Preparation of new 2,4-disubstituted oxazoles from N-acylaziridines

Article abstract of DOI:10.1039/a604091h

The efficiency of the ring enlargement of 2-substituted N-acylaziridines to dihydrooxazoles followed by nickel peroxide oxidation to give 2,4-disubstituted oxazoles as a synthetic route is examined. Sodium iodide-promoted ring enlargements work well for N-acylaziridines bearing electron-donating 2-substituents. For N-acylaziridines bearing electron-withdrawing 2-substituents, the best results are obtained using acid-promoted rearrangement.

Full text of DOI:10.1039/a604091h

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Preparation of new 2,4-disubstituted oxazoles from N-acylaziridines
Frank W. Eastwood, Patrick Perlmutter* and Qi Yang
Department of Chemistry, Monash University, Clayton Victoria 3168, Australia
The efficiency of the ring enlargement of 2-substituted N-acylaziridines to dihydrooxazoles followed by
nickel peroxide oxidation to give 2,4-disubstituted oxazoles as a synthetic route is examined. Sodium
iodide-promoted ring enlargements work well for N-acylaziridines bearing electron-donating
2-substituents. For N-acylaziridines bearing electron-withdrawing 2-substituents, the best results are
obtained using acid-promoted rearrangement.
The isolation and structural characterisation of naturally-
occurring tris(oxazole)-containing molecules such as halichon-
dramide1,2 have sparked new interest in the synthesis of 2,4-
propyl ester was used as the electron-withdrawing group on the
aziridine since isopropyl aziridine-2-carboxylate 1 was readily
available from isopropyl acrylate by sequential bromination
and treatment with ammonia.13 For those aziridines bearing an
electron-donating group, 5a–d, azido-iodination 14 of a suitable
terminal alkene, 3a-d, followed by lithium aluminium hydride
disubstituted oxazoles. The methods which have been
developed may be divided into two main approaches. The first
involves the preparation of 2,4-disubstituted oxazoles via the
corresponding dihydrooxazole derivatives. The most widely
used such method employs a coupling reaction between imino
ethers and 1,2-amino alcohols.3 The dihydrooxazoles produced
in this way may then be oxidised, usually with nickel peroxide.4
Alternatively, the intermediate dihydrooxazoles may be pre-
pared by the rearrangement of N-acylaziridines.5 The second
approach involves preparation of 2,4-disubstituted oxazoles
without the intermediacy of dihydrooxazoles. Apart from
the classical method using imino ethers developed by the
Cornforths,6 this approach includes reaction of amides with
2-halogeno ketones,7–9 rearrangement of 2-acyloxy-N,N-
bis(trimethylsilyl)enamines10 and the rhodium()-promoted
coupling of nitriles with dialkyl diazomalonates.11
We were interested in developing the rearrangement of N-
acylaziridines carrying substituents which would allow the
eventual preparation of bis- and tris-(oxazoles). In this paper we
provide details of the regioselective preparation of a variety of
new 2,4-disubstituted oxazoles bearing such substituents using
both iodide- and acid-promoted rearrangement of N-acyl-
aziridines.12 It was found that the iodide-promoted route is very
effective with N-acylaziridines bearing electron-donating sub-
stituents but generates several products when an electron-
withdrawing substituent is attached to the aziridine. Acid-
promoted ring enlargement provided a useful solution to this
problem and yielded 2,4-disubstituted dihydrooxazoles in good
yield and with good regioselectivity.
reduction, was employed. Acylation of all the new aziridines,
most of which were not very stable, with benzoyl chloride,
cinnamoyl chloride, 2-phenyl-1,3-oxazole-4-carbonyl chloride
or benzyloxyacetyl chloride completed the syntheses of the
starting materials, 2a–d and 6a–e.
Results and discussion
Ring enlargement of N-acylaziridines bearing an electron-
withdrawing substituent at C-2
Preparation of 2-substituted N-acylaziridines
The method used for preparing the aziridines in this study was
governed by the nature of the aziridine substituent. An iso-
Mente et al. have reported that 2-vinyl-N-acylaziridines suc-
cessfully undergo nucleophile-promoted ring enlargement with
J. Chem. Soc., Perkin Trans. 1, 1997
35

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Table 1 Ring enlargement of N-acylaziridines 2a–d
Yield
(%)
Ratio
7: 8: 9
Method a t/h
1
2
3
4
5
6
7
2a
2b
A
B
C
A
C
A
A
20
20
0.7
20
0.5
89
40
79
100
83
94
34:50:16
85:15:0b
91:9:0
25:25:50
94:6:0
2c
2d
24
24
50:46:4
0:0:100
100
a
Method A: NaI, acetone (2a, 2b, 2d), DMF (2c), room temperature.
Method B: H2SO4, diethyl ether, room temperature. Method C:
CF3SO3H, benzene–hexane, room temperature. b Isopropyl 2-benzoyl-
amino-3-hydroxypropanoate (17% yield) and isopropyl 3-benzoyl-
amino-2-hydroxypropanoate (10%) were isolated.
good regioselectivity.14 Thus we attempted the ring enlargement
of 2a using iodide as the nucleophilic promoter and acetone as
solvent (Dewar’s conditions15) (Table 1, entry 1). This pro-
duced a mixture of dihydrooxazole regioisomers (7a and 8a) as
oxazoles was achieved using nickel peroxide as oxidant.4,17 We
briefly examined this procedure and found that significantly
improved yields could be obtained by adding the oxidant in
portions over several hours and by adding triethylamine to the
well as some ring-opened enamide 9a. Treatment of 2b in
acetone and of 2c in dimethylformamide with sodium iodide
gave similar results (Table 1, entries 4 and 6). Treatment of 2d in
acetone gave only the enamide 9d (Table 1, entry 7). In attempts
to improve this procedure we employed sodium bromide, chloro-
trimethylsilane or iodotrimethylsilane as the nucleophile in a
variety of solvents but none of these variations was satisfactory.
As it is known that acid also promotes the ring enlargement
of N-acylaziridines,16 we subjected a solution of 2a in diethyl
ether to concentrated sulfuric acid at room temperature (Table
1, entry 2). A mixture of products was obtained, consisting of
7a and 8a as well as the ring-opened products 10 and 11.
Although the ratio of the required isomer 7a to its regioisomer
8a was much improved (5.7:1), the yield of 7a was still unsatis-
factory. To avoid any hydrolysis products, attributed to the
presence of extraneous water, we attempted the ring enlarge-
ment using anhydrous trifluoromethanesulfonic acid. Pleas-
ingly, this modification provided a 10:1 mixture of 7a and 8a in
excellent yield (Table 1, entry 3). Similar results were obtained
for ring enlargement of 2b (Table 1, entry 5).
hot reaction mixture immediately prior to work-up (the latter in
order to displace any product complexed to the nickel salts).
The yields obtained are shown alongside the structures. The
yields were not always high but in some experiments the
unoxidised oxazoline was recovered and this could, if necessary,
be recycled.
Ring enlargement of N-acylaziridines bearing an electron-
donating substituent at C-2
In contrast to the reactions just described, ring enlargements of
6a–e using sodium iodide in acetone all proceeded with com-
plete regioselectivity, providing oxazolines 12a–e in excellent
yields.
Experimental
Melting points (mps) were determined on a Büchi SMP-20
melting point apparatus or a Kofler hotstage and are un-
corrected. IR Spectra were recorded on a Perkin-Elmer IR-
1600 spectrometer as mull in Nujol unless otherwise stated.
Low resolution mass spectra were recorded on a VG Micromass
7070F or a VG TRIO-1 mass spectrometer at 70 eV, with a
Conversion of dihydrooxazoles to oxazoles
Oxidation of all the dihydrooxazoles described in this work to
36
J. Chem. Soc., Perkin Trans. 1, 1997

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source temperature of 200 ЊC. Chemical ionisation mass
spectra (CI) were obtained using methane as the reagent gas.
Fast atom bombardment mass spectra (FAB) were performed
at the Victorian College of Pharmacy, Monash University.
High resolution NMR spectra were obtained either on a Bruker
AC-200 spectrometer or on a Bruker AM-300 spectrometer in
CDCl3 solution. Chemical shifts (δ) are given in ppm and the
coupling constants (J) in Hz. Ether refers to diethyl ether and
light petroleum refers to the hydrocarbon fraction bp 60–70 ЊC.
1:1) to give aziridine 2d (1.17 g, 96%) as a colourless oil (Found:
C, 64.9; H, 6.8; N, 5.0. C15H19NO4 requires C, 65.0; H, 6.9; N,
5.1%); m/z 278 (M + 1, 6%), 91 (100); νmax/cmϪ1 1733, 1704,
1455, 1279, 1219, 1183, 1107, 911, 871, 818, 741, 699; δH 7.34 (5
H, s, C6H5), 5.03 (1 H, septet, J 6.2, CHMe2), 4.61 (2 H, AB q, J
11.8, OCH2), 4.15 (2 H, AB q, J 16.5, OCH2), 3.23 (1 H, dd, J
5.3 and 3.1, 2-H), 2.56 (1 H, dd, J 3.1 and 1.3, 3-H), 2.47 (1 H,
dd, J 5.3 and 1.3, 3-H), 1.23 (3 H, d, J 6.2, CH3), 1.20 (3 H, d, J
6.2, CH3); δC 180.3, 167.9, 137.1, 128.4, 127.9, 127.7, 73.4,
70.51, 69.8, 35.2, 29.4, 21.6.
Isopropyl N-benzoylaziridine-2-carboxylate 2a
The following preparation of 2a illustrates the general method
for the acylation of aziridines. To a solution of isopropyl
aziridine-2-carboxylate 1 (583 mg, 4.2 mmol) and triethylamine
(423 mg, 4.2 mmol) in benzene (35 cm3) cooled in an ice-water
bath was added dropwise a solution of benzoyl chloride (590
mg, 4.2 mmol) in benzene (15 cm3). The mixture was allowed to
warm to room temperature, and then stirred for a further 3 h.
The reaction mixture was filtered and the filtrate washed twice
with water, dried (MgSO4) and the benzene evaporated in vacuo
to give a colourless residue (967 mg, 99%) which was
purified by flash column chromatography (silica gel, ether–light
petroleum, 1:1) to give aziridine 2a (928 mg, 96%) as a colour-
less oil (Found: C, 66.9; H, 6.2; N, 5.9. C13H15NO3 requires C,
Preparation of 1-azido-3-(1,1-dimethylethoxy)-2-iodopropane 4a
The preparation of 4a exemplifies the general method employed
for the addition of iodo azide to alkenes 3a–d. To a stirred
suspension of sodium azide (8.00 g, 125 mmol) in acetonitrile
(50 cm3) cooled in an ethanol–ice bath was added iodine mono-
chloride (9.36 g, 57 mmol) over a 20 min period. The reaction
mixture was stirred for an additional 10 min and 3-(1,1-
dimethylethoxy)prop-1-ene20 3a (6.57 g, 57 mmol) was added
dropwise. The mixture was allowed to warm to room temper-
ature and stirred for 18 h. The red–brown mixture was poured
into water (125 cm3) and extracted with ether. The ether
extracts were combined and washed with 5% aqueous sodium
thiosulfate to give a colourless solution. This ethereal solution
was washed with water and dried (MgSO4). Evaporation of the
ether in vacuo at room temperature gave a yellow liquid
(11.64 g, 73%) whose 1H NMR spectrum displayed a mixture of
4a and its regioisomer 2-azido-3-(1,1-dimethylethoxy)-1-iodo-
propane in a ratio of 1:3; νmax/cmϪ1 2105. 1-Azido-3-(1,1-
dimethylethoxy)-2-iodopropane 4a; δH 1.20 (s, Me). Other sig-
nals were mixed with those of the regioisomer and not able to
be distinguished. δC 73.8, 64.6, 55.3, 28.6, 27.5. 2-Azido-3-(1,1-
dimethylethoxy)-1-iodopropane; δH 3.24 (dd, J 10 and 5.9), 1.22
(s, Me), other signals were mixed with those of 4a and could not
be distinguished. δC 73.8, 63.8, 61.5, 27.4, 24.5. These two
regioisomers were not separated and were used as such in fur-
ther reactions.
66.9; H, 6.3; N, 6.0%); m/z 191 (M Ϫ 42, 4.2), 105 (100); νmax
/
cmϪ1 1735, 1686, 1233, 1204, 897, 719; δH 8.04–7.60 (2 H, m)
and 7.58–7.40 (3 H, m, C6H5), 4.99 (1 H, septet, J 6.3, CHMe2),
3.24 (1 H, dd, J 5.7 and 3.2, 2-H), 2.76 (1 H, dd, J 3.2 and 1.3,
3-H), 2.66 (1 H, dd, J 5.7 and 1.3, 3-H), 1.18 (3 H, d, J 6.3, Me),
1.15 (3 H, d, J 6.2, Me); δC 176.7, 167.6, 133.0, 132.7, 128.9,
128.5, 69.6, 36.2, 30.8, 21.5, 21.7.
Isopropyl N-cinnamoylaziridine-2-carboxylate 2b. The reac-
tion of cinnamoyl chloride (334 mg, 2 mmol) with isopropyl
aziridine-2-carboxylate 1 (260 mg, 2 mmol) and triethylamine
(0.5 cm3) in benzene gave a light yellow oil (483 mg). Purific-
ation of the crude product by preparative radial chrom-
atography (silica gel, ether–light petroleum, 1:2) yielded pure
aziridine 2b (471 mg, 91%) as a colourless oil (Found: C, 69.2;
H, 6.7; N, 5.6. C15H17NO3 requires C, 69.5; H, 6.6; N, 5.4%);
m/z 260 (M + 1, 6.4%), 131 (100); νmax/cmϪ1 1734, 1684, 1692,
1105, 770, 687; δH 7.72 (1 H, d, J 16.1, 3Ј-H), 7.58–7.49 (2 H, m)
and 7.46–7.36 (3 H, m, C6H5), 6.62 (1 H, d, J 16.1, 2Ј-H), 5.09 (1
H, septet, J 6.3, CHMe2), 3.20 (1 H, dd, J 5.6 and 3.1, 2-H),
2.69 (1 H, dd, J 3.1 and 1.6, 3-H), 2.58 (1 H, dd, J 5.6 and 1.6,
3-H), 1.27 (3 H, d, J 6.3, CH3), 1.26 (3 H, d, J 6.3, CH3); δC
175.8, 167.7, 144.3, 134.2, 130.4, 128.9, 128.1, 120.2, 69.7, 35.1,
30.7, 21.7, 21.6.
3-Azido-1,1-dimethoxy-2-iodopropane 4b. The reaction of
sodium azide (3.00 g, 46 mmol), iodine monochloride (3.80 g,
23 mmol) and prop-2-enal dimethyl acetal 3b (2.40 g, 23 mmol)
yielded a yellow liquid as the crude product (4.65 g, 75%)
which was purified by flash column chromatography (ether–
light petroleum, 1: 10) (Rf 0.36), m/z 271 (M+, 0.26%), 240 (1.9),
184 (6.7), 75 (100); νmax/cmϪ1 2934, 2834, 2104, 1117, 1066;
δH 4.31 (1 H, d, J 5.3, 1-H), 4.15 (1 H, q, J 5.9, 2-H), 3.76 (2 H,
d, J 5.9, 3-H), 3.46 (6 H, s, 2 × OCH3); δC 104.7, 55.8, 55.4, 54.8,
29.7.
Isopropyl
N-(2-phenyl-1,3-oxazol-4-ylcarbonyl)aziridine-2-
3-Azido-1,1-diethoxy-2-iodopropane 4c. The reaction of
sodium azide (8.5 g, 131 mmol), iodine monochloride (10.8 g,
66 mmol) and prop-2-enal diethyl acetal 3c21 (8.50 g, 65 mmol)
gave 4c (14.98 g, 77%) as a light yellow liquid which was puri-
fied by flash column chromatography (ether–light petroleum,
1:50) (Rf 0.30), m/z (FAB) 300 (M + 1, 4%), 286 (28), 274 (6),
240 (18), 228 (22), 200 (17), 183 (13), 129 (37), 114 (13), 103
(100); νmax/cmϪ1 2978, 2104, 1059; δH 4.49 (1 H, d, J1,2 5.2, 1-H),
4.14 (1 H, dt, J2,3, 2,1 6.4 and 5.2, 2-H), 3.79–3.69 (4 H, m, OCH
and 3-H), 3.63–3.58 (2 H, m, OCH), 1.25 (6 H, t, J 7.0,
2 × CH3); δC 102.7, 64.2, 63.8, 54.8, 31.0, 15.13, 15.10.
2-(2-Azido-1-iodoethyl)-1,3-dioxolane 4d. The reaction of
sodium azide (6.60 g, 0.1 mol) and iodine monochloride (8.30 g,
50 mmol) with 2-vinyl-1,3-dioxolane 3d22 (5.16 g, 50 mmol)
gave 8.41 g of red–brown liquid, which was separated by flash
column chromatography (silica gel, ether–light petroleum, 1:5)
into two compounds. 2-(2-Azido-1-iodoethyl)-1,3-dioxolane 4d
(Rf 0.42) was obtained as a light yellow liquid (4.84 g, 36%); m/z
(CI) 269 (M+, 0.2%), 73 (100); νmax/cmϪ1 2103; δH 4.78 (1 H, d,
J2,1Ј 4, 2-H), 4.17 (1 H, ddd, J1Ј,2Ј, 1Ј, 2Ј, 1Ј,2 7, 6 and 4, 1Ј-H), 4.13–
4.08 (2 H, m, 4-H a and 5-Ha ), 4.03–3.97 (2 H, m, 4-H b and 5-
Hb ), 3.79 (2 H, br d, J 7, 2Ј-H); δC 102.7, 65.88, 65.85, 54.5,
31.0. 2Ј-Hydroxyethyl 3-azido-2-iodopropanoate (Rf 0.02) was
carboxylate 2c. The reaction of isopropyl aziridine-2-
carboxylate 1 (129 mg, 1 mmol) and 2-phenyl-1,3-oxazole-4-
carbonyl chloride18 (220 mg, 1.05 mmol) in the presence of
triethylamine gave the crude product (310 mg) as a white solid.
The product was dissolved in ether and filtered through a short
silica gel column (eluent ether–light petroleum, 1:1) to give
pure aziridine 2c (287 mg, 96%) as a white solid, mp 113.5–
114 ЊC (Found: C, 64.2; H, 5.2; N, 9.2. C16H16N2O4 requires C,
64.0; H, 5.4; N, 9.3%); m/z 300 (M+, 24%), 172 (100); νmax/cmϪ1
1742, 1693, 1571, 1207, 848, 712, 686; δH 8.32 (1 H, s, 5Ј-H),
8.10–8.05 (2 H, m) and 7.52–7.45 (3 H, m, C6H5), 5.01 (1 H,
septet, J 6.3, CHMe2), 3.46 (1 H, dd, J 5.2 and 3.2, 2-H), 2.75 (1
H, dd, J 3.2 and 1.1, 3-H), 2.69 (1 H, dd, J 5.2 and 1.1, 3-H),
1.19 (3 H, d, J 6.3, Me), 1.18 (3 H, d, J 6.3, Me); δC 169.8, 167.8,
161.8, 142.7, 137.4, 131.1, 128.8, 126.7, 126.5, 69.6, 36.3, 30.3,
21.6, 21.5.
Isopropyl N-benzyloxyacetylaziridine-2-carboxylate 2d. Reac-
tion of isopropyl aziridine-2-carboxylate 1 (651 mg, 5 mmol)
and 2-benzyloxyacetyl chloride19 (921 mg, 5 mmol) in the pres-
ence of triethylamine (509 mg, 5 mmol) gave a light yellow oil
(1.37 g, 99%) as the crude product which was further purified by
flash column chromatography (silica, ether–light petroleum,
J. Chem. Soc., Perkin Trans. 1, 1997
37

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obtained as an orange oil (3.03 g, 22%); m/z 268 (M Ϫ OH,
2.5%), 45 (100); νmax/cmϪ1 3406, 2108, 1728; δH 4.44 (1 H, dd, J
10 and 5, 2-H), 4.34 (2 H, dt, J 9 and 5, 2Ј-H) 3.93 (1 H, dd, J 13
and 10, 3-H), 3.86 (2 H, t, J 5, 1Ј-H), 3.65 (1 H, dd, J 13 and 5,
3-H), 1.91, (1 H, br s, OH); δC 170.0, 67.6, 60.5, 54.5, 14.8.
product by chromatography (silica gel, ether–light petroleum,
1:5) gave two products. N-Benzoyl-2-(dimethoxymethyl)-
aziridine 6b (Rf 0.35) (482 mg) (Found: C, 65.3; H, 7.0; N,
6.2. C12H15NO3 requires C, 65.1; H, 6.8; N, 6.3%); m/z 221
(M+, 0.68%), 220 (M Ϫ 1, 1.5), 75 (100); νmax/cmϪ1 1681,
1324, 1228, 1070, 862, 714, 689; δH 8.12–8.07 (2 H, m) and
7.60–7.41 (3 H, m, C6H5), 4.43 (1 H, d, J 4.4, 1Ј-H), 3.44 (3 H,
s, OCH3), 3.41 (3 H, s, OCH3), 2.88 (1 H, ddd, J 6.0, 4.4 and
3.6, 2-H), 2.53–2.49 (2 H, m, 3-H); δC 178.5, 132.8, 132.7,
129.2, 128.3, 102.4, 54.4, 53.1, 37.6, 28.4. (E)-3-Benzoylamino-
1-methoxyprop-1-ene (Rf 0.2) (80 mg) [Found: (M + 1),
192.1015. C11H14NO2 requires (M + 1) 192.1025.1538]; m/z 191
(M+, 11%), 105 (100); νmax/cmϪ1 3318, 3066, 2935, 1640, 1603,
1578, 1490, 1213, 940, 804, 712, 689; δH 7.80–7.74 (2 H, m) and
7.48–7.36 (3 H, m, C6H5), 6.55 (1 H, d, J 12.6, 1-H), 6.40 (1 H,
br s, NH), 4.88 (1 H, dt, J 12.6 and 7.5, 2-H), 3.96 (2 H, ddd, J
6.5, 5.5 and 0.94, 3-H2), 3.53 (3 H, s, Me); δC 167.2, 150.7, 134.5,
131.3, 128.4, 126.8, 98.5, 55.9, 38.4.
Preparation of N-acylaziridines
The following procedure for the preparation of 6a from 4a
exemplifies the general method employed for the preparation of
N-acyl derivatives 6a–e. (As the aziridine products 5a–d
obtained from the reductions were not very stable, they were
immediately acylated.)
N-Benzoyl-2-(1,1-dimethylethoxymethyl)aziridine 6a. To a
suspension of LiAlH4 (5.24 g, 0.13 mol) in ether (250 ml) at
0 ЊC was added dropwise the crude mixture of 4a and its regio-
isomer (23.8 g, 0.084 mol). The reaction was allowed to warm
to room temperature and stirred for 12 h. A solution of 20%
aqueous NaOH (20 cm3) was added slowly and the mixture was
stirred for a further 45 min. The white precipitate was removed
by filtration and the filtrate was dried (MgSO4) and concen-
trated under vacuum to give 9.80 g (90%) of a colourless liquid.
N-Benzoyl-2-(diethoxymethyl)aziridine 6c. Using the same
procedure as that described for the preparation of 5a, 3-azido-
1,1-diethoxymethyl-2-iodopropane 4c (3.00 g, 0.01 mol) was
reduced with LiAlH4 (625 mg, 0.016 mol) in ether (40 cm3) to
1
The H NMR spectrum of the crude product indicated a mix-
1
ture of 2-(1,1-dimethylethoxymethyl)aziridine 5a and 2-amino-
1-(1,1-dimethylethoxy)propane in a ratio of 5:3. Aziridine 5a;
νmax/cmϪ1 3222, 1364, 1253, 1198, 1079, 858, 668; δH 3.38 (1 H, d,
J 5, 1Ј-H), 3.40 (1 H, d, J 5, 1Ј-H), 2.13–2.23 (1 H, m, 2-H), 1.77
(1 H, d, J 6, 3-H), 1.51 (1 H, d, J 4, 3-H), 1.19, (9 H, s, 3× Me).
2-Amino-1-(1,1-dimethylethoxy)propane; δH 3.28 (1 H, dd, J 13
and 8, 1-H), 3.10–2.93 (1 H, m, 2-H), 3.02, (1 H, dd, J 13 and 8,
1-H), 1.64 (2 H, br s, NH), 1.18 (9 H, s, 3 × Me), 1.03 (3 H, d, J
6, 3-H). The crude mixture of 2-(1,1-dimethylethoxy-
methyl)aziridine 5a and 2-amino-1-(1,1-dimethylethoxy)pro-
pane (1.05 g, 8 mmol) was treated with benzoyl chloride
(1.01 g, 8 mmol) in the presence of triethylamine (1.00 g, 10
mmol) to give a light yellow oil (1.89 g, 98%). A portion of the
crude mixture (285 mg) was purified by preparative chroma-
tography (silica gel, ether–light petroleum, 1:2). N-Benzoyl-2-
(1,1-dimethylethoxymethyl)aziridine 6a (Rf 0.6) was obtained as
a light yellow oil (157 mg, 55%) [Found: (FAB), (M + 1),
234.1509. C14H20NO2 (M + 1) requires 243.1494]; m/z 232
(M Ϫ 1, 0.25%), 105 (100); νmax/cmϪ1 1677, 1227, 1086, 877,
668; δH 8.22–8.17 (2 H, m) and 7.63–7.39 (3 H, m, C6H5), 3.56 (2
H, ddd, J 10.2, 5.5 and 4.8, 1Ј-H), 2.78 (1 H, dddd, J 5.8, 5.5,
4.8 and 3.6, 2-H), 2.56 (1 H, d, J 6.0, 3-Ha), 2.29 (1 H, d, 3.6,
3-Hb), 1.19 (9 H, s, 3 × CH3); δC 178.5, 132.9, 132.5, 129.4,
128.0, 73.2, 62.5, 38.3, 28.5, 27.2. 1-(1,1-Dimethylethoxy)-2-
benzoylaminopropane (Rf 0.53) was obtained as a colourless
solid (97 mg, 34%) [Found: (M + 1) 236.165 ± 0.002.
C14H22NO2 (M + 1) requires 236.1645]; m/z 236 (M + 1, 18%),
105 (100); νmax/cmϪ1 3321, 1637; δH 7.79–7.44 (2 H, m) and
7.53–7.37 (3 H, m, C6H5), 6.58 (1 H, br d, NH), 4.36–4.27 (1 H,
m, 2-H), 3.49 (1 H, dd, J 8.9 and 4.1, 1-Ha), 3.39 (1 H, dd, J 8.9
and 3.3, 1-Hb), 1.28 (3 H, d, J 6.7, 3-H3), 1.20 (9 H, s, 3 × CH3);
δC 166.6, 134.9, 131.1, 128.3, 126.7, 72.76, 64.3, 45.5, 27.4, 17.7.
N-Benzoyl-2-(dimethoxymethyl)aziridine 6b. Using the same
procedure as that described for 5a, reduction of 3-azido-1,1-
dimethoxy-2-iodopropane 4b (1.40 g) with LiAlH4 (325 mg) in
ether gave 479 mg (80% of crude product) of a colourless
afford a colourless liquid (1.19 g, 82%). The H NMR spec-
trum of the crude product indicated a mixture which contained
mainly 2-(diethoxymethyl)aziridine 5c; νmax/cmϪ1 3300, 2976,
2930, 1227, 1060, 668; δH 4.43 (1 H, d, J 4.7, 1Ј-H), 3.83–3.46
(4 H, m, 2 × OCH2), 2.21–2.15 (1 H, m, 2-H), 1.70 (1 H, d,
J 5.5, 3-H), 1.66 (1 H, d, J 3.5, 3-H), 1.221 (3 H, t, J 7.0, CH3),
1.219 (3 H, t, J 7.0, CH3); δC 101.7, 62.0, 61.6, 31.5, 21.4, 15.2.
Benzoyl chloride (548 mg, 3.9 mmol) was treated with crude
2-(diethoxymethyl)aziridine 5c (566 mg, 3.9 mmol) in the pres-
ence of triethylamine (450 mg, 4.5 mmol) to give a light yellow
oil (970 mg) whose 1H NMR spectrum showed a mixture of the
desired aziridine 6c and (E)-3-benzoylamino-1-ethoxyprop-1-
ene. Separation by flash column chromatography (ether–light
petroleum, 1:10) gave the aziridine 6c (Rf 0.32) as a colourless
oil (622 mg, 64%) (Found: C, 67.7; H, 7.6; N, 5.7. C14H19NO3
requires C, 67.5; H, 7.7; N, 5.6%); m/z (CI) 250 (M + 1, 1.5%),
105 (100); νmax/cmϪ1 2976, 1680, 1321, 1277, 1062, 875, 715, 689;
δH (300 MHz) 8.15– 8.11 (2 H, m), 7.58–7.52 (1 H, m) and 7.46–
7.41 (2 H, m, C6H5), 4.52 (1 H, d, 1Ј-H), 3.82–3.50 (4 H, m,
2 × OCH2), 2.87 (1 H, ddd, J 6.1, 4.5 and 3.6, 2-H), 2.52 (1 H,
d, J 6.1, 3-Ha), 2.50 (1 H, d, J 3.6, 3-Hb), 1.26 (3 H, t, J 7.0,
CH3), 1.22 (3 H, t, J 7.0, CH3); δC 178.4, 132.8, 132.7, 129.3,
128.2, 101.2, 62.7, 61.8, 38.6, 28.1, 15.2.
N-Benzoyl-2-(1,3-dioxolan-2-yl)aziridine 6d. Using the same
procedure as that described for the preparation of 5a, 2-(2-
azido-1-iodoethyl)-1,3-dioxolane 4d (4.20 g, 15.6 mmol) was
reduced with LiAlH4 (1.20 g, 31 mmol) in ether (45 cm3) to give
1.245 g (69%) of light yellow liquid as the crude product which
contained ca. 80% of 2-(1,3-dioxolan-2-yl)aziridine 5d accord-
1
ing to the H NMR spectrum; νmax/cmϪ1 3299, 1233, 868, 668;
δH 4.72 (1 H, d, J 4, 2Ј-H), 4.06–3.87 (4 H, m, 2 × OCH2), 2.75
(1 H, br s, NH), 2.25 (1 H, ddd, J 6, 4 and 4, 2-H), 1.82 (1 H, d,
J 6, 3-H), 1.68 (1 H, d, J 3.5, 3-H); δC 104.5, 65.1, 30.9, 21.3.
Benzoyl chloride (1.40 g, 9.8 mmol) was treated with the crude
mixture of 2-(1,3-dioxolan-2-yl)aziridine 5d (1.10 g, 9.6 mmol)
in the presence of triethylamine (1.00 g, 10 mmol) to yield 1.87
g of a yellow oil. The crude product was separated by flash
column chromatography (silica gel, ether–light petroleum, 1:1)
to give title compound 6d (Rf, 0.31) (1.05 g, 49%) (Found: C,
66.0; H, 5.8; N, 6.8. C12H13NO3 requires C, 65.7; H, 6.0; N,
6.4%); m/z 218 (M Ϫ 1, 2%), 105 (100); νmax/cmϪ1 2893, 1674,
1223, 858, 713, 688, 659; δH 8.18–8.13 (2 H, m) and 7.57–7.42
(3 H, m, C6H5), 4.94 (1 H, d, J 4.6, 2Ј-H), 4.09–3.94 (4 H, m,
2 × OCH2), 2.80 (1 H, ddd, J 6.3, 4.6 and 3.5, 2-H), 2.57 (1 H,
d, J 6.3, 3-Ha), 2.45 (1 H, d, J 3.5, 3-Hb); δC 178.4, 132.9, 132.5,
129.4, 128.4, 103.5, 65.5, 65.2, 38.5, 27.8.
1
liquid. The H NMR spectrum displayed signals of a mixture
which contained the desired aziridine 5b as the major product,
m/z (CI) 118 (M + 1, 5%), 86 (100); νmax/cmϪ1 3300, 1458, 1274,
1213, 1193, 1115, 1057, 844; δH 4.31 (1 H, J 3.7, 1Ј-H), 3.41 (3
H, s, OMe), 3.39 (3 H, s, OMe), 2.22–2.15 (1 H, m, 2-H), 1.73 (1
H, d, J 5.7, 3-H), 1.66 (1 H, d, J 3.4, 3-H), 1.46 (1 H, br s, NH);
δC 103.3, 53.6, 53.3, 30.7, 21.2. The reaction of benzoyl chloride
(548 mg, 3.9 mmol) and crude 2-(dimethoxymethyl) azidirine
5b (458 mg) in the presence of triethylamine (450 mg) gave
a light yellow liquid (831 mg) whose 1H NMR spectrum
showed a mixture of aziridine 6b and (E)-3-benzoylamino-
1-methoxyprop-1-ene in a ratio of 5:1. Purification of the crude
N-Cinnamoyl-2-(diethoxymethyl)aziridine 6e. From the re-
action of cinnamoyl chloride (632 mg, 3.58 mmol) and crude
38
J. Chem. Soc., Perkin Trans. 1, 1997

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1
2-(diethoxymethyl)aziridine 5c (500 mg) in the presence of tri-
ethylamine (700 mg) in benzene, a yellow oil (992 mg) was
obtained. Separation by flash column chromatography (silica,
ether–light petroleum, 1:10) of the crude product gave aziridine
6e as a colourless oil (Rf 0.38) (676 mg, 69%) (Found: C, 69.4;
H, 7.5; N, 5.0. C16H21NO3 requires C, 69.8; H, 7.7; N, 5.1%);
m/z (CI) 276 (M + 1, 12%), 103 (100); νmax/cmϪ1 2976, 1677,
1628, 1337, 1258, 1062, 884, 770, 688; δH 7.76 (1 H, d, J 16.0, 3Љ-
H), 7.57–7.51 (2 H, m) and 7.42–7.35 (3 H, m, C6H5), 6.75 (1 H,
d, J 16.0, 2Љ-H), 4.43 (1 H, d, J 5.0, 1Ј-H), 3.91–3.53 (4 H, m,
2 × OCH2), 2.79 (1 H, ddd, J 6.0, 5.0 and 3.4, 2-H), 2.50 (1 H,
d, J 6.0, 3-Ha), 2.39 (1 H, d, J 3.4, 3-Hb), 1.29 (3 H, t, J 7.1,
CH3), 1.24 (3 H, t, J 7.1, CH3); δC 177.5, 143.5, 134.4, 130.1,
128.7, 127.9, 120.5, 101.6, 62.6, 62.5, 38.1, 27.7, 15.2, 15.1.
(1.5 cm3) gave a white solid product. The H NMR spectrum
displayed signals for isomers 7c, 8c and 9c in a ratio of 9:8.3:1.
Separation by preparative TLC (silica gel, ether–light petrol-
eum, 1:1) gave the three isomeric products as white solids. Iso-
propyl 2-(2-phenyl-1,3-oxazol-4-ylcarbonylamino)propenoate 9c
(Rf 0.5) (2 mg, 4%), mp 86–89 ЊC (Found: M+, 300.112 ± 0.003.
C16H16N2O4 requires M, 300.1108); m/z 300 (M+, 23%), 105
(100); νmax/cmϪ1 3366, 1717, 1684, 1588, 1516, 1321, 1197, 1107,
854, 779, 705; δH 9.43 (1 H, br s, NH), 8.28 (1 H, s, 5Ј-H), 8.12–
8.07 (2 H, m) and 7.53–7.46 (3 H, m, C6H5), 6.73 (1 H, s, 3-Hcis,
5.99 (1 H, d, J 1.6, 3-Htrans), 5.20 (1 H, septet, J 6.3, CHMe2),
1.38 (6 H, d, J 6.3, 2 × CH3); δC 163.3, 161.5, 159.2, 141.2,
137.3, 131.4, 128.9, 131.2, 126.8, 126.4, 108.8, 70.2, 21.7. Iso-
propyl 2-(2-phenyl-1,3-oxazol-4-yl)-4,5-dihydro-1,3-oxazole-4-
carboxylate 7c (Rf 0.3) (25 mg, 47%), mp 126–127 ЊC (Found:
C, 64.0; H, 5.2; 9.3. C16H16N2O4 requires C, 64.0; H, 5.4; N,
9.3%); m/z 300 (M+, 10%), 213 (100); νmax/cmϪ1 1734, 1677,
1560, 1108, 987, 954, 889; δH 8.24 (1 H, s, 5Ј-H), 8.21–8.08 (2 H,
m) and 7.53–7.41 (3 H, m, C6H5), 5.11 (1 H, septet J 6.3,
CHMe2), 4.92 (1 H, dd, J 10.6 and 7.9, 4-H), 4.56–4.72 (2 H, m,
5-H2), 1.31 (3 H, d, J 6.3, Me), 1.30 (3 H, d, J 6.3, CH3); δC
170.2, 162.5, 160.0, 141.2, 131.3, 131.0, 128.7, 126.8, 126.4,
69.9, 69.5, 68.8, 21.7, 21.66. Isopropyl 2-(2-phenyl-1,3-oxazol-4-
yl)-4,5-dihydro-1,3-oxazole-5-carboxylate 8c (Rf 0.22) (23 mg,
43%), mp 122.5–123.5 ЊC (Found: C, 64.0; H, 5.4; N, 9.3.
C16H16N2O4 required C, 64.0; H, 5.4; N, 9.3%); m/z 300 (M+,
22%), 213 (100); νmax/cmϪ1 1747, 1682, 1563, 1225, 1107, 888,
856, 776, 706, 689; δH 8.24 (1 H, s, 5Ј-H) 8.21–8.09 (2 H, m) and
7.53–7.41 (3 H, m, C6H5), 5.13 (1 H, septet, J 6.3, CHMe2), 5.06
(1 H, dd, J 10.8 and 7.2, 5-H), 4.39 (1 H, dd, J 15.3 and 10.8, 4-
Ha), 4.14 (1 H, dd, J 15.3 and 7.2, 4-Hb), 1.29 (6 H, d, J 6.3,
2 × CH3); δC 169.7, 160.6, 157.8, 140.9, 131.1, 131.0, 128.8,
126.8, 126.5, 76.0, 69.6, 59.3, 21.6. Reaction of aziridine 2c (15
mg) and sodium iodide (15 mg) in [2H]6acetone (0.5 cm3) pro-
vided 7c, 8c and 9c in a ratio of 2:2:1.
General method for the iodide-promoted ring expansion of
N-acylaziridines
Aziridines 2a–d and 6a–e were mixed with sodium iodide in
acetone or dimethylformamide (DMF). The reaction was
stirred at room temperature for 2–24 h. The solvent was removed
in vacuo and the residue extracted with ether where acetone was
used, or where DMF was used as reaction solvent, the reaction
mixture was partitioned between water and benzene. The
organic phase was dried (MgSO4) and concentrated to give
crude products which were purified by chromatography.
Reaction of isopropyl N-benzoylaziridine-2-carboxylate 2a.
Treatment of isopropyl N-benzoylaziridine-2-carboxylate 2a
(2.38 g, 10.23 mmol) with sodium iodide (19.19 g, 130 mmol) in
acetone (250 cm3) gave a yellow oil. The 1H NMR spectrum of
the crude product indicated a mixture of isomers 7a, 8a and 9a
in a ratio of 1.7:3.4:1. The mixture was separated by flash
chromatography (silica gel, ether–light petroleum, 1:1) into
three compounds. Isopropyl 2-phenyl-4,5-dihydro-1,3-oxazole-
4-carboxylate 7a (Rf 0.34) (733 mg, 31%) crystallised from light
petroleum as colourless crystals, mp 41.8–42 ЊC (lit., 23 40–
42 ЊC). Isopropyl 2-phenyl-4,5-dihydro-1,3-oxazole-5-carboxyl-
ate 8a (Rf 0.26) (1.048 g, 44%) crystallised from light petroleum
as colourless crystals, mp 67.2–67.8 ЊC (Found: C, 66.9; H, 6.3;
N, 6.2. C13H15NO3 requires C, 66.9; H, 6.5; N, 6.0%); m/z 234
(M + 1, 35%), 57 (100); νmax/cmϪ1 1739, 1658, 1580, 1222, 1109,
1062, 1023, 986, 899, 780, 698, 681; δH 8.01–7.90 (2 H, m) and
7.54–7.38 (3 H, m, C6H5), 5.12 (1 H, septet, J 6.3, CHMe2), 5.04
(1 H, dd, J 10.8 and 7.2, 5-H), 4.36 (1 H, dd, J 15.1 and 10.8, 4-
Ha), 4.12 (1 H, dd, J 15.1 and 7.2, 4-Hb), 1.29 (6 H, d, J 6.3,
2 × CH3); δC 170.1, 164.1, 131.6, 128.4, 127.0, 75.9, 69.4, 59.4,
21.7. Isopropyl 2-benzamidopropenoate 9a (Rf 0.6) was obtained
as a pale yellow oil (340 mg, 14%) (Found: M+, 233.105 ± 0.002.
C13H15NO3 requires M, 233.1048); m/z 233 (M+, 32%), 105 (100);
νmax/cmϪ1 3408, 1710, 1678, 1637, 1602, 1581, 1518, 1363, 1319,
1195, 1105, 905, 828, 807, 758, 698; δH 8.60 (1 H, br s, NH),
7.88–7.82 (2 H, m) and 7.58–7.42 (3 H, m, C6H5), 6.76 (1 H, s,
3-Hcis), 5.98 (1 H, d, J 13.3, 3-Htrans), 5.16 (1 H, septet, J 6.3,
CHMe2), 1.34 (6 H, d, J 6.3, 2 × CH3); δC 165.7, 163.8, 134.3,
132.0, 131.5, 128.8, 126.9, 108.3, 70.3, 21.7.
Reaction of isopropyl N-cinnamoylaziridine-2-carboxylate 2b.
Aziridine 2b (25 mg) was treated with sodium iodide (20 mg) in
acetone (1 cm3) to give a light yellow oil as the crude product
(27 mg). The 1H NMR spectrum of the crude mixture displayed
all the distinguishing signals for isomeric products 7b, 8b and 9b
in a ratio of 1 : 1 : 2. The same reaction in DMF gave a crude
mixture of 7b, 8b and 9b in a ratio of 1.6: 1.5 : 1. Isopropyl 2-
(cinnamoylamino)propenoate 9b; δH 7.96 (1 H, br s), 7.71–7.50 (2
H, m, C6H5), 7.69 (1 H, d, J 15.5, 3Ј-H), 7.40–7.35 (3 H, m,
C6H5), 6.50 (1 H, d, J 15.5, 2Ј-H), 6.72 (1 H, s, 3-Hcis), 5.93 (1 H,
d, J 1.4, 3-Htrans), 5.15 (1 H, septet, J 6.2, CHMe2), 1.34 (6 H, d,
J 6.2, 2 × CH3). (For the analytical data of oxazoline isomers
7b and 8b, see the following part of this section.)
Reaction of isopropyl N-benzyloxyacetylaziridine-2-carboxy-
late 2d. The ester 2d (277 mg, 1 mmol) and sodium iodide (1.871
g, 12.5 mmol) were dissolved in dry acetone (25 cm3) and
the mixture was stirred at room temperature for 24 h. The
solvent was evaporated in vacuo and the residue was extracted
with warm benzene (10 cm3). The extract was dried (MgSO4),
filtered and the benzene evaporated to give isopropyl 2-
(benzyloxyacetylamino)propenoate 9d as a pale yellow liquid
(216 mg, 78%) (Found: C, 64.8; H, 7.2; N, 5.1. C15H19NO4
requires C, 65.0; H, 6.9; N, 5.1%); m/z 277 (M+, 0.3%), 218 (1.5),
171 (24), 129 (19), 111 (35), 91 (100); νmax/cmϪ1 3377, 1785, 1695,
1634, 1521, 1107; δH 8.94 (1 H, br s, NH), 7.37 (5 H, s, C6H5),
6.60 (1 H, s, ᎐CH), 5.92 (1 H, d, J 1.6, ᎐CH), 5.13 (1 H, septet, J
6.3, CHMe2), 4.63 (2 H, s, PhCH2O), 4.04 (2 H, s, OCH2CO),
1.31 (6 H, d, J 6.3, 2 × CH3); δC 168.33, 163.10, 136.56, 130.99,
128.62, 128.23, 127.86, 108.84, 73.55, 70.00, 69.45, 21.68.
Reaction of N-benzoyl-2-(1,1-dimethylethoxymethyl)aziridine
6a. The reaction of N-benzoyl-2-(1,1-dimethylethoxymethyl)-
aziridine 6a (201 mg, 0.86 mmol) and sodium iodide (263 mg,
1.75 mmol) in acetone (15 cm3) for 24 h followed by ether
extraction gave a yellow oil (201 mg, 100%). Purification by
preparative TLC (silica gel, ether–light petroleum, 1:1, Rf
0.39) gave 4-(1,1-dimethylethoxymethyl)-2-phenyl-4,5-dihydro-
1,3-oxazole 12a (190 mg, 95%) as a light yellow oil (Found: M+,
233.142 ± 0.002. C14H19NO2 requires M, 233.1411); m/z 233
(M+, 0.6%), 146 (100); νmax/cmϪ1 1649, 1604, 1581, 1195, 1085,
946, 883, 782, 696; δH (300 MHz) 7.96–7.93 (2 H, m) and 7.50–
7.37 (3 H, m, C6H5), 4.51–4.46 (1 H, m, 5-Ha), 4.44–4.37 (1 H,
m, 4-H), 4.29 (1 H, dd, J 7.2 and 6.4, 5-Hb), 3.76 (1 H, dd, J 8.7
and 4.2, 1Ј-Ha), 3.27 (1 H, t, J 8.5, 1Ј-Hb), 1.20 (9 H, s,
3 × CH3); δC 164.7, 131.3, 128.2, 127.7, 73.1, 71.5, 66.8, 64.5,
27.5.
᎐
᎐
Reaction of isopropyl N-(2-phenyl-1,3-oxazol-4-ylcarbonyl)-
aziridine-2-carboxylate 2c. The reaction of aziridine 2c (53 mg,
0.18 mmol) with sodium iodide (50 mg, 0.33 mmol) in DMF
Reaction of N-benzoyl-2-(dimethoxymethyl)aziridine 6b. The
reaction of aziridine 6b (430 mg, 1.95 mmol) and sodium iodide
(300 mg, 2 mmol) in acetone (20 cm3) for 24 h followed by ether
J. Chem. Soc., Perkin Trans. 1, 1997
39

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extraction gave pure 4-(dimethoxymethyl)-2-phenyl-4,5-dihydro-
1,3-oxazole 12b (421 mg, 98%) as a yellow oil (Found: C, 65.2;
H, 7.2; N, 6.1. C12H15NO3, requires C, 65.1; H, 6.8; N, 6.3%);
m/z (CI) 222 (M + 1, 6%), 75 (100); νmax/cmϪ1 1650, 1358, 1090,
1067, 697; δH 8.00–7.95 (2 H, m) and 7.49–7.40 (3 H, m, C6H5),
4.47–4.41 (4 H, m, 4-H, 5-H2, 1Ј-H), 3.50 (3 H, s, OCH3), 3.45
(3 H, s, OCH3); δC 165.4, 131.4, 128.4, 128.2, 127.6, 106.0, 69.1,
68.4, 56.1, 55.0.
Reaction of N-benzoyl-2-(diethoxymethyl)aziridine 6c. The
reaction of aziridine 6c (468 mg, 1.88 mmol) with sodium iod-
ide (282 mg, 1.88 mmol) in acetone (20 cm3) gave reasonably
pure 4-(diethoxymethyl)-2-phenyl-4,5-dihydro-1,3-oxazole 12c
(433 mg, 93%) as a yellow oil. Further purification for the
microanalytical sample was achieved by radial chromatography
(silica gel, ether–light petroleum, 1:3, Rf 0.34) (Found: C, 67.6;
H, 7.9; N, 6.0. C14H19NO3 requires C, 67.5; H, 7.7; N, 5.6%);
m/z (CI) 250 (M + 1, 40%), 103 (100); νmax/cmϪ1 1649, 1088, 1064,
697; δH 7.99–7.94 (2 H, m) and 7.52–7.36 (3 H, m, C6H5), 4.61 (1
H, dd, J 2.4 and 1.5, 1Ј-H), 4.52–4.41 (3 H, m, 4-H, 5-H2), 3.86–
3.50 (4 H, m, 2 × OCH2), 1.26 (3 H, t, J 7.1, CH3), 1.14 (3 H, t, J
7.1, CH3); δC 165.3, 131.3, 128.3, 128.2, 127.7, 103.62, 69.8,
68.4, 64.6, 63.1, 15.3, 15.2.
NMR spectroscopy, was a mixture of 4-isopropoxycarbonyl- 7a
and 5-isopropoxycarbonyl-2-phenyl-4,5-dihydro-1,3-oxazole 8a
in a ratio of 5.7:1 (60 mg, 40%). Fraction B, a colourless solid
was identified as isopropyl 2-benzoylamino-3-hydroxypropano-
ate (27 mg, 17%) [Found: (M + 1) 252.123 ± 0.002. C13H18NO4
(M + 1) requires 252.1236]; m/z 252 (M + 1, 6%), 221 (9), 164
(32), 122 (22), 105 (100), 77 (78), 51 (24); νmax/cmϪ1 3406, 3333,
1742, 1639, 1533, 827, 800, 720; δH 7.86–7.54 (2 H, m) and 7.53–
7.36 (3 H, m, C6H5), 7.23 (1 H, br d, J 6.7, NH), 5.11 (1 H,
septet, J 6.3, CHMe2), 4.80 (1 H, dt, J 7.0 and 3.6, 2-H), 4.03 (2
H, d, J 3.6, 3-H2), 3.09 (1 H, br s, OH), 1.30 (3 H, d, J 6.3, CH3)
and 1.28 (3 H, d, J 6.3, CH3); δC 170.0, 167.7, 133.5, 131.9,
128.6, 127.1, 69.9, 63.7, 55.4, 21.7. Fraction C was identified as
isopropyl 3-benzoylamino-2-hydroxypropanoate 11 and was
obtained as an oil (16 mg, 10%) [Found: (M+) 251.116 ± 0.002.
C13H17NO4 requires M, 251.1157]; m/z 251 (M+, 9%), 192 (9),
164 (12), 134 (23), 105 (100), 77 (36), 51 (12); νmax/cmϪ1, 3334,
1734, 1646, 1540, 1105, 713, 690, 669; δH 7.86–7.73 (2 H, m) and
7.54–7.29 (3 H, m, C6H5), 5.08 (1 H, septet, J 6.3, CHMe2), 4.36
(1 H, t, J2,3 4.9, 2-H), 3.82 (2 H, dd J 5.7 and 4.9, 3-H2), 3.21
(1 H, br s, OH), 1.27 (3 H, d, J 6.3, CH3), 1.26 (3 H, d, J 6.3,
CH3); δC 172.6, 167.9, 134.1, 131.6, 128.5, 126.9, 70.3, 70.0,
43.0, 21.6.
Reaction of N-benzoyl-2-(1,3-dioxolan-2-yl)aziridine 6d
The reaction of aziridine 6d (900 mg, 4.1 mmol) with sodium
iodide (1.3 g, 8.6 mmol) in acetone (60 cm3) gave 928 mg of a
yellow oil as crude product which was purified in the same
manner as the previous dihydrooxazole to give 4-(1,3-dioxan-2-
yl)-2-phenyl-4,5-dihydro-1,3-oxazole 12d (878 mg, 98%) as a
light yellow oil [Found: (FAB), (M + 1) 220.096 94; C12H14NO3
Reaction of isopropyl N-benzoylaziridine-2-carboxylate 2a with
trifluoromethanesulfonic acid
Trifluoromethanesulfonic acid (140 mm3) was added dropwise
via a microsyringe into a solution of isopropyl N-benzoyl-
aziridine-2-carboxylate 2a (250 mg, 1.07 mmol) in hexane (24
cm3) and benzene (8 cm3) at room temperature and the reac-
tion was stirred for 40 min. Triethylamine (0.5 cm3) was then
added and the reaction was stirred for a further 40 min. The
reaction mixture was washed with saturated aqueous NaCl
(3 × 10 cm3) and dried (MgSO4). After filtration and concen-
tration of the solution in vacuo the crude product was obtained
as a yellow oil (220 mg). Purification of the crude product (210
mg) by radial chromatography gave two fractions. The higher
Rf fraction, identified as isopropyl 2-phenyl-4,5-dihydro-1,3-
oxazole-4-carboxylate 7a, was obtained as colourless crystals
(171 mg, 72%), mp 39.5–40.5 ЊC. The NMR spectral signals
matched the literature data. The lower Rf fraction, isopropyl
2-phenyl-4,5-dihydro-1,3-oxazole-5-carboxylate 8a, was ob-
tained as colourless crystals (18 mg, 7%), mp 66–67 ЊC. All the
NMR spectral signals matched the previous data for the
compound.
requires (M + 1) 220.097 37]; m/z 219 (M+, 5%), 73 (100); νmax
/
cmϪ1 1646, 1604, 1579, 1364, 1289, 1050, 1026, 936, 695; δH (300
MHz) 8.01–7.96 (2 H, m) and 7.51–7.37 (3 H, m, C6H5), 5.08 (1
H, d, J 3.6, 2Ј-H); 4.52 (1 H, td, J 8.5 and 3.6, after irradiation
at 5.08, this group of peaks collapsed into a triplet, J 8.4, 4-H),
4.45 (1 H, overlapping dd, J 12.1 and 8.1, 5-Hb), 4.41 (1 H,
overlapping dd, J 12.1 and 8.3, 5-Ha), 4.08–4.03 (2 H, m, 4Ј-Ha
and 5Ј-Ha), 4.00-3.92 (2 H, m, 4Ј-Hb and 5Ј-Hb); δC 165.6, 131.5,
128.5, 128.2, 127.2, 103.9, 69.2, 67.8, 65.5.
Reaction of N-cinnamoyl-2-(diethoxymethyl)aziridine 6e
The reaction of aziridine 6e (350 mg, 1.3 mmol) and sodium
iodide (250 mg, 1.4 mmol) in acetone (15 cm3) for 20 h gave 400
mg of yellow oil. Purification of the crude product by radial
chromatography (silica, ether–light petroleum, 1:2) gave pure
4-(diethoxymethyl)-2-(2-phenylvinyl)-4,5-dihydro-1,3-oxazole
12e (290 mg, 83%) as a colourless oil which became solid while
being stored in a freezer, mp 39–40 ЊC (Found: C, 70.0; H, 7.7;
N, 5.0. C16H21NO3 requires C, 69.8; H, 7.7; N, 5.1%); m/z (CI)
276 (M + 1, 14%), 230 (17), 103 (100), 75 (23); νmax/cmϪ1 2976,
1655, 1609, 1363, 1064, 760, 697; δC 7.51–7.42 (2 H, m) and
7.41–7.32 (4 H, m, C6H5, 2Љ-H), 6.66 (1 H, d, J 16.3, 1Љ-H), 4.54
(1 H, d, J 4.0, 1Ј-H), 4.45–4.31 (3 H, m, 4-H, 5-H2), 3.85–3.51 (4
H, m, 2 × OCH2), 1.26 (3 H, t, J 7.0, CH3), 1.18 (3 H, t, J 7.0,
CH3); δC 164.9, 140.1, 135.1, 129.4, 128.7, 127.4, 115.0, 103.5,
69.4, 68.1, 64.2, 62.4, 15.3, 15.2.
Reaction of isopropyl N-cinnamoylaziridine-2-carboxylate 2b
with trifluoromethanesulfonic acid
Trifluoromethanesulfonic acid (160 mm3) was added dropwise
via a microsyringe to a solution of isopropyl N-cinnamoyl-
aziridine-2-carboxylate 2b (322 mg, 1.24 mmol) in light
petroleum (30 cm3)–benzene (10 cm3) at room temperature
and the reaction was stirred for 30 min. Triethylamine (0.6
cm3) was added and the reaction was stirred for 1 h. After
being worked up as described in the previous experiment, the
crude product (298 mg) was obtained as a light yellow solid
as a mixture of 2,4- and 2,5-disubstituted 4,5-dihydro-1,3-
oxazoles in a ratio of 6.5 : 1. The crude product (286 mg) was
purified by radial chromatography (silica, ether–light petrol-
eum, 1:3). Isopropyl 2-(2-phenylvinyl)-4,5-dihydro-1,3-oxazole-
4-carboxylate 7b (Rf 0.35) was obtained as colourless crystals
(246 mg, 78%), mp 93–94.5 ЊC (Found: C, 69.4; H, 6.6; N, 5.3.
C15H17NO3 requires C, 69.5; H, 6.6; N, 5.4%); m/z (CI) 260
(M + 1, 87%), 218 (29), 172 (100), 144 (21), 115 (30); νmax/cmϪ1
1734, 1650, 1596, 1465, 1026, 1106, 999, 979, 764; δH (300 MHz)
7.50–7.46 (2 H, m) and 7.40–7.31 (3 H, m, C6H5), 7.41 (1 H, d,
J 16.3, 2Ј-H), 6.67 (1 H, d, J 16.3, 1Ј-H), 5.11 (1 H, septet, J
6.3, CHMe2), 4.83 (1 H, dd, J 10.5 and 7.9, 4-H), 4.59–4.46 (2
H, m, 5-H2), 1.31 (3 H, d, J 6.2, CH3), 1.30 (3 H, d, J 6.3 CH3);
δC 170.6, 165.7, 69.2, 69.3, 114.5, 141.1, 134.9, 129.7, 128.8,
Reaction of isopropyl N-benzoylaziridine-2-carboxylate 2a with
concentrated sulfuric acid
Concentrated sulfuric acid (40 mm3) was added dropwise with a
microsyringe to a solution of isopropyl N-benzoylaziridine-2-
carboxylate 2a (150 mg) in anhydrous ether (20 cm3). After
being stirred at room temperature for 20 h the solution was
washed with aqueous sodium carbonate (2 × 5 cm3) and water
(2 × 5 cm3). The ethereal solution was dried (MgSO4) and con-
1
centrated in vacuo to give 128 mg of a colourless oil. The H
NMR spectrum showed four compounds to be present. Separ-
ation of the crude product by radial chromatography (silica,
ether–light petroleum, 1:1, changed to 2:1 and then pure ether
at the end) gave three fractions. Fraction A, as identified by 1H
40
J. Chem. Soc., Perkin Trans. 1, 1997

View Online
127.6, 68.8, 21.71, 21.69. Isopropyl 2-(2-phenylvinyl)-4,5-
dihydro-1,3-oxazole-5-carboxylate 8b (Rf 0.28) was obtained as
colourless crystals (16 mg, 5%), mp 105–108 ЊC [Found:
(M Ϫ 1) 258.112 ± 0.002. C15H16NO3 requires (M Ϫ 1)
258.1130]; m/z 259 (M+, 13%), 258 (24), 216 (100), 172 (75), 144
(27), 131 (68), 115 (87), 103 (28), 77 (34); νmax/cmϪ1 1752, 1656,
1613, 1215, 1108, 1061, 995, 762, 697; δH 7.63–7.45 (3 H, m)
and 7.41–7.34 (3 H, m, C6H5 and 2Ј-H), 6.64 (1 H, d, J 16.3, 1Ј-
H), 5.12 (1 H, septet, J 6.2, CHMe2), 4.96 (1 H, dd, J 10.9 and
7.1, 5-H), 4.29 (1 H, dd, J 15.3 and 10.9, 4-Ha) and 4.04 (1 H,
dd, J 15.3 and 7.1, 4-Hb), 1.30 (3 H, d, J 6.2, CH3), 1.29 (3 H, d,
J 6.2, CH3); δC 171.0, 169.8, 140.8, 135.0, 129.5, 128.8, 127.5,
114.2, 75.47, 69.4, 59.3, 21.6.
1559, 1528, 1161, 1100, 987, 964, 914, 836, 774, 712, 689, 666;
δH 8.43 (1 H, s, 5Ј-H), 8.30 (1 H, s, 5-H), 8.12–8.18 (2 H, m) and
7.45–7.54 (3 H, m, C6H5), 5.31 (1 H, septet, J 6.3, CHMe2), 1.39
(6 H, d, J 6.3, 2 × CH3); δC 162.8, 160.6, 155.8, 143.5, 139.4,
135.0, 131.2, 131.0, 128.9, 126.8, 126.3, 69.2, 21.9. Starting
material 7c (3 mg) was recovered.
Isopropyl 2-phenyl-1,3-oxazole-5-carboxylate 14
Isopropyl 2-phenyl-4,5-dihydro-1,3-oxazole-5-carboxylate 8a
(111 mg, 0.48 mmol) and nickel peroxide NiO2 (263 mg) were
mixed in toluene (11 cm3) and the mixture was heated at reflux
for 24 h. After being filtered, the solution was concentrated and
the residue was purified by flash chromatography (silica gel,
ether–light petroleum, 1:1). The recovery of the starting
material was 27 mg (24%). Oxazole 14 was obtained as colour-
less crystals from light petroleum (43 mg, 39%), mp 81–81.5 ЊC
(Found: C, 67.6; H, 5.9; N, 6.3. C13H13NO3 requires C, 67.5; H,
5.7; N, 6.1%); m/z 231 (M+, 28%), 116 (100); νmax/cmϪ1 1714,
1578, 1535, 985, 836; δH 8.14–8.12 (2 H, m) and 7.53–7.47 (3 H,
m, C6H5), 7.82 (1 H, s, 4-H) 5.29 (1 H, septet, J 6.3, CHMe2),
1.39 (6 H, d, J 6.3, 2 × CH3); δC 164.1, 157.5, 142.6, 135.1,
128.9, 127.2, 131.5, 126.4, 69.3, 21.9.
Isopropyl 2-phenyl-1,3-oxazole-4-carboxylate 13a
Isopropyl 2-phenyl-4,5-dihydro-1,3-oxazole-4-carboxylate 7a
(170 mg, 0.7 mmol) and nickel peroxide NiO2 (170 mg) were
mixed in benzene (20 cm3) and the mixture was heated at reflux
for 9 h. More nickel peroxide (170 mg) was added and the reac-
tion was heated for a further 19 h. Triethylamine (0.3 cm3) was
added to the reaction and the mixture was heated for 1 h. After
being filtered, the solution was concentrated in vacuo to give the
crude product as a solid (160 mg) which was purified by radial
chromatography (silica gel, ether–light petroleum, 1: 3) to give
oxazole 13a as colourless crystals (125 mg, 74%), mp 55–56 ЊC
(Found: C, 67.5; H, 6.0; N, 6.2. C13H13NO3 requires C, 67.5; H,
5.7; N, 6.1%); m/z 231 (M+, 14%), 105 (100); νmax/cmϪ1 1732,
1564, 1155, 1111, 1059, 985, 824, 837, 786, 714, 692; δH 8.24
(1 H, s, 5-H), 8.22–8.07 (2 H, m) and 7.53–7.41 (3 H, m, C6H5),
5.31 (1 H, septet, J 6.3, CHMe2), 1.39 (6 H, d, J 6.3, 2 × CH3);
δC 162.4, 160.9, 143.4, 134.9, 131.0, 128.7, 126.8, 126.5, 68.9,
21.8. Hydrolysis of 13a in aqueous NaOH followed by acidify-
ing to pH 4.0 gave 2-phenyl-1,3-oxazole-4-carboxylic acid in
90% yield, mp 210 ЊC (lit.,24 210 ЊC).
4-(1,1-Dimethylethoxymethyl)-2-phenyl-1,3-oxazole 15a
4-(1,1-Dimethylethoxymethyl)-2-phenyl-4,5-dihydro-1,3-oxa-
zole 12a (220 mg, 0.94 mmol) and nickel peroxide (230 mg) were
mixed in dry benzene (15 cm3). After the mixture was heated at
reflux for 18 h, 250 mg of nickel peroxide was added and the
mixture was heated for a further 22 h. Another portion of 230
mg of nickel peroxide was added and the mixture was heated
for 30 h. The reaction was tested by TLC before each addition
of nickel peroxide. The mixture was filtered and the solid was
washed with ether (15 cm3). Evaporation of the solvent gave
1
168 mg of crude product whose H NMR spectrum indicated
the oxazole and starting material in a ratio of 1:1.6. Separation
by preparative chromatography (silica, ether–light petroleum,
1:3) gave recovered starting material (80 mg, 36%) and the oxa-
zole 15a (Rf 0.4) (58 mg, 27%) (Found: M+, 231.126 ± 0.002.
C14H17NO2 requires M, 231.1255); m/z 231 (M+, 22%), 158
(100); νmax/cmϪ1 3133, 3067, 2974, 1554, 1095, 1063, 1026, 932,
891, 779, 714, 692, 668; δH 8.04–7.99 (2 H, m) and 7.44–7.40 (3
H, m, C6H5), 7.61 (1 H, t, J 1.2, 5-H), 4.46 (2 H, d, J 1.2, 1Ј-H),
1.29 (9 H, s, 3 × CH3); δC 161.9, 140.9, 135.6, 130.2, 128.6,
127.5, 126.3, 73.8, 57.2, 27.5.
Isopropyl 2-(2-phenylvinyl)-1,3-oxazole-4-carboxylate 13b
Isopropyl 2-(2-phenylvinyl)-4,5-dihydro-1,3-oxazole-4-carbox-
ylate 7b (150 mg, 0.58 mmol) and nickel peroxide (250 mg) were
mixed in anhydrous benzene (20 cm3). The mixture was heated
at reflux for 16 h. Triethylamine (0.3 cm3) was then added to the
reaction mixture which was then refluxed for a further 10 min.
After being worked up as described above the crude product
was obtained as a light yellow solid (151 mg). Purification by
radial chromatography (silica gel, ether–light petroleum, 1:4)
gave oxazole 13b (108 mg, 72%) as colourless crystals, mp 89.5–
90 ЊC (Found: C, 70.0; H, 5.8; N, 5.3. C15H15NO3 requires C,
70.0; H, 5.9; N, 5.4%); m/z 258 (M + 1, 76%), 257 (M+, 68), 214
(100); νmax/cmϪ1 1725, 1644, 1540, 1316, 1155, 1105, 986, 965;
δH (300 MHz) 8.17 (1 H, s, 5-H), 7.61 (1 H, d, J 16.4, 2Ј-H),
7.54–7.51 (2 H, m) and 7.42–7.35 (3 H, m, C6H5), 6.97 (1 H, d, J
16.4, 1Ј-H), 5.29 (1 H, septet, J 6.1, CHMe2), 1.39 (6 H, d, J 6.1,
2 × CH3); δC 162.1, 160.9, 143.1, 138.1, 135.0, 129.6, 128.9,
127.4, 113.0, 68.9, 21.9.
4-(Dimethoxymethyl)-2-phenyl-1,3-oxazole 15b
4-(Dimethoxymethyl)-2-phenyl-4,5-dihydro-1,3-oxazole
12b
(320 mg, 1.45 mmol) and nickel peroxide (325 mg) were mixed
in benzene (20 cm3). The mixture was heated in an oil bath at
reflux for 24 h, 150 mg of nickel peroxide was added and the
mixture was heated for a further 24 h. The reaction mixture was
filtered and the solid was washed with ether (10 cm3). Evapor-
1
ation of the solvent gave 260 mg of crude product whose H
NMR spectrum showed a mixture of the desired oxazole and
the starting material in a ratio of 2:1. Purification of the crude
product with preparative chromatography (silica, ether–light
petroleum, 1:3) gave oxazole 15b (Rf 0.3) as a colourless oil (158
mg, 50%) (Found: C, 65.7; H, 5.8; N, 6.4. C12H13NO3 requires
C, 65.7; H, 6.0; N, 6.4%); m/z (CI) 220 (M + 1, 11%), 219 (M+,
14), 188 (100); νmax/cmϪ1 3144, 2983, 1589, 1556, 1102, 1061,
981, 909, 854, 781, 717, 693; δH 8.10–8.05 (2 H, m) and 7.46–
7.42 (3 H, m, C6H5), 7.72 (1 H, d, J 1.0, 5-H), 5.51 (1 H, d, J 1.0,
1Ј-H) 3.41 (6 H, s, 2 × OCH3); δC 162.0, 139.5, 136.8, 130.4,
128.6, 127.2, 126.4, 98.3, 52.7.
Isopropyl 2-(2-phenyl-1,3-oxazol-4-yl)-1,3-oxazole-4-
carboxylate 13c
2-(2-Phenyl-1,3-oxazol-4-yl)-4,5-dihydro-1,3-oxazole-4-carb-
oxylate 7c (25 mg, 0.083 mmol) was mixed with nickel per-
oxide (20 mg) in benzene (8 cm3). The mixture was heated at
reflux for 5 h and tested by TLC. More nickel peroxide was
added to the reaction and the reaction was kept at 75–80 ЊC
(bath) for 10 h. The TLC displayed the same fractions as before.
Triethylamine (30 mg) was added to the reaction and the mix-
ture was stirred for 30 min. The mixture was filtered and the
filtrate evaporated to give the crude product as a solid (21 mg)
which was purified by preparative TLC (silica gel, ethyl acetate–
light petroleum, 1:3). The bis(oxazole) 13c (Rf 0.45) was
obtained as a colourless solid (8 mg, 32%), mp 164 ЊC [Found:
(M + 1) 299.102 76. C16H15N2O4 requires (M + 1) 299.103 18];
m/z 298 (M+, 25%), 172 (100); νmax/cmϪ1 3140, 2925, 1719, 1633,
4-(Diethoxymethyl)-2-phenyl-1,3-oxazole 15c
4-(Diethoxymethyl)-2-phenyl-4,5-dihydro-1,3-oxazole 12c (350
mg, 1.4 mmol) and nickel peroxide (350 mg) were mixed in
benzene (20 cm3). The mixture was heated in an oil bath at
reflux for 24 h, 150 mg of nickel peroxide was added and the
J. Chem. Soc., Perkin Trans. 1, 1997
41

View Online
mixture was heated for a further 24 h. Another portion of
nickel peroxide (50 mg) was added and the reaction was
refluxed overnight (16 h). The reaction mixture was then fil-
tered and the solid was washed with ether (10 cm3). Evapor-
Acknowledgements
We thank the Australian Research Council for financial support
and Professor T. F. Molinski (University of California, Davis)
for useful discussions.
1
ation of the solvent gave 278 mg of crude product whose H
NMR spectrum showed a mixture of the oxazole and the
starting material in a ratio of 5:1. After separation of the
crude product by preparative chromatography (ether–light
petroleum, 1:3), oxazole 15c (Rf 0.4) was obtained as a col-
ourless oil (212 mg, 61%) (Found: C, 67.9; H, 6.8; N, 6.0.
C14H17NO3 requires C, 68.0; H, 6.9; N, 5.7%); m/z (CI) 248
(M + 1, 3.6%), 247 (M+, 3), 202 (100); νmax/cmϪ1 2976, 1589,
1555, 1059, 993, 848, 780, 716, 692; δH 8.09–8.04 (2 H, m) and
7.47–7.41 (3 H, m, C6H5), 7.72 (1 H, d, J 1.0, 5-H), 5.60 (1 H,
d, J 1.0, 1Ј-H), 3.77–3.60 (4 H, m, 2 × OCH2), 1.26 (6 H, t, J
7.0, 2 × CH3); δC 161.9, 140.7, 136.5, 130.3, 128.6, 127.4,
126.5, 97.0, 61.4, 15.2.
References
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2 For a recent review on the synthesis of bioactive marine cyclo-
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4-(1,3-Dioxolan-2-yl)-2-phenyl-1,3-oxazole 15d
4-(1,3-dioxolan-2-yl)-2-phenyl-4,5-dihydro-1,3-oxazole 12d (90
mg, 0.41 mmol) was mixed with nickel peroxide (200 mg) in
benzene (8 cm3). The mixture was heated at reflux for 48 h. The
reaction mixture was filtered and the residue was washed with
ether. After being concentrated, the crude product was separ-
ated by preparative thin layer chromatography (silica gel, ether–
light petroleum, 2 : 1) to give recovered starting material (70
mg, 78%) and oxazole 15d (14 mg, 16%) (Found: C, 66.0; H, 5.2;
N, 6.3. C12H11NO3 requires C, 66.35; H, 5.1; N, 6.5%); m/z 217
(M+, 23%), 174 (100); νmax/cmϪ1 2891, 1556, 1486, 1450, 1094,
942, 817, 782, 713, 693; δH 8.09–8.04 (2 H, m) and 7.43–7.47
(3 H, m, C6H5), 7.76 (1 H, br d, J 0.53, 5-H), 5.99 (1 H, br s, 2Ј-
H), 4.12–4.21 (2 H, m, 4Ј-Ha and 5Ј-Ha), 4.04–4.10 (2 H, m, 4Ј-
Hb and 5Ј-Hb); δC 162.5, 140.0, 136.3, 130.5, 128.7, 127.1, 126.6,
98.2, 65.2.
4-(Diethoxymethyl)-2-(2-phenylvinyl)-1,3-oxazole 15e
4-(Diethoxymethyl)-2-(2-phenylvinyl)-4,5-dihydro-1,3-oxazole
12e (180 mg, 0.65 mmol) and nickel peroxide (360 mg) were
mixed in anhydrous benzene (20 cm3). The mixture was refluxed
for 24 h. Extra nickel peroxide (200 mg) was added in two por-
tions during the 24 h time period. Triethylamine (0.5 cm3) was
added to the reaction mixture and the reaction was refluxed for
a further 10 min. After being worked up as described above the
crude product was obtained as a yellow oil (169 mg). Purific-
ation by radial chromatography (ether–light petroleum, 1:4)
gave pure oxazole 15e (Rf 0.36) (151 mg, 85%) as a colourless
solid, mp 43.5–44 ЊC (Found: C, 70.4; H, 7.1; N, 5.0. C16H19-
NO3 requires C, 70.3; H, 7.0; N, 5.1%); m/z (CI) 273 (M+, 19%),
228 (100); νmax/cmϪ1 3060, 2975, 1644, 1579, 1530, 1098, 1058,
967, 911, 850, 755, 689; δH 7.64 (1 H, d, J 0.7, 5-H), 7.52 (1 H, d,
J 16.4, 2Ј-H), 7.54–7.49 (2 H, m) and 7.43–7.32 (3 H, m, C6H5),
6.94 (1 H, d, J 16.5, 1Ј-H), 5.56 [1 H, d, J 0.9, CH(OEt)2], 3.79–
3.55 (4 H, m, 2 × OCH2), 1.26 (6 H, t, J 7.1, 2 × CH3); δC 161.7,
140.7, 136.3, 136.1, 135.3, 129.1, 128.8, 127.1, 113.8, 96.8, 61.3,
15.1.
24 J. W. Cornforth and E. Cookson, J. Chem. Soc., 1952, 1085.
Paper 6/04091H
Received 11th June 1996
Accepted 21st August 1996
42
J. Chem. Soc., Perkin Trans. 1, 1997