Generation of aziridinyllithiums from sulfinylaziridines with tert- butyllithium: Properties, reactivity, and application to a synthesis of α,α-dialkylamino acid esters and amides including an optically active form

Article abstract of DOI:10.1016/S0040-4020(00)00375-6

Aziridinyllithiums were generated from sulfinylaziridines by a sulfoxide-lithium exchange reaction of sulfoxides with tertbutyllithium at low temperature. The generated aziridinyllithiums were found to be stable in THF at below -30°C and they are reactive with several electrophiles such as carbonyl compounds, ethyl chloroformate, and phenyl isocyanate. The reactivities of the aziridinyllithiums having several alkyl groups were investigated. As an extension of this method, a synthesis of α,α- dialkylamino acid esters, including an optically active form, and amides was realized via the aziridinyllithiums. N-Non substituted α,α-dialkylamino acid esters were synthesized starting from N-(4-methoxyphenyl) aldimine. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00375-6

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 4415±4425
Generation of Aziridinyllithiums from Sul®nylaziridines with
tert-Butyllithium: Properties, Reactivity, and Application to a
Synthesis of a,a-Dialkylamino Acid Esters and Amides Including
an Optically Active Form
a
b
a
a
Tsuyoshi Satoh,a, Masaki Ozawa, Koji Takano, Tosio Chyouma and Akihiro Okawa
*
aDepartment of Chemistry, Faculty of Sciences, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
bFaculty of Pharmaceutical Sciences, Science University of Tokyo, Ichigaya-funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan
Received 21 March 2000; accepted 1 May 2000
AbstractÐAziridinyllithiums were generated from sul®nylaziridines by a sulfoxide±lithium exchange reaction of sulfoxides with tert-
butyllithium at low temperature. The generated aziridinyllithiums were found to be stable in THF at below 2308C and they are reactive with
several electrophiles such as carbonyl compounds, ethyl chloroformate, and phenyl isocyanate. The reactivities of the aziridinyllithiums
having several alkyl groups were investigated. As an extension of this method, a synthesis of a,a-dialkylamino acid esters, including an
optically active form, and amides was realized via the aziridinyllithiums. N-Non substituted a,a-dialkylamino acid esters were synthesized
starting from N-(4-methoxyphenyl) aldimine. q 2000 Elsevier Science Ltd. All rights reserved.
Aziridines have widely been recognized as being extremely
versatile synthetic intermediates in organic synthesis.1
Attributable to ring strain, the reaction of aziridines with a
variety of nucleophiles leads to highly regio- and stereo-
selective ring-opening with carbon±carbon or carbon±
heteroatom bond-formation. Aziridine rings are sometimes
found in the substances which exhibit antitumor and
antibiotic activities, for example, mitomycins and azino-
mycins.2 It is now recognized that the aziridine ring is essen-
tial for such activities.3 In all the reactions mentioned above,
aziridines act as electrophiles 1. In contrast to this, a very
limited number of reactions in which aziridines act as
nucleophiles has been reported. One such aziridine is a car-
banion of aziridine, named aziridinyl anion 2 (Fig. 1).4
magnesium bromide.6d,e In continuation of our studies on
the generation of aziridinyl anions by the sulfoxide±metal
exchange reaction, herein we report in detail a new method
for the generation of aziridinyllithiums 5b from 4 with tert-
butyllithium.8 The properties and reactivity of the generated
aziridinyllithiums 5b and some applications to the synthesis
of a,a-dialkylamino acid derivatives 7, including an optic-
ally active form, from 6 are also described (Scheme 1).
Aziridinyl anions are classi®ed into two categories. One is
the aziridinyl anions having a carbanion stabilizing group on
the carbanionic carbon 3a (stabilized aziridinyl anion).5 The
other is the aziridinyl anions having a hydrogen or a car-
banion destabilizing group on the carbanionic carbon 3b
(nonstabilized aziridinyl anion).6
We previously reported the ®rst generation of aziridinyl-
magnesium 5a from sul®nylaziridines 4 by a sulfoxide±
magnesium exchange reaction of sulfoxides7 with ethyl-
Keywords: aziridinyllithiums; sul®nylaziridines; sulfoxide±lithium
exchange; a,a-dialkylamino acid esters.
* Corresponding author. Tel.:181-3-3260-4271; fax: 181-3-3235-2214;
e-mail: tsatoh@ch.kagu.sut.ac.jp
Figure 1.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00375-6

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T. Satoh et al. / Tetrahedron 56 (2000) 4415±4425
Scheme 1.
Results and Discussion
First, (E)-2-methyl-1,3-diphenyl-2-(p-tolylsul®nyl)aziridine
8 (see Table 1), which is easily synthesized from 1-chloro-
ethyl p-tolyl sulfoxide and benzalaniline in two steps in high
yield,6e in THF at 2788C was treated with t-BuLi (a solution
of t-BuLi was added to a solution of 8 in THF). The reaction
took place immediately. After 1 min, the reaction was
quenched by adding deuterio methanol (CD3OD) to give a
quantitative yield of the desul®nylated product 10a (see
Table 1, entry 1). Though special precaution was taken to
remove the proton source, the rate of deuterium incorpora-
tion was only less than 67%. To increase the deuterium
incorporation we tried other experimental conditions
Generation of aziridinyllithiums from sul®nylaziridines
with tert-butyllithium and studies on the properties and
reactivity
We previously reported a method for generation of aziri-
dinylmagnesiums 5a from 4.6d,e Also, we extensively
studied generation of oxiranyl anions from sul®nyloxi-
ranes.9 Based on these studies we investigated if generation
of aziridinyllithium 5b was feasible by the sulfoxide±lithium
exchange reaction of the sul®nylaziridine 4 with t-BuLi.
Table 1. Generation of 2-lithioaziridine 9 from N-phenylsul®nylaziridine 8 and reaction with deuterio methanol and carbonyl compound
Entry
Alkylmetal (equiv.)
Temp. (8C)
Electrophile
Product/yield (%)a
1
2
3
4
5
6
7
8
9
t-BuLi (1.8)
t-BuLi (2)c
278
278
2100
270
270
270t230
270t230
270tr.t.
278
CD3OD
CD3OD
H2O
CD3OD
CD3OD
CD3OD
CD3OD
CD3OD
CH3CH2CHO
10a 99 (EˆD; 67%)b
10a 55 (EˆD; 65%)b
10b 58 (EˆH)
t-BuLi (3)c
t-BuMgCl (1.5),t-BuLi (1.5)
MeMgBr (1), t-BuLi (1.5)
t-BuMgCl (1.5), t-BuLi (1.5)
MeMgBr (1), t-BuLi (1.5)
MeMgBr (1), t-BuLi (1.5)
t-BuLi (1.8)
10a 96 (EˆD; 92%)b
10a 94 (EˆD; 90%)b
10a 91 (EˆD; 83%)b
10a 96 (EˆD; 86%)b
10b 90 (EˆH)
10c (L)d 30 (EˆCH(OH)Et)
(P)d 40
10
11
t-BuMgCl (1.5), t-BuLi (1.5)
MeMgBr (1), t-BuLi (1.2)
270
PhCHO
PhCHO
10d (L)d 18 (EˆCH(OH)Ph)
(P)d 15
2100
10d (L)d 37 (EˆCH(OH)Ph)
(P)d 33
12
13
MeMgBr (1), t-BuLi (1.8)
MeMgBr (1), t-BuLi (1.5)
278
2100
CH3COCH3
CH3COCH3
10e 29 (EˆC(OH)Me2)
10e 41 (EˆC(OH)Me2)
14
15
MeMgBr (1), t-BuLi (1.5)
MeMgBr (1), t-BuLi (1.5)
270
10f 28 (Eˆ
)
2100
10f 38 (Eˆ
)
16
MeMgBr (1), t-BuLi (2)
268
10g 35 (Eˆ
)
a Isolated yield after silica gel column chromatography.
b The deuterium incorporation was measured from 1H NMR.
c A solution of 8 in THF was added to a solution of t-BuLi (inverse addition).
d Less polar diastereomer (L) and more polar diastereomer (P) on silica gel TLC.

T. Satoh et al. / Tetrahedron 56 (2000) 4415±4425
4417
Table 2. Generation of 2-lithioaziridine 9 from N-phenylsul®nylaziridine 8 and reaction with electrophiles
Entry
1
Alkylmetal (equiv.)
Temp (8C)
270
Electrophile
ClCO2Et
Product/yield (%)a
10h 47 (EˆCO2Et)
MeMgBr (1), t-BuLi (1.5)
10i 38 (Eˆ
)
2
3
4
5
6
MeMgBr (2), t-BuLi (2)
MeMgBr (2), t-BuLi (2)
MeMgBr (1), t-BuLi (1.5)
MeMgBr (1), t-BuLi (2)
MeMgBr (1), t-BuLi (2)
2100
2100
270t230
278t230
278t230
ClCO2Et
ClCO2Me
(EtO)2POCl
CH3I/DMPUb
C6H5CH2Br/DMPUb
10h 75 (EˆCO2Et)
10j 61 (EˆCO2Me)
10k 43 (EˆPO(OEt)2)
0c
0c
a Isolated yield after silica gel column chromatography.
b DMPUˆN,N-dimethylpropyleneurea.
c This reaction gave the N-phenylaziridine 10b (EˆH) in 95 and 89% yields, respectively.
which were found to be effective in our oxiranyllithium
case.9 Thus, a THF solution of 8 was added to a THF solu-
tion of t-BuLi (entries 2 and 3, Table 1). However, in
contrast to the oxiranyllithium case, this treatment markedly
reduced the yield of 10a and gave similar deuterium incor-
poration.
electrophiles was investigated and the results are summar-
ized in Table 1 (entries 9±16). Propionaldehyde reacted
with 9 in good yield without the Grignard reagent (entry
9). Benzaldehyde gave adducts; however, the yields were
low (entry 10). In this case, lowering the reaction tempera-
ture to 21008C was found to be effective (entry 11). The
reaction with ketones also gave adducts; however, the yields
were less than 41%. In these cases, slightly better yields
were obtained at 21008C (entries 12±15). In case of the
reaction with 9-¯uorenone, higher temperature was required
to give the adduct 10g.
At this stage we considered that a trace of moisture in THF
was the proton source of the above-mentioned reaction. In
our previous study we found that the sul®nylaziridine 8 did
not react at all with t-BuMgCl and MeMgBr.6d,e We tried to
use these Grignard reagents for removing the moisture in
THF. Thus, t-BuMgCl was ®rst added to a solution of 8 in
THF at 2708C and the reaction mixture was stirred for
10 min, then t-BuLi was added. After 1 min, the reaction
was quenched with CD3OD to afford 10a in 96% yield with
up to 92% deuterium content (entry 4). Entry 5 shows that
MeMgBr works equally well. Both t-BuMgCl and MeMgBr
were used in this study. From these experiments we were
indeed able to generate the nonstabilized aziridinyllithium.
Table 2 shows the results of the reaction of the aziridinyl-
lithium 9 with other electrophiles. The reaction of 9 with
ethyl chloroformate at 2708C gave the desired ester 10h in
47% yield with ring-opened urethane derivative 10i (entry
1). The formation of the urethane was prevented when this
reaction was carried out at 21008C and the desired 10h was
obtained in 75% yield (entry 2). In the case with diethyl-
chlorophosphate, the reaction did not proceed at 2708C
(entry 4). Trials to obtain the alkylated aziridine were fruit-
less under several reaction conditions (entry 5 and 6).
Next, we investigated the stability of the generated aziri-
dinyllithium 9. As shown in entries 6 and 7, the generated 9
was slowly warmed to 2308C and then quenched with
CD3OD. The chemical yield of 10a was found to be similar
compared with the results in entries 4 and 5; however, a
slight decrease of the deuterium incorporation was
observed. Next, the solution of 9 was slowly warmed to
room temperature and then quenched with CD3OD (entry
8). The reaction mixture was still very clean and the yield of
the desul®nylated aziridine was 90%. Somewhat to our
surprise, no deuterium incorporation was observed in the
product. In this reaction it is noted that tert-butyl p-tolyl
sulfoxide was obtained as a by-product of the sulfoxide±
lithium exchange reaction. As no deuterium incorporation
was found in this tert-butyl p-tolyl sulfoxide, it is certain
that the generated aziridinyllithium 9 picks up the hydrogen
on THF at above 2308C.
We next investigated the generation of aziridinyllithiums
from the sul®nylaziridines 11a, 11b, and 11c (see Table
3). The sul®nylaziridine having 2-phenylethyl group 11a
gave the desul®nylated aziridine 12a and 12b in quantitative
yield; however, the deuterium incorporation was found to be
less than 83% (entry 3). Ethoxycarbonylation of the gener-
ated aziridinyllithium gave the ester 12c. In this case, the
establishment of the reaction conditions was found to be
rather dif®cult (see entries 5 and 6).
The sul®nylaziridine having 4-phenylbutyl group 11b also
gave aziridinyllithium in good yield (entries 7 and 8). The
aziridinyllithium gave the adducts 13c with propion-
aldehyde in moderate yields (entries 9 and 10). The aziri-
dinyllithium gave the adduct with acetone in low yield
(entries 11 and 12). The reaction of the aziridinyllithium
with ethyl chloroformate was again found to be dif®cult
Reactivity of the generated aziridinyllithium 9 with several

4418
T. Satoh et al. / Tetrahedron 56 (2000) 4415±4425
Table 3. Generation of 2-lithioaziridine from N-phenylsul®nylaziridine 11 and reaction with electrophiles
Entry
Alkylmetal (equiv.)
Temp (8C)
Electrophile
Product/yield (%)a
1
2
3
4
5
6
7
8
9
11a
11a
11a
11a
11a
11a
11b
11b
11b
MeMgBr (2), t-BuLi (1.5)
t-BuMgCl (3), t-BuLi (1.5)
t-BuMgCl (3), t-BuLi (2)
t-BuMgCl (2.3), t-BuLi (2)
t-BuMgCl (2), t-BuLi (2)
t-BuMgCl (2), t-BuLi (4)
t-BuLi (1.5)
270
270
280
270
2100
280
270
270
278
CD3OD
CD3OD
CD3OD
CH3OH
ClCO2Et
ClCO2Et
H2O
12a 99 (EˆD; 63)b
12a 99 (EˆD; 73)b
12a 99 (EˆD; 83)b
12b 94 (EˆH)
12c 22 (EˆCO2Et)
12c 60 (EˆCO2Et)
13a 86 (EˆH)
MeMgBr (1), t-BuLi (1.5)
MeMgBr (1), t-BuLi (1.5)
CD3OD
CH3CH2CHO
13b 99 (EˆD; 82)b
13c (L) 21
(P) 27 (EˆCH(OH)Et)
10
11b
MeMgBr (1), t-BuLi (1.5)
2100
CH3CH2CHO
13c (L) 34
(P) 28 (EˆCH(OH)Et)
13d 10 (EˆC(OH)Me2)
13d 27 (EˆC(OH)Me2)
13e 28 (EˆCO2Et)
11
12
13
11b
11b
11b
MeMgBr (1), t-BuLi (1.5)
MeMgBr (1), t-BuLi (1.5)
MeMgBr (1), t-BuLi (1.5)
270
2100
270
CH3COCH3
CH3COCH3
ClCO2Et
13f 12 (Eˆ
)
14
15
16
11c
11c
11c
t-BuMgCl (3), t-BuLi (2)
t-BuMgCl (3), t-BuLi (2)
MeMgBr (3), t-BuLi (4)
280
280
280
CH3OH
CD3OD
ClCO2Et
14a 99 (EˆH)
14b 99 (EˆD; 72)b
14c 81 (EˆCO2Et)
a Isolated yield after silica gel column chromatography.
b The deuterium incorporation was measured from 1H NMR.
and the urethane derivative 13f was obtained as a byproduct
(entry 13).
are found to be stable at low temperature. The nucleo-
philicity of the generated aziridinyllithum to ketones and
aldehydes was found to be relatively low. The reaction of
the aziridinyllithiums with ethyl chloroformate gave moder-
ate to good yields of the esters. But this reaction required
some special conditions, for example, with regard to
temperature of the reaction and the amount of t-BuLi, to
get good yields.
The sul®nylaziridine having decyl group 11c gave the desul-
®nylated aziridine in quantitative yield. In this case, the
reaction of the generated aziridinyllithium with ethyl chloro-
formate gave the desired ester 14c in relatively good yield
(entry 16).
In summary of the results mentioned above, we concluded
that the sul®nylaziridines 8 and 11 reacted with t-BuLi at
low temperature, even at 21008C, to give nonstabilized
aziridinyllithiums in high yields. The aziridinyllithiums
Synthesis of racemic and optically active a,a-dialkyl-
amino acid esters
In order to extend our new method to a synthesis of
Scheme 2. Catalytic hydrogenation of 2-carbethoxy aziridines 10h, 12c, and 14c.

T. Satoh et al. / Tetrahedron 56 (2000) 4415±4425
4419
Table 4. Ring-opening of the aziridines 10h and 14c with thiols and reduction of the sul®des 17 and 18
Entry
R0SH
Yield of sul®de
Reducing agent
Product
1
2
3
4
10h
14c
14c
PhSH
PhSH
PhCH2SH
17
74%
92%
87%
Raney-Ni/EtOH
Raney-Ni/EtOH
Raney-Ni/EtOH
Bu3SnH/AIBN Benzene, re¯ux
15
19
19
19
42%
18a
18b
18b
34%
53%
62%
a,a-dialkylamino acid esters, we investigated regioselective
ring-opening of the aziridinyl esters 10h, 12c, and 14c. First,
catalytic hydrogenation10 of the aziridinyl esters was studied
and the results are summarized in Scheme 2. The aziridinyl
ester having a methyl group 10h was smoothly hydro-
genated with a Pd±C or Pd(OH)2 catalyst in alcohol as a
solvent under H2 atmosphere. Even Raney-nickel in ethanol
at room temperature was effective for the reduction.
reduction conditions. The results are shown in entries 3 and
4. The ring-opening of 14c with benzyl mercaptan gave a
similar yield of the sul®de 18b (compare entry 3 with entry
2). Reductive desulfurization of 18b with Raney-nickel
gave 53% yield of 19. When this reduction was conducted
with tributyltin hydride12 in the presence of AIBN the yield
of 19 was improved to 62% yield (entry 4).
In order to extend the above-mentioned method to a synth-
esis of optically active a,a-dialkylamino acid esters, optic-
ally pure sul®nylaziridine (2)-8 was synthesized from
optically active 1-chloroethyl p-tolyl sulfoxide6e (Scheme
3). Optically active (2)-8 was converted to ethylester
(2)-10h, which was hydrogenated with Pd±C under hydro-
gen atmosphere, as described above, to give optically pure
a,a-dialkylamino acid ester (S)-(2)-15. Optical purity was
unambigously determined by HPLC using a chiral station-
ary column.13
In contrast to this result, hydrogenation of the aziridinyl
ester having 2-phenylethyl group 12c took place very slowly
and the desired product 16 was obtained in only 36% yield.
Hydrogenation of 12c with Rh-Al2O3 did not proceed at all.
The hydrogenation of 14c showed a much worse result. The
reaction did not proceed when even excess Pd(OH)2 was
used and prolonging the reaction gave a complex mixture,
from which we could not obtain the desired product.
Next, we studied the regioselective ring-opening of the
aziridinyl esters 10h and 14c with a thiol11 and the reduction
of the resultant sul®des (see Table 4). After some investi-
gation we found that a thiol in the presence of BF3OEt2 in
CH2Cl2 was the conditions of choice for the ring-opening.
Under these conditions both aziridinyl esters 10h and 14c
gave good yields of the sul®des 17 and 18a, respectively
(entries 1 and 2). Reductive desulfurization of the sul®des
with Raney-nickel under the usual conditions, however,
gave only moderate yields of the esters 15 and 19 (entries
1 and 2).
Reaction of the aziridinyllithiums with phenyl
isocyanate and a synthesis of a,a-dialkylamino acid
amides
As described above, generation of the aziridinyllithiums and
trapping them with several electrophiles were successful.
Especially, reaction of aziridinyllithiums with ethyl chlor-
oformate led to a new method for asymmetric synthesis of
a,a-disubstituted amino acid esters. However, we found
that the ethoxycarbonylation required rather delicate con-
ditions and the reproducibility of the yield was sometimes
low.
As we were eagerly seeking a method to get the a,a-dialkyl-
amino ester 19, we further investigated another thiol and the
Scheme 3.

4420
T. Satoh et al. / Tetrahedron 56 (2000) 4415±4425
Scheme 4.
In order to overcome this problem, we investigated the reac-
tion with other electrophiles and found that phenyl isocya-
nate was the reagent of choice. For example, reaction of the
aziridinyllithium generated from 8 with excess phenyl iso-
cyanate at 21008C for 10 min gave the desired aziridinyl
amide 20a in 64% yield (Scheme 4). This yield is not so
high compared with the best yield of the ethoxycarbonyl-
ation (75%; see Table 2, entry 2); however, the yield for the
amide 20a was found to be reproducible. In a similar
manner, 11c gave 20b in moderate yield.
the ®nal products, a,a-dialkylamino acid esters and amides,
have an aryl group on the nitrogen. In order to synthesize
N-non substituted amino acid derivatives, we investigated
the above-mentioned procedure by using N-(p-methoxy-
phenyl)aldimin 22 and obtained quite interesting results
(Scheme 5).
Addition of the lithium a-sul®nyl carbanion of 1-chloro-
alkyl p-tolyl sulfoxides to the imine 22 at 2788C gave the
adducts 23a and 23b, respectively, as crystals in good
yields. These adducts are single diastereomers as described
in the previous paper.6e Treatment of 23 with t-BuOK at
708C gave the desired N-(4-methoxyphenyl) sul®nylaziri-
dines 24a and 24b in high yields.
Catalytic hydrogenation of the aziridine ring of 20a and 20b
is quite interesting. Under similar conditions for the hydro-
genation of ester 10h (see Scheme 2), amide 20a gave the
ring-opened product in much higher yield (85%) within 1 h.
In the case of ester 10h, the yield was 59% and required 3 h
for completion of the reaction. In the case of the hydrogena-
tion of amide 20b, the reaction required 5.5 h. The reaction
gave a rather clean reaction mixture and the desired amide
21b was obtained in 57% yield. Note that the corresponding
ester 14c gave only a complex mixture under similar con-
ditions for 100 h (see Scheme 2).
Generation of the aziridinyllithium of 23a was carried out in
a similar way as described above at 2808C and the gener-
ated aziridinyllithium was treated with ethyl chloroformate
for 1 min. This reaction worked quite well to afford the
ethoxycarbonylated aziridine 25a in 81% yield. Moreover,
this reaction was found to be reproducible and no ring-
opened urethane derivative was obtained. In the case of
the reaction with 24b, again the ring-opened urethane was
not observed and the ethoxycarbonylation was found to be
reproducible to give 25b in 64% yield.
Synthesis of N-(4-methoxyphenyl) sul®nylaziridines and
conversion of them to N-non substituted a,a-dialkyl-
amino acid esters
Hydrogenolysis of the aziridine ring of 25a and 25b was
also very interesting. The aziridine ring of both 25a and 25b
was reduced by using Pd(OH)2 as a catalyst in methanol at
Because all the sul®nylaziridines 4 were synthesized starting
from 1-chloroalkyl p-tolyl sulfoxides and N-arylaldimines,
Scheme 5.

T. Satoh et al. / Tetrahedron 56 (2000) 4415±4425
4421
room temperature within 3 h. Compared with the result in
the same reaction of 14c (Scheme 2), the 4-methoxyphenyl
group is thought to activate the hydrogenolysis of the N±C
bond. Removal of the 4-methoxyphenyl group of 26 was
carried out with ceric (IV) ammonium nitrate (CAN)14
smoothly to give N-non substituted a,a-dialkylamino acid
ethyl esters 27a and 27b in good yields.
was puri®ed by silica gel column chromatography to give
36 mg (94%) of 10a6e as a colorless oil.
(E)-2-(1-Hydroxypropyl)-2-methyl-1,3-diphenylaziridine
(10c). t-BuLi (0.41 mmol) was added to a solution of 8
(79 mg; 0.23 mmol) in 12 ml of THF with stirring at
2788C. After 1 min, propionaldehyde (0.69 mmol) was
added and the reaction mixture was stirred at 2788C for
10 min. The reaction was quenched by adding sat. aq.
NH4Cl and the whole was extracted with ether±hexane.
The products were puri®ed by silica gel column chroma-
tography to afford the adducts 10c±L (18 mg; 30%) and
10c±P (24.5 mg; 40%) together with 10b6e (14.6 mg;
30%). 10c±L: colorless viscous oil; IR (neat) 3585, 3447
Experimental
All melting points are uncorrected and were measured with
a Yanagimoto micro melting point apparatus. H NMR
1
1
(OH), 1596, 1488 cm21; H NMR d 0.97 (3H, t, Jˆ7 Hz),
spectra were measured in a CDCl3 solution with JEOL
JNM-LA 400 and 500 spectrometer. Electrom-impact
mass spectra (MS) were obtained at 70 eV by direct inser-
tion. Optical rotations were taken with a JASCO DIP-1000
didital polarimeter. Silical gel 60 (MERCK) and silica gel
60N for ¯ash chromatography (Kanto Chemical Co.)
containing 0.5% ¯uorescence reagent 254 and quartz
column were used for column chromatography and the
¯ash column chromatography and the products having UV
absorption were detected by UV irradiation. In experiments
requiring a dry reagent and solvent, diisopropylamine was
distilled from CaH2 and THF was distilled from sodium
diphenylketyl. All the reagents are commercially available
and puri®ed by recrystallization or distillation before use.
Methanol and liquid N2 were used for the cooling bath at
21008C.
1.08 (3H, s), 1.63 (1H, m), 1.79 (1H, m), 3.75 (1H, s), 3.86
(1H, dd, Jˆ7.9, 2.6 Hz), 6.9±7.5 (10H, m). MS m/z (%) 267
(M1, 8), 220 (1), 208 (3), 182 (100). Calcd for C18H21NO:
M, 267.1622. Found: m/z 267.1628. 10c±P: colorless
viscous oil; IR (neat) 3585, 3450 (OH), 1597, 1489 cm21
;
1H NMR d 0.97 (3H, t, Jˆ7.3 Hz), 1.15 (3H, s), 1.6±1.7
(2H, m), 3.07 (1H, m), 3.18 (1H, s), 6.9±7.5 (10H, m). MS
m/z (%) 267 (M1, 9), 250 (2), 208 (12), 176 (100). Calcd for
C18H21NO: M, 267.1622. Found: m/z 267.1634.
(E)-2-[(Hydroxy)phenylmethyl]-2-methyl-1,3-diphenyl-
aziridine (10d). 10d±L: colorless viscous oil; IR (neat)
1
3565, 3450 (OH), 1595, 2489 cm21; H NMR d 0.85 (3H,
s), 1.18 (1H, d, Jˆ3 Hz, OH), 4.23 (1H, s), 5.05 (1H, d, Jˆ
3 Hz), 6.9±7.5 (15H, m). MS m/z (%) 315 (M1, 9), 296 (3),
224 (22), 182 (100). Calcd for C22H21NO: M, 315.1622.
Found: m/z 315.1637. 10d±P: colorless needles; mp 74±
788C (AcOEt±hexane); IR (KBr) 3580, 3290 (OH), 1595,
Sul®nylaziridines.15 The sul®nylaziridines 8 and 11c were
reported previously.6e The sul®nylaziridines 11a and 11b
were synthesized from 1-chloro-3-phenylpropyl p-tolyl
sulfoxide and 1-chloro-5-phenylpentyl p-tolyl sulfoxide
and benzalaniline in a similar manner described previously6e
in high overall yields. (E)-1,3-Diphenyl-2-(2-phenylethyl)-
2-(p-tolylsul®nyl)aziridine (11a): colorless crystals; mp
159±1618C (AcOEt±hexane). IR (KBr) 1596, 1492, 1058
(SO) cm21; 1H NMR d 1.3±1.6 (2H, m), 2.41 (3H, s), 2.99
(2H, t, Jˆ8.4 Hz), 4.70 (1H, s), 6.9±7.7 (19H, m). Anal.
Calcd for C29H27NOS: C, 79.60; H, 6.22; N, 3.20; S, 7.33.
Found: C, 79.26; H, 6.11; N, 3.10; S, 7.38. (E)-1,3-Diphenyl-
2-(4-Phenylbutyl)-2-(p-tolylsul®nyl)aziridine (11b): color-
less crystals; mp 103±1058C (CHCl3-hexane). IR (KBr)
1
1489 cm21; H NMR d 1.11 (3H, s), 2.08 (1H, d, Jˆ3 Hz,
OH), 3.52 (1H, s), 4.33 (1H, d, Jˆ3 Hz), 7.0±7.5 (15H, m).
MS m/z (%) 315 (M1, 12), 296 (4), 224 (19), 182 (100).
Calcd for C22H21NO: M, 315.1622. Found: m/z 315.1627.
(E)-2-(1-Hydroxy-1-methylethyl)-2-methyl-1,3-diphenyl-
aziridine (10e). Colorless needles; mp 86±888C (AcOEt±
hexane); IR (KBr) 3572 (OH), 1593, 1485 cm21; 1H NMR d
1.15, 1.30, 1.56 (each 3H, s), 3.95 (1H, s), 6.9±7.4 (10H, m).
MS m/z (%) 267 (M1, 10), 234 (3), 208 (6), 182 (100). Calcd
for C18H21NO: M, 267.1622. Found: m/z 267.1624.
1
1597, 1493, 1057 (SO) cm21; H NMR d 1.0±1.2 (2H,
(E)-2-(1-Hydroxycyclohexyl)-2-methyl-1,3-diphenylaziri-
dine (10f). Colorless viscous oil; IR (neat) 3572, 3470 (OH),
1597, 1491 cm21; 1H NMR d 1.14 (3H, s), 1.5±1.7 (8H, m),
1.8±2.0 (2H, m), 3.94 (1H, s), 6.8±7.0 (3H, m), 7.2±7.4
(7H, m). MS m/z (%) 307 (M1, 10), 216 (18), 182 (100).
Calcd for C21H25NO: M, 307.1934. Found: m/z 307.1925.
m), 1.3±1.6 (2H, m), 1.7±1.9 (2H, m), 2.41 (3H, s), 2.54
(2H, m), 4.63 (1H, s), 7.0±7.6 (19H, m). MS m/z (%) 465
(M1, 0.5), 449 (2), 339 (1), 326 (36), 236 (71), 182 (94), 91
(100). Calcd for C31H31NOS: M, 465.2126. Found: m/z
465.2139.
Aziridine (10g). Colorless needles; mp 162±1648C
General procedure for a generation of aziridinyllithium 9.
A synthesis of 2-deuterio-2-methyl-1.3-diphenylaziridine
10a (Table 1, entry 5) is described. A solution of MeMgBr
(0.18 mmol) in THF was added dropwise to a solution of 8
(62 mg; 0.18 mmol) in 4 ml of THF at 2708C under Ar
atmosphere. The reaction mixture was stirred at 2708C
for 10 min. t-BuLi (0.27 mmol) in pentane was added to
the reaction mixture and after 2 min, the reaction was
quenched by adding 0.2 ml of CD3OD. The solution was
stirred for 15 min, then sat. aq. NH4Cl was added. The
whole was extracted with ether±hexane and the product
(AcOEt±hexane); IR (KBr) 3410 (OH), 1597, 1491 cm21
;
1H NMR d 0.68 (3H, s), 3.94 (1H, s), 4.56 (1H, s, OH), 6.8±
7.5 (18H, m). MS m/z (%) 389 (M1, 11), 208 (100), 181
(94). Anal. Calcd for C28H23NO: C, 86.33; H, 5.96; N, 3.60.
Found: C, 85.90; H, 5.93; N, 3.49.
(E)-2-Ethoxycarbonyl-2-methyl-1,3-diphenylaziridine
(10h). Colorless oil; IR (neat) 1724 (CO), 1491, 1275,
1
1151 cm21; H NMR d 0.96 (3H, t, Jˆ7 Hz), 1.33 (3H, s),
3.97 (2H, m), 4.15 (1H, s), 6.8±7.0 (3H, m), 7.3±7.5 (7H,

4422
T. Satoh et al. / Tetrahedron 56 (2000) 4415±4425
1
m). MS m/z (%) 281 (M1, 15), 252 (21), 236 (28), 208 (43),
118 (100). Calcd for C18H19NO2: M, 281.1415. Found: m/z
281.1425. (2)-10h: [a]2D5ˆ294.258 (c 0.2, acetone).
1597, 1489, 698 cm21; H NMR d 0.54 (1H, d, Jˆ4 Hz),
0.99 (3H, t, Jˆ7 Hz), 1.0±1.2 (2H, m), 1.3±1.9 (6H, m),
2.58 (2H, t, Jˆ7 Hz), 3.86 (1H, s), 4.09 (1H, m), 6.9±7.5
(15H, m). MS m/z (%) 385 (M1, 5), 367 (3), 326 (12), 294
(77), 182 (76), 91 (100). Calcd for C27H31NO: M, 385.2406.
Found: m/z 385.2403. 13c±P: colorless viscous oil; IR
Ethyl N-(1-methyl-2-phenylethyl)-N-phenylcarbamate
(10i). Colorless oil; IR (neat) 1713 (CO), 1304,
1079 cm21; H NMR d 1.27 (3H, t, Jˆ7 Hz), 2.12 (3H, s),
(neat) 3570 (OH), 1597, 1489, 698 cm21; H NMR d 0.96
1
1
4.23 (2H, q, Jˆ7 Hz), 6.48 (1H, s), 7.1±7.4 (10H, m). MS
m/z (%) 281 (M1, 100), 208 (70), 193 (52), 167 (50). Calcd
for C18H19NO2: M, 281.1415. Found: m/z 281.1429.
(3H, t, Jˆ7 Hz), 1.0±1.2 (2H, m), 1.5±2.0 (7H, m), 2.53
(2H, t, Jˆ8 Hz), 3.11 (1H, m), 3.20 (1H, s), 6.9±7.4 (15H,
m). MS m/z (%) 385 (M1, 6), 367 (3), 326 (8), 294 (100),
182 (66). Calcd for C27H31NO: M, 385.2406. Found: m/z
385.2399.
(E)-2-Methoxycarbonyl-2-methyl-1,3-diphenylaziridine
(10j). Colorless oil; IR (neat) 1730 (CO), 1599, 1489, 1277,
1149 cm21; 1H NMR d 1.33 (3H, s), 3.53 (3H, s), 4.14 (1H,
s), 6.8±7.0 (3H, m), 7.2±7.5 (7H, m). MS m/z (%) 267 (M1,
35), 236 (83), 208 (100). Calcd for C17H17NO2: M,
267.1258. Found: m/z 267.1265.
(E)-2-(1-Hydroxy-1-methylethyl)-1,3-diphenyl-2-(4-phenyl-
butyl)aziridine (13d). Colorless oil; IR (neat) 3570 (OH),
1597, 1494, 1488, 698 cm21; H NMR d 1.1±1.8 (6H, m),
1
1.33, 1.47 (each 3H, s), 2.54 (2H, t, Jˆ7.5 Hz), 3.96 (1H, s),
6.9±7.4 (15H, m). MS m/z (%) 385 (M1, 7), 352 (4), 326
(35), 182 (100). 167 (45). Calcd for C27H31NO: M,
385.2406. Found: m/z 385.2395.
(E)-2-Diethylphosphonyl-2-methyl-1,3-diphenylaziridine
1
(10k). Colorless oil; IR (neat) 1259, 1049, 1026 cm21; H
NMR d 1.1±1.4 (6H, m), 1.50 (3H, s), 3.8±4.3 (5H, m),
6.9±7.5 (10H, m). MS m/z (%) 345 (M1, 95), 316 (6), 288
(7), 207 (100). Calcd for C19H24NO3P: M, 345.1492. Found:
m/z 345.1483.
(E)-2-Ethoxycarbonyl-1,3-diphenyl-2-(4-phenylbutyl)-
aziridine (13e). Colorless oil; IR (neat) 1724 (CO), 1599,
1273, 1174 cm21; 1H NMR d 0.93 (3H, t, Jˆ7 Hz), 1.4±1.7
(6H, m), 2.46 (2H, t, Jˆ7 Hz), 3.95 (2H, q, Jˆ7 Hz), 4.15
(1H, s), 6.8±7.5 (15H, m). MS m/z (%) 399 (M1, 49), 370
(34), 354 (8), 326 (56), 280 (36), 236 (74), 91 (100). Calcd
for C27H29NO2: M, 399.2199. Found: m/z 399.2210.
(Z)-2-Deuterio-1,3-diphenyl-2-(2-phenylethyl)aziridine
(12a). Colorless oil; IR (neat) 1599, 1488, 1453, 697 cm21
;
1H NMR d 1.63±1.78 (2H, m), 2.68±2.87 (2H, m), 3.33
(1H, s), 6.9±7.5 (15H, m). MS m/z (%) 300 (M1, 20), 209
(100), 105 (93). Calcd for C22H20DN: M, 300.1736. Found:
m/z 300.1737.
Ethyl N-[2-phenyl-1-(4-phenylbutyl)ethenyl]-N-phenyl-
carbamate (13f). Colorless oil; IR (neat) 1718 (CO),
1
1597, 1302 cm21; H NMR d 1.25 (3H, t, Jˆ7 Hz), 1.5±
(Z)-2,3-Diphenyl-2-(2-phenylethyl)aziridine (12b). Color-
1.7 (4H, m), 2.36 (2H, t, Jˆ7 Hz), 2.53 (2H, t, Jˆ7 Hz),
4.21 (2H, q, Jˆ7 Hz), 6.54 (1H, s), 7.1±7.4 (15H, m). MS
m/z (%) 399 (M1, 56), 370 (2), 326 (12), 308 (31), 281 (24),
91 (100). Calcd for C27H29NO2: M, 399.2198. Found: m/z
399.2217.
1
less oil; IR (neat) 1599, 1488, 1454 cm21; H NMR d
1.64±1.75 (2H, m), 2.49 (1H, q, Jˆ6.5 Hz), 2.68±2.87
(2H, m), 3.34 (1H, d, Jˆ6.5 Hz), 6.9±7.5 (15H, m). MS
m/z (%) 299 (M1, 30), 208 (100), 104 (87). Calcd for
C22H21N: M, 299.1673. Found: m/z 299.1676.
(Z)-2-Decyl-2-deuterio-1,3-diphenylaziridine (14b). Color-
1
(E)-2-Ethoxycarbonyl-1,3-diphenyl-2-(2-phenylethyl)-
aziridine (12c). Colorless oil; IR (neat) 1722 (CO), 1598,
less oil; IR (neat) 1599, 1488, 694 cm21; H NMR d 0.88
(3H, t, Jˆ7 Hz), 1.2±1.6 (18H, m), 3.30 (1H, s), 6.9±7.4
(10H, m). MS m/z (%) 336 (M1, 78), 337 (19), 256 (16), 223
(86), 105 (100). Calcd for C24H32NO: M, 336.2675. Found:
m/z 336.2677.
1
1490, 1177 cm21; H NMR d 1.00 (3H, t, Jˆ7 Hz), 1.84±
2.06 (2H, m), 2.62±2.81 (2H, m), 4.01 (2H, q, Jˆ7 Hz),
4.24 (1H, s), 6.9±7.5 (15H, m). MS m/z (%) 371 (M1, 8),
281 (21), 280 (100), 208 (16). Calcd for C25H25O2N: M,
371.1886. Found: m/z 371.1884.
(E)-2-Octyl-2-ethoxycarbonyl-1,3-diphenylaziridine (14c).
Colorless oil; IR (neat) 1726 (CO), 1598, 1490, 1272,
1
(Z)-1,3-Diphenyl-2-(4-phenylbutyl)aziridine (13a). Color-
less oil; IR (neat) 1601, 1489, 698 cm21; 1H NMR d 1.3±1.7
(6H, m), 2.41 (1H, q, Jˆ6.6 Hz), 2.55 (2H, t, Jˆ7 Hz), 3.30
(1H, d, Jˆ6.6 Hz), 6.9±7.5 (15H, m). MS m/z (%) 327 (M1,
100), 326 (49), 222 (49), 208 (37), 194 (29). Calcd for
C24H25N: M, 327.1987. Found: m/z 327.1980.
1174 cm21; H NMR d 0.86, 0.95 (each 3H, t, Jˆ7 Hz),
1.1±1.7 (18H, m), 3.95 (2H, q, Jˆ7 Hz), 4.12 (1H, s),
6.9±7.5 (10H, m). MS m/z (%) 407 (M1, 34), 378 (45),
334 (82), 280 (41), 244 (100). Calcd for C27H37NO2: M,
407.2824. Found: m/z 407.2824.
Ethyl 2-methyl-3-phenyl-2-phenylaminopropionate (15).
A mixture of 10h (79.5 mg) and 10% Pd±C (300 mg) in
2 ml of ethanol was stirred under H2 atmosphere at room
temperature for 2.3 h. The Pd±C was ®ltered off and the
solvent was evaporated under vacuum. The residue was
puri®ed by silica gel column chromatography to afford
45 mg (64%) of 15 as colorless prisms; mp 79±828C
(AcOEt±hexane). IR (KBr) 3408 (NH), 1728 (CO), 1603,
(Z)-2-Deuterio-1,3-diphenyl-2-(4-phenylbutyl)aziridine
1
(13b). Colorless oil; IR (neat) 1599, 1489, 694 cm21; H
NMR d 1.3±1.7 (6H, m), 2.55 (2H, t, Jˆ7 Hz), 3.29 (1H,
s), 6.9±7.5 (15H, m). MS m/z (%) 328 (M1, 100), 327 (49),
223 (41), 209 (33). Calcd for C24H24DN: M, 328.2045.
Found: m/z 328.2057.
1
(E)-2-(1-Hydroxypropyl)-1,3-diphenyl-2-(4-phenylbutyl)-
aziridine (13c). 13c±L: colorless oil; IR (neat) 3571 (OH),
1508 cm21; H NMR d 1.19 (3H, t, Jˆ7 Hz), 3.21 (1H, d,
Jˆ14 Hz), 3.31 (1H, d, Jˆ14 Hz), 4.18 (2H, q, Jˆ7 Hz),

T. Satoh et al. / Tetrahedron 56 (2000) 4415±4425
4423
6.6±7.3 (10H, m). MS m/z (%) 283 (M1,4), 210 (33), 192
(100), 182 (11), 118 (48). Anal. Calcd for C18H21NO2: C,
76.29; H, 7.41; N, 4.96. Found: C, 76.21; H, 7.34; N, 4.79.
(S)-(2)-15: Mp 93±948C (AcOEt±hexane); [a]2D5ˆ234.158
(c 0.2 acetone).
(0.14 ml; 0.51 mmol) and AIBN (13 mg; 0.08 mmol) were
added to a solution of 18b (90.3 mg; 0.17 mmol) in 3 ml of
benzene. The solution was stirred at room temperature for
10 min, then re¯uxed for 2 h under Ar atmosphere. The
solvent was evaporated under vacuum and the product
was puri®ed by silica gel column chromatography to give
19 (62%).
Ethyl 2-benzyl-4-phenyl-2-phenylaminobutanoate (16).
Colorless oil; IR (neat) 3402 (NH), 1731 (CO), 1602,
1
1496, 1198 cm21; H NMR d 1.28 (3H, t, Jˆ7 Hz), 2.3±
Synthesis of amide 20a. MeMgBr (0.36 mmol) was added
with stirring to a solution of 8 (62 mg; 0.18 mmol) in 2 ml of
THF at 2508C under Ar atmosphere. The reaction mixture
was stirred at 2508C for 10 min, then was cooled to
21008C. t-BuLi (0.36 mmol) was added to the reaction
mixture and after 1 min phenyl isocyanate (0.75 mmol)
was added. The reaction mixture was stirred at 21008C
for 10 min, then the reaction was quenched by adding sat.
aq. NH4Cl. The whole was extracted with CHCl3. The
product was puri®ed by ¯ash column chromatography to
give 38 mg (64%) of 20a as colorless crystals; mp 153±
1558C (AcOEt-hexane). IR (KBr) 3312 (NH), 1654 (CO),
1596, 1522, 1440 cm21; 1H NMR d 1.49 (3H, s), 4.15 (1H,
s), 6.9±7.4 (15H, m). MS m/z (%) 328 (M1,43), 236 (35),
208 (31), 182 (100). Anal. Calcd for C22H20N2O: C, 79.46;
H, 6.14; N, 8.53. Found: C, 79.73; H, 6.04; N, 8.31.
2.7 (4H, m), 3.18, 3.51 (each 1H, d, Jˆ14 Hz), 4.0±4.3 (3H,
m), 6.7±7.7 (15H, m). MS m/z (%) 373 (M1, 1), 282 (50),
230 (19), 178 (75), 91 (100). Calcd for C25H27NO2: M,
373.2041. Found: m/z 373.2059.
Ethyl 2-methyl-3-phenyl-2-phenylamino-3-phenylthio-
propionate (17). In a 30-ml dried ¯ask was added thio-
phenol (0.04 ml) followed by BF3-etherate (0.023 ml) at
08C under Ar. A solution of 10h (50 mg; 0.18 mmol) in
4 ml of CH2Cl2 was added dropwise to the mixture. The
resulting reaction mixture was stirred at 08C for 10 min,
then at room temperature for 30 min. The reaction was
quenched by adding aq. K2CO3 and the whole was extracted
with CHCl3. The product was puri®ed by silica gel column
chromatography to give 60 mg (85%) of 17 as a colorless
oil. IR (neat) 3401 (NH), 1731 (CO), 1601, 1504,
1
1236 cm21; H NMR d 1.17 (3H, t, Jˆ7 Hz), 1.62 (3H, s),
Amide 20b. Colorless crystals; mp 95±988C (AcOEt±hex-
ane). IR (KBr) 3364 (NH), 1663 (CO), 1598, 1531, 1441,
4.13 (2H, q, Jˆ7 Hz), 4.43 (1H, bs), 4.53 (1H, s), 6.7±7.5
(15H, m). MS m/z (%) 391 (M1, 0.2), 318 (2), 299 (1), 192
(100). Calcd for C24H25NO2S: M, 391.1606. Found: m/z
391.1610.
1
748, 697 cm21; H NMR d 0.87 (3H, t, Jˆ7 Hz), 1.1±1.4
(13H, m), 1.4±1.7 (4H, m), 1.88 (1H, t, Jˆ9 Hz), 4.10 (1H,
s), 7.0±7.5 (15H, m). MS m/z (%) 454 (M1, 70), 362 (18),
244 (55), 182 (100). Anal. Calcd for C31H38N2O: C, 81.90;
H, 8.42; N, 6.16. Found: C, 81.76; H, 8.54; N, 6.02.
Ethyl 2-[(phenyl)phenylthiomethyl]-2-phenylamino-
dodecanoate (18a). Colorless oil; IR (neat) 3401, 3368
1
(NH), 1732 (CO), 1601, 1496, 1259, 1211 cm21; H NMR
Catalytic hydrogenation of 20a and 20b. To a solution of
20a (33 mg) in 1 ml of distilled methanol was added
Pd(OH)2 on carbon (10 mg) and the suspension was stirred
under H2 atmosphere at room temperature for 1 h. The
catalyst was ®ltered off and the product was puri®ed by
silica gel column chromatography to give 21a (26 mg;
85%) as colorless crystals; mp 112±1158C (AcOEt±hex-
ane). IR (KBr) 3297 (NH), 1667 (CO), 1602, 1532, 1495,
1439 cm21; 1H NMR d 1.46 (3H, s), 3.23, 3.44 (each 1H, d,
Jˆ14 Hz), 3.90 (1H, s), 6.6±7.5 (15H, m), 8.77 (1H, s). MS
m/z (%) 330 (M1, 3), 239 (44), 210 (100). Calcd for
C22H22N2O: M, 330.1732. Found: m/z 330.1722. 21b:
Colorless crystals; mp 64±658C (hexane). IR (KBr) 3342
(NH), 1668 (CO), 1602, 1515, 1497, 1441 cm21; 1H NMR d
0.87 (3H, t, Jˆ7 Hz), 1.1±1.9 (18H, m), 3.30, 3.49 (each
1H, d, Jˆ14 Hz), 3.81 (1H, s), 6.6±7.5 (15H, m), 8.63 (1H,
s). MS m/z (%) 456 (M1, 2), 336 (100), 244 (23). Calcd for
C31H40N2O: M, 456.3140. Found: m/z 456.3150.
d 0.86 (3H, t, Jˆ7 Hz), 1.1±1.4 (19H, m), 1.94 (1H, m),
2.20 (1H, m), 4.21 (2H, m), 4.58 (1H, s), 5.10 (1H, s),
6.8±7.5 (15H, m). MS m/z (%) 517 (M1, 0.1), 407 ([M-
C6H5SH]1, 29), 378 (37), 334 (92), 318 (84), 224 (100).
Ethyl
dodecanoate (18b). Colorless oil; IR (neat) 3376 (NH),
1731 (CO), 1601, 1494, 1259, 1210 cm21 1H NMR d
2-[(benzylthio)phenylmethyl]-2-phenylamino-
;
0.87 (3H, t, Jˆ7 Hz), 1.0±1.4 (19H, m), 1.78 (1H, m),
2.05 (1H, m), 3.26, 3.50 (each 1H, d, Jˆ13.3 Hz), 4.09
(1H, s), 4.15 (2H, m), 4.92 (1H, bs), 6.7±7.3 (15H, m).
MS m/z (%) 531 (M1, 0.1), 458 (1), 366 (1), 318 (100).
Calcd for C34H45NO2S: M, 531.3171. Found: m/z 531.3163.
Ethyl 2-benzyl-2-phenylaminododecanoate (19). Raney
nickel (W2, about 230 mg) was added to a solution of 18b
(58 mg; 0.11 mmol) in 2 ml of EtOH and the suspension
was stirred at room temperature for 30 min. The nickel
was ®ltered off and the EtOH was evaporated. The product
was puri®ed by silica gel column chromatography to afford
23.5 mg (53%) of 19 as a colorless oil. IR (neat) 3406 (NH),
1731 (CO), 1603, 1511, 1196 cm21; 1H NMR d 0.87 (3H, t,
Jˆ7 Hz), 1.1±1.4 (19H, m), 1.90 (1H, m), 2.10 (1H, m),
3.23, 3.40 (each 1H, d, Jˆ13.8 Hz), 4.18 (2H, m), 4.43
(1H, bs), 6.7±7.3 (10H, m). MS m/z (%) 409 (M1, 1), 336
(16), 318 (100), 244 (18). Calcd for C27H39NO2: M,
409.2978. Found: m/z 409.2969.
(1Rp, 2Rp)-2-Chloro-1-(4-methoxyphenylamino)-1-phenyl-
2-(p-tolylsul®nyl)propane (23a). To a solution of LDA
(2.4 mmol) in 7 ml of THF at 2788C was added a solution
of 1-chloroethyl p-tolyl sulfoxide (405 mg; 2 mmol) in 2 ml
of THF dropwise with stirring. After 10 min, a solution of
the imine 22 (508 mg; 2.4 mmol) in THF was added to the
reaction mixture and the reaction mixture was stirred at
2788C for 30 min. The reaction was quenched by sat. aq.
NH4Cl and the whole was extracted with CHCl3. The
organic layer was washed once with sat. aq. NH4Cl and
dried over MgSO4. The solvent was evaporated to give
Reductive desulfurization of 18b with Bu3SnH. Bu3SnH

4424
T. Satoh et al. / Tetrahedron 56 (2000) 4415±4425
1
colorless crystals, which was ®ltered and washed with a
mixture of AcOEt±hexane (10:1) to give pure 23a
(570 mg; 69%); colorless crystals; mp 165±1688C
(AcOEt±hexane). IR (KBr) 3302 (NH), 1509, 1252, 1037
(SO) cm21; 1H NMR d 1.84 (3H, s), 2.39 (3H, s), 3.68 (3H,
s), 4.36 (1H, d, Jˆ3 Hz), 5.75 (1H, d, Jˆ3 Hz, NH), 6.39,
6.63 (each 2H, d, Jˆ9 Hz), 7.2±7.6 (9H, m). MS m/z (%)
413 (M1, 9), 361 (4), 273 (74), 238 (78), 212 (84), 122
(100). Anal. Calcd for C23H24ClNO2S: C, 66.74; H, 5.84;
Cl, 8.56; N, 3.38; S, 7.75. Found: C, 66.49; H, 5.72; Cl, 8.72;
N, 3.18; S, 7.80.
1506, 1274, 1241, 1150 cm21; H NMR d 1.02 (3H, t,
Jˆ7 Hz), 1.31 (3H, s), 3.76 (3H, s), 3.83±4.10 (2H, m),
4.20 (1H, s), 6.75±6.85 (4H, m), 7.33±7.43 (5H, m). MS
m/z (%) 311 (M1, 21), 282 (14), 238 (39), 189 (37), 148
(100). Calcd for C19H21NO3: M, 311.1520. Found: m/z
311.1515.
(E)-2-Decyl-2-ethoxycarbonyl-1-(4-methoxyphenyl)-3-
phenylaziridine (25b). Colorless oil; IR (neat) 1724 (CO),
1507, 1241, 1177 cm21; H NMR d 0.88 (3H, t, Jˆ7 Hz),
1
1.02 (3H, t, Jˆ7 Hz), 1.12±1.48 (18H, m), 3.76 (3H, s),
3.93±4.02 (2H, m), 4.13 (1H, s), 6.75±6.85 (4H, m),
7.28±7.44 (5H, m). MS m/z (%) 437 (M1, 52), 408 (31),
364 (45), 276 (100), 274 (58). Calcd for C28H39NO3: M,
437.2929. Found: m/z 437.2924.
(1Rp, 2Rp)-2-Chloro-1-(4-methoxyphenylamino)-1-phenyl-
2-(p-tolylsul®nyl)dodecane (23b). Colorless crystals; mp
127±1308C (AcOEt-hexane). IR (KBr) 3293 (NH), 1514,
1251, 1039 (SO) cm21
;
1H NMR d 0.88 (3H, t, Jˆ
6.4 Hz), 1.2±2.0 (18H, m), 2.36 (3H, s), 3.68 (3H, s), 4.06
(1H, s), 6.23, 6.60 (each 2H, d, Jˆ9 Hz), 7.1±7.7 (9H,
m). MS m/z (%) 539 (M1, 0.6), 399 (100), 272 (82).
Anal. Calcd for C32H42ClNO2S: C, 71.15; H, 7.84; Cl, 6.56,
N, 2.59; S, 5.94. Found: C, 71.36; H, 7.82; Cl, 6.67; N, 2.41;
S, 5.99.
Ethyl 2-benzyl-2-(4-methoxyphenyl)aminopropionate
(26a). To a solution of 25a (185 mg; 0.59 mmol) in distilled
methanol (10 ml) was added 45 mg of Pd(OH)2 (10% on
carbon). The reaction mixture was stirred under H2 atmos-
phere for 1 h. The catalyst was ®ltered off and the methanol
was evaporated to give a residue, which was puri®ed by
silica gel column chromatography to give 125 mg (67%)
of 26a as a colorless oil. IR (neat) 3400 (NH), 1729 (CO),
(E)-2-Methyl-1-(4-methoxyphenyl)-3-phenyl-2-(p-tolyl-
sul®nyl)aziridine (24a). To a solution of 23a (621 mg;
1.5 mmol) in a mixture of THF (25 ml) and t-BuOH
(25 ml) at 708C was added a suspension of t-BuOK
(450 mg; 4 mmol) in 5 ml of t-BuOH. The reaction mixture
was stirred at 708C for 40 min. After cooling the reaction
mixture to room temperature, the reaction was quenched by
sat. aq. NH4Cl. The whole was extracted with a mixture of
benzene±ether. The product was puri®ed by silica gel
column chromatography to give 24a (532 mg; 94%) as
colorless crystals; mp 88±918C (AcOEt±hexane). IR
1513, 1239 cm21; H NMR d 1.19 (3H, t, Jˆ7 Hz), 1.42
1
(3H, s), 3.15, 3.24 (each 1H, d, Jˆ13 Hz), 3.75 (3H, s), 4.16
(2H, q, Jˆ7 Hz), 6.65, 6.76 (each 2H, d, Jˆ8.8 Hz), 7.10±
7.32 (5H, m). MS m/z (%) 313 (M1, 10), 240 (32), 222
(100), 148 (67), 91 (13). Calcd for C19H23NO3: M,
313.1676. Found: m/z 313.1672.
Ethyl 2-benzyl-2-(4-methoxyphenyl)aminododecanoate
(26b). Colorless oil; IR (neat) 3407 (NH), 1731 (CO),
1
1513, 1239, 1195, 1040 cm21; H NMR d 0.88 (3H, t,
1
(KBr) 1505, 1238, 1228, 1046 (SO) cm21; H NMR d
Jˆ7 Hz), 1.10±1.46 (21H, m), 3.21, 3.32 (each 1H, d,
Jˆ13 Hz), 3.77 (3H, s), 4.10±4.23 (2H, m), 6.63±6.79
(4H, m), 6.99±7.26 (5H, m). MS m/z (%) 439 (M1, 7),
348 (100), 274 (17). Calcd for C28H41NO3: M, 439.3087.
Found: m/z 439.3090.
1.03 (3H, s), 2.41 (3H, s), 3.78 (3H, s), 4.51 (1H, s), 6.86,
6.98 (each 2H, d, Jˆ9 Hz), 7.2±7.7 (9H, m). MS m/z (%)
377 (M1, 7), 361 (25), 238 (52), 212 (63), 148 (100). Anal.
Calcd for C23H23NO2S: C, 73.18; H, 6.14; N, 3.71; S, 8.49.
Found: C, 73.31; H, 6.01; N, 3.52; S, 8.51.
Ethyl 2-amino-2-benzylpropionate (27a). A solution of
CAN (804 mg; 1.47 mmol) in 7 ml of water was added to
a solution of 26a (92 mg; 0.29 mmol) in 9 ml of CH3CN at
08C with stirring. The reaction mixture was stirred at 08C for
30 min, then the solution was neutralized with 5% aq.
NaHCO3. Na2SO3 (110 mg) was added to the reaction
mixture with stirring and after 10 min, the whole was
extracted with ethyl acetate. The product was puri®ed by
silica gel column chromatography to afford 46.2 mg (76%)
of 27a as a colorless oil. IR (neat) 3376, 3310 (NH), 1730
(E)-2-Decyl-1-(4-methoxyphenyl)-3-phenyl-2-(p-tolylsul-
®nyl)aziridine (24b). Colorless oil; IR (neat) 1505, 1241,
1
1084, 1057 (SO) cm21; H NMR d 0.88 (3H, t, Jˆ7 Hz),
1.0±1.3 (16H, m), 1.6±1.8 (2H, m), 2.41 (3H, s), 3.78 (3H,
s), 4.62 (1H, s), 6.87, 7.05 (each 2H, d, Jˆ9 Hz), 7.2±7.7
(9H, m). MS m/z (%) 503 (M1, trace), 478 (1.4), 364 (28),
274 (100). Calcd for C32H41NO2S: M, 503.2858. Found: m/z
503.2869.
1
(E)-2-Ethoxycarbonyl-1-(4-methoxyphenyl)-2-methyl-3-
phenylaziridine (25a). To a solution of 24a (280 mg;
0.74 mmol) in 25 ml of dry THF in a ¯ame-dried ¯ask
was added MeMgBr (0.96 mmol) at 2508C with stirring.
The reaction mixture was stirred at 2508C for 15 min, then
the solution was cooled to 2808C. t-BuLi (1.48 mmol) was
added to the reaction mixture dropwise with stirring and
after 1 min, ethyl chloroformate 0.27 ml (2.8 mmol) was
added. The reaction mixture was stirred for 1 min, then
the reaction was quenched by adding sat. aq. NH4Cl. The
whole was extracted with ether±benzene. The product was
puri®ed by silica gel ¯ash chromatography to afford 25a
(187 mg; 81%) as a colorless oil. IR (neat) 1723 (CO),
(CO), 1194, 1104 cm21; H NMR d 1.26 (3H, t, Jˆ7 Hz),
1.39 (3H, s), 2.80, 3.13 (each 1H, d, Jˆ13 Hz), 4.10±4.20
(2H, m), 7.10±7.40 (5H, m). MS (FAB) m/z (%) 208
([M1H]1, 100), 134 (52), 116 (21), 91 (17). Calcd for
C12H18NO2: M, 208.1338. Found: m/z 208.1341.
Ethyl 2-amino-2-benzyldodecanoate (27b). Colorless oil;
1
IR (neat) 3388 (NH), 1732 (CO), 1182, 1031 cm21; H
NMR d 0.88 (3H, t, Jˆ7 Hz), 1.10±1.70 (22H, m), 1.85±
1.95 (1H, m), 2.76, 3.18 (each 1H, d, Jˆ13 Hz), 4.09±4.23
(2H, m), 7.10±7.40 (5H, m). MS (FAB) m/z (%) 334
([M1H]1, 100), 260 (51), 242 (21), 91 (15). Calcd for
C21H36NO2: M, 334.2746. Found: m/z 334.2734.

T. Satoh et al. / Tetrahedron 56 (2000) 4415±4425
4425
7. Oae, S. In Revies on Heteroatom Chemistry; MYU: Tokyo,
1991; 4, p 195; Satoh, T. J. Syn. Org. Chem. Jpn. 1996, 54, 481.
8. Preliminary results of this study were reported as a communi-
cation: Satoh, T.; Ozawa, M.; Takano, K.; Kudo, M. Tetrahedron
Lett. 1998, 39, 2345.
Acknowledgements
This work was supported by Grants-in-Aid for Scienti®c
Research No. 08672451 and No. 11640545 from the
Ministry of Education, Science, Sports, and Culture, and
the Fugaku Foundation for Drug Discovery, which are
gratefully acknowledged.
9. Satoh, T.; Horiguchi, K. Tetrahedron Lett. 1995, 36, 8235.
Satoh, T.; Kobayashi, S.; Nakanishi, S.; Horiguchi, K.; Irisa, S.
Tetrahedron 1999, 55, 2515.
10. Atkinson, R. S.; Coogan, M. P.; Lochrie, I. S. T. Tetrahedron
Lett 1996, 37, 5179. Davis, F. A.; Liu, H.; Reddy, G. V.;
Tetrahedron Lett. 1996, 37, 5473. Choi, S.-K.; Lee, J.-S.; Kim,
J.-H.; Lee, W. K. J. Org. Chem. 1997, 62, 743. Davis, F. A.;
Liang, C.-H.; Liu, H. J. Org. Chem. 1997, 62, 3796. Kim, D. Y.;
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