDCl3) 139.2 (s), 132.4 (s), 128.8 (d), 128.1
(d), 127.9 (d), 124.4 (d), 73.3 (t), 70.4 (t), 30.3 (t), 26.2 (q), 25.1
(t), 18.1 (q); m/z (EIϩ) 204 (Mϩ), 161, 113, 91, 69; observed:
204.1511. C14H20O (Mϩ) requires 204.1514.
7-Methyloct-6-en-1-ol benzyl ether 17
Prepared from the alcohol following the procedure described
above for 16. Colourless oil (70%), Rf 0.70 (petrol–ethyl acetate
10 : 1); νmax (film) 2929, 1496, 1453, 1362 and 1104 cmϪ1; δH (400
MHz, CDCl3) 7.36–7.28 (5H, m, Ph), 5.13 [1H, t, J 1.5 Hz,
(2R,3R,1ЈS,3ЉE )-3-(Hept-3Љ-enyl)-2-(1Ј-phenylethyl)-
oxaziridine 23e. Colourless oil (21%), Rf 0.48 (petrol–
dichloromethane 1 : 1); [α]2D0 Ϫ40.0 (c 0.72, CHCl3); νmax (film)
2958, 1494, 1452, 1373, 970, 761 and 701 cmϪ1; δH (400 MHz,
HC᎐C(CH ) ], 4.52 (2H, s, PhCH O), 3.48 (2H, t, J 6.5 Hz,
᎐
3
2
2
CDCl ) 7.38–7.31 (5H, m, Ph), 5.23–5.13 (2H, m, HC᎐CH),
CH OCH Ph), 2.02–1.98 (2H, m, CH CH᎐C), 1.70 (3H, d,
᎐
3
᎐
2
2
2
3.82 [1H, dd, J 5.5, 4.5 Hz, HCN(O)], 3.03 [1H, q, J 6.5 Hz,
J 1.0 Hz, CH3), 1.67–1.62 (2H, m, one of CH2), 1.61 (3H, s,
CH3), 1.40–1.34 (4H, m, two of CH2); δC (68 MHz, CDCl3)
138.7 (s), 131.3 (s), 128.3 (d), 127.8 (d), 127.5 (d), 124.7 (d), 72.9
(t), 70.5 (t), 29.7 (t), 29.7 (t), 28.0 (t), 25.9 (q), 25.7 (t), 17.7 (q);
m/z (EIϩ) 232 (Mϩ), 141, 123, 91; observed: 232.1821. C16H24O
(Mϩ) requires 232.1827.
PhCH(CH )N], 1.97–1.83 (4H, m, 2 CH CH᎐), 1.69–1.64 [1H,
᎐
3
2
m, CHHCHN(O)], 1.59 [3H, d, J 6.5 Hz, PhCH(CH3)N], 1.56–
1.50 [1H, m, CHHCHN(O)], 1.32–1.24 (2H, m, CH2CH3), 0.84
(3H, t, J 7.5 Hz, CH2CH3); δC (68 MHz, CDCl3) 140.5 (s), 131.8
(d), 129.2 (d), 128.7 (d), 128.5 (d), 127.8 (d), 81.9 (d), 71.4 (d),
35.0 (t), 32.7 (t), 27.6 (t), 23.0 (t), 22.0 (q), 14.1 (q); m/z (CIϩ)
245 (Mϩ), 230, 140, 120, 105, 77; observed: 245.1775. C16H23NO
(Mϩ) requires 245.1780.
(4Z )-7-(3,3-Dimethyloxiranyl)hept-4-en-1-ol 18
To a stirred solution of (Z)-9-methyldeca-4,8-dien-1-ol 9 (25
mg, 0.149 mmol) in dichloromethane (3.8 ml) at 0 ЊC was added
3-chloroperbenzoic acid (82%, 31.2 mg, 0.149 mmol). After
45 minutes the reaction was quenched by addition of saturated
aqueous sodium bisulfite (1.0 ml). The organic layer was
washed with water, saturated aqueous NaHCO3 and brine
before being dried (MgSO4), filtered and the solvent removed
under reduced pressure. Flash column chromatography (petrol–
ethyl acetate 1 : 1) yielded dienol 9 (3.5 mg, 14% recovery) and
the epoxy alcohol 18 (20.5 mg, 75%) as colourless oils. Data for
18: Rf 0.43 (petrol–ethyl acetate 1 : 1); νmax (film) 3430 (br),
2929, 1654, 1457, 1379, 1119 and 1060 cmϪ1; δH (270 MHz,
CDCl ) 5.49–5.40 (2H, m, HC᎐CH), 3.65 (2H, t, 6.5 Hz,
(2S,3S,1ЈS,3ЉE )-3-(Hept-3Љ-enyl)-2-(1Ј-phenylethyl)-
oxaziridine 24e. Colourless oil (15%), Rf 0.57 (petrol–
dichloromethane 1 : 1); [α]2D0 Ϫ85.0 (c 0.72, CHCl3); νmax (film)
2927, 1685, 1495, 1448, 1360, 969, 758 and 699 cmϪ1; δH (400
MHz, CDCl ) 7.42–7.27 (5H, m, Ph), 5.54–5.41 (2H, m, HC᎐
᎐
3
CH), 3.88 [1H, dd, J 5.5, 4.5 Hz, HCN(O)], 3.14 [1H, q, J 7.0
Hz, PhCH(CH )N], 2.25–2.20 (2H, m, CHHCH᎐), 2.01–1.96
᎐
3
(2H, m, CHHCH᎐), 1.87–1.80 [1H, m, CHHCHN(O)], 1.79–
᎐
1.69 [1H, m, CHHCHN(O)], 1.44 [3H, d, J 7.0 Hz, PhCH-
(CH3)N], 1.43–1.31 (2H, m, CH2CH3), 0.89 (3H, t, J 7.5 Hz,
CH2CH3); δC (68 MHz, CDCl3) 142.0 (s), 131.6 (d), 128.5 (d),
128.4 (d), 127.5 (d), 126.8 (d), 81.8 (d), 69.7 (d), 34.6 (t), 32.3 (t),
27.4 (t), 22.6 (t), 19.5. (q), 13.6 (q); m/z (FABϩ) 246 (M ϩ H),
176, 136, 120, 105, 77; observed: 246.1859. C16H24NO (M ϩ H)
requires 246.1858.
᎐
3
CH2OH), 2.75 [1H, t, 6.5 Hz, HC(O)C(CH3)2], 2.27–2.13 (4H,
m, 2CH CHC᎐), 1.78 (1H, s, OH), 1.69–1.56 (4H, m, 2CH ),
᎐
2
2
1.31 (3H, s, CH3), 1.27 (3H, s, CH3); δC (68 MHz, CDCl3) 130.0
(d), 129.1 (d), 64.0 (d), 62.1 (t), 58.6 (s), 32.4 (t), 28.7 (t), 24.8
(q), 24.1 (t), 23.4 (t), 18.7 (q); m/z (FABϩ) 185 (M ϩ H), 154,
136, 121, 109, 95, 81, 69; observed 185.1530. C11H21O2 (M ϩ H)
requires 185.1541.
(2R,3R,1ЈS)-3-(3Љ-Butylbut-3Љ-enyl)-2-(1Ј-phenylethyl)-
oxaziridine 23d. Colourless oil (54%), Rf 0.44 (petrol–ethyl
acetate 15 : 1); [α]2D5 Ϫ26.7 (c 1.07, CHCl3) (Found C: 78.66; H:
2870
J. Chem. Soc., Perkin Trans. 1, 2001, 2861–2873

View Article Online
9.77; N: 5.67. C17H25NO requires C: 78.72; H: 9.71; N: 5.40%);
reaction was complete. Saturated aqueous NaHCO3 (3.0 ml)
νmax (film) 2930, 1645, 1493, 1452, 1372 and 890 cmϪ1; δH (400
was added and the reaction stirred vigorously for 20 minutes
before separation and extraction of the aqueous layer with
dichloromethane (3 × 10 ml). The combined organic extracts
were dried (MgSO4), filtered and the solvent removed under
reduced pressure to yield a yellow oil. Flash column chrom-
atography (petrol–ethyl acetate 5 : 1) yielded the epoxyaldehyde
as a colourless oil (15a 62%; ent-15a 40%; 15e 35%; ent-15e
47%; 15d 55%; ent-15d 70%; 39 81%; ent-39 76%). Epoxyalde-
hydes 15 gave spectroscopic data as described for the racemic
series.
MHz, CDCl ) 7.37–7.29 (5H, m, Ph), 4.61 (1H, s, HHC᎐C),
᎐
3
4.50 (1H, s, HHC᎐C), 3.82 [1H, t, J 5.0 Hz, HCN(O)], 3.04 [1H,
᎐
q, J 6.5 Hz, PhCH(CH )N], 1.93–1.87 (4H, m, 2 CH C᎐), 1.81–
᎐
2
3
1.72 [1H, m, CHHCHN(O)], 1.66–1.58 [1H, m, CHHCHN(O)],
1.59 [3H, d, J 6.5 Hz, PhCH(CH3)N], 1.31–1.21 (4H, m,
CH2CH2CH3), 0.87 (3H, t, J 7.0 Hz, CH2CH3); δC (68 MHz,
CDCl3) 148.1 (s), 140.0 (s), 128.7 (d), 128.0 (d), 127.3 (d), 109.2
(t), 81.5 (d), 70.9 (d), 35.6 (t), 30.3 (t), 30.2 (t), 29.8 (t), 22.4 (t),
21.6 (q), 13.9 (q); m/z (FABϩ) 260 (M ϩ H), 244, 154, 136,
120, 105; observed: 260.2024. C17H26NO (M ϩ H) requires
260.2014.
4-(3Ј-Ethyloxiranyl)butyraldehyde 39 and ent-39. Rf 0.46
(petrol–ethyl acetate 2 : 1); [α]2D6 39 Ϫ2.6 (c 0.97, CHCl3), ent-39
ϩ2.3 (c 1.2, CHCl3); νmax (film) 2970, 2728, 1723, 1458, 1390
and 906 cmϪ1; δH (400 MHz, CDCl3) 9.80 (1H, t, J 1.5 Hz,
(2S,3S,1ЈS)-3-(3Љ-Butylbut-3Љ-enyl)-2-(1Ј-phenylethyl)-
oxaziridine 24d. Colourless oil (15%), Rf 0.39 (petrol–ethyl
acetate 15 : 1); [α]2D5 Ϫ88.9 (c 1.10, CHCl3); νmax (film) 2928,
1644, 1495, 1447, 1370 and 889 cmϪ1; δH (400 MHz, CDCl3)
HC᎐O), 2.95–2.90 [1H, m, HC(O)CH], 2.88 [1H, dd, J 6.5, 4.0
᎐
Hz, HC(O)CH], 2.57–2.52 (2H, m, CH2CHO), 1.87–1.79 [2H,
m, one of CH2CH(O)CH], 1.67–1.59 [2H, m, one of CH2-
CH(O)CH], 1.58–1.48 (2H, m, CH2CH2CH2), 1.04 (3H, t,
J 7.5 Hz, CH3); δC (68 MHz, CDCl3) 202.0 (d), 58.2 (d), 56.8
(d), 43.4 (t), 27.0 (t), 21.1 (t), 19.2 (t), 10.6 (q); m/z (CIϩ) 143
(M ϩ H), 141, 123, 100, 95; observed: 143.1061. C8H15O2
requires 143.1070.
7.42–7.27 (5H, m, Ph), 4.79 (2H, s, H C᎐C), 3.89 [1H, t, J 5.0
᎐
2
Hz, HCN(O)], 3.14 [1H, q, J 7.0 Hz, PhCH(CH3)N], 2.22 (2H,
t, J 8.0 Hz, one of CH C᎐), 2.05 (2H, t, J 7.5 Hz, one of CH C᎐),
᎐
᎐
2
2
1.95–1.80 [2H, m, CH2CHN(O)], 1.44 [3H, d, J 7.0 Hz,
PhCH(CH3)N], 1.44–1.39 (2H, m, CH2CH2CH3), 1.32 (2H, q,
J 7.5 Hz, CH2CH2CH3), 0.91 (3H, t, J 7.5 Hz, CH2CH3); δC (68
MHz, CDCl3) 148.3 (s), 142.0 (s), 128.5 (d), 127.5 (d), 126.8 (d),
109.5 (t), 81.9 (d), 69.7 (d), 35.7 (t), 30.5 (t), 30.5 (t), 29.9 (t),
22.4 (t), 19.4 (q), 14.0 (q); m/z (FABϩ) 260 (M ϩ H), 244, 154,
136, 120, 105; observed: 260.2010. C17H26NO (M ϩ H) requires
260.2014.
Conversion of epoxyaldehydes 15a,e to benzyl ethers 28a,e:
preparation of (3R)-3-(3Ј-benzyloxypropyl)-2,2-dimethyloxirane
28a
To epoxyaldehyde 15a (20 mg, 0.156 mmol), derived from
intramolecular epoxidation of 23a, in dichloromethane (0.50
ml) at 0 ЊC under nitrogen was added dropwise DIBAL-H
(1.5M in toluene, 0.125 ml, 0.188 mmol). After 20 minutes the
reaction was quenched by addition of methanol (0.50 ml) and
saturated aqueous potassium sodium tartrate (0.40 ml) before
being extracted with dichloromethane (3 × 2.0 ml). The com-
bined organics were washed with brine and dried (MgSO4).
Filtration and removal of solvent under reduced pressure gave
the alcohol (20 mg) as a colourless oil which was carried onto
the next stage without purification. Sodium hydride as a 60%
dispersion in oil (3.7 mg, 0.092 mmol) was washed with hexane,
triturated and dried over a stream of nitrogen. DMF (0.50 ml)
was added and the solution cooled to 0 ЊC. To this was added
dropwise the alcohol (10 mg) in DMF (0.50 ml) followed, after
10 minutes, by Bu4NI (1.4 mg, 0.005 mmol) in DMF and benzyl
bromide (0.010 ml, 0.085 mmol). After 1 hour the reaction was
quenched by addition of water followed by saturated NH4Cl
before separation and extraction of the aqueous layer with
ether (3 × 5 ml). The combined organic extracts were washed
successively with 2 M NaOH, water and brine and dried
(MgSO4). Filtration and removal of solvent under reduced
pressure gave a yellow oil. Flash column chromatography
(petrol–ethyl acetate 10 : 1) yielded the benzyl ether 28a as a
colourless oil (5.7 mg, 33%) with spectroscopic data as for 28a
prepared by epoxidation of 16 (vide infra), shown by chiral
HPLC to be of 81% ee. Retention times: 28a, 51.5 min; ent-28a,
55.2 min.
(2R,3R,1ЈS,4ЉZ )-3-(Hept-4Љ-enyl)-2-(1Ј-phenylethyl)-
oxaziridine 37. Colourless oil (55%), Rf 0.45 (petrol–ethyl
acetate 15 : 1); [α]2D6 Ϫ28.7 (c 1.62, CHCl3) (Found C: 78.35; H:
9.59; N: 5.68. C16H23NO requires C: 78.32; H: 9.45; N: 5.70%);
νmax (film) 2931, 1493, 1453, 1372, 762 and 701 cmϪ1; δH (500
MHz, CDCl3) 7.36–7.29 (5H, m, Ph), 5.34–5.29 (1H, m,
HC᎐CH), 5.19–5.14 (1H, m, HC᎐CH), 3.80 [1H, t, J 5.0 Hz,
᎐
᎐
HCN(O)], 3.04 [1H, q, J 6.5 Hz, PhCH(CH3)N], 1.96–1.87 (4H,
m, 2CH C᎐), 1.65–1.60 [1H, m, CHHCHN(O)], 1.59 [3H, d,
᎐
2
J 6.5 Hz, PhCH(CH3)N], 1.53–1.46 [1H, m, CHHCHN(O)],
1.31–1.23 (2H, m, CH2CH2CH2), 0.90 (3H, t, J 7.5 Hz,
CH2CH3); δC (68 MHz, CDCl3) 140.0 (s), 132.3 (d), 128.7 (d),
128.1 (d), 128.1 (d), 127.3 (d), 81.8 (d), 71.0 (d), 31.8 (t), 26.5 (t),
24.0 (t), 21.5 (q), 20.4 (t), 14.3 (q); m/z (EIϩ) 245 (Mϩ), 163,
105, 77; observed: 245.1774. C16H23NO (Mϩ) requires 245.1780.
(2S,3S,1ЈS,4ЉZ )-3-(Hept-4Љ-enyl)-2-(1Ј-phenylethyl)-
oxaziridine 38. Colourless oil (10%), Rf 0.40 (petrol–ethyl acet-
ate 15 : 1); [α]2D6 Ϫ89.9 (c 1.27, CHCl3); νmax (film) 2962, 1495,
1451, 1359, 758 and 698 cmϪ1; δH (500 MHz, CDCl3) 7.42–7.27
(5H, m, Ph), 5.44–5.39 (1H, m, HC᎐CH), 5.35–5.30 (1H, m,
᎐
HC᎐CH), 3.86 [1H, t, J 5.0 Hz, HCN(O)], 3.14 [1H, q, J 7.0 Hz,
᎐
PhCH(CH )N], 2.15–2.10 (2H, m, one of CH C᎐), 2.07–2.00
᎐
3
2
(2H, m, one of CH C᎐), 1.78–1.66 [2H, m, CH CHN(O)],
᎐
2
2
1.59–1.53 (2H, m, CH2CH2CH2), 1.45 [3H, d, J 7.0 Hz, PhCH-
(CH3)N], 0.96 (3H, t, J 7.5 Hz, CH2CH3); δC (68 MHz, CDCl3)
142.0 (s), 132.5 (d), 128.5 (d), 128.1 (d), 127.5 (d), 126.8 (d), 82.1
(d), 69.7 (d), 32.0 (t), 26.8 (t), 24.3 (t), 20.5 (t), 19.5 (q), 14.3
(q); m/z (EIϩ) 245 (Mϩ), 163, 105, 77; observed: 245.1779.
C16H23NO (Mϩ) requires 245.1780.
Epoxyaldehydes ent-15a, 15e and ent-15e were converted to
the corresponding benzyl ethers ent-28a, 28e and ent-28e
respectively following the same procedure. The spectroscopic
data were consistent in all cases with those for epoxy ethers 28a
and 28e prepared by MCPBA and Shi19 epoxidation of the
corresponding alkenes (vide infra). Enantiomeric excesses were
determined by chiral HPLC: ent-28a 94% ee; 28e 93% ee; ent-
28e 92% ee. Retention times: 28e, 54.2 min; ent-28e, 58.8 min.
General procedure for methylation of non-racemic oxaziridines
23, 24 and 37 and hydrolysis to epoxyaldehydes 15 and 39
To a stirred solution of oxaziridine (0.25 mmol) and 2,6-di-tert-
butylpyridine (0.11 ml, 0.50 mmol) in dichloromethane (6.0 ml)
at 0 ЊC under nitrogen was added dropwise methyl trifluoro-
methanesulfonate (0.056 ml, 0.50 mmol). The reaction was
followed by TLC, with a further amount of methyl trifluoro-
methanesulfonate (0.50 mmol) added every 2 hours until
(3R)-3-(3Ј-Benzyloxypropyl)-2,2-dimethyloxirane 28a
To benzyl ether 16 (18.8 mg, 0.092 mmol) in acetonitrile–
dimethoxymethane (1.38 ml, 1 : 2 v/v) were added a 0.05 M
solution of Na2B4O7ؒ10H2O in aqueous Na2EDTA (4 × 10Ϫ4
J. Chem. Soc., Perkin Trans. 1, 2001, 2861–2873
2871

View Article Online
M, 0.92 ml), tetrabutylammonium hydrogen sulfate (1.4 mg,
0.0040 mmol), and ketone 2919 (7.12 mg, 0.028 mmol) with
stirring. The mixture was cooled to Ϫ10ЊC and solutions of
Oxone® (78.2 mg, 0.127 mmol) in aqueous Na2EDTA (4 × 10Ϫ4
M, 0.60 ml) and K2CO3 (73.6 mg, 0.532 mmol) in water (0.60
ml) were added dropwise separately over 2 hours via syringe
pumps. The reaction was quenched by addition of pentane and
water and the mixture extracted with pentane (3 × 10 ml). The
combined organic extracts were washed with brine and dried
(Na2SO4). Filtration and removal of solvent under reduced
pressure gave a yellow oil. Flash column chromatography
(petrol–ethyl acetate 10 : 1) yielded the epoxide 28a (17 mg,
84%) as a colourless oil shown by chiral HPLC to be of 75% ee.
Rf 0.38 (petrol–ethyl acetate 10 : 1); [α]2D4 Ϫ36.5 (c 0.20, CHCl3);
νmax (film) 2958, 1496, 1454, 1378, 1102 and 897 cmϪ1; δH (400
MHz, CDCl3) 7.37–7.27 (5H, m, Ph), 4.51 (2H, s, PhCH2O),
3.58–3.48 (2H, m, CH2OCH2Ph), 2.74 [1H, dd, J 6.5, 6.0 Hz,
CH(O)C(CH3)2], 1.74–1.70 [2H, m, CH2CH(O)C], 1.69–1.56
(2H, m, CH2CH2CH2), 1.30 (3H, s, CH3), 1.26 (3H, s, CH3);
δC (68 MHz, CDCl3) 138.5 (s), 128.7 (d), 128.1 (d), 127.6 (d),
72.9 (t), 69.8 (t), 64.2 (d), 58.2 (s), 26.8 (t), 25.7 (t), 24.9 (q), 18.7
(q); m/z (EIϩ) 220 (Mϩ), 149, 113, 91; observed: 220.1467.
C14H20O2 (Mϩ) requires 220.1463.
hexane, triturated and dried over a stream of nitrogen. DMF
(0.50 ml) was added and the solution cooled to 0 ЊC. To this
was added dropwise the alcohol in DMF (0.5 ml) followed,
after 10 minutes, by Bu4NI (1.7 mg, 0.0050 mmol) in DMF and
benzyl bromide (0.012 ml, 0.10 mmol). After 1 hour the reac-
tion was quenched by addition of water followed by saturated
NH4Cl before separation and extraction of the aqueous layer
with ether (3 × 5 ml). The combined organic extracts were
washed successively with 2 M NaOH, water and brine and dried
(MgSO4). Filtration and removal of solvent under reduced
pressure gave a yellow oil. Flash column chromatography
(petrol–ethyl acetate 10 : 1) yielded the epoxide 28d (11 mg,
50%) as a colourless oil shown by chiral HPLC to be of >98%
ee. Rf 0.40 (petrol–ethyl acetate 10 : 1); [α]2D4 ϩ2.2 (c 0.86,
CHCl3); νmax (film) 2932, 1495, 1454, 1362 and 1101 cmϪ1
;
δH (400 MHz, CDCl3) 7.35–7.27 (5H, m, Ph), 4.50 (2H, s,
PhCH2O), 3.50–3.47 (2H, m, CH2OCH2Ph), 2.58 [2H, s,
H2C(O)C], 1.70–1.59 [4H, m, 2 CH2C(O)], 1.52–1.46 (2H, m,
one of CH2), 1.35–1.30 (4H, m, two of CH2), 0.90 (3H, t, J 7.0
Hz, CH2CH3); δC (68 MHz, CDCl3) 138.5 (s), 128.4 (d), 127.6
(d), 127.5 (d), 72.9 (t), 70.2 (t), 59.3 (s), 52.5 (t), 34.0 (t), 30.8 (t),
27.0 (t), 25.1 (t), 22.8 (t), 14.0 (q); m/z (EIϩ) 248 (Mϩ), 140, 107,
91; observed: 248.1776. C16H24O2 (Mϩ) requires 248.1776.
ent-28d (47%) was prepared from ent-15d following the same
procedure and was shown by chiral HPLC to be of 84% ee.
Retention times 28d, 52.4 min; ent-28d, 57.1 min.
(E )-Oct-4-en-1-ol benzyl ether 30
Prepared from (E)-oct-4-en-1-ol following the procedure
described above for preparation of 16. Colourless oil (96%),
Rf 0.67 (petrol–ethyl acetate 10 : 1); νmax (film) 2930, 1696, 1454,
1363, 1103 and 967 cmϪ1; δH (400 MHz, CDCl3) 7.34–7.27 (5H,
(2S)-2-(3Ј-Benzyloxypropyl)-2-butyloxirane ent-28d
2-Butylprop-2-en-1-ol34 32 was prepared from n-butylacrolein
by reduction with sodium borohydride.35 Asymmetric Sharpless
epoxidation23 with -(ϩ)-DET (diethyl tartrate) generated
(2S)-(2-butyloxiranyl)methanol36 33. Oxidation using the
Swern procedure37 yielded (2S)-2-butyloxirane-2-carbaldehyde
as a colourless oil (77%); Rf 0.44 (petrol–ethyl acetate 10 : 1);
[α]2D1 ϩ56.7 (c 0.393, CHCl3); νmax (CHCl3 soln.) 2959, 1732,
1458 and 867 cmϪ1; δH (400 MHz, CDCl ) 8.90 (1H, s, HC᎐O),
m, Ph), 5.41–5.38 (2H, m, HC᎐CH), 4.50 (2H, s, PhCH O), 3.47
᎐
2
(2H, t, J 6.5 Hz, CH2OCH2Ph), 2.08–2.05 (2H, m, one of
CH CH᎐), 1.97–1.93 (2H, m, one of CH CH᎐), 1.71–1.64 (2H,
᎐
᎐
2
2
m, CH2CH2CH2), 1.35 (2H, q, J 7.5 Hz, CH2CH3), 0.87 (3H, t,
J 7.5 Hz CH2CH3); δC (68 MHz, CDCl3) 139.1 (s), 131.2 (s),
130.1 (d), 128.8 (d), 128.2 (d), 127.9 (d), 73.3 (t), 70.3 (t), 35.1
(t), 30.1 (t), 29.6 (t), 23.1 (t), 14.1 (q); m/z (EIϩ) 218 (Mϩ), 161,
127, 109, 107, 91; observed: 218.1664. C15H22O (Mϩ) requires
218.1671.
᎐
3
3.02 [2H, s, C(O)CH2], 1.98–1.91 [1H, m, CHHC(O)CH2], 1.76–
1.68 [1H, m, CHHC(O)CH2], 1.41–1.31 (4H, m, CH2CH2), 0.90
(3H, t, J 7.0 Hz, CH3); δC (68 MHz, CDCl3) 199.2 (d), 61.4 (s),
49.6 (t), 27.3 (t), 26.5 (t), 22.8 (t), 13.9 (q); m/z (EIϩ) 128 (Mϩ),
99, 86, 85, 70; observed: 128.0835. C7H12O2 (Mϩ) requires
128.0837. To (2S)-2-butyloxirane-2-carbaldehyde (900 mg,
7.02 mmol) stirred in dichloromethane at 0 ЊC was added
(ethoxycarbonylmethylene)triphenylphosphorane (2.69 g, 7.72
mmol). The reaction was stirred for 2.5 hours after which the
solvent was removed under reduced pressure to leave a white
solid which was slurried with petrol. Filtration and removal of
solvent under reduced pressure gave a yellow oil. Flash column
chromatography (petrol–ethyl acetate 10 : 1) yielded ester 34 as
a colourless oil (1.34 g, 96%); Rf 0.34 (petrol–ethyl acetate 10 :
1); [α]2D1 ϩ59.4 (c 0.633, CHCl3); νmax (film) 2958, 1720, 1657,
1467, 1367, 1303, 1177, 1036 and 980 cmϪ1; δH (400 MHz,
(2R,3R)-trans-2-(3Ј-Benzyloxypropyl)-3-propyloxirane 28e
Prepared from 30 with Oxone® and ketone 29 following the
procedure described above for 28a to yield 28e (75%) as a
colourless oil shown by chiral HPLC to be of 90% ee. Rf 0.27
(petrol–ethyl acetate 10 : 1); [α]2D4 Ϫ2.7 (c 0.40, CHCl3); νmax
(film) 2960, 1496, 1454, 1363, 1204, 1100 and 909 cmϪ1; δH (400
MHz, CDCl3) 7.34–7.29 (5H, m, Ph), 4.51 (2H, s, PhCH2O),
3.54–3.48 (2H, m, CH2OCH2Ph), 2.70–2.67 [2H, m, CH(O)-
CH], 1.79–1.67 [2H, m, one of CH2CH(O)CH], 1.65–1.50 [2H,
m, one of CH2CH(O)CH], 1.49–1.43 (4H, m, CH2CH3 and
CH2CH2CH2), 0.95 (3H, t, J 7.0 Hz, CH2CH3); δC (68 MHz,
CDCl3) 138.4 (s), 128.3 (d), 127.6 (d), 127.5 (d), 72.9 (t), 69.7 (t),
58.7 (d), 58.5 (d), 34.1 (t), 28.9 (t), 26.3 (t), 19.3 (t), 13.9 (q); m/z
(EIϩ) 234 (Mϩ), 216, 191, 173, 143, 127, 107, 91; observed:
234.1629. C15H22O2 (Mϩ) requires 234.1620.
CDCl ) 6.87 (1H, d, 15.5 Hz, HC᎐CHCO Et), 6.04 (1H, d, 15.5
᎐
3
2
Hz, HC᎐CHCO Et), 4.20 (2H, q, 7.0 Hz, OCH CH ), 2.87
᎐
2
2
3
[1H, d, 5.5 Hz, C(O)CHH], 2.70 [1H, d, 5.5 Hz, C(O)CHH],
1.84–1.78 [1H, m, CHHC(O)CH2], 1.69–1.62 [1H, m,
CHHC(O)CH2], 1.46–1.34 (4H, m, CH2CH2), 1.29 (3H, t, J 7.0
Hz, OCH2CH3), 0.91 (3H, t, J 7.0 Hz, CH2CH3); δC (68 MHz,
CDCl3) 166.1 (s), 147.0 (d), 121.9 (d), 60.5 (t), 57.9 (s), 55.6 (t),
33.2 (t), 27.1 (t), 22.7 (t), 14.2 (q), 13.9 (q); m/z (EIϩ) 198 (Mϩ),
180, 170, 152, 125, 109; observed: 198.1259. C11H18O3 (Mϩ)
requires 198.1256. To 34 (400 mg, 2.02 mmol) stirred in ethyl
acetate (17 ml) under nitrogen was added 10% palladium on
charcoal (42.9 mg). The reaction flask was evacuated and
flushed with hydrogen. This process was repeated five times
before the reaction was allowed to stir under hydrogen for
18 hours. The reaction was filtered through a Celite pad and
solvent removed under reduced pressure to give a colourless oil.
Flash column chromatography (petrol–ethyl acetate 10 : 1 and
Conversion of epoxyaldehyde 15d to benzyl ether 28d.
Preparation of (2R)-2-(3Ј-benzyloxypropyl)-2-butyloxirane 28d
Tosodiumborohydride(10mg, 0.26mmol)wereaddeddichloro-
methane (1.5 ml) and methanol (0.75 ml). The reaction was
stirred for 5 minutes after which an aliquot (0.95 ml) was
removed and added to 3-(2Ј-butyloxiranyl)propionaldehyde 15d
(14.5 mg, 0.093 mmol) stirred in dichloromethane (0.60 ml) at
0 ЊC. After 20 minutes the reaction was quenched by addition
of acetaldehyde, diluted with dichloromethane, washed with
saturated aqueous NaHCO3 and the organic phase dried
(MgSO4). Filtration and removal of solvent under reduced
pressure gave the alcohol as a colourless oil which was carried
onto the next stage without purification. Sodium hydride as a
60% dispersion in oil (4.5 mg, 0.11 mmol) was washed with
2872
J. Chem. Soc., Perkin Trans. 1, 2001, 2861–2873

View Article Online
and P. Milliet, Tetrahedron Lett., 1988, 29, 3941; (i) X. Lusinchi and
petrol–ether 10 : 1) yielded unsaturated ester 34 (160 mg, 40%
recovery) and (2ЈS)-3-(2Ј-butyloxiranyl)propionic acid ethyl
ester 35 (79 mg, 20%) as colourless oils; data for 35: Rf 0.29
(petrol–ether 5 : 1); [α]2D1 Ϫ0.75 (c 1.13, CHCl3); νmax (film) 2933,
1736, 1371 and 1180 cmϪ1; δH (400 MHz, CDCl3) 4.13 (2H, q,
7.0 Hz, OCH2CH3), 2.59 [2H, s, C(O)CH2], 2.36–2.32 (2H, m,
CH2CO2Et), 1.99–1.93 (2H, m CH2CH2CO2Et), 1.66–1.61 [1H,
m, CHHC(O)CH2], 1.52–1.45 [1H, m, CHHC(O)CH2], 1.36–
1.29 (4H, m, CH2CH2), 1.26 (3H, t, J 7.0 Hz, OCH2CH3), 0.90
(3H, t, J 7.0 Hz, CH2CH3); δC (68 MHz, CDCl3) 174.0 (s), 61.3
(t), 59.4 (s), 52.9 (t), 35.1 (t), 30.3 (t), 29.7 (t), 27.7 (t), 23.6 (t),
15.0 (q), 14.8 (q); m/z (CIϩ) 201 (M ϩ H), 183, 171, 155, 127;
observed: 201.1472. C11H21O3 (Mϩ) requires 201.1490. Ester 35
was reduced with DIBAL-H (2 equiv.) using the procedure
previously described (preparation of 28a) and converted to
benzyl ether ent-28d (spectroscopic data as previously prepared
28d) as a colourless oil (48%), shown by chiral HPLC to be of
91% ee.
G. Hanquet, Tetrahedron, 1997, 53, 13727.
7 (a) V. K. Aggarwal and M. F. Wang, Chem. Commun., 1996, 191; (b)
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cis-2-(4Ј-Benzyloxybutyl)-3-ethyloxirane 40 and ent-40
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40 (68%) and ent-40 (43%) were prepared from 39 and ent-39
respectively following the procedure described above for con-
version of 15d to 28d and were shown to be of 77% ee (40) and
76% ee (ent-40) by chiral HPLC. Rf 0.33 (petrol–ethyl acetate
10 : 1); (Found C: 76.67; H: 9.64. C15H22O2 requires C: 76.88;
H: 9.46%); νmax (film) 2935, 1495, 1454, 1361, 1102 and 907 cmϪ1
;
δH (400 MHz, CDCl3) 7.39–7.26 (5H, m, Ph), 4.50 (2H, s,
PhCH2O), 3.49 (2H, t, J 6.5 Hz, CH2OCH2Ph), 2.94–2.84 [2H,
m, HC(O)CH], 1.71–1.65 [2H, m, one of CH2CH(O)], 1.62–
1.47 (6H, m, 3CH2), 1.03 (3H, t, J 7.5 Hz, CH2CH3); δC (68
MHz, CDCl3) 138.5 (s), 128.3 (d), 127.6 (d), 127.5 (d), 72.9 (t),
70.1 (t), 58.3 (d), 57.2 (d), 29.5 (t), 27.5 (t), 23.3 (t), 21.1 (t), 10.6
(q); m/z (EIϩ) 234 (Mϩ), 216, 187, 143, 125, 107, 91; observed:
234.1612. C15H22O2 (Mϩ) requires 234.1620. Chiral HPLC
retention times 40, 94.3 min; ent-40, 99.1 min.
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Acknowledgements
We thank the EPSRC for their support of this work. This work
benefited from access to the EPSRC Chemical Database
Service.38
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