Synthesis and radical reactions of isomeric alkenyl oxaziridines

Article abstract of DOI:10.1055/s-2006-942380

Several alkenyl oxaziridines were prepared either by photoisomerisation of the precursor nitrones, or by peracid oxidation of the analogous pyrrolines. In each case the oxaziridines were produced as separable mixtures of diastereoisomers, and reasons for

Full text of DOI:10.1055/s-2006-942380

PAPER
1981
Synthesis and Radical Reactions of Isomeric Alkenyl Oxaziridines
S
ynthesis andRad
a
ical
R
eactio
v
ns of Isome
r
i
ic
A
lke
d
nyl
O
xaziridines StC. Black,* Gavin L. Edwards,* Sean M. Laaman
School of Chemistry, University of New South Wales, Sydney, NSW, 2052, Australia
Fax +61(2)93856141; E-mail: d.black@unsw.edu.au; E-mail: g.edwards@unsw.edu.au
Received 3 February 2006
The authors wish to dedicate this paper to Professor Glen Deacon on the occasion of his 70th birthday.
EtO2C
H
Abstract: Several alkenyl oxaziridines were prepared either by
photoisomerisation of the precursor nitrones, or by peracid oxida-
tion of the analogous pyrrolines. In each case the oxaziridines were
produced as separable mixtures of diastereoisomers, and reasons for
the observed stereoselectivity are discussed. Reaction of the oxazir-
idines with iron(II) sulfate, tributyltin hydride, or copper(I)triphe-
nylphosphine chloride tetramer gave products arising from
deoxygenation in many cases; however the trans-isomers also gave
products derived from cyclisation of the intermediate aminyl radi-
cals onto the pendant alkenyl chains.
EtO2C
H
Ph
Ph
N
N
O
1
R
2
for compounds 3–6
1. NaH
2. RX
a:
CH2CH=CH2
1. NaH
2. RX
b:
c:
d:
e:
(CH2)2CH=CH2
(CH2)3CH=CH2
(CH2)4CH=CH2
(CH2)2CH=CMe2
EtO2C
R
EtO2C
R
Ph
Ph
N
N
O
3
Key words: oxaziridines, radical reactions, nitrones, stereoselec-
tivity, aminyl radicals
4
MMPP
hν (300 nm)
Alkaloids, especially those containing saturated nitrogen
heterocycles, can possess remarkably varied structures
and display significant and varied biological activity.1,2
Potent examples of this class are found among the bicyclic
structures such as pyrrolizidines,3 indolizidines and quin-
olizidines,4 where extreme toxicities have been observed.
While many approaches have been adopted for the synthe-
sis of these important skeletons,5 aminyl radical
chemistry6 appears to have found relatively little applica-
tion thus far in pyrrolizidine synthesis.7 We have previ-
ously reported8 our initial investigations on the use of
oxaziridines as precursors for aminyl radicals, where re-
ductive cleavage of the N–O bond and subsequent cycli-
sation onto a pendant alkenyl group provided a new route
to the bicyclic core. We now wish to present full details of
our studies on oxaziridine-derived aminyl radicals as a
novel route to these fascinating structures.
Ph
EtO2C
Ph
+
R
R
N
EtO2C
N
O
O
5
"cis"
isomer
6
"trans"
isomer
Scheme 1
routinely successful, it was disappointing that attempted
alkylation with 4-iodobut-1-yne gave no identifiable
products.
In all cases the alkenylation was entirely regioselective,
with no evidence of the isomeric C-2 alkylated product in
the 1H NMR spectra of the crude products. Spectroscopic
characterisation of the alkylated nitrones 3 and pyrrolines
4 showed many similarities; however, there were two
noteworthy differences. In the 1H NMR spectra of the pyr-
rolines 4, the ethyl esters behaved as simple first-order
systems where the OCH2 was observed as a well-resolved
quartet. In contrast, the corresponding NMR spectra of the
nitrones 3 gave an extremely complex pattern for these
two diastereotopic protons. The second key difference
was noted in the 13C NMR spectra: for the pyrrolines 4,
the imine carbon resonance was observed at a similar
chemical shift to that of the ester carbon, whereas in the
corresponding nitrones 3, this resonance was shifted up-
field by about 40 ppm.
The initial phase of the investigation focussed on develop-
ment of a reliable synthesis of alkenyl oxaziridines; these
useful intermediates have been employed by us previous-
ly in a new approach to tropane alkaloids.9 Synthesis of
the precursor oxaziridines was effected by two routes:
peracid oxidation of imines,10 or electrocyclic ring closure
of imine N-oxides (nitrones).11 Both synthetic strategies
had similar initial stages: deprotonation of the known ni-
trone 112 or the pyrroline 212 with sodium hydride and sub-
sequent treatment of the resonance-stabilised anions with
the appropriate alkenyl halide gave good to excellent
yields of the monoalkylated products 3 and 4 respectively
(Scheme 1). While the reactions with alkenyl halides were
Preparation of the desired oxaziridines was carried out by
photoisomerisation of the nitrones 3 in benzene solution,
and also by oxidation of methanolic solutions of the pyr-
rolines 4 with magnesium monoperphthalate (MMPP).
SYNTHESIS 2006, No. 12, pp 1981–1990
Advanced online publication: 08.05.2006
DOI: 10.1055/s-2006-942380; Art ID: P01306SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
6

1982
D. StC. Black et al.
PAPER
Both modes of reaction produced mixtures of two isomer- as major products by MMPP oxidation of the pyrrolines)
ic oxaziridines 5 and 6 (Scheme 1) that could be separated are believed to be the stereoisomers where the Ph and es-
by careful preparative thin layer chromatography; their ter groups are cis. This results in the alkenyl chain and the
identity could be deduced readily from analysis of the 1H oxaziridine oxygen being cis. For the sake of conve-
NMR spectra, as outlined below. In all cases the peracid nience, these isomers are therefore designated as cis iso-
oxidation favoured the cis structures 5 (where the alkenyl mers. The more polar isomers, produced as major
chain and the oxaziridine oxygen are on the same face; products by photoisomerisation of the nitrones, have the
isolated as the less polar isomers i.e., those compounds alkenyl sidechain and oxaziridine oxygen trans; in this
with higher Rf), whereas the photocyclisation favoured the study they are called the trans isomers. (While Cahn–In-
trans isomers 6 (the more polar isomers i.e., the com- gold–Prelog based nomenclature is formally more correct,
pounds with lower Rf). Yields are given in Tables 1 and 2. assignment of priorities to the alkenyl chains sees the des-
ignations change: the cis-allyl compound 5a is 2R*,5S*,
while the other cis compounds 5b to 5e are 2R*,5R*.)
The NMR spectra of the isomeric oxaziridines were quite
similar; however, three distinct differences were noted. In
all cases, the less polar isomers (those with higher Rf) con-
sistently displayed both the CH3 and CH2 resonances for
the ethyl esters at lower chemical shift (upfield) in the 1H
NMR spectra compared with the more polar compounds.
O
H
O
C
O
N
Also two multiplets were observed quite close together in
the region d = ca. 2.5–3.0 for the less polar isomers; these
multiplets were well separated for the more polar (low Rf)
isomers. These factors suggested that all of the high Rf iso-
mers have similar stereochemistry, and all of the low Rf
isomers likewise are structurally related.
CH3
C
H
H2
Figure 1 Key NOE interaction for 5b
The observed deshielding of the ester group in the trans
isomer (where the ester and the oxaziridine oxygen are on
the same face) is consistent with the observations of Crotti
and co-workers13 where synthesis of cis and trans isomers
of methyl 2,3-epoxycyclopentane-1-carboxylate and their
1H NMR analysis showed that the methyl signal appeared
further downfield when the epoxide oxygen and ester
group were cis.
In order to facilitate assignment of stereochemistry to
each of the sets of isomers, a NOESY experiment was car-
ried out on each of the butenyl isomers. The less polar iso-
mer 5b showed a weak but real and positive interaction
between the ester methyl group and the aromatic ortho
protons (Figure 1). No such interaction was observed for
the more polar isomer 6b. Therefore the less polar isomers
5 (with the ester signals at lower chemical shift, produced
Table 1 Preparation of Oxaziridines from Photocyclisation of Nitrones 3
Nitrone
Alkenyl chain
Total yield (%)
Yield of
Yield of
Ratio
cis isomer 5 (%)
trans isomer 6 (%)
cis/trans
3a
3b
3c
3d
3e
CH2CH=CH2
67
81
81
78
77
19
30
36
37
14
48
51
45
41
63
1:2.5
1:1.7
1:1.3
1:1.1
1:4.5
(CH2)2CH=CH2
(CH2)3CH=CH2
(CH2)4CH=CH2
(CH2)2CH=CMe2
Table 2 Preparation of Oxaziridines from Peracid Oxidation of Pyrrolines 4
Pyrroline
Alkenyl chain
Total yield (%)
Yield of
Yield of
Ratio
cis isomer 5 (%)
trans isomer 6 (%)
cis/trans
4a
4b
4c
4d
4e
CH2CH=CH2
90
91
95
89
97
72
72
70
62
66
18
19
25
27
31
4.0:1
3.8:1
2.8:1
2.3:1
2.1:1
(CH2)2CH=CH2
(CH2)3CH=CH2
(CH2)4CH=CH2
(CH2)2CH=CMe2
Synthesis 2006, No. 12, 1981–1990 © Thieme Stuttgart · New York

PAPER
Synthesis and Radical Reactions of Isomeric Alkenyl Oxaziridines
1983
While hydrogen-bond formation has been invoked as a di- boiling ethanol and, as can be seen from Table 3, a major
recting influence for peracid oxidations by Crotti13 in the outcome in many cases was simple deoxygenation to give
epoxidation of methyl cyclopent-2-ene-1-carboxylate us- the pyrroline 4. Iron(II)-promoted reaction of the allyl
ing m-chloroperbenzoic acid (MCPBA), it appears to have compounds 5a and 6a gave not only the pyrroline 4a in ca.
little, if any, effect as both Crotti,13 and Koga,14 have dem- 40% yield, but also a significant amount of the pyrrole 712
onstrated that MCPBA epoxidation of this alkene gave (ca. 30%) resulting from deoxygenation and accompany-
(essentially) a 1:1 mixture of diastereoisomers. In our ing loss of the pendant allyl group (Scheme 2).
case, use of MMPP for epoxidation of the related pyrro-
lines 4 has produced a consistent (if sometimes small) ex-
Ph
EtO2C
EtO2C
Ph
cess of the cis diastereoisomer 5. This is consistent with
chelation of the magnesium ion between the imine nitro-
gen and ester carbonyl generating a ∪-shaped bicyc-
lo[3.3.0]octane-like structure (Figure 2). Attack on the
endo face would be disfavoured and hence the peracid
preferentially attacks the imine from the less hindered exo
face, trans to the ester group. It is noteworthy that the dia-
stereoselectivity decreases as the size of the alkenyl group
increases.
H2C=CHCH2
H2C=CHCH2
N
N
O
5a
4a
+
FeSO4
EtOH
OR
Ph
H2C=CHCH2
EtO2C
EtO2C
Ph
N
N
H
O
6a
7
Scheme 2
Ar
O
O
C
O
The facile loss of the allyl group is in stark contrast to the
fact that no dealkylation is observed for any other oxazir-
idines in this study. Both isomeric allyl compounds be-
haved similarly, except that the reaction of the trans
compound 6a produced a small amount of unidentified
cyclic materials in addition to the pyrroline 4a and pyrrole
7. Treatment of the isomeric oxaziridines 5a and 6a with
Bu3SnH and AIBN in boiling benzene gave poor yields of
pyrroline 4a along with unreacted starting material. A
third approach saw the oxaziridines reduced using cop-
per(I) triphenylphosphine chloride tetramer17 in THF; this
reaction protocol again saw deoxygenation as the major
outcome, with substantially more pyrrole 7 being isolated
in each case. In a similar manner to the iron(II) case, reac-
tion of the trans isomer 6a with [Cu(PPh3)Cl]4 also gave
small amounts of unidentified cyclic materials.
H
R
EtO
N
C
O
Mg
O
O
O
C
H
Ar
Figure 2 Possible formation of cis-oxaziridine by imine epoxida-
tion
While MMPP oxidation of the pyrrolines 4 favours the cis
isomers 5, synthesis of the oxaziridines by photocyclisa-
tion of the nitrones 3 consistently produces a small excess
of the trans diastereoisomer 6. As the 2p + 2s electrocy-
clic ring closure progresses, the transition state leading to-
wards the cis isomer would bring the bulkier ester and
phenyl groups closer together and, thus, formation of the
cis isomer would have a somewhat higher energy of acti-
vation (see Figure 3). As a result, the trans isomer is
formed preferentially. Again, as the size of the alkenyl
group increases, the diastereoselectivity decreases; the
higher preference for the trans isomer 6e is intriguing.
Iron(II) sulfate reduction of the butenyl compounds pro-
duced starkly different results (Scheme 3). Treatment of
the cis-isomer 5b gave the pyrroline 4b in 83% yield,
however the trans compound 6b gave the pyrroline 4b in
only 14% yield, accompanied by the pyrrolizidine 8
(46%). This bicyclic compound arises from initial 5-exo-
trig cyclisation of the aminyl radical onto the alkene, fol-
lowed by a subsequent attack of the intermediate carbon-
centred radical on the phenyl ring leading to migration of
the aromatic group (Scheme 3). Such phenyl migrations
under radical conditions have been observed by Aubé17
and, in another sense, by Sherburn.18 The structure of the
pyrrolizidine 8 was established using NMR correlation
techniques including COSY, HMQC and HMBC experi-
ments. The stereochemistry at the newly created stereo-
genic centre can be predicted by consideration of two
possible transition states. In the Beckwith model for 5-
exo-trig radical cyclisations,19 a chair-like transition state
is preferred over the boat-like alternative, and bulky sub-
stituents (such as the sterically demanding ethyl ester)
should preferentially be pseudoequatorial in the newly de-
veloping ring (Figure 4). This chair-like transition state
R
R
O
Ph
N
N
O
O
O
Et
Ph
O
O
Et
(I)
(II)
Figure 3 Possible transition structures leading to trans I and cis II
oxaziridines
Generation of aminyl radicals from oxaziridines is
achieved by reductive cleavage of the N–O bond;15 this
normally requires a transition metal such as iron(II). Ini-
tial studies focussed on reactions with iron(II) sulfate16 in
Synthesis 2006, No. 12, 1981–1990 © Thieme Stuttgart · New York

1984
D. StC. Black et al.
PAPER
FeSO4
EtOH
Ph
EtO2C
EtO2C
Ph
H2C=CH(CH2)2
H2C=CH(CH2)2
N
N
O
5b
4b
Ph
EtO2C
EtO2C
H2C=CH(CH2)2
EtO2C
FeSO4
EtOH
+
Ph
N
O
H2C=CH(CH2)2
N
O
N
6b
8
4b
Ph
Fe(II)
elimination
O
Fe(III)
Ph
EtO2C
EtO2C
O
Fe(III)
EtO2C
5-exo-trig
N
N
N
O
Fe(III)
H2C
Scheme 3
also leaves the intermediate radical more suitably dis- products. Deoxygenation to give the pyrroline was also
posed for the subsequent attack on the neighbouring phe- the major pathway for the trans isomers 6c and 6d, with
nyl group.
some evidence for formation of other cyclic products.
While the H NMR spectra of the cyclic material arising
1
Reaction of the butenyl isomers with Bu3SnH also gave
different results – the cis isomer 5b gave mostly pyrroline
4b, whereas the trans isomer 6b gave pyrroline 4b, ac-
companied by pyrrolizidine 8. Use of [Cu(PPh3)Cl]4 gave
the cleanest reactions: the cis isomer 5b gave the pyrroline
4b exclusively, while the trans isomer 6b gave pyrrolizi-
dine 8 in 89% yield.
from pentenyl compound 6c showed some similarities to
the pyrrolizidine 8, the absence of a pair of doublets of
doublets required for the benzylic CH2 (an ABX system)
makes the indolizidine 9 unlikely (Scheme 4). In fact, the
initial 6-exo-trig aminyl radical cyclisation is somewhat
less favourable, as these cyclisations are usually much
slower than the corresponding 5-exo-trig cyclisations.20
Reactions of all other cis isomers 5c–e with iron(II),
Bu3SnH, or [Cu(PPh3)Cl]4 gave the pyrrolines 4c–e, re-
spectively, in high yields, with no evidence of other cyclic
The successful cyclisation of the trans-butenyl isomer 6b
led to investigation of the dimethyl analogue 6e. Treat-
ment of oxaziridine 6e with [Cu(PPh3)Cl]4 gave an excel-
lent yield (89%) of the aziridine 10 as the sole product of
the reaction (Scheme 5). The reaction presumably follows
a similar path initially: reductive cleavage of the N–O
bond, followed by 5-exo cyclisation onto the alkene to
generate a tertiary radical. This more hindered radical is
less able to attack the aromatic ring, and therefore phenyl
migration does not occur and the pyrrolizidine 11 is not
formed. Instead, the result is cleavage of the five-mem-
Fe(III)
Fe(III)
O
E
O
E
δ•
Ph
Ph
CH2
δ•
δ•
N
N
H
H
CH
δ•
2
chair-like
boat-like
Figure 4 Possible transition states leading to pyrrolizidine 8
FeSO4
or
[Cu(PPh3)Cl]4
Ph
EtO2C
EtO2C
Ph
H2C=CH(CH2)3
H2C=CH(CH2)3
N
N
O
6c
4c
Ph
M
O
M
EtO2C
EtO2C
EtO2C
6-exo-trig
O
N
N
N
Ph
O
CH2
Ph
9
Scheme 4
Synthesis 2006, No. 12, 1981–1990 © Thieme Stuttgart · New York

PAPER
Synthesis and Radical Reactions of Isomeric Alkenyl Oxaziridines
1985
Table 3 Reductions of Oxaziridines
Alkenyl chain
CH2CH=CH2
Oxaziridine
(cis/trans)
Reducing agent
Recovered starting Pyrroline (%)
material (%)
Other
products (%)
5a (cis)
FeSO4
0
76
0
39
12
34
38
pyrrole 7 (32)
–
Bu3SnH
[Cu(PPh3)Cl]4
FeSO4
pyrrole 7 (44)
6a (trans)
0
pyrrole 7 (30), unidentified cyclic
products (ca. 10)
Bu3SnH
66
0
16
29
pyrrole 7 (1.5)
[Cu(PPh3)Cl]4
pyrrole 7 (41), unidentified cyclic
products (ca. 15)
(CH2)2CH=CH2
5b (cis)
FeSO4
0
21
0
83
71
92
14
44
0
–
Bu3SnH
–
[Cu(PPh3)Cl]4
FeSO4
–
6b (trans)
5c (cis)
0
pyrrolizidine 8 (46)
Bu3SnH
16
0
pyrrolizidine 8 (20)
[Cu(PPh3)Cl]4
FeSO4
pyrrolizidine 8 (89)
(CH2)3CH=CH2
0
89
84
81
66
–
–
–
Bu3SnH
0
[Cu(PPh3)Cl]4
FeSO4
0
6c (trans)
0
unidentified cyclic products
(ca. 26)
Bu3SnH
0
0
82
41
—
[Cu(PPh3)Cl]4
unidentified cyclic products
(ca. 40)
(CH2)4CH=CH2
5d (cis)
FeSO4
0
0
0
0
94
92
87
0
–
6d (trans)
FeSO4
–
(CH2)4CH=CMe2 5e (cis)
6e (trans)
[Cu(PPh3)Cl]4
[Cu(PPh3)Cl]4
–
aziridine 10 (89)
bered ring and accompanying cyclisation to give the azir- In this study we have shown that stereoselective formation
idine 10.
of oxaziridines can be achieved by variation of reaction
conditions, and the isomeric oxaziridines can be used as
aminyl radical precursors. While the cis compounds 5, on
treatment with a suitable reducing agent, generally gave
products resulting from deoxygenation, the trans isomers
6b and 6e led to products that could only have arisen from
intermediate aminyl radicals undergoing a 5-exo-trig cy-
clisation onto a pendant alkenyl chain. There is a clear ste-
reochemical demand in these reactions for the alkenyl
chain to be trans to the breaking N–O bond for cyclisa-
tions to occur. The particularly successful formation of
the bicyclic compounds 8 and 10 suggests that this proce-
dure could be useful for the synthesis of a range of alka-
loid derivatives.
The final challenge was an attempt to effect radical reac-
tions in the absence of metal-containing reagents. p-Tolu-
enesulfonyl iodide (tosyl iodide) has proved a useful
reagent for sulfone-directed synthesis of nitrogen21 and
oxygen22 heterocycles, and reports of its involvement in
single electron transfer processes23 prompted us to inves-
tigate its reaction with the alkenyl oxaziridines 5 and 6.
1
While there was evidence in the H NMR spectra of the
crude reaction mixtures that addition to the alkene had oc-
curred, unfortunately the reactions gave complex mix-
tures and no useful products could be obtained.
Synthesis 2006, No. 12, 1981–1990 © Thieme Stuttgart · New York

1986
D. StC. Black et al.
PAPER
Ph
Ph
O
Cu(II)
EtO2C
EtO2C
EtO2C
[Cu(PPh3)Cl]4
THF
Me2C=CH(CH2)2
N
N
N
Ph
O
O
Cu(II)
Me2C
6e
Me
Me
CO2Et
Ph
EtO2C
N
N
O
Ph
Me
Me
O
10
11
Scheme 5
Melting points are uncorrected. IR spectra were recorded using a
Hitachi model EPI-G spectrophotometer and refer to thin films of
liquids or paraffin mulls of solids between KBr plates. Absorptions
Anal. Calcd for C16H19NO3: C, 70.3; H, 7.0; N, 5.1. Found: C, 70.1;
H, 7.1; N, 5.1.
1
of medium to strong intensity only are reported here in cm–1. H
Ethyl 5-(But-3¢-en-1¢-yl)-2-phenyl-1-pyrroline-5-carboxylate 1-
Oxide (3b)
Waxy yellow solid; yield: 443 mg (72%); mp 52 °C.
IR (paraffin): 1740, 1550, 1360, 1275, 1180, 720, 650 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.1 Hz, 3 H, CH3),
2.06–2.29 (m, 4 H, H-1¢, H-4), 2.37–2.53 (m, 2 H, H-2¢), 3.04–3.25
(m, 2 H, H-3), 4.17–4.30 (m, 2 H, OCH2), 4.96 (d, J = 10.3 Hz, 1 H,
H-4¢a) 5.05 (dd, J = 17.0, 1.6 Hz, 1 H, H-4¢b), 5.83 (ddt, J = 17.0,
10.3, 6.3 Hz, 1 H, H-3¢), 7.41–7.46 (m, 3 H, ArH), 8.34–8.37 (m, 2
H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 13.9 (CH3), 26.0 (CH2), 27.4
(CH2), 28.5 (CH2), 32.5 (CH2), 62.0 (OCH2), 83.9 (C-5), 115.2 (C-
4¢), 127.4 (ArCH), 128.4 (ArCH), 129.0 (C-2), 130.5 (ArCH), 137.2
(C-3¢), 141.1 (ArC), 170.2 (C=O).
NMR (300 MHz) and 13C (75.5 MHz) NMR spectra were recorded
using a Bruker CXP300 instrument as CDCl3 solutions. Chemical
shifts are reported in parts per million downfield from tetramethyl-
silane (internal references: dH = 7.26 relative to residual CHCl3;
dC = 77.04 relative to the central peak of the CDCl3 triplet). 13C
NMR assignments were made using DEPT spectra, and ArC refers
to a quaternary aromatic carbon and ArCH refers to an aromatic car-
bon bearing one hydrogen. Mass spectra, in electron ionisation
mode, were obtained using an AEI MS12 instrument with 8000 V
accelerating voltage and with an ion source temperature of 200 °C.
Elemental analyses were performed by the School of Chemistry Mi-
croanalysis Service, UNSW. Reagents and solvents were purified
where necessary by standard procedures.
Alkylation of Nitrone 1; General Procedure
MS (EI): m/z = 287 (M, 8%).
NaH (0.07 g of an 80% dispersion in paraffin oil, 2.36 mmol) was
added to a stirred solution of ethyl 2-phenyl-1-pyrroline-5-carbox-
ylate 1-oxide (1; 0.50 g, 2.15 mmol) in anhyd THF (10 mL) at r.t.
After 5 min, DMF (0.5 mL) was added, and stirring was continued
for a further 5 min, whereupon the desired alkylating agent (2.15
mmol) was added slowly over 10 min. Stirring was continued for 24
to 48 h, when H2O (1 mL) was added. The mixture was concentrated
under reduced pressure, and the product was extracted into CHCl3
(3 × 15 mL). The combined organic extracts were dried (MgSO4),
concentrated under reduced pressure and purified by flash chroma-
tography (Et2O–light petroleum as eluent) to give the pure C-5 sub-
stituted nitrone 3.
Anal. Calcd for C17H21NO3: C, 71.1; H, 7.4; N, 4.9. Found: C, 70.8;
H, 7.5; N, 4.8.
Ethyl 5-(Pent-4¢-en-1¢-yl)-2-phenyl-1-pyrroline-5-carboxylate
1-Oxide (3c)
Colourless waxy solid; yield: 712 mg (81%); mp 52 °C.
IR (paraffin): 1735, 1645, 1570, 1545, 1280, 1250, 1210, 1080, 900,
700, 680 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.24 (t, J = 7.2 Hz, 3 H, CH3),
1.26–1.39 (m, 2 H, H-2¢), 2.07–2.31 (m, 5 H, H-1¢, H-3¢, H-4a),
2.42–2.49 (m, 1 H, H-4b), 3.08–3.20 (m, 2 H, H-3), 4.15–4.28 (m,
2 H, OCH2), 4.93 (d, J = 10.3 Hz, 1 H, H-5¢a), 4.99 (d, J = 17.2 Hz,
1 H, H-5¢b), 5.72–5.78 (m, 1 H, H-4¢), 7.40–7.43 (m, 3 H, ArH),
8.33–8.36 (m, 2 H, ArH).
Ethyl 2-Phenyl-5-(prop-2¢-en-1¢-yl)-1-pyrroline-5-carboxylate
1-Oxide (3a)
Waxy yellow solid; yield: 390 mg (66%); mp 46 °C.
13C NMR (CDCl3, 75.5 MHz): d = 13.9 (CH3), 22.4 (CH2), 26.0
(CH2), 28.5 (CH2), 32.9 (CH2), 33.6 (CH2), 62.0 (OCH2), 84.1 (C-
5), 115.0 (C-5¢), 127.3 (ArCH), 128.4 (ArCH), 129.1 (C-2), 130.4
(ArCH), 137.9 (C-4¢), 141.3 (ArC), 170.4 (C=O).
IR (paraffin): 1735, 1543, 1360, 1275, 1250, 1205, 1175, 1120,
1068, 1025, 910, 760 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.1 Hz, 3 H, CH3),
2.21–2.43 (m, 2 H, H-4), 2.76 (dd, J = 14.3, 8.5 Hz, 1 H, H-1¢a),
2.99–3.20 (m, 3 H, H-1¢b, H-3), 4.16–4.30 (m, 2 H, OCH2), 5.16 (d,
J = 10.0 Hz, 1 H, H-3¢a), 5.22 (d, J = 17.2 Hz, 1 H, H-3¢b), 5.63–
5.71 (m, 1 H, H-2¢), 7.41–7.44 (m, 3 H, ArH), 8.33–8.36 (m, 2 H,
ArH).
MS (EI): m/z = 301 (M, 10%).
Anal. Calcd for C18H23NO3: C, 71.7; H, 7.7; N, 4.65. Found: C,
72.0; H, 7.8; N, 4.6.
13C NMR (CDCl3, 75.5 MHz): d = 13.8 (CH3), 25.2 (CH2), 28.3
(CH2), 37.4 (CH2), 61.9 (OCH2), 84.1 (C-5), 120.5 (C-3¢), 127.2
(ArCH), 128.2 (ArCH), 129.1 (C-2), 130.3 (C-2¢), 131.3 (ArCH), 141.3
(ArC), 170.0 (C=O).
Ethyl 5-(Hex-5¢-en-1¢-yl)-2-phenyl-1-pyrroline-5-carboxylate 1-
Oxide (3d)
Waxy yellow solid; yield: 530 mg (79%); mp 48–49 °C.
IR (paraffin): 1745, 1640, 1575, 1540, 1260, 1220, 1180, 1020, 910,
850, 760, 690 cm–1.
MS (EI): m/z = 273 (M, 28%).
Synthesis 2006, No. 12, 1981–1990 © Thieme Stuttgart · New York

PAPER
Synthesis and Radical Reactions of Isomeric Alkenyl Oxaziridines
1987
1H NMR (CDCl3, 300 MHz): d = 1.22 (t, J = 7.2 Hz, 3 H, CH3),
1.35–1.52 (m, 4 H, H-2¢, H-3¢), 1.98–2.24 (m, 5 H, H-1¢, H-4¢, H-
4a), 2.39–2.48 (m, 1 H, H-4b), 3.01–3.18 (m, 2 H, H-3), 4.13–4.26
(m, 2 H, OCH2) 4.86–4.97 (m, 2 H, H-6¢), 5.69–5.77 (m, 1 H, H-5¢),
7.39–7.42 (m, 3 H, ArH), 8.31–8.34 (m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 13.9 (CH3), 22.3 (CH2), 25.9
(CH2), 28.4 (CH2), 28.8 (CH2), 33.2 (CH2), 33.3 (CH2), 61.9
(OCH2), 84.1 (C-5), 114.4 (C-6¢), 127.3 (ArCH), 128.3 (ArCH), 129.1
(C-2), 130.4 (ArCH), 138.4 (C-5¢), 142.7 (ArC), 170.4 (C=O).
Ethyl 5-(But-3¢-en-1¢-yl)-2-phenyl-1-pyrroline-5-carboxylate
(4b)
Yellow oil; yield: 1.10 g (89%).
IR (film): 1740, 1630, 1410, 1380, 1320, 1200, 780, 680 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.1 Hz, 3 H, CH3),
1.93–2.20 (m, 5 H, H-1¢, H-2¢, H-4¢a), 2.48 (ddd, J = 13.3, 9.7, 5.6
Hz, 1 H, H-4¢b), 3.00–3.09 (m, 2 H, H-3), 4.19 (q, J = 7.1 Hz, 2 H,
OCH2), 4.93 (d, J = 10.3 Hz, 1 H, H-4¢a), 5.02 (d, J = 17.4 Hz, 1 H,
H-4¢b), 5.75–5.90 (m, 1 H, H-3¢), 7.36–7.43 (m, 3 H, ArH), 7.85–
7.88 (m, 2 H, ArH).
MS (EI): m/z = 315 (M, 15%).
Anal. Calcd for C19H25NO3: C, 72.35; H, 8.0; N, 4.4. Found: C,
72.4; H, 7.8; N, 4.25.
13C NMR (CDCl3, 75.5 MHz): d = 14.1 (CH3), 28.7 (CH2), 31.4
(CH2), 35.5 (CH2), 37.9 (CH2), 60.9 (OCH2), 83.1 (C-5), 114.5 (C-
4¢), 127.9 (ArCH), 128.3 (ArCH), 130.7 (ArCH), 134.0 (ArC), 138.0 (C-
2¢), 173.9 (C-2 or C=O), 174.1 (C=O or C-2).
Ethyl 5-(4¢-Methylpent-3¢-en-1¢-yl)-2-phenyl-1-pyrroline-5-car-
boxylate 1-Oxide (3e)
Waxy yellow solid; yield: 699 mg (from 500 mg of 1, 69%); mp 50–
52 °C.
MS (EI): m/z = 271 (M, 16%).
Anal. Calcd for C17H21NO2: C, 75.25; H, 7.8; N, 5.2. Found: C,
75.2; H, 7.9; N, 4.9.
IR (paraffin): 1730, 1540, 1210, 1160, 930, 755, 690 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.27 (t, J = 7.2 Hz, 3 H,
OCH2CH3), 1.58 (s, 3 H, =CCH3), 1.64 (s, 3 H, =CCH3), 1.92–2.35
(m, 5 H, H-1¢, H-2¢, H-4a), 2.46–2.54 (m, 1 H, H-4b), 3.10–3.23 (m,
2 H, H-3), 4.17–4.30 (m, 2 H, OCH2), 5.10–5.18 (m, 1 H, H-3¢),
7.41–7.46 (m, 3 H, ArH), 8.35–8.38 (m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.0 (CH2CH3), 17.7 (=CCH3),
21.9 (CH2), 25.6 (=CCH3), 26.1 (CH2), 28.5 (CH2), 33.4 (CH2), 62.0
(OCH2), 84.0 (C-5), 122.9 (C-3¢), 127.4 (ArCH), 128.4 (ArCH), 129.2
(C-2), 130.4 (ArCH), 132.5 (C-4¢), 141.0 (ArC), 170.4 (C=O).
Ethyl 5-(Pent-4¢-en-1¢-yl)-2-phenyl-1-pyrroline-5-carboxylate
(4c)
Yellow oil; yield: 1.18 g (90%).
IR (film): 1735, 1640, 1400, 1365, 1325, 780, 690 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.26 (t, J = 7.2 Hz, 3 H, CH3),
1.42–1.55 (m, 2 H, H-2¢), 1.93–2.02 (m, 3 H, H-1¢, H-4a), 2.09 (q,
J = 7.2 Hz, 2 H, H-3¢), 2.43–2.51 (m, 1 H, H-4b), 3.01–3.09 (m, 2
H, H-3), 4.21 (q, J = 7.0 Hz, 2 H, OCH2), 4.93–5.03 (m, 2 H, H-5¢),
5.74–5.85 (m, 1 H, H-4¢), 7.37–7.44 (m, 3 H, ArH), 7.86–7.89 (m,
2 H, ArH).
MS (EI): m/z = 315 (M, 4%).
Anal. Calcd for C19H25NO3: C, 72.35; H, 8.0; N, 4.4. Found: C,
72.3; H, 8.3; N, 4.1.
13C NMR (CDCl3, 75.5 MHz): d = 14.2 (CH3), 23.7 (CH2), 31.4
(CH2), 33.9 (CH2), 35.5 (CH2), 38.3 (CH2) 61.0 (OCH2), 83.5 (C-5),
114.7 (C-5¢), 128.0 (ArCH), 128.3 (ArCH), 130.7 (ArCH), 134.1 (ArC),
138.4 (C-4¢), 173.7 (C-2 or C=O), 174.3 (C=O or C-2).
Alkylation of Pyrroline 2; General Procedure
Ethyl 2-phenyl-1-pyrroline-5-carboxylate (2; 1.00 g, 4.61 mmol)
was dissolved in anhyd THF (10 mL) at r.t., and DMF (1 mL) was
added followed by NaH (152 mg of an 80% dispersion in paraffin
oil, 5.10 mmol). The cloudy yellow solution was stirred for 10 min
and then the appropriate alkylating agent (5.76 mmol) was added,
and the mixture was stirred under N2 overnight. The mixture was
concentrated under reduced pressure, and the residue was parti-
tioned between H2O and CH2Cl2. The aqueous layer was extracted
with CH2Cl2 (2 × 5 mL), and the combined organic extracts were
dried (MgSO4), concentrated under reduced pressure and purified
by flash chromatography (Et2O–light petroleum as eluent) to give
the pure C-5 substituted pyrroline 4.
MS (EI): m/z = 285 (M, 5%).
Anal. Calcd for C18H23NO2: C, 75.8; H, 8.1; N, 4.9. Found: C, 76.2;
H, 8.2; N, 4.6.
Ethyl 5-(Hex-5¢-en-1¢-yl)-2-phenyl-1-pyrroline-5-carboxylate
(4d)
Yellow oil; yield: 1.12 g (82%).
IR (film): 1705, 1630, 1420, 1355, 1215, 760, 710, 690 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.26 (t, J = 7.1 Hz, 3 H, CH3),
1.30–1.45 (m, 4 H, H-2¢, H-3¢), 1.88–2.09 (m, 5 H, H-1¢, H-4¢, H-
4a), 2.48 (ddd, J = 13.3, 9.7, 5.6 Hz, 1 H, H-4b), 3.00–3.08 (m, 2 H,
H-3), 4.21 (q, J = 7.1 Hz, 2 H, OCH2), 4.90–5.01 (m, 2 H, H-6¢),
5.72–5.83 (m, 1 H, H-5¢), 7.37–7.45 (m, 3 H, ArH), 7.86–7.89 (m,
2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.2 (CH3), 23.8 (CH2), 29.2
(CH2), 31.3 (CH2), 33.5 (CH2), 35.5 (CH2), 38.7 (CH2) 61.0
(OCH2), 83.6 (C-5), 114.4 (C-6¢), 128.0 (ArCH), 128.3 (ArCH), 130.7
(ArCH), 134.1 (ArC), 138.8 (C-5¢), 173.7 (C-2 or C=O), 174.4 (C=O
or C-2).
Ethyl 2-Phenyl-5-(prop-2¢-en-1¢-yl)-1-pyrroline-5-carboxylate
(4a)
Yellow oil; yield: 1.10 g (92%).
IR (film): 1735, 1615, 1450, 1375, 910, 755, 690 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.23 (t, J = 7.1 Hz, 3 H, CH3),
1.98 (ddd, J = 13.3, 9.6, 6.5 Hz, 1 H, H-4a), 2.40 (ddd, J = 13.3, 9.9,
5.8 Hz, 1 H, H-4b), 2.61–2.75 (m, 2 H, H-1¢), 2.88–3.10 (m, 2 H, H-
3), 4.16 (q, J = 7.1 Hz, 2 H, OCH2), 5.03–5.13 (m, 2 H, H-3¢), 5.64–
5.78 (m, 1 H, H-2¢), 7.31–7.43 (m, 3 H, ArH), 7.82–7.84 (m, 2 H,
ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.2 (CH3), 30.4 (CH2), 35.1
(CH2), 42.7 (CH2), 61.1 (OCH2), 83.1 (C-5), 118.7 (C-3¢), 128.0
(ArCH), 128.3 (ArCH), 130.8 (ArCH), 133.1 (C-2¢), 134.0 (ArC), 173.9
(C-2 or C=O), 174.3 (C=O or C-2).
MS (EI): m/z = 299 (M, 8%).
Anal. Calcd for C19H25NO2: C, 76.2; H, 8.4; N, 4.7. Found: C, 76.1;
H, 8.2; N, 4.5.
Ethyl 5-(4¢-Methylpent-3¢-en-1¢-yl)-2-phenyl-1-pyrroline-5-car-
boxylate (4e)
Viscous colourless oil; yield: 602 mg (from 500 mg of 2, 83%).
1H NMR (CDCl3, 300 MHz): d = 1.28 (t, J = 7.2 Hz, 3 H, CH2CH3),
1.59 (s, 3 H, =CCH3), 1.66 (s, 3 H, =CCH3), 1.92–2.09 (m, 5 H, H-
1¢, H-2¢, H-4a), 2.48 (ddd, J = 13.2, 9.6, 6.0 Hz, 1 H, H-4b), 3.01–
MS (EI): m/z = 257 (M, 15%).
Anal. Calcd for C16H19NO2: C, 74.7; H, 7.4; N, 5.4. Found: C,
74.75; H, 7.3; N, 5.3.
Synthesis 2006, No. 12, 1981–1990 © Thieme Stuttgart · New York

1988
D. StC. Black et al.
PAPER
3.09 (m, 2 H, H-3), 4.21 (q, J = 7.2 Hz, 2 H, OCH2), 5.07–5.14 (m,
1 H, H-3¢), 7.37–7.44 (m, 3 H, ArH), 7.86–7.92 (m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.3 (CH3), 26.6 (CH2), 27.8
(CH2), 39.5 (CH2), 61.5 (OCH2), 76.6 (C-2), 88.1 (C-5), 119.6 (C-
3¢), 127.1 (ArCH), 128.3 (ArCH), 129.5 (ArCH), 131.5 (C-2¢), 134.5
(ArC), 171.4 (C=O).
13C NMR (CDCl3, 75.5 MHz): d = 14.2 (CH2CH3), 17.6 ( =CCH3),
23.2 (CH2), 25.6 ( =CCH3), 31.4 (CH2), 35.5 (CH2), 38.9 (CH2),
61.0 (OCH2), 83.4 (C-5), 123.7 (C-3¢), 128.0 (ArCH), 128.3 (ArCH),
130.7 (ArCH), 131.9 (C-4¢), 134.2 (ArC), 173.8 (C-2 or C=O), 174.2
(C=O or C-2).
MS (EI): m/z = 273 (M, 22%).
Anal. Calcd for C16H19NO3: C, 70.3; H, 7.0; N, 5.1. Found: C,
70.75; H, 7.2; N, 4.8.
Anal. Calcd for C19H25NO2: C, 76.2; H, 8.4; N, 4.7. Found: C, 75.8;
H, 8.3; N, 4.3.
Ethyl cis-2-(But-3¢-en-1¢-yl)-5-phenyl-6-oxa-1-azabicy-
clo[3.1.0]hexane-2-carboxylate (5b)
Yellow oil.
Irradiation of Nitrones 3; General Procedure
A solution of the appropriate nitrone 3 (0.97 mmol) in anhyd, de-
gassed benzene (20 mL) was placed in a quartz tube in a fan-cooled
Oliphant ‘Merry-Go-Round’ reactor equipped with an ultraviolet
lamp. The solution was irradiated for 16 h, and the solvent was re-
moved to give the crude mixture of oxaziridines which was purified
by preparative TLC using Et2O–light petroleum as the eluent. The
yields of isomeric oxaziridines 5 and 6 are given in Table 1. The cis
isomers 5 routinely migrated with higher Rf than the trans isomers
6.
IR (film): 1730, 1650, 1545, 1420, 1270, 1150, 895, 820 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.34 (t, J = 7.1 Hz, 3 H, CH3),
1.75 (ddd, J = 13.5, 11.6, 5.1 Hz, 1 H), 1.84–1.96 (m, 2 H), 2.09–
2.27 (m, 3 H), 2.47 (ddd, J = 14.5, 10.5, 8.6 Hz, 1 H), 2.72 (dd,
J = 14.5, 8.3 Hz, 1 H), 4.25–4.36 (m, 2 H, OCH2), 4.94–5.04 (m, 2
H, H-4¢), 5.69–5.83 (m, 1 H, H-3¢), 7.35–7.40 (m, 3 H, ArH), 7.50–
7.54 (m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.3 (CH3), 27.5 (CH2), 27.8
(CH2), 28.5 (CH2), 34.3 (CH2), 61.4 (OCH2), 76.6 (C-2), 87.9 (C-5),
115.3 (C-4¢), 127.2 (ArCH), 128.4 (ArCH), 129.6 (ArCH), 134.6 (ArC),
137.1 (C-3¢), 171.8 (C=O).
Oxidation of 1-Pyrrolines 4 with Peracid; General Procedure
The appropriate 1-pyrroline 4 (0.97 mmol) in MeOH (5 mL) was
treated with magnesium monoperoxyphthalate (240 mg, 0.48
mmol) in MeOH (5 mL) and the solution was stirred for 30 min at
r.t. A dilute aq solution of Na2SO3 (2 mL) was added, and the
MeOH was removed under reduced pressure. The aqueous residue
was extracted with CH2Cl2 (2 × 5 mL). The combined organic ex-
tracts were washed with aq NaHCO3 (2 × 5 mL) and then H2O, and
the organic layer was dried (MgSO4) and evaporated to dryness un-
der reduced pressure. The crude mixture of isomeric oxaziridines
was separated by preparative TLC using Et2O–light petroleum as
eluent. The yields of isomeric oxaziridines 5 and 6 are given in
Table 2.
MS (EI): m/z = 287 (M, 2%).
Anal. Calcd for C17H21NO3: C, 71.1; H, 7.4; N, 4.9. Found: C, 71.4;
H, 7.5; N, 4.7.
Ethyl trans-2-(But-3¢-en-1¢-yl)-5-phenyl-6-oxa-1-azabicy-
clo[3.1.0]hexane-2-carboxylate (6b)
Yellow oil.
IR (film): 3040, 2990, 2820, 1725, 1010, 920, 890 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.2 Hz, 3 H, CH3),
1.70 (ddd, J = 13.1, 10.5, 8.2 Hz, 1 H), 1.81–2.15 (m, 5 H), 2.51
(ddd, J = 14.4, 10.2, 8.2 Hz, 1 H), 2.64 (dd, J = 14.4, 7.7 Hz, 1 H),
4.14–4.26 (m, 2 H, OCH2), 4.97 (dd, J = 10.2, 2.0 Hz, 1 H, H-4¢a),
5.00–5.07 (m, 1 H, H-4¢b), 5.78–5.87 (m, 1 H, H-3¢), 7.36–7.39 (m,
3 H, ArH), 7.52–7.57 (m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.1 (CH3), 29.2 (CH2), 29.4
(CH2), 30.5 (CH2), 34.5 (CH2), 61.3 (OCH2), 76.7 (C-2), 88.6 (C-5),
114.7 (C-4¢), 126.9 (ArCH), 128.3 (ArCH), 129.3 (ArCH), 134.8 (ArC),
138.0 (C-3¢), 171.7 (C=O).
Ethyl cis-5-Phenyl-2-(prop-2¢-en-1¢-yl)-6-oxa-1-azabicy-
clo[3.1.0]hexane-2-carboxylate (5a)
Yellow oil.
IR (film): 1725, 1010, 920, 890 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.20 (t, J = 7.3 Hz, 3 H, CH3),
1.74 (ddd, J = 13.3, 10.7, 8.2 Hz, 1 H, H-4a), 2.05 (dd, J = 13.3, 8.2
Hz, 1 H, H-4b), 2.50–2.77 (m, 4 H, H-3, H-1¢), 4.13–4.23 (m, 2 H,
OCH2), 5.13 (dd, J = 10.3, 1.0 Hz, 1 H, H-3¢a), 5.20 (d, J = 16.9 Hz,
1 H, H-3¢b), 5.93 (m, 1 H, H-2¢), 7.36–7.38 (m, 3 H, ArH), 7.52–
7.55 (m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.0 (CH3), 29.2 (CH2), 29.7
(CH2), 39.5 (CH2), 61.4 (OCH2), 76.7 (C-2), 88.6 (C-5), 118.5 (C-
3¢), 126.9 (ArCH), 128.3 (ArCH), 129.3 (ArCH), 133.0 (C-2¢), 134.7
(ArC), 171.3 (C=O).
MS (EI): m/z = 287 (M, 2%).
Anal. Calcd for C17H21NO3: C, 71.1; H, 7.4; N, 4.9. Found: C, 71.0;
H, 7.5; N, 4.75.
Ethyl cis-2-(Pent-4¢-en-1¢-yl)-5-phenyl-6-oxa-1-azabicy-
clo[3.1.0]hexane-2-carboxylate (5c)
Yellow oil.
MS (EI): m/z = 273 (M, 8%).
IR (film): 1725, 1640, 1600, 1540, 1420, 1350, 1240, 1190, 980,
890, 700 cm–1.
Anal. Calcd for C16H19NO3: C, 70.3; H, 7.0; N, 5.1. Found: C, 70.8;
H, 7.2; N, 5.0.
1H NMR (CDCl3, 300 MHz): d = 1.36 (t, J = 7.2 Hz, 3 H, CH3),
1.42–1.70 (m, 3 H), 1.79–1.89 (m, 2 H), 2.04 (br q, J = 7.2 Hz, 2 H),
2.12–2.24 (m, 1 H), 2.41–2.50 (m, 1 H), 2.72 (dd, J = 14.9, 8.2 Hz,
1 H), 4.26–4.33 (m, 2 H, OCH2), 4.92–5.01 (m, 2 H, H-5¢), 5.68–
5.74 (m, 1 H, H-4¢), 7.37–7.41 (m, 3 H, ArH), 7.50–7.54 (m, 2 H,
ArH).
Ethyl trans-5-Phenyl-2-(prop-2¢-en-1¢-yl)-6-oxa-1-azabicy-
clo[3.1.0]hexane-2-carboxylate (6a)
Yellow oil.
IR (film): 1730, 1640, 1360, 1340, 1175, 1080, 920, 840 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.29 (t, J = 7.2 Hz, 3 H, CH3),
1.87 (dd, J = 13.3, 8.2 Hz, 1 H, H-4a), 2.19 (ddd, J = 13.3, 10.5, 8.5
Hz, 1 H, H-4b), 2.34–2.50 (m, 2 H, H-3 or H-1¢), 2.58 (dd, J = 13.8,
7.2 Hz, 1 H, H-3 or H-1¢), 2.66 (dd, J = 14.3, 8.0 Hz, 1 H, H-3 or H-
1¢), 4.18–4.34 (m, 2 H, OCH2), 5.07–5.14 (m, 2 H, H-3¢), 5.64–5.78
(m, 1 H, H-2¢), 7.31–7.36 (m, 3 H, ArH), 7.44–7.50 (m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.1 (CH3), 24.3 (CH2), 29.1
(CH2), 30.5 (CH2), 33.8 (CH2), 34.8 (CH2), 61.2 (OCH2), 76.8 (C-
2), 88.5 (C-5), 114.7 (C-5¢), 126.9 (ArCH), 128.0 (ArCH), 129.2
(ArCH), 134.7 (ArC), 138.2 (C-4¢), 171.9 (C=O).
MS (EI): m/z = 301 (M, 5%).
Synthesis 2006, No. 12, 1981–1990 © Thieme Stuttgart · New York

PAPER
Synthesis and Radical Reactions of Isomeric Alkenyl Oxaziridines
1989
Anal. Calcd for C18H23NO3: C, 71.7; H, 7.7; N, 4.65. Found: C,
71.5; H, 7.6; N, 4.5.
IR (film): 1725, 1440, 1350, 1260, 1215, 750, 690 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.35 (t, J = 7.2 Hz, 3 H, CH2CH3),
1.55 (s, 3 H, =CCH3), 1.64 (s, 3 H, =CCH3), 1.64–1.71 (m, 2 H),
1.79–1.92 (m, 2 H), 2.02–2.26 (m, 2 H), 2.46 (ddd, J = 14.4, 10.7,
8.7 Hz, 1 H), 2.72 (dd, J = 14.4, 8.0 Hz, 1 H), 4.25–4.36 (m, 2 H,
OCH2), 5.02–5.07 (m, 1 H, H-3¢), 7.36–7.40 (m, 3 H, ArH), 7.51–
7.54 (m, 2 H, ArH).
Ethyl trans-2-(Pent-4¢-en-1¢-yl)-5-phenyl-6-oxa-1-azabicy-
clo[3.1.0]hexane-2-carboxylate (6c)
Yellow oil.
IR (film): 1725, 1600, 1410, 1280, 1240, 1150, 880, 825 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.2 Hz, 3 H, CH3),
1.40–1.51 (m, 2 H), 1.71 (ddd, J = 13.3, 10.8, 8.2 Hz, 1 H), 1.78–
2.15 (m, 5 H), 2.51 (ddd, J = 14.4, 10.8, 8.2 Hz, 1 H), 2.64 (dd,
J = 14.4, 7.2 Hz, 1 H), 4.14–4.27 (m, 2 H, OCH2), 4.95–5.08 (m, 2
H, H-5¢), 5.78–5.87 (m, 1 H, H-4¢), 7.36–7.39 (m, 3 H, ArH), 7.52–
7.55 (m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.2 (CH3), 23.5 (CH2), 27.3
(CH2), 27.7 (CH2), 33.6 (CH2), 34.4 (CH2), 61.2 (OCH2), 76.8 (C-
2), 87.8 (C-5), 114.7 (C-5¢), 127.1 (ArCH), 128.0 (ArCH), 129.5
(ArCH), 134.6 (ArC), 137.6 (C-4¢), 171.9 (C=O).
13C NMR (CDCl3, 75.5 MHz): d = 14.3 (CH2CH3), 17.5 ( =CCH3),
23.1 (CH2), 25.5 ( =CCH3), 27.4 (CH2), 27.8 (CH2), 35.1 (CH2),
61.3 (OCH2), 76.8 (C-2), 87.9 (C-5), 122.8 (C-3¢), 127.1 (ArCH),
128.3 (ArCH), 129.5 (ArCH), 132.8 (C-4¢), 134.6 (ArC), 171.9 (C=O).
MS (EI): m/z = 315 (M, 1%).
Anal. Calcd for C19H25NO3: C, 72.35; H, 8.0; N, 4.4. Found: C,
72.1; H, 8.3; N, 4.2.
Ethyl trans-2-(4¢-Methylpent-3¢-en-1¢-yl)-5-phenyl-6-oxa-1-
azabicyclo[3.1.0]hexane-2-carboxylate (6e)
Yellow oil.
MS (EI): m/z = 301 (M, 3%).
Anal. Calcd for C18H23NO3: C, 71.7; H, 7.7; N, 4.65. Found: C,
71.4; H, 7.6; N, 4.5.
IR (film): 1725, 1445, 1350, 1175, 1000, 740, 690 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.26 (t, J = 7.2 Hz, 3 H, CH2CH3),
1.64 (s, 3 H, =CCH3), 1.69 (s, 3 H, =CCH3), 1.60–1.76 (m, 2 H),
1.92–2.10 (m, 4 H), 2.51 (ddd, J = 14.4, 10.8, 8.2 Hz, 1 H), 2.64 (dd,
J = 14.4, 7.2 Hz, 1 H), 4.15–4.27 (m, 2 H, OCH2), 5.13–5.19 (m, 1
H, H-3¢), 7.37–7.40 (m, 3 H, ArH), 7.53–7.56 (m, 2 H, ArH).
Ethyl cis-2-(Hex-5¢-en-1¢-yl)-5-phenyl-6-oxa-1-azabicy-
clo[3.1.0]hexane-2-carboxylate (5d)
Yellow oil.
IR (film): 1725, 1595, 1395, 1325, 1230, 1000, 880, 810, 690 cm–1.
MS (EI): m/z = 315 (M, 1%).
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.2 Hz, 3 H, CH3),
1.38–1.52 (m, 3 H), 1.65–1.75 (m, 2 H), 1.89–1.98 (m, 2 H), 2.03–
2.10 (m, 3 H), 2.45–2.67 (m, 2 H), 4.14–4.27 (m, 2 H, OCH2), 4.94
(dt, J = 10.3, 1.0 Hz, 1 H, H-6¢a), 5.01 (br d, J = 17.2 Hz, 1 H, H-
6¢b), 5.77–5.86 (m, 1 H, H-5¢), 7.36–7.39 (m, 3 H, ArH), 7.52–7.55
(m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.2 (CH3), 23.6 (CH2), 27.2
(CH2), 27.6 (CH2), 28.9 (CH2), 32.3 (CH2), 35.0 (CH2), 61.6
(OCH2), 77.0 (C-2), 87.7 (C-5), 114.7 (C-6¢), 127.1 (ArCH), 127.3
(ArCH), 129.5 (ArCH), 134.7 (ArC), 137.3 (C-5¢), 172.0 (C=O).
Anal. Calcd for C19H25NO3: C, 72.35; H, 8.0; N, 4.4. Found: C,
72.3; H, 8.25; N, 4.2.
Reaction of Oxaziridines with Iron(II) Sulfate; General Proce-
dure
The desired oxaziridine 5 or 6 (250 mg) in absolute EtOH (5 mL)
was treated with an equimolar amount of FeSO4 and the mixture
was refluxed for 24 h. The solvent was removed under reduced pres-
sure and the resulting residue was partitioned between H2O (5 mL)
and CH2Cl2 (5 mL). The aqueous layer was extracted with CH2Cl2
(2 × 5 mL) and the combined organic extracts were dried (MgSO4)
and concentrated under reduced pressure to give the crude reaction
product. Purification was effected using preparative TLC with
Et2O–light petroleum as eluent. Results are given in Table 3.
MS (EI): m/z = 316 (M + 1, 1%).
Anal. Calcd for C19H25NO3: C, 72.35; H, 8.0; N, 4.4. Found: C,
72.6; H, 8.1; N, 4.4.
Ethyl trans-2-(Hex-5¢-en-1¢-yl)-5-phenyl-6-oxa-1-azabicy-
clo[3.1.0]hexane-2-carboxylate (6d)
Yellow oil.
Reaction of Oxaziridines with Tributyltin Hydride/AIBN; Gen-
eral Procedure
The desired oxaziridine 5 or 6 (250 mg) was dissolved in anhyd de-
gassed benzene (5 mL) and Bu3SnH (29 mg, 0.09 mmol, in a 0.2 M
solution) was added by syringe to the stirred solution. A small por-
tion (ca. 2 mg) of AIBN was added and the solution was heated at
reflux under argon for 12 h. H2O (1 mL) was added and the organic
solvent was removed under reduced pressure. The residue was ex-
tracted with CH2Cl2 (3 × 5 mL) and the combined organic extracts
were dried (MgSO4) and concentrated under reduced pressure to
give the crude reaction product. Purification was effected using pre-
parative TLC with Et2O–light petroleum as eluent. Results are giv-
en in Table 3.
IR (film): 1725, 1620, 1535, 1420, 1365, 1240, 1190, 1020, 965,
890, 705 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.34 (t, J = 7.2 Hz, 3 H, CH3),
1.35–1.45 (m, 4 H), 1.58–1.66 (m, 1 H), 1.80–1.89 (m, 2 H), 2.02
(br q, J = 6.7 Hz, 2 H), 2.14–2.25 (m, 1 H), 2.45 (ddd, J = 14.4,
10.7, 8.7 Hz, 1 H), 2.71 (dd, J = 14.4, 8.2 Hz, 1 H), 4.25–4.33 (m, 2
H, OCH2), 4.89–4.99 (m, 2 H, H-6¢), 5.69–5.79 (m, 1 H, H-5¢),
7.36–7.39 (m, 3 H, ArH), 7.50–7.53 (m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.3 (CH3), 23.8 (CH2), 27.3
(CH2), 27.8 (CH2), 28.9 (CH2), 33.3 (CH2), 34.8 (CH2), 61.3
(OCH2), 76.9 (C-2), 87.8 (C-5), 114.7 (C-6¢), 127.1 (ArCH), 128.3
(ArCH), 129.5 (ArCH), 134.7 (ArC), 138.3 (C-5¢), 172.0 (C=O).
Reaction of Oxaziridines with Tetrameric Copper(I)triphe-
nylphosphine Chloride [Cu(PPh3)Cl]4; General procedure
The desired oxaziridine 5 or 6 (250 mg) was dissolved in anhyd
THF (5 mL), [Cu(PPh3)Cl]4 (5 mol%) was added and the solution
was refluxed until the starting material had been consumed (24–48
h). The solvent was removed under reduced pressure and the result-
ing residue was extracted with CH2Cl2 (3 × 5 mL). The combined
organic extracts were dried (MgSO4) and concentrated under re-
duced pressure to give the crude reaction product. Purification was
MS (EI): m/z = 316 (M + 1, 1%).
Anal. Calcd for C19H25NO3: C, 72.35; H, 8.0; N, 4.4. Found: C,
72.7; H, 8.1; N, 4.3.
Ethyl cis-2-(4¢-Methylpent-3¢-en-1¢-yl)-5-phenyl-6-oxa-1-azabi-
cyclo[3.1.0]hexane-2-carboxylate (5e)
Yellow oil.
Synthesis 2006, No. 12, 1981–1990 © Thieme Stuttgart · New York

1990
D. StC. Black et al.
PAPER
effected using preparative TLC with Et2O–light petroleum as elu-
ent. Results are given in Table 3.
(3) Liddell, J. R. Nat. Prod. Rep. 2002, 19, 773; and references
cited therein.
(4) Michael, J. P. Nat. Prod. Rep. 2005, 22, 603; and references
cited therein.
Ethyl 8-Benzyl-1-azabicyclo[3.3.0]octan-2-one-5-carboxylate
(8)
(5) For some recent examples, see: (a) Cossy, J. Chem. Rec.
2005, 5, 70. (b) Baker, S. R.; Parsons, A. F.; Pons, J.-F.;
Wilson, M. Tetrahedron Lett. 1998, 39, 7197.
(6) (a) Newcomb, M.; Horner, J. H.; Shahin, H. Tetrahedron
Lett. 1993, 34, 5523. (b) Bowman, W. R.; Coghlan, D. R.;
Shah, H. C. R. Chem. 2001, 4, 625. (c) Callier-Dublanchet,
A.-C.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron Lett. 1995,
36, 8791.
Pale-yellow oil; yield: 115 mg (46%).
IR (film): 3450, 1680, 1440, 1375, 1310, 1250, 1175, 1010, 790,
690 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.08–1.20 (m, 1 H, H-6a), 1.21 (t,
J = 7.2 Hz, CH3), 1.79 (dt, J = 12.3, 8.7 Hz, 1 H, H-4a), 1.88–2.08
(m, 3 H, H-6b, H-7), 2.29 (dd, J = 12.3, 7.7 Hz, 1 H, H-4b), 2.47
(dd, J = 16.4, 8.7 Hz, 1 H, H-3a), 2.73 (dddd, J = 16.4, 12.3, 7.7, 1.0
Hz, 1 H, H-3b), 2.89 (dd, J = 13.3, 8.2 Hz, 1 H, PhCHa), 3.44 (dd,
J = 13.3, 3.6 Hz, 1 H, PhCHb), 3.92–3.99 (m, 1 H, H-8), 4.14 (q,
J = 7.2 Hz, 2 H, OCH2), 7.13–7.30 (m, 5 H, ArH).
(7) (a) Prévost, N.; Shipman, M. Org. Lett. 2001, 3, 2383.
(b) Bowman, W. R.; Clark, D. N.; Marmon, R. J.
Tetrahedron Lett. 1992, 33, 4993.
(8) Black, D. StC.; Edwards, G. L.; Laaman, S. M. Tetrahedron
13C NMR (CDCl3, 75.5 MHz): d = 14.0 (CH3), 31.6 (C-7), 31.9 (C-
4), 32.5 (C-6), 36.0 (PhCH2), 36.2 (C-3), 54.3 (C-8), 61.5 (OCH2),
75.7 (C-5), 126.2 (ArCH), 128.1 (ArCH), 129.5 (ArCH), 137.8 (ArC),
172.4 (NC=O), 173.6 (OC=O).
Lett. 1998, 39, 5853.
(9) Black, D. StC.; Craig, D. C.; Edwards, G. L.; Laaman, S. M.
Bioorg. Chem. 1999, 27, 91.
(10) Ningsanont, N.; Black, D. StC.; Chanphen, R.;
Thebtaranonth, Y. J. Med. Chem. 2003, 46, 2397.
(11) (a) Bapat, J. B.; Black, D. StC. J. Chem. Soc., Chem.
Commun. 1967, 73. (b) Bapat, J. B.; Black, D. StC. Aust. J.
Chem. 1968, 21, 2507.
MS (EI): m/z = 288 (M + 1, 7%).
Anal. Calcd for C17H21NO3·0.5H2O: C, 68.9; H, 7.5; N, 4.7. Found:
C, 69.3; H, 7.2; N, 4.4.
(12) Black, D. StC.; Edwards, G. L.; Evans, R. H.; Keller, P. A.;
Laaman, S. M. Tetrahedron 2000, 56, 1889.
(13) Colombini, M.; Crotti, P.; Di Bussolo, V.; Favero, L.;
Gardelli, C.; Macchia, F.; Pineschi, M. Tetrahedron 1995,
51, 8089.
Ethyl 6,6-Dimethyl-2-(3¢-phenyl-3¢-oxoprop-1¢-yl)-1-azabicy-
clo[3.1.0]hexane-2-carboxylate (10)
Yellow-green oil; yield: 222 mg (46%).
IR (film): 3400, 1690, 1640, 1420, 1260, 730, 720, 690 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.03 (s, 3 H, CH3), 1.14 (s, 3 H,
CH3), 1.30 (t, J = 7.2 Hz, 3 H, CH2CH3), 1.90–1.98 (m, 2 H), 2.07–
2.13 (m, 2 H), 2.23 (t, J = 7.7 Hz, 2 H), 2.25–2.28 (m, 1 H), 3.03 (dt,
J = 17.4, 7.2 Hz, 1 H, CHaC=O), 3.26 (dt, J = 17.4, 7.7 Hz, 1 H,
CHbC=O), 4.17–4.22 (m, 2 H, OCH2), 7.42–7.47 (m, 2 H, ArH),
7.51–7.54 (m, 1 H, ArH), 7.97–8.00 (m, 2 H, ArH).
13C NMR (CDCl3, 75.5 MHz): d = 14.0 (CH3), 15.6 (CH3), 24.0
(CH2), 27.8 (CH3), 33.7 (CH2), 36.1 (CH2), 36.7 (CH2), 51.7 (CH),
60.5 (OCH2), 72.9 (C-2), 127.9 (ArCH), 128.1 (ArCH), 132.5 (ArCH),
137.1 (ArC), 175.4 (OC=O), 200.0 (PhC=O).
(14) Tanaka, M.; Tomioka, K.; Koga, K. Tetrahedron 1994, 50,
12829.
(15) Aubé, J. Chem. Soc. Rev. 1997, 26, 269.
(16) (a) Black, D. StC.; Watson, K. G. Aust. J. Chem. 1973, 26,
2505. (b) Black, D. StC.; Johnstone, L. M. Angew. Chem.,
Int. Ed. Engl. 1981, 20, 669; Angew. Chem. 1981, 93, 703.
(c) Black, D. StC.; Johnstone, L. M. Angew. Chem. Int. Ed.
Engl. 1981, 20, 670; Angew. Chem. 1981, 93, 704.
(d) Black, D. StC.; Johnstone, L. M. Aust. J. Chem. 1984, 37,
109. (e) Black, D. StC.; Johnstone, L. M. Aust. J. Chem.
1984, 37, 599.
(17) Aubé, J.; Peng, X.; Wang, Y.; Takusagawa, F. J. Am. Chem.
Soc. 1992, 114, 5466.
(18) Reynolds, A. J.; Scott, A. J.; Turner, C. I.; Sherburn, M. S. J.
Am. Chem. Soc. 2003, 125, 12108.
MS (EI): m/z = 315 (M, 1%).
Anal. Calcd for C19H25NO3·0.5H2O: C, 70.3; H, 7.8; N, 4.3. Found:
C, 70.1; H, 8.2; N, 4.0.
(19) (a) Beckwith, A. L. J.; Easton, C. J.; Lawrence, T.; Serelis,
A. K. Aust. J. Chem. 1983, 36, 545. (b) Beckwith, A. L. J.;
Schiesser, C. H. Tetrahedron 1985, 41, 3925.
(20) Horner, J. H.; Martinez, F. N.; Musa, O. M.; Newcomb, M.;
Shahin, H. E. J. Am. Chem. Soc. 1995, 117, 11124.
(21) Craig, D. C.; Edwards, G. L.; Muldoon, C. A. Synlett 1997,
1441.
Acknowledgment
We thank the Australian Research Council for an Australian Post-
graduate Award (to S.M.L.).
(22) (a) Edwards, G. L.; Muldoon, C. A.; Sinclair, D. J.
Tetrahedron 1996, 52, 7779. (b) Edwards, G. L.; Sinclair,
D. J. Synthesis 2005, 3613.
(23) Pigou, P. E.; Stirling, C. J. M. J. Chem. Soc., Perkin Trans.
2 1988, 725.
References
(1) Urban, S.; Hickford, S. J. H.; Blunt, J. W.; Munro, M. H. G.;
Kelly, M. Curr. Org. Chem. 2000, 4, 765.
(2) Daly, J. W.; Spande, T. F.; Garraffo, H. M. J. Nat. Prod.
2005, 68, 1556.
Synthesis 2006, No. 12, 1981–1990 © Thieme Stuttgart · New York