Highly Stereoselective Ylide Aziridination of N-Sulfonylimines with Sulfonium Propargylides: A Simple Way to Synthesize Scalemic Acetylenylaziridines

Article abstract of DOI:10.1021/jo9800964

Under phase-transfer or low-temperature conditions, the ylide generated from diphenylsulfonium salt 2 readily reacts with N-sulfonylimines 1 to give acetylenylaziridines in excellent yields, but low to moderate cis/trans selectivity. When using n-BuLi as the base to generate the ylide at low termperature, product 3 with an intact silyl protecting group is obtained. t-BuOK, however, leads to desilylation product 4. With Cs₂CO₃ as the base, dimethylsulfonium salts 6, 21, and 22 show much better cis/trans selectivity (>98:2) than diphenylsulfonium salt 2. The asymmetric version of the above aziridination reaction using camphor-derived sulfonium salts 12-14 and 20 gives chiral aziridines with ee values up to 85percent. Both (2R,3S)-(-)-3 and (2S,3A)-(+)-3 can be prepared from 12/20 or 13/14, respectively. Ylides produced from telluronium salt 7 failed to react with imine la at room temperature, but the reaction succeeded at low temperature. Arsonium ylides from 8 cannot react with N-sulfonylimines under both sets of conditions.

Full text of DOI:10.1021/jo9800964

4338
J . Org. Chem. 1998, 63, 4338-4348
High ly Ster eoselective Ylid e Azir id in a tion of N-Su lfon ylim in es
w ith Su lfon iu m P r op a r gylid es: A Sim p le Wa y To Syn th esize
Sca lem ic Acetylen yla zir id in es
An-Hu Li,† Yong-Gui Zhou,† Li-Xin Dai,*,† Xue-Long Hou,† Li-J un Xia,‡ and Lin Lin‡
Laboratory of Organometallic Chemistry and Analytic Chemistry Department, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received J anuary 21, 1998
Under phase-transfer or low-temperature conditions, the ylide generated from diphenylsulfonium
salt 2 readily reacts with N-sulfonylimines 1 to give acetylenylaziridines in excellent yields, but
low to moderate cis/trans selectivity. When using n-BuLi as the base to generate the ylide at low
termperature, product 3 with an intact silyl protecting group is obtained. t-BuOK, however, leads
to desilylation product 4. With Cs2CO3 as the base, dimethylsulfonium salts 6, 21, and 22 show
much better cis/trans selectivity (>98:2) than diphenylsulfonium salt 2. The asymmetric version
of the above aziridination reaction using camphor-derived sulfonium salts 12-14 and 20 gives
chiral aziridines with ee values up to 85%. Both (2R,3S)-(-)-3 and (2S,3R)-(+)-3 can be prepared
from 12/20 or 13/14, respectively. Ylides produced from telluronium salt 7 failed to react with
imine 1a at room temperature, but the reaction succeeded at low temperature. Arsonium ylides
from 8 cannot react with N-sulfonylimines under both sets of conditions.
In tr od u ction
aza-Darzens reaction,4d,e and the Lewis acid method,4f the
present ylide approach has several advantages: (a) There
are a wide range of ylide reagents from which to choose,
most of them easily accessible. (b) A variety of sub-
strates, either aromatic or aliphatic aldimines or
ketimines, can be used. (c) The reaction conditions are
generally mild, and the operations are simple. (d) The
ylide precursor reagents are recyclable.
During the course of our studies on the reactivity of
imines in developing imine-based synthetic methodolo-
gies,6,9 we found that in contrast to the common N-aryl-
or N-alkylimines, N-sulfonylimines showed extremely
high reactivity toward semistabilized or stabilized sul-
fonium allylides. This has led to an efficient, convenient,
and mild route to various vinylaziridines.6 However, the
trans/cis selectivity of these reactions was not satisfactory
despite many efforts that had been made. Fortunately,
when we extended these allylic ylide reagents to corre-
sponding propargylic sulfonium ylides, exclusive cis
selectivity was eventually achieved. On this basis, an
efficient asymmetric ylide aziridination, which produced
acetylenylaziridines, a type of new chiral aziridine de-
rivative, was realized.10 Herein, we report the full details
of this new asymmetric aziridination.
The great synthetic utility of chiral aziridines stimu-
lates the development of efficient methods for preparing
this type of nitrogen-containing strained ring com-
pounds.1 Among various strategies2 starting from
prochiral CdC3 and CdN4 double bonds, the aziridination
through the reaction of an imine with an ylide (i.e., ylide
aziridination) has recently showed great promise in
obtaining various functionalized aziridines by the results
of Aggarwal,5 our group,6 and other laboratories4,7 (al-
though there were also a few other examples8 earlier).
Compared with other direct aziridinating reactions with
a CdN double bond, e.g., the carbene approach,4a-c the
† Laboratory of Organometallic Chemistry.
‡ Analytic Chemistry Department.
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J . D.; Gadamasetti, K. G. Synlett 1990, 433.
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S0022-3263(98)00096-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/11/1998

Simple Synthesis of Scalemic Acetylenylaziridines
J . Org. Chem., Vol. 63, No. 13, 1998 4339
Ta ble 1. P r ep a r a tion of N-Su lfon yla cetylen yla zir id in es 3 a n d 4 by Rea ction of N-Su lfon ylim in es 1 a n d
3-(Tr im eth ylsilyl)p r op a r gyld ip h en ylsu lfon iu m P er ch lor a te (2) u n d er P h a se-Tr a n sfer Con d ition sa
a
All reactions were carried out in a ratio of imine:sulfonium salt:KOH(s) ) 1:1.2:1.2 at a 0.5-mmol scale in CH3CN at room temperature.
Isolated yields based on imine. c Determined by 300-MHz 1H NMR analysis.
b
Resu lts a n d Discu ssion
are presented in Table 2. Compared with the results
obtained under phase-transfer conditions (entry 2 in
Table 1), the cis/trans selectivity is significantly improved
in some cases (entries 1 and 4-6 in Table 2). In addition,
some interesting new phenomena were also observed:
the silyl-retained aziridine 3b was the only product in
all cases on using Li+-containing bases (entries 1-4 in
Table 2), and the desilylated aziridine 4b was the only
Rea ction of N-Su lfon ylim in es w ith Dip h en ylsu l-
fon iu m 3-(Tr im eth ylsilyl)p r op a r gylid e. Among al-
lylic, benzylic, and propargylic, these being three types
of semistabilized sulfonium ylides, the last one has been
least studied. The only known reaction of propargylic
sulfonium ylide is the [2,3]-σ-rearrangement.11 Com-
monly known ylide cyclization reactions including epoxi-
dation, cyclopropanation, and aziridination with propar-
gylic sulfonium ylides, to our knowledge, have not been
previously reported, although the first two types of
cyclization reactions have been realized with propar-
gylides of other heteroatoms.12 Considering the struc-
tural similarity between allylic and propargylic ylides
(both belong to semistabilized ylides), we thought that
they should show similar reactivity in many reactions.
Therefore we prepared silylated propargylic sulfonium
salt 2 and tested it in the previously reported ylide
aziridination reaction in place of the corresponding allylic
sulfonium salt.6c Some results from the reaction of
diphenylsulfonium salt 2 with N-sulfonylimines 1 under
solid-liquid phase-transfer conditions are summarized
in Table 1.
Under solid-liquid phase-transfer conditions, ylides
generated in situ from silylated propargylic diphenylsul-
fonium salt 2 rapidly reacted with N-sulfonylimines 1 to
give the expected aziridination product 3 together with
desilylated product 4. Although the total yield (3 + 4)
in all runs was nearly quantitative, the cis/trans selectiv-
ity was, as observed in earlier cases of aziridination using
silylated allylic diphenylsulfonium salt,6c not high (rang-
ing from 1:1 to 3:1 infavor of cis). To improve the utility
of the present procedure, efforts were then made to
improve the cis/trans selectivity by changing the reaction
conditionsswith preformed ylide and at low termpera-
ture.
product when using t-BuOK (entry 8 in Table 2).
A
mixture of both aziridines was obtained in other cases.
To further confirm the above observations, reactions
with some other N-tosylarylaldimines were carried out
using n-BuLi or t-BuOK as the base (Table 3). When
using n-BuLi as the base, the silylated aziridines 3 were
formed as the only products (entries 1-5 in Table 3),
while using t-BuOK as the base, desilylated aziridines 4
became the sole products (entries 6-9 in Table 3). Yields
were excellent in all cases, and the cis/trans selectivity
was generally larger than 3:1. It is noteworthy that
desilylated aziridines 4 are not easily accessible from
simple propargylic ylides because their precursors (pro-
pargylsulfonium salts) easily isomerize into allenylsul-
fonium salt under basic conditions, rather than forming
the corresponding ylides.13 Therefore the direct forma-
tion of simple acetylenylaziridines 4 by using t-BuOK is
synthetically useful. Although a plausible explanation
for the above results is not available yet, it does not
prevent us from preparing either silylated or desilylated
products with good stereoselectivity just by using two
different bases.
Up to now, an efficient aziridination of N-sulfon-
ylimines with silylated propargylic sulfonium ylides has
been successfully realized, and either silylated or de-
(12) For epoxidation: (a) Zhou, Z.-L.; Huang, Y.-Z.; Shi, L.-L.; Hu,
J . J . Org. Chem. 1992, 57, 6598. For cyclopropanation: (b) Liao, Q.-
M. Ph.D. Thesis, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai, China, 1989.
(13) (a) Appleyard, G. D.; Stirling, C. J . M. J . Chem. Soc. C 1969,
1904. (b) Veniard, L.; Pourcelot, G. C. R. Acad. Sci., Ser. C 1971, 273,
1190. (c) Pourcelot, G.; Veniard, L.; Cadiot, P. Bull. Soc. Chim. Fr.
1975, 1275. (d) Griffiths, G.; Howes, P. D.; Stirling, C. J . M. J . Chem.
Soc., Chem. Commun. 1976, 296. (e) Baldwin, J . E.; Hackler, R. E.;
Kelly, D. P. Chem. Commun. 1968, 1083.
(14) Two reports on the rearrangement of an acetylenyl-substituted
vinylaziridine from a multistep sequence: (a) Manisse, N.; Chuche, J .
Tetrahedron 1977, 33, 2399. (b) Manisse, N.; Chuche, J . J . Am. Chem.
Soc. 1977, 99, 1272.
Results from the reaction of imine 1b with the pre-
formed ylide 5 (generated from 2 with different bases)
(11) (a) Cagle, P. C.; Arif, A. M.; Gladysz, J . A. J . Am. Chem. Soc.
1994, 116, 3655. (b) Cagle, P. C.; Meyer, O.; Weickhardt, K.; Arif, A.
M.; Gladysz, J . A. J . Am. Chem. Soc. 1995, 117, 11730. For recent
reviews: (c) Meyer, O.; Cagle, P. C.; Weickhardt, K.; Vichard, D.;
Gladysz, J . A. Pure Appl. Chem. 1996, 68, 79. (d) Li, A.-H.; Dai, L.-X.;
Aggarwal, V. K. Chem. Rev. 1997, 97, 2431.

4340 J . Org. Chem., Vol. 63, No. 13, 1998
Li et al.
Ta ble 2. Rea ction of N-Su lfon ylim in es 1b w ith P r efor m ed Dip h en ylsu lfon iu m 3-(Tr im eth ylsilyl)p r op a r gylid e (5)
Gen er a ted in Situ fr om 3-(Tr im eth ylsilyl)p r op a r gyld ip h en ylsu lfon iu m P er ch lor a te (2) w ith Differ en t Ba sesa
a
All reactions were carried out in a ratio of imine:sulfonium salt:base ) 1:1.2:1.2 at a 0.5-mmol scale in THF at -78 °C under N2.
Isolated yields based on imine. c Determined by 300-MHz 1H NMR analysis.
b
Ta ble 3. P r ep a r a tion of N-Su lfon yl-â-(tr im eth ylsilyl)a cetylen yla zir id in es 3 or 4 by Rea ction of N-Su lfon ylim in es 1 w ith
P r efor m ed Dip h en ylsu lfon iu m 3-(Tr im eth ylsilyl)p r op a r gylid e (5) Gen er a ted in Situ fr om
3-(Tr im eth ylsilyl)p r op a r gyld ip h en ylsu lfon iu m P er ch lor a te (2) w ith n -Bu Li or t-Bu OKa
a
All reactions were carried out in a ratio of imine:sulfonium salt:base ) 1:1.2:1.2 at a 0.5-mmol scale in THF at -78 °C under N2.
Isolated yields based on imine. c Determined by 300-MHz 1H NMR analysis.
b
silylated acetylenylaziridines could be obtained in high
yield. To our knowledge, the aziridination of imines with
propargylic ylides has not been previously reported
(except for our preliminary communication10), although
corresponding epoxidation and cyclopropanation with
propargylides of telluronium and arsonium are known.12

Simple Synthesis of Scalemic Acetylenylaziridines
J . Org. Chem., Vol. 63, No. 13, 1998 4341
Sch em e 1
became even lower (eq 1 in Scheme 2). The ylides
generated from telluronium salt 7 could also react with
1a to afford silylated aziridine 3a in 33% yield, but the
stereoselectivity was almost lost (eq 2 in Scheme 2).
Arsonium ylides from 8 still failed to proceed in the
aziridination reaction with imine 1b. In these runs,
although the yields were not satisfactory, the desired
high stereoselectivity was eventually achieved in two
cases (Scheme 1 and eq 1 in Scheme 2).
Rea ction of N-Su lfon ylim in es w ith Dim eth ylsu l-
fon iu m 3-(Tr im eth ylsilyl)p r op a r gylid e. The very
high cis/trans selectivity observed in the aziridination of
N-sulfonylimines with 6 showed us its great potential as
a stereoselective reagent for the preparation of acetyle-
nylaziridines. Therefore, we next examined various
bases and solvents (Table 4). We found that strong base
(e.g., KOH) and polar solvent (e.g., CH3CN) would cause
side reactions and thus decrease the yields. Weak base
(e.g., LiOH and K2CO3) and ethereal solvents (entries 4
and 5 in Table 4) would also decrease the yields because
of hydrolysis of the imines. The best base/solvent com-
bination for the reaction of N-sulfonylimines with 6
turned out to be Cs2CO3/CH2Cl2, with which both high
yield and high stereoselectivity could be achieved (entry
9 in Table 4). Using the optimized conditions, a variety
of substrates were examined. The results are listed in
Table 5.
Sch em e 2
°
°
°
°
It was found that with all the examined 15 substrates,
reaction was generally completed within 0.5-2.5 h. High
yields were achieved in most cases, and very high cis
selectivity was observed in all cases (with only one
exception, entry 3 in Table 5). Various imines, including
aromatic, heteroaromatic, R,â-unsaturated, and aliphatic
aldimines, were all workable substrates for this reaction.
Even with unreactive ketimine 1q, high yield was still
obtained (entry 15 in Table 5). Such a wide span of
substrates is seldom seen in ylide epoxidation and
cyclopropanation and never found in ylide aziridination.
In addition, the very high cis/trans selectivity and the
use of aliphatic sulfide to form a sulfonium salt (6)
created the possibility of a chiral version for this reaction,
which would lead to optically active acetylenylaziridines.
Rea ction of N-Su lfon ylim in es w ith Ca m p h or -
Der ived Ch ir a l Su lfon iu m 3-(Tr im eth ylsilyl)p r op -
a r gylid e. The usefulness of chiral aziridines in the
synthesis of biologically and medicinally important mol-
ecules prompted the development of efficient asymmetric
aziridination methodologies.2 Among various existing
methods, asymmetric aziridination via an ylide route,
although appearing very late and only a few examples5,7,10
have been reported to date, has shown much promise in
obtaining optically active functionalized aziridines. The
very high cis/trans selectivity obtained in reactions using
propargylic dimethylsulfonium salt 6 (see Table 5) and
our previous experience in ylide epoxidation16 encouraged
us to transform the present aziridination into its asym-
metric version.
°
°
°
In addition, the product acetylenylaziridines are also a
type of rarely reported functionalized aziridine deriva-
tives.14
The above method suffered from several drawbacks:
the difficulty in preparation of diphenylsulfonium salt 2
(silver salt is necessary and Ph2S must be in great
excess15), the requirements for low-temperature and
moisture/oxygen-free conditions, and the unsatisfactory
cis/trans selectivity (∼3:1). To develop a more economic,
convenient, and highly stereoselective method for prepar-
ing acetylenylaziridines and to explore the reactivity of
propargylides of other heteroatoms with N-sulfonylimines,
dimethylsulfonium salt 6 (much easier to prepare than
the diphenyl counterpart) and telluronium and arsonium
salts 7 and 8 were prepared and then tested in the
reaction with imine 1a (Scheme 1). Under the same
reaction conditions as shown in Table 1, the reaction of
1a with ylides generated from 6 gave aziridines 3a and
4a in 48% total yield as expected, together with signifi-
cant amounts of side products. However, the stereose-
lectivity in this case is very high: only the cis isomer was
formed. Telluronium salt 7 and arsonium salt 8 failed
to react with imine 1a under the same phase-transfer
conditions.
Camphor-derived chiral sulfonium salts 12-14 were
easily prepared by reacting bromide 15 with sulfides
9-11, respectively (Scheme 3).16 We then used sulfonium
salt 12 instead of dimethylsulfonium salt 6 to perform
the reaction shown in Table 5. It was found that under
the same conditions, ylides generated from chiral 12
Lowering the reaction temperature to suppress the side
reactions and consequently to improve the yields was also
attempted (Scheme 2). Similar to the results under the
phase-transfer conditions, exclusive cis selectivity was
again observed with sulfonium salt 6, although the yield
(15) LaRochelle, R. W.; Trost, B. M.; Krepski, L. J . Org. Chem. 1971,
36, 1126.
(16) Li, A.-H.; Dai, L.-X.; Hou, X.-L.; Huang, Y.-Z.; Li, F.-W. J . Org.
Chem. 1996, 61, 489.

4342 J . Org. Chem., Vol. 63, No. 13, 1998
Li et al.
Ta ble 4. Effects of Solven t a n d Ba se on Rea ction of N-Su lfon ylim in es 1b a n d
3-(Tr im eth ylsilyl)p r op a r gyld im eth ylsu lfon iu m Br om id e (6) u n d er Solid -Liqu id P h a se-Tr a n sfer Con d ition sa
a
All reactions were carried out in a ratio of imine:sulfonium salt:base ) 1:1.2:1.2 at a 0.5-mmol scale in solvent at room temperature.
Isolated yields based on imine. c Determined by 300-MHz 1H NMR analysis.
b
Ta ble 5. P r ep a r a tion of N-Su lfon yl-â-(tr im eth ylsilyl)a cetylen yla zir id in es 3 by Rea ction of N-Su lfon ylim in es 1 a n d
3-(Tr im eth ylsilyl)p r op a r gyld im eth ylsu lfon iu m Br om id e (6) u n d er P h a se-Tr a n sfer Con d ition sa
a
All reactions were carried out in a ratio of imine:sulfonium salt:Cs2CO3 ) 1:1.2:1.2 at a 0.5-mmol scale in CH2Cl2 at room temperature.
Isolated yields based on imine. c Determined by 300-MHz 1H NMR analysis. 8% of desilylated product was also isolated. cis/trans:
b
d
95/5.
reacted smoothly with imines 1 to give optically active
acetylenylaziridines (-)-3 (Table 6) in high yields with
excellent cis/trans selectivities (>98/2). The ee values,
however, varied considerably (18-85%). Like the reac-

Simple Synthesis of Scalemic Acetylenylaziridines
J . Org. Chem., Vol. 63, No. 13, 1998 4343
Sch em e 3
changed from the original 2R,3S (with sulfonium salt 12)
to 2S,3R. Opposite asymmetric induction was again
achieved in aziridination, as observed in asymmetric
epoxidation.16
To examine the asymmetric effect of other chiral
sulfides, compound 1917 was synthesized and transformed
to chiral sulfonium salt 20 (Scheme 5). However, when
20 was reacted with imine 1b in the presence of Cs2CO3,
only 32.5% (56% ee from salt 12) ee was obtained. The
lower ee may be attributed to the fact that the reacting
site was far away from the chiral centers.
Rea ction of N-Su lfon ylim in es w ith Oth er P r op -
a r gyl-Typ e Su lfon iu m Ylid es. In all the above aziri-
dination reactions, the used ylides are various sulfonium
3-(trimethylsilyl)propargylides. From these reactions,
both silylated and unsubstituted acetylenylaziridines can
be highly efficiently prepared. There is still a problem
to be answered: How about the scope of ylide reagents?
Can other types of propargylic sulfonium ylides also be
used? Thus phenyl-substituted sulfonium salt 21 and
sulfonium salt containing an aliphatic long chain (22)
were synthesized and utilized to perform an aziridination
(Scheme 6). Under the same conditions as with other
3-(trimethylsilyl)propargylsulfonium salts, we found that
the ylides produced from both 21 and 22 could react
smoothly with imine 1b to give aziridines 23 and 24 in
85% and 96% yields, respectively. However, the cis/trans
selectivities (95/5 for 23 and 92/8 for 24) were a little bit
lower than that obtained with sulfonium salt 6 (99/1,
entry 2 in Table 5). To examine the asymmetric induc-
tion, compound 25 was synthesized from chiral sulfide 9
and used to perform aziridination under the same condi-
tions; only 31.1% ee (cf. 56% ee from salt 12) was obtained
(Scheme 7). The lower ee may be understood as a phenyl
is smaller than a trimethylsilyl group.
tions with achiral sulfonium salt 6, this asymmetric
version had the same wide substrate span: it works well
with not only aromatic imines but also aliphatic imines
and ketimines. The highest ee (84.9%) was achieved with
the imine (1n ) derived from cyclohexanecarboxaldehyde
(entry 13 in Table 6). Although the ee values obtained
for many substrates were only moderate, we found that
they could be improved by recrystallization. For ex-
ample, the ee values of aziridines 3f,3r were raised from
77.5% and 69.5% to 99.1% and 96.6%, respectively, by
only a single recrystallization from n-hexane (entries 5
and 9 in Table 6). Although the above reaction was
stoichiometric, the ylide precursor sulfide 9 could be
easily recovered in >80% yields without losing its optical
purity.
It is known that the reaction temperature usually has
a pronounced effect on the enantioselectivity of a reaction.
However, this does not seem to be the case here. With
p-ClC6H4CHdNTs (1b) as a model substrate, we ran the
reaction at different temperatures (-78, -20, 0, and 25
°C and reflux temperature) and found that the ee values
of the products fell in the range between 55.8% and
59.0%. Therefore, room temperature is later used as the
“optimum temperature” for the asymmetric aziridination
reaction.
The absolute configuration of phenylaziridine 3a was
determined as follows (Scheme 4): Aziridine (-)-3a was
first desilylated to produce compound 16, which was
further converted by oxidation and esterification to (+)-
18. On the basis of the known sign of optical rotation
and absolute configuration of compound 18,4d the config-
uration of (-)-3a is unambiguously assigned as 2R,3S.
The configurations of other aziridines are deduced based
on the signs of the optical rotations because of the
structural similarity.
In our asymmetric epoxidation with chiral sulfonium
ylides, we found that sulfides with an exo-sulfonium
group and the ones with an endo-sulfonium group showed
opposite asymmetric induction.16 Does this phenomenon
exist in the asymmetric aziridination? To find out,
sulfonium salts 13 and 14 with an endo-sulfonium group
were synthesized and used to replace exo-sulfonium salt
12 in the asymmetric aziridination reactions. Some
results are summarized in Table 7. J ust like sulfonium
salt 12, ylides produced from both 13 and 14 could
smoothly aziridinate imine 1 to give 3 in excellent yields,
with exclusive cis selectivity and moderate ee values, but
this time all products possess a positive optical rotation.
That means the absolute configuration of the product
Exclusive cis selectivity was achieved by the reaction
of N-sulfonylimines with proparglic sulfonium ylides
under phase-transfer conditions. This may be explained
by an intermediate formed by [2 + 2]-cycloaddition of
imines and ylide (Scheme 8). The [2 + 2]-cycloaddition
is the rate-determining step. Due to steric hindrance,
only trans intermediate III was formed. Then intramo-
lecular trans elimination of Me2S gave cis-aziridines. This
is similar to epoxidation and olefination reactiona of
carbonyl compounds with telluronium ylides18a and phos-
18b
phine ylides.
Until now, four types of acetylenylaziridines could be
efficiently prepared, i.e., unsubstituted and trimethyl-
silyl-, aryl-, and alkyl-substituted ones. The last type of
acetylenylaziridine is especially noteworthy. It lets us
believe that our present aziridination strategy may be
developed into a general methodology for synthesizing
various substituted N-sulfonylacetylenylaziridines and
may really become a synthetically useful reaction. Stud-
ies on the reactivities of the above acetylenylaziridines
and exploration of the possibility to use the present
aziridination method in organic synthesis are now in
progress in our laboratory.
(17) Furukawa, N.; Sugihara, Y.; Fujihara, H. J . Org. Chem. 1989,
54, 4222.
(18) (a) Zhou, Z.-L.; Huang, Y.-Z.; Shi, L.-L.; Hu, J . J . Org. Chem.
1992, 57, 6598. (b) Vedejs, E.; Meier, G. P.; Snoble, K. A. J . J . Am.
Chem. Soc. 1981, 103, 2823 and references therein.

4344 J . Org. Chem., Vol. 63, No. 13, 1998
Li et al.
Ta ble 6. P r ep a r a tion of (-)-N-Tosyl-â-(tr im eth ylsilyl)a cetylen yla zir id in es 3 by Asym m etr ic Azir id in a tion Rea ction of
N-Su lfon ylim in es 1 a n d D-(+)-Ca m p h or -Der ived Su lfon iu m Sa lt 12 u n d er P h a se-Tr a n sfer Con d ition sa
a
All reactions were carried out in a ratio of imine:sulfonium salt:Cs2CO3 ) 1:1.2:1.2 at a 0.5-mmol scale in CH2Cl2 at room temperature.
b
Sulfide 9 was recovered in >80% yields without losing the optical purity after workup in all cases. Isolated yields based on imine.
c Determined by 300-MHz 1H NMR analysis. Determined by chiral HPLC on a Chiralcel OD column or a Chiralpak AD column. e The
d
ee values refer to those after single recrystallization from n-hexane. f Determined by chemical transformations (see the Experimental
Section). The configuration in parentheses is estimated by analogy with phenylacetylenylaziridine 3a .
Sch em e 4
moderate cis/trans selectivity. The cis/trans ratios of
products obtained under low-temperature conditions are
generally better than those obtained under phase-
transfer conditions. In low-temperature reactions, when
using n-BuLi as the base to generate ylides, silylated
products 3 were obtained exclusively, while employing
t-BuOK as the base led to desilylated aziridines 4 as the
only products. The stereoselectivity of the present aziri-
dination was greatly improved by using dimethylsulfo-
nium 3-(trimethylsilyl)propargylide. A cis/trans ratio of
>99/1 was achieved in most cases. Under Cs2CO3/CH2-
Cl2-rt conditions, in situ-generated dimethylsulfonium
3-(trimethylsilyl)propargylide can react with a variety of
substituted N-sulfonylaldimines and -ketimines to give
silylated acetylenylaziridines in excellent yields. When
using camphor-derived sulfonium salts 12-14 and 20,
an efficient asymmetric aziridination with varying ee
values (up to 85%) was realized. Opposite asymmetric
induction was just achieved when using sulfonium salt
12 or 20 and 13 or 14. It allows either (2R,3S)-(-)-3 or
(2S,3R)-(+)-3 to be prepared. 3-Phenyl- or 3-alkyl-
substituted propargylsulfonium salts can also be used to
perform the above aziridination. Among sulfonium,
telluronium, and arsonium (three types of propargylides),
sulfonium ylides are the most efficient reagents to effect
aziridination of N-sulfonylimines and the arsonium ones
are the worst ones.
°
Con clu sion s
A highly stereoselective ylide aziridination based on
the reaction of N-sulfonylimines with various propargylic
ylides has been described. Simple unsubstituted prop-
argylic sulfonium ylides cannot be prepared by the basic
deprotonation of the corresponding sulfonium salt due
to the isomerization of precursor propargylic salt into
allenic salt and therefore cannot be used directly to react
with imines. Both preformed (low-temperature condi-
tions) or in situ-formed (phase-transfer conditions) diphen-
ylsulfonium 3-(trimethylsilyl)propargylide (5) can react
with N-sulfonylimines 1 to give silylated and/or desily-
lated acetylenylaziridines in excellent yields with low to

Simple Synthesis of Scalemic Acetylenylaziridines
J . Org. Chem., Vol. 63, No. 13, 1998 4345
Ta ble 7. P r ep a r a tion of (+)-N-Su lfon yl-â-(tr im eth ylsilyl)a cetylen yla zir id in es 3 by Asym m etr ic Azir id in a tion Rea ction of
N-Su lfon ylim in es 1 a n d D-(+)-Ca m p h or -Der ived Su lfon iu m Sa lts 13 a n d 14 u n d er P h a se-Tr a n sfer Con d ition sa
a
All reactions were carried out in a ratio of imine:sulfonium salt:Cs2CO3 ) 1:1.2:1.2 at a 0.5-mmol scale in CH2Cl2 at room temperature.
b
Sulfide 10 or 11 was recovered in >80% yields without losing the optical purity after workup in all cases. Isolated yields based on imine.
The cis/trans ratio in all cases was >99/1. c Determined by chiral HPLC on a Chiralcel OD column or a Chiralpak AD column. All ee
d
values belong to the major products. Determined by chemical transformations (see the Experimental Section). The configuration in
parentheses is estimated by comparison with the phenyl analogue.
Sch em e 5
Sch em e 7
Sch em e 6
Sch em e 8
Exp er im en ta l Section
12-14, 20, and 25 were prepared by the reaction of corre-
sponding bromides with sulfides in the presence of a small
amount of acetone at room temperature. Sulfonium salts 2
was obtained following a literature procedure15 except for using
AgClO4 instead of AgBF4. Arsonium salt 8 was prepared by
the reaction of Ph3As with 3-bromo-1-(trimethylsilyl)propyne
(15).21 Telluronium salts 7 was prepared by the reaction of
i-Bu2Te22 with compound 15 without solvent at room temper-
ature.23 Chiral sulfides 9-11 were synthesized according to
Ma ter ia ls a n d Gen er a l P r oced u r e. All reagents and
solvents, unless otherwise specified, are from commercial
sources and used without further purification. THF was
distilled immediately prior to use from sodium/benzophenone
ketyl under nitrogen. All N-sulfonylimines 1 were prepared
according to the literature method.19 Compound 15 was
prepared by a well-established method.20 Sulfonium salts 6,
(19) (a) Love, B. E.; Raje, P. S.; Williams, T. C., II. Synlett 1994,
493. (b) J ennings, W. B.; Lovely, C. J . Tetrahedron Lett. 1988, 29, 3725.
(20) J ones, T. K.; Denmark, S. E. Org. Synth. 1990, 7, 524.
(21) Ousset, J . B.; Mioskowski, C.; Solladie, G. Tetrahedron Lett.
1983, 24, 4419.

4346 J . Org. Chem., Vol. 63, No. 13, 1998
Li et al.
our previous paper.16 Compound 19 were prepared according
N-Tosyl-3-(p -ch lor op h en yl)-2-(â-(t r im et h ylsilyl)a cet -
ylen yl)a zir id in e (3b). cis-3b: 1H NMR (CDCl3) δ 0.01 (s, 9
H), 2.44 (s, 3 H), 3.62 (d, J ) 6.85 Hz, 1 H), 3.90 (d, J ) 6.93
Hz, 1 H), 7.26 (m, 4 H), 7.34 (d, J ) 8.33 Hz, 2 H), 7.86 (d, J
) 8.26 Hz, 2 H); MS m/z 406 (3.7), 404 (11), 267 (2), 250 (37),
248 (100), 179 (3), 163 (5.8), 139 (4), 123 (6), 111 (13.3), 91
(21), 83 (50), 69 (22), 47 (3); HRMS calcd for C13H15ClNSi (M+
to Furukawa’s method.17
An a lysis of En a n tiom er ic Excess. Chromatographic
separations were achieved using a liquid chromatograph
constructed from the following components: a Waters M510
pump operating at 0.7 mL/min, a M440 UV detector (Waters,
UV 254 nm), a Rheodyne M 7725 injector, and 250- × 4.6-mm
i.d. Chiralpak and Chiralcel OD columns (Chiral Technologies).
The detector output was stored and reprocessed using a
Perkin-Elmer Nelson 1022. The temperature was about 20
°C. 3a : Chiralpak AD, hexane/i-PrOH (100/1.5); 20.3 min
(2R,3S), 21.8 min (2S,3R). 3b: Chiralcel OD, hexane/i-PrOH
(100/2.5); 13.8 min (2R,3S), 16.7 min (2S,3R). 3d : Chiralpak
AD, hexane/i-PrOH (100/2.5); 16.4 min (2R,3S), 20.9 min
(2S,3R). 3e: Chiralcel OD, hexane/i-PrOH (100/2.5); 35.3 min
(2R,3S), 44.9 min (2S,3R). 3f: Chiralcel OD, hexane/i-PrOH
(100/2.5); 17.3 min (2R,3S), 23.8 min (2S,3R). 3h : Chiralpak
AD, hexane/i-PrOH (90/10); 11.5 min (2R,3S), 13.1 min
(2S,3R). 3i: Chiralpak AD, hexane/i-PrOH (80/20); 9.5 min
(2R,3S), 13.9 min (2S,3R). 3j: Chiralpak AD, hexane/i-PrOH
(90/10); 15.4 min (2R,3S), 19.6 min (2S,3R). 3k : Chiralpak
AD, hexane/i-PrOH (100/2.5); 15.6 min (2R,3S), 17.3 min
(2S,3R). 3m : Chiralcel OD, hexane/i-PrOH (100/1.0); 20.8 min
(2R,3S), 25.8 min (2S,3R). 3b: Chiralcel OD, hexane/i-PrOH
(100/2.5); 13.8 min (2R,3S), 16.7 min (2S,3R). 3n : Chiralpak
AD, hexane/i-PrOH (100/2.5); 7.6 min (2R,3S), 11.9 min
(2S,3R). 3p : Chiralpak AD, hexane/i-PrOH (100/0.5); 16.9 min
(2R,3S), 18.2 min (2S,3R). 3q: Chiralpak AD, hexane/i-PrOH
(100/1.0); 12.2 min (2R), 13.8 min (2S). 3r : Chiralcel OD,
hexane/i-PrOH (100/2.5); 13.1 min (2R,3S), 15.7 min (2S,3R).
3s: Chiralcel OD, hexane/i-PrOH (100/2.5); 14.0 min (2R,3S),
16.3 min (2S,3R). 23: Chiralcel OD, hexane/i-PrOH (80/20);
14.5 min (2R,3S), 18.3 min (2S,3R).
Gen er a l P r oced u r e for Azir id in a tion u n d er Solid -
Liqu id P h a se-Tr a n sfer Con d ition s. A 25-mL flask con-
taining a magnetic stirring bar was charged with imines 2 (1.0
equiv), sulfonium salts 2, 6-8, 12-14, 20, or 25 (1.2 equiv),
or arsonium salts 8 (1.2 equiv) and solvent (CH3CN, Et2O,
THF, or CH2Cl2, 3 mL, reagent grade; it need not be dried
before use). Powdered inorganic base (KOH, K2CO3, LiOH‚H2O,
Cs2CO3, or KF‚Al2O3, 1.2 equiv) was subsequently added with
stirring. After reaction was complete according to TLC, the
reaction mixture was filtered through a short silica gel column
to remove the inorganic salts. The filtrate was concentrated
and chromatographed on a silica gel column eluting with a
mixture of light petroleum (bp 60-90 °C), ethyl acetate, and
NEt3 (8:1:1) to give pure products (chiral sulfides were also
recovered). The results are shown in Tables 1, 4-7.
- Ts) 248.0662, found 248.0623. Anal. Calcd for C20H22
-
ClNO2SSi: C, 59.46; H, 5.49; N, 3.47. Found: C, 59.42; H,
5.45; N, 3.79. trans-3b: 1H NMR (CDCl3) δ 0.24 (s, 9 H), 2.44
(s, 3 H), 3.10 (d, J ) 3.9 Hz, 1 H), 4.10 (d, J ) 3.9 Hz, 1 H),
7.26 (m, 4 H), 7.34 (m, 2 H), 7.86 (m, 2 H).
N-Tosyl-3-(p-ch lor op h en yl)-2-a cetylen yla zir id in e (4b).
cis-4b: 1H NMR (CDCl3) δ 2.07 (d, J ) 1.9 Hz, 1 H), 2.44 (s,
3 H), 3.61 (dd, J ) 1.89, 6.86 Hz, 1 H), 3.95 (d, J ) 6.89 Hz,
1 H), 7.28 (m, 4 H), 7.35 (d, J ) 8.26 Hz, 2 H), 7.88 (d, J )
8.26 Hz, 2 H); MS m/z 333 (M+ (37Cl), 0.4), 332 (M+ (35Cl), 1.33),
241 (0.54), 178 (39), 176 (100), 151 (11), 149 (32), 141 (5.4),
114 (6), 91 (9), 75 (1.4), 65 (5.4), 51 (1); HRMS calcd for C10H7-
ClN (M+ - Ts) 176.0267, found 176.0272. Anal. Calcd for
C
17H14ClNO2S: C, 61.53; H, 4.25; N, 4.22. Found: C, 61.25;
H, 4.11; N, 4.01. trans-4b: 1H NMR (CDCl3) δ 2.44 (s, 3 H),
2.62 (d, J ) 2.16 Hz, 1 H), 3.20 (dd, J ) 2.17, 3.97 Hz, 1 H),
4.17 (d, J ) 3.97 Hz, 1 H), 7.30 (m, 4 H), 7.38 (d, J ) 8.27 Hz,
2 H), 7.93 (d, J ) 8.27 Hz, 2 H).
N-Tosyl-3-(1-n a p h t h yl)-2-(â-(t r im et h ylsilyl)a cet ylen -
yl)a zir id in e (3c). cis-3c: 1H NMR (CDCl3) δ 0.01 (s, 9 H),
2.73 (s, 3 H), 4.18 (d, J ) 6.67 Hz, 1 H), 4.82 (d, J ) 6.84 Hz,
1 H), 7.55-7.85 (m, 6 H), 8.15-8.18 (m, 2 H), 8.26-8.31 (m, 2
H), 8.39 (m, 1 H); MS m/z 420 (M+ + 1, 2.1), 302 (0.8), 264
(100), 249 (10), 228 (1.3), 192 (3.2), 166 (7), 141 (6), 115 (1.6),
91 (6.6), 73 (21), 65 (3), 45 (0.6); HRMS calcd for C17H18NSi
(M+ - Ts) 264.1209, found 264.1213. Anal. Calcd for
C
24H25NO2SSi: C, 68.69; H, 6.01; N, 3.34. Found: C, 68.78;
H, 5.72; N, 2.98. trans-3c: 1H NMR (CDCl3) δ 0.62 (s, 9 H),
2.74 (s, 3 H), 3.50 (d, J ) 4.32 Hz, 1 H), 5.00 (d, J ) 4.27 Hz,
1 H), 7.55-7.85 (m, 6 H), 8.07 (m, 2 H), 8.26-8.31 (m, 2 H),
8.42 (m, 1 H).
N-Tosyl-3-(1-n a p h t h yl)-2-a cet ylen yla zir id in e
(4c).
cis-4c: 1H NMR (CDCl3) δ 1.81 (d, J ) 1.63 Hz, 1 H), 2.45 (s,
3 H), 3.86 (dd, J ) 1.66, 6.58 Hz, 1 H), 4.52 (d, J ) 6.77 Hz,
1 H), 7.14-7.59 (m, 6 H), 7.79-8.09 (m, 5 H); MS m/z 348
(M++1, 1.8), 282 (0.5), 269 (0.2), 192 (100), 177 (4), 165 (46),
153 (3.8), 141 (24), 127 (4.7), 115 (7), 91 (15), 77 (1.7), 65 (7.5),
51 (1.3); HRMS calcd for C14H10N (M+ - Ts) 192.0813, found
192.0809. Anal. Calcd for C21H17NO2S: C, 72.60; H, 4.93; N,
4.03. Found: C, 72.01; H, 4.55; N, 3.69. trans-4c: 1H NMR
(CDCl3) δ 2.45 (s, 3 H), 2.71 (d, J ) 2.16 Hz, 1 H), 3.19 (dd, J
) 2.11, 3.91 Hz, 1 H), 4.70 (d, J ) 4.22 Hz, 1 H), 7.14-7.59
(m, 6 H), 7.79-8.09 (m, 5 H).
N-Tosyl-3-p h en yl-2-(â-(tr im eth ylsilyl)a cetylen yl)a zir -
id in e (3a ). cis-3a : 1H NMR (CDCl3/TMS) δ -0.02 (s, 9 H),
2.43 (s, 3 H), 3.62 (d, J ) 6.78 Hz, 1 H), 3.94 (d, J ) 6.89 Hz,
1 H), 7.25-7.34 (m, 7 H), 7.88 (d, J ) 8.22 Hz, 2 H); EIMS
m/z (relative intensity) 370 (M+ + 1, 1.3), 354 (2.5), 243 (1.4),
214 (100), 199 (2.9), 173 (0.6), 159 (5.7), 155 (2.5), 111 (3.2),
97 (3.9), 91 (11), 83 (10), 73 (3), 65 (4.6). Anal. Calcd for
N-Tosyl-3-(o-m eth oxyp h en yl)-2-(â-(tr im eth ylsilyl)a cet-
ylen yl)a zir id in e (3d ). cis-3d : 1H NMR (CDCl3) δ -0.04 (s,
9 H), 2.42 (s, 3 H), 3.66 (d, J ) 7.04 Hz, 1 H), 3.81 (s, 3 H),
4.28 (d, J ) 6.98 Hz, 1 H), 6.80-6.99 (m, 2 H), 7.22-7.34 (m,
4 H), 7.93 (dd, J ) 1.47, 8.26 Hz, 2 H); MS m/z 400 (M+ + 1,
0.98), 244 (100), 229 (3.2), 214 (2.2), 187 (2.5), 138 (3), 111
(1.4), 91 (7), 73 (3); HRMS calcd for C14H18NOSi (M+ - Ts)
244.1158, found 244.1163. Anal. Calcd for C21H25NO3SSi: C,
63.12; H, 6.31; N, 3.51. Found: C, 63.28; H, 6.47; N, 3.29.
trans-3d : 1H NMR (CDCl3) δ 0.26 (s, 9 H), 2.42 (s, 3 H), 3.16
(d, J ) 4.30 Hz, 1 H), 3.81 (s, 3 H), 4.44 (d, J ) 4.26 Hz, 1 H),
6.80-6.99 (m, 2 H), 7.22-7.34 (m, 4 H), 7.89 (d, J ) 8.33 Hz,
2 H).
N-Tosyl-3-(o-m eth oxyph en yl)-2-acetylen ylazir idin e (4d).
cis-4d : 1H NMR (CDCl3) δ 1.97 (d, J ) 2.00 Hz, 1 H), 2.43 (s,
3 H), 3.64 (dd, J ) 1.99, 6.95 Hz, 1 H), 3.83 (s, 3 H), 4.27 (d,
J ) 6.95 Hz, 1 H), 6.80-6.92 (m, 2 H), 7.21-7.35 (m, 4 H),
7.88-7.92 (m, 2 H); MS m/z 328 (M+ + 1, 2.2), 173 (15), 172
(100), 157 (4.4), 145 (14), 115 (5), 102 (3.4), 91 (14), 77 (2.5),
66 (16), 51 (2.2); HRMS calcd for C11H10NO (M+ - Ts)
172.0762, found 172.0720. trans-4d : 1H NMR (CDCl3) δ 2.42
(s, 3 H), 2.60 (d, J ) 2.16 Hz, 1 H), 3.14 (dd, J ) 2.18, 4.24 Hz,
1 H), 3.82 (s, 3 H), 4.43 (d, J ) 4.16 Hz, 1 H), 6.80-6.92 (m,
2 H), 7.21-7.35 (m, 4 H), 7.88-7.92 (m, 2 H).
C
20H23NO2SSi: C, 65.00; H, 6.27; N, 3.79. Found: C, 65.13;
H, 5.77; N, 3.75. trans-3a : 1H NMR (CDCl3/TMS) δ 0.24 (s, 9
H), 2.61 (s, 3 H), 3.12 (d, J ) 4.01 Hz, 1 H), 4.14 (d, J ) 4.01
Hz, 1 H), 7.25-7.34 (m, 7 H), 7.89 (d, J ) 8.22 Hz, 2 H).
N-Tosyl-3-p h en yl-2-a cetylen yla zir id in e (4a ). cis-4a : 1H
NMR (CDCl3) δ 2.07 (d, J ) 1.92 Hz, 1 H), 2.40 (s, 3 H), 3.62
(dd, J ) 1.69, 6.80 Hz, 1 H), 3.99 (d, J ) 6.88 Hz, 1 H), 7.15-
7.34 (m, 7 H), 7.88 (d, J ) 8.17 Hz, 2 H); MS m/z 297 (M+,
0.1), 217 (0.7), 182 (0.7), 142 (100), 115 (37), 104 (0.6), 91 (8.7),
89 (6), 77 (2), 69 (1), 65 (6.6); HRMS calcd for C10H8N (M+
-
Ts) 142.0657, found 142.0652. trans-4a : 1H NMR (CDCl3) δ
2.38 (s, 3 H), 2.62 (d, J ) 2.08 Hz, 1 H), 3.17 (dd, J ) 2.07,
4.01 Hz, 1 H), 4.15 (d, J ) 4.01 Hz, 1 H), 7.15-7.34 (m, 7 H),
7.88 (d, J ) 8.17 Hz, 2 H).
(22) Balfe, M. P.; Chaplin, C. A.; Phillips, H. J . Chem. Soc. 1938,
341.
(23) Zhou, Z.-L.; Huang, Y.-Z.; Tang, Y.; Chen, Z.-C.; Shi, L.-P.; J in,
X.-L.; Yang, Q.-C. J . Org. Chem. 1994, 59, 914.

Simple Synthesis of Scalemic Acetylenylaziridines
J . Org. Chem., Vol. 63, No. 13, 1998 4347
N -Tosyl-3-(p -n it r op h e n yl)-2-(â-(t r im e t h ylsilyl)a ce t -
ylen yl)a zir id in e (3e). cis-3e: 1H NMR (CDCl3) δ -0.02 (s,
9 H), 2.45 (s, 3 H), 3.69 (d, J ) 7.01 Hz, 1 H), 4.00 (d, J ) 6.90
Hz, 1 H), 7.36 (d, J ) 8.37 Hz, 2 H), 7.50 (dd, J ) 1.93, 6.94
Hz, 2 H), 7.88 (dd, J ) 1.78, 8.39 Hz, 2 H), 8.16 (dd, J ) 1.78,
6.74 Hz, 2 H); MS m/z 399 (0.8), 342 (0.9), 259 (100), 231 (1.6),
204 (4.7), 187 (1.6), 171 (3), 155 (4.4), 139 (2.7), 111 (13), 97
(9), 91 (19), 83 (35.4), 65 (7.7), 43 (4.6); HRMS calcd for
N-Tosyl-3-(â-p h en ylvin yl)-2-(â-(t r im et h ylsilyl)a cet y-
len yl)a zir id in e (3m ). cis-3m : 1H NMR (CDCl3) δ 0.14 (s, 9
H), 2.44 (s, 3 H), 3.55-3.58 (m, 2 H), 6.02 (m, 1 H), 6.79 (d, J
) 16.04 Hz, 1 H), 7.26-7.36 (m, 7 H), 7.86 (dd, J ) 1.52, 8.26
Hz, 2 H); MS m/z 395 (M+, 0.8), 240 (100), 224 (10), 210 (4.4),
185 (7.6), 168 (8), 155 (3.8), 149 (9.3), 115 (63), 91 (22), 73
(45.6), 65 (6.2); HRMS calcd for C15H18NSi (M+ - Ts) 240.1209,
found 240.1230.
N-Tosyl-3-cycloh exyl-2-(â-(tr im eth ylsilyl)a cetylen yl)-
a zir id in e (3n ). cis-3n : 1H NMR (CDCl3) δ 0.13 (s, 9 H), 0.95-
1.79 (m, 11 H), 2.44 (s, 3 H), 2.56 (dd, J ) 6.83, 9.45 Hz, 1 H),
3.34 (d, J ) 7.02 Hz, 1 H), 7.33 (d, J ) 7.86 Hz, 2 H), 7.82 (d,
J ) 8.26 Hz, 2 H); MS m/z 376 (M+ + 1, 1.6), 360 (1.5), 220
(100), 204 (12), 192 (2.7), 178 (2.6), 155 (5.5), 152 (26), 138
(12), 126 (95.5), 111 (8.5), 95 (57), 91 (34), 73 (51), 67 (18), 55
(13.8); HRMS calcd for C13H22NSi (M+ - Ts) 220.1522, found
220.1547.
N-Tosyl-3-(ter t-bu tyl)-2-(â-(tr im eth ylsilyl)a cetylen yl)-
a zir id in e (3p ). cis-3p : 1H NMR (CDCl3) δ 0.12 (s, 9 H), 0.92
(s, 9 H), 2.43 (s, 3 H), 2.51 (d, J ) 7.4 Hz, 1 H), 3.25 (d, J )
7.25 Hz, 1 H), 7.33 (d, J ) 8.05 Hz, 2 H), 7.83 (d, J ) 8.26 Hz,
2 H); MS m/z 350 (M+ + 1, 0.5), 334 (0.8), 280 (2), 264 (1.3),
228 (0.7), 194 (100), 178 (2.9), 155 (5), 149 (6), 126 (20), 110
(4), 100 (5.5), 96 (16), 91 (22), 83 (10.5), 77 (1.7), 73 (78), 69
(27), 65 (7.6), 57 (6.4), 43 (5.4); HRMS calcd for C11H20NSi (M+
- Ts) 194.1365, found 194.1381.
C
13H15N2O2Si (M+ - Ts) 259.0903, found 259.0877.
N-Tosyl-3-(p-n itr op h en yl)-2-a cetylen yla zir id in e (4e).
cis-4e: 1H NMR (CDCl3) δ 2.08 (d, J ) 2.0 Hz, 1 H), 2.43 (s, 3
H), 3.68 (dd, J ) 2.03, 6.97 Hz, 1 H), 4.01 (d, J ) 6.90 Hz, 1
H), 7.36 (d, J ) 8.22 Hz, 2 H), 7.50 (d, J ) 8.74 Hz, 2 H), 7.87
(d, J ) 8.27 Hz, 2 H), 8.15 (d, J ) 8.71 Hz, 2 H); MS m/z 343
(M+ + 1, 0.6), 342 (M+, 0.5), 259 (27.5), 243 (1.6), 187 (100),
171 (5.5), 155 (5.7), 141 (21.5), 129 (2.6), 114 (13), 102 (4), 91
(25), 65 (15), 51 (3.4); HRMS calcd for C10H7N2O2 (M+ - Ts)
187.0508, found 187.0509.
N-Tosyl-3-(3-p yr id in yl)-2-(â-(t r im et h ylsilyl)a cet ylen -
yl)a zir id in e (3f). cis-3f: 1H NMR (CDCl3) δ 0.00 (s, 9 H),
2.45 (s, 3 H), 3.68 (d, J ) 6.77 Hz, 1 H), 3.95 (d, J ) 6.84 Hz,
1 H), 7.26 (m, 1 H), 7.35 (d, J ) 8.16 Hz, 2 H), 7.65 (m, 1H),
7.88 (d, J ) 8.34 Hz, 2 H), 8.56 (m, 2 H); MS m/z 371 (M+
+
1, 0.1), 355 (0.2), 260 (0.3), 233 (0.6), 228 (1.3), 215 (100), 200
(3.8), 187 (1.9), 160 (5.6), 130 (1.6), 111 (7.4), 97 (7.8), 91 (21),
83 (29), 65 (8.3), 55 (2.5), 43 (4.5). Anal. Calcd for C19H22N2O2-
SSi: C, 61.58; H, 5.98; N, 7.56. Found: C, 61.87; H, 6.00; N,
7.71.
N-Tosyl-3,3-d im eth yl-2-(â-(tr im eth ylsilyl)a cetylen yl)-
a zir id in e (3q): 1H NMR (CDCl3) δ 0.11 (s, 9 H), 1.41 (s, 3
H), 1.73 (s, 3 H), 2.41 (s, 3 H), 3.39 (s, 1 H), 7.30 (d, J ) 8.19
Hz, 2 H), 7.82 (d, J ) 8.27 Hz, 2 H); MS m/z 322 (M+ + 1,
0.68), 306 (1.5), 166 (100), 155 (2), 149 (4.2), 138 (11.5), 109
(4.8), 97 (20.7), 91 (14), 83 (12), 73 (16), 68 (14), 65 (7), 59 (5);
HRMS calcd for C9H16NSi (M+ - Ts) 166.1052, found 166.1031.
N-Tosyl-3-(p -flu or op h en yl)-2-(â-(t r im et h ylsilyl)a cet -
ylen yl)a zir id in e (3r ). cis-3r : 1H NMR (CDCl3) δ 0.00 (s, 9
H), 2.44 (s, 3 H), 3.61 (d, J ) 6.98 Hz, 1 H), 3.92 (d, J ) 6.81
Hz, 1 H), 6.98 (m, 2 H), 7.26-7.36 (m, 4 H), 7.87 (d, J ) 8.27
Hz, 2 H); MS m/z 388 (M+ + 1, 0.1), 372 (0.65), 253 (0.5), 232
(100), 217 (3.9), 202 (1.6), 177 (13), 160 (3.1), 155 (2), 133 (2.5),
111 (9.3), 97 (6.9), 91 (14), 83 (32), 77 (2), 65 (6.8); HRMS calcd
for C13H15FNSi (M+ - Ts) 232.0957, found 232.0945.
N-Tosyl-3-(p -b r om op h en yl)-2-(â-(t r im et h ylsilyl)a cet -
ylen yl)a zir id in e (3s). cis-3s: 1H NMR (CDCl3) δ 0.00 (s, 9
H), 2.44 (s, 3 H), 3.63 (d, J ) 6.62 Hz, 1 H), 3.88 (d, J ) 6.89
Hz, 1 H), 7.19 (dd, J ) 1.94, 6.63 Hz, 2 H), 7.34 (m, 2 H), 7.42
(dd, J ) 1.97, 6.55 Hz, 2 H), 7.86 (dd, J ) 1.81, 6.57 Hz, 2 H);
MS m/z 448 (M+(81Br), 0.2), 446 (M+(79Br), 0.2), 432 (0.6), 430
(0.6), 294 (100), 292 (95), 279 (2.7), 277 (2.6), 239 (8), 237 (8.2),
213 (4.6), 198 (3), 183 (2.5), 155 (4.4), 149 (4), 139 (4.4), 111
(12), 97 (9.9), 91 (18), 83 (39), 77 (2), 65 (7); HRMS calcd for
N-(Ben zen esu lfon yl)-3-(p-m eth ylp h en yl)-2-(â-(tr im eth -
ylsilyl)a cetylen yl)a zir id in e (3g). cis-3g: 1H NMR (CDCl3)
δ -0.08 (s, 9 H), 2.22 (s, 3 H), 3.55 (d, J ) 6.68 Hz, 1 H), 3.86
(d, J ) 6.87 Hz, 1 H), 7.00 (d, J ) 8.04 Hz, 2 H), 7.14 (m, 2 H),
7.40-7.55 (m, 3 H), 7.91 (m, 2 H); MS m/z 370 (M+ + 1, 1.34),
354 (1.8), 228 (100), 213 (4.8), 198 (2), 186 (1.6), 173 (13.7),
159 (2.4), 135 (2.7), 111 (3.9), 97 (9), 83 (21), 77 (18), 69 (2.7),
59 (3.6), 51 (6); HRMS calcd for C20H23NO2SSi (M+) 369.1219,
found 369.1190.
N-Tosyl-3-(p-m eth oxyp h en yl)-2-(â-(tr im eth ylsilyl)a cet-
ylen yl)a zir id in e (3h ). cis-3h : 1H NMR (CDCl3) δ 0.00 (s, 9
H), 2.38 (s, 3 H), 3.58 (d, J ) 6.93 Hz, 1 H), 3.73 (s, 3 H), 3.88
(d, J ) 6.82 Hz, 1 H), 6.80 (d, J ) 8.70 Hz, 2 H), 7.22-7.30
(m, 4 H), 7.84 (d, J ) 8.23 Hz, 2 H); MS m/z 400 (M+ + 1, 0.2),
244 (100), 229 (4.2), 214 (2.7), 202 (3), 189 (14.4), 149 (2.6),
121 (3.7), 111 (3.7), 97 (6.7), 91 (18), 83 (18.5), 73 (10.7), 65
(6.9), 55 (2); HRMS calcd for C14H18NOSi (M+ - Ts) 244.1158,
found 244.1164.
N-Tosyl-3-(p-a cetoxyp h en yl)-2-(â-(tr im eth ylsilyl)a cet-
ylen yl)a zir id in e (3i). cis-3i: 1H NMR (CDCl3) δ 0.00 (s, 9
H), 2.26 (s, 3 H), 2.43 (s, 3 H), 3.62 (d, J ) 6.76 Hz, 1 H), 3.91
(d, J ) 6.84 Hz, 1 H), 7.01 (d, J ) 8.60 Hz, 2 H), 7.21-7.34
(m, 4 H), 7.86 (d, J ) 8.27 Hz, 2 H); MS m/z 428 (M+ + 1, 0.1),
272 (55), 230 (100), 215 (2.7), 188 (1.5), 175 (10.7), 149 (3),
111 (3.7), 97 (5.3), 91 (11.6), 83 (15.8), 73 (5.5), 65 (4.5), 55
C
C
13H15NSiBr79 (M+ - Ts) 292.0157, found 292.0233; calcd for
13H15NSiBr81 (M+ - Ts) 294.0136, found 294.0165.
N-Tosyl-3-(p-ch lor op h en yl)-2-(p h en yla cetylen yl)a zir i-
d in e (23). cis-23: 1H NMR (CDCl3) δ 2.45 (s, 3 H), 3.88 (d, J
) 6.66 Hz, 1 H), 4.05 (d, J ) 6.77 Hz, 1 H), 7.10-7.40 (m, 11
H), 7.92 (d, J ) 8.25, 2 H); MS m/z 254 (M(37Cl) - Ts, 100),
252 (M(35Cl) - Ts, 35), 225 (32.2), 189 (18.2), 115 (13.0), 91
(27.3), 65 (14.9); HRMS calcd for C16H21Cl35N (M+ - Ts)
252.0580, found 252.2582. trans-23: 1H NMR (CDCl3) δ 2.44
(s, 3 H), 3.35 (d, J ) 3.90 Hz, 1 H), 4.22 (d, J ) 3.99 Hz, 1 H),
7.10-7.40 (m, 11 H), 7.92 (d, J ) 8.20, 2 H).
(1.6), 43 (4.5); HRMS calcd for
272.1107, found 272.1103.
C
15H18NO2Si (M+ - Ts)
N-Tosyl-3-(p -m et h ylt h iop h en yl)-2-(â-(t r im et h ylsilyl)-
a cetylen yl)a zir id in e (3j). cis-3j: 1H NMR (CDCl3) δ 0.00
(s, 9 H), 2.44 (s, 3 H), 2.46 (s, 3 H), 3.60 (d, J ) 6.86 Hz, 1 H),
3.88 (d, J ) 6.83 Hz, 1 H), 7.17 (d, J ) 8.46 Hz, 2 H), 7.23 (d,
J ) 8.90 Hz, 2 H), 7.32 (d, J ) 8.16 Hz, 2 H), 7.86 (d, J ) 8.22
Hz, 2 H); MS m/z 416 (M+ + 1, 1.1), 400 (0.8), 260 (100), 245
(2.5), 213 (8.8), 205 (8.6), 188 (2.0), 155 (3.7), 137 (3), 126 (2.6),
111 (3), 97 (5), 91 (19), 83 (13.5), 77 (2.3), 73 (6.3), 65 (8), 55
(1.7); HRMS calcd for C14H18NSSi (M+ - Ts) 260.0929, found
260.0916.
N-Tosyl-3-(2-fu r yl)-2-(â-(tr im eth ylsilyl)a cetylen yl)a zir -
id in e (3k ). cis-3k : 1H NMR (CDCl3) δ 0.09 (s, 9 H), 2.44 (s,
3 H), 3.63 (d, J ) 6.85 Hz, 1 H), 3.96 (d, J ) 6.76 Hz, 1 H),
6.32 (dd, J ) 1.83, 3.32 Hz, 1 H), 6.42 (d, J ) 3.23 Hz, 1 H),
7.32-7.37 (m, 3 H), 7.86 (dd, J ) 1.61, 8.27 Hz, 2 H); MS m/z
360 (M+ + 1, 2.0), 359 (M+, 0.9), 204 (100), 177 (4.1), 155 (2.3),
139 (3.5), 111 (2), 97 (2.5), 91 (13), 83 (2.7), 77 (1.2), 65 (7.2);
HRMS calcd for C11H14NOSi (M+ - Ts) 204.0845, found
204.0861.
N-Tosyl-3-(p-ch lor op h en yl)-2-(n -h exyla cetylen yl)a zir i-
d in e (24). cis-24: 1H NMR (CDCl3) δ 0.89 (t, 3 H), 1.05-
1.40 (m, 2 H), 1.98 (m, 2 H), 2.50 (s, 3 H), 3.63 (d, t, J ) 6.73,
1.60 Hz, 1 H), 3.90 (d, J ) 6.96 Hz, 1 H), 7.27 (m, 4 H), 7.33
(d, J ) 8.32 Hz, 2 H), 7.87 (d, J ) 8.23 Hz, 2 H); MS m/z 418
(M+ + 2, 7.80), 416 (M+, 3.09), 260 (100), 125 (7.64), 91 (13.2),
65 (5.1); HRMS calcd for C23H26Cl35NO2S (M+) 252.1451, found
416.1467. trans-24: 1H NMR (CDCl3) δ 0.89 (t, 3 H), 1.05-
1.40 (m, 2 H), 1.98 (m, 2 H), 2.51 (s, 3 H), 3.12 (d, t, J ) 3.98,
1.60 Hz, 1 H), 4.03 (d, J ) 3.98 Hz, 1 H), 7.27 (m, 4 H), 7.33
(d, J ) 8.32 Hz, 2 H), 7.87 (d, J ) 8.23 Hz, 2 H).
Gen er a l P r oced u r e for Azir id in a tion a t -78 °C.
A
solution of the base (n-BuLi in hexanes, LiN(SiMe3)2, NaN-
(SiMe3)2, KN(SiMe3)2, NaN(SiMe3)2 + LiBr, LDA, NaH, or

4348 J . Org. Chem., Vol. 63, No. 13, 1998
Li et al.
t-BuOK in THF, 1.2 equiv) was added dropwise to a solution
of a sulfonium (2 or 6), telluronium (7), or arsonium (8) in 6
mL of THF at -78 °C under nitrogen. The mixture was stirred
for 5-30 min (5 min for 6, 30 min for others), and imine (1.0
equiv) in 4 mL of THF was subsequently added. The reaction
mixture was then allowed to warm to room temperature within
2-3 h; the reaction mixture was filtered on a short neutral
Al2O3 column to hydrolyze the excess active species and remove
the inorganic salt. The filtrate was concentrated and chro-
matographed on a silica gel column with petroleum ether (60-
90 °C) and ethyl actate (4/1) as the eluent to give pure product.
The results are shown in Tables 2 and 3.
solvent) was added. The reaction mixture was further stirred
for 24 h. After workup according to the literature procedure,24
solid acid 17 was obtained in 79% yield (206 mg). It was
treated with CH2N2 in ether at 0 °C for 12 h to give ester 18
in 64% yield: [R]20 ) +15.3 (c ) 2.0 in CHCl3); 1H NMR (300
D
MHz, CDCl3, 25 °C, TMS) δ 2.44 (s, 3 H, CH3), 3.49 (s, 3 H,
OCH3), 3.70 (d, J ) 7.5 Hz, 1 H), 4.11 (d, J ) 7.4 Hz, 1 H),
7.29 (m, 5 H), 7.35 (d, J ) 8.0 Hz, 2 H), 7.92 (d, J ) 8.1 Hz, 2
H). By comparison of the optical rotations with the known
compound, (+)-18 should have a configuration of 2S,3S,7d and
therefore, the absolute configuration of (-)-cis-3a is unam-
biguously assigned as 2R,3S.
Deter m in a tion of Absolu te Con figu r a tion of Azir id in e
(-)-cis-3a . Silylated aziridine (-)-cis-3a (369 mg, 1 mmol)
and powdered KOH (56 mg, 1 mmol) were stirred in 4 mL of
CH3CN at room temperature. After completion of the reaction
(about 30 min), the reaction mixture was filtered and evapo-
rated to leave a white solid (16) (291 mg, 98% yield). It was
pure enough for further use. Acid 17 was prepared according
to the literature procedure:24 PhIO (490 mg, 2.23 mmol) in 8
mL of CH2Cl2 was added to 2 mL of a CH2Cl2 solution of
RuCl2(PPh3)3 (18 mg). After stirring for 2 min, a CH2Cl2
solution of compound 16 (245 mg, 0.82 mmol, in 2 mL of
Ack n ow led gm en t. Financial support from the Na-
tional Natural Science Foundation of China (29790127)
and Chinese Academy of Sciences is gratefully acknowl-
edged.
Su p p or tin g In for m a tion Ava ila ble: Copies of NMR
spectra (24 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
(24) Mu¨ller, P.; Godoy, J . Helv. Chim. Acta 1981, 64, 2531.
J O9800964