Asymmetric N1 unit transfer to olefins with a chiral nitridomanganese complex: Novel stereoselective pathways to aziridines or oxazolines

Article abstract of DOI:10.1021/jo016146d

Chiral nitridomanganese complex 1 was found to be a highly potential N1 unit source for the asymmetric synthesis of aziridines and 2-oxazolines from olefins such as styrene and its derivatives. When sulfonyl chlorides were employed as activators of the complex in the presence of pyridine, pyridine N-oxide, and a silver salt, the reaction of olefins with complex 1 proceeded smoothly to afford the N-sulfonylated aziridines. The aziridination of styrene derivatives with complex 1 using 2-trimethylsilylethanesulfonyl chloride (SESC1) gave the N-SES-aziridines, which were easily converted into chiral N-unsubstituted aziridines. It was found that the reaction was applicable to the asymmetric synthesis of 2-oxazolines from olefins when acyl chlorides were employed as activators. Complex I provided an effective asymmetric environment for trans-disubstituted styrenes in the reaction (up to 92% ee). This is the first example of a direct asymmetric synthesis of 2-oxazolines from olefins. Additional experiments, conducted during the course of this investigation, suggest that the isomerization of the N-acylaziridine intermediate is involved in this reaction.

Full text of DOI:10.1021/jo016146d

J . Org. Chem. 2002, 67, 2101-2110
2101
Asym m etr ic N1 Un it Tr a n sfer to Olefin s w ith a Ch ir a l
Nitr id om a n ga n ese Com p lex: Novel Ster eoselective P a th w a ys to
Azir id in es or Oxa zolin es
Masaaki Nishimura, Satoshi Minakata,* Toru Takahashi, Yoji Oderaotoshi, and
Mitsuo Komatsu*
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Yamadaoka 2-1,
Suita, Osaka 565-0871, J apan
komatsu@ap.chem.eng.osaka-u.ac.jp
Received September 25, 2001
Chiral nitridomanganese complex 1 was found to be a highly potential N1 unit source for the
asymmetric synthesis of aziridines and 2-oxazolines from olefins such as styrene and its derivatives.
When sulfonyl chlorides were employed as activators of the complex in the presence of pyridine,
pyridine N-oxide, and a silver salt, the reaction of olefins with complex 1 proceeded smoothly to
afford the N-sulfonylated aziridines. The aziridination of styrene derivatives with complex 1 using
2-trimethylsilylethanesulfonyl chloride (SESCl) gave the N-SES-aziridines, which were easily
converted into chiral N-unsubstituted aziridines. It was found that the reaction was applicable to
the asymmetric synthesis of 2-oxazolines from olefins when acyl chlorides were employed as
activators. Complex 1 provided an effective asymmetric environment for trans-disubstituted styrenes
in the reaction (up to 92% ee). This is the first example of a direct asymmetric synthesis of
2-oxazolines from olefins. Additional experiments, conducted during the course of this investigation,
suggest that the isomerization of the N-acylaziridine intermediate is involved in this reaction.
In tr od u ction
transfer reactions have been developed by employing
some nitrogen sources such as [N-(p-toluenesulfonyl)-
imino]phenyliodinane (PhIdNTs)2,5 and Chloramine-T,6
as well as others,7 and these reagents have also been
applied to asymmetric reactions.2,7a-c As an alternative
approach, nitrido complexes, which contain a metal-
nitrogen triple bond unit, have been utilized for nitrogen
atom transfer reactions.8,9 One of the earliest examples
of a nitrogen atom transfer using a nitrido complex was
Asymmetric heteroatom transfer reactions to carbon-
carbon double bonds using catalytic or stoichiometric
amounts of transition-metal complexes have recently
attracted considerable interest for use in the synthesis
of chiral three-membered heterocycles.1,2 This class of
heterocycles represents a useful chiral building block and
is also found in a large number of natural products as
well as biologically active compounds.3,4 A variety of
oxygen atom transfer reactions have been described, and
some highly stereoselective reactions have been reported.
On the other hand, during the past decade, N1 unit
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10.1021/jo016146d CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/08/2002

2102 J . Org. Chem., Vol. 67, No. 7, 2002
Nishimura et al.
Ta ble 1. Asym m etr ic Azir id in a tion of Styr en e w ith
Com p lex 1 Usin g Su lfon yl Ch lor id esa
reported by Groves’s group for the aziridination of
cyclooctene in the presence of trifluoroacetic anhydride
(TFAA),8a but they mentioned no other olefins in their
paper. Several years ago, Carreira and co-workers ex-
tended this type of reaction to the amination of silyl enol
ethers and glycals with new types of nitridomanganese
complexes.8c-e More recently, we reported the first ex-
ample of the asymmetric aziridination of olefins using a
chiral nitridomanganese complex with good to high yields
and excellent enantioselectivities.9a In this reaction,
p-toluenesulfonic anhydride (Ts2O) played an important
role as an activator of the complex to achieve the
aziridination. An appropriate choice of activator might
be important in controlling the reactivity, stereoselectiv-
ity, and product selectivity. To extend the utility of the
present nitrogen atom transfer reactions, which use a
nitridomanganese complex, we investigated the reaction
of olefins with the chiral complex using sulfonyl chlorides
or acyl chlorides, which constitute readily available
activators of the complex. Moreover, the employment of
an acyl chloride would be expected to lead directly to
chiral 2-oxazolines from olefins, since it is known that
N-acylaziridines isomerize to oxazolines under, for ex-
ample, Lewis acidic conditions.10 Optically active oxazo-
lines are found as components of a variety of natural
products and biologically active compounds.11,12 It has
also been revealed in the past decade that they act as
potential chiral ligands for asymmetric synthesis.13 The
reagent-controlled synthesis of chiral 2-oxazolines is a
useful method, but only a few examples have been
reported to date.14
activator
yield eeb
entry
(EX)
additive conditions product
(%)
(%)
1
2
3
4
5
6
TsCl
TsCl
TsCl
NsCl
MsCl
Ts2O
none
rt, 24 h
rt, 3 h
0 °C, 6 h
0 °C, 3 h
0 °C, 18 h
0 °C, 3 h
2a
2a
2a
2b
2c
2a
76
77
78
46
87
78
26c
38c
40c
43d
42d
41c
AgClO4
AgClO4
AgClO4
AgClO4
none
a
Reaction conditions: (R,R)-complex 1 (1 equiv), EX (1.2 equiv),
additive (1.2 equiv), pyridine (0.5 equiv), pyridine N-oxide (1.2
b
equiv), styrene (10 equiv). Enantiomeric excesses were deter-
mined by HPLC analysis using a Daicel Chiralcel OJ column.
c Absolute configurations were determined to be (R) by comparison
d
of the measured optical rotations with reported values.15c Ab-
solute configurations were established as (R) by a comparison of
the measured optical rotations with that of 2a .
of the direct asymmetric synthesis of 2-oxazolines from
olefins was achieved using an acyl chloride as an activa-
tor.
Resu lts a n d Discu ssion
Asym m etr ic Azir id in a tion Usin g Su lfon yl Ch lo-
r id es a s Activa tor s. As mentioned above, the asym-
metric aziridination has been achieved by the reaction
of olefins with complex 1 in the presence of Ts2O as the
activator of the complex.
In this paper, we report the asymmetric nitrogen atom
transfer to olefins using a chiral nitridomanganese
complex in the presence of readily available activators.
Asymmetric aziridination was found to proceed smoothly
when a sulfonyl chloride was employed as an activator
in the presence of a silver salt, while the first example
(8) (a) Groves, J . T.; Takahashi, T. J . Am. Chem. Soc. 1983, 105,
2073-2074. (b) Groves, J . T.; Takahashi, T.; Butlar, W. M. Inorg. Chem.
1983, 22, 884-887. (c) Du Bois, J .; Hong, J .; Carreira, E. M.; Day, M.
W. J . Am. Chem. Soc. 1996, 118, 915-916. (d) Du Bois, J .; Tomooka,
C. S.; Hong, J .; Carreira, E. M. J . Am. Chem. Soc. 1997, 119, 3179-
3180. (e) Du Bois, J .; Tomooka, C. S.; Hong, J .; Carreira, E. M.; Day,
M. W. Angew. Chem., Int. Ed. Engl. 1997, 36, 1645-1647. (f) Du Bois,
J .; Tomooka, C. S.; Hong, J .; Carreira, E. M. Acc. Chem. Res. 1997,
30, 364-372. (g) Svenstrup, N.; Bøgevig, A.; Hazell, R. G.; J ørgensen,
K. A. J . Chem. Soc., Perkin Trans. 1 1999, 1559-1565. (h) Ho, C. T.;
Lau, T. C.; Kwong, H. L.; Wong, W. T. J . Chem. Soc., Dalton Trans.
1999, 2411-2413.
(9) (a) Minakata, S.; Ando, T.; Nishimura, M.; Ryu, I.; Komatsu, M.
Angew. Chem., Int. Ed. Engl. 1998, 37, 3392-3394. (b) Nishimura,
M.; Minakata, S.; Thongchant, S.; Ryu, I.; Komatsu, M. Tetrahedron
Lett. 2000, 41, 7089-7092.
(10) (a) Ferraris, D.; Drury, W. J ., III; Cox, C.; Lectka, T. J . Org.
Chem. 1998, 63, 4568-4569. (b) Tomasini, C.; Vecchione, A. Org. Lett.
1999, 1, 2153-2156.
Although Ts2O is an effective reagent for aziridination,
it is relatively expensive and other sulfonyl anhydrides
are not readily available. Thus, sulfonyl chlorides were
applied to the aziridination, since they are more readily
available and the diversity of substituents on the nitrogen
of the formed aziridines is expanded. The results are
summarized in Table 1. p-Toluenesulfonyl chloride (TsCl)
was initially employed in the reaction in an attempt to
verify whether sulfonyl chlorides are able to act as an
activator or not. When styrene was treated with complex
1 at room temperature for 24 h in the presence of
pyridine, pyridine N-oxide, and TsCl, N-(p-toluenesul-
fonyl)-2-phenylaziridine (2a ) was obtained in 76% yield
with 26% ee. While the aziridination took place even
(11) (a) Davidson, B. S. Chem. Rev. 1993, 93, 1771-1791. (b)
Michael, J . P.; Pattenden, G. Angew. Chem., Int. Ed. Engl. 1993, 32,
1-23. (c) Sone, H.; Kigoshi, H.; Yamada, K. Tetrahedron 1997, 53,
8149-8154. (d) Rudi, A.; Aknin, M.; Gaydou, E. M.; Kashman, Y.
Tetrahedron 1998, 54, 13203-13210. (e) Boden, C. D. J .; Norley, M.;
Pattrnden, G. J . Chem. Soc., Perkin Trans. 1 2000, 883-888 and
references therein.
(12) For reviews on 2-oxazolines: (a) Frump, J . A. Chem. Rev. 1971,
71, 483-505. (b) Meyers, A. I.; Mihelich, E. D. Angew. Chem., Int. Ed.
Engl. 1976, 15, 270-281. (c) Reuman, M.; Meyers, A. I. Tetrahedron
1985, 41, 837-860. (d) Gant, T. G.; Meyers, A. I. Tetrahedron 1994,
50, 2297-2360. (e) Ager, D. J .; Prakash, I.; Schaad, D. R. Chem. Rev.
1996, 96, 835-875.
(13) For recent reviews: (a) Ghosh, A. K.; Mathivanan, P.; Cappiello,
J . Tetrahedron: Asymmetry 1998, 9, 1-45. (b) J ohnson, J . S.; Evans,
D. A. Acc. Chem. Res. 2000, 33, 325-335. (c) Helmchen, G.; Pfaltz, A.
Acc. Chem. Res. 2000, 33, 336-345.
(14) (a) Ito, Y.; Sawamura, M.; Hayashi, T. J . Am. Chem. Soc. 1986,
108, 6405-6406. (b) Sawamura, M.; Ito, Y. Chem. Rev. 1992, 92, 857-
871. (c) Soloshonok, V. A.; Hayashi, T. Tetrahedron Lett. 1994, 35,
2713-2716. (d) Sawamura, M.; Nakayama, Y.; Kato, T.; Ito, Y. J . Org.
Chem. 1995, 60, 1727-1732. (e) Soloshonok, V. A.; Kacharov, A. D.;
Hayashi, T. Tetrahedron 1996, 52, 245-254. (f) Suga, H.; Ikai, K.;
Ibata, T. Tetrahedron Lett. 1998, 39, 869-872. (g) Suga, H.; Ikai, K.;
Ibata, T. J . Org. Chem. 1999, 64, 7040-7047. (h) Evans, D. A.; J aney,
J . M.; Magomedov, N.; Tedrow, J . S. Angew. Chem., Int. Ed. Engl. 2001,
40, 1884-1888.

Novel Stereoselective Pathways to Aziridines or Oxazolines
J . Org. Chem., Vol. 67, No. 7, 2002 2103
Ta ble 2. Asym m etr ic Azir id in a tion of Styr en e a n d Its
Der iva tives w ith Com p lex 1 Usin g SESCla
Ta ble 3. Desu lfon yla tion of N-SES-Azir id in es 3a
entry
R1
R2
time (h) product
yield(%) ee (%)b
entry
R1
R2 N-SES-aziridine product yield (%) eeb (%)
1
2
3
4
5
6
H
Me
n-Pr
i-Pr
c-Hex
H
H
H
H
H
H
Me
9
12
12
12
12
24
3a
3b
3c
3d
3e
3f
60
70
50
62
62
37
40c
83d
85e
90e
93e
24f
1
2
3
4
5
6
H
Me
n-Pr
i-Pr
c-Hex
H
H
H
H
H
H
Me
3a (40% ee)
3b (83% ee)
3c (85% ee)
3d (90% ee)
3e (93% ee)
3f (24% ee)
4a
4b
4c
4d
4e
4f
65
79
80
81
85
72
40c
83d
85e
90e
93e
24f
a
Reaction conditions: (R,R)-complex 1 (1 equiv), SESCl (1.2
equiv), AgClO4 (1.2 equiv), pyridine (0.5 equiv), pyridine N-oxide
a
Reaction conditions: N-SES-aziridine 3 (1 equiv) and TASF
b
(4 equiv). Enantiomeric excesses were determined by HPLC
b
(1.2 equiv), olefin (10 equiv). Enantiomeric excesses were deter-
analysis. c Absolute configuration was determined to be (R) by
comparison of HPLC analysis of the N-tosyl derivative with that
mined by HPLC analysis. c Absolute configuration was determined
d
to be (R) from that of 4a . Absolute configuration was determined
d
of 2a . Absolute configuration was determined to be (2R,3R) by
to be (2R,3R) from that of 4b. e Absolute configurations were
established to be (2R,3R) by comparison of the measured optical
rotations with that of 3b. f Absolute configuration was determined
to be (2S,3R) from that of 4f.
comparison of the measured optical rotation with reported val-
ues.24 e Absolute configurations were established to be (2R,3R)
by comparison of the measured optical rotations with that of 4b.
f Absolute configuration was determined to be (2S,3R) by com-
parison of the measured optical rotation with reported values.25
when TsCl was used instead of Ts2O, the enantioselec-
tivity was rather low compared to that for Ts2O. Several
additives were examined in an attempt to improve the
enantiomeric excess. The addition of silver perchlorate
(AgClO4) was found to increase the enantioselectivity and
decrease the reaction time. The use of AgClO4 at 0 °C
afforded the same results as those found for Ts2O. These
results prompted us to employ other sulfonyl chlorides
in the reaction. The aziridination was performed with
p-nitrobenzensulfonyl chloride (NsCl) to furnish the
desired product in moderate yield. An alkyl sulfonyl
chloride, methanesulfonyl chloride, was found to function
as an activator of the complex to afford N-mesylaziridine
2c in good yield. It turned out that sulfonyl chlorides also
acted as activators of the complex in the presence of a
silver salt to perform the aziridination, and the enan-
tioselectivities were not influenced by the nature of the
sulfonyl moiety of the activators.
Although N-sulfonyl groups attached to the nitrogen
of aziridines can be removed under reductive conditions,
undesirable reactions such as the ring-opening of aziri-
dines sometimes occur.15 To obtain N-unsubstituted
aziridines more readily,8h the successful introduction of
an alkyl sulfonyl group to the nitrogen of an aziridine
led us to synthesize N-(2-trimethylsilylethanesulfonyl)-
aziridines (N-SES-aziridine), the SES group of which can
be easily removed under mild conditions.16 2-Trimethyl-
silylethanesulfonyl chloride (SESCl) was employed in the
aziridination using AgClO4 (Table 2). When styrene was
treated with complex 1 in the presence of SESCl and
AgClO4, N-SES-aziridine 3a was obtained in 60% yield
with 40% ee. The aziridination of trans-â-methylstyrene
afforded the corresponding aziridine 3b with 83% ee.
Other trans-disubstituted styrene derivatives were also
smoothly aziridinated with excellent enantioselectivities.
cis-â-Methylstyrene was transformed to cis-aziridine 3f
with no detectable formation of the trans-isomer. The
removal of the SES group was performed under condi-
tions using tris(dimethylamino)sulfonium difluorotri-
methylsilicate (TASF) to provide N-H aziridines 4 with
no change in optical purity (Table 3).
Asym m etr ic Syn th esis of 2-Oxa zolin es Usin g Acyl
Ch lor id es a s Activa tor s. Sulfonyl chlorides were found
to be good activators of a nitridomanganese complex for
achieving asymmetric aziridination. To extend the scope
of the N1 unit transfer using a nitridomanganese com-
plex, acyl chlorides were employed as activators. As
described in the Introduction, acyl chlorides might be
potent candidates as activators for the reaction leading
to N-acylaziridines and/or 2-oxazolines.17
Benzoyl chloride was initially applied to the reaction
of olefins with complex 1. As a model substrate for
optimization of the reaction conditions, trans-â-methyl-
styrene was selected for the reaction because it gave good
results in the previously described aziridination method.9a
When trans-â-methylstyrene was treated with complex
1 at room temperature for 48 h in the presence of
pyridine, pyridine N-oxide, and benzoyl chloride, 4-meth-
yl-2,5-diphenyl-2-oxazoline (5a ) was obtained in 77%
yield with 81% ee (Table 4, entry 1). Although the
reaction proceeded at 0 °C with good enantioselectivity
(86% ee), the chemical yield of 5a was lower than the
yield at room temperature. To obtain a higher chemical
yield at 0 °C while retaining the enantioselectivity,
additives for this reaction were investigated (Table 4,
entries 3-10). The addition of a silver salt such as
AgClO4 or AgBF4 was found to dramatically improve the
chemical yield with no significant loss in enantioselec-
tivity. However, the use of AgNO3 reduced the chemical
yield of 5a , indicating that counteranions might be a key
determinant in this reaction. The same reactions in the
presence of sodium salts (NaClO4 and NaBF4) proceeded
in moderate yields. The addition of a lithium or magne-
sium salt had no effect on the course of the reaction. A
reaction conducted in the presence of AgBF4 but without
(15) (a) Bellos, K.; Stamm, H.; Speth, D. J . Org. Chem. 1991, 56,
6846-6849. (b) Vedejs, E.; Lin, S. J . Org. Chem. 1994, 59, 1602-1603.
(c) Alonso, D. A.; Andersson, P. G. J . Org. Chem. 1998, 63, 9455-9461.
(16) (a) Weinreb, S. M.; Chase, C. E.; Wipf, P.; Venkatraman, S.
Org. Synth. 1998, 75, 161-169. (b) Dauban, P.; Dodd, R. H. J . Org.
Chem. 1999, 64, 5304-5307.
(17) Carreira et al. reported that the use of (CF3CO)2O as an
activator for a nitrido complex leads to the formation of ring-opening
products, amino alcohols; see: ref 8e.

2104 J . Org. Chem., Vol. 67, No. 7, 2002
Nishimura et al.
Ta ble 4. Asym m etr ic Syn th esis of Oxa zolin e 5a fr om
Ta ble 5. Effect of Acid Ch lor id es on th e Rea ction of
tr a n s-â-Meth ylstyr en e a n d Com p lex 1a
tr a n s-â-Meth ylstyr en e w ith Com p lex 1a
entry
additive
temp
yield (%)
ee (%)b,c
entry
R3
time (h) oxazoline yield (%) ee (%)b
1
2
3
4
5
6
7
8
none
none
rt
77
34
65
77
15
56
50
29
23
81
81
86
87
87
84
86
86
87
86
86
1
2
3
4
5
Ph
48
24
168
48
5a
5b
5c
5d
5e
81
88
80
75
45f
86c
86d
86d
85e
87g
0 °C
0 °C
0 °C
0 °C
0 °C
0 °C
0 °C
0 °C
0 °C
p-CF3C6H4-
p-MeOC6H4-
t-Bu
AgClO4
AgBF4
AgNO3
NaClO4
NaBF4
LiClO4
Mg(ClO4)2
AgBF4
i-Pr
24
a
Reaction conditions: (R,R)-complex 1 (1 equiv), PhCOCl (1.2
equiv), AgBF4 (1.2 equiv), pyridine N-oxide (1.2 equiv), trans-â-
b
methylstyrene (10 equiv). Enantiomeric excesses were deter-
9
mined by HPLC analysis using a Daicel Chiralcel OD column or
10d
a Chiralpak AD column. c Absolute configuration was determined
a
to be (4R,5R).26 Absolute configurations were established to be
d
Reaction conditions: (R,R)-complex 1 (1 equiv), PhCOCl (1.2
equiv), additive (1.2 equiv), pyridine (0.5 equiv), pyridine N-oxide
(1.2 equiv), trans-â-methylstyrene (10 equiv). Enantiomeric ex-
(4R,5R) by comparison of the measured optical rotations with that
of 5a . e Absolute configuration was determined to be (4R,5R) using
the corresponding amino alcohol derived from 5d . f Compound 6
was obtained in 25% yield with 86% ee. Absolute configuration
was established as (4R,5R) by comparison of the measured optical
rotation with that of 5d .
b
cesses were determined by HPLC analysis using a Daicel Chiralcel
OD column. c Absolute configurations were determined to be
(4R,5R) by a comparison of the measured optical rotations with
g
reported values.26 Reaction was run without pyridine.
d
pyridine afforded the best result.18 These results repre-
sent the first example of the direct asymmetric synthesis
of an oxazoline from an olefin. Although N-aroylnitrenes
generally add to olefins to give aziridines,19 oxazoline 5a
was selectively produced with no detectable formation of
the corresponding N-benzoylaziridine. Moreover, the
reaction gave trans-oxazolines exclusively with the con-
servation of the stereochemistry of the starting olefins.
To investigate the influence of activators of complex 1
on the synthesis of oxazolines, several acyl chlorides were
examined, and the results are listed in Table 5. When
p-(trifluoromethyl)benzoyl chloride was employed in the
reaction, trans-â-methylstyrene was found to react
smoothly and the corresponding oxazoline was obtained
in 88% yield with 86% ee. Although a considerable length
of time was required to complete the reaction in the case
of p-methoxybenzoyl chloride, the yield and enantiomeric
excess of the produced oxazoline were the same as those
for the product obtained via the use of benzoyl chloride.
These results show that an electron-deficient substituent
on the phenyl ring of an acyl chloride enhances the
reaction rate. Aliphatic acyl chlorides such as pivaloyl
chloride and isobutyryl chloride are also applicable to the
reaction, yielding the corresponding oxazolines in moder-
ate to good yields with high ee. From these results, the
enantioselectivities in the synthesis of oxazolines do not
appear to be dependent on the structure of the acyl
chlorides. The ee value of compound 6 obtained in entry
5 was the same as that of 5e, suggesting that the
byproduct might not be formed via the ring-opening of
an N-acylaziridine intermediate but, rather, by the
hydrolysis of the acylated oxazoline or the acylation of
the hydrolyzed oxazoline. The acylation of 5e proceeded
more easily in comparison with that of 5d because of the
less bulky environment around the nitrogen on 5e to
provide compound 6.
The present reaction was successfully applied to the
synthesis of oxazolines from styrene and its derivatives,
as shown in Table 6. When styrene, a simple olefin, was
treated with complex 1 using benzoyl chloride under
optimal conditions, oxazoline 7a was obtained in 74%
yield, albeit with a lower enantioselectivity. In the case
of R-methylstyrene, the corresponding oxazoline was
produced in a better yield with low enantioselectivity. The
fact that the use of trans-â-methylstyrene resulted in
high enantioselectivity (vide ante) encouraged us to
investigate the reaction of other trans-disubstituted
styrene derivatives with complex 1. The reaction of trans-
1-phenyl-1-pentene with 1 afforded the desired oxazoline
in good yield with high enantioselectivity. trans-3-Phenyl-
1-methyl-2-butene and trans-â-cyclohexylstyrene were
transformed to the corresponding oxazolines in over 90%
ee, respectively. In these reactions, the trans-oxazolines
were obtained as the sole products and no cis-isomers
were detected. Although the present reaction permitted
the conversion of cyclic olefins such as 1,2-dihydrona-
phthalene and 1-phenylcyclohexene to the polycyclic
compounds, the yields and enantioselectivities were
moderate. The complex was found to be a good chiral
source for inducing high enantioselectivities when trans-
substituted styrene derivatives were used as substrates.
The tendency of a substituent effect on enantiomeric
excesses in the reactions is similar to that observed for
the aziridination of these styrene derivatives using
complex 1 and Ts2O.
(18) When trans-â-methylstyrene was treated with (S,S)-complex
1, (4S,5S)-5a was obtained (82% yield, 85% ee).
(19) (a) Mishra, A.; Rice, S. N.; Lwowski, W. J . Org. Chem. 1968,
33, 481-486. (b) Hayashi, Y.; Swern, D. J . Am. Chem. Soc. 1973, 95,
5205-5210. (c) Semenov, V. P.; Khusainova, A. K.; Studenikov, A. N.;
Ogloblin, K. A. Zh. Org. Khim. 1977, 13, 963-968. (d) Semenov, V. P.;
Studenikov, A. N.; Bespalov, A. D.; Ogloblin, K. A. Zh. Org. Khim. 1977,
13, 2202-2207. (e) Semenov, V. P.; Studenikov, A. N.; Prosypkina, A.
P.; Ogloblin, K. A. Zh. Org. Khim. 1977, 13, 2207-2212. (f) Semenov,
V. P.; Studenikov, A. N.; Ivanov, B. B.; Ogloblin, K. A. Zh. Org. Khim.
1990, 26, 331-335. (g) Buck, K.; J acobi, D.; Plo¨gert, Y.; Abraham, W.
J . Prakt. Chem. 1994, 336, 678-685.

Novel Stereoselective Pathways to Aziridines or Oxazolines
J . Org. Chem., Vol. 67, No. 7, 2002 2105
Ta ble 6. Asym m etr ic Syn th esis of Oxa zolin es fr om
Styr en e a n d Its Der iva tives Usin g Com p lex 1a
clearly converted to the cis- and trans-oxazolines 12 and
13, respectively. These experiments indicate that an
aziridine intermediate is involved in the reaction under
the conditions employed herein.
a
Reaction conditions: (R,R)-complex 1 (1 equiv), PhCOCl (1.2
equiv), AgBF4 (1.2 equiv), pyridine N-oxide (1.2 equiv), olefin (10
b
equiv), CH2Cl2, 0 °C. Enantiomeric excesses were determined by
Given these results, a proposal for the most likely
pathway for the present reaction using acyl chlorides is
shown in Scheme 1. Initially, acyl chlorides, activated by
AgBF4, react with complex 1 to generate the imido
complex 14, the formation of which was proposed by
Groves on the basis of spectral analysis.8a The different
efficiencies of metal salts shown in Table 4 can be
explained as follows. It is clear that Ag+ has a good ability
to activate acyl chlorides compared to Na+, Li+, and Mg+.
The counteranions of the metal salts result in those of
the pyridinium ion of pyridine N-oxide acting as an axial
ligand.9a,21 The reason for the low yield in the case where
AgNO3 is used can be explained by assuming that the
coordination of a nitrate anion might disturb that of
pyridine N-oxide. In the next step, the N-COR units are
transferred from intermediate 14 to olefins to afford
N-acylaziridines and/or 2-oxazolines. The fact that an
electron-deficient acyl chloride accelerated the reaction
(Table 5) is consistent with the proposed mechanism.
Namely, the acyl chloride reacts with complex 1 more
smoothly, and in addition, complex 14, activated by the
acyl chloride, which is a type of metal nitrenoid, is more
reactive toward olefins. Two routes are conceivable for
the formation of oxazolines from olefins and 14. One is a
HPLC analysis using a Daicel Chiralcel OD column or a Chiralpak
AD column. c Absolute configuration was determined to be (R) by
comparison of the measured optical rotation with reported val-
d
ues.27 Absolute configurations were not determined. e Absolute
configurations were established to be (4R,5R) by comparison of
the measured optical rotations with that of 5a .
To study the stereospecificity of this reaction, cis-â-
methylstyrene was employed in the synthesis of oxazoline
using benzoyl chloride. When cis-â-methylstyrene was
treated with 1 at room temperature for 48 h, cis-(4S,5R)-
oxazoline 8 was obtained along with a larger amount of
trans-(4S,5S)-oxazoline 9 (eq 1). Thus, stereospecificity
was not observed in the synthesis of oxazolines from
trans- and cis-â-methylstyrene in contrast to the aziri-
dination of these compounds using Ts2O.9a On the other
hand, cis-(2S,3R)-aziridine 10 was formed as a major
product along with oxazolines 8 and 9 at 0 °C. These
results are consistent with the present reactions proceed-
ing via aziridine intermediates. To determine whether
such intermediates are in fact involved, the reaction of
cis-â-methylstyrene with racemic complex 1 was carried
out at 0 °C in the presence of cis-aziridine 1120 labeled
with an m-toluoyl group on the nitrogen (eq 2). As a
consequence, the yield of the produced aziridine 10 was
increased and those of oxazolines 8 and 9 were decreased
compared to the reaction in the absence of aziridine 11.
In addition, a portion of the labeled aziridine 11 was
(20) Werry, J .; Stamm, H.; Lin, P.-Y.; Falkenstein, R.; Gries, S.;
Irngartinger, H. Tetrahedron 1989, 45, 5015-5028.
(21) Irie, R.; Ito, Y.; Katsuki, T. Synlett 1991, 265-266.

2106 J . Org. Chem., Vol. 67, No. 7, 2002
Nishimura et al.
Sch em e 1
Sch em e 2
tion of a mixture of cis- and trans-oxazolines from cis-â-
methylstyrene can be accounted for by the generation of
a benzylic cation and free rotation about the C-C bond
to a more stable intermediate, in which a trans relation-
ship exists between the Me and Ph groups. The difference
in ee values between produced oxazolines 8 and 9 and
aziridine 10 suggests that a chiral manganese complex
might be involved in the isomerization as a Lewis acid.
This isomerization mechanism through a benzylic cation
intermediate supports the observed low enantioselectivi-
ties in the case of styrene and R-methylstyrene.
The produced oxazolines could be easily converted into
â-amino alcohols (eq 3). Optically active â-amino alcohols
are useful synthetic tools for the preparation of natural
products and chiral ligands and have been found in wide
variety of biologically important compounds.12e,22 When
oxazoline 5a was treated with 1.2 N HCl at reflux for 30
h, norpseudoephedrine (17) was obtained in good yield
with retention of the stereochemistry. The hydrolysis of
oxazoline 7e also took place under similar conditions to
give the non-natural â-amino alcohol 18 in high yield.
direct [3 + 2]-type addition between the N-COR unit of
complex 14 and an olefin (route a), and the other involves
the isomerization of an aziridine intermediate (route b).
Evidence for the existence of the aziridine intermediate
can be obtained from eqs 1 and 2 as described above.
Moreover, the ee values of the oxazolines produced from
trans-substituted styrene derivatives were the same as
those of aziridines from the reaction when Ts2O was used
as an activator. These results provide strong support for
a scenario where the reactions of olefins with 14 proceed
via aziridination and a subsequent Lewis acid-promoted
isomerization by AgBF4 or the Mn(III) complex generated
from 1. Although we speculate that the reactions of cis-
and trans-â-methylstyrene occur via the same mecha-
nism, the former gave oxazolines 8 and 9 and aziridine
10 and the latter gave oxazoline 5a as the sole product.
The difference can be explained as follows (Scheme 2).
trans-N-Benzoylaziridine 15, coordinated by the metal
acting as a Lewis acid, isomerizes to the oxazoline more
readily than cis-aziridine 16, because of steric repulsion
between the metal and the substituents on the cis-16.
As a consequence, the reaction of cis-â-methylstyrene
affords cis-aziridine 10 along with oxazolines. The forma-
Con clu sion s
We have shown here that the chiral nitridomanganese
complex is an effective reagent for asymmetric N1 unit
transfer reaction to olefins to give chiral aziridines or
2-oxazolines. The asymmetric aziridination of olefins was
achieved by using sulfonyl chlorides as activators of the
complex in the presence of a silver salt. 2-Trimethylsi-
lylethanesulfonyl chloride (SESCl) also served as an
activator for the reaction to give the corresponding
(22) (a) Shioiri, T.; Hamada, Y. Heterocycles 1988, 27, 1035-1050.
(b) Sasai, H.; Itoh, N.; Suzuki, T.; Shibasaki, M. Tetrahedron Lett. 1993,
34, 855-858 and references therein.

Novel Stereoselective Pathways to Aziridines or Oxazolines
J . Org. Chem., Vol. 67, No. 7, 2002 2107
(R)-N-[2-(Tr im eth ylsilyl)eth a n esu lfon yl]-2-p h en yla zir -
id in e (3a ):16b colorless oil; TLC Rf 0.51 (hexane/EtOAc, 2:1);
1H NMR (CDCl3, 270 MHz) δ 0.03 (s, 9H), 1.09-1.16 (m, 2H),
2.42 (d, 1H, J ) 4.3 Hz), 2.97 (d, 1H, J ) 7.3 Hz), 3.08-3.16
aziridines, which were readily converted to N-unsubsti-
tuted aziridines. On the other hand, chiral 2-oxazolines
were directly produced from olefins when acyl chlorides
were employed as activators of the complex. The reaction
of trans-substituted styrene derivatives gave rise to
trans-2-oxazolines stereoselectively in good yields with
high enantioselectivities. These results represent the first
example of a three-component coupling to chiral oxazo-
lines. The reaction of cis-â-methylstyrene and related
experiments suggest that the present reaction proceeds
via aziridination and subsequent isomerization by Lewis
acids.
(m, 2H), 3.70 (dd, 1H, J ) 4.3, 7.3 Hz), 7.27-7.42 (m, 5H); 13
C
NMR (CDCl3, 68 MHz) δ -2.0, 9.8, 35.2, 40.5, 49.1, 126.4,
128.3, 128.6, 135.0; [R]30 -59.8 (c 0.704, CHCl3) (40% ee);
D
HPLC (Daicel Chiralcel OJ , hexane/2-propanol, 97:3, 1.0 mL/
min, 254 nm, 30 °C) t ) 13.8 (S) and 17.7 min (R).
(2R,3R)-N-[2-(Tr im eth ylsilyl)eth a n esu lfon yl]-2-m eth -
yl-3-p h en yla zir id in e (3b): colorless oil; TLC Rf 0.49 (hexane/
1
EtOAc, 2:1); IR (neat) 2953, 1323, 1252, 1171, 1146 cm-1; H
NMR (CDCl3, 270 MHz) δ -0.05 (s, 9H), 0.91-1.17 (m, 2H),
1.80 (d, 3H, J ) 6.1 Hz), 2.89 (dt, 1H, J ) 4.3, 6.1 Hz), 2.97-
3.12 (m, 2H), 3.64 (d, 1H, J ) 4.3 Hz), 7.23-7.42 (m, 5H); 13
C
NMR (CDCl3, 68 MHz) δ -2.0, 10.0, 14.5, 48.5, 49.3, 51.5,
126.1, 128.2, 128.5, 135.7; MS (CI, methane) m/z (relative
Exp er im en ta l Section
intensity, %) 298 (M+ + H, 100); [R]21 -101.7 (c 1.18, CHCl3)
D
Gen er a l Meth od s. Melting points were determined on a
1
(83% ee); HPLC (Daicel Chiralpak AS, hexane/2-propanol, 98:
2, 0.5 mL/min, 254 nm, 25 °C) t ) 16.5 (2R,3R) and 20.4 min
(2S,3S); HRMS (CI, methane) calcd for C14H24NO2SSi (M +
H)+ 298.1296, found 298.1291. Anal. Calcd for C14H23NO2SSi:
C, 56.52; H, 7.79; N, 4.71. Found: C, 56.48; H, 7.84; N, 4.70.
(2R,3R)-N-[2-(Tr im eth ylsilyl)eth a n esu lfon yl]-2-p h en -
yl-3-p r op yla zir id in e (3c): colorless oil; TLC Rf 0.55 (hexane/
Yanaco melting point apparatus and are uncorrected. H and
13C NMR spectra were recorded at 270 and 68 MHz, respec-
tively. Elemental analyses were performed at the Analytical
Center, Faculty of Engineering, Osaka University. Products
were purified by chromatography on silica gel FL60D (Fuji
Silysia Chemical Co.) or silica gel 60N (spherical, neutral)
(Kanto Chemical Co.) and, if necessary, further purified by
Recycling Preparative HPLC (J apan Analytical Industry Co.,
Ltd., LC-908) equipped with a GPC column (J AIGEL-1H, 2H)
using chloroform as an eluent. Analytical thin-layer chroma-
tography was performed on precoated silica gel glass plates
(silica gel 60 F254, 0.25 mm thickness) (Merck Co.). Visualiza-
tion was accomplished with UV light or treatment with an
ethanolic solution of phosphomolybdic acid followed by heating.
All reactions were carried out under an atmosphere of nitro-
gen, unless otherwise noted. Organic solvents were dried and
distilled prior to use.
1
EtOAc, 2:1); IR (neat) 2956, 1325, 1252, 1171, 1146 cm-1; H
NMR (CDCl3, 270 MHz) δ -0.05 (s, 9H), 0.89-1.19 (m, 2H),
0.99 (t, 3H, J ) 7.4 Hz), 1.42-1.74 (m, 2H), 1.83-1.99 (m, 1H),
2.23-2.38 (m, 1H), 2.77 (dt, 1H, J ) 4.5, 9.0 Hz), 2.98-3.12
(m, 2H), 3.64 (d, 1H, J ) 4.5 Hz), 7.24-7.40 (m, 5H); 13C NMR
(CDCl3, 68 MHz) δ -2.0, 10.1, 13.8, 21.3, 30.8, 49.0, 51.4, 52.9,
126.1, 128.1, 128.6, 135.8; MS (CI, methane) m/z (relative
intensity, %) 326 (M+ + H, 100); [R]22 -101.1 (c 1.47, CHCl3)
D
(85% ee); HPLC (Daicel Chiralcel OD, hexane/2-propanol, 99:
1, 0.5 mL/min, 254 nm, 25 °C) t ) 19.0 (2S,3S) and 21.6 min
(2R,3R); HRMS (CI, methane) calcd for C16H28NO2SSi (M +
H)+ 326.1608, found 326.1621. Anal. Calcd for C16H27NO2SSi:
C, 59.03; H, 8.36; N, 4.30. Found: C, 59.09; H, 8.34; N, 4.41.
(2R,3R)-N-[2-(Tr im eth ylsilyl)eth a n esu lfon yl]-2-isop r o-
p yl-3-p h en yla zir id in e (3d ): white solid; mp 50-52 °C; TLC
Rf 0.55 (hexane/EtOAc, 2:1); IR (KBr) 2968, 1313, 1250, 1178,
1146 cm-1; 1H NMR (CDCl3, 270 MHz) δ -0.06 (s, 9H), 0.93-
1.16 (m, 2H), 1.09 (d, 3H, J ) 6.7 Hz), 1.30 (d, 3H, J ) 6.7
Hz), 2.17-2.35 (m, 1H), 2.65 (dd, 1H, J ) 4.5, 9.6 Hz), 2.95-
Gen er a l P r oced u r e for Asym m etr ic Azir id in a tion of
Olefin s. Pyridine (0.15 mmol), olefin (3.0 mmol), and sulfonyl
chloride (0.36 mmol) were added to a mixture of 1 (0.3 mmol),
silver salt (0.36 mmol), and pyridine N-oxide (0.36 mmol) in
CH2Cl2 (3 mL) at the indicated temperature. After the mixture
was stirred for the indicated time, pentane (20 mL) was added.
The mixture was then passed through a 3-cm pad of silica gel
using diethyl ether (125 mL) as the eluent. The filtrate was
concentrated in vacuo, and the residue was purified by flash
column chromatography on silica gel (hexane/EtOAc). Enan-
tiomeric excesses of the aziridines were determined by chiral
HPLC analysis.
3.05 (m, 2H), 3.64 (d, 1H, J ) 4.5 Hz), 7.25-7.40 (m, 5H); 13
C
NMR (CDCl3, 68 MHz) δ -2.0, 10.1, 21.3, 21.7, 29.1, 48.2, 51.2,
59.5, 126.4, 128.2, 128.6, 135.5; MS (CI, methane) m/z (relative
intensity, %) 326 (M+ + H, 100); [R]20 -92.9 (c 1.02, CHCl3)
D
(R)-N-(p -Tolu en esu lfon yl)-2-p h en yla zir id in e (2a ):15c
white solid; TLC Rf 0.40 (hexane/EtOAc, 2:1); 1H NMR (CDCl3,
270 MHz) δ 2.38 (d, 1H, J ) 4.5 Hz), 2.43 (s, 3H), 2.98 (d, 1H,
J ) 7.3 Hz), 3.77 (dd, 1H, J ) 4.5, 7.3 Hz), 7.19-7.35 (m, 7H),
7.87 (d, 2H, J ) 8.2 Hz); 13C NMR (CDCl3, 68 MHz) δ 21.7,
36.0, 41.1, 126.5, 127.8, 128.2, 128.4, 129.6, 134.9, 134.9, 144.5;
(90% ee); HPLC (Daicel Chiralpak AD, hexane/2-propanol, 97:
3, 0.5 mL/min, 254 nm, 25 °C) t ) 13.2 (2S,3S) and 17.5 min
(2R,3R); HRMS (CI, methane) calcd for C16H28NO2SSi (M +
H)+ 326.1608, found 326.1632.
(2R,3R)-N-[2-(Tr im eth ylsilyl)eth a n esu lfon yl]-2-cyclo-
h exyl-3-p h en yla zir id in e (3e): white solid; mp 104-106 °C;
TLC Rf 0.65 (hexane/EtOAc, 2:1); IR (KBr) 2953, 2925, 2851,
[R]31 -41.9 (c 1.10, CHCl3) (40% ee); HPLC (Daicel Chiralcel
D
OJ , hexane/2-propanol, 7:3, 0.7 mL/min, 254 nm, 30 °C) t )
16.0 (S) and 19.1 min (R).
1318, 1247, 1165, 1143 cm-1 1H NMR (CDCl3, 270 MHz) δ
;
-0.06 (s, 9H), 0.92-1.45 (m, 7H), 1.62-2.04 (m, 5H), 2.31-
2.44 (m, 1H), 2.67 (dd, 1H, J ) 4.3, 9.4 Hz), 2.93-3.08 (m,
2H), 3.64 (d, 1H, J ) 4.3 Hz), 7.23-7.42 (m, 5H); 13C NMR
(CDCl3, 68 MHz) δ -2.0, 10.1, 25.4, 25.7, 26.1, 31.6, 32.2, 37.9,
47.9, 51.2, 58.2, 126.3, 128.1, 128.5, 135.6; MS (CI, methane)
(R)-N-(p-Nitr oben zen esu lfon yl)-2-ph en ylazir idin e (2b):
23
white solid; TLC Rf 0.40 (hexane/EtOAc, 2:1); 1H NMR
(CDCl3, 270 MHz) δ 2.51 (d, 1H, J ) 4.6 Hz), 3.12 (d, 1H, J )
7.3 Hz), 3.90 (dd, 1H, J ) 4.6, 7.3 Hz), 7.18-7.24 (m, 2H),
7.28-7.35 (m, 3H), 8.19 (d, 2H, J ) 9.1 Hz), 8.38 (d, 1H, J )
9.1 Hz); 13C NMR (CDCl3, 68 MHz) δ 36.6, 41.9, 124.2, 126.3,
m/z (relative intensity, %) 366 (M+ + H, 64); [R]29 -57.0 (c
D
1.34, CHCl3) (93% ee); HPLC (Daicel Chiralpak AD, hexane/
128.6, 129.1, 129.1, 134.0, 143.8, 150.5; [R]29 -31.4 (c 0.784,
D
2-propanol, 97:3, 1.0 mL/min, 254 nm, 30 °C) t ) 7.8 (2S,3S)
CHCl3) (43% ee); HPLC (Daicel Chiralcel OJ , hexane/2-
propanol, 1:1, 0.7 mL/min, 254 nm, 30 °C) t ) 36.7 (S) and
52.5 min (R).
and 10.8 min (2R,3R); HRMS (CI, methane) calcd for C19H32
-
NO2SSi (M + H)+ 366.1921, found 366.1909. Anal. Calcd for
19H31NO2SSi: C, 62.42; H, 8.55; N, 3.83. Found: C, 62.35;
C
(R)-N-(Meth a n esu lfon yl)-2-p h en yla zir id in e (2c):6b col-
H, 8.56; N, 3.85.
1
orless oil; TLC Rf 0.28 (hexane/EtOAc, 2:1); H NMR (CDCl3,
(2S,3R)-N-[2-(Tr im eth ylsilyl)eth a n esu lfon yl]-2-m eth yl-
3-p h en yla zir id in e (3f): colorless oil; TLC Rf 0.51 (hexane/
270 MHz) δ 2.44 (d, 1H, J ) 4.3 Hz), 2.98 (d, 1H, J ) 7.3 Hz),
3.11 (s, 1H), 3.72 (dd, 1H, J ) 4.3, 7.3 Hz), 7.26-7.40 (m, 5H);
13C NMR (CDCl3, 68 MHz) δ 35.5, 39.8, 40.8, 126.4, 128.5,
1
EtOAc, 2:1); IR (neat) 2954, 1325, 1252, 1171, 1144 cm-1; H
NMR (CDCl3, 270 MHz) δ 0.05 (s, 9H), 1.10 (d, 3H, J ) 5.9
Hz), 1.12-1.22 (m, 2H), 3.08-3.22 (m, 3H), 3.90 (d, 1H, J )
7.3 Hz), 7.27-7.42 (m, 5H); 13C NMR (CDCl3, 68 MHz) δ -1.9,
9.9, 12.0, 41.0, 45.7, 49.1, 127.5, 127.9, 128.3, 132.7; MS (CI,
128.6, 134.7; [R]28 -88.8 (c 1.08, CHCl3) (42% ee); HPLC
D
(Daicel Chiralcel OJ , hexane/2-propanol, 1:1, 0.5 mL/min, 254
nm, 30 °C) t ) 19.2 (S) and 25.4 min (R).

2108 J . Org. Chem., Vol. 67, No. 7, 2002
Nishimura et al.
isobutane) m/z (relative intensity, %) 298 (M+ + H, 3); [R]28
δ 0.94-1.40 (m, 7H), 1.58-2.01 (m, 6H), 2.74 (d, 1H, J ) 3.0
Hz), 7.13-7.36 (m, 5H); 13C NMR (CDCl3, 68 MHz) δ 25.8, 25.9,
26.3, 30.8, 31.0, 38.4, 43.0, 47.3, 125.5, 126.8, 128.4, 140.8; MS
D
-31.2 (c 1.07, CHCl3) (24% ee); HPLC (Daicel Chiralcel OJ ,
hexane/2-propanol, 97:3, 0.5 mL/min, 254 nm, 30 °C) t ) 13.8
(2R,3S) and 18.7 min (2S,3R); HRMS (CI, methane) calcd for
(EI) m/z (relative intensity, %) 201 (M+, 100); [R]31 +53.3 (c
D
C
14H24NO2SSi (M + H)+ 298.1296, found 298.1288. Anal. Calcd
0.666, CHCl3) (93% ee); HPLC (Daicel Chiralcel OD, hexane/
2-propanol, 9:1, 0.5 mL/min, 254 nm, 30 °C) t ) 10.4 (2S,3S)
and 14.6 min (2R,3R); HRMS (EI) calcd for C14H19N (M)+
201.1517, found 201.1525. Anal. Calcd for C14H19N: C, 83.53;
H, 9.51; N, 6.96. Found: C, 83.40; H, 9.67; N, 6.88.
for C14H23NO2SSi: C, 56.52; H, 7.79; N, 4.71. Found: C, 56.80;
H, 7.98; N, 4.64.
(R)-2-P h en yla zir id in e (4a ).16b A solution of aziridine 3a
(41.2 mg, 0.15 mmol, 40% ee) and TASF (162.5 mg, 0.59 mmol)
in DMF (1 mL) was stirred at room temperature for 48 h. The
mixture was purified by flash column chromatography on silica
gel (hexane/Et2O, 1:1) and Kugelrohr distillation (70 °C, 5
mmHg) to afford a colorless oil of 4a (11.2 mg, 65% yield, 40%
ee). The enantiomeric excess was determined by HPLC analy-
sis of the N-tosyl derivative. 4a : colorless oil; TLC Rf 0.26
(hexane/EtOAc, 1:2); 1H NMR (CDCl3, 270 MHz) δ 1.22 (br s,
1H), 1.81 (d, 1H, J ) 3.3 Hz), 2.22 (d, 1H, J ) 5.9 Hz), 3.02
(dd, 1H, J ) 3.3, 5.9 Hz), 7.21-7.38 (m, 5H); HPLC (Daicel
Chiralcel OJ , hexane/2-propanol, 7:3, 0.5 mL/min, 254 nm, 30
°C) t ) 16.0 (S) and 19.1 min (R).
(2S,3R)-2-Meth yl-3-p h en yla zir id in e (4f).25 A solution of
aziridine 3f (55.1 mg, 0.19 mmol, 24% ee) and TASF (201.2
mg, 0.73 mmol) in DMF (1 mL) was stirred at room temper-
ature for 48 h. The mixture was purified by flash column
chromatography on silica gel (hexane/EtOAc, 7:3) and Kugel-
rohr distillation (70 °C, 5 mmHg) to afford a white solid of 4f
(17.8 mg, 72% yield, 24% ee). The enantiomeric excess was
determined by HPLC analysis of the N-benzoyl derivative. 4f:
white solid; TLC Rf 0.20 (hexane/EtOAc, 2:1); 1H NMR (CDCl3,
270 MHz) δ 0.92 (d, 3H, J ) 5.6 Hz), 1.36 (br s, 1H), 2.42 (dq,
1H, J ) 5.6, 6.6 Hz), 3.25 (d, 1H, J ) 6.6 Hz), 7.18-7.38 (m,
5H); 13C NMR (CDCl3, 68 MHz) δ 13.7, 32.3, 37.2, 126.5, 127.7,
(2R,3R)-2-Meth yl-3-p h en yla zir id in e (4b).24 A solution of
aziridine 3b (64.6 mg, 0.22 mmol, 83% ee) and TASF (242.2
mg, 0.88 mmol) in DMF (1 mL) was stirred at room temper-
ature for 48 h. The mixture was purified by flash column
chromatography on silica gel (hexane/Et2O, 1:1) and Kugelrohr
distillation (70 °C, 5 mmHg) to afford a colorless oil of 4b (22.8
mg, 79% yield, 83% ee). 4b: colorless oil; TLC Rf 0.08 (hexane/
EtOAc, 2:1); 1H NMR (CDCl3, 270 MHz) δ 1.22 (br s, 1H), 1.37
(d, 3H, J ) 5.4 Hz), 2.07-2.22 (m, 1H), 2.66 (d, 1H, J ) 2.8
Hz), 7.15-7.37 (m, 5H); 13C NMR (CDCl3, 68 MHz) δ 19.7, 37.1,
127.8, 137.5; [R]30 -14.7 (c 0.334, CHCl3) (24% ee); HPLC
D
(Daicel Chiralpak AS, hexane/2-propanol, 97:3, 0.5 mL/min,
254 nm, 30 °C) t ) 15.2 (2R,3S) and 18.9 min (2S,3R).
Gen er a l P r oced u r e for Asym m etr ic Syn th esis of 2-Ox-
a zolin es fr om Olefin s. Pyridine (0.15 mmol), olefin (3.0
mmol), and acyl chloride (0.36 mmol) were added to a mixture
of 1 (0.3 mmol), silver salt (0.36 mmol), and pyridine N-oxide
(0.36 mmol) in CH2Cl2 (3 mL) at the indicated temperature.
After the mixture was stirred for the indicated time, pentane
(20 mL) was added. The mixture was then passed through a
3-cm pad of silica gel using diethyl ether (125 mL) as the
eluent. The filtrate was concentrated in vacuo, and the residue
was purified by flash column chromatography on silica gel
(hexane/EtOAc). Enantiomeric excesses of the oxazolines were
determined by chiral HPLC analysis.
(4R,5R)-4-Meth yl-2,5-d ip h en yl-2-oxa zolin e (5a ):26 color-
less oil; TLC Rf 0.40 (hexane/EtOAc, 2:1); IR (neat) 2966, 2926,
1650, 1497, 1450, 1331, 1059 cm-1; 1H NMR (CDCl3, 270 MHz)
δ 1.49 (d, 3H, J ) 6.6 Hz), 4.21 (dq, 1H, J ) 6.6, 7.7 Hz), 5.10
(d, 1H, J ) 7.7 Hz), 7.30-7.54 (m, 8H), 8.00-8.06 (m, 2H);
13C NMR (CDCl3, 68 MHz) δ 21.5, 70.9, 88.1, 125.5, 127.6,
128.2, 128.2, 128.2, 128.7, 131.3, 140.3, 162.6; MS (EI) m/z
(relative intensity, %) 237 (M+, 6); [R]25D -60.4 (c 1.07, MeOH)
(86% ee); HPLC (Daicel Chiralcel OD, hexane/2-propanol, 95:
5, 0.5 mL/min, 254 nm, 30 °C) t ) 9.7 (4S,5S) and 17.4 min
(4R,5R); HRMS (EI) calcd for C16H15NO (M)+ 237.1154, found
237.1138.
40.5, 125.4, 126.8, 128.3, 140.3; [R]22 +50.8 (c 0.378, CHCl3)
D
(83% ee); HPLC (Daicel Chiralcel OD, hexane/2-propanol, 9:1,
0.5 mL/min, 254 nm, 25 °C) t ) 12.4 (2S,3S) and 15.2 min
(2R,3R).
(2R,3R)-2-P h en yl-3-p r op yla zir id in e (4c). A solution of
aziridine 3c (81.8 mg, 0.25 mmol, 85% ee) and TASF (277.5
mg, 1.01 mmol) in DMF (1 mL) was stirred at room temper-
ature for 48 h. The mixture was purified by flash column
chromatography on silica gel (hexane/Et2O, 7:3) and Kugelrohr
distillation (120 °C, 2 mmHg) to afford a colorless oil of 4c
(32.3 mg, 80% yield, 85% ee). 4c: colorless oil; TLC Rf 0.22
(hexane/EtOAc, 2:1); IR (neat) 3242, 2958, 2927, 2872, 1606,
1497, 1458 cm-1; 1H NMR (CDCl3, 270 MHz) δ 0.93-1.04 (m,
4H), 1.45-1.65 (m, 4H), 2.00-2.13 (m, 1H), 2.69 (d, 1H, J )
2.8 Hz), 7.15-7.35 (m, 5H); 13C NMR (CDCl3, 68 MHz) δ 14.1,
20.9, 36.8, 39.6, 42.0, 125.4, 126.8, 128.3, 140.4; MS (EI) m/z
(relative intensity, %) 161 (M+, 13); [R]22 +47.1 (c 0.512,
D
CHCl3) (85% ee); HPLC (Daicel Chiralcel OD, hexane/2-
propanol, 95:5, 0.5 mL/min, 254 nm, 25 °C) t ) 14.5 (2S,3S)
and 19.2 min (2R,3R); HRMS (EI) calcd for C11H15N (M)+
161.1204, found 161.1206.
(4R,5R)-2-[(p-Tr iflu or om eth yl)ph en yl]-4-m eth yl-5-ph en -
yl-2-oxa zolin e (5b): colorless oil; TLC Rf 0.45 (hexane/EtOAc,
2:1); IR (neat) 2968, 2929, 1653, 1414, 1324, 1072 cm-1 1H
;
(2R,3R)-2-Isop r op yl-3-p h en yla zir id in e (4d ). A solution
of aziridine 3d (74.7 mg, 0.23 mmol, 90% ee) and TASF (255.3
mg, 0.92 mmol) in DMF (1 mL) was stirred at room temper-
ature for 48 h. The mixture was purified by flash column
chromatography on silica gel (hexane/Et2O, 7:3) and Kugelrohr
distillation (120 °C, 2 mmHg) to afford a colorless oil of 4d
(29.9 mg, 81% yield, 90% ee). 4d : colorless oil; TLC Rf 0.25
(hexane/EtOAc, 2:1); IR (neat) 3238, 2958, 2868, 1603, 1497,
NMR (CDCl3, 270 MHz) δ 1.51 (d, 3H, J ) 6.6 Hz), 4.25 (dq,
1H, J ) 6.6, 7.7 Hz), 5.14 (d, 1H, J ) 7.7 Hz), 7.31-7.44 (m,
5H), 7.70 (d, 2H, J ) 8.2 Hz), 8.14 (d, 2H, J ) 8.2 Hz); 13C
NMR (CDCl3, 68 MHz) δ 21.4, 71.1, 88.5, 123.7 (q, J C-F ) 272
Hz), 125.3, 125.5, 128.4, 128.6, 128.8, 131.0, 132.9 (q, J C-F
)
33 Hz), 139.9, 161.4; MS (EI) m/z (relative intensity, %) 305
(M+, 0.8); [R]24D -47.3 (c 2.58, CHCl3) (86% ee); HPLC (Daicel
Chiralcel OD, hexane/2-propanol, 170:1, 0.5 mL/min, 254 nm,
30 °C) t ) 14.8 (4R,5R) and 20.8 min (4S,5S); HRMS (EI) calcd
for C17H14F3NO (M)+ 305.1027, found 305.1036. Anal. Calcd
for C17H14F3NO: C, 66.88; H, 4.62; N, 4.59. Found: C, 66.66;
H, 4.78; N, 4.58.
1
1458 cm-1; H NMR (CDCl3, 270 MHz) δ 1.00-1.48 (m, 8H),
1.90 (dd, 1H, J ) 2.8, 7.6 Hz), 2.73 (d, 1H, J ) 2.8 Hz), 7.15-
7.37 (m, 5H); 13C NMR (CDCl3, 68 MHz) δ 20.2, 20.4, 33.5,
38.8, 48.6, 125.4, 126.8, 128.3, 140.5; MS (EI) m/z (relative
intensity, %) 161 (M+, 25); [R]22 +29.5 (c 0.464, CHCl3) (90%
D
ee); HPLC (Daicel Chiralcel OD, hexane/2-propanol, 95:5, 0.5
mL/min, 254 nm, 25 °C) t ) 13.8 (2S,3S) and 17.6 min (2R,3R);
HRMS (EI) calcd for C11H15N (M)+ 161.1204, found 161.1198.
(2R,3R)-2-Cycloh exyl-3-p h en yla zir id in e (4e). A solution
of aziridine 3e (63.7 mg, 0.17 mmol, 93% ee) and TASF (198.3
mg, 0.72 mmol) in DMF (1 mL) was stirred at room temper-
ature for 48 h. The mixture was purified by flash column
chromatography on silica gel (hexane/EtOAc, 8:2) to afford a
white solid of 4e (29.8 mg, 85% yield, 93% ee). 4e: white solid;
mp 35-37 °C; TLC Rf 0.30 (hexane/EtOAc, 2:1); IR (KBr) 3284,
2924, 2848, 1605, 1495, 1448 cm-1; 1H NMR (CDCl3, 270 MHz)
(4R,5R)-2-(p-Meth oxyp h en yl)-4-m eth yl-5-p h en yl-2-ox-
a zolin e (5c): colorless oil; TLC Rf 0.25 (hexane/EtOAc, 2:1);
1
IR (neat) 2962, 2927, 1649, 1608, 1512, 1257, 1171 cm-1; H
NMR (CDCl3, 270 MHz) δ 1.48 (d, 3H, J ) 6.6 Hz), 3.85 (s,
3H), 4.18 (dq, 1H, J ) 6.6, 7.7 Hz), 5.07 (d, 1H, J ) 7.7 Hz),
6.93 (d, 2H, J ) 8.9 Hz), 7.29-7.42 (m, 5H), 7.97 (d, 2H, J )
8.9 Hz); 13C NMR (CDCl3, 68 MHz) δ 21.5, 55.4, 70.9, 88.1,
113.6, 120.1, 125.5, 128.1, 128.6, 130.0, 140.5, 162.0, 162.4;
MS (EI) m/z (relative intensity, %) 267 (M+, 23); [R]24 -81.6
D
(c 1.04, CHCl3) (86% ee); HPLC (Daicel Chiralcel OD, hexane/
2-propanol, 9:1, 0.5 mL/min, 254 nm, 30 °C) t ) 11.2 (4R,5R)

Novel Stereoselective Pathways to Aziridines or Oxazolines
J . Org. Chem., Vol. 67, No. 7, 2002 2109
and 18.5 min (4S,5S); HRMS (EI) calcd for C17H17NO2 (M)+
267.1258, found 267.1257.
(CDCl3, 270 MHz) δ 1.01 (d, 3H, J ) 6.6 Hz), 1.07 (d, 3H, J )
6.9 Hz), 1.90-2.12 (m, 1H), 4.04 (dd, 1H, J ) 6.3, 6.3 Hz), 5.28
(d, 1H, J ) 6.3 Hz), 7.27-7.54 (m, 8H), 8.00-8.07 (m, 2H);
13C NMR (CDCl3, 68 MHz) δ 18.2, 18.6, 32.9, 81.0, 83.2, 125.5,
127.6, 127.9, 128.1, 128.2, 128.6, 131.1, 141.6, 162.2; MS (EI)
(4R,5R)-2-ter t-Bu tyl-4-m eth yl-5-ph en yl-2-oxazolin e (5d):
colorless oil; TLC Rf 0.37 (hexane/EtOAc, 2:1); IR (neat) 2974,
2927, 2872, 1660, 1456, 1363, 1300, 1250, 1140 cm-1; 1H NMR
(CDCl3, 270 MHz) δ 1.30 (s, 9H), 1.37 (d, 3H, J ) 6.6 Hz),
3.96 (dq, 1H, J ) 6.6, 7.3 Hz), 4.87 (d, 1H, J ) 7.3 Hz), 7.24-
7.41 (m, 5H); 13C NMR (CDCl3, 68 MHz) δ 21.7, 27.9, 33.3,
70.6, 87.7, 125.2, 127.9, 128.6, 141.0, 172.3; MS (EI) m/z
(relative intensity, %) 217 (M+, 1); [R]24D +13.7 (c 0.346, CHCl3)
(85% ee); HPLC (Daicel Chiralpak AD, hexane/2-propanol, 170:
1, 0.5 mL/min, 254 nm, 30 °C) t ) 12.1 (4S,5S) and 16.6 min
(4R,5R); HRMS (EI) calcd for C14H19NO (M)+ 217.1466, found
217.1453.
m/z (relative intensity, %) 265 (M+, 2); [R]26 -46.3 (c 0.816,
D
CHCl3) (90% ee); HPLC (Daicel Chiralpak AD, hexane/2-
propanol, 99:1, 0.5 mL/min, 254 nm, 30 °C) t ) 19.8 (4S,5S)
and 24.9 min (4R,5R); HRMS (EI) calcd for C18H19NO (M)+
265.1467, found 265.1490. Anal. Calcd for C18H19NO: C, 81.47;
H, 7.22; N, 5.28. Found: C, 81.28; H, 7.02; N, 5.16.
(4R,5R)-4-Cycloh exyl-2,5-d ip h en yl-2-oxa zolin e (7e):
white solid; mp 90-92 °C; TLC Rf 0.41 (hexane/EtOAc, 9:1);
IR (KBr) 2926, 2852, 1647, 1452, 1383, 1333, 1174, 1068 cm-1
;
(4R,5R)-4-Meth yl-2-isopr opyl-5-ph en yl-2-oxazolin e (5e):
colorless oil; TLC Rf 0.25 (hexane/EtOAc, 2:1); IR (neat) 2972,
2926, 1668, 1456, 1200, 1147 cm-1; 1H NMR (CDCl3, 270 MHz)
δ 1.28 (d, 6H, J ) 6.9 Hz), 1.37 (d, 3H, J ) 6.6 Hz), 2.67 (qq,
1H, J ) 6.9, 6.9 Hz), 3.97 (dq, 1H, J ) 6.6, 7.6 Hz), 4.88 (d,
1H, J ) 7.6 Hz), 7.25-7.41 (m, 5H); 13C NMR (CDCl3, 68 MHz)
δ 19.8, 21.6, 28.4, 70.3, 87.7, 125.3, 128.0, 128.6, 140.8, 170.7;
MS (EI) m/z (relative intensity, %) 203 (M+, 1); [R]26D +24.9 (c
0.716, CHCl3) (87% ee); HPLC (Daicel Chiralcel OD, hexane/
2-propanol, 200:1, 0.5 mL/min, 254 nm, 30 °C) t ) 11.8 (4S,5S)
and 14.1 min (4R,5R); HRMS (EI) calcd for C13H17NO (M)+
203.1309, found 203.1322.
1H NMR (CDCl3, 270 MHz) δ 1.05-1.40 (m, 5H), 1.60-1.88
(m, 5H), 1.88-2.00 (m, 1H), 4.03 (dd, 1H, J ) 6.1, 6.6 Hz),
5.33 (d, 1H, J ) 6.6 Hz), 7.26-7.53 (m, 8H), 8.01-8.05 (m,
2H); 13C NMR (CDCl3, 68 MHz) δ 26.2, 26.2, 26.6, 29.0, 29.4,
43.0, 80.5, 83.4, 125.7, 127.7, 128.0, 128.2, 128.3, 128.6, 131.2,
141.7, 162.2; MS (EI) m/z (relative intensity, %) 305 (M+, 24);
[R]26D -18.6 (c 0.878, CHCl3) (92% ee); HPLC (Daicel Chiralpak
AD, hexane/2-propanol, 150:1, 0.5 mL/min, 254 nm, 30 °C) t
) 22.8 (4S,5S) and 31.7 min (4R,5R); HRMS (EI) calcd for
C
21H23NO (M)+ 305.1778, found 305.1790. Anal. Calcd for
C21H23NO: C, 82.58; H, 7.59; N, 4.59. Found: C, 82.41; H, 7.66;
N, 4.45.
(1R,2R)-2-Isobu tyr yla m in o-1-isobu tyr yloxy-1-p h en yl-
p r op a n e (6): white solid; mp 75-77 °C; TLC Rf 0.25 (hexane/
EtOAc, 2:1); IR (KBr) 3323, 2970, 2933, 1732, 1647, 1539, 1269,
1198 cm-1; 1H NMR (CDCl3, 270 MHz) δ 1.01-1.22 (m, 15H),
2.28 (qq, 1H, J ) 6.9, 6.9 Hz), 2.61 (qq, 1H, J ) 6.9, 6.9 Hz),
4.40-4.55 (m, 1H), 5.54 (br s, 1H), 5.73 (d, 1H, J ) 7.3 Hz),
7.27-7.38 (m, 5H); 13C NMR (CDCl3, 68 MHz) 17.9, 19.0, 19.1,
19.5, 19.6, 34.2, 35.8, 48.8, 126.8, 128.2, 128.4, 137.3, 175.9,
cis-2-P h en yl-3a ,4,5,9b -t et r a h yd r on a p h t h o[2,1-d ]oxa -
zole (7f): colorless oil; TLC Rf 0.32 (hexane/EtOAc, 2:1); IR
(neat) 2929, 2850, 1647, 1495, 1450, 1344, 1084, 1065 cm-1
;
1H NMR (CDCl3, 270 MHz) δ 1.87-2.18 (m, 2H), 2.53-2.64
(m, 1H), 2.72-2.87 (m, 1H), 4.74 (dt, 1H, J ) 4.9, 9.6 Hz), 5.68
(d, 1H, J ) 9.6 Hz), 7.05-7.55 (m, 7H), 7.91-7.96 (m, 2H);
13C NMR (CDCl3, 68 MHz) δ 25.8, 28.7, 64.8, 78.9, 126.5, 127.6,
128.1, 128.2, 128.3, 128.4, 130.4, 131.2, 132.6, 139.7, 164.0;
MS (EI) m/z (relative intensity, %) 249 (M+, 2); HPLC (Daicel
Chiralpak AD, hexane/2-propanol, 9:1, 0.5 mL/min, 254 nm,
30 °C) t ) 10.2 and 20.6 min; HRMS (EI) calcd for C17H15NO
(M)+ 249.1153, found 249.1138.
176.3; MS (EI) m/z (relative intensity, %) 291 (M+, 1); [R]22
D
-31.8 (c 0.630, CHCl3) (86% ee); HPLC (Daicel Chiralcel OJ ,
hexane/2-propanol, 98:2, 0.5 mL/min, 254 nm, 30 °C) t ) 14.8
(1S,2S) and 19.4 min (1R,2R); HRMS (EI) calcd for C17H25
-
-
NO3 (M)+ 291.1833, found 291.1835. Anal. Calcd for C17H25
2,7a-Diph en yl-3a,4,5,6,7,7a-h exah ydr oben zoxazole (7g):
white solid; mp 80-82 °C; TLC Rf 0.40 (hexane/EtOAc, 2:1);
NO3: C, 70.07; H, 8.65; N, 4.81. Found: C, 69.92; H, 8.50; N,
4.67.
1
IR (KBr) 2927, 2850, 1633, 1448, 1344, 1064 cm-1; H NMR
(R)-2,5-Dip h en yl-2-oxa zolin e (7a ):27 colorless oil; TLC Rf
(CDCl3, 270 MHz) δ 1.52-1.73 (m, 4H), 1.98-2.10 (m, 4H),
4.38 (t, 1H, J ) 4.6 Hz), 7.24-7.52 (m, 8H), 8.03-8.08 (m, 2H);
13C NMR (CDCl3, 68 MHz) δ 17.4, 18.3, 26.7, 33.5, 70.7, 87.7,
124.3, 127.2, 128.1, 128.2, 128.2, 128.3, 131.2, 145.7, 162.7;
1
0.32 (hexane/EtOAc, 2:1); H NMR (CDCl3, 270 MHz) δ 4.00
(dd, 1H, J ) 7.9, 14.8 Hz), 4.49 (dd, 1H, J ) 10.2, 14.8 Hz),
5.67 (dd, 1H, J ) 7.9, 10.2 Hz), 7.32-7.51 (m, 8H), 8.00-8.04
(m, 2H); 13C NMR (CDCl3, 68 MHz) δ 63.1, 81.0, 125.6, 127.5,
MS (EI) m/z (relative intensity, %) 277 (M+, 96); [R]29 -39.4
D
128.2, 128.2, 128.3, 128.7, 131.3, 140.9, 163.8; [R]26 -27.3 (c
(c 0.898, CHCl3) (32% ee); HPLC (Daicel Chiralpak AD,
hexane/2-propanol, 95:5, 0.5 mL/min, 254 nm, 30 °C) t ) 22.7
and 31.4 min; HRMS (EI) calcd for C19H19NO (M)+ 277.1466,
found 277.1467. Anal. Calcd for C19H19NO: C, 82.28; H, 6.90;
N, 5.05. Found: C, 82.02; H, 6.95; N, 4.84.
D
1.08, CHCl3) (16% ee); HPLC (Daicel Chiralcel OD, hexane/
2-propanol, 9:1, 0.5 mL/min, 254 nm, 30 °C) t ) 11.8 (S) and
35.5 min (R).
5-Meth yl-2,5-p h en yl-2-oxa zolin e (7b):28 colorless oil; TLC
Rf 0.25 (hexane/EtOAc, 2:1); IR (neat) 2929, 2868, 1649, 1497,
(4S,5R)-4-Meth yl-2,5-d ip h en yl-2-oxa zolin e (8):29 color-
less oil; TLC Rf 0.34 (hexane/EtOAc, 2:1); IR (neat) 2976, 2929,
1651, 1495, 1450, 1342, 1099, 1066 cm-1; 1H NMR (CDCl3, 270
MHz) δ 0.89 (d, 3H, J ) 6.9 Hz), 4.67 (dq, 1H, J ) 6.9, 9.9
Hz), 5.77 (d, 1H, J ) 9.9 Hz), 7.25-7.56 (m, 8H), 8.03-8.07
(m, 2H); 13C NMR (CDCl3, 68 MHz) δ 17.8, 65.4, 83.9, 125.9,
1448, 1348, 1267, 1060 cm-1 1H NMR (CDCl3, 270 MHz) δ
;
1.80 (s, 3H), 4.15 (s, 2H), 7.25-7.54 (m, 8H), 8.02-8.07 (m,
2H); 13C NMR (CDCl3, 68 MHz) δ 28.3, 69.0, 86.7, 124.2, 127.3,
128.0, 128.1, 128.3, 128.5, 131.3, 145.4, 162.9; MS (EI) m/z
(relative intensity, %) 237 (M+, 16); HPLC (Daicel Chiralcel
OD, hexane/2-propanol, 9:1, 0.5 mL/min, 254 nm, 30 °C) t )
9.2 and 13.7 min; HRMS (EI) calcd for C16H15NO3 (M)+
237.1154, found 237.1152.
127.5, 127.6, 128.1, 128.1, 128.2, 131.2, 136.9, 162.8; [R]24
D
-81.1 (c 0.724, CHCl3) (23% ee); HPLC (Daicel Chiralcel OD,
hexane/2-propanol, 9:1, 0.5 mL/min, 254 nm, 30 °C) t ) 10.2
and 24.3 min.
(4R,5R)-2,5-Dip h en yl-4-p r op yl-2-oxa zolin e (7c): color-
less oil; TLC Rf 0.55 (hexane/EtOAc, 2:1); IR (neat) 2958, 2929,
2872, 1651, 1450, 1330, 1062 cm-1; 1H NMR (CDCl3, 270 MHz)
δ 0.97 (t, 3H, J ) 7.3 Hz), 1.45-1.90 (m, 4H), 4.16 (dt, 1H, J
) 6.7, 7.2 Hz), 5.18 (d, 1H, J ) 7.2 Hz), 7.28-7.53 (m, 8H),
8.00-8.05 (m, 2H); 13C NMR (CDCl3, 68 MHz) δ 14.2, 19.2,
38.4, 75.4, 86.3, 125.6, 127.7, 128.1, 128.2, 128.2, 128.7, 131.2,
141.0, 162.4; MS (EI) m/z (relative intensity, %) 265 (M+, 13);
[R]28D -36.2 (c 0.418, CHCl3) (88% ee); HPLC (Daicel Chiralcel
OD, hexane/2-propanol, 99:1, 0.5 mL/min, 254 nm, 30 °C) t )
(2S,3R)-N-Ben zoyl-2-m eth yl-3-p h en yla zir id in e (10):20
colorless oil; TLC Rf 0.50 (hexane/EtOAc, 2:1); IR (neat) 3062,
2929, 1678, 1450, 1414, 1317, 1286 cm-1; 1H NMR (CDCl3, 270
MHz) δ 1.18 (d, 3H, J ) 5.6 Hz), 2.96 (dq, 1H, J ) 5.6, 6.6
Hz), 3.77 (d, 1H, J ) 6.6 Hz), 7.28-7.59 (m, 8H), 8.03 (d, 2H,
J ) 7.9 Hz); 13C NMR (CDCl3, 68 MHz) δ 12.6, 40.1, 44.2,
127.4, 127.6, 128.1, 128.3, 128.9, 132.6, 132.8, 134.6, 179.5;
[R]28D -58.5 (c 0.242, CHCl3) (27% ee); HPLC (Daicel Chiralpak
AS, hexane/2-propanol, 97:3, 0.5 mL/min, 254 nm, 30 °C) t )
15.2 (2R,3S) and 18.9 min (2S,3R).
10.7 (4S,5S) and 16.0 min (4R,5R); HRMS (EI) calcd for C18H19
-
NO (M)+ 265.1466, found 265.1458.
Rea ction of cis-â-Meth ylstyr en e w ith Com p lex 1 in th e
P r esen ce of cis-N-(m -Tolu oyl)-2-m eth yl-3-p h en yla zir i-
d in e (11) (eq 2). cis-â-Methylstyrene (354.5 mg, 0.3 mmol),
benzoyl chloride (50.6 mg, 0.36 mmol), and aziridine 11 (20.7
(4R,5R)-4-Isopr opyl-2,5-diph en yl-2-oxazolin e (7d): white
solid; mp 51-53 °C; TLC Rf 0.53 (hexane/EtOAc, 2:1); IR (KBr)
2958, 2931, 2872, 1653, 1450, 1333, 1063 cm-1 1H NMR
;

2110 J . Org. Chem., Vol. 67, No. 7, 2002
Nishimura et al.
mg, 0.27 mmol) were added to a mixture of 1 (118.1 mg, 0.3
mmol), silver tetrafluoroborate (70.1 mg, 0.36 mmol), and
pyridine N-oxide (34.2 mg, 0.36 mmol) in CH2Cl2 (3 mL) at 0
°C. After the mixture was stirred for 72 h, pentane (20 mL)
was added. The mixture was then passed through a 3-cm pad
of silica gel using diethyl ether (125 mL) as the eluent. The
filtrate was concentrated in vacuo, and the residue was
purified by flash column chromatography on silica gel (hexane/
EtOAc, 98:2) to afford cis-oxazoline 8 (2.8 mg, 4%), trans-
oxazoline 9 (4.1 mg, 6%), aziridine 10 (35.6 mg, 49%), aziridine
11 (13.2 mg, 17%), cis-2-(m-tolyl)-4-methyl-5-phenyl-2-oxazo-
line (1.3 mg, 2%), and trans-2-(m-tolyl)-4-methyl-5-phenyl-2-
oxazoline (2.7 mg, 4%). cis-N-(m -Tolu oyl)-2-m eth yl-3-p h en -
yla zir id in e (11): colorless oil; TLC Rf 0.54 (hexane/EtOAc,
J ) 6.3 Hz), 1.99 (br s, 3H), 2.94-3.11 (m, 1H), 4.24 (d, 1H, J
) 6.6 Hz), 7.21-7.38 (m, 5H); 13C NMR (CDCl3, 68 MHz) δ
20.5, 52.9, 78.6, 126.4, 127.4, 128.2, 142.6; [R]28D -26.5 (c 0.554,
MeOH) (86% ee).
(1R,2R)-2-Am in o-2-cycloh exyl-1-p h en yleth a n ol (18). A
mixture of oxazoline (4R,5R)-7e (52.0 mg, 0.17 mmol, 92% ee)
and 12 M hydrochloric acid (0.6 mL) in EtOH (1 mL) and water
(2.5 mL) was stirred at reflux for 30 h. After cooling to room
temperature, the mixture was washed with Et2O (10 mL). The
aqueous layer was made basic via the addition of an aqueous
5% sodium hydroxide solution (10 mL) and then extracted with
CH2Cl2 (5 × 10 mL). The organic layer was dried over Na2SO4
and evaporated in vacuo to give a white solid of 18 (32.9 mg,
88% yield, 92% ee). The enantiomeric excess was determined
by HPLC analysis of the N-benzoyl derivative. 18: white solid;
mp 81-83 °C; TLC Rf 0.20 (MeOH/CH2Cl2, 2:1); IR (KBr) 3332,
3269, 2918, 2850, 1605, 1448, 1348, 1061, 993 cm-1; 1H NMR
(CDCl3, 270 MHz) δ 0.95-1.35 (m, 7H), 1.55-1.80 (m, 6H),
2.64 (dd, 1H, J ) 5.3, 5.6 Hz), 4.55 (d, 1H, J ) 5.6 Hz), 7.20-
7.35 (m, 5H); 13C NMR (CDCl3, 68 MHz) δ 26.2, 26.3, 26.5,
27.6, 30.8, 39.2, 62.3, 73.2, 126.2, 127.1, 128.2, 143.1; MS (CI,
2:1); IR (neat) 3030, 2927, 1678, 1454, 1414, 1306, 1284 cm-1
;
1H NMR (CDCl3, 270 MHz) δ 1.18 (d, 3H, J ) 5.9 Hz), 2.35 (s,
3H), 2.94 (dq, 1H, J ) 5.9, 6.3 Hz), 3.76 (d, 1H, J ) 6.3 Hz),
7.27-7.45 (m, 7H), 7.81 (d, 1H, J ) 7.3 Hz), 7.85 (s, 1H); 13C
NMR (CDCl3, 68 MHz) δ 12.7, 21.4, 40.2, 44.2, 126.1, 127.4,
127.6, 128.1, 128.2, 129.6, 132.8, 133.4, 134.7, 138.1, 179.8;
MS (EI) m/z (relative intensity, %) 251 (M+, 4); HRMS (EI)
calcd for C17H17NO (M)+ 251.1309, found 251.1319. cis-2-(m -
Tolyl)-4-m eth yl-5-p h en yl-2-oxa zolin e (12): colorless oil;
TLC Rf 0.40 (hexane/EtOAc, 2:1); IR (neat) 2974, 2927, 1651,
isobutane) m/z (relative intensity, %) 220 (M+ + H, 100); [R]29
D
-6.64 (c 0.354, CHCl3) (92% ee); HPLC (Daicel Chiralpak AD,
hexane/2-propanol, 8:2, 0.5 mL/min, 254 nm, 30 °C) t ) 13.0
(1R,2R) and 16.5 min (1S,2S); HRMS (CI, isobutane) calcd for
1454, 1342, 1192, 1101 cm-1 1H NMR (CDCl3, 270 MHz) δ
;
C
14H22NO (M + H)+ 220.1700, found 220.1715. Anal. Calcd
0.89 (d, 3H, J ) 6.9 Hz), 2.41 (s, 3H), 4.66 (dq, 1H, J ) 6.9,
9.6 Hz), 5.76 (d, 1H, J ) 9.6 Hz), 7.23-7.41 (m, 7H), 7.81-
7.86 (m, 1H), 7.89 (s, 1H); 13C NMR (CDCl3, 68 MHz) δ 17.9,
21.3, 65.4, 84.0, 125.3, 126.1, 127.4, 127.7, 128.2, 128.2, 128.8,
132.1, 137.0, 138.1, 163.1; MS (EI) m/z (relative intensity, %)
251 (M+, 2); HRMS (EI) calcd for C17H17NO (M)+ 251.1309,
found 251.1314. tr a n s-2-(m-Tolyl)-4-m eth yl-5-ph en yl-2-oxa-
zolin e (13): colorless oil; TLC Rf 0.47 (hexane/EtOAc, 2:1);
for C14H21NO: C, 76.67; H, 9.65; N, 6.39. Found: C, 76.46; H,
9.62; N, 6.39.
Ack n ow led gm en t. This work was supported, in
part, by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Science, Sports and Culture of
J apan and The Naito Foundation. We also acknowledge
the Instrumental Analysis Center, Faculty of Engineer-
ing, Osaka University.
1
IR (neat) 2964, 2924, 1651, 1454, 1325, 1194, 1061 cm-1; H
NMR (CDCl3, 270 MHz) δ 1.49 (d, 3H, J ) 6.6 Hz), 2.39 (s,
3H), 4.20 (dq, 1H, J ) 6.6, 7.6 Hz), 5.09 (d, 1H, J ) 7.6 Hz),
7.29-7.42 (m, 7H), 7.80-7.84 (m, 1H), 7.86 (s, 1H); 13C NMR
(CDCl3, 68 MHz) δ 21.3, 21.5, 70.9, 88.1, 125.3, 125.5, 127.5,
128.2, 128.2, 128.6, 128.8, 132.1, 138.0, 140.4, 162.7; MS (EI)
m/z (relative intensity, %) 251 (M+, 1); HRMS (EI) calcd for
C17H17NO (M)+ 251.1309, found 251.1305.
J O016146D
(23) Mu¨ller, P.; Baud, C.; J acquier, Y. Tetrahedron 1996, 52, 1543-
1548.
(24) (a) Tomie, M.; Sugimoto, H.; Yoneda, N. Chem. Pharm. Bull.
1976, 24, 1033-1039. (b) Poelert, M. A.; Hof, R. P.; Peper, N. C. M.
W.; Kellogg, R. M. Heterocycles 1994, 37, 461-475.
(25) Galindo, A.; Orea, F. L.; Gnecco, D.; Enr´ıquez, R. G.; Toscano,
R. A.; Reynolds, W. F. Tetrahedron: Asymmetry 1997, 8, 2877-2879.
(26) Colman, B.; de Sousa, S. E.; O’Brien, P.; Towers, T. D.; Watson,
W. Tetrahedron: Asymmetry 1999, 10, 4175-4182.
(27) Meyers, A. I.; Hanagan, M. A.; Trefonas, L. M.; Baker, R. J .
Tetrahedron 1983, 39, 1991-1999.
(1R,2R)-2-Am in o-1-p h en ylp r op a n ol ((-)-Nor p seu d o-
ep h ed r in e) (17).26 A solution of oxazoline (4R,5R)-5a (75.5
mg, 0.32 mmol, 86% ee) in 1.2 M hydrochloric acid (2.4 mL)
was stirred at reflux for 30 h. After cooling to room temper-
ature, the mixture was filtrated. Aqueous 5% sodium hydrox-
ide solution (10 mL) was added to the filtrate, and the aqueous
layer was extracted with CH2Cl2 (5 × 10 mL). The combined
organic layer was dried over Na2SO4 and evaporated in vacuo
to give 17 (44.7 mg, 93% yield, 86% ee). The enantiomeric
excess was determined by a comparison of the optical rotation
with the reported value.30 17:31 white solid; TLC Rf 0.10
(MeOH/CH2Cl2, 2:1); 1H NMR (CDCl3, 270 MHz) δ 1.04 (d, 3H,
(28) Tsuge, O.; Kanemasa, S.; Yamada, T.; Matsuda, K. J . Org.
Chem. 1987, 52, 2523-2530.
(29) Kamata, K.; Agata, I.; Meyers, A. I. J . Org. Chem. 1998, 63,
3113-3116.
(30) Kalm, M. J . J . Org. Chem. 1960, 25, 1929-1937.
(31) Tlahuext, H.; Contreras, R. Tetrahedron: Asymmetry 1992, 3,
727-730.