Cross-coupling of nonstabilized aziridinylmagnesiums with alkylhalides catalyzed by Cu(I) iodide: A new synthesis of amines bearing a quaternary chiral center and an asymmetric synthesis of both enantiomers of the amines from one chiral starting material

Article abstract of DOI:10.1016/S0040-4020(01)00278-2

Treatment of sulfinylaziridines, which were synthesized from 1-chloroalkyl p-tolyl sulfoxides and imines, with ethylmagnesium bromide gave nonstabilized aziridinylmagnesiums by a sulfoxide-magnesium exchange reaction. The cross-coupling of the aziridinylmagnesiums with various kinds of alkylhalides was realized in high yields by using Cu(I) iodide as a catalyst, and the reaction was found to be stereospecific. The coupling products were hydrogenated with Pd(OH)₂ in alcohol to give the amines bearing a quaternary chiral center in quantitative yields. Synthesis of both enantiomers of the amines bearing a quaternary chiral center was realized starting from optically active (R)-chloromethyl p-tolyl sulfoxide in good overall yields with perfect asymmetric induction.

Full text of DOI:10.1016/S0040-4020(01)00278-2

TETRAHEDRON
Pergamon
Tetrahedron 57 ,2001) 3891±3898
Cross-coupling of nonstabilized aziridinylmagnesiums with
alkylhalides catalyzed by CuꢀI) iodide: a new synthesis of amines
bearing a quaternary chiral center and an asymmetric synthesis of
both enantiomers of the amines from one chiral starting material
Tsuyoshi Satoh,p Rie Matsue, Toshinari Fujii and Satoshi Morikawa
Department of Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Received 24 January 2001; accepted 28 February 2001
AbstractÐTreatment of sul®nylaziridines, which were synthesized from 1-chloroalkyl p-tolyl sulfoxides and imines, with ethylmagnesium
bromide gave nonstabilized aziridinylmagnesiums by a sulfoxide-magnesium exchange reaction. The cross-coupling of the aziridinylmag-
nesiums with various kinds of alkylhalides was realized in high yields by using Cu,I) iodide as a catalyst, and the reaction was found to be
stereospeci®c. The coupling products were hydrogenated with Pd,OH)2 in alcohol to give the amines bearing a quaternary chiral center in
quantitative yields. Synthesis of both enantiomers of the amines bearing a quaternary chiral center was realized starting from optically active
,R)-chloromethyl p-tolyl sulfoxide in good overall yields with perfect asymmetric induction. q 2001 Elsevier Science Ltd. All rights
reserved.
Asymmetric synthesis of a quaternary carbon center has
been a formidable but quite interesting challenge in
synthetic organic chemistry.1 Especially, amino compounds
in which a nitrogen is bound to a stereogenic carbon have
received wide attention these days, because these amines,
including quaternary a-amino acids2 and quaternary
b-amino acids,3 are medicinally and biochemically quite
important. However, few methods for the creation of a
chiral quaternary carbon center bound to an amino group
have so far been reported.4
4a5 and aziridinylmagnesiums 4b6 from sul®nylaziridines 3,
which were easily synthesized from 1-chloroalkyl p-tolyl
sulfoxides 1 and imines via the adducts 2, with an alkyl-
lithium or Grignard reagent by sulfoxide-metal exchange.7
The aziridinyllithiums were ethoxycarbonylated and in two
steps they were derived to the a,a-dialkylamino acid
esters.5 In continuation of our studies on the generation of
aziridinylmetals 48 from sul®nylaziridines 3 and develop-
ment of the chemistry to new synthetic methods, here we
describe in detail a cross-coupling of the aziridinylmag-
nesiums 4b with alkylhalides and synthesis of amines bear-
ing a quaternary chiral carbon 6.9 A novel synthesis of both
We previously reported the generation of aziridinyllithiums
Scheme 1.
Keywords: sulfoxide-magnesium exchange; aziridinylmagnesium; cross-coupling; quaternary chiral center; asymmetric synthesis of amines.
Corresponding author. Tel.: 181-3-3260-4271; fax: 181-3-3235-2214; e-mail: tsatoh@ch.kagu.sut.ac.jp
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020,01)00278-2

3892
T. Satoh et al. / Tetrahedron 57 ,2001) 3891±3898
Scheme 2.
enantiomers of the amines 6 from one chiral starting
material, ,R)-chloromethyl p-tolyl sulfoxide, was also
quite successful by this method ,Scheme 1).
equivalents) is added to the reaction mixture. In the case of
iodoethane, the reaction with 10 mol% of Cu,I) iodide at
room temperature for 30 min gave the coupling product 9 in
86% yield as a single product ,Scheme 2).
The stereochemistry of the product 9 was investigated with
the H NMR NOESY spectrum. Clear nOe between the
1. Results and discussion
1
hydrogen on the aziridine ring and the methyl group of
the ethyl substituent was observed. From this result, the
structure of 9 was unambiguously determined to be E. At
the same time, it developed that the stereochemistry of the
carbon bearing the sul®nyl group of 7 was retained; namely,
this reaction took place stereospeci®cally.
1.1. Cross-coupling of the aziridinylmagnesiums with
alkylhalides in the presence of CuꢀI) iodide as a catalyst
In a previous paper, we reported the synthesis of sul®nyl-
aziridine 7 and generation of the aziridinylmagnesium 8
from 7 with EtMgBr.6 The aziridinylmagnesium 8 was
found to be stable even at room temperature for several
hours; however, nucleophilicity of 8 was low and, for
example, the reaction of 8 with iodomethane did not take
place at all.6 We recently reinvestigated the cross-coupling
of 8 with alkylhalides by using metal catalysts.10 After
some examination, we found that Cu,I) iodide worked
excellently.11
The results for the cross-coupling of the aziridinylmag-
nesium 8 with several halides are summarized in Table 1.
Entries 1±3 show that primary iodoalkanes gave quite good
yields of the desired cross-coupling products. The reaction
of allyl bromide and benzyl bromide with 8 took place even
more vigorously to give the desired products in high yields
within 5 min at 08C ,entries 4 and 5).
A representative example is reported as follows. To a solu-
tion of EtMgBr ,3.5 equivalents) in THF at 2788C is added
dropwise a solution of 7 in a minimum amount of THF. At
this stage, EtMgBr does not react with 7 at all; however, the
trace moisture in the solution is completely removed by the
Grignard reagent. After 10 min, the cooling bath is removed
,or replaced with an ice bath) and the reaction mixture is
stirred for 30 min. By this treatment the sulfoxide-metal
exchange takes place and the aziridinylmagnesium 8 is
obtained quantitatively. To this solution, powdered and
dried Cu,I) iodide is added and the reaction mixture is
stirred for 5 min. Finally, the appropriate alkylhalide ,3.5
In contrast to these good results, secondary iodoalkane,
2-iodopropane, did not react with 8 even though 40 mol%
of Cu,I) iodide and longer reaction time were used ,entry 6).
In order to develop the presented method to a new synthesis
of aziridines having functional groups, iodoacetonitrile,
ethyl iodoacetate, bromoacetaldehyde diethyl acetal, and
THP-protected iodoethanol were treated with 8; however,
all these reactions failed ,entries 7±10). Finally, reaction
with iodobenzene was tried ,entry 11); however, this
again gave none of the desired cross-coupling product.
We investigated this cross-coupling reaction with other
Table 1. Generation of aziridinylmagnesium 8 and cross-coupling with alkyl halides
Conditions
8C ,min)
Entry
R3X
CuI/mol%
Yield/%a
1
2
3
4
5
6
7
8
CH3I
C5H11I
C10H21I
CH2vCHCH2Br
PhCH2Br
,CH3)2CHI
NCCH2I
EtOCOCH2I
,EtO)2CHCH2Br
THPOCH2CH2I
PhI
10
10
10
10
10
40
40
40
40
40
40
rt ,30)
rt ,30)
rt ,30)
0 ,5)
10a 87
10b 87
10c 94
10d 92
10e 87
0 ,5)
b
0 ,120)
0 ,120)
rt ,180)
rt ,180)
0 ,180)
rt ,120)
±
±
±
±
b
b
b
9
10
11
b
±
b
±
a
1
Isolated yield after silica gel column chromatography. All the products were fully characterized by IR, H NMR, MS ,low and high-resolution).
A complex mixture.
b

T. Satoh et al. / Tetrahedron 57 ,2001) 3891±3898
Table 2. Generation of aziridinylmagnesium 12 and cross-coupling with alkyl halides
3893
Conditions
8C ,min)
Entry
R3X
CuI/mol%
Yield/%a
1
2
3
4
5
CH3I
C5H11I
C10H21I
CH2vCHCH2Br
PhCH2Br
10
10
10
10
10
rt ,30)
rt ,30)
rt ,30)
0 ,10)
0 ,10)
13a 94
13b 88
13c 83
13d 90
13e 94
6
10
0 ,15)
13f 93
7
8
9
10
11
12
CH2Br2
CH2I2
TBDMSOCH2CH2I
EtOCOCH2I
NCCH2I
10
20
40
10
20
20
rt ,15)
rt ,20)
rt ,180)
rt ,15)
rt ,20)
rt ,20)
13g 15
±
c
13h 66 b
d
±
±
c
c
CH3OCH2Cl
±
13
H3COCOCl
20
rt ,20)
14 83e
a
1
Isolated yield after silica gel column chromatography. All the products were fully characterized by IR, H NMR, MS ,low and high-resolution).
This product was isolated after deprotection of the TBDMS group by treatment of the initial product with TBAF.
A complex mixture.
b
c
d
e
The main product is the reduced aziridine 13 ,R3ˆH, 85% yield).
Single isomer. The structure has not been determined.
metal catalysts, for example, Pd,11a Fe,12a Ni;12b however,
these reactions only gave a complex mixture.
momethane gave the desired product 13g in low yield;
however, diiodomethane gave only a complex mixture
,entries 7 and 8). The reaction with TBDMS-protected
2-iodoethanol was found to be successful; however, this
reaction required 40 mol% of Cu,I) iodide and longer reac-
tion time. The product was isolated as an alcohol after treat-
ment of the initial product with TBAF ,entry 9). The
reactions with ethyl iodoacetate, iodoacetonitrile, and
chloromethyl methyl ether were unsuccessful ,entries
10±12). Methyl chlorocarbonate reacted with the nitrogen
of the aziridinyl magnesium 12 to give ring-opened product
14 in good yield ,entry 13).
In order to discover the steric effect of this cross-coupling
reaction at the carbon bearing the magnesium, the sul®nyl-
aziridine having decyl group 11 was synthesized and the
reaction was investigated ,Table 2). As shown in Table 2,
primary iodoalkanes gave high to quantitative yields of the
desired cross-coupling products ,entries 1±3). Allyl bro-
mide and benzyl bromide also gave almost quantitative
yields of the products ,entries 4±6). No difference in reac-
tivity between the aziridinyl magnesiums 8 and 12 with
these haloalkanes was observed. The reaction with dibro-
1.2. Hydrogenolysis of the cross-coupling products
Table 3. Hydrogenation of the alkylated aziridines to the amines bearing a
quaternary chiral center
It has been known that aziridines are highly strained, and
many types of ring-opening are possible.13 We planned ring-
opening of the cross-coupling products between the nitrogen
and the benzylic carbon. The reaction would give us the
amines bearing a quaternary carbon. We investigated the
hydrogenolysis of the aziridines 9, 10c, and 13 and found
that Pd,OH)2 on carbon worked excellently.14
Pd,OH)2
weight %
Entry
R1
R2
Yield/%
As shown in Table 3, the hydrogenolysis of the aziridines
was conducted in a mixture of methanol and ethanol,
because the solubility of 9, 10c, and 13 is somewhat low
in methanol. The reaction took place excellently when 100±
300 weight percent of 20% Pd,OH)2 on carbon was used.
However, when these reactions were conducted with less
amount of Pd,OH)2, considerable amounts of the starting
materials remained. Prolonging these reactions was found
not to be effective. It is worth noting that the product in entry
7 is g,g-disubstituted g-amino alcohol.
1
2
3
4
5
9
10c
13a
CH3
CH3
C10H21
C2H5
C10H21
CH3
C5H11
PhCH2
13
15a 98
15b 99
15b 93
15c 98
15d 97
200
120
300
300
13b C10H21
C10H21
13e
6
13f
C10H21
140
200
15e 98
15f 95a
7
13h C10H21
HOCH2CH2
a
Methanol was used as the solvent.

3894
T. Satoh et al. / Tetrahedron 57 ,2001) 3891±3898
Scheme 3. Asymmetric synthesis of both enantiomers of the optically active amines starting from one chiral starting material, ,R)-chloromethyl p-tolyl
sulfoxide 16
1.3. The asymmetric synthesis of both enantiomers of the
amines bearing a quaternary chiral carbon from one
chiral starting material
was decylated to give 17 as a mixture of two diastereomers.
The lithium a-carbanion of 17 was added to benzalaniline
to afford stereoselectively only one adduct 18, which was
treated with potassium tert-butoxide to give the optically
active sul®nylaziridine ,2)-11 in high overall yield. As
already reported, the absolute con®guration of the sul®nyl-
aziridine ,2)-11 was determined to be as shown in
Scheme 3.6
As shown in Scheme 1, the ®nal products amines 6 have two
substituents, R1 and R2, on the stereogenic carbon. The ®rst
one ,R1) is introduced into the sul®nylaziridines 3 from 1 via
the adducts 2. The addition of the lithium a-sul®nyl carb-
anion of 1 to the imine was found to be highly stereoselec-
tive.6 The second one ,R2) is introduced into the aziridine
ring stereospeci®cally as described above. If the order of the
introduction of the two substituents is changed and optically
active sulfoxide is used, we would be able to obtain both
enantiomers of the amines bearing a quaternary chiral center
from one chiral starting material, ,R)-chloromethyl p-tolyl
sulfoxide 1615 ,Scheme 3).
The optically active ,2)-11 was treated with 3.5 equivalents
of EtMgBr followed by iodomethane in the presence of 10
mol% of Cu,I) iodide to give the aziridine ,2)-13a in 94%
yield. The reaction with 3-,4-methoxyphenyl)-1-iodopro-
pane gave ,2)-19 in somewhat lower yield ,60%). The
aziridines were hydrogenolized with Pd,OH)2 in a mixture
of methanol-ethanol to give ,S)-,1)-15b and ,R)-,1)-20 in
almost quantitative yields. The optical purity of these two
amines was easily determined by using a chiral stationary
First, optically pure ,R)-chloromethyl p-tolyl sulfoxide 16

T. Satoh et al. / Tetrahedron 57 ,2001) 3891±3898
3895
column ,CHIRALCEL OD ,Daicel); hexane or hexane:
2-propanolˆ200:1 as a developing solvent). The enantio-
meric excess ,ee) of both amines was found to be over 99%.
,about 0.5 ml) of dry THF was added dropwise with stirring
to a solution of EtMgBr ,1.02 mol/l in THF; 0.83 ml, 0.84
mmol) in 5 ml of THF in a ¯ame-dried ¯ask at 2788C. After
being stirred for 10 min, the cooling bath was removed and
the reaction mixture was allowed to warm to room tempera-
ture and stirred for 30 min to give aziridinylmagnesium 8.
To this solution, Cu,I) iodide ,4 mg, 10 mol%) was added
and after 5 min, iodoethane ,0.067 ml, 0.84 mmol) was
added and the reaction mixture was stirred for 30 min.
The reaction was quenched by adding saturated aqueous
NH4Cl and the solution was extracted with CHCl3. The
organic layer was dried over MgSO4 and the solvent was
evaporated to give an oil, which was puri®ed by silica gel
column chromatography to afford 49 mg ,86%) of 9 as a
colorless oil. IR ,neat) 3026, 2962, 2924, 1598, 1493, 1269
Next, we tried to synthesize the enantiomers of the amines
from the same starting sulfoxide ,R)-16. ,R)-Chloromethyl
p-tolyl sulfoxide 16 was alkylated with iodomethane and
3-,4-methoxyphenyl)-1-iodopropane to give 21a and 21b,
respectively, in high yields as a mixture of two diastereo-
mers. The products were again treated with lithium diiso-
propylamide followed by benzalaniline to afford the adducts
22a and 22b stereoselectively as single isomers. These were
treated with potassium tert-butoxide to give the sul®nyl-
aziridines ,2)-7 and ,2)-23 in good overall yields. Genera-
tion of the aziridinylmagnesiums and the cross-coupling
with iododecane were carried out as described above to
give the desired aziridines ,2)-10c and ,2)-24. The yield
of the optically active aziridine ,2)-10c was excellent;
however, again the cross-coupling with 3-,4-methoxy-
phenyl)-1-iodopropane gave somewhat lower yield. The
hydrogenolysis of the aziridines ,2)-10c and ,2)-24 gave
the amines ,R)-,2)-15b and ,S)-,2)-20, respectively, in
93% and 95% yields. As shown in Scheme 3, the values
of the speci®c rotation of the optically active amines 15b
and 20 are almost the same; however, the signs are opposite.
The enantiomeric excess of the products ,R)-,2)-15b and
,S)-,2)-20 was determined with a chiral column as
described above and ee of these amines was found to be
over 99%.
1
cm21; H NMR d 0.86±0.94 ,1H, m), 1.07 ,3H, t, Jˆ7.5
Hz), 1.09 ,3H, s), 1.69±1.76 ,1H, m), 3.13 ,1H, s), 6.88±
7.00 ,3H, m), 7.20±7.41 ,7H, m). MS m/z ,%) 237 ,M1, 37),
167 ,75), 91 ,100). Calcd for C17H19N: M, 237.1516. Found:
m/z 237.1510.
2.1.3. 2,2-Dimethyl-1,3-diphenylaziridine ꢀ10a). Color-
1
less oil; IR ,neat) 2955, 2922, 1597, 1488, 1255 cm21; H
NMR d 1.11 ,3H, s), 1.17 ,3H, s), 3.14 ,1H, s), 6.91±6.98
,3H, m), 7.22±7.43 ,7H, m). MS m/z ,%) 223 ,M1, 42), 208
,18), 167 ,100). Calcd for C16H17N: M, 223.1359. Found:
m/z223.1359.
2.1.4. ꢀE)-2-Methyl-2-pentyl-1,3-diphenylaziridine ꢀ10b).
Colorless oil; IR ,neat) 3027, 2929, 1597, 1487, 1270 cm21
;
In conclusion, we have established a new method for
synthesizing amines bearing a quaternary chiral carbon
from 1-chloroalkyl p-tolyl sulfoxides, imines, and alkyl-
halides. The key step of this method is the generation of
aziridinylmagnesiums and stereospeci®c cross-coupling of
the anions with alkylhalides. Based on the presented
method, we were able to synthesize both enantiomers of
the amines from one chiral starting material, ,R)-chloro-
methyl p-tolyl sulfoxide, in optically pure form.
1H NMR d 0.70±0.85 ,1H, m), 0.89 ,3H, t, Jˆ6.7 Hz), 1.10
,3H, s), 1.20±1.80 ,7H, m), 3.12 ,1H, s), 6.90±7.00 ,3H, m),
7.18±7.44 ,7H, m). MS m/z ,%) 279 ,M1, 30), 236 ,59), 167
,60), 118 ,60), 91 ,100). Calcd for C20H25N: M, 279.1985.
Found: m/z 279.1970.
2.1.5. ꢀE)-2-Decyl-2-methyl-1,3-diphenylaziridine ꢀ10c).
Colorless oil; IR ,neat) 2924, 2853, 1598, 1488, 1266
1
cm21; H NMR d 0.78 ,2H, m), 0.88 ,3H, t, Jˆ7.0 Hz),
1.08 ,3H, s), 1.24 ,10H, m), 1.42±1.77 ,6H, m), 3.13 ,1H, s),
6.91±6.97 ,3H, m), 7.20±7.42 ,7H, m). MS m/z ,%) 349
,M1, 25), 236 ,75), 91 ,100). Calcd for C25H35N: M,
349.2767. Found: m/z 349.2767. ꢀ2)-10c: Colorless oil;
[a]D29 2106.68 ,c 0.1, acetone).
2. Experimental
2.1. General
2.1.6. ꢀE)-2-Allyl-2-methyl-1,3-diphenylaziridine ꢀ10d).
Colorless oil; IR ,neat) 3062, 3029, 1639, 1596, 1488,
Melting points were measured with a Yanagimoto micro
melting point apparatus and are uncorrected. 1H NMR spec-
tra were measured in a CDCl3 solution with JEOL JNM-LA
400 and 500 spectrometer. Electron-impact mass spectra
,MS) were obtained at 70 eV by direct insertion. Silica
gel 60 ,MERCK) containing 0.5% ¯uorescence reagent
254 and a quartz column were used for column chroma-
tography and the products having UV absorption were
detected by UV irradiation. In experiments requiring a dry
solvent, THF was distilled from benzophenone ketyl;
HMPA and diisopropylamine were distilled from CaH2.
1
1264 cm21; H NMR d 1.10 ,3H, s), 1.67 ,1H, dd, Jˆ6.7,
14 Hz), 2.44 ,1H, dd, Jˆ6.7, 14 Hz), 3.22 ,1H, s), 5.06 ,1H,
d, Jˆ5.0 Hz), 5.09 ,1H, s), 5.83±5.91 ,1H, m), 6.93±6.98
,3H, m), 7.22±7.41 ,7H, m). MS m/z ,%) 249 ,M1, 37), 248
,100), 234 ,30). Calcd for C18H19N: M, 249.1515. Found:
m/z 249.1497.
2.1.7. ꢀE)-2-Benzyl-2-methyl-1,3-diphenylaziridine ꢀ10e).
Colorless oil; IR ,neat) 3060, 3027, 2923, 1598, 1487, 1261
cm21; 1H NMR d 1.04 ,3H, s), 2.16 ,1H, d, Jˆ14 Hz), 3.00
,1H, d, Jˆ14 Hz), 3.52 ,1H, s), 7.00±7.13 ,3H, m), 7.23±
7.37 ,12H, m). MS m/z ,%) 299 ,M1, 60), 208 ,76), 167
,100), 91 ,87). Calcd for C22H21N: M, 299.1672. Found: m/z
299.1664.
2.1.1. Sul®nylaziridines 7, 11, ꢀ2)-7, and ꢀ2)-11. The
synthesis of these sul®nylaziridines has been reported in a
previous paper; see lit.6
2.1.2. ꢀE)-2-Ethyl-2-methyl-1,3-diphenylaziridine ꢀ9). A
solution of 7 ,80 mg, 0.24 mmol) in a minimum amount
2.1.8. ꢀZ)-2-Decyl-2-methyl-1,3-diphenylaziridine ꢀ13a).

3896
T. Satoh et al. / Tetrahedron 57 ,2001) 3891±3898
Colorless oil; IR ,neat) 2924, 2853, 1733, 1598, 1488, 1272
cm21; 1H NMR d 0.87 ,3H, t, Jˆ7.0 Hz), 1.13 ,3H, s), 1.11±
1.46 ,18H, m), 3.15 ,1H, s), 6.90±6.98 ,3H, m), 7.22±7.43
,7H, m). MS m/z ,%) 349 ,M1, 32), 236 ,80), 91 ,100).
Calcd for C25H35N: M, 349.2767. Found: m/z 349.2764.
ꢀ2)-13a: Colorless oil; [a]D28 280.08 ,c 0.17, acetone).
THF in a ¯ame-dried ¯ask at 2788C. After 10 min, the
reaction mixture was allowed to warm to room temprature
and stirred for 30 min to give aziridinylmagnesium 12. To
this solution, Cu,I) iodide ,76 mg, 40 mol%) was added.
The reaction mixture was stirred for 5 min and then 1-O-
,tert-butyldimethylsilyl)-2-iodoethane ,1 g, 3.5 mmol) was
added and the reaction mixture was stirred for 180 min. To
this solution tetrabutylammonium ¯uoride ,TBAF; THF
solution, 9.8 mmol) was added and the reaction was
monitored on TLC. The reaction was quenched by adding
saturated aqueous NH4Cl and the whole solution was
extracted with CHCl3. The organic layer was dried over
MgSO4 and the solvent was evaporated to give an oil,
which was puri®ed by silica gel column chromatography
to afford 250 mg ,66%) of 13h as a colorless oil; IR
2.1.9. ꢀZ)-2-Decyl-2-pentyl-1,3-diphenylaziridine ꢀ13b).
Colorless oil; IR ,neat) 2925, 2854, 1598, 1488, 1270
1
cm21; H NMR d 0.57±0.63 ,2H, m), 0.88 ,6H, t, Jˆ7.0
Hz), 1.24±1.30 ,16H, m), 1.39±1.44 ,2H, m), 1.45±1.57
,4H, m), 1.85±1.91 ,2H, m), 3.16 ,1H, s), 6.91±6.97 ,3H,
m), 7.21±7.41 ,7H, m). MS m/z ,%) 405 ,M1, 33), 223 ,60),
91 ,100). Calcd for C29H43N: M, 405.3396. Found: m/z
405.3386.
1
,neat) 3385 ,OH), 2925, 2854, 1598, 1488 cm21; H NMR
2.1.10. 2,2-Didecyl-1,3-diphenylaziridine ꢀ13c). Colorless
d 0.88 ,3H, t, Jˆ7.0 Hz), 1.24±1.34 ,18H, m), 1.37±1.43
,1H, m), 1.58 ,1H, m), 2.14 ,1H, ddd, Jˆ6.8, 4.9, 13 Hz),
3.29 ,1H, s), 3.78±3.84 ,2H, m), 6.91±6.99 ,3H, m), 7.22±
7.42 ,7H, m). MS m/z ,%) 379 ,M1, 24), 253 ,30), 167 ,29),
91 ,100). Calcd for C26H37NO: M, 379.2875. Found: m/z
379.2874.
1
oil; IR ,neat) 2923, 2853, 1598, 1488 cm21; H NMR d
0.56±0.62 ,2H, m), 0.88 ,6H, t, Jˆ7.0 Hz), 1.19±1.29
,34H, m), 3.16 ,1H, s), 6.91±6.97 ,3H, m), 7.21±7.41
,7H, m). MS m/z ,%) 475 ,M1, 1), 405 ,17), 335 ,25),
223 ,50), 91 ,100). Calcd for C34H53N: M, 475.4174.
Found: m/z 475.4161
2.1.16. Methyl N-ꢀ1-decyl-2-phenylethenyl)-N-phenyl
carbamate ꢀ14). Colorless oil; IR ,neat) 2924, 2853, 1714
,CO), 1597, 1494, 1439, 1318 cm21; 1H NMR d 0.88 ,3H, t,
Jˆ6.8 Hz), 1.17±1.37 ,14H, m), 1.49±1.58 ,2H, m), 2.32
,2H, t, Jˆ8 Hz), 3.76 ,3H, s), 6.53 ,1H, s), 7.20±7.40 ,10H,
m). MS m/z ,%) 393 ,M1, 78), 302 ,43), 267 ,100). Calcd
for C26H35NO2: M, 393.2668. Found: m/z 393.2671.
2.1.11. ꢀE)-2-Allyl-2-decyl-1,3-diphenylaziridine ꢀ13d).
Colorless oil; IR ,neat) 3062, 3028, 2924, 2853, 1639,
1
1598, 1487, 1261 cm21; H NMR d 0.87 ,3H, t, Jˆ7.0
Hz), 1.23 ,14H, m), 1.40±1.59 ,5H, m), 2.57 ,1H, dd,
Jˆ7.9, 14 Hz), 3.25 ,1H, s), 5.06 ,1H, m), 5.09 ,1H, m),
5.86 ,1H, m), 6.92±6.98 ,3H, m), 7.22±7.40 ,7H, m). MS
m/z ,%) 375 ,M1, 35), 374 ,100), 360 ,9). Cacld for
C27H37N: M, 375.2924. Found: m/z 375.2896.
2.1.17. 1-Methyl-1-phenyl-2-phenylaminododecane ꢀ15b).
Palladium hydroxide ,20 wt% Pd ,dry basis) on carbon; 140
mg, 200 wt%) was added to a solution of 10c ,70.7 mg) in 6
ml of a mixture of MeOH:EtOHˆ 2:1. The reaction mixture
was stirred for 15 min under hydrogen atmosphere. The
catalyst was ®ltered off and the solvent was evaporated
under vacuum to afford 70.7mg ,99%) of pure 15b as a
colorless oil; IR ,neat) 3421 ,NH), 3025, 2925, 2852,
1600, 1496 cm21; 1H NMR d 0.88 ,3H, t, Jˆ7.0 Hz), 1.20
,3H, s), 1.24 ,12H, m), 1.39±1.41 ,2H, m), 1.48±1.56 ,2H,
m), 1.73±1.81 ,2H, m), 2.82 ,1H, d, Jˆ13 Hz), 3.07 ,1H, d,
Jˆ13 Hz), 3.40 ,1H, b), 6.69±6.72 ,3H, m), 7.07±7.42 ,7H,
m). MS m/z ,%) 351 ,M1, 3), 260 ,100). Calcd for C25H37N:
M, 351.2923. Found: m/z 351.2918. ꢀR)-ꢀ2)-15b: Colorless
oli; [a]D28 241.78 ,c 0.14, acetone). ꢀS)-ꢀ1)-15b: Colorless
oli; [a]D32 141.38 ,c 0.11, acetone).
2.1.12. ꢀE)-2-Benzyl-2-decyl-1,3-diphenylaziridine ꢀ13e).
Colorless oil; IR ,neat) 3062, 3027, 2923, 2853, 1599, 1487,
1
1255 cm21; H NMR d 0.79±0.83 ,1H, m), 0.87 ,3H, t,
Jˆ7.0 Hz), 1.20±1.33 ,15H, m), 1.60±1.77 ,2H, m), 2.00
,1H, d, Jˆ14 Hz), 3.14 ,1H, d, Jˆ14 Hz), 3.54 ,1H, s),
6.98±7.03 ,3H, m), 7.20±7.38 ,12H, m). MS m/z ,%) 425
,M1, 10), 167 ,37), 91 ,100). Calcd for C31H39N: M,
425.3080. Found: m/z 425.3079.
2.1.13. ꢀE)-2-Decyl-2-ꢀ4-methylphenyl)methyl-1,3-diphe-
nylaziridine ꢀ13f). Colorless oil; IR ,neat) 3024, 2923,
1
2853, 1597, 1488, 1453, 1270 cm21; H NMR d 0.77 ,2H,
dt, Jˆ4.6, 13 Hz), 0.88 ,3H, t, Jˆ7 Hz), 1.23±1.72 ,16H,
m), 1.95 ,1H, d, Jˆ14 Hz), 2.32 ,3H, s), 3.10 ,1H, d, Jˆ14
Hz), 3.53 ,1H, s), 6.95±7.43 ,14H, m). MS m/z ,%) 439
,M1, 50), 181 ,83), 91 ,100). Calcd for C32H41N: M,
439.3239. Found: m/z 439.3253.
2.1.18. 2-Benzyl-2-phenylaminobutane ꢀ15a). Colorless
oil; IR ,neat) 3415 ,NH), 2968, 1599, 1495, 1453, 1313
1
cm21; H NMR d 0.94 ,3H, t, Jˆ7.7 Hz), 1.17 ,3H, s),
2.1.14. ꢀE)-2-Bromomethyl-2-decyl-1,3-diphenylaziri-
dine ꢀ13g). Colorless oil; IR ,neat) 2924, 2853, 1599,
1.57, 1.85 ,each 1H, dq, Jˆ7.5, 15 Hz), 2.84, 3.07 ,each
1H, d, Jˆ13 Hz), 6.61±6.76 ,3H, m), 7.09±7.31 ,7H, m).
MS m/z ,%) 239 ,M1, 0.9), 148 ,100). Cacld for C17H21N:
M, 239.1688. Found: m/z 239.1680.
1
1488, 1452, 1410 cm21; H NMR d 0.88 ,3H, t, Jˆ7.0
Hz), 1.23±1.81 ,18H, m), 2.96 ,1H, dd, Jˆ1.2, 11 Hz),
3.41 ,1H, s), 3.62 ,1H, d, Jˆ11 Hz), 6.96±7.45 ,10H, m).
MS m/z ,%) 427 ,M1, 0.4), 348 ,56), 244 ,100). Cacld for
C25H34NBr: M, 427.1874. Found: m/z 427.1870.
2.1.19. 6-Benzyl-6-phenylaminohexadecane ꢀ15c). Color-
less oil; IR ,neat) 3417 ,NH), 3027, 2927, 2853, 1600, 1495,
1454 cm21; 1H NMR d 0.87 ,3H, t, Jˆ7.3 Hz), 0.88 ,3H, t,
Jˆ6.6 Hz), 1.24±1.64 ,26H, m), 2.93 ,2H, s), 3.31 ,1H, b),
6.64±6.73 ,3H, m), 7.05±7.27 ,7H, m). MS m/z ,%) 407
,M1, 0.8), 316 ,100). Cacld for C29H45N: M, 407.3550.
Found: m/z 407.3561.
2.1.15. ꢀE)-2-Decyl-2-ꢀ2-hydroxyethyl)-1,3-diphenylaziri-
dine ꢀ13h). A solution of 11 ,473.7 mg, 1 mmol) in a mini-
mum amount ,about 0.5 ml) of dry THF was added dropwise
with stirring to a solution of EtMgBr ,3.5 mmol) in 20 ml of

T. Satoh et al. / Tetrahedron 57 ,2001) 3891±3898
3897
2.1.20. 2-Benzyl-1-phenyl-2-phenylaminododecane ꢀ15d).
Colorless oil; IR ,neat) 3420 ,NH), 2924, 2853, 1600, 1497,
1456 cm21; 1H NMR d 0.82±0.89 ,3H, m), 1.24±1.38 ,18H,
m), 2.90 ,2H, d, Jˆ14 Hz), 3.26 ,2H, d, Jˆ14 Hz), 6.71±
6.76 ,2H, m), 7.13±7.25 ,13H, m). MS m/z ,%) 426
,[M-H]1, 0.5), 336 ,100). Cacld for C31H40N: M,
426.3158. Found: m/z 426.3150.
2.1.26. ꢀ1R*,2R*,R*S)-2-Chloro-5-ꢀ4-methoxyphenyl)-1-
phenyl-1-ꢀphenylamino)-2-ꢀp-tolylsul®nyl)pentane ꢀ22b).
A solution of 21b ,49 mg, 0.14 mmol) in a minimum
amount ,about 0.5 ml) of dry THF was added dropwise
with stirring to a solution of LDA ,0.52 mmol) in 3.6 ml
of THF in a ¯ame-dried ¯ask at 2608C. After 10 min, a
solution of benzalaniline ,94 mg, 0.52 mmol) in THF was
added to the reaction mixture and the reaction mixture was
stirred for 10 min. The reaction was quenched with saturated
aqueous NH4Cl. The whole solution was extracted with
CHCl3. The organic layer was dried over MgSO4, and the
solvent was evaporated to give an oil, which was puri®ed by
silica gel column chromatography to give racemic 22b ,74
mg, 98%) as crystals. Recrystallization of the product from
AcOEt-hexane gave colorless crystals; mp 151±152.58C. IR
2.1.21. 2-Benzyl-1-ꢀ4-methylphenyl)-2-phenylaminodo-
decane ꢀ15e). Colorless oil; IR ,neat) 3386 ,NH), 2922,
1
2851, 1600, 1598, 1508, 1496, 1456 cm21; H NMR d
0.87 ,3H, t, Jˆ7.0 Hz), 1.20±1.54 ,18H, m), 2.30 ,3H, s),
2.89 ,2H, t, Jˆ14 Hz), 3.23 ,2H, t, Jˆ14 Hz), 3.45 ,1H, bs),
6.70±6.77 ,3H, m), 7.03±7.25 ,11H, m). MS m/z ,%) 441
,M1, 0.3), 440 ,0.8), 350 ,60), 336 ,100). Calcd for
C32H43N: M, 441.3395. Found: m/z 441.3384.
,KBr) 3291 ,NH), 2952, 1700, 1512, 1244, 1037 ,SO) cm21
;
1H NMR d 1.92±2.74 ,6H, m), 2.34 ,3H, s), 3.79 ,3H, s),
4.14 ,1H, s), 6.26±7.70 ,18H, m). MS m/z ,%) 517 ,M1,
0.2), 377 ,26), 140 ,34), 121 ,100). Anal. Cacld for
C31H32ClNO2S: C, 71.93; H, 6.23; Cl, 6.76; N, 2.71; S,
6.19. Found: C, 71.62; H, 6.12; Cl, 7.02; N, 2.69; S, 6.12.
High Mass: M, 517.1842. Found: m/z 517.1848. ꢀ1R,2R,RS)-
ꢀ2)-22b: Colorless crystals; mp 167±1688C ,Hex:EtOAcˆ
1:1); IR ,KBr) 3294 ,NH), 2952, 1700, 1599, 1512, 1246,
1037 ,SO) cm21; [a]D23 22308 ,c 0.1, CHCl3).
2.1.22. 3-Benzyl-3-phenylamino-1-tridecanol ꢀ15f).
Colorless oil; IR ,neat) 3370 ,NH, OH), 2925, 2853,
1
1600, 1496 cm21; H NMR d 0.89 ,3H, t, Jˆ7.0 Hz),
1.20±1.60 ,18H, m), 1.88 ,1H, m), 2.03 ,1H, m), 2.9 ,1H,
d, Jˆ11 Hz), 3.05 ,1H, d, Jˆ11 Hz), 3.83±3.91 ,2H, m),
6.77±7.28 ,10H, m). MS m/z ,%) 381 ,M1, 1), 290 ,100).
Calcd for C26H39NO: M, 381.3031. Found: m/z 381.3036.
2.1.23. ꢀ2R,3R)-ꢀ2)-2-Decyl-2-[3-ꢀ4-methoxyphenyl)pro-
pyl]-1,3-diphenylaziridine ꢀ19). Colorless oil; IR ,neat)
2.1.27. ꢀ2R*,3R*,R*S)-2-[3-ꢀ4-Methoxyphenyl)propyl]-2-
ꢀp-tolylsul®nyl)-1,3-diphenylaziridine ꢀ23). To a solution
of 22b ,174 mg, 0.34 mmol) in a 1:1 mixture of t-BuOH-
THF ,8.6 ml) was added 110 mg ,0.98 mmol) of t-BuOK.
The reaction mixture was stirred and heated at 708C for 20
min. The reaction was quenched with saturated aqueous
NH4Cl and the whole was extracted with CHCl3. The
organic layer was washed with water and dried over
MgSO4. After usual work-up, the product was puri®ed by
silica gel column chromatograpyh to give 127.8 mg ,79%)
of 23 as colorless crystals; mp 170±1718C ,Hex:EtOAcˆ
1:1); IR ,KBr) 3027, 2920, 1595, 1509, 1253, 1034 ,SO)
1
2923, 2853, 1597, 1513, 1487, 1453, 1246 cm21; H NMR
d 0.70 ,1H, m), 0.88 ,3H, t, Jˆ6.8 Hz), 0.91±0.95 ,1H, m),
1.24±2.47 ,20H, m), 2.43±2.61 ,2H, m), 3.17 ,1H, s), 3.79
,3H, s), 6.80±7.40 ,14H, m). MS m/z ,%) 483 ,M1, 26), 362
,100). Calcd for C34H45NO: M, 483.3501. Found: m/z
483.3489. [a]D27 271.68 ,c 0.18, acetone).
2.1.24. ꢀR)-ꢀ1)-4-Benzyl-1-ꢀ4-methoxyphenyl)-4-phenyl-
aminotetradecane ꢀ20). Colorless oil; IR ,neat) 3422 ,NH),
2924, 2853, 1600, 1513, 1456, 1246 cm21; 1H NMR d 0.88
,3H, t, Jˆ7.0 Hz), 1.20±1.30 ,20H, m), 1.59±1.65 ,2H, m),
2.51 ,4H, m), 3.78 ,3H, s), 6.63±7.26 ,14H, m). MS m/z ,%)
485 ,M1, 0.6), 484 ,1), 394 ,100). Cacld for C34H47NO: M,
1
cm21; H NMR d 1.01±1.20 ,2H, m), 1.91±2.02 ,1H, m),
2.06±2.17 ,1H, m), 2.28±2.34 ,1H, m), 2.36 ,3H, s), 2.53±
2.60 ,1H, m), 3.81 ,3H, s), 4.60 ,1H, s), 6.79±7.46 ,18H, m).
MS m/z ,%) 481 ,M1, 0.3), 465 ,0.7), 342 ,100). Anal.
Cacld for C31H31NO2S: C, 77.30; H, 6.49; N, 2.91; S,
6.66. Found: C, 77.00; H, 6.32; N, 2.89; S, 6.67. High
Mass: M, 481.2075. Found: m/z 481.2083. ꢀ2R,3R,RS)-
ꢀ2)-23: Colorless crystals; mp 110±1118C ,Hex:EtOAcˆ
1:1); IR ,KBr) 2925, 1595, 1511, 1234, 1051, 1034 ,SO)
cm21; [a]D22 22.38 ,c 0.1, acetone),
24
485.3658. Found: m/z 485.3676. [a]D 14.78 ,c 0.10,
acetone). ꢀS)-ꢀ2)-20: [a]D 24.48 ,c 0.12, acetone).
25
2.1.25. 1-Chloro-4-ꢀ4-methoxyphenyl)-1-ꢀp-tolylsul®nyl)-
butane ꢀ21b). A solution of 16 ,164 mg, 0.87 mmol) in a
minimum amount of dry THF was added dropwise with
stirring to a solution of LDA ,1.11mmol) in 2 ml of THF
in a ¯ame-dried ¯ask at 2708C. After 10 min, 314 mg ,1.13
mmol) of 3-,4-methoxyphenyl)-1-iodopropane was added
to the reaction mixture. The reaction mixture was stirred
and allowed to warm to 2358C and then saturated aqueous
NH4Cl was added. The solution was extracted with CHCl3.
The organic layer was dried over MgSO4 and the
solvent was evaporated to give an oil, which was puri-
®ed by silica gel column chromatography to afford 21b
,289 mg, 99%) as a colorless oil; a mixture of two
diastereomers; IR ,neat) 2944, 1513, 1245, 1055 ,SO),
2.1.28. ꢀ2S*,3R*)-2-Decyl-2-[3-ꢀ4-methoxyphenyl)propyl]-
1,3-diphenylaziridine ꢀ24). Colorless oil; IR ,neat) 2926,
2855, 1598, 1512, 1487, 1453, 1415, 1300, 1245, 1175, 1037
cm21; 1H NMR d 0.58 ,1H, m), 0.86 ,3H, t, Jˆ7.0 Hz), 0.98
,1H, m), 1.23 ,14H, m), 1.46 ,2H, m), 1.85 ,4H, m), 2.46 ,1H,
m), 2.55 ,1H, m), 3.17 ,1H, s), 3.78 ,3H, s), 6.79±7.39 ,14H,
m). MS m/z ,%) 483 ,M1, 24), 362 ,100), 342 ,29), 223 ,71).
Cacld for C34H45NO: M, 483.3501. Found: m/z 483.3499.
ꢀ2S,3R)-ꢀ2)-24: Colorless oil; [a]D26 299.78 ,c 0.11, acetone).
811 cm21 1H NMR d 1.58±2.01 ,3H, m), 2.19±2.28
;
,1H, m), 2.43 ,3H, s), 2.52±2.63 ,2H, m), 3.80 ,3H, s),
4.38 ,0.5H, dd, Jˆ3.0, 9.5 Hz), 4.48 ,0.5H, dd, Jˆ3.9, 9.7
Hz), 6.80±7.61 ,8H, m). MS m/z ,%) 336 ,M1, 1), 319 ,1),
197 ,25), 161 ,71), 121 ,100). Cacld for C18H21ClO2S: M,
336.0950. Found: m/z 336.0960.
Acknowledgements
This work was supported by a Grant-in-Aid for Scienti®c

3898
T. Satoh et al. / Tetrahedron 57 ,2001) 3891±3898
7. Satoh, T. J. Syn. Org. Chem. Jpn. 1996, 54, 481.
8. A review for the aziridinyl anions: Satoh, T. Chem. Rev. 1996,
96, 3303.
Research No. 11640545 from the Ministry of Education,
Science, Sports and Culture, which is gratefully acknowl-
edged. We also thank Ms Yoshimi Yanagida for her assis-
tance in this study.
9. Preliminary results of this study were reported as a communi-
cation:Satoh, T.; Matsue, R.; Fujii, T.; Morikawa, S.
Tetrahedron Lett. 2000, 41, 6495.
References
10. Metal-catalyzed Cross-coupling Reactions, Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998.
11. ,a) Nunomoto, S.; Kawakami, Y.; Yamashita, Y. Bull. Chem.
Soc. Jpn. 1981, 54, 2831. ,b) Cahiez, G.; Chaboche, C.;
Jezequel, M. Tetrahedron 2000, 56, 2733.
1. Some recent reviews for the construction of quaternary carbon
centers: ,a)Martin, S. F. Tetrahedron 1980, 36, 419. ,b) Fuji,
K. Chem. Rev. 1993, 93, 2037. ,c) Corey, E. J.; Guzman-
Perez, A. Angev. Chem. Int. Ed. 1998, 37, 388. ,d) Sannigrahi,
M. Tetrahedron 1999, 55, 9007.
12. ,a) Neumann, S. M.; Koch, J. K. J. Org. Chem. 1975, 40, 599.
,b) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199.
,c) Wake®eld, B. J. In Organomagnesium Methods in Organic
Synthesis, Academic Press: London, 1995; pp 151±169.
13. ,a) Kametani, T.; Honda, T. Advances in Heterocyclic
Chemistry, Katritzky, A. R., Ed.; Academic Press: New
York, 1986; 39, pp 181. ,b) Sekar, G.; Singh, V. K. J. Org.
Chem. 1999, 64, 2537. ,c) McCoull, W. M.; Davis, F. A.
Synthesis 2000, 1347.
2. ,a) Cativiela, C.; Diaz-de-Villegas, M. D. Tetrahedron:
Asymmetry 1998, 9, 3517. ,b) Cativiela, C.; Diaz-de-Villegas,
M. D. Tetrahedron: Asymmetry 2000, 11, 645. ,c) Sano, S.;
Nagao, Y. J. Syn. Org. Chem. Jpn. 2000, 58, 756.
3. ,a) Cole, D. C. Tetrahedron 1994, 50, 9517. ,b) In Enantio-
selective Synthesis of a-Amino Acids, Juaristi, E., Ed.; Wiley-
VCH: New York, 1997. ,c) Tang, T. P.; Ellman, J. A. J. Org.
Chem. 1999, 64, 12 and references therein.
14. ,a) Lim, Y.; Lee, W. K. Tetrahedron Lett. 1995, 36, 8431.
,b) Choi, S.-K.; Lee, J.-S.; Kim, J.-H.; Lee, W. K. J. Org.
Chem. 1997, 62, 743. ,c) Davis, F. A.; Liang, C.-H.; Liu, H.
J. Org. Chem. 1997, 62, 3796. ,d) Chang, J.-W.; Bae, J. H.;
Shin, S.-H.; Park, C. S.; Choi, D.; Lee, W. K. Tetrahedron
Lett. 1998, 39, 9193.
4. ,a) Willems, J. G. H.; de Vries, J. G.; Nolte, R. J. M.;
Zwanenburg, B. Tetrahedron Lett. 1995, 36, 3917. ,b) Enders,
D.; Reinhold, U. Tetrahedron: Asymmetry 1997, 8, 1895.
,c) Cogan, D. A.; Liu, G.; Ellman, J. Tetrahedron 1999, 55,
8883. ,d) North, M. J. Chem. Soc., Perkin Trans. 1 1999, 2209.
5. ,a) Satoh, T.; Ozawa, M.; Takano, K.; Kudo, M. Tetrahedron
Lett. 1998, 39, 2345. ,b) Satoh, T.; Ozawa, M.; Takano, K.;
Chyouma, T.; Okawa, A. Tetrahedron 2000, 56, 4415.
6. Satoh, T.; Sato, T.; Oohara, T.; Yamakawa, K. J. Org. Chem.
1989, 54, 3973.
15. Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K. J. Org. Chem.
1989, 54, 3130.