Stereocontrolled aziridination of imines via a sulfonium ylide route and a mechanistic study

Article abstract of DOI:10.1021/jo0257389

The reaction of N-diphenylphosphinoyl imines 1 with [3- (trimethylsilyl)allyl]dimethylsulfonium bromide (5) in the presence of NaH at room temperature predominantly gave trans-vinylaziridines 4. On the other hand, cis-vinylaziridines 4 were the main products when the preformed ylide prepared from the reaction of [3-(trimethylsilyl)allyl]diphenylsulfonium perchlorate (6) was reacted with the same imines 1 at low temperature. trans-Aziridines were also obtained when imines 1 and sulfinimines 9 were reacted with N,N-dimethylacetamide-2-dimethylsulfonium bromide (7) in the presence of a base, respectively. A mechanistic study showed that the stereochemistry of these reactions was controlled by the reactivity of the imines and ylides. A higher reactivity of imines and ylides favors the formation of cis-aziridines, whereas a lower reactivity leads to trans-products.

Full text of DOI:10.1021/jo0257389

Ster eocon tr olled Azir id in a tion of Im in es via a Su lfon iu m Ylid e
Rou te a n d a Mech a n istic Stu d y
Xiao-Fang Yang, Ming-J ie Zhang, Xue-Long Hou,* and Li-Xin Dai
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fengling Road, Shanghai 200032, China
xlhou@pub.sioc.ac.cn
Received March 20, 2002
The reaction of N-diphenylphosphinoyl imines 1 with [3-(trimethylsilyl)allyl]dimethylsulfonium
bromide (5) in the presence of NaH at room temperature predominantly gave trans-vinylaziridines
4. On the other hand, cis-vinylaziridines 4 were the main products when the preformed ylide
prepared from the reaction of [3-(trimethylsilyl)allyl]diphenylsulfonium perchlorate (6) was reacted
with the same imines 1 at low temperature. trans-Aziridines were also obtained when imines 1
and sulfinimines 9 were reacted with N,N-dimethylacetamide-2-dimethylsulfonium bromide (7) in
the presence of a base, respectively. A mechanistic study showed that the stereochemistry of these
reactions was controlled by the reactivity of the imines and ylides. A higher reactivity of imines
and ylides favors the formation of cis-aziridines, whereas a lower reactivity leads to trans-products.
In tr od u ction
stereoselectivity was achieved with allyl and propargyl
S-ylides, or when a Lewis acid was used as an activating
reagent.4f-h Later, we found that when diphenylphosphi-
noyl imines were used, either cis- or trans-vinylaziridines
were obtained stereoselectively.6 Further studies showed
that trans-aziridines could also be obtained by using
other weakly activated imines, and the stereoselectivity
of the reactions could be controlled by choosing the
activating group on the nitrogen atom of the imines, the
sulfonium ylides, and the reaction conditions. We report
here our detailed investigation of the trans- and cis-
selectivities of aziridination via sulfonium ylide routes
and important aspects of the reaction mechanism.
Aziridines are versatile building blocks that have many
uses in organic synthesis.1 They are also subunits in some
natural products.2 Thus, the synthesis of aziridines is an
active field. Recently, several procedures have been
reported regarding the preparation of these useful com-
pounds. Among them, the direct approach to formation
of the aziridine ring via a carbene or nitrene route is the
most attractive because of its efficiency.3,4 However, most
of these procedures normally give cis-aziridines or a mix-
ture of cis- and trans-aziridines with low stereoselectivity,
and only a few give trans-aziridines or provide a means
to control the stereochemistry of the reaction.3g,5 Recently,
we developed a convenient and facile way to prepare
aziridines with various functionalities through the reac-
tion of sulfonium ylides and N-tosyl imines.4 High cis-
Resu lts a n d Discu ssion
Ster eocon tr olled Azir idin ation of Su lfon iu m Ylides
w ith N-Dip h en ylp h osp h in oyl Im in es 1. In our previ-
ous study, we found that the reaction of N-tosyl imine
with S-ylide proceeded very rapidly.4a-d,g,h Thus, we
reasoned that the lower stereoselectivity of the reaction
might be related to the higher reactivity of N-tosyl imine.
To verify this notion, a competition reaction between
N-tosyl imine 2 and N-diphenylphosphinoyl imine 1 with
sulfonium salt 5 in the presence of NaH was carried out
(eq 1). The reaction gave N-tosyl- and N-diphenylphos-
phinoylaziridines in a ratio of 7:1, indicating that N-
diphenylphosphinoyl imine is less active. Therefore,
(1) (a) Stamm, H. J . Prakt. Chem. 1999, 341, 319. (b) Osborn, H.
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Cocuzza, A. J .; Kishi, Y. Tetrahedron Lett. 1977, 295.
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C.; Bernardinelli, G.; J acquier, Y.; Moran, M.; Muller, P. Helv. Chim.
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P.; Reddy, G. V. J . Org. Chem. 1994, 59, 3243. (o) Cantrill, A. A.; Hall,
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(b) Li, A.-H.; Dai, L.-X.; Hou, X.-L. J . Chem. Soc., Perkin Trans. 1 1996,
867. (c) Li, A.-H.; Dai, L.-X.; Hou, X.-L.; Chen, M.-B. J . Org. Chem.
1996, 61, 4641. (d) Li, A.-H.; Dai, L.-X.; Hou, X.-L. J . Chem. Soc., Perkin
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1317. (h) Li, A.-H.; Zhou, Y.-G.; Dai, L.-X.; Hou, X.-L.; Xia, L.-J .; Tang,
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(6) Part of this work appeared as a preliminary communication (see
ref 4j).
10.1021/jo0257389 CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/22/2002
J . Org. Chem. 2002, 67, 8097-8103
8097

Yang et al.
TABLE 1. Ster eoselective P r ep a r a tion of Azir id in es 4
TABLE 2. Rea ction s of N-Dip h en ylp h osp h in oyl Im in es
w ith Sta bilized Su lfon iu m Ylid ea
entry
Ar
sulfonium salt
base
yielda (%) cis:transb
entry
Ar
base
solvent
yieldb (%) trans:cisc
1
2
3
4
5
6
7
8
9
Ph
Ph
5
5
5
5
5
6
6
6
6
6
6
6
NaHc
92
78
93
95
86
93
90
94
84
72
91
93
10:90
24:76
12:88
20:80
22:78
91:9
99:<1
99:<1
85:15
85:15
87:13
85:15
KOHc
NaHc
NaHc
NaHc
1
2
Ph
Ph
Ph
Ph
Ph
KOH
Cs2CO3
NaH
CH3CNd
CH3CNd
CH3CN
CH2Cl2
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
79
75
98
92
82
90
89
98
98
79:21
80:20
95:5
p-ClC6H4
p-MeOC6H4
1-naphthyl
Ph
3
4
NaH
91:9
d
NaN(TMS)2d
NaN(TMS)2d
NaN(TMS)2d
NaN(TMS)2d
NaN(TMS)2e,f
NaN(TMS)2f
NaN(TMS)2
5e
6
80:20
93:7
89:11
90:10
96:4
p-MeOC6H4
p-MeC6H4
p-ClC6H4
p-MeC6H4
p-MeOC6H4
p-ClC6H4
NaH
NaH
NaH
NaH
7
8
10 p-CF3C6H4
11 Ph
9
1-naphthyl
a
12 Ph
All reactions were carried out at rt on a scale of 1 mmol with
a ratio of imine to sulfonium salt to base of 1:1.1:1.5 at rt. b Isolated
yields based on imine. c Determined by 300 MHz 1H NMR spectra
a
b
Isolated yield. Determined by 300 MHz 1H NMR spectra.
c Run at rt. A 1 equiv sample of LiBr was added, and the reaction
d
d
before purification. The solvent was commercially available and
proceeded at -100 °C. e A 1 equiv sample of LiBr was added.
f Reaction temperature -78 °C.
used without further purification. e The reaction was carried out
with preformed ylide.
N-diphenylphosphinoyl imines 1 were tried in the aziri-
dination reaction.
Table 1 shows that the cis- and trans-aziridines were
obtained in satisfactory yields. Stereocontrol was realized
simply by changing the ligand on the S-atom (i.e., phenyl
or methyl) or by changing the reaction conditions. The
reactions at room temperature with dimethylsulfonium
salt gave trans-aziridines 4, with trans:cis ratios between
78:22 and 90:10, although cis-aziridines were considered
to be thermodynamically more stable and were often
formed as the main products.3o,8 In this reaction, the
selection of the base is important. High stereoselectivity
is obtained when NaH is used (entry 1), while a lower
stereoselectivity is obtained if KOH is used (entry 2).
NaOH, K2CO3, and LiOH gave a selectivity similar to
that of KOH. In addition, the stereoselectivity of the reac-
tion in CH2Cl2 was better than that in CH3CN, benzene,
or DMF. At low temperature, the reaction of preformed
ylide produced from sulfonium salt 6 with imines 1 gave
cis-aziridines in high stereoselectivity. A lower temper-
ature favored the cis-isomer (entry 6 vs entry 12). In some
cases, the reaction gave cis-products almost exclusively
(entries 7, 8, and 10). In contrast to epoxidation and cyclo-
propanation reactions, the presence of LiBr was not cru-
cial for the stereochemistry of this aziridination reaction
(entries 12 and 13).9
N-Diphenylphosphinoyl imines 17 reacted with [3-(tri-
methylsilyl)allyl]dimethylsulfonium bromide (5) in the
presence of a base at room temperature to give trans-
vinylaziridines 4 predominantly. On the other hand, cis-
vinylaziridines 4 were the main products when the
preformed ylide prepared from [3-(trimethylsilyl)allyl]-
diphenylsulfonium perchlorate (6) reacted with the same
imines 1 at low temperature (eq 2, Table 1).
These results suggest that trans-selectivity can be
realized if we decrease the reactivity of the imines. To
show whether trans-products can be favored by decreas-
ing the reactivities of the sulfonium ylides and the
imines, the aziridination of diphenylphosphinoyl imines
1 with stabilized sulfonium salt 7 was further investi-
gated (eq 3), and the results are summarized in Table 2.
We initially carried out this aziridination of diphen-
ylphosphinoyl imine 1a with sulfonium salt 7 in CH3-
(7) (a) Krzyzanowska, B.; Stec, W. J . Synthesis 1978, 521. (b)
Krzyzanowska, B.; Stec, W. J . Synthesis 1982, 270. (c) Zweierzak, A.;
Napieraj, A. Tetrahedron 1996, 52, 8789.
(8) Ibuka, T.; Mimura, N.; Ohno, H.; Nakai, K.; Akaji, M.; Habashita,
H.; Tamamura, H.; Miwa, Y.; Taga, T.; Fuji, N.; Yamamoto, Y. J . Org.
Chem. 1997, 62, 2982.
8098 J . Org. Chem., Vol. 67, No. 23, 2002

Stereocontrolled Aziridination of Imines
CN using KOH as the base. The reaction proceeded
smoothly and generated the expected product 8a with a
trans:cis ratio of 79:21 (entry 1, Table 2). This result was
slightly better than that in the reaction of N-tosyl imines
with sulfonium salt 7.4e To increase the trans:cis selectiv-
ity, the effects of the solvent and base on this reaction
were investigated. We found that acetonitrile and dichlo-
romethane were suitable for this reaction, and acetoni-
trile gave the best results (entry 3, Table 2). Among
various bases, NaH gave the highest yield and stereose-
lectivity (entry 3 vs entries 1 and 2, Table 2). When KOH
or Cs2CO3 was used as the base, small amounts of
diphenylphosphoramide and aldehyde were detected,
which may be produced from hydrolysis of the imine. The
yield and stereoselectivity decreased if preformed ylide
was used (entry 5, Table 2). The aziridination of various
diphenylphosphinoyl imines was further investigated.
The reaction was usually complete within 1 h in almost
quantitative yields with a high trans:cis ratio. This result
is in contrast to the Darzens reaction, which gave similar
aziridinyl carboxylic acid derivatives in high cis-ster-
eoselectivity.3n,o Interestingly, the reaction of imines 1
with sulfonium salt derived from methyl 2-bromoacetate
did not give the corresponding aziridines.4e
the group on the nitrogen is other than in the trans- and
cis-isomers. When 10 was oxidized to the corresponding
N-tosylaziridine by NaIO4, 1H NMR showed that the
trans:cis ratio was 97:3. Imines 9b also reacted smoothly
with sulfur ylide derived from 7. Good yields were
achieved, and the trans:cis ratio was 92:8. However,
perhaps due to low reactivity, some sulfinimines such as
tert-butanesulfinyl imines10b,c and N-(p-methoxyben-
zylidene)-p-toluenesulfinamide did not react with this
sulfur ylide.
Mech a n ism of Azir id in a tion via
a Su lfon iu m
Ylid e Rou te. J ohnson studied the mechanism of nucleo-
philic alkylidene transfer by sulfonium and oxosulfonium
ylides and proposed a two-step process for epoxidation
via sulfonium and oxosulfonium ylides, where the first
step, the initial attack of carbonyl groups by an oxosul-
fonium ylide, was “reversible”, and the attack by a simple
sulfonium ylide was “irreversible”.12 We conjectured that
the initial attack of a CdN bond by sulfonium ylide was
also reversible.
To verify this assumption, analogues of the proposed
intermediates of the reaction of imines 1 and N-tosyl
imines with sulfonium salt 7, i.e., sulfonium salts 17 and
18, were synthesized. Reactions of imines with 2-thioac-
etamide 14 under basic conditions provided compounds
15 and 16. Treatment of compounds 15 and 16 with MeI
in the presence of silver perchlorate afforded sulfonium
salts 17 and 18 (Scheme 1). Under basic conditions, 17
and 18 were converted to aziridines 11 through an anion
intermediate. If the initial attack is irreversible (path a),
17 and 18 will give only cis- and trans-aziridines,
respectively. On the other hand, if the initial attack is
reversible (path b), a mixture of cis- and trans-aziridines
will be obtained regardless of whether 17 or 18 is the
starting material (Scheme 2).
Azir id in a tion of Su lfon iu m Ylid es w ith Su lfin -
im in e 9.10 The reaction of sulfinimines 9 with sulfonium
salt 7 was also carried out to further examine the
relationship between trans-selectivity and the reactivity
of the imine. The reaction of sulfinimine 9a 10a with
sulfonium salt 7 proceeded in CH3CN with NaH as the
base (eq 4). After workup, a mixture of two isomers was
The reaction of sulfonium salt 17 or 18 with base was
carried out (eq 5), and the results are shown in Table 3.
1
obtained in a ratio of ca. 2:1 by 300 MHz H NMR. The
coupling constants of the two hydrogens on the rings of
the two isomers were 3.8 and 4.3 Hz, respectively, while
those of the trans- and cis-isomers were ca. 4 and 7 Hz,
respectively.3n,11 On the basis of a comparison with known
compounds, we thought that the coupling constants of
3.8 and 4.3 Hz might be caused by the hydrogens on the
rings of isomers in which the stereochemistry regarding
As shown in Table 3, the ratio of trans- and cis-
products strongly depends on the groups on the nitrogen
and the sulfur atoms. When EWG is a strong electron-
withdrawing group, such as a tolylsulfonyl group, a lower
ratio of trans- and cis-aziridines is obtained (entries 1
and 2, Table 3). When EWG is a weak electron-
withdrawing group, such as a tolylsulfinyl group, a trans-
sulfonium salt gives a trans-product (entries 5 and 6,
Table 3), even though a different base is used. On the
other hand, the group on the sulfur atom also influenced
the results. When the R group was Ph, cis- and trans-
aziridines were obtained with 17 and 18, respectively
(entries 3 and 4 vs entries 1 and 2, Table 3).
(9) (a) Tang, Y.; Huang, Y.-Z.; Dai, L.-X.; Chi, Z.-F.; Shi, L.-P. J .
Org. Chem. 1996, 61, 5762. (b) Tang, Y.; Huang, Y.-Z.; Dai, L.-X.; Sun,
J .; Xia, W. J . Org. Chem. 1997, 62, 954. (c) Huang, Z. Z.; Ye, S.; Xia,
W.; Tang, Y. Chem. Commun. 2001, 1384. (d) Zhou, Y. G.; Li, A. H.;
Hou, X. L.; Dai, L. X. Chem. Commun. 1996, 1353. (e) Zhou, Y. G.; Li,
A. H.; Dai, L. X.; Hou, X. L. Huaxue Xuebao 2000, 58, 473.
(10) (a) Davis, F. A.; Zhang, Y.; Andemichael, Y.; Fang, T.; Fanelli,
D. L. and Zhang, H., J . Org. Chem. 1999, 64, 1403. (b) Cogan, D. A.;
Liu, G.; Kim, K.; Backes, B. J .; Ellman, J . A. J . Am. Chem. Soc. 1998,
120, 8011. (c) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman,
J . A. J . Org. Chem. 1999, 64, 1278.
(12) (a) J ohnson, C. R.; Schroeck, C. W. J . Am. Chem. Soc. 1971,
93, 5303. (b) J ohnson, C. R.; Schroeck, C. W.; Shanklin, J . R. J . Am.
Chem. Soc. 1973, 95, 7424.
(11) Davis, F. A.; Zhou, P. Tetrahedron Lett. 1994, 35, 7525.
J . Org. Chem, Vol. 67, No. 23, 2002 8099

Yang et al.
SCHEME 1. Syn th esis of Su lfon iu m Sa lts 17 a n d 18
SCHEME 2. Azir id in a tion of 17 a n d 18
TABLE 3. Azir id in a tion of 17 a n d 18a ,b
Con clu sion s
reaction
time (min)
yield
(%)
Stereoselective syntheses of cis- and trans-aziridines
via an S-ylide route were realized. Mechanistic studies
showed that the stereochemistry of the reactions could
be controlled by the reactivities of the imines and ylides.
Imines and ylides with a higher reactivity favor the
formation of cis-aziridines, whereas those with a lower
reactivity prefer trans-products. This study provides one
of the simplest direct routes to aziridines with different
substituents in high stereoselectivity.
entry
substrate
base
trans:cisc
1
2
3
4
5
6
17a
18a
17b
18b
18c
18c
KOH
KOH
KOH
KOH
KOH
NaH
30
30
30
20
20
15
94
92
95
95
81
82
56:44
69:31
5:95
94:6
97:3
97:3
a
All reactions were carried out on a scale of 0.5 mmol at a molar
b
ratio of substrate to base of 1:1. The products were oxidized to
11a with NaIO4 when substrate 18c was used. c Determined by
Exp er im en ta l Section
300 MHz 1H NMR before purification.
Ma ter ia ls a n d Gen er a l P r oced u r es. All reagents and
solvents, unless otherwise specified, were treated according
to standard methods. N-Diphenylphosphinoyl imines 1,7 N-
sulfonyl imine 214 and N-sulfinyl imines 910 were prepared
according to literature methods. 1H NMR spectra were re-
corded in CDCl3 at rt. Chemical shifts are given in parts per
million relative to that of TMS as an internal standard. IR
spectra were recorded neat and are measured in inverse
centimeters.
Gen er a l P r oced u r e for th e Room -Tem p er a tu r e Rea c-
tion of Im in e 1 w ith Su lfon iu m 5. To a solution of sulfonium
salt 5 (0.44 mmol) and diphenylphosphinoyl imine 1 (0.4 mmol)
in CH2Cl2 (4 mL) was added NaH (15 mg, 0.6 mmol) at rt.
The resulting mixture was stirred at rt until the starting
material 1 disappeared (monitored by TLC). Water (10 mL)
was added, and the mixture was extracted by CH2Cl2 (15 mL
× 3). The organic solution was combined and dried by MgSO4.
Removal of solvent under reduced pressure and flash chro-
matography (silicon gel, eluted by petroleum ether/acetate, 5:1)
afforded pure trans-aziridine 4 and cis-aziridine 4.
On the basis of these results, the following mechanism
can be proposed for the reaction of imines with sulfonium
(Scheme 3). The reaction proceeds in two steps. First, the
sulfonium ylide attacks the imine to form intermediates
A and C, which rotate to their conformers, intermediates
B and D, leading to the products through anti-elimina-
tion. In this mechanism, the first step, the initial attack
of the CdN bond by sulfonium ylide, is reversible. Two
intermediates, A and B or C and D, are involved, where
B and C are favorable and A and D are unfavorable
because of steric repulsion. The formation of intermediate
A or C is driven by electrostatic attraction.13 Imines with
a high reactivity will benefit the first step (relatively large
k1), while a better “leaving group” will increase the rate
of elimination.
(13) Ferna´ndez, M. V.; Durante-Lanes, P. and Lo´pez-Herrera, F. J .
Tetrahedron 1990, 46, 7911.
(14) Love, B. E.; Raje, P. S.; Williams, T. C., II. Synlett 1994, 493.
8100 J . Org. Chem., Vol. 67, No. 23, 2002

Stereocontrolled Aziridination of Imines
SCHEME 3. Mech a n ism of Azir id in a tion via a n Ylid e Rou te
Gen er a l P r oced u r e for Low -Tem p er a tu r e Rea ction . To
a solution of sulfonium salt 6 (0.48 mmol) in THF (6 mL) under
argon at -100 °C was added NaN(SiMe3)2 (2 M in THF, 0.24
mL, 0.48 mmol). The resulting mixture was stirred for 10 min.
The solution of imine 1 (0.4 mmol) in THF (2 mL) was added
and the stirring continued for another 1 h. Then the reaction
temperature was allowed to rise to rt. Workup as above and
flash chromatography provided pure trans-aziridine 4 and cis-
aziridine 4.
6.93. Found: C, 69.68; H, 6.82; N, 3.32; P, 6.96. Data for cis-
4c. Colorless thick oil. 1H NMR (300 MHz, CDCl3): δ 7.93 (m,
4H), 7.45 (m, 6H), 7.22 (d, J ) 8.7 Hz, 2H), 6.82 (d, J ) 8.7
Hz, 2H), 6.01 (d, J ) 18.7 Hz, 1H), 5.61 (dd, J 1 ) 7.4 Hz, J 2
)
18.7 Hz, 1H), 4.04 (dd, J 1 ) 6.1 Hz, J 2 ) 16.5 Hz, 1H), 3.78 (s,
3H), 3.48 (m, 1H), -0.07 (s, 9H). 31P NMR: 33.4 ppm. EIMS
(m/z, relative intensity): 452 (63, M+), 250 (100). Anal. Calcd
for C26H30NO2PSi: C, 69.77; H, 6.76; N, 3.13. Found: C, 70.01;
H, 6.87; N, 3.17.
N-Diphenylphosphinoyl-2-(â-trimethylsilyl)vinyl-3-phen-
yla zir id in e (4a ). Data for trans-4a . White solid. Mp: 146-
147 °C. 1H NMR (300 MHz, CDCl3): δ 7.94-7.88 (m, 4H),
7.46-7.23 (m, 11H), 6.39 (dd, J 1 ) 9.2 Hz, J 2 ) 18.5 Hz, 1H),
5.87 (d, J ) 18.5 Hz, 1H), 3.98 (dd, J 1 ) 2.8 Hz, J 2 ) 13 Hz,
1H), 3.13 (ddd, J 1 ) 2.8 Hz, J 2 ) 9.2 Hz, J 3 ) 12.2 Hz, 1H),
-0.03 (s, 9H). 31P NMR: 30.2 ppm. EIMS (m/z, relative
N-Dip h en ylp h osp h in oyl-2-(â-tr im eth ylsilyl)vin yl-3-(p-
m eth yl)p h en yla zir id in e (4d ). Data for trans-4d . White
1
solid. Mp: 145-147 °C. H NMR (300 MHz, CDCl3): δ 7.93-
7.86 (m, 4H), 7.45-7.33 (m, 6H), 7.22 (d, J ) 8.1 Hz, 2H), 6.95
(d, J ) 8.1 Hz, 2H), 6.37 (dd, J 1 ) 9.2 Hz, J 2 ) 18.6 Hz, 1H),
5.85 (d, J ) 18.5 Hz, 1H), 3.94 (dd, J 1 ) 2.9 Hz, J 2 ) 16.0 Hz,
1H), 3.09 (ddd, J 1 ) 2.9 Hz, J 2 ) 9.2 Hz, J 3 ) 12.4 Hz, 1H),
2.33 (s, 3H), -0.04 (s, 9H). 31P NMR: 30.2 ppm. EIMS (m/z,
relative intensity): 432 (81, M+), 431 (100). Anal. Calcd for
intensity): 417 (8, M+), 201 (100). Anal. Calcd for C25H28
-
NOPSi: C, 71.91; H, 6.76; N, 3.36; P, 7.42. Found: C, 71.89;
H, 6.82; N, 3.56; P, 7.31. Data for cis-4a . Colorless thick oil.
1H NMR (300 MHz, CDCl3): δ 7.98-7.92 (m, 4H), 7.47-7.24
(m, 11H), 6.02 (d, J ) 18.7 Hz, 1H), 5.59 (dd, J 1 ) 7.6 Hz, J 2
) 18.7 Hz, 1H), 4.10 (dd, J 1 ) 6.1 Hz, J 2 ) 16.4 Hz, 1H), 3.53
(m, 1H), -0.08 (s, 9H). 31P NMR: 33.3 ppm. EIMS (m/z,
relative intensity): 417 (27, M+), 216 (100), 201 (79). Anal.
Calcd for C25H28NOPSi: C, 71.91; H, 6.76; N, 3.36. Found: C,
72.05; H, 7.06; N, 3.23.
N-Dip h en ylp h osp h in oyl-2-(â-tr im eth ylsilyl)vin yl-3-(p-
ch lor o)p h en yla zir id in e(4b). Data for trans-4b. White solid.
Mp: 172-174 °C. 1H NMR (300 MHz, CDCl3): δ 7.92-7.84
(m, 4H), 7.50-7.26 (m, 10H), 6.35 (dd, J 1 ) 9.1 Hz, J 2 ) 18.5
C
26H30NOPSi: C, 72.36; H, 7.01; N, 3.25; P, 7.18. Found: C,
72.33; H, 6.97; N, 2.82; P, 7.20. Data for cis-4d . Colorless thick
1
oil. H NMR (300 MHz, CDCl3): δ 7.98-7.90 (m, 4H), 7.51-
7.38 (m, 6H), 7.20 (d, J ) 8.0 Hz, 2H), 7.09 (d, J ) 8.0 Hz,
2H), 6.01 (d, J ) 18.7 Hz, 1H), 5.62 (dd, J 1 ) 7.5 Hz, J 2 ) 18.7
Hz, 1H), 4.06 (dd, J 1 ) 6.1 Hz, J 2 ) 16.5 Hz, 1H), 3.51 (m,
1H), 2.31 (s, 3H), -0.06 (s, 9H). 31P NMR: 33.4 ppm. EIMS
(m/z, relative intensity): 431 (27, M+), 230 (100). Anal. Calcd
for C26H30NOPSi: C, 72.36; H, 7.01; N, 3.25; P, 7.18. Found:
C, 72.29; H, 6.90; N, 2.78; P, 7.07.
N-Dip h en ylp h osp h in oyl-2-(â-tr im eth ylsilyl)vin yl-3-(p-
tr iflu or om eth yl)p h en yla zir id in e (4e). Data for trans-4e.
1
Hz, 1H), 5.87 (d, J ) 18.5 Hz, 1H), 3.93 (dd, J 1 ) 2.8 Hz, J 2
)
White solid. Mp: 169-170 °C. H NMR (300 MHz, CDCl3): δ
13 Hz, 1H), 3.08 (ddd, J 1 ) 2.8 Hz, J 2 ) 9.2 Hz, J 3 ) 12.3 Hz,
7.79-7.71 (m, 4H), 7.46-7.22 (m, 10H), 6.37 (dd, J 1 ) 9.1 Hz,
J 2 ) 18.5 Hz, 1H), 5.90 (d, J ) 18.5 Hz, 1H), 4.02 (dd, J 1 ) 2.4
Hz, J 2 ) 15.6 Hz, 1H), 2.96 (m, 1H), -0.2 (s, 9H). 31P NMR:
30.3 ppm. EIMS (m/z, relative intensity): 486 (100, M + 1),
485 (74, M+). Anal. Calcd for C26H27F3NOPSi: C, 64.31; H,
5.61; N, 2.89; P, 6.38. Found: C, 64.20; H, 5.75; N, 2.64; P,
6.18. Data for cis-4e. 1H NMR (300 MHz, CDCl3): δ 7.98-
7.90 (m, 4H), 7.55-7.39 (m, 10H), 6.04 (d, J ) 18.5 Hz, 1H),
5.52 (dd, J 1 ) 6.9 Hz, J 2 ) 18.5 Hz, 1H), 4.12 (dd, J 1 ) 5.5 Hz,
J 2 ) 15.9 Hz, 1H), 3.58 (m, 1H), -0.09 (s, 9H). 31P NMR: 33.4
ppm. EIMS (m/z, relative intensity): 485 (42, M+), 284 (100).
Anal. Calcd for C26H27F3NOPSi: C, 64.31; H, 5.61; N, 2.89; P,
6.38. Found: C, 64.29; H, 5.70; N, 2.64; P, 6.11.
1H), -0.04 (s, 9H). 31P NMR: 30.3 ppm. EIMS (m/z, relative
intensity): 452 (40, M+), 250 (100). Anal. Calcd for C25H27
-
ClNOPSi: C, 66.50; H, 6.03; N, 3.10; P, 6.87. Found: C, 66.71;
H, 6.15; N, 3.22; P, 6.77. Data for cis-4b. Colorless thick oil.
1H NMR (300 MHz, CDCl3): δ 7.96-7.56 (m, 4H), 7.51-7.25
(m, 10H), 6.03 (d, J ) 18.7 Hz, 1H), 5.57 (dd, J 1 ) 7.3 Hz, J 2
) 18.7 Hz, 1H), 4.05 (dd, J 1 ) 6.2 Hz, J 2 ) 16.2 Hz, 1H), 3.54
(m, 1H), -0.05 (s, 9H). 31P NMR: 33.4 ppm. EIMS (m/z,
relative intensity): 452 (63, M+), 250 (100). Anal. Calcd for
C
25H27ClNOPSi: C, 66.50; H, 6.03; N, 3.10. Found: C, 66.62;
H, 6.15; N, 3.10.
N-Dip h en ylp h osp h in oyl-2-(â-tr im eth ylsilyl)vin yl-3-(p-
m eth oxy)p h en yla zir id in e (4c). Data for trans-4c. White
N-Dip h en ylp h osp h in oyl-2-(â-tr im eth ylsilyl)vin yl-3-(1-
n a p h th yl)a zir id in e (4f). Data for trans-4f. White solid. Mp:
134-136 °C. 1H NMR (300 MHz, CDCl3): δ 8.06-8.00 (m, 5H),
1
solid. Mp: 146-147 °C. H NMR (300 MHz, CDCl3): δ 7.92-
7.85 (m, 4H), 7.45-7.34 (m, 6H), 7.25 (dd, J 1 ) 1.6 Hz, J 2
)
8.6 Hz, 2H), 6.85 (dd, J 1 ) 1.8 Hz, J 2 ) 6.9 Hz, 2H), 6.36 (dd,
J 1 ) 9.1 Hz, J 2 ) 18.4 Hz, 1H), 5.86 (d, J ) 18.4 Hz, 1H), 3.92
(dd, J 1 ) 2.9 Hz, J 2 ) 16.0 Hz, 1H), 3.10 (ddd, J 1 ) 2.9 Hz, J 2
) 9.2 Hz, J 3 ) 12.2 Hz, 1H), -0.04 (s, 9H). 31P NMR: 30.2
ppm. EIMS (m/z, relative intensity): 447 (29, M+), 246 (100).
Anal. Calcd for C26H30NO2PSi: C, 69.77; H, 6.76; N, 3.13; P,
7.84 (m, 1H), 7.74 (m, 1H), 7.50-7.39 (m, 10H), 6.53 (dd, J 1 )
9.2 Hz, J 2 ) 18.5 Hz, 1H), 5.91 (d, J ) 18.5 Hz, 1H), 4.63 (dd,
J 1 ) 3.00 Hz, J 2 ) 15.7 Hz, 1H), 3.17 (m, 1H), -0.03 (s, 9H).
31P NMR: 30.3 ppm. EIMS (m/z, relative intensity): 266 (100),
467 (29, M+). Anal. Calcd for C29H30NOPSi: C, 74.49; H, 6.47;
N, 3.00; P, 6.63. Found: C, 74.53; H, 6.55; N, 2.62; P, 6.28.
J . Org. Chem, Vol. 67, No. 23, 2002 8101

Yang et al.
1
Data for cis-4f. H NMR (300 MHz, CDCl3): δ 8.06-8.00 (m,
3H), 2.78 (s, 3H). MS (m/z, relative intensity): 440 (40, M+),
201 (100). Anal. Calcd for C27H25N2O2P: C, 73.61; H, 5.72; N,
6.36; P, 7.04. Found: C, 73.52; H, 5.81; N, 6.53; P, 6.95.
5H), 7.91-7.57 (m, 2H), 7.38-7.20 (m, 10H), 5.85 (d, J ) 18.7
Hz, 1H), 5.25 (dd, J 1 ) 7.5 Hz, J 2 ) 18.7 Hz, 1H), 4.44 (dd, J 1
) 6.2 Hz, J 2 ) 16.0 Hz, 1H), 3.64 (m, 1H), -0.02 (s, 9H). 31P
NMR: 33.9 ppm. EIMS (m/z, relative intensity): 201 (100),
467 (39, M+). Anal. Calcd for C29H30NOPSi: C, 74.49; H, 6.47;
N, 3.00; P, 6.63. Found: C, 74.19; H, 6.87; N, 3.10; P, 6.33.
Gen er a l P r oced u r e for th e Rea ction of Im in es 1 w ith
Su lfon iu m Sa lt 7. To a solution of imine 1 (1 mmol) and
sulfonium salt 7 (251 mg, 1.1 mmol) in acetonitrile (10 mL)
was added NaH (1.1 mmol). The mixture was allowed to stir
at rt till the disappearance of imine from TLC. The mixture
was then diluted with 20 mL of methylene chloride and washed
with 10 mL of water and 20 mL of brine successively. After
the solution was dried over magnesium sulfate, the solvent
was evaporated to give a solid. This solid was determined by
N-(p-Br om oben zylid en e)-p-tolu en esu lfin a m id e (9b).
To a solution of p-toluenesulfinamide (1 g, 6.45 mmol) and
p-bromobenzaldehyde (1.193 g, 6.45 mmol) in methylene
chloride (60 mL) was added titanium(IV) ethoxide (6.8 mL,
32.3 mmol). After being refluxed for 5 h and monitored by TLC,
the reaction mixture was quenched at 0 °C by addition of H2O
(10 mL). The turbid solution was filtered through Celite, and
the filter cake was washed with CH2Cl2 (2 × 50 mL). The
phases were separated, the aqueous phase was washed with
10 mL of CH2Cl2, and the combined organic portions were dried
(MgSO4) and concentrated. Chromatography of the residue on
a short column of silica gel gave 1.974 g (95%) of 9b as a white
solid. Mp: 96-98 °C. IR (KBr): 3050, 1914, 1606, 1587, 1561,
1
300 MHz H NMR for its ratio of trans to cis and purified by
chromatography on a short column of silica gel with 1:1 ethyl
acetate/petroleum ether to provide aziridine 8.
1
1484, 1398, 1107, 1068 cm-1. H NMR (300 MHz, CDCl3): δ
8.36 (s, 1H), 7.70 (d, J ) 8.6 Hz, 2H), 7.64-7.57 (m, 4H), 7.32
(d, J ) 8.3 Hz, 2H), 2.40 (s, 3H). EIMS (m/z, relative
intensity): 323 (2, M + 1), 139 (100), 102 (24), 183 (23), 181
(22), 91 (20), 140 (20), 75 (9). Anal. Calcd for C14H12BrNOS:
C, 52.18; H, 3.75; N, 4.35. Found: C, 52.19; H, 3.83; N, 4.21.
P r oced u r e for th e Rea ction of Im in es 1 w ith P r e-
for m ed Ylid e Der ived fr om Su lfon iu m Sa lt 7. To a solution
of sulfonium salt 7 (250 mg, 1.1 mmol) in acetonitrile (7 mL)
was added NaH (27 mg, 1.1 mmol). The resulting mixture was
allowed to stir for 2 h at rt. The mixture was then diluted with
20 mL of methylene chloride and quickly washed with 10 mL
of water and 20 mL of brine successively to provide the
expected ylide, which was used without further purification.
To a solution of imine 1 (1 mmol) in acetonitrile (7 mL) was
added preformed ylide obtained in the above procedure. The
mixture was allowed to stir at rt till the disappearance of imine
from TLC. Workup as above provided aziridine 8.
N-Diph en ylph osph in oyl-2-(N,N-dim eth ylam in ocar bon -
yl)-3-p h en yla zir id in e (8a ). White solid. Mp: 157-158 °C.
1H NMR (300 MHz, CDCl3): δ 7.97-7.91 (m, 2H), 7.80-7.74
(m, 2H), 7.42-7.23 (m, 11H), 4.10 (dd, J 1 ) 3.1 Hz, J 2 ) 14.2
Hz, 1H), 3.80 (dd, J 1 ) 3.1 Hz, J 2 ) 13.7 Hz, 1H), 2.92 (s, 3H),
2.86 (s, 3H). MS (m/z, relative intensity): 390 (47, M+), 201
(100). Anal. Calcd for C23H23N2O2P: C, 70.74; H, 5.94; N, 7.18;
P, 7.94. Found: C, 70.74; H, 5.92; N, 7.07; P, 7.69.
N-Diph en ylph osph in oyl-2-(N,N-dim eth ylam in ocar bon -
yl)-3-(p-m eth ylph en yl)azir idin e (8b). White solid. Mp: 183-
184 °C. 1H NMR (300 MHz, CDCl3): δ 7.98-7.91 (m, 2H),
7.80-7.74 (m, 2H), 7.42-7.33 (m, 6H), 7.18 (d, J ) 8.1 Hz,
2H), 7.05 (d, J ) 8.0 Hz, 2H), 4.06 (dd, J 1 ) 3.1 Hz, J 2 ) 14.2
Hz, 1H), 3.79 (dd, J 1 ) 3.1 Hz, J 2 ) 13.8 Hz, 1H), 2.86 (s, 3H),
2.30 (s, 3H). MS (m/z, relative intensity): 404 (49, M+), 201
(100). Anal. Calcd for C24H25N2O2P: C, 71.26; H, 6.23; N, 6.93;
P, 7.66. Found: C, 71.25; H, 6.23; N, 6.99; P, 7.74.
Gen er a l P r oced u r e for th e Rea ction of Im in es 9 w ith
Su lfon iu m Ylid e 7. To a solution of 1 mmol of imine 9 and
251 mg (1.1 mmol) of sulfonium salt 7 in 10 mL of acetonitrile
was added 27 mg (1.1 mmol) of NaH. This mixture was allowed
to stir at rt till the disappearance of imine from TLC. The
mixture was then diluted with 20 mL of methylene chloride
and washed with 10 mL of water and 20 mL of brine
successively. After the solution was dried over magnesium
sulfate, the solvent was evaporated. The residue was solved
with 10 mL of acetonitrile, and then to the solution were added
10 mL of water, 321 mg (1.5 mmol) of sodium periodate, and
a catalytic amount of ruthenium(III) chloride hydrate. The
mixture was stirred for about 30 min. After normal workup a
solid was obtained. This solid was determined by 300 MHz
1H NMR for its ratio of trans to cis and purified by chroma-
tography on a short column of silica gel with 1:1 ethyl acetate/
petroleum ether.
N-(p-Tolu en esu lfon yl)-2-(N,N-dim eth ylam in ocar bon yl)-
3-p h en yla zir id in e (11a ). 1H NMR (300 MHz, CDCl3): (trans)
δ 7.76 (d, J ) 8.3 Hz, 2H), 7.27-7.18 (m, 7H), 4.45 (d, J ) 4.2
Hz, 1H), 3.55 (d, J ) 4.2 Hz, 1H), 3.24 (s, 3H), 3.04 (s, 3H),
2.39 (s, 3H).
N-(p-Tolu en esu lfon yl)-2-(N,N-dim eth ylam in ocar bon yl)-
3-(p-ch lor op h en yl)a zir id in e (11b). 1H NMR (300 MHz,
CDCl3): (trans) δ 7.78 (dd, J 1 ) 6.8 Hz, J 2 ) 1.5 Hz, 2H), 7.30-
7.13 (m, 6H), 4.42 (d, J ) 4.1 Hz, 1H), 3.53 (d, J ) 4.1 Hz,
1H), 3.25 (s, 3H), 3.05 (s, 3H), 2.42 (s, 3H).
N-Diph en ylph osph in oyl-2-(N,N-dim eth ylam in ocar bon -
yl)-3-(p-m eth oxyp h en yl)a zir id in e (8c). White solid. IR
(KBr): 3054, 1655, 1410, 1140, 1074, 823, 750 cm-1. H NMR
1
Com p etition Rea ction of N-Dip h en ylp h osp h in oyl Im i-
n e 1a a n d N-Tosyl Im in e 2 w ith Su lfon iu m Sa lt 5. To a
solution of diphenylphosphinoyl imine 1a (153 mg, 0.5 mmol),
N-tosyl imine 2 (130 mg, 0.5 mmol), and sulfonium salt 5 (128
mg, 0.5 mmol) in CH2Cl2 (10 mL) was added NaH (18 mg, 0.75
mmol) in one portion at rt. The mixture was stirred and
monitored by TLC. After the disappearance of sulfonium,
water (10 mL) was added. The organic layer was separated,
and the aqueous layer was washed with CH2Cl2 (10 mL × 3).
The organic layer was combined and dried with anhydrous
MgSO4. The solvent was evaporated. The crude mixture
showed the ratio of N-tosylaziridine 3 and N-diphenylphos-
phinoylaziridine 4a was 7:1. Flash chromatography provided
146 mg (78%) of N-tosylaziridine 3 and 20 mg (10%) of
N-diphenylphosphinoylaziridine 4a .
N-Tosyl-2-ph en yl-3-(â-tr im eth ylsilyl)vin ylazir idin e (3).4c
1H NMR (300 MHz, CDCl3): (cis-3) δ 7.89 (d, J ) 8.3 Hz, 2
H), 7.15-7.34 (m, 7 H), 6.12 (d, J ) 18.5 Hz, 1 H), 5.41(dd, J
) 7.3, 18.71 Hz, 1 H), 4.01 (d, J ) 7.3 Hz, 1 H), 3.63 (dd, J )
7.6, 7.0 Hz, 1 H), 2.43 (s, 3 H), -0.04 (s, 9 H); (trans-3) δ 7.82
(d, J ) 8.3 Hz, 2 H), 7.15-7.34 (m, 7 H), 6.42 (dd, J ) 8.9,
(300 MHz, CDCl3): δ 7.82-7.77 (m, 2H), 7.61-7.55 (m, 2H),
7.22-7.14 (m, 6H), 7.06 (d, 2H), 6.61 (d, 2H), 3.87 (dd, J 1
)
3.2 Hz, J 2 ) 14.1 Hz, 1H), 3.71 (dd, J 1 ) 3.2 Hz, J 2 ) 14.0 Hz,
1H), 3.63 (s, 3H), 2.78 (s, 3H), 2.74 (s, 3H). MS (m/z, relative
intensity): 420 (18, M+), 201 (100). Anal. Calcd for
C
24H25N2O3P: C, 68.55; H, 6.00; N, 6.67; P, 7.37. Found: C,
68.53; H, 6.02; N, 6.54; P, 7.15.
N-Diph en ylph osph in oyl-2-(N,N-dim eth ylam in ocar bon -
yl)-3-(p-ch lor op h en yl)a zir id in e (8d ). White solid. IR
1
(KBr): 3050, 1660, 1500, 1450, 1380, 1140, 980, 740 cm-1. H
NMR (300 MHz, CDCl3): δ 7.96-7.90 (m, 2H), 7.81-7.75 (m,
2H), 7.47-7.19 (m, 10H), 4.08 (dd, J 1 ) 3.0 Hz, J 2 ) 14.1 Hz,
1H), 3.78 (dd, J 1 ) 3.0 Hz, J 2 ) 13.7 Hz, 1H), 2.93 (s, 3H),
2.84 (s, 3H). MS (m/z, relative intensity): 424 (19, M+), 201
(100). Anal. Calcd for C23H23N2O2P: C, 65.08; H, 5.23; N, 6.60;
P, 7.30. Found: C, 64.89; H, 5.24; N, 6.42; P, 7.23.
N-Diph en ylph osph in oyl-2-(N,N-dim eth ylam in ocar bon -
yl)-3-(1-n a p h th yl)a zir id in e (8e). White solid. Mp: 168-170
1
°C. H NMR (300 MHz, CDCl3): δ 8.04-7.98 (m, 2H), 7.81-
7.74 (m, 2H), 7.50-7.26 (m, 13H), 4.82 (dd, J 1 ) 3.2 Hz, J 2
)
14.9 Hz, 1H), 3.78 (dd, J 1 ) 3.2 Hz, J 2 ) 13.6 Hz, 1H), 2.96 (s,
8102 J . Org. Chem., Vol. 67, No. 23, 2002

Stereocontrolled Aziridination of Imines
18.3 Hz, 1 H), 6.21 (d, J ) 18.4 Hz, 1 H), 4.08 (d, J ) 4.1 Hz,
1 H), 3.27 (dd, J ) 4.0, 9.0 Hz, 1 H), 2.40 (s, 3 H), 0.03 (s, 9
H).
3H). EIMS (m/z, relative intensity): 455 (11, M + 1), 195 (100),
72 (46), 91 (37), 155 (19), 260 (12), 178 (4). Anal. Calcd for
C24H26N2O3S2: C, 63.41; H, 5.76; N, 6.16; S, 14.11. Found: C,
63.27; H, 5.74; N, 6.01; S, 14.50. Data for 16b. White solid
(threo). Mp: 116-117 °C. IR (KBr): 3261, 3050, 1624, 1495,
Gen er a l P r oced u r e for th e P r ep a r a tion of Com p ou n d s
15 a n d 16. To a solution of N,N-dimethyl-2-bromoacetamide
(13) (1.66 g, 10 mmol) and Et3N (1.4 mL, 10 mmol) in 40 mL
of methylene chloride was added 1.1 g (1 mL, 10 mmol) of
phenylthiol at 0 °C under argon. This mixture was allowed to
stir for 20 min. The solution was then washed with water.
After the solution was dried over magnesium sulfate, the
solvent was evaporated to give the residue. Chromatography
on a short column of silica gel with 1:1 ethyl acetate/petroleum
ether gave N,N-dimethyl-2-n-butylthioacetamide (14) as a light
yellow oil: IR (film): 2956, 2931, 1645, 1496, 1466, 1427, 1395
cm-1. 1H NMR (400 MHz, CDCl3): δ 3.30 (s, 2H), 3.08 (s, 3H),
2.97 (s, 3H), 2.66 (t, J ) 7.6 Hz, 2H), 1.63-1.55(m, 2H), 1.45-
1.37 (m, 2H), 0.91 (t, J ) 7.3 Hz, 3H). EIMS (m/z, relative
intensity): 175 (8, M), 87 (100), 72 (47), 45 (40), 42 (9).
To a solution of 14 (5 mmol) in THF (10 mL) was added
LDA (2 M in THF/n-heptane, 2.5 mL, 5 mmol) under argon at
-78 °C, and the resulting solution was stirred for 30 min. To
the mixture was then added the solution of imine (5 mmol) in
THF (10 mL) dropwise. After the mixture was stirred for
another 40 min at the same temperature, the reaction was
broken with saturated NH4Cl (20 mL). The mixture was
extracted with ethyl acetate (2 × 30 mL). After the organic
layer was dried with magnesium sulfate, chromatography on
a short column (silica gel, eluted by petroleum ether/acetate/
Et3N with a ratio of 75:25:1) gave the expected products.
N,N-Dim et h yl-2-b u t ylt h io-3-(p -t olu en esu lfon yl)a m i-
n op h en ylp r op ion a m id e. Flash chromatography gave 0.43
g (33%) of 15a and 0.86 g (67%) of 16a . Data for 15a . White
solid (erythro). Mp: 177-178 °C. IR (KBr): 3242, 2930, 1635,
1
1454, 1400, 1328, 1162 cm-1. H NMR (300 MHz, CDCl3): δ
7.58 (d, J ) 8.3 Hz, 2H), 7.48 (d, J ) 7.7 Hz, 1H), 7.39 (m,
2H), 7.31 (m, 3H), 7.14-7.04 (m, 7H), 4.79 (dd, J 1 ) 3.8 Hz,
J 2 ) 7.7 Hz, 1H), 4.15 (d, J ) 3.8 Hz, 1H), 2.73 (s, 3H), 2.35
(s, 3H), 2.32 (s, 3H). EIMS (m/z, relative intensity): 195
(100.00), 72 (67.28), 91 (64.58), 155 (35.53), 196 (14.00), 260
(8.38), 77 (10.45). Anal. Calcd for C24H26N2O3S2: C, 63.41; H,
5.76; N, 6.16; S, 14.11. Found: C, 63.35; H, 5.81; N, 6.09; S,
14.34.
N,N-Dim et h yl-2-b u t ylt h io-3-(p -t olu en esu lfin yl)a m i-
n op h en ylp r op ion a m id e. Flash chromatography gave 1.126
g (54%) of 16c as a white solid (threo). Mp: 158-159 °C. IR
(film): 3205, 2925, 1620, 1494, 1456, 1408, 1095, 1071 cm-1
.
1H NMR (300 MHz, CDCl3): δ 7.59 (d, J ) 8.2 Hz, 2H), 7.42-
7.26 (m, 7H), 5.92 (d, J ) 5.4 Hz, 1H), 4.73 (dd, J 1 ) 5.4 Hz,
J 2 ) 6.6 Hz, 1H), 3.79 (d, J ) 6.6 Hz, 1H), 2.85 (s, 3H), 2.77
(s, 3H), 2.40 (s, 3H), 2.53-2.34 (m, 2H), 1.48-1.29 (m, 4H),
0.87 (t, J ) 7.2 Hz, 3H). EIMS (m/z, relative intensity): 419
(3, M + 1), 175 (100), 139 (63), 72 (30), 119 (29), 87 (28), 91
(19), 77 (12). Anal. Calcd for C22H30N2O2S2: C, 63.12; H, 7.22;
N, 6.69; S, 15.32. Found: C, 63.32; H, 6.97; N, 6.71; S, 15.48.
A 0.685 g (33%) sample of an unseparated mixture of various
isomers was also obtained.
P r oced u r e for th e Meth yla tion of 15 a n d Its Azir id i-
n a tion Rea ction . To a solution of 15 (1 mmol) in methyl
iodide (4 mL) was added silver perchlorate (208 mg, 1 mmol).
The mixture was stirred for 2 h at rt and then filtered through
a pad of Celite, the filtrate was washed with methylene
chloride (50 mL) and concentrated to ca. 10 mL, and then 70
mL of ether was added for recrystallization. Such recrystal-
lization gave the required salt 17 as a white solid, which was
used without further purification.
To a solution of 17 (0.5 mmol) in CH2Cl2 (5 mL) was added
base (0.5 mmol). The mixture was stirred for ca. 30 min at rt.
The reaction was quenched with 10 mL of water, and the
mixture was extracted with methylene chloride (2 × 15 mL).
The organic layer was dried with anhydrous magnesium
sulfate, and the solvent was then evaporated. The residue was
determined for its ratio of trans to cis by NMR and separated
by chromatography on a short column of silica gel.
1497, 1457, 1412, 1327, 1160 cm-1 1H NMR (300 MHz,
.
CDCl3): δ 7.53 (d, J ) 8.3 Hz, 2H), 7.25 (m, 2H), 7.14 (m, 5H),
5.86 (d, J ) 1.8 Hz, 1H), 4.58 (dd, J 1 ) 1.8 Hz, J 2 ) 9.9 Hz,
1H), 3.60 (d, J ) 9.9 Hz, 1H), 2.75 (s, 3H), 2.71 (s, 3H), 2.39
(m, 1H), 2.36 (s, 3H), 2.20 (m, 1H), 1.41-1.27 (m, 4H), 0.87 (t,
J ) 7.2 Hz, 3H). EIMS (m/z, relative intensity): 435 (11, M +
1), 175 (100), 91 (74), 87 (46), 155 (37), 72 (37), 119 (29), 176
(27), 118 (22). Anal. Calcd for C22H30N2O3S2: C, 60.80; H, 6.96;
N, 6.45; S, 14.76. Found: C, 60.86; H, 7.19; N, 6.42; S, 14.89.
Data for 16a . White solid (threo). Mp: 122-123 °C. IR (KBr):
3196, 2930, 1620, 1496, 1461, 1409, 1331, 1162 cm-1. 1H NMR
(300 MHz, CDCl3): δ 7.25 (d, J ) 7.3 Hz, 2H), 7.34 (d, J ) 7.1
Hz, 1H), 7.18-7.08 (m, 7H), 4.75 (dd, J 1 ) 4.0 Hz, J 2 ) 7.1
Hz, 1H), 3.84 (d, J ) 4.0 Hz, 1H), 2.78 (s, 3H), 2.60 (s, 3H),
2.56 (m, 1H), 2.44 (m, 1H), 2.33(s, 3H), 1.48-1.31 (m, 4H),
0.90 (t, J ) 7.1 Hz, 3H). EIMS (m/z, relative intensity): 434
(0.43, M), 175 (100), 91 (79), 87 (52), 155 (38), 72 (35), 119
(33), 118 (28), 176 (23). Anal. Calcd for C22H30N2O3S2: C, 60.80;
H, 6.96; N, 6.45; S, 14.76. Found: C, 60.82; H, 7.25; N, 6.42;
S, 14.81.
P r oced u r e for th e Meth yla tion of 16 a n d Its Azir id i-
n a tion Rea ction . Salt 18 was prepared by using the same
procedure as that to prepare salt 17. The same procedure was
also used for the aziridination reaction of salt 18.
Ack n ow led gm en t. This work was supported by the
National Natural Science Foundation of China, Major
Basic Research Development Program (Grant No.
G2000077506), National Outstanding Youth Fund, Chi-
nese Academy of Sciences, and Shanghai Committee of
Science and Technology. This paper is dedicated to
Professor Yao-Zeng Huang on the occasion of his 90th
birthday.
N,N-Dim eth yl-2-p h en ylth io-3-(p-tolu en esu lfon yl)a m i-
n op h en ylp r op ion a m id e. Flash chromatography gave 0.636
g (30%) of 15b and 1.501 g (70%) of 16b. Data for 15b. White
solid (erythro). Mp: 195-197 °C. IR (film): 3222, 3050, 1625,
1495, 1461, 1401, 1328, 1160 cm-1 1H NMR (300 MHz,
.
CDCl3): δ 7.52 (d, J ) 8.3 Hz, 2H,), 7.37-7.12 (m, 12H), 6.00
(d, J ) 3.3 Hz, 1H), 4.58 (dd, J 1 ) 3.3 Hz, J 2 ) 9.2 Hz, 1H),
4.09 (d, J ) 9.2 Hz, 1H), 2.64 (s, 3H), 2.53 (s, 3H), 2.37 (s,
J O0257389
J . Org. Chem, Vol. 67, No. 23, 2002 8103