Electronically mediated selectivity in ring opening of 1-azirines. The 3-X mode: Convenient route to 3-oxazolines

Article abstract of DOI:10.1021/jo9518866

The mild base-promoted reaction of methyl 2-phenyl-1-azirine-3-acetate (1) with aldehydes and acetone provides a new and simple route to the 3-oxazolines 5, which are formed in good yields by the electrophilic trapping of an imino anion produced by C-N bond cleavage in the 1-azirine enolate intermediate 6. Chloranil oxidation of 5 containing an aromatic substituent at C-2 affords oxazoles 7, while reaction of 5 containing an aliphatic group at C-2 produces 5-methylene-3-oxazolines 8 and 5-spiro-2-oxazolines 9 in addition to 7.

Full text of DOI:10.1021/jo9518866

J . Org. Chem. 1996, 61, 3749-3752
3749
Electr on ica lly Med ia ted Selectivity in Rin g Op en in g of 1-Azir in es.
Th e 3-X Mod e: Con ven ien t Rou te to 3-Oxa zolin es
Marcus C. M. Sa´ and Albert Kascheres*
Instituto de Quı´mica, Universidade Estadual de Campinas,
CP 6154, Campinas, Sa˜o Paulo, Brazil 13083-970
Received October 23, 1995X
The mild base-promoted reaction of methyl 2-phenyl-1-azirine-3-acetate (1) with aldehydes and
acetone provides a new and simple route to the 3-oxazolines 5, which are formed in good yields by
the electrophilic trapping of an imino anion produced by C-N bond cleavage in the 1-azirine enolate
intermediate 6. Chloranil oxidation of 5 containing an aromatic substituent at C-2 affords oxazoles
7, while reaction of 5 containing an aliphatic group at C-2 produces 5-methylene-3-oxazolines 8
and 5-spiro-2-oxazolines 9 in addition to 7.
Sch em e 1
While the chemistry of simple alkyl- and aryl-substi-
tuted 1-azirines has been extensively studied,1 no meth-
odology has been developed utilizing higher order func-
tionality as an electronic probe for selective ring opening
of the 1-azirine nucleus. In the present study, we focus
attention on what shall be referred to as the “3-X mode”
(eq 1), wherein an electron-rich substituent at the 3-posi-
IN3
DABCO
4 h
Ph(H)C
C(H)CH2COOMe
PhCHN3CHICH2CO2Me
2
3
N
H
∆
PhH
Ph(N3)C C(H)CH2CO2Me
Ph
CH2CO2Me
4
1
N
N–
Sch em e 2
(1)
N
N
X
X
–
R
CO
R1
H
H
DABCO
Ph
Ph
CH2CO2Me
CH2CO2Me
tion exerts a “pushing” effect on the three-membered ring.
To the extent that this process results in C-N bond
cleavage, the resulting imino anion might be induced to
undergo reaction with electrophiles. As a simple precur-
sor to a 3-X-substituted 1-azirine, we chose the 3-acetate
derivative 1. We herein report the mild base-catalyzed
reaction of 1 with aldehydes and ketones, with special
emphasis on synthetic and mechanistic implications.
–
1
6
R
N
R1
O
R1
O
–
N
R
CH2CO2Me
Ph
CO2Me
Ph
H
5
compd
R
R1
yield (%)
5a
5b
5c
5b
5e
5f
CH3
(CH3)3C
C6H5
H
H
H
H
H
H
CH3
75
70
50
55
50
70
55
Resu lts a n d Discu ssion
Methyl 2-phenyl-1-azirine-3-acetate (1) was conve-
niently prepared from methyl 4-phenyl-3-butenoate (2)
via iodine azide addition (Scheme 1).1b While no reaction
occurred between 1 and a series of aldehydes and ketones
used as solvents in the absence of base, the presence of
DABCO (1.5 equiv, 40 h, 25 °C) in the reaction medium
resulted in a smooth conversion to 3-oxazolines 5, as a
1:1 mixture of diastereomers where these exist (Scheme
2). The presence of the 3-oxazoline nucleus in 5 was
p-CH3OC6H4
C6H5CHdCH
C4H3O
5g
CH3
conveniently made on the basis of characteristic J H-2-H-5
values. Thus, values observed in this study of 3.0-3.5
Hz (cis) and 4.5-5.5 (trans) are in total agreement with
those previously reported2 for 3-oxazoline isomers. In
addition, an NOE difference experiment performed on 5d
(Figure 1) further confirms this designation.
Formation of 5 is consistent with participation of the
intermediate 3-X-substituted 1-azirine 6, generated in
low concentration through proton abstraction from 1 by
DABCO (Scheme 2). An alternative concerted process
involving proton abstraction with ring opening in 1 must
also be considered and, in fact, does not alter our original
proposal. A nucleophilic role for DABCO in this reaction,
which would invoke the participation of aziridine inter-
mediates, was discarded inasmuch as potassium carbon-
ate also produces 5, albeit at a slower rate.
1
suggested by the appearance, in the H NMR spectra, of
two strongly deshielded methine protons (δ 5.5-6.8, H-2
and H-5) in addition to diastereotopic methylene protons
(δ 2.4-2.8). Each of these latter nuclei appeared as a
doublet of doublets containing a J value identical with
that found in the multiplet of the H-5 partner. In the
cases of formation of diastereomers, the cis isomers could
be conveniently obtained as colorless solids upon tritu-
ration of the purified product (see Experimental Section).
A distinction between cis and trans isomers could be
X Abstract published in Advance ACS Abstracts, May 1, 1996.
(1) (a) Padwa, A.; Woolhouse, A. D. In Comprehensive Heterocyclic
Chemistry; Katritzky, A. R., Ed.; Pergamon Press: Oxford, U.K., 1984;
Vol. 7, p 47. (b) Anderson, D. J .; Hassner, A. Synthesis 1975, 483.
(2) Huisgen, R.; Raab, R.; Bunge, K.; Stangl, H. Chem. Ber. 1972,
105, 1279.
S0022-3263(95)01886-X CCC: $12.00 © 1996 American Chemical Society

3750 J . Org. Chem., Vol. 61, No. 11, 1996
Sa´ and Kascheres
Sch em e 3
OCH3
OCH3
R
R
N
R
O
chloranil
+
N
O
H
α
H
H
1.1%
0.6%
2.1%
CH2CO2Me
2
2
Ph
Ph
CH2CO2Me
N
O
N
O
H
5
5
H
CH2COOCH3
7
5
CH2COOCH3
H
Cl
Cl
H
14.7%
14.4%
H
H
R
N
H
O
R
O
Cl
+
N
5d (cis)
5d (trans)
O
Cl
CO2Me
Ph
Ph
F igu r e 1.
H
9
In contrast to the well-known 2-oxazoline isomers,3
3-oxazolines are a rare class of compounds and only a
few methods have been elaborated for their preparation.
Of these methods,2,4 one approach4a is extremely perti-
nent to the present discussion. Aldehydes and ketones
react with nitrile ylides produced from 1-azirines by
photochemically promoted C-C bond cleavage (eq 2). In
8
product (yield, %)
5a , R ) CH3
7a (20)
7b (30)a
7c (50)
7d (60)
7e (50)
7f (55)
8a (20)
9a (25)
5b, R ) (CH3)3C
5c, R ) C6H5
8b (10)a
9b (30)a
5d , R ) p-CH3OC6H4
5e, R ) C6H5CHdCH
5f, R) C4H3O
O
N
R1 R2
a
Yield based upon consumed 5b (see Experimental Section).
R1
–
+
N
hν
A
B
R1
R2
N
O
(2)
Ph
R2
Ph
1
readily deduced from the H NMR spectra, wherein H-4
B
Ph
A
appeared 1 ppm upfield relative to H-2 of 5a ,b .7 The
reaction of 5b revealed a severe steric effect of the tert-
butyl group with recovery of 91% of the trans-5b isomer.
When submitted separately to the reaction conditions,
7a and 8a were recovered unchanged, thus ruling out a
route to 9 involving cycloaddition of 7 or 8 with chloranil.
While one might be tempted to invoke the participation
of nitrile ylides analogous to those of eq 2, generated from
an oxidized form of 5, in the formation of 9 by way of
participation of chloranil as a dipolarophile, an experi-
ment using benzaldehyde (a known probe for nitrile ylide
intermediates4a) as an external carbonyl source in the
oxidation of 5a failed to produce any product of incorpo-
ration of the aldehyde. Also, the use of 5 equiv of
chloranil in the reaction of 5a did not significantly alter
the product composition. The results of the above control
experiments strongly suggest the participation of a
reduced form of chloranil (perhaps an oxy anion species)
in the formation of 9. Interestingly, production of 9 may
be totally suppressed by use of a quinone of higher
oxidation potential (DDQ, 2,5-dichloro-3,6-dicyano-1,4-
benzoquinone). With this reagent reaction of 5a afforded
7a and 8a exclusively, as a 1:1 mixture, on the basis of
1H NMR analysis of the crude product. We have been
unable to determine the fate of the propionate fragment
in 5 in the reactions producing 9. The complex nature
of the redox system involved in these transformations
precludes further mechanistic interpretation.
R1
Ph
N
+
R2
–
this case, the carbonyl moiety becomes the 1,5-fragment
in the resulting 3-oxazoline. In the present study, the
1,2-fragment in 5 originates from the carbonyl compo-
nent. The two methodologies are therefore complemen-
tary, although it should be noted that acceptable yields
of 3-oxazolines in the photochemical process require the
presence of electron-withdrawing substituents on the
carbonyl moiety. The mild reaction conditions employed
in the present study permit, for the first time, construc-
tion of a 3-oxazoline nucleus containing versatile func-
tional groups at the 2-position (i.e. styryl (5e) and furyl
(5f)).
2,4-Diaryl- and 2,4,5-triaryl-3-oxazolines may be readily
converted to oxazoles utilizing chloranil (tetrachloro-1,4-
benzoquinone) as the dehydrogenation agent.2 The be-
havior of 3-oxazolines 5 (as 50:50 mixtures of diastere-
omers) under these oxidation conditions (1.5 equiv of
chloranil, toluene, 40 h under reflux) proved to be a
function of the electronic nature of the substituent at the
2-position.
Thus, derivatives containing an aromatic group (5c-
f, including the styryl analogue 5e) afforded oxazoles
7c-f in 50-60% yields (Scheme 3). However, derivatives
containing an aliphatic group (5a ,b) furnished, in addi-
tion to oxazoles 7a ,b (20-30%),5 5-methylene-3-oxazo-
lines 8a ,b (10-20%)6 and 5-spiro-2-oxazolines 9a ,b (25-
30%). That the latter are, in fact, 2-oxazolines was
Investigations of the reactions of the imino anion
derived from 6 with various dicarbonyl compounds and
other C-electrophiles are in progress in our laboratory.
(3) For reviews see: (a) Maryanoff, B. E. In Oxazoles and Oxazolines
in Organic Synthesis; Turchi, I. J ., Ed.; Interscience: New York, 1986;
p 963. (b) Gant, T. G.; Meyers, A. I. Tetrahedron 1994, 50, 2297.
(4) (a) For a review see: Nair, V. Azirines. In The Chemistry of
Heterocyclic Compounds; Hassner, A., Ed.; Interscience: New York,
1983; Vol. 42 (Small Ring Heterocycles, Pt. 1), p 215. (b) Pfoertner,
K.-H.; Bernauer, K.; Kaufmann, F.; Lorch, E. Helv. Chim. Acta 1985,
68, 584. (c) Hassner, A.; Amarasekara, A. S.; Andisik, D. J . Org. Chem.
1988, 53, 27. (d) Singh, G. S. Indian J . Chem. 1987, 26B, 270.
(5) Oxazole 7a has been cited in a patent: Meguro, K.; Fujita, T.
(Takeda Chem. Ind. Ltd.) Eur. Pat. Appl. Ep 92,239, Oct 26, 1983.
(6) The isomer shown is suggested on the basis of a NOE difference
experiment performed on 8a , wherein irradiation of the phenyl
hydrogens produced an enrichment (0.3%) of the vinyl hydrogen signal.
Exp er im en ta l Section
Gen er a l Con sid er a tion s. All chemicals were of reagent
grade and were used as received. Melting points are uncor-
rected. 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra
were recorded in CDCl3 solution, using TMS as internal
standard. Elemental analyses were performed by UNICAMP,
(7) In addition, a COLOC experiment (8 Hz) performed on 9a showed
a correlation (3J H-C) between the methyl protons and C5 in support of
the CH3-C4-C5 connectivity.

Ring Opening of 1-Azirines
J . Org. Chem., Vol. 61, No. 11, 1996 3751
Instituto de Qu´ımica, Campinas, Sa˜o Paulo, Brazil. Column
chromatography utilized Florisil (Merck; 100-200 mesh par-
ticle size).
(s, 3H), 2.65 (dd, J ) 16.0, 3.0 Hz, 1H), 2.43 (dd, J ) 16.0, 8.5
Hz, 1H), 0.95 (s, 9H); 13C NMR δ 169.7, 167.9, 131.0, 130.7,
128.5, 127.9, 112.2, 80.8, 51.2, 38.1, 35.3, 25.0. IR and NMR
data were taken from the spectra of the trans-5b-enriched
petroleum ether soluble fraction.
Elemental analysis was obtained for the 50:50 diastereo-
meric mixture. Anal. Calcd for C16H21NO3: C, 69.79; H, 7.69;
N, 5.09. Found: C, 69.99; H, 7.82; N, 5.28.
Meth yl 2-P h en yl-1-a zir in e-3-a ceta te (1). A stirred sus-
pension of NaN3 (5.07 g, 78 mmol) in acetonitrile (38 mL) was
treated with ICl (2.2 mL, 44 mmol) at -10 °C. After 15 min,
methyl (E)-4-phenyl-3-butenoate (2;8 6.30 g, 36 mmol) was
added; the resulting mixture was stirred for 12 h at room
temperature, poured into water, and extracted with CH2Cl2
(2 × 50 mL). The organic layer containing crude iodo azide 3
was washed with 5% Na2S2O3 solution, dried (MgSO4), and
reduced to half-volume in vacuo. DABCO (5.86 g, 51.9 mmol)
was added and, after 4 h at room temperature, the DABCO.
HI salt was separated and washed with CH2Cl2, and the
combined organic fractions were washed with water and dried.
Evaporation of the solvent under reduced pressure afforded
the crude vinyl azide 4 as a yellow oil (7.32 g), which was
immediately dissolved in benzene (900 mL). The resulting
solution was heated at 80 °C for 20 h, after which time the
solvent was removed under reduced pressure and the resulting
oil was purified by column chromatography with benzene-
hexane (1:1) as eluant to give 6.19 g (91%) of 1 as a pale yellow
oil: IR (film) 1740 cm-1; 1H NMR δ 7.90 (m, 2H), 7.50 (m, 3H),
3.66 (s, 3H), 2.94 (dd, J ) 16.5, 4.0 Hz, 1H), 2.34 (dd, J ) 6.5,
4.0 Hz, 1H), 2.09 (dd, J ) 16.5, 6.5 Hz, 1H); 13C NMR δ 171.0,
169.7, 132.4, 129.6, 128.8, 125.4, 51.0, 38.7, 27.2. Anal. Calcd
for C11H11NO2: C, 69.83; H, 5.86; N, 7.40. Found: C, 70.02;
H, 5.91; N, 7.29.
Meth yl 2,4-Dip h en yl-3-oxa zolin e-5-a ceta te (5c). The
reaction of azirine 1 (200 mg, 1.1 mmol) and benzaldehyde (1.5
mL, 15 mmol) using PhH-Et2O (20:1) as eluant gave 3-ox-
azoline 5c (155 mg, 50%) as a colorless oil which was a 50:50
mixture of diastereomers (based on 1H NMR). When this oil
was allowed to stand with petroleum ether (6 mL), solid cis-
5c (60 mg) could be isolated: mp 67-68.5 °C; IR (KBr) 1730,
1
1630 cm-1; H NMR δ 7.70 (m, 2H), 7.20-7.30 (m, 8H), 6.71
(d, J ) 3.5 Hz, 1H), 5.70 (ddd, J ) 8.5, 3.5, 3.5 Hz, 1H), 3.58
(s, 3H), 2.77 (dd, J ) 16.0, 3.5 Hz, 1H), 2.42 (dd, J ) 16.0, 8.5
Hz, 1H); 13C NMR δ 169.6, 168.0, 126.0-139.8, 105.4, 81.1,
51.3, 38.0.
trans-5c: IR (film) 1740, 1630 cm-1 1H NMR δ 7.70 (m,
;
2H), 7.20-7.30 (m, 8H), 6.68 (d, J ) 5.5 Hz, 1H), 5.80 (ddd,
8.5, 5.5, 3.5 Hz, 1H), 3.64 (s, 3H), 2.75 (dd, 16.0, 3.5 Hz, 1H),
2.55 (dd, 16.0, 8.5 Hz, 1H); 13C NMR δ 169.6, 168.2, 126.0-
140.4, 105.5, 81.4, 51.4, 39.6. IR and NMR data were taken
from the spectra of the trans-5c-enriched petroleum ether
soluble fraction.
Elemental analysis was obtained for the 50:50 diastereo-
meric mixture. Anal. Calcd for C18H17NO3: C, 73.20; H, 5.80;
N, 4.74. Found: C, 73.44; H, 5.67; N, 4.69.
Gen er a l P r oced u r e for Obta in in g 3-Oxa zolin es 5. A
solution containing azirine 1 (189 mg, 1.0 mmol), aldehyde or
acetone (1.5 mL), and DABCO (168 mg, 1.5 mmol) was stirred
at 25 °C for 40 h. Excess aldehyde was removed either by
evaporation in vacuo (aliphatic aldehydes and acetone) or by
treatment with saturated NaHSO3 solution (aromatic alde-
hydes). A CH2Cl2 extract was washed with water, dried, and
concentrated “in vacuo”. The residue was purified by column
chromatography.
Met h yl 2-(p-m et h oxyp h en yl)-4-p h en yl-3-oxa zolin e-5-
a ceta te (5d ) was obtained from the reaction of azirine 1 (190
mg, 1.0 mmol) and anisaldehyde (1.5 mL, 12 mmol). Elution
with PhH-Et2O (32:1) afforded 3-oxazoline 5d (178 mg, 55%)
as a colorless oil which was a 50:50 mixture of diastereomers
(based on 1H NMR). When this oil was allowed to stand with
petroleum ether (6 mL), crystalline cis-5d (65 mg) separated:
1
mp 109-109.5 °C; IR (KBr) 1730, 1630 cm-1; H NMR δ 7.80
Met h yl 2-m et h yl-4-p h en yl-3-oxa zolin e-5-a cet a t e (5a )
was obtained from the reaction of azirine 1 (189 mg, 1.0 mmol)
and acetaldehyde (1.5 mL, 27 mmol). Elution with PhH-Et2O
(32:1) afforded 3-oxazoline 5a (175 mg, 75%) as a colorless oil
which was a 50:50 mixture of diastereomers (based on 1H
NMR). When this oil was allowed to stand with petroleum
ether (30-60 °C, 5 mL) in the refrigerator, 50 mg of pure and
crystalline cis-5a could be isolated: mp 60-62 °C; IR (KBr)
(m, 2H), 7.40 (m, 3H), 7.32 (d, J ) 8.5 Hz, 2H), 6.80 (d, J )
8.5 Hz, 2H), 6.69 (d, J ) 3.0 Hz, 1H), 5.69 (ddd, J ) 8.5, 3.0,
3.0 Hz, 1H), 3.80 (s, 3H), 3.63 (s, 3H), 2.77 (dd, J ) 16.0, 3.0
Hz, 1H), 2.41 (dd, J ) 16.0, 8.5 Hz, 1H); 13C NMR δ 169.1,
167.2, 159.0, 132.0, 130.5, 128.3, 127.9, 127.1, 113.2, 105.3,
81.0, 54.4, 51.1, 39.6.
trans-5d : IR (film) 1740, 1630 cm-1 1H NMR δ 7.80 (m,
;
1
1735, 1630 cm-1; H NMR δ 7.80 (m, 2H), 7.40 (m, 3H), 5.83
2H), 7.40 (m, 3H), 7.28 (d, J ) 8.5 Hz, 2H), 6.77 (d, J ) 8.5
Hz, 1H), 6.64 (d, J ) 5.0 Hz, 1H), 5.76 (ddd, J ) 8.5, 5.0, 3.0
Hz, 1H), 3.77 (s, 3H), 3.69 (s, 3H), 2.76 (dd, J ) 16.0, 3.0 Hz,
1H), 2.56 (dd, J ) 16.0, 8.5 Hz, 1H); 13C NMR δ 169.4, 167.6,
159.5, 132.0, 131.0, 130.9, 128.5, 128.3, 127.6, 113.3, 105.2,
80.8, 54.5, 51.3, 38.1. IR and NMR data were taken from the
spectra of the trans-5d -enriched petroleum ether soluble
fraction.
(m, 1H), 5.51 (ddd, J ) 9.0, 3.0, 3.0 Hz, 1H), 3.63 (s, 3H), 2.81
(dd, J ) 15.0, 3.0 Hz, 1H), 2.40 (dd, J ) 15.0, 9.0 Hz, 1H),
1.45 (d, J ) 6.0 Hz, 3H); 13C NMR δ 169.5, 167.3, 131.7, 131.6,
129.2, 129.0, 102.6, 80.8, 51.2, 40.4, 23.0.
trans-5a : IR (film) 1740, 1635 cm-1 1H NMR δ 7.80 (m,
;
2H), 7.40 (m, 3H), 5.82 (m, 1H), 5.63 (ddd, J ) 9.0, 5.5, 3.0
Hz, 1H), 3.63 (s, 3H), 2.62 (dd, J ) 15.0, 3.0 Hz, 1H), 2.41 (dd,
J ) 15.0, 9.0 Hz, 1H), 1.44 (d, J ) 6.0 Hz, 3H); 13C NMR δ
169.6, 167.4, 131.3, 129.1, 128.0, 101.8, 80.4, 51.3, 37.9, 21.9.
IR and NMR data were taken from the spectra of the trans-
5a -enriched petroleum ether soluble fraction.
Elemental analysis was obtained for the 50:50 diastereo-
meric mixture. Anal. Calcd for C19H19NO4: C, 70.14; H, 5.89;
N, 4.31. Found: C, 70.03; H, 5.79; N, 4.47.
Meth yl 4-P h en yl-2-styr yl-3-oxa zolin e-5-a ceta te (5e).
The reaction of azirine 1 (328 mg, 1.7 mmol) and cinnamal-
dehyde (2.6 mL, 21 mmol) using benzene as eluant gave
3-oxazoline 5e (275 mg, 50%) as a colorless oil which was a
50:50 mixture of diastereomers (based on 1H NMR). When
this oil was allowed to stand with petroleum ether (10 mL),
solid cis-5e (110 mg) could be isolated: mp 133-135 °C; IR
(KBr) 1735, 1625 cm-1; 1H NMR δ 7.75 (m, 2H), 7.40 (m, 3H),
7.10-7.30 (m, 5H), 6.74 (d, J ) 16.0 Hz, 1H), 6.30 (dd, J )
5.0, 3.0 Hz, 1H), 6.21 (dd, J ) 16.0, 5.0 Hz, 1H), 5.62 (ddd, J
) 8.5, 3.0, 3.0 Hz, 1H), 3.64 (s, 3H), 2.78 (dd, J ) 16.0, 3.0 Hz,
1H), 2.49 (dd, J ) 16.0, 8.5 Hz, 1H); 13C NMR δ 170.6, 169.1,
136.2, 132.7, 131.5, 130.6, 128.9, 128.2, 128.1, 127.4, 126.9,
105.8, 81.2, 52.0, 40.0.
Elemental analysis was obtained for the 50:50 diastereo-
meric mixture. Anal. Calcd for C13H15NO3: C, 66.94; H, 6.48;
N, 6.00. Found: C, 67.08; H, 6.30; N, 6.12.
Meth yl 2-ter t-bu tyl-4-p h en yl-3-oxa zolin e-5-a ceta te (5b)
was obtained from the reaction of azirine 1 (107 mg, 0.6 mmol)
and trimethylacetaldehyde (0.75 mL, 6.9 mmol). Elution with
benzene afforded 3-oxazoline 5b (110 mg, 70%) as a colorless
oil which was a 50:50 mixture of diastereomers (based on 1H
NMR). When this oil was allowed to stand with petroleum
ether (4 mL), crystalline cis-5b (35 mg) separated: mp 108-
1
111 °C; IR (KBr) 1740, 1635 cm-1; H NMR δ 7.75 (m, 2H),
7.40 (m, 3H), 5.55 (ddd, J ) 9.0, 4.5, 3.0 Hz, 1H), 5.34 (d, J )
4.5 Hz, 1H), 3.67 (s, 3H), 2.80 (dd, J ) 16.0, 3.0 Hz, 1H), 2.41
(dd, J ) 16.0, 8.5 Hz, 1H), 0.98 (s, 9H); 13C NMR δ 169.7, 168.1,
131.4, 130.8, 128.6, 128.2, 112.6, 80.8, 51.3, 39.5, 36.2, 25.3.
trans-5e: IR (film) 1740, 1630 cm-1 1H NMR δ 7.75 (m,
;
2H), 7.40 (m, 3H), 7.10-7.30 (m, 5H), 6.73 (d, J ) 16.0 Hz,
1H), 6.27 (dd, J ) 5.0, 5.0 Hz, 1H), 6.17 (dd, J ) 16.0, 5.0 Hz,
1H), 5.71 (ddd, J ) 8.5, 5.0, 3.0 Hz, 1H), 3.65 (s, 3H), 2.74 (dd,
J ) 16.0, 3.0 Hz, 1H), 2.51 (dd, J ) 16.0, 8.5 Hz, 1H); 13C NMR
δ 169.6, 168.1, 127-136.5, 104.8, 80.6, 51.3, 38.0. IR and NMR
trans-5b: IR (film) 1740, 1635 cm-1 1H NMR δ 7.75 (m,
;
2H), 7.40 (m, 3H), 5.57 (m, 1H), 5.39 (d, J ) 5.5 Hz, 1H), 3.64
(8) Linstead, R. P.; Williams, L. T. D. J . Chem. Soc. 1926, 2735.

3752 J . Org. Chem., Vol. 61, No. 11, 1996
Sa´ and Kascheres
data were taken from the spectra of the trans-5e-enriched
petroleum ether soluble fraction.
Elemental analysis was obtained for the 50:50 diastereo-
meric mixture. Anal. Calcd for C20H19NO3: C, 74.75; H, 5.96;
N, 4.36. Found: C, 74.94; H, 6.07; N, 4.19.
δ 7.65 (m, 2H), 7.45 (m, 3H), 6.30 (q, J ) 6.0 Hz, 1H), 5.30 (s,
1H), 3.65 (s, 3H), 1.65 (d, J ) 6.0 Hz, 3H); 13C NMR δ 164.3,
164.1, 160.4, 130.5, 130.4, 128.3, 128.2, 105.6, 91.5, 50.3, 20.5.
Anal. Calcd for C13H13NO3: C, 67.52; H, 5.67; N, 6.06.
Found: C, 67.66; H, 5.79; N, 6.18.
Meth yl 2-F u r yl-4-p h en yl-3-oxa zolin e-5-a ceta te (5f) was
obtained from the reaction of azirine 1 (150 mg, 0.8 mmol) and
2-furaldehyde (1.2 mL, 15 mmol). Elution with benzene
afforded 3-oxazoline 5f (160 mg, 70%) as a colorless oil which
was a 50:50 mixture of diastereomers (based on 1H NMR).
When this oil was allowed to stand with petroleum ether (5
mL), crystalline cis-5f (60 mg) separated: mp 104.5-105.5 °C;
Meth yl 2-ter t-bu tyl-4-p h en yloxa zole-5-a ceta te (7b) was
obtained from the reaction of 3-oxazoline 5b (110 mg). The
first component was unreacted trans-5b (50 mg, 91%). The
second component was 5-spiro-2-oxazoline 9b (27 mg, 30%,
based upon consumed 5b), a colorless solid: mp 160-162 °C;
1
IR (KBr) 1680, 1665 cm-1; H NMR δ 7.95 (m, 2H), 7.50 (m,
3H), 4.58 (s, 1H), 1.06 (s, 9H); 13C NMR δ 168.7, 162.3, 149.8,
148.3, 132.2, 131.6, 131.1, 128.7, 128.5, 125.8, 89.4, 82.1, 29.0,
18.1. Anal. Calcd for C18H15NO2Cl4: C, 51.57; H, 3.61; N, 3.34.
Found: C, 51.81; H, 3.79; N, 3.17.
1
IR (KBr) 1730, 1630 cm-1; H NMR δ 7.75 (m, 2H), 7.40 (m,
4H), 6.68 (d, J ) 3.0 Hz, 1H), 6.40 (d, J ) 3.0 Hz, 1H), 6.35
(dd, J ) 3.0, 2.0, 1H), 5.75 (ddd, J ) 8.5, 3.0, 3.0 Hz, 1H), 3.62
(s, 3H), 2.80 (dd, J ) 16.0, 3.0 Hz, 1H), 2.53 (dd, J ) 16.0, 8.5
Hz, 1H); 13C NMR δ 170.2, 169.8, 151.6, 142.6, 131.3, 130.4,
128.7, 128.3, 110.1, 108.0, 99.8, 81.1, 51.5, 39.5.
The third component was oxazole 7b (18 mg, 30%, based
upon consumed 5b), a pale yellow oil: IR (film) 1745 cm-1; 1H
NMR δ 7.40-7.70 (m, 5H), 3.78 (s, 2H), 3.73 (s, 3H), 1.41 (s,
9H); 13C NMR δ 168.3, 167.8, 138.8, 137.4, 131.7, 128.3, 127.5,
126.8, 51.8, 31.8, 23.2, 18.3. Anal. Calcd for C16H19NO3: C,
70.31; H, 7.01; N, 5.12. Found: C, 70.12; H, 7.18; N, 5.26.
The fourth component was 5-methylene-3-oxazoline 8b (6
mg, 10%, based upon consumed 5b), a pale yellow oil. IR (film)
trans-5f: IR (film) 1740, 1630 cm-1; 1H NMR δ 7.75 (m, 2H),
7.40 (m, 3H), 7.35 (m, 1H), 6.65 (d, J ) 4.5 Hz, 1H), 6.25-
6.35 (m, 2H), 5.78 (ddd, J ) 8.5, 4.5, 3.0 Hz, 1H), 3.60 (s, 3H),
2.77 (dd, J ) 16.0, 3.0 Hz, 1H), 2.62 (dd, J ) 16.0, 8.5 Hz,
1H); 13C NMR δ 169.7, 169.6, 152.0, 142.3, 131.1, 130.5, 128.8,
128.6, 110.0, 107.7, 99.4, 80.9, 51.4, 38.0. IR and NMR data
were taken from the spectra of the trans-5f-enriched petroleum
ether soluble fraction.
1
1720, 1650 cm-1; H NMR δ 7.65 (m, 2H), 7.40 (m, 3H), 5.89
(s, 1H), 5.28 (s, 1H), 3.66 (s, 3H), 1.07 (s, 9H); 13C NMR δ 164.4,
164.1, 160.5, 130.7, 130.3, 128.4, 128.1, 116.2, 91.4, 50.3, 34.1,
23.1. Anal. Calcd for C16H19NO3: C, 70.31; H, 7.01; N, 5.12.
Found: C, 70.20; H, 7.15; N, 5.01.
Elemental analysis was obtained for the 50:50 diastereo-
meric mixture. Anal. Calcd for C16H15NO4: C, 67.36; H, 5.30;
N, 4.91. Found: C, 67.54; H, 5.14; N, 5.02.
Meth yl 2,4-d ip h en yloxa zole-5-a ceta te (7c) was obtained
from the reaction of 3-oxazoline 5c (116 mg): yield 55 mg (50%,
Met h yl 2.2-Dim et h yl-4-p h en yl-3-oxa zolin e-5-a cet a t e
(5g). The reaction of azirine 1 (125 mg, 0.7 mmol) and acetone
(1.0 mL, 14 mmol) using PhH-Et2O (20:1) as eluant gave
3-oxazoline 5g (90 mg, 55%) as a colorless oil: IR (KBr) 1740,
1
a colorless solid); mp 67.0-67.5 °C; IR (KBr) 1735 cm-1; H
NMR δ 8.10 (m, 2H), 7.70 (m, 2H), 7.20-7.40 (m, 6H), 3,89 (s,
2H), 3.76 (s, 3H); 13C NMR δ 167.5, 159.7, 139.1, 138.5, 131.5,
129.6, 128.1, 128.0, 127.5, 127.4, 126.9, 126.1, 51.8, 31.9. Anal.
Calcd for C18H15NO3: C, 73.70; H, 5.16; N, 4.78. Found: C,
73.91; H, 5.33; N, 4.62.
1
1635 cm-1; H NMR δ 7.75 (m, 2H), 7.40 (m, 3H), 5.59 (dd, J
) 9.0, 3.0 Hz, 1H), 3.66 (s, 3H), 2.75 (dd, J ) 15.5, 3.0 Hz,
1H), 2.38 (dd, J ) 15.5, 9.0 Hz, 1H), 1.49 (s, 3H), 1.45 (s, 3H);
13C-NMR δ 169.5, 165.5, 131.2, 130.5, 128.4, 128.1, 109.0, 80.5,
51.2, 40.2, 28.8, 28.2. Anal. Calcd for C14H17NO3: C, 68.00;
H, 6.93; N, 5.66. Found: C, 67.88; H, 6.84; N, 5.81.
Met h yl 2-(p -m et h oxyp h en yl)-4-p h en yloxa zole-5-a c-
eta te (7d ) was obtained from the reaction of 3-oxazoline 5d
(129 mg): yield 78 mg (60%, a colorless solid); mp 94-95 °C;
IR (KBr) 1735 cm-1; 1H NMR δ 8.00 (d, J ) 8.5 Hz, 2H), 7.25-
7.65 (m, 5H), 6.88 (d, J ) 8.5 Hz, 2H), 3.85 (s, 2H), 3.81 (s,
3H), 3.74 (s, 3H); 13C NMR δ 167.9, 160.9, 159.9, 138.5, 138.3,
131.6, 128.2, 127.8, 127.3, 126.9, 120.2, 113.6, 54.7, 51.9, 31.9.
Anal. Calcd for C19H17NO4: C, 70.58; H, 5.30; N, 4.33.
Found: C, 70.40; H, 5.46; N, 4.23.
Gen er a l P r oced u r e for Ch lor a n il Oxid a tion of 3-Ox-
a zolin es (5). A solution of 3-oxazoline 5 (0.4 mmol, 50:50
mixture of diastereomers) and chloranil (148 mg, 0.6 mmol)
in toluene (8.0 mL) was heated at 110 °C for 40 h. After it
was cooled to room temperature, the solution was washed with
2 N NaOH (4.0 mL), dried, and concentrated “in vacuo”. The
residue was purified by column chromatography using 20 g of
Florisil with benzene as eluant.
Met h yl 4-p h en yl-2-st yr yloxa zole-5-a cet a t e (7e) was
obtained from the reaction of 3-oxazoline 5e (126 mg): yield
Meth yl 2-m eth yl-4-p h en yloxa zole-5-a ceta te (7a ) was
obtained from the reaction of 3-oxazoline 5a (94 mg). The first
component was 5-spiro-2-oxazoline 9a (36 mg, 25%), a colorless
1
62 mg (50%, a pale yellow oil); IR (film) 1745, 1640 cm-1; H
NMR δ 7.25-7.65 (m, 11H), 6.88 (d, J ) 16.0 Hz, 1H), 3.84 (s,
2H), 3.75 (s, 3H); 13C NMR δ 167.5, 159.5, 138.8, 138.6, 135.5,
135.4, 131.4, 128.5, 128.4, 128.1, 127.4, 126.9, 126.8, 113.9,
51.8, 31.9. Anal. Calcd for C20H17NO3: C, 75.22; H, 5.37; N,
4.39. Found: C, 75.03; H, 5.55; N, 4.34.
Meth yl 2-fu r yl-4-p h en yloxa zole-5-a ceta te (7f) was ob-
tained from the reaction of 3-oxazoline 5f (120 mg): yield 64
mg (55%, a colorless solid); mp 68.5-69.0 °C; IR (KBr) 1735
cm-1; 1H NMR δ 7.70 (m, 2H), 7.49 (m, 1H), 7.40 (m, 3H), 6.98
(d, J ) 3.5 Hz, 1H), 6.45 (dd, J ) 3.5, 2.0 Hz, 1H), 3.84 (s,
2H), 3.69 (s, 3H); 13C NMR13C NMR δ 168.9, 153.3, 144.4,
142.7, 139.4, 138.5, 131.0, 128.7, 128.2, 127.1, 111.9, 111.7,
52.6, 32.0. Anal. Calcd for C16H13NO4: C, 67.84; H, 4.63; N,
4.94. Found: C, 67.92; H, 4.70; N, 4.87.
1
solid: mp 130-133 °C; IR (KBr) 1680, 1665 cm-1; H NMR δ
7.95 (m, 2H), 7.50 (m, 3H), 4.80 (q, J ) 7.0 Hz, 1H), 1.47 (d, J
) 7.0 Hz, 3H); 13C NMR δ 168.2, 160.7, 149.6, 148.0, 131.9,
131.6, 131.0, 128.7, 128.4, 126.0, 88.0, 75.1, 15.2. Anal. Calcd
for C15H9NO2Cl4: C, 47.78; H, 2.41; N, 3.71. Found: C, 47.99;
H, 2.57; N, 3.52.
The second component was oxazole 7a (18 mg, 20%), a pale
1
yellow oil: IR (film) 1745 cm-1; H NMR δ 7.55 (m, 2H), 7.30
(m, 3H), 3.75 (s, 2H), 3.73 (s, 3H), 2.47 (s, 3H); 13C NMR δ
167.9, 159.2, 138.9, 137.3, 131.8, 128.3, 127.4, 126.9, 51.8, 31.7,
13.6. Anal. Calcd for C13H13NO3: C, 67.52; H, 5,67; N, 6.06.
Found: C, 67.71; H, 5.53; N, 6.21.
The third component was 5-methylene-3-oxazoline 8a (18
mg, 20%), a pale yellow oil: IR (film) 1720, 1650 cm-1; 1H NMR
J O9518866