Addition reactions of chloro- Or iodomethyllithium to imines. Synthesis of enantiopure aziridines and β-chloroamines

Article abstract of DOI:10.1021/jo802596y

We report a novel, simple, and efficient synthesis of aziridines and l-chloroalkan-2-amines by the reaction of imines derived from various aldehydes and p-toluenesulfonamide or benzenesulfonamide with iodoor chloromethyllithium, respectively. Both halogenated anions were generated in situ by treatment of diiodo- or chloroiodomethane with methyllithium at -78 or 0 °C. The reaction of in situ generated iodoor chloromethyllithium could also be performed from chiral 2-aminoaldimines to yield enantiopure aziridines or (2S,3S)-2,3-diamino- l-chloroalkanes with high stereoselectivity.

Full text of DOI:10.1021/jo802596y

Addition Reactions of Chloro- or Iodomethyllithium to Imines.
Synthesis of Enantiopure Aziridines and ꢀ-Chloroamines
Jose´ M. Concello´n,* Humberto Rodr´ıguez-Solla, Pablo L. Bernad, and Carmen Simal
Departamento de Qu´ımica Orga´nica e Inorga´nica, Facultad de Qu´ımica, UniVersidad de OViedo,
Julia´n ClaVer´ıa 8, 33071 OViedo, Spain
jmcg@unioVi.es
ReceiVed December 10, 2008
We report a novel, simple, and efficient synthesis of aziridines and 1-chloroalkan-2-amines by the reaction
of imines derived from various aldehydes and p-toluenesulfonamide or benzenesulfonamide with iodo-
or chloromethyllithium, respectively. Both halogenated anions were generated in situ by treatment of
diiodo- or chloroiodomethane with methyllithium at -78 or 0 °C. The reaction of in situ generated iodo-
or chloromethyllithium could also be performed from chiral 2-aminoaldimines to yield enantiopure
aziridines or (2S,3S)-2,3-diamino-1-chloroalkanes with high stereoselectivity.
Introduction
related to mitosanes and mytomycins and bearing the aziridine
ring have been synthesized and have been demonstrated to
possess activity against a variety of cancers.5
Aziridines and their precursors ꢀ-haloamines are important
building blocks in organic synthesis. The former heterocycles
can undergo highly regioselective nucleophilic ring opening
reactions1 and can be employed as starting materials for the
synthesis of important biomolecules such as amino acids,
ꢀ-lactams, and alkaloids.2
Moreover, the aziridine ring is present in molecules that show
biological activity. Naturally occurring compounds with the
aziridine moiety exhibit antitumor and/or antibiotic activity, due
to their ability to cross-link DNA,3 or inhibit the bacterial
enzyme diaminopimelic acid epimerase.4 Other molecules
As a result of this, a large number of methods for the
preparation of aziridines have been reported in recent years.6
The main synthetic routes toward aziridines have included the
addition of nitrenes to alkenes,7 R-metalation/electrophile trap-
ping of N-protected aziridines,8addition reactions to azirines,9
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2452 J. Org. Chem. 2009, 74, 2452–2459
10.1021/jo802596y CCC: $40.75 2009 American Chemical Society
Published on Web 02/18/2009

Synthesis of Aziridines and ꢀ-Chloroamines
and methods based on the use of epoxides,10 ꢀ-amino alcohols,11
or imines12 as starting materials. This last class of compounds
has been most widely employed as starting materials to obtain
aziridines, and several protocols have been developed to
transform imines into aziridines through methylene transfer by
using sulfur ylides13 or a mixture of dihalomethanes and
diethylzinc13f or potassium.14 Generally, the reported methods
to obtain aziridines required long reaction times and took place
in low yields.
ꢀ-Chloroamines have also been extensively used as starting
compounds to prepare aziridines. As well as being precursors
to aziridines, ꢀ-chloroamines are important building blocks in
organic synthesis, which could complement those synthetic
applications of aziridines. Generally, ꢀ-chloroamines have been
prepared by nucleophilic addition of various nucleophiles
(hydride, cyanide, Grignard reagents, etc.) to R-chloroimines.15
An improvement of these reported syntheses could be the
addition reaction of chloromethyllithium to imines, since the
starting imines are simpler compounds and are more readily
available than 2-chloroimines.
the successful aziridination. In addition, both the removal of
the N-substituent and the ring opening of this aziridine with
various nucleophiles could not be performed.16 As expected,
preparation of enantiopure aziridines by reaction of chiral
aldimines with halomethyllithium has not been reported to date,
despite enantiopure compounds having greater value than the
corresponding racemic compounds.
The use of halomethyllithium compounds in synthesis
presents a drawback given their instability: These reagents
spontaneously decompose through an R-elimination process
even at -100 °C. In order to use these organometallic
compounds as anionic reagents, halomethyllithium compounds
must be generated in situ, in the presence of the corresponding
electrophile to avoid decomposition prior to the reaction with
the electrophile.17 Generally, chloro-, bromo-, or iodomethyl-
lithium are prepared in situ by treating a mixture of chloroiodo-,
dibromo-, or diiodomethane and the corresponding electrophile
with methyllithium at low temperature (-78 °C).18 Indeed, the
reaction of in situ generated halomethyllithium with aldehydes
or ketones,19 esters,20 carboxylic acid chlorides,21 boronic
esters,22 or N-protected 3-oxazolidin-5-ones23 has been reported.
However, the in situ generated halomethyllithium compounds
did not react with less electrophilic reagents, such as imines,
and suffer an R-elimination reaction. The lack of reactivity of
imines could explain the absence of precedents concerning the
reaction of halomethyllithium compounds with imines. Given
this background, the development of a novel and efficient
method to obtain aziridines or chloroamines, including the
In this context, and to the best of our knowledge, only one
example of an aziridine ring has been prepared through the
reaction of in situ generated chloromethyllithium and a specific
imine derived from 2-pyridinecarboxaldehyde. However, when
the method was applied to other imines without the 2-pyridi-
neimine moiety, such as those derived from benzaldehyde, no
reaction took place. Thus, the authors assumed that the presence
of the 2-pyridineimine moiety was a necessary requirement for
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J. Org. Chem. Vol. 74, No. 6, 2009 2453

Concello´n et al.
TABLE 1. Synthesis of Aziridines 2
reaction with chiral imines to afford a range of enantiopure
aziridines and chloroamines without racemization, would be
desirable.
Recently, we reported our preliminary results concerning the
synthesis of aziridines by reaction of imines derived from
p-toluenesulfonamide with in situ generated iodomethyllithium.
The synthesis of the enantiopure (2R,1′S)-2-(1′-dibenzylamino-
2′-phenylethyl)aziridine with high stereoselectivity in good yield
from the aziridination of the enantiopure N-tosylimine derived
from phenylalaninal was also described.24
The main advantage of this reported method is that the
experimental protocol is simple and rapid. Taking into account
the synthetic interest of this procedure, in this paper we describe
a generalization of the reported aziridination of racemic imines
from p-toluene and benzenesulfonamide and the synthesis of
enantiopure aziridines from the chiral R-aminoimines. In ad-
dition, a new method to obtain ꢀ-chloroamines by reaction of
the imines derived from p-toluenesulfonamide and benzene-
sulfonamide, including the chiral version using enantiopure
aminoimines, with chloromethyllithium instead of iodomethyl-
lithium is also reported.
entry
2
R1
R2
yield (%)a
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
n-C7H15
s-Bu
c-Hex
PhCH2
Ph
c-Hex
Ts
Ts
Ts
Ts
80
71
87
58
88
98
62
75
Ts
SO2Ph
SO2Ph
SO2Ph
2g
2h
p-ClC6H4
p-MeOC6H4
a Isolated yield after column chromatography based on compound 1.
TABLE 2. Deprotection of N-Tosyl Aziridines
entry
3
R1
yield (%)a
1
2
3
3a
3c
3d
n-C7H15
c-Hex
PhCH2
62
65
75
Results and Discussion
Synthesis of Aziridines 2 Starting from Imines Derived
from Sulfonamides 1. Initial attempts to prepare aziridines were
performed by starting from the imines derived from p-meth-
oxyphenylamine and octanal or benzaldehyde, which were
prepared according to a previously reported method.25 The
iodomethyllithium was generated in situ by treatment of
diiodomethane with methyllithium in the presence of the
corresponding imine at -78 °C. Unfortunately, no addition of
iodomethyllithium to either imine took place under various
reaction conditions. To overcome this problem, we tried to find
the appropriate amine in order to enhance the electrophilicity
of the carbonyl to facilitate the addition of iodomethyllithium.
This objective was achieved using imines derived from p-
toluenesulfonamide and octanal or benzaldehyde which were
prepared according to literature procedures.26 The reactions of
imines 1a and 1e with iodomethyllithium at low temperature
(-78 °C) afforded the corresponding aziridine in both cases
2aand 2e, respectively. After testing several reaction conditions,
the best results were obtained by treatment of a solution of 1.5
equiv of diiodomethane and 1 equiv of imine 1 in THF with
1.2 equiv of MeLi at 0 °C for 30 min, and further stirring at
the same temperature for 30 min (Table 1).
To study the generality of the aziridination reaction, additional
imines derived from p-toluenesulfonamide and a range of
aldehydes were prepared and allowed to react with iodometh-
yllithium. As can be observed in Table 1, the reaction seems to
be general and aziridines derived from linear, branched, and
cyclic aliphatic or aromatic aldehydes afforded the correspond-
ing aziridines in good to high yields. The reaction could also
be generalized by using other imines derived from benzene-
sulfonamide 1f-h (prepared by the same method as that used
for p-toluenesulfonamide),26 and the corresponding aziridines
2f-h were obtained, under the same reaction conditions
(LiCH2I, 0 °C), without showing any major differences in
a Isolated yield after column chromatography based on the compound
2.
comparison to those reactions of LiCH2I with imines derived
from p-toluenesulfonamide (Table 1).
The N-substituent on aziridines derived from p-toluene-
sulfonamide 1a,c,d, has been readily removed by using lithium-
naphthalenide following a method previously reported,27 in
which the isolation and purification of the obtained aziridines
were modified by us, since the previously described purification
by column chromatography resulted in poor yields of depro-
tected aziridines 3. To improve the yields of isolated compounds
3a,c,d an acid-base treatment of the crude reaction products
was performed yielding compounds 3a,c,d as they are shown
in Table 2.
The use of chloromethyllithium instead of iodomethyllithium
to prepare aziridines was also tested under the same reaction
conditions, furnishing the corresponding aziridines in yields 10%
lower than those observed for the previous case. Therefore,
taking into account that diiodomethane is cheaper than chlor-
oiodomethane, the aziridination reaction of imines was carried
out using iodomethyllithium instead of chloromethyllithium.
Synthesis of ꢀ-Chloroamines 4. The synthesis of ꢀ-chloro-
amines could be interesting, since the synthetic applications of
aziridines and ꢀ-chloroamines could be complementary. Thus,
we attempted the development of a method to transform imines
1 into ꢀ-chloroamines 4 instead of the aziridines 2. So, to avoid
the heterocyclization of ꢀ-chloroamines, the reaction was
performed at lower temperature starting from the same imines
derived from p-toluenesulfonamide 1a-e and benzenesulfona-
mide 1f-g. After we tested several reaction conditions, the best
yields of ꢀ-chloroamines were obtained by treating a solution
of 2.5 equiv of chloroiodomethane and the corresponding
N-sulfonyl imine (1 equiv) in THF with 2.5 equiv of methyl-
lithium at -78 °C and hydrolyzing at the same temperature. In
(24) Concello´n, J. M.; Rodr´ıguez-Solla, H.; Simal, C. Org. Lett. 2008, 10,
4457–4460.
(25) Reetz, M. T.; Lee, W. K. Org. Lett. 2001, 3, 3119–3120.
(26) Wang, Y.; Song, J.; Hong, R.; Li, H.; Deng, L. J. Am. Chem. Soc. 2006,
128, 8156–8157.
(27) Alonso, D. A.; Andersson, P. G. J. Org. Chem. 1998, 63, 9455–9461.
2454 J. Org. Chem. Vol. 74, No. 6, 2009

Synthesis of Aziridines and ꢀ-Chloroamines
TABLE 3. Synthesis of ꢀ-Chloroamines 4
SCHEME 2. Synthesis of Chiral 2-(1-Dibenzylaminoalkyl)-
aziridines 11
entry
4
R1
R2
yield (%)a
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
n-C7H15
s-Bu
c-Hex
PhCH2
Ph
c-Hex
Ts
Ts
Ts
Ts
71
81
72
65
69
>98
78
60
TABLE 4. Synthesis of Enantiopure 2-(1-Dibenzylaminoalkyl)-
aziridines 11
entry
11
R1
dr
yield (%)a
Ts
SO2Ph
SO2Ph
SO2Ph
1
2
3
11a
11b
11c
Me
i-Bu
PhCH2
7/1
5/1
9/1
54
58
61
4g
4h
p-ClC6H4
p-MeOC6H4
a Isolated yield after column chromatography based on compound 1.
a Isolated yield after column chromatography based on the starting
aminoaldehyde 9.
SCHEME 1. Proposed Mechanism for the Synthesis of
Compounds 2 and 4
aminoalkyl aziridines by reaction of chiral aminoaldimines
derived from anisidine with sulfur ylides.25
Given the synthetic utility of optically active syn-aminoaziri-
dines,28 we performed the aziridination reaction described above,
with enantiopure aldimines 10 derived from chiral N,N-dibenzyl
2-aminoaldehydes 9, with the goal of synthesizing the anti-
aminoaziridine (the diastereoisomer of that syn-diastereoisomer
previously reported by us),12e and improving the stereoselectivity
of the synthesis of syn-aminoaziridines reported by Reetz.25 The
required N-tosylimines 10 were prepared by the Weinreb
procedure.29 The obtained imines were unstable and could not
be purified. Thus, the reaction with iodomethyllithium was
carried out using crude aminoimines, rendering aminoaziridines
11 (Scheme 2). After testing several reaction conditions, the
best result was obtained by treating a solution of crude
aminoimines 10 in THF with 4.0 equiv of diiodomethane and
4.0 equiv of MeLi at -78 °C for 2 h (Scheme 2).30
Table 3, the results obtained in the synthesis of compounds 4
are compiled, showing that yields of chloroamines 4 at -78 °C
were similar to those obtained in the syntheses of aziridines 2
using iodomethyllithium at 0 °C.
The synthesis of ꢀ-bromoamines with bromomethyllithium
(generated in situ from the reaction of dibromomethane with
methyllithium) was also tested. However, when the reaction of
bromomethyllithium and imines 1a and 1c was performed, under
the same reaction conditions as those used in the synthesis of
chloroamines 4, the corresponding aziridines 2a and 2c were
obtained instead of ꢀ-bromoamines. The use of other reaction
conditions (lower temperature, amounts of solvent, reaction time,
etc.) in order to obtain the ꢀ-bromoamines was tested. Unfor-
tunately, the corresponding aziridines were always obtained,
instead of the ꢀ-bromoamines, in yields similar to those obtained
with iodomethyllithium compiled in Table 1.
The synthesis of aziridines 2 and ꢀ-chloroamines 4 can be
explained by assuming an addition process of iodo-, bromo-,
or chloromethyllithium to the imine group generating an iodated,
bromated, or chlorinated lithium amide 5, 6, or 7. The obtained
lithium 2-iodoamide or 2-bromoamide undergoes a spontaneous
heterocyclization to afford the corresponding aziridines 2 in both
cases; in contrast, no heterocyclization took place from 2-chlo-
roamides at -78 °C and the corresponding ꢀ-chloroamines 4
were finally isolated (Table 3). The isolation of ꢀ-chloroamines
when chloromethyllithium was used at -78 °C could proceed
via the proposed mechanism, in which the generation of
halomethyllithium, rather than a carbene, was the suggested
active intermediate to carry out the aziridination process
(Scheme 1).
After hydrolysis and the usual workup, crude aminoaziridines
11 were obtained in good yields (79% from the imine derived
from phenylalaninal). Purification by conventional column
chromatography, afforded the expected pure aminoaziridines 11
in low yields (42% from imine derived from phenylalaninal),
which disagreed with the good purity observed in the crude
reaction material (1H and 13C NMR). The yields of the pure
aziridines 11 were increased by avoiding the hydrolysis step
and directly purifying the crude material by column chroma-
tography. Table 4 shows the overall yields of the two-step
transformations of aminoaldehydes 9 into aminoaziridines 11,
which were determined after column chromatography purifica-
tion of compounds 11 using a simpler isolation method in which
the hydrolysis of the crude reactions was not carried out.
The good stereoselectivity of the addition reaction of iodom-
ethyllithium (Table 4) was determined, on the crude reaction
1
products, by 300 MHz H NMR. It is noteworthy that the
previously reported synthesis of (2R,1′S)-2-(1′-dibenzylamino-
(28) (a) Concello´n, J. M. Riego, E. J. Org. Chem. 2003, 68, 6407–6410. (b)
´
Concello´n, J. M. Riego, E.Alvarez, J. R. J. Org. Chem. 2003, 68, 9242–9246.
(c) Concello´n, J. M. Riego, E. Rivero, I. A. Ochoa, A. J. Org. Chem. 2004, 69,
6244–6248. (d) Concello´n, J. M. Riego, E. Sua´rez, J. R. Garc´ıa-Granda, S. D´ıaz,
M. R. Org. Lett. 2004, 6, 4499–4501. (e) Concello´n, J. M. Bernad, P. L. Sua´rez,
J. R. Chem. Eur. J. 2005, 11, 4492–4501. (f) Concello´n, J. M. Bernad, P. L.
Sua´rez, J. R. Garc´ıa-Granda, S. D´ıaz, M. R. J. Org. Chem. 2005, 70, 9411–
9416(g) Reference 8b.
Synthesis of Enantiopure 2-(1-Dibenzylaminoalkyl)aziri-
dines 11. Previously, we reported the synthesis of nonactivated
enantiopure syn-aminoalkyl aziridines by reduction of R-amino
ketimines derived from 1-aminoalkyl chloromethyl ketones.12e
In addition, Reetz published the synthesis of enantiopure anti-
(29) Sisko, J.; Weinreb, S. M. J. Org. Chem. 1990, 55, 393–395.
(30) An excess of iodomethyllithium was necessary due to the presence of
N-tosylamine in the mixture reaction, as a consequence of the N-sulfinyl-p-
toluenesulfonamide required for the synthesis of aminoaldimines 10, which is
purchased with a purity of ∼70%.
J. Org. Chem. Vol. 74, No. 6, 2009 2455

Concello´n et al.
SCHEME 3. Deprotection/Benzylation of Compound 11c
SCHEME 4. Synthesis of (2S,3S)-2,3-Diamino-1-chloroalkanes 15
SCHEME 5. Proposed Addition Reaction of Chloro- and
Iodomethyllithium to Aminoimines 10
2′-phenylethyl)-1-(4-methoxyphenyl)aziridine by reaction of the
corresponding R-aminoaldimine with dimethylsulfonium me-
thylide took place with lower stereoselectivity.25
In general terms, it is noteworthy that this reported method
for the synthesis of aziridines 2 and 11 is experimentally simple,
the reaction times are short and proceed with high stereoselec-
tivity in the case of compounds 11.
The structure and absolute configuration of the aziridine ring
of aminoaziridines 11 was unambiguously established by
transformation of the aminoaziridine 11c into the corresponding
N-benzyl aziridine through a deprotection/benzylation protocol
1
(Scheme 3). H and 13C NMR of the minor product 13 was
consistent with the syn-aminoaziridine previously reported by
us starting from the corresponding chloromethyl ketimine
derived from phenylalaninal.20 Consequently, we deduced that
the absolute configuration of the major stereoisomer 11c was
2R. The assigned structure for compound 13 shown in Scheme
3 was corroborated by its spectroscopic data. The absolute
configuration of the other aziridines 11 were assigned by
analogy.
Synthesis of Enantiopure (2S,3S)-2,3-Diamino-1-chloroal-
kanes 15. The synthesis of chiral ꢀ-chloroamines derived from
aminoimines 10 was also carried out by using a methodology
similar to that developed for the synthesis of chloroamines 4.
Thus, when 4 equiv of methyllithium was added to a mixture
of 4 equiv of chloroiodomethane and crude aminoimines 10 at
-78 °C, the corresponding chloroamines 15 were obtained after
hydrolysis in yields similar to those observed in the synthesis
of aminoaziridines 11b and 11c (Table 4).
to R-aminoimines 10 under nonchelation control. This fact could
be explained by assuming that the energetically more favored
transition state has the larger substituent (N,N-dibenzylamino
group) anti to the attack of the halomethyllithium (Scheme 5).
The same stereochemical course was established to explain the
reduction of chloromethyl ketones19f or chloromethyl keti-
mines.19i In addition, the stereochemistry of aziridine 11 was
also in agreement with the anti epoxides, previously described
by treatment from R-aminoaldehydes with iodomethyllithium.19f
Finally, the enantiomeric purities of compounds 11 and 15
were evaluated by chiral HPLC. To carry out this analysis, a
racemic mixture of 11c was previously prepared from the imine
obtained with racemic phenylalaninal (()-9b. The chiral HPLC
analysis of this racemic mixture allowed the discovery of the
best conditions to separate both enantiomers. These conditions
were used to analyze the aziridine 11c obtained from the
treatment of 10c with iodomethyllithium at -78 °C or chlo-
romethyllithium at -78 °C allowing the reaction mixture to
reach room temperature. After obtaining 11c through both
pathways, HPLC analysis showed an enantiomeric purity >98%
in both cases. This fact excluded a partial racemization from
phenylalaninal 9c during its transformation into 11c or 15c.31
In conclusion, an efficient, simple, and rapid aziridination
process by reaction of imines derived from p-toluenesulfonamide
The stereoselectivity of the addition reaction of chlorometh-
yllithium to imines 10 (Scheme 4) was also determined, on the
1
crude reaction products, by 300 MHz H NMR. The structure
of diaminochloroalkanes 15 was established on the basis of
spectroscopic data for compounds 15b,c and by allowing the
reaction mixture to reach room temperature, in the case of
compound 15c, to promote the heterocyclization. In this latter
experiment, aminoaziridine 11c was obtained instead of 15c in
a 55% yield (Scheme 4).
(31) The determination of the absence of racemization was carried out with
the phenylalaninal, due to its high proclivity to racemize: Rittle, K. E.; Homnick,
C. F.; Ponciello, G. S.; Evans, B. E. J. Org. Chem. 1982, 47, 3016–3018.
The absolute configuration of compounds 11 and 15 was
according to an addition reaction of chloro- or iodomethyllithium
2456 J. Org. Chem. Vol. 74, No. 6, 2009

Synthesis of Aziridines and ꢀ-Chloroamines
7.68-7.52 (m, 3 H), 7.27 (d, J ) 8.5 Hz, 2 H), 7.15 (d, J ) 8.3
Hz, 2 H), 3.77 (dd, J ) 7.1, 4.5 Hz, 1 H), 3.01 (d, J ) 7.1 Hz, 1
H), 2.37 (d, J ) 4.5 Hz, 1 H); 13C NMR (75 MHz, CDCl3) δ )
137.8 (C), 134.2 (C), 133.7 (CH), 133.4 (C), 129.1 (2×CH), 128.8
(2×CH), 127.8 (4×CH), 40.3 (CH), 36.1 (CH2); MS (70 eV) m/z
(%) 293 [M+] (<1), 152 (100), 125 (92); HRMS calcd for
C14H12ClNO2S 293.0277, found 293.0279; IR (neat) ν˜ ) 3056,
1327, 1266, 1000, 739 cm-1; Rf ) 0.27 (hexane:ethyl acetate 3:1).
2-(4-Methoxyphenyl)-1-phenylsulfonylaziridine (2h): orange
with in situ generated iodomethyllithium at 0 °C is reported.
The addition reaction of chloromethyllithium to imines derived
from p-toluenesulfonamide at -78 °C afforded the correspond-
ing chloroamines. The reaction with aldimines derived from
various aminoaldehydes afforded the corresponding enantiopure
(2R,1′S)-2-(1′-aminoalkyl)aziridine and (2S,3S)-2,3-diamino-1-
chloroalkanes with very high diastereoselectivity.
1
oil; H NMR (300 MHz, CDCl3) δ ) 7.98 (d, J ) 8.5 Hz, 2 H),
Experimental Section
7.68-7.53 (m, 3 H), 7.27 (d, J ) 8.6 Hz, 2 H), 7.15 (d, J ) 8.5
Hz, 2 H), 3.89 (s, 3 H), 3.77 (dd, J ) 7.2, 4.4 Hz, 1 H), 3.01 (d,
J ) 7.2 Hz, 1 H), 2.37 (d, J ) 4.4 Hz, 1 H); 13C NMR (50 MHz,
CDCl3) δ ) 159.4 (C), 139.7 (C), 133.4 (CH), 128.9 (2×CH), 127.7
(2×CH), 127.6 (2×CH), 126.1 (C), 113.8 (2×CH), 55.0 (CH3),
40.8 (CH), 35.6 (CH2); MS (70 eV) m/z (%) 289 [M+] (24), 267
(10), 231 (22), 148 (100), 121 (25); HRMS calcd for C15H15NO3S
289.0773, found 289.0778; IR (neat) ν˜ ) 3292, 1514, 1266, 1165,
999 cm-1; Rf ) 0.22 (hexane:ethyl acetate 3:1).
Compounds 2a-e, 3a,c,d, 11c, 12, and 13 displayed analytical
data in accordance with the published values.24
Synthesis of Sulfonylimines 1. N-Sulfonylimines 1 were
synthesized following the method reported in ref 26.
Cyclohexyl-N-phenylsufonylmethanimine (1f): white solid; 1H
NMR (300 MHz, CDCl3) δ ) 8.51 (d, J ) 4.3 Hz, 1 H), 7.93 (d,
J ) 7.1 Hz, 2 H), 7.64-7.52 (m, 3 H), 2.46-2.43 (m, 1 H),
1.86-1.64 (m, 5 H), 1.35-1.25 (m, 5 H); 13C NMR (75 MHz,
CDCl3) δ ) 181.6 (CH), 137.8 (C), 133.5 (CH), 129.0 (2×CH),
127.9 (2×CH), 43.6 (CH), 28.2 (2×CH2), 25.5 (CH2), 25.0
(2×CH2); MS (70 eV) m/z (%) 251 [M+] (20), 196 (34), 183 (51),
141 (39), 110 (74), 77 (100), 55 (47), 41 (39); HRMS (ESI)+ calcd
for C13H18NO2S [M + H]+ 252.1058, found 252.1053; IR (neat) ν˜
) 3343, 1565, 1266, 1012, 738 cm-1; Rf ) 0.37 (hexane:ethyl
acetate 3:1).
Synthesis of Aziridines 3. To a cooled (-78 °C) suspension of
Li powder (1.44 mmol) and naphthalene (1.62 mmol) in dry THF
(4 mL) previously stirred for 1 h at rt was added under N2
atmosphere the corresponding N-sulfonylaziridine 2 (0.36 mmol).
The mixture was then stirred for an additional hour at the same
temperature and then was quenched with brine (10 mL). The
corresponding pure aziridine was obtained in a good yield after an
acid-base extraction.
(4-Chlorophenyl)-N-phenylsulfonylmethanimine (1g): white
solid; 1H NMR (300 MHz, CDCl3) δ ) 9.02 (s, 1 H), 8.01 (d, J )
8.6 Hz, 2 H), 7.88 (d, J ) 8.6 Hz, 2 H), 7.68-7.46 (m, 5 H); 13C
NMR (75 MHz, CDCl3) δ ) 169.0 (CH), 141.5 (C), 137.9 (C),
133.6 (CH), 132.4 (2×CH), 130.7 (C), 129.6 (2×CH), 129.1
(2×CH), 128.0 (2×CH); MS (70 eV) m/z (%) 279 [M+] (11), 141
(59), 77 (100); HRMS calcd for C13H10ClNO2S 279.0121, found
279.0097; IR (neat): ν˜ ) 3338, 1593, 1266, 1008, 738 cm-1; Rf )
0.32 (hexane:ethyl acetate 3:1).
(4-Methoxyphenyl)-N-phenylsulfonylmethanimine (1h): white
solid; 1H NMR (300 MHz, CDCl3) δ ) 8.96 (s, 1 H), 7.98 (d, J )
6.9 Hz, 2 H), 7.88 (d, J ) 8.9 Hz, 2 H), 7.63-7.49 (m, 3 H), 6.96
(d, J ) 8.9 Hz, 2 H), 3.87 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ
) 169.6 (CH), 165.3 (C), 138.6 (C), 133.7 (2×CH), 133.2 (CH),
128.9 (2×CH), 127.7 (2×CH), 125.0 (C), 114.6 (2xCH), 55.6
(CH3); MS (70 eV) m/z (%) 275 [M+] (56), 134 (100), 77 (70),
155 (49), 133 (51), 91 (100), 65 (28); HRMS calcd for C14H13NO3S
275.0616, found 275.0618; IR (neat) ν˜ ) 3318, 1590, 1266, 1005,
738 cm-1; Rf ) 0.25 (hexane:ethyl acetate 3:1).
Synthesis of Chloroamines 4. To a mixture of N-sulfonyl imine
(0.4 mmol) and CH2ICl (1 mmol, 2.5 equiv) in dry THF (2 mL)
was added at -78 °C a solution of MeLi in ether (1.5 M, 1 mmol,
2.5 equiv). The solution was stirred at the same temperature for
3 h and then was quenched with NH4Cl (aq) at the same
temperature. The organic layer was extracted with diethyl ether (3
× 10 mL), and the combined extracts were dried over Na2SO4 and
concentrated under vacuum to yield the N-sulfonylchloroamine
which was purified by flash chromatography on silica gel (hexane/
EtOAc 10/1) to afford pure products.
1
1-Chloro-N-tosylnonan-2-amine (4a): white solid; H NMR
(300 MHz, CDCl3) δ ) 7.77 (d, J ) 8.2 Hz, 2 H), 7.31 (d, J ) 8.2
Hz, 2 H), 4.84 (d, J ) 8.1 Hz, 1 H), 3.55-3.42 (m, 3 H), 2.43 (s,
3 H), 1.68-1.00 (m, 12 H), 0.86 (t, J ) 7.0 Hz, 3 H); 13C NMR
(50 MHz, CDCl3) δ ) 143.5 (C), 137.7 (C), 129.7 (2×CH), 126.9
(2×CH), 53.7 (CH), 48.1 (CH2), 32.3 (CH2), 31.6 (CH2), 28.9
(2×CH2), 25.2 (CH2), 22.5 (CH2), 21.4 (CH3), 14.0 (CH3); MS (70
eV) m/z (%) 331 [M+] (<1), 282 (100), 232 (24), 155 (68), 91 (89),
65 (19), 41 (17); HRMS calcd for C16H26ClNO2S 331.1373, found
331.1378; IR (neat) ν˜ ) 3370, 3055, 1265, 1012, 740 cm-1; Rf )
0.45 (hexane:ethyl acetate 3:1).
1-Chloro-3-methyl-N-tosylpentan-2-amine (4b): white solid;
1H NMR (300 MHz, CDCl3) δ ) 7.77 (d, J ) 8.3 Hz, 4 H), 7.30
(d, J ) 8.3 Hz, 4 H), 5.01 (d, J ) 8.6 Hz, 2 H), 3.58-3.52 (m, 2
H), 3.42-3.22 (m, 4 H), 2.43 (s, 6 H), 1.79-1.51 (m, 2 H),
1.28-1.19 (m, 2 H), 1.12-0.95 (m, 2 H), 0.80 (d, J ) 6.9 Hz, 6
H), 0.74 (d, J ) 7.4 Hz, 6 H); 13C NMR (75 MHz, CDCl3) (major
stereoisomer) δ ) 143.5 (C), 137.6 (C), 129.6 (2×CH), 127.0
(2×CH), 57.7 (CH), 45.4 (CH2), 35.0 (CH), 25.5 (CH2), 21.4 (CH3),
13.8 (CH3), 11.0 (CH3); 13C NMR (75 MHz, CDCl3) (minor
stereoisomer) δ ) 143.5 (C), 137.7 (C), 129.6 (2×CH), 126.9
(2×CH), 58.1 (CH), 45.9 (CH2), 35.7 (CH), 24.3 (CH2), 21.4 (CH3),
14.9 (CH3), 10.9 (CH3); MS (70 eV) m/z (%) 240 [M+ - CH2Cl]
(32), 232 (65), 155 (92), 91 (100), 65 (28), 41 (17); HRMS calcd
for C13H20ClNO2S 289.0903, found 289.0943; IR (neat) ν˜ ) 3373,
1599, 1266, 1161, 989 cm-1; Rf ) 0.30 (hexane:ethyl acetate 3:1).
2-Chloro-1-cyclohexyl-N-tosylethanamine (4c): white solid; 1H
NMR (300 MHz, CDCl3) δ ) 7.78 (d, J ) 8.3 Hz, 2 H), 7.30 (d,
J ) 8.3 Hz, 2 H), 5.11 (d, J ) 9.1, 1 H), 3.58 (dd, J ) 11.4, 3.3
Hz, 1 H), 3.41 (dd, J ) 11.4, 4.7 Hz, 1 H), 3.28-3.20 (m, 1 H),
2.43 (s, 3 H), 1.82-1.55 (m, 6 H), 1.35-0.69 (m, 5 H); 13C NMR
(75 MHz, CDCl3) δ ) 143.4 (C), 137.8 (C), 129.5 (2×CH), 126.9
Synthesis of Sulfonylaziridines 2. To a mixture of the requisite
N-sulfonylimine 1 (0.4 mmol) and CH2I2 (0.6 mmol, 1.5 equiv) in
dry THF (2 mL) was added at 0 °C a solution of MeLi in ether
(1.5 M, 0.48 mmol, 1.2 equiv). The solution was stirred at the same
temperature for 30 min and then was left to stir at room temperature
for an additional 30 min. The reaction mixture was then quenched
with NH4Cl (aq), and the organic layer was then extracted with
diethyl ether (3 × 10 mL). The combined extracts were dried over
Na2SO4 and concentrated under vacuum to yield crude N-sulfony-
laziridines 2 which were purified by flash chromatography on silica
gel (hexane/EtOAc 10/1).
1
2-Cyclohexyl-1-phenylsulfonylaziridine (2f): white solid; H
NMR (300 MHz, CDCl3) δ ) 7.92 (d, J ) 8.2 Hz, 2 H), 7.64-7.48
(m, 3 H), 2.60 (d, J ) 7.0 Hz, 1 H), 2.55-2.49 (m, 1 H), 2.09 (d,
J ) 4.5 Hz, 1 H), 1.70-1.40 (m, 5 H), 1.19-0. 80 (m, 6 H); 13C
NMR (75 MHz, CDCl3) δ ) 137.9 (C), 133.3 (CH), 128.8 (2×CH),
127.8 (2×CH), 45.1 (CH), 39.1 (CH), 32.6 (CH2), 29.9 (CH2), 29.4
(CH2), 25.8 (CH2), 25.3 (CH2), 25.1 (CH2); MS (70 eV) m/z (%)
265 [M+] (<1), 124 (91), 95 (100), 77 (74), 67 (30), 51 (27), 42
(73); HRMS calcd for C14H19NO2S 265.1136, found 265.1110; IR
(neat) ν˜ ) 3055, 1449, 1265, 1012, 738 cm-1; Rf ) 0.40 (hexane:
ethyl acetate 3:1).
2-(4-Chlorophenyl)-1-phenylsulfonylaziridine (2g): pale yellow
solid; 1H NMR (300 MHz, CDCl3) δ ) 7.98 (d, J ) 8.3 Hz, 2 H),
J. Org. Chem. Vol. 74, No. 6, 2009 2457

Concello´n et al.
(2×CH), 58.5 (CH), 45.6 (CH2), 38.3 (CH), 29.1 (CH2), 28.3 (CH2),
25.9 (CH2), 25.7 (CH2), 25.6 (CH2), 21.4 (CH3); MS (70 eV) m/z
(%) 315 [M+] (<1), 266 (64), 232 (79), 184 (18), 155 (97), 65
(28), 55 (25), 41 (28); HRMS calcd for C14H20NO2S [M+ - CH2Cl]
266.1214, found 266.1208; IR (neat) ν˜ ) 3282, 2930, 1265, 1161,
1010 cm-1; Rf ) 0.45 (hexane:ethyl acetate 3:1).
1-Chloro-3-phenyl-N-tosylpropan-2-amine (4d): pale yellow
solid; 1H NMR (300 MHz, CDCl3) δ ) 7.64 (d, J ) 8.2 Hz, 2 H),
7.27-7.03 (m, 7 H), 4.90 (d, J ) 8.2 Hz, 1 H), 3.75-3.65 (m, 1
H), 3.52-3.42 (m, 1 H), 2.89 (dd, J ) 13.8, 7.7 Hz, 1 H), 2.77
(dd, J ) 13.8, 6.7 Hz, 1 H), 2.42 (s, 3 H); 13C NMR (50 MHz,
CDCl3) δ ) 143.4 (C), 137.1 (C), 136.0 (C), 129.6 (2×CH), 129.1
(2×CH), 128.7 (2×CH), 126.9 (CH), 126.8 (2×CH), 55.0 (CH),
45.8 (CH2), 38.1 (CH2), 21.4 (CH3); MS (70 eV) m/z (%) 323 [M+]
(<1), 232 (70), 151 (76), 91 (100), 65 (35); HRMS calcd for
C15H16NO2S [M+ - CH2Cl] 274.0902, found 274.0933; IR (neat)
ν˜ ) 3288, 2947, 1598, 1334, 1011 cm-1; Rf ) 0.40 (hexane:ethyl
acetate 3:1).
followed by a solution of MeLi in ether (1.5 M, 1.6 mmol, 4 equiv).
The reaction mixture was stirred for 30 min and then warmed to
room temperature and left to stir for an additional 30 min. The
reaction mixture was then quenched with NH4Cl (aq), and the
organic layer was then extracted with diethyl ether (3 × 10 mL).
The combined extracts were dried over Na2SO4 and concentrated
under vacuum to yield crude aminoaziridines 11 which were purified
by flash chromatography on silica gel (hexane/EtOAc 10/1).
(2S,1′R)-1-Tosyl-2-[1′-(dibenzylamino)ethyl]aziridine (11a):
yellow oil; 1H NMR (300 MHz, CDCl3) δ ) 7.82 (d, J ) 8.4 Hz,
2 H), 7.35-7.20 (m, 12 H), 3.82 (d, J ) 13.8 Hz, 2 H), 3.62 (d, J
) 13.8 Hz, 2 H), 2.85-2.75 (m, 2 H), 2.44 (s, 3 H), 2.39-2.32
(m, 1 H), 2.15 (d, J ) 4.4 Hz, 1 H), 1.14 (d, J ) 6.6 Hz, 3 H); 13
C
NMR (75 MHz, CDCl3) δ ) 144.9 (C), 139.3 (2×C), 135.1 (C),
129.9 (2×CH), 129.7 (2×CH), 128.6 (4×CH), 128.3 (4×CH),
127.1 (2×CH), 59.8 (CH), 53.9 (2×CH2), 39.9 (CH), 33.4 (CH2),
21.6 (CH3), 13.5 (CH3); MS (70 eV) m/z (%) 420 [M+] (<1), 405
(7), 329 (100), 224 (30), 196 (12), 91 (69); HRMS (ESI+) calcd
for C25H29N2O2S [M + H]+ 421.1949, found 421.1944; IR (neat)
ν˜ ) 2957, 1495, 1455, 1326, 1161 cm-1; [R]20 ) -12.2 (c ) 0.75,
CHCl3); Rf ) 0.43 (hexane:ethyl acetate 5:1).
(2R,1′S)-1-Tosyl-2-[1′-(dibenzylamino)-3′-(methyl)butyl]aziri-
dine (11b): pale yellow oil; 1H NMR (300 MHz, CDCl3) δ ) 7.83
(d, J ) 8.4 Hz, 2 H), 7.35-7.24 (m, 12 H), 3.80 (d, J ) 13.7 Hz,
2 H), 3.56 (d, J ) 13.7 Hz, 2 H), 2.85-2.76 (m, 2 H), 2.45 (s, 3
H), 2.39-2.32 (m, 1 H), 2.16 (d, J ) 4.3 Hz, 1 H), 1.78-1.69 (m,
1 H), 1.57-1.41 (m, 1 H), 0.93-0.80 (m, 1 H), 0.72 (d, J ) 6.5
Hz, 3 H), 0.45 (d, J ) 6.5 Hz, 3 H); 13C NMR (75 MHz, CDCl3)
δ ) 144.6 (C), 139.5 (2×C), 135.0 (C), 129.6 (2×CH), 129.0
(2×CH), 128.5 (4×CH), 128.2 (4×CH), 127.0 (2×CH), 61.0 (CH),
56.8 (CH), 56.0 (CH), 53.9 (2×CH2), 53.0 (2×CH2), 40.1 (CH),
38.5 (CH2), 33.9 (CH2), 33.2 (CH2), 25.4 (CH), 23.9 (CH), 23.2
(CH3), 22.0 (CH3), 21.8 (CH3), 21.5 (CH3); MS (70 eV) m/z (%)
419 [M+ - iPr] (5), 371 (100), 331 (14), 266 (35), 196 (65); HRMS
calcd for C28H34N2O2S 462.2341, found 462.2311; IR (neat) ν˜ )
2956, 1495, 1455, 1325, 1162 cm-1; [R]20 ) -13.4 (c ) 0.82,
CHCl3); Rf ) 0.40 (hexane:ethyl acetate 5:1).
Deprotection/Benzylation Protocol of 11c toward the Synthesis
of Compounds 12 and 13. To a cooled (-78 °C) suspension of Li
powder (1.44 mmol) and naphthalene (1.62 mmol) in dry THF (4
mL) previously stirred for 1 h at rt was added under a N2 atmosphere
0.36 mmol of 11c. The mixture was stirred for an additional hour
at the same temperature, and then benzyl bromide (1.44 mmol)
was added. The reaction was stirred overnight and quenched with
NaHCO3 subsequently. The organic layer was extracted with diethyl
ether (3 × 10 mL), and the combined extracts were dried over
Na2SO4 and concentrated under vacuum. The N-benzylaziridine
crude was purified by flash chromatography on silica gel (hexane/
EtOAc 20/1) to afford the pure products 12 and 13.
Synthesis of Enantiopure Chloroamines 15. After applying the
Weinreb conditions to aminoaldehydes 9b,c, CH2Cl2 was removed
and THF (5 mL) was added. The reaction mixture was cooled to
-78 °C and CH2ICl (1.6 mmol, 4 equiv) was added followed by a
solution of MeLi in ether (1.5 M, 1.6 mmol, 4 equiv). The reaction
mixture was stirred for 3 h at -78 °C and then quenched with
NH4Cl (aq), and the organic layer was then extracted with diethyl
ether (3 × 10 mL). The combined extracts were dried over Na2SO4
and concentrated under vacuum to yield crude chloroamines 15
which were purified by flash chromatography on silica gel (hexane/
EtOAc 10/1).
2-Chloro-1-phenyl-N-tosylethanamine (4e): white solid; 1H
NMR (300 MHz, CDCl3) δ ) 7.64 (d, J ) 8.3 Hz, 2 H), 7.28-7.16
(m, 7 H), 5.39 (d, J ) 6.2 Hz, 1 H), 4.59 (q, J ) 6.2 Hz, 1 H),
3.74 (d, J ) 6.2 Hz, 1 H), 2.41 (s, 3 H); 13C NMR (75 MHz, CDCl3)
δ ) 143.6 (C), 137.1 (C), 136.9 (C), 129.5 (2×CH), 128.6 (2×CH),
128.3 (CH), 127.1 (2×CH), 126.8 (2×CH), 58.3 (CH), 47.8 (CH2),
21.4 (CH3); MS (70 eV) m/z (%) 260 [M+ - CH2Cl] (100), 155
(43), 91 (86), 65 (21); HRMS calcd for C14H14NO2S [M+ - CH2Cl]
260.0745, found 260.0750; IR (neat) ν˜ ) 3338, 3055, 1632, 1007,
673 cm-1; Rf ) 0.30 (hexane:ethyl acetate 3:1).
2-Chloro-1-cyclohexyl-N-sulfonylphenylethanamine (4f): white
solid; 1H NMR (300 MHz, CDCl3) δ ) 7.77 (d, J ) 7.6 Hz, 2 H),
7.47-7.35 (m, 3 H), 5.16 (d, J ) 8.6, 1 H), 3.44 (dd, J ) 11.4, 3.4
Hz, 1 H), 3.28 (dd, J ) 11.4, 4.5 Hz, 1 H), 3.19-3.08 (m, 1 H),
1.68-1.33 (m, 6 H), 1.12-0.54 (m, 5 H); 13C NMR (75 MHz,
CDCl3) δ ) 140.7 (C), 132.6 (CH), 128.9 (2×CH), 126.8 (2×CH),
58.6 (CH), 45.6 (CH2), 38.3 (CH), 29.0 (CH2), 28.2 (CH2), 25.8
(CH2), 25.6 (CH2), 25.5 (CH2); MS (70 eV) m/z (%) 252 [M+
-
CH2Cl] (79), 218 (90), 170 (25), 141 (69), 95 (16), 77 (100), 55
(29), 41 (29); HRMS calcd for C13H18NO2S [M+ - CH2Cl]
252.1058, found 252.1057; IR (neat) ν˜ ) 3371, 2930, 1266, 1164,
997 cm-1; Rf ) 0.42 (hexane:ethyl acetate 3:1).
2-Chloro-1-(4-chlorophenyl)-N-sulfonylphenylethanamine (4g):
white solid; 1H NMR (300 MHz, CDCl3) δ ) 7.73 (d, J ) 7.6 Hz,
2 H), 7.54 (t, J ) 7.6 Hz, 1 H), 7.41 (t, J ) 7.6 Hz, 2 H), 7.19 (d,
J ) 8.3 Hz, 2 H), 7.06 (d, J ) 8.3 Hz, 2 H), 5.45 (d, J ) 6.1 Hz,
1 H), 4.60 (q, J ) 6.1 Hz, 1 H), 3.68 (d, J ) 6.1 Hz, 2 H); 13C
NMR (75 MHz, CDCl3) δ ) 139.6 (C), 135.5 (C), 134.2 (C), 132.8
(CH), 128.9 (2×CH), 128.7 (2×CH), 128.2 (2×CH), 127.0
(2×CH), 57.7 (CH), 47.6 (CH2); MS (70 eV) m/z (%) 330 [M+]
(8), 280 (97), 141 (100); HRMS calcd for C13H11ClNO2S [M+
-
CH2Cl] 280.0199, found 280.0197; IR (neat) ν˜ ) 3252, 1448, 1266,
1014, 738 cm-1; Rf ) 0.62 (hexane:ethyl acetate 1:1).
2-Chloro-1-(4-methoxyphenyl)-N-sulfonylphenylethanamine
(4h): pale yellow solid;1H NMR (300 MHz, CDCl3) δ ) 7.73 (d,
J ) 7.4 Hz, 2 H), 7.52 (t, J ) 7.4 Hz, 1 H), 7.41 (t, J ) 7.4 Hz,
2 H), 7.02 (d, J ) 8.6 Hz, 2 H), 6.74 (d, J ) 8.6 Hz, 2 H), 5.28 (d,
J ) 6.3, 1 H), 4.54 (q, J ) 6.3 Hz, 1 H), 3.76 (s, 3 H), 3.70 (d, J
) 6.3 Hz, 2 H); 13C NMR (75 MHz, CDCl3) δ ) 159.5 (C), 139.9
(C), 132.6 (CH), 129.0 (C), 128.9 (2×CH), 128.0 (2×CH), 127.1
(2×CH), 114.0 (2×CH), 57.9 (CH), 55.2 (CH3), 47.8 (CH2); MS
(70 eV) m/z (%) 325 [M+] (2), 276 (100), 141 (20), 134 (39), 77
(65), 51 (16); HRMS calcd for C15H16ClNO3S 325.0539, found
325.0535; IR (neat) ν˜ ) 3338, 1514, 1266, 1006, 738 cm-1; Rf )
0.47 (hexane:ethyl acetate 1:1).
Synthesis of Aminoaziridines 11. R-Aminoimines 10 were
prepared using the method described by Weinreb (see ref 29).
However, no isolation of 10 was carried out due to its instability.
Therefore, after applying the Weinreb conditions, CH2Cl2 was
removed and THF (5 mL) was added. The reaction mixture was
cooled to -78 °C, and CH2I2 (1.6 mmol, 4 equiv) was added
(2S,3S)-1-Chloro-N3,N3-dibenzyl-5-methyl-N2-tosylhexane-2,3-di-
amine (15b): orange oil; 1H NMR (300 MHz, CDCl3) δ ) 7.50 (d,
J ) 8.2 Hz, 2 H), 7.41-7.24 (m, 12 H), 4.86 (d, J ) 9.3 Hz, 1 H),
3.87 (dd, J ) 10.9, 3.0 Hz, 1 H), 3.66 (d, J ) 13.9 Hz, 2 H), 3.48
(d, J ) 13.9 Hz, 2 H), 3.44-3.35 (m, 1 H), 3.22 (dd, J ) 10.9, 5.8
Hz, 1 H), 2.73 (q, J ) 7.0 Hz, 1 H), 2.43 (s, 3 H), 1.78-1.40 (m,
3 H), 0.84 (d, J ) 6.3 Hz, 3 H), 0.76 (d, J ) 6.5 Hz, 3 H); 13C
NMR (75 MHz, CDCl3) δ ) 144.5 (C), 139.5 (2×C), 137.3 (C),
129.6 (2×CH), 128.9 (4×CH), 128.4 (4×CH), 127.2 (2×CH),
2458 J. Org. Chem. Vol. 74, No. 6, 2009

Synthesis of Aziridines and ꢀ-Chloroamines
127.0 (2×CH), 57.0 (CH), 54.9 (2×CH2), 54.7 (CH), 45.8 (CH2),
34.8 (CH2), 25.8 (CH), 23.0 (CH3), 22.1 (CH3), 21.4 (CH3); MS
(70 eV) m/z (%) 455 [M+ - iPr] (52), 330 (35), 316 (23), 230
(36), 210 (100), 169 (51), 118 (30); HRMS calcd for C21H27N2O2S
[M+ - CH2Ph, - HCl] 371.1793, found 371.1790; IR (neat) ν˜ )
3060, 1601, 1495, 1456, 1162 cm-1; [R]20 ) -4.9 (c ) 0.90,
CHCl3); Rf ) 0.30 (hexane:ethyl acetate 5:1).
1162 cm-1; [R]20 ) +9.1 (c ) 0.82, CHCl3); Rf ) 0.25 (hexane:
ethyl acetate 5:1).
Acknowledgment. We acknowledge the Ministerio de Edu-
cacio´n y Cultura (CTQ2007-61132), the Principado de Asturias
(FICYT IB08-028), and the European Union (Fondo Europeo
de Desarrollo Regional) for financial support. J.M.C. thanks his
wife Carmen Ferna´ndez-Flo´rez for her time. H.R.-S. and C.S.
thank the MEC for a Ramo´n y Cajal Contract (Fondo Social
Europeo) and for a predoctoral fellowship, respectively. Our
thanks to Euan C. Goddard (CRL, University of Oxford) for
his revision of the English.
(2S,3S)-1-Chloro-N3,N3-dibenzyl-4-phenyl-N2-tosylbutane-2,3-di-
amine (15c): orange oil; 1H NMR (300 MHz, CDCl3) δ )
7.42-7.15 (m, 19 H), 4.70 (d, J ) 9.42 Hz, 1 H), 3.93-3.79 (m,
1H), 3.81 (d, J ) 13.56 Hz, 2 H), 3.58-3.43 (m, 1 H), 3.50 (d, J
) 13.65 Hz, 2 H), 3.19-3.04 (m, 4 H), 2.42 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ ) 143.3 (C), 140.0 (C), 139.1 (2×C), 137.3
(C), 129.6 (2×CH), 129.2 (2×CH), 128.8 (5×CH), 128.5 (5×CH),
127.3 (2×CH), 126.8 (2×CH), 126.0 (CH), 61.2 (CH), 55.2 (CH),
55.1 (2xCH2), 45.4 (CH2), 31.9 (CH2), 21.5 (CH3); MS (70 eV)
m/z (%) 533 [M+] (100), 497 (71), 441 (12), 393 (20), 300 (26),
91 (27); HRMS calcd for C24H25N2O2S [M+ - CH2Ph, - HCl]
405.1636, found 405.1633; IR (neat) ν˜ ) 3063, 1600, 1496, 1455,
1
Supporting Information Available: Copies of H and 13C
NMR spectra for all new compounds 2, 4, 11, and 15. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO802596Y
J. Org. Chem. Vol. 74, No. 6, 2009 2459