Sulfur ylide promoted synthesis of N-protected aziridines: A combined experimental and computational approach

Article abstract of DOI:10.1002/chem.201001436

A range of N-protected aziridines [N-Tosyl (N-Ts), N-2- trimethylsilylethanesulfonamide (N-SES), N-tertbutoxycarbonylamido (N-Boc), and N-o-nitrobenzenesulfonamide (oNs)] were prepared in moderate to good yield and with high enantiomeric excess of both isomers starting from N-protected imines, using a sulfonium salt derived from Eliel's oxathiane. The diastereoselectivities of the reactions are influenced by the imine N-protecting group, the imine substituent, and the sulfide structure. An unusual cis selectivity was observed in the formation of N-tosyl-2-phenyl-3-tert- butylaziridine and N-o-trimethylsilylethanesulfonamide-2-phenyl-3-tert- butylaziridine, which was explained by using computational models. The analysis suggests that betaine formation in the case of N-tosyl-tert-butylaldimine aziridination using oxathiane benzyl sulfonium ylide 1′ is reversible and that the selectivity is determined at the rotation step, which is unusual for semistabilized ylide aziridination. We have shown herein that the steric bulk of an imine substituent, in combination with a sterically demanding sulfonium ylide, can also affect the reversibility of the reaction. This is the first example of this sort involving aziridinations using semistabilized ylides.

Full text of DOI:10.1002/chem.201001436

DOI: 10.1002/chem.201001436
Sulfur Ylide Promoted Synthesis of N-Protected Aziridines: A Combined
Experimental and Computational Approach
Irena Dokli,[a] Ivana Matanovic´,[b] and Zdenko Hamersˇak*[a]
Abstract: A range of N-protected aziri-
dines [N-Tosyl (N-Ts), N-2-trimethylsi-
lylethanesulfonamide (N-SES), N-tert-
butoxycarbonylamido (N-Boc), and N-
lectivity was observed in the formation
of N-tosyl-2-phenyl-3-tert-butylaziridine
using oxathiane benzyl sulfonium ylide
1’ is reversible and that the selectivity
is determined at the rotation step,
which is unusual for semistabilized
ylide aziridination. We have shown
herein that the steric bulk of an imine
substituent, in combination with a steri-
cally demanding sulfonium ylide, can
also affect the reversibility of the reac-
tion. This is the first example of this
sort involving aziridinations using semi-
stabilized ylides.
and
N-o-trimethylsilylethanesulfona-
mide-2-phenyl-3-tert-butylaziridine,
o-nitrobenzenesulfonamide
(oNs)]
which was explained by using computa-
tional models. The analysis suggests
that betaine formation in the case of
N-tosyl-tert-butylaldimine aziridination
were prepared in moderate to good
yield and with high enantiomeric
excess of both isomers starting from N-
protected imines, using a sulfonium salt
derived from Elielꢀs oxathiane. The
diastereoselectivities of the reactions
are influenced by the imine N-protect-
ing group, the imine substituent, and
the sulfide structure. An unusual cis se-
Keywords: asymmetric synthesis ·
azomethine ylides · density func-
tional calculations · diastereoselec-
tivity · ylides
Introduction
for asymmetric epoxidation and cyclopropanation.[5] This ox-
athiane also proved to be a very efficient chiral auxiliary for
the synthesis of aziridines. Solladiꢁ-Cavallo et al. reported a
two-step asymmetric synthesis of disubstituted N-tosyl (N-
Ts) aziridines using (R,R,R,S)-(À)-benzylsulfonium salt 1
derived from Elielꢀs oxathiane.[6] Phosphazene base (EtP2)
was used to generate the ylide. Even though cis/trans mix-
tures were obtained, both isomers had high enantiomeric
purity (98.7–99.9%) and the method was applicable for
gram-quantity synthesis. Furthermore, the chiral auxiliary
could be recovered and reused. However, the practicality of
this procedure is limited by the use of expensive phospha-
zene base.
Chiral aziridines are highly useful synthetic intermediates.
The strained three-membered ring can undergo a range of
transformations, especially, ring opening to afford versatile,
optically active compounds. During the past two decades,
many different methods for asymmetric aziridination have
been developed.[1] Amongst them, a significant number in-
volve imine aziridinations using a carbene,[2] or a carbene
equivalent, such as sulfur ylides. The reactions of chiral
sulfur ylides with imines have proven to be a very powerful
method for asymmetric aziridinations.[3]
Elielꢀs oxathiane[4] was first used by Solladiꢁ-Cavalloꢀs
group as a precursor of diastereo- and enantiopure ylides
Recently, we reported an application of the above method
for the asymmetric synthesis of the N-Ts, N-2-trimethylsilyl-
AHCTUNGTREGeNNUN thanesulfonamide (N-SES), and N-tert-butoxycarbonylami-
ˇ
[a] I. Dokli, Dr. Z. Hamersak
do (N-Boc) disubstituted aziridines, also in high enantiomer-
ic excess (ee).[7] Sodium hydride was successfully used as a
substitute for the sensitive phosphazene base EtP2 without
any loss of yield, enantio- or diastereoselectivity. Herein, we
present a further investigation into the influence of the
imine substituent on diastereoselectivity in a combined ex-
perimental and computational approach.
Department of Organic Chemistry and Biochemistry
ˇ
´
Rudjer Boskovic Institute
P. O. Box 180, 10002 Zagreb (Croatia)
Fax : (+385)14680108
E-mail: hamer@irb.hr
´
[b] Dr. I. Matanovic
ˇ
´
Department of Physical Chemistry, Rudjer Boskovic Institute
P. O. Box 180, 10002 Zagreb (Croatia)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201001436.
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Chem. Eur. J. 2010, 16, 11744 – 11752

FULL PAPER
Table 2. Synthesis of aziridines using ylide derived from salt 2.
Results and Discussion
Two sulfonium salts were used as ylide precursors in imine
aziridinations:
(R,R,R,Ss)-hexahydro-4,4,7-trimethyl-3-
benzyl-1,3-benzoxathiane trifluoromethanesulfonate (1),
which is a chiral benzyl sulfonium salt derived from 1,3-oxa-
thiane for the synthesis of chiral aziridines, and benzyldime-
thylsulfonium triflate (2) for achiral aziridinations.
Entry R1
R2
Imine Product Yield [%][a] cis/trans[b]
1
phenyl
Boc
SES
Ts
oNs
Boc
SES
Ts
oNs 11
Boc 12
SES 13
4
5
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
68
86
70
58
54
67
76
35
78
84
86
53
66
64
67
76
39
81
53
n.i.[c]
5:95
9:91
2
phenyl
3
phenyl
6
7
8
19:81
29:71
2:98
4
phenyl
5
PMP
6
PMP
9
10
12:88
14:86
21:78
0:100
26:74
33:67
38:62
67:33
69:31
30:70
39:61
41:59
77:23
57:43
–
7
PMP
8
PMP
9
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
tert-butyl
tert-butyl
9-phenanthryl SES 18
9-phenanthryl Ts 19
9-phenanthryl oNs 20
10
11
12
13
14
15
16
17
18
19
20
Ts
oNs 15
SES 16
Ts
14
The sulfonium salt 1 was prepared from (R,R,R)-(+)-oxa-
thiane[4] 3 and benzyl alcohol by using the triflate method
reported by Vedejs et al.,[8] and was isolated as a single dia-
stereomer with (R,R,R,Ss)-(À) configuration.[9] N-SES, N-
Boc, and N-Ts imines were prepared according to literature
procedures[10] and are all known compounds, except for N-
(9-phenanthrylmethylidene)-2-trimethylsilylethanesulfon-
17
9-anthryl
9-anthryl
9-anthryl
SES 21
Ts 22
oNs 23
ACHTUNGTRENNUNG
[a] Isolated yield after column chromatography. [b] The cis/trans ratios
were determined by 1H NMR spectroscopy of the crude product. [c] Not
isolated due to decomposition.
ACHTUNGTRENNUNG
oNs) imines were prepared according to a slightly modified
literature procedure[11] to that used for the preparation of N-
pNs imines, and are new compounds except for phenyl- (7)
and 4-methoxyphenyl-substitut-
ed (11) imines.[11b] Chiral aziri-
Table 1. Asymmetric synthesis of chiral aziridines.
dines 24–42 were prepared
from the corresponding N-pro-
tected imines 4–22 and oxa-
thiane benzyl sulfonium salt 1
by using sodium hydride to gen-
erate the ylide (Table 1). Reac-
tions were carried out in THF
overnight at À408C. Aziridines
24–42 were also prepared in
racemic form from imines 4–22
Entry
R1
R2
Imine Product Yield [%][a] cis/trans[b] cis ee [%][c]
trans ee [%][c]
1
2
3
4
5
6
7
8
phenyl
phenyl
phenyl
phenyl
PMP
PMP
PMP
PMP
Boc
SES
Ts
oNs
Boc
SES
Ts
oNs
Boc
SES 13
4
5
6
7
8
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
60
70
60
67
31
47
57
55
75
63
60
65
61
68
80
76
76
53
88
n.i.[e]
10:90
44:56
60:40
53:47
9:91
63:37
58:42
61:39
2:98
24:76
31:69
58:42
100:0
100:0
44:56
45:55
70:30
9:91
meso
meso
meso
meso
–
>99
98
99
–
97
96
97
98
97
97
98
98
–
99
–
97
>99
97
98
96
and benzyl sulfonium salt
2
9
98
under the same reaction condi-
tions used for the preparation
of chiral aziridines (Table 2).
We have successfully pre-
10
11
12
n.d.[d]
n.d.[d]
96
9
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
tert-butyl
tert-butyl
9-phenanthryl SES 18
9-phenanthryl Ts
9-phenanthryl oNs
10
11
12
13
14
15
16
17
18
19
20
98
96
98
–
–
97
99
98
pared
N-(9-anthrylmethyli-
Ts
oNs
SES 16
Ts 17
14
15
dene)-2-nitrobenzenesulfona-
mide (23) but, although we ob-
served conversion of the imine
into the aziridine, we were not
able to isolate pure aziridine
because of its instability during
purification. Lower yields were
observed for 4-methoxyphenyl-
substituted aziridines (Tables 1
and 2, entries 5–8), due to the
19
20
9-anthryl
9-anthryl
9-anthryl
SES 21
Ts
oNs
98
99
–
22
23
24:76
–
1
[a] Isolated yield after column chromatography. [b] The cis/trans ratios were determined by H NMR spectros-
copy of the crude product. [c] Determined by chiral HPLC on the cis/trans mixture. [d] Enantiomers could not
be separated on the following columns: Chiralcel OJ, OD, OB, Chiralpak AS, or AD. [e] Product not isolated
presence of the electron-donat- due to decomposition.
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11745

ˇ
Z. Hamersak et al.
ing aromatic substituent, which led to partial ring opening
during the purification step.
imines (Tables 1 and 2). By comparing the diastereoselectiv-
ity, the protecting groups can be arranged in the following
order of decreasing trans selectivity: Boc>SES>Ts>oNs.
The structure of the sulfonium salt affected the diastereo-
selectivity in almost all cases. The larger oxathiane benzyl
sulfonium salt 1 induced the formation of more cis isomer,
compared with the smaller sulfonium salt 2. There is no gen-
eral explanation for the influence of the imine substituent.
The most interesting case appeared to be reactions of sulfo-
nium salt 1 with tert-butylaldimines 16 and 17, which gave
the aziridine product with 100% cis de (Table 1, entries 13
and 14). In these cases, the N-protecting group had no effect
on selectivity. In contrast, the sulfide structure had signifi-
cant influence; the reaction with the smaller benzyl sulfoni-
um salt 2 gave aziridines with a cis de of 24–38% (Table 2,
entries 13 and 14).
Enantiomeric purities of all the prepared chiral aziridines
were very high (Table 1). We previously showed that the
choice of base, solvent, and imine reagent had no effect on
the enantioselectivity in the case of the aziridination reac-
tion using ylide 1’ derived from oxathiane benzyl sulfonium
salt 1.[7] The excellent enantioselectivities of both isomers
observed in all cases is in accordance with Solladie-Cavalloꢀs
model, which states that the approach of the aldimine
occurs highly selectively at the Re face of the C2 carbon of
the ylide 1’ (Scheme 1).[6] The absolute configurations were
To explain this selectivity, we conducted a computational
investigation into the reaction profiles of the two aziridina-
tion reactions that resulted in the formation of aziridines
with opposite diastereoselectivity. Until now, only a few
DFT studies on aziridination reaction mechanisms and the
stereoselectivity processes involved have been reported.[12]
These include a theoretical study on the stability of different
structures of the ylide carbanions and imines and their role
in the aziridination reaction.[12d] The generally accepted
mechanism for sulfonium ylide promoted aziridine forma-
tion involves the addition of the ylide to the imine to form a
Scheme 1. Solladie-Cavalloꢀs model for enantioselectivity.[6]
previously determined by X-ray analysis using the Bijvoet
method to be (2R,3S) for cis-N-Ts-2-phenyl-3-tert-butylaziri-
dine and (2R,3R) for trans-N-Ts-2-phenyl-3-naphthylaziri-
dine. The R-configuration found at C-2 is consistent with the
proposed model. Therefore, all of the trans aziridines were
assigned (2R,3R) configuration, and all the cis aziridines,
(2R,3S) configuration.[6] To further confirm this postulation,
we deprotected cis-N-SES-2-phenyl-3-tert-butylaziridine (36)
using tetrabutylammonium fluoride, and converted the un-
protected cis-2-phenyl-3-tert-butylaziridine into cis-N-Ts-2-
phenyl-3-tert-butylaziridine using tosyl chloride and diiso-
propylethylamine. The measured optical rotation of the
product was in accordance with the literature data for the
(2R,3S)-N-Ts-2-phenyl-3-tert-butylaziridine.[6]
À
betaine, rotation around the formed C C bond, and elimina-
tion of the sulfide, which is accompanied by ring closure to
the aziridine (Scheme 2).[3d,13]
The reactions of benzyl sulfonium ylide 1’ with N-Ts-
naphthaldimine (14) and N-Ts-tert-butylaldimine (17) repre-
The influence of the N-protecting group, imine substitu-
ent, and the sulfonium salt structure on the diastereoselec-
tivity of the reaction was studied and found to be highly
substrate dependent. The cis/trans ratios were determined
1
by H NMR spectroscopic analysis of the crude product. As
expected,[3c] the best trans selectivity was obtained in the re-
actions with imines bearing the N-Boc substituent (trans dia-
stereomeric excess (de) 80–100%, Tables 1 and 2). A combi-
nation of the N-Boc group and a smaller sulfonium salt 2 re-
sulted in 90–100% trans de for the synthesis of aziridines 24,
28, and 32. By using the larger, chiral salt 1, somewhat
lower trans de values of 80–96% were obtained. Unfortu-
nately, we were unable to fully explore the effect of the
imine substituent on the diastereoselectivity in the case of
N-Boc imines because, so far, we could not prepare N-Boc
imines with anthryl and phenanthryl substituents. We suc-
cessfully prepared N-Boc-tert-butylaldimine, however, the
reaction with both sulfonium salts failed. N-SES imines gave
mostly cis/trans mixtures of aziridines with low trans selec-
tivity. N-Ts and N-oNs imines behaved in a similar manner,
but with somewhat reduced trans selectivity than N-SES
Scheme 2. Generally accepted aziridination mechanism. TS-Ac and TS-
À
At refer to the cisoid and transoid addition transition states in the C C
bond-forming step, I-t and I-c refer to the intermediate betaines with the
transoid and cisoid orientation, TS-R denotes the transition state for
cisoid to transoid rotation, and TS-E denotes the transition state for the
elimination step.
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N-Protected Aziridines
FULL PAPER
À
sent two aziridination reactions in which the change of an
imine substituent induces a large difference in the diastereo-
selectivity of the reaction: N-Ts-2-phenyl-3-(1-naph-
and the imine substituent (R) around the newly formed C
C bond. The approach of the ylide and the imine can be
cisoid or transoid according to the arrangement of the aza
À
thyl)aziridine (34) cis/trans=31:69 and N-Ts-2-phenyl-3-tert-
and sulfonium groups around the formed C C bond (cisoid:
butylaziridine (37) cis/trans=100:0. To gain a better insight
into the reaction mechanisms of the experimentally studied
reactions, we calculated the energy profiles for the two rep-
resentative reactions using DFT including solvent effects.
The B3LYP/6-31G(d)[18] level of calculation was chosen to
obtain optimal trade-off between the computational cost
and the accuracy of the results; for this reason, the obtained
energy profiles provide only a qualitative picture of the
studied mechanisms. A reliable explanation or the ability to
predict the extent of diastereoselectivity requires knowledge
of the activation barriers for all of the elementary steps in-
volved in the reaction.[12] The calculated energy profiles for
the two aziridination reactions are shown in Figure 1.
S+ and NÀ on the same side; transoid: S+ and NÀ on oppo-
site sides). In this way, four betaine structures can be
formed: cisoid-syn, cisoid-anti, transoid-syn, and transoid-
anti betaine (Scheme 2). In the case of the anti pathway, in
both aziridination reactions, only a cisoid transition state
(TS-Ac) was located. Every attempt to obtain a transoid
structure (TS-At) of an anti orientation revealed the higher
energy of such a geometry and led to a cisoid transition
state.[14] The tendency to adopt the cisoid orientation in an
anti pathway was previously observed in the addition of an
ylide to an aldehyde, and was attributed to the favorable
Coulombic interactions between the charged aza and sulfo-
nium groups.[12,15] However, besides the electrostatic effects,
an important role in the stability of these structures can be
attributed to the steric effects. The close proximity of the
ylidic substituent (phenyl) and the imine substituent (1-
naphthyl or tert-butyl) is destabilizing and leads to a lower
barrier for the cisoid orientation in an anti approach. In the
syn approach, the same steric effect favors the transoid ori-
entation. The calculated barriers for betaine formation are
shown in Figure 2. Consequently, it is reasonable to assume
that, in the addition step, only two betaine intermediates are
formed: the cisoid-anti betaine (I-c) and the transoid-syn be-
taine (I-t).
In the first step in the mechanism of aziridine formation,
addition of the ylide to the imine leads to the formation of
intermediate betaines, which are designated syn or anti de-
pending on the relative position of the ylidic phenyl group
A careful analysis of the transoid-syn (I-t) and cisoid-anti
(I-c) betaine structures, revealed that, in addition to the fa-
vorable Coulombic interactions between the charged S+ and
NÀ groups and the favorable steric arrangement of the sub-
À
stituents, the presence of a C H···O hydrogen bond between
the oxygen of the N-Ts group and an ylidic hydrogen atom
contributes to the greater stability of these structures. Short
À
H···O distances and C H···O angles in the range of 120–1558
in the structures of transoid-syn and cisoid-anti betaines in-
À
dicate the formation of stabilizing C H···O hydrogen
bonds.[16] For instance, in the case of the reaction with 14,
the H···O distance is 2.06 ꢃ for the transoid-syn and 2.16 ꢃ
À
for the cisoid-anti betaine, while the C H···O angles have
values of 129 and 1548.
Transoid-syn betaine (I-t) directly eliminates an oxathiane
group to yield the cis aziridine as a product. In the case of
the anti approach, the elimination reaction also occurs from
À À À
the transoid betaine, in which the S C C N dihedral angle
is close to 1808, and thus the cisoid intermediate must first
À
undergo rotation around the newly formed C C bond to
form a transoid intermediate. The elimination reaction in
transoid-anti betaine will then lead to the formation of a
trans aziridine (Figure 1, top). The calculated energy profiles
(Figure 1) reveal that the transoid-anti betaine formed in the
rotation is much higher in energy than the cisoid-anti be-
taine. In the case of the reaction of 14, the transoid-anti be-
taine is higher in energy than the cisoid-anti betaine by
6.4 kcalmolÀ1 and, in the reaction of 17, by more than
11.5 kcalmolÀ1.
Figure 1. A schematic representation of the reaction profiles for the aziri-
dination reaction of 14 (top) and 17 (bottom). DE [kcalmolÀ1] values
were calculated at the PCMACHTNUTRGNE(NUG THF)/B3LYP/6-31G(d)//B3LYP/6-31G(d)
level of theory and are given relative to separate reactants. c: anti ap-
proach, a: syn approach.
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ˇ
Z. Hamersak et al.
ylide 1’ with 14, the highest points on the energy profile are
the addition transition states, which lead to the formation of
the cisoid-anti and transoid-syn betaine intermediates
(Figure 1). This indicates that the overall cis/trans selectivity
is determined by the relative energies of syn and anti addi-
tion transition states. This case is similar to the previously
reported aziridine reactions in which the difference in
energy between the transition states for the addition step
can correctly predict the observed trans/cis ratio.[12d] Since
the barrier for the formation of an anti betaine (6.1 kcal
molÀ1; Figure 1, top) is slightly lower than for the formation
of the syn betaine (7.4 kcalmolÀ1), our calculations predict a
low trans selectivity in the reaction of ylide 1’ with 14. This
is in good agreement with the experimental observations,
which gives a cis/trans ratio of 31:69 of the aziridine product
(Table 1, entry 11). In the reaction of ylide 1’ with 17, the
energy profile indicates that both intermediates can form in
the course of the reaction (Figure 1, bottom); the transoid-
syn betaine, which can directly undergo elimination of sul-
fide and yield the cis product, and the cisoid-anti betaine,
which can ultimately lead to the formation of the trans prod-
uct. However, for a trans product to form in the elimination
reaction, the cisoid-anti betaine must transform into a trans-
À
oid-anti betaine by rotating around the newly formed C C
bond. As the barrier for the cisoid to transoid rotation is too
high (16.9 kcalmolÀ1), the rotation is slow and reversion to
reactants occurs instead. This leads to the domination of the
syn pathway and to the high selectivity for the cis product.
We can thus conclude that the aziridination reaction of 17 is
similar to epoxidation[15] and cyclopropanation[17] reactions
in which the cisoid–transoid interconversion of betaines
through a torsional motion was determined to be the rate-
limiting step. In the case of the aziridination reaction of 14,
the barrier for the cisoid to transoid-anti betaine rotation is
much lower than in the aziridination reaction of 17 (7.4 vs.
16.9 kcalmolÀ1). The large difference in rotation barriers for
the two cases can be attributed to a large difference in the
size of the imine substituents. Clearly, rotation of a bulky
À
tert-butyl group around a C C bond induces much more
steric strain than rotation of a flat naphthyl group.
Conclusion
We have successfully prepared a range of N-Ts, N-SES, N-
Boc, and N-oNs aziridines in moderate to good yield and
high enantiomeric excess of both isomers. The diastereose-
lectivities of the reactions are variable and are influenced by
the imine N-protecting group, the imine substituent, and the
sulfide structure. By comparing the diastereoselectivities, we
can arrange the protecting groups in the following order of
decreasing trans selectivity: Boc>SES>Ts>oNs. The un-
usual 100% cis selectivity in the formation of N-SES-2-
phenyl-3-(tert-butyl)aziridine (36) and N-Ts-2-phenyl-3-tert-
butylaziridine (37) was explained through the use of compu-
tational models. The analysis suggests that betaine formation
in the case of aziridination of N-Ts-tert-butylaldimine (17)
Figure 2. Transition-state structures for the addition of ylide 1’ to 14 (a)
and 17 (b) obtained at the B3LYP/6-31G(d) level of theory. The energies
were obtained at the PCMACTHNUTRGNE(NUG THF)/B3LYP/6-31G(d)//B3LYP/6-31G(d)
level and are given relative to separate reactants.
The calculated energy profiles (Figure 1) can easily ex-
plain the difference in the diastereoselectivity of the two
aziridination reactions. In the reaction of benzyl sulfonium
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N-Protected Aziridines
FULL PAPER
collected by filtration and dried under vacuum. Product 11 was isolated
as an olive-green powder (552 mg, 78%). M.p. 152.9–153.48C; 1H NMR
(300 MHz, CDCl3): d=3.90 (s, 3H), 6.98–7.02 (m, 2H), 7.75–7.80 (m,
3H), 7.94–7.97 (m, 2H), 8.36–8.38 (m, 1H), 8.97 ppm (s, 1H); 13C NMR
(75 MHz, CDCl3): d=55.8, 114.9, 124.6, 124.9, 131.8, 132.3, 132.5, 134.3,
134.4, 166.0, 172.6 ppm; IR (KBr): n˜ =1683, 1604, 1540, 1513, 1364, 1273,
using benzyl sulfonium ylide 1’ is reversible and that the se-
lectivity is determined at the rotation step. Previous investi-
gations suggested that the degree of reversibility might be
affected by the steric bulk and the electron-withdrawing
ability of the N substituent.[1g,3g] We have shown here that
the steric bulk of the imine substituent, in combination with
a sterically demanding sulfonium ylide, can also affect the
reversibility of the reaction. This is the first example of this
sort of aziridination using a semistabilized ylide.
1162, 1123, 808 cmÀ1
.
N-(1-Naphthylmethylidene)-2-nitrobenzenesulfonamide (15): Compound
15 was prepared as described above, starting from 1-naphthaldehyde
(300 mg, 1.92 mmol, 1 equiv), 2-nitrobenzenesulfonamide (390 mg,
1.95 mmol, 1.01 equiv), and tetraethyl orthosilicate (0.79 mL, 3.5 mmol,
1.8 equiv), and was isolated as a brown powder after recrystallization
from EtOAc/hexane (470 mg, 72%). M.p. 148.5–149.18C; 1H NMR
(300 MHz, CDCl3): d=7.60–7.65 (m, 2H), 7.70–7.75 (m, 1H), 7.78–7.85
(m, 3H), 7.96 (d, 1H, J=8.4 Hz), 8.18 (d, 1H, J=8.2 Hz), 8.27 (dd, J1 =
1.0, J2 =7.2 Hz, 1H), 8.46–8.49 (m, 1H), 9.01 (d, J=8.5 Hz, 1H),
9.69 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d=124.2, 124.8, 125.2,
127.1, 127.4, 129.2, 129.3, 132.1, 132.6, 133.8, 134.6, 135.7, 137.0, 148.6,
Experimental Section
Computational details: The gas-phase geometries of the intermediates,
transition states, reactants, and products in the aziridine formation mech-
anism were obtained by using DFT with the B3LYP[18] exchange-correla-
tion functional and the 6-31G(d) basis set. The energies in THF (total
free energies in solution) were obtained by using the self-consistent reac-
tion field approach with the polarizable continuum model (SCRF-PCM)
as implemented in the Gaussian 03 quantum chemical software pack-
age.[19] Because of the large size of the studied molecules, the solvation
effect in all of the calculated energy profiles was included only by means
of single-point energy evaluation using the gas-phase geometries [PCM-
173.4 ppm; IR (KBr): n˜ =1563, 1533, 1358, 1317, 1159, 1121, 811 cmÀ1
.
N-(9-Phenanthrylmethylidene)-2-nitrobenzenesulfonamide (20): Com-
pound 20 was prepared as described above, starting from 9-phenantralde-
hyde (300 mg, 1.45 mmol, 1 equiv), 2-nitrobenzenesulfonamide (303 mg,
1.5 mmol, 1.03 equiv), and tetraethyl orthosilicate (1 mL, 4.5 mmol,
3 equiv), and isolated as a brown powder after recrystallization from
EtOAc/hexane (266 mg, 47%). M.p. 170.8–171.58C; 1H NMR (300 MHz,
CDCl3): d=7.63–7.84 (m, 7H), 7.98–8.01 (m, 1H), 8.47 (dt, J1 =1.3, J2 =
6.9 Hz, 1H), 8.51 (s, 1H), 8.66 (d, J=8.4 Hz, 1H), 8.69–8.72 (m, 1H),
9.10–9.13 (m, 1H), 9.63 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d=
122.4, 122.7, 124.3, 124.9, 125.0, 126.0, 127.0, 127.3, 127.8, 128.5, 129.6,
130.2, 130.4, 130.5, 131.6, 132.2, 133.1, 134.1, 140.1, 148.1, 173.6 ppm; IR
ACHTUNGTRENNUNG(THF)/B3LYP/6-31G(d)//B3LYP/6-31G(d) level of theory]. To validate
the quality of our computations, the first step in aziridine formation, that
À
is, the C C bond-forming step, was studied by performing the optimiza-
tions in the solvent. The changes in energy between the gas-phase geo-
metries and fully optimized solvent-phase geometries were very small
(less than 2 kcalmolÀ1), which confirmed previous findings that gas-phase
geometry optimization followed by single-point energy evaluation can
give satisfactory estimates of the mechanism and stereoselectivity in
sulfur ylide promoted aziridination reactions.[12b] Because of the low sym-
metry of the molecules and the high flexibility of the studied systems,
transition states were located by calculating the relaxed energy scans
(KBr): n˜ =1570, 1550, 1330, 1162, 1126, 826 cmÀ1
.
N-(9-Anthrylmethylidene)-2-nitrobenzenesulfonamide (23): Compound
23 was prepared as described above starting from 9-anthraldehyde
(300 mg, 1.45 mmol, 1 equiv), 2-nitrobenzenesulfonamide (295 mg,
1.47 mmol, 1.02 equiv), and tetraethyl orthosilicate (1 mL, 4.5 mmol,
3 equiv), and isolated as an orange powder after recrystallization from
EtOAc/hexane (368 mg, 65%). M.p. 181.9–182.88C; 1H NMR (300 MHz,
CDCl3): d=7.55–7.60 (m, 2H), 7.71–7.82 (m, 5H), 8.07 (d, J=8.4 Hz,
2H), 8.52 (d, J=7.2 Hz, 1H), 8.76 (s, 1H), 9.12 (d, J=9.0 Hz, 2H),
10.49 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d=120.8, 124.3, 124.8,
126.1, 129.7, 130.1, 131.1, 132.2, 132.3, 132.7, 133.7, 134.5, 137.8,
À
along an appropriate internal coordinate (C C bond length or S-C-C-N
dihedral angle). The geometry with a highest energy along the calculated
energy profile was used as a starting point for the transition state optimi-
zation using the Berny algorithm, as implemented in Gaussian 03. Fre-
quency calculations otherwise used to confirm the nature of the obtained
stationary points were not performed in this case due to the fact that it is
extremely unlikely that the obtained geometries would correspond to
anything other than transition states.
171.4 ppm; IR (KBr): n˜ =1552, 1523, 1343, 1325, 1164, 1122 cmÀ1
.
N-(9-Phenanthrylmethylidene)-2-trimethylsilylethanesulfonamide (18): A
mixture of phenanthrene-9-carboxaldehyde (300 mg, 1.45 mmol, 1 equiv),
2-(trimethylsilyl)ethanesulfonamide (272 mg, 1.5 mmol, 1.1 equiv), and
anhydrous triethylamine (0.82 mL, 5.8 mmol, 4 equiv) in anhydrous
CH2Cl2 (15 mL), under argon, was cooled to 08C. A solution of TiCl4
(1.45 mL, 1m in CH2Cl2, 1 equiv) was added slowly with a syringe, and
the reaction mixture was stirred at 08C for 1 h, and then at RT for 20 h.
The reaction mixture was filtered through Celite, concentrated, and tolu-
ene (20 mL) was added to the solid residue. After 10 min of stirring, the
mixture was filtered again, and the filtrate was concentrated under re-
duced pressure. Product 18 was found to decompose on silica gel and was
therefore used in the next step without further purification (327 mg,
63%). 1H NMR (300 MHz, CDCl3): d=0.07 (s, 9H), 1.13–1.16 (m, 2H),
3.23–3.26 (m, 2H), 7.67 (ddd, J1 =7.7, J2 =7.1, J3 =0.9 Hz, 1H), 7.72–7.77
(m, 2H), 7.81 (ddd, J1 =8.3, J2 =7.0, J3 =1.3 Hz, 1H), 7.99 (dd, J1 =7.8,
J2 =0.7 Hz, 1H), 8.42 (s, 1H), 8.67 (d, J=8.3 Hz, 1H), 8.72–8.73 (m, 1H),
9.16–9.17 (m, 1H), 9.55 ppm (s, 1H). 13C NMR (75 MHz, CDCl3): d=
À2.5, 9.1, 48.7, 122.4, 122.7, 125.1, 126.1, 127.0, 127.2, 127.7, 128.5, 129.6,
130.1, 130.2, 130.3, 132.8, 139.4, 172.2 ppm; IR (KBr): n˜ =2953, 2889,
General methods: All reactions were conducted under an argon atmos-
phere unless otherwise noted. THF was distilled from sodium/benzophe-
none ketyl and CH2Cl2 was distilled from CaH2. All other reagents and
solvents were purchased from commercial sources and used without pu-
rification. TLC was performed on aluminum-backed silica plates (60 F254
,
Merck) or aluminum-backed alox plates (neutral 60 F254, Merck). UV
light (254 nm) or phosphomolybdic acid were used for visualizing.
Column chromatography was performed on silica gel (Silica gel 60, 70–
230 mesh, Fluka) or aluminum oxide (Merck Aluminum oxide 90 active,
neutral, activity I). 1H and 13C NMR spectra were recorded with Bruker
AV 300 and AV 600 spectrometers. Chemical shifts (d) are quoted in
parts per million (ppm), referenced to TMS. Optical rotations were mea-
sured with an Optical Activity AA-10 automatic polarimeter. Melting
points were determined with an Electrothermal 9100 apparatus in open
capillaries. IR spectra were recorded with a Bruker ABB Bowen instru-
ment.
N-(4-Methoxyphenylmethylidene)-2-nitrobenzenesulfonamide (11):[11b]
A
1579, 1314, 1246, 1141, 1132, 833, 815 cmÀ1
.
mixture of 4-methoxybenzaldehyde (300 mg, 2.2 mmol, 1 equiv), 2-nitro-
benzenesulfonamide (295 mg, 2.3 mmol, 1.04 equiv), and tetraethyl ortho-
silicate (0.9 mL, 4.0 mmol, 1.8 equiv) was heated under argon at 1708C
for 3 h. After cooling, warm ethyl acetate (10 mL) was added and the
mixture was stirred for 10 min and then filtered. The filtrate was concen-
trated under vacuum and the residue was washed with hexane (3ꢄ
10 mL) and then recrystallized from EtOAc/hexane. The crystals were
N-(9-Anthrylmethylidene)-2-trimethylsilylethanesulfonamide (21):
A
mixture of anthracene-9-carboxaldehyde (300 mg, 1.45 mmol, 1 equiv), 2-
trimethylsilylethanesulfonamide (270 mg, 1.49 mmol, 1.1 equiv), and
BF3·Et2O (20 mL, 0.22 mmol) in toluene (20 mL) was heated under argon
in a flask equipped with a Dean–Stark separator, at 1108C for 5 h. After
cooling, a 10% aqueous solution of NaOH (20 mL) was added and the
Chem. Eur. J. 2010, 16, 11744 – 11752
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11749

ˇ
Z. Hamersak et al.
layers were separated and the organic layer was washed with brine
(10 mL). The organic layer was dried over Na2SO4, filtered, and concen-
trated under vacuum. Compound 21 was isolated as an orange powder
after chromatography (360 mg, 68%). Rf =0.2 (hexane/EtOAc 9:1); m.p.
119–1208C; 1H NMR (300 MHz, CDCl3): d=0.11 (s, 9H), 1.19–1.25 (m,
2H), 3.28–3.34 (m, 2H), 7.59–7.60 (m, 2H), 7.72–7.77 (m, 2H), 8.11 (d,
J=8.0 Hz, 2H), 8.76 (s, 1H), 9.04 (d, J=8.0 Hz, 2H), 10.45 ppm (s, 1H);
13C NMR (75 MHz, CDCl3): d=À2.0, 9.8, 49.2, 121.1, 124.2, 125.9, 129.6,
129.7, 131.1, 133.1, 136.6, 170.3 ppm; IR (KBr): n˜ =2950, 1581, 1314,
gel chromatography (88 mg, 61%); Rf =0.39 (hexane/EtOAc 8:1). Prod-
uct 36 was a pure cis isomer: ee 98% (Chiralcel OJ; hexane/2-propanol
95:5; 210 nm; 1 mLminÀ1; tminor =7.2 min, tmajor =10.1 min); [a]2D5 =À133
1
(c=1.09 in CHCl3); H NMR (300 MHz, CDCl3): d=0.08 (s, 9H), 0.80 (s,
9H), 1.22–1.29 (m, 2H), 2.82 (d, J=7.6 Hz, 1H), 3.15–3.21 (m, 2H), 3.91
(d, J=7.6 Hz, 1H), 7.27–7.38 ppm (m, 5H); 13C NMR (75 MHz, CDCl3):
d=À1.8, 10.1, 27.9, 32.3, 46.2, 49.0, 53.6, 127.8, 128.5, 134.0 ppm; IR
(KBr): n˜ =3062, 3033, 2956, 1328, 1250, 1141 cmÀ1; elemental analysis
calcd (%) for C17H29NO2SSi (339): C 60.13, H 8.61, N 4.12; found: C
60.52, H 8.54, N 3.89. Data are in the accordance with the literature.[3c]
1248, 1137, 859, 795 cmÀ1
.
2-Phenyl-3-(9-phenanthryl)-1-(2-trimethylsilylethanesulfonyl)aziridine
(38): NaH (36 mg, 60% dispersion in paraffin, 0.9 mmol, 2 equiv) was
added to a stirred solution of benzyl sulfonium salt 1 (198 mg, 0.45 mmol,
1.1 equiv) under argon in anhydrous THF (8 mL), cooled to À408C.
After 1 h, a solution of 18 (150 mg, 0.40 mmol, 1 equiv) in THF (2 mL)
was added dropwise. The reaction mixture was stirred for 20 h at À408C,
then cold H2O (15 mL) was added, and the mixture was extracted with
dichloromethane (3ꢄ10 mL). The combined organic extracts were dried
over Na2SO4, filtered, and concentrated under vacuum. The crude prod-
uct was analyzed by 1H NMR spectroscopy to determine the diastereo-
meric ratio and then purified by column chromatography on silica gel
eluting with hexane/EtOAc 8:1. The first fraction contained recovered
(R,R,R)-oxathiane 3 (72 mg, 90%); Rf =0.8 (hexane/EtOAc 8:2). The
title compound 38 was isolated as a yellow oil (145 mg, 80%); Rf =0.21
(hexane/EtOAc 8:1). Isomers of 38 were separated by chiral HPLC.
Trans isomer: ee>97% (Chiralpak AD; hexane/ethanol 97:3; 254 nm;
2-Phenyl-3-(4-methoxyphenyl)-1-(2-nitrobenzenesulfonyl)aziridine (31):
Prepared as described above starting from 11 (100 mg, 0.31 mmol), and
isolated as a light-yellow powder after workup and chromatography on
neutral alumina, activity I (70 mg, 55%); Rf =0.35 (hexane/EtOAc 7:3).
Although the crude product 31 was a cis/trans (61:39) mixture, after chro-
matography, only the cis isomer was isolated. Cis isomer: ee 99% (Chir-
alcel OD; hexane/2-propanol 80:20; 229 nm; 1 mLminÀ1; tminor =28.0 min,
t
major =31.2 min); m.p. 128.2–128.88C; 1H NMR (300 MHz, CDCl3): d=
3.69 (s, 3H), 4.40 (d, J=7.3 Hz, 1H), 4.43 (d, J=7.3 Hz, 1H), 6.66–6.69
(m, 2H), 7.02–7.03 (m, 2H), 7.12–7.14 (m, 2H), 7.15–7.17 (m, 3H), 7.75–
7.77 (m, 3H), 8.29–8.31 ppm (m, 1H); 13C NMR (75 MHz, CDCl3): d=
49.1, 49.3, 55.1, 113.5, 123.7, 124.6, 127.9, 127.9, 128.1, 129.1, 131.4, 131.8,
131.8, 132.2, 134.6, 159.3 ppm; IR (KBr): n˜ =3093, 2935, 1544, 1515, 1364,
1341, 1252, 1169, 1127, 1028 cmÀ1; elemental analysis calcd (%) for
C21H18N2O5S (410): C 61.45, H 4.42, N 6.83; found: C 61.15, H 4.68, N
6.55.
1 mLminÀ1
; tmajor =21.9 min, t
minor =25.3 min); [a]2D5 =+54 (c=0.57 in
2-Phenyl-3-(1-naphthyl)-1-(2-nitrobenzenesulfonyl)aziridine (35): Pre-
pared as described above starting from 15 (120 mg, 0.35 mmol), and iso-
lated as a light-brown viscous oil after workup and chromatography
(102 mg, 65%); Rf =0.27 (hexane/EtOAc 7:3). Product 35 was obtained
as a cis/trans mixture. Isomers of 35 were separated by chiral HPLC.
Trans isomer: ee 98% (Chiralcel OD; hexane/ethanol 80:20; 254 nm;
CHCl3); 1H NMR (300 MHz, CDCl3): d=À0.04 (s, 9H), 1.07–1.13 (m,
2H), 2.95–3.14 (m, 2H), 4.36 (d, J=4.8 Hz, 1H), 4.84 (d, J=4.8 Hz, 1H),
7.42–7.49 (m, 3H), 7.61–7.72 (m, 6H), 7.91 (dd, J1 =7.8, J2 =1.5 Hz, 1H),
7.94 (s, 1H), 8.29–8.33 (m, 1H), 8.69 (d, J=8.0 Hz, 1H), 8.74–8.77 ppm
(m, 1H); 13C NMR (75 MHz, CDCl3): d=À2.1, 9.7, 48.7, 49.7, 51.1, 122.6,
123.3, 124.4, 126.4, 127.0, 127.0, 127.0, 127.4, 128.4, 128.5, 128.8, 129.0,
129.1, 130.6, 130.6, 130.9, 131.1, 133.1 ppm; IR (KBr): n˜ =3067, 2953,
1715, 1448, 1323, 1246, 1143, 844 cmÀ1. Cis isomer: ee 97% (Chiralpak
1 mLminÀ1 minor =20.6 min); [a]2D5 =+258 (c=0.55 in
; tmajor =17.3 min, t
CH2Cl2); 1H NMR (300 MHz, CDCl3): d=4.52 (d, J=5.0 Hz, 1H), 4.97
(d, J=5.0 Hz, 1H), 7.38–7.43 (m, 4H), 7.48–7.54 (m, 4H), 7.60–7.65 (m,
4H), 7.80 (d, J=8.3 Hz, 1H), 7.87–7.84 (m, 2H), 8.14–8.15 ppm (m, 1H);
13C NMR (75 MHz, CDCl3): d=50.9, 51.4, 123.5, 124.2, 125.2, 125.3,
126.1, 126.7, 128.3, 128.7, 128.7, 129.0, 129.1, 129.5, 130.8, 131.8, 132.5,
132.9, 133.2, 133.4, 134.0 ppm; IR (KBr): n˜ =3065, 1541, 1367, 1341, 1166,
781 cmÀ1. Cis isomer: ee 97% (Chiralcel OD; hexane/ethanol 90:10;
254 nm; 1 mLminÀ1; tminor =21.3 min, tmajor =27.9 min); [a]2D5 =+203 (c=
0.36 in CH2Cl2); 1H NMR (300 MHz, CDCl3): d=4.69 (d, J=7.3 Hz,
1H), 4.96 (d, J=7.3 Hz, 1H), 6.99–7.01 (m, 3H), 7.11–7.15 (m, 2H),
7.30–7.35 (m, 1H), 7.41–7.56 (m, 4H), 7.67–7.70 (m, 1H), 7.75–7.78 (m,
1H), 7.81–7.82 (m, 2H), 8.02–8.04 (m, 1H), 8.36–8.39 ppm (m, 1H);
13C NMR (75 MHz, CDCl3): d=48.5, 46.6, 122.8, 124.7, 125.0, 125.8,
126.4, 127.3, 127.3, 127.8, 127.9, 128.5, 128.6, 131.1, 131.5, 131.6, 131.7,
132.3, 133.1, 134.8 ppm; IR (KBr): n˜ =3062, 1544, 1367, 1341, 1169, 1127,
AD; hexane/ethanol 97:3; 254 nm; 1 mLminÀ1; tmajor =13.4 min, tminor
=
16.5 min); [a]2D5 =+29 (c=0.61 in CHCl3); 1H NMR (300 MHz, CDCl3):
d=0.07 (s, 9H), 1.29–1.32 (m, 2H), 3.33–3.36 (m, 2H), 4.44 (d, J=
7.3 Hz, 1H), 4.68 (d, J=7.3 Hz, 1H), 6.99–7.01 (m, 3H), 7.19–7.21 (m,
2H), 7.56–7.62 (m, 4H), 7.86 (dd, J1 =7.9, J2 =1.1 Hz, 1H), 7.89 (s, 1H),
8.10–8.12 (m, 1H), 8.58 (d, J=8.0 Hz, 1H), 8.60–8.62 ppm (m, 1H);
13C NMR (75 MHz, CDCl3): d=À2.5, 9.5, 45.8, 47.0, 48.8, 122.0, 122.6,
123.1, 125.8, 126.2, 126.3, 126.3, 126.4, 126.7, 126.8, 127.4, 128.2, 129.6,
129.7, 130.5, 131.5 ppm; IR (KBr): n˜ =3067, 2958, 1690, 1450, 1328, 1252,
1145, 833 cmÀ1; elemental analysis calcd (%) for cis/trans mixture of
C27H29NO2SSi (459): C 70.55, H 6.36, N 3.05; found: C 70.64, H 6.64, N
3.11.
2-Phenyl-3-(9-anthryl)-1-(2-trimethylsilylethanesulfonyl)aziridine
(41):
Compound 41 was prepared as described above starting from 21 (150 mg,
0.42 mmol), and isolated as a yellow oil after workup and silica gel chro-
matography (100 mg, 53%); Rf =0.15 (hexane/CH2Cl2/methyl tert-butyl
ether 8:1:1). Product 41 was obtained as a cis/trans mixture (9:91). Iso-
mers of 41 were separated by chiral HPLC and the assignments below
are for the major trans isomer. Trans isomer: ee 98% (Chiralpak AD;
906 cmÀ1
; elemental analysis calcd (%) for cis/trans mixture of
C24H18N2O4S (430): C 66.96, H 4.21, N 6.51; found: C 66.78, H 4.56, N
6.82.
2-Phenyl-3-(9-phenanthryl)-1-(2-nitrobenzenesulfonyl)aziridine (40): Pre-
pared as described above starting from 20 (100 mg, 0.25 mmol), and iso-
lated as a light-brown viscous oil after workup and chromatography
(93 mg, 76%); Rf =0.26 (hexane/EtOAc 7:3). Product 40 was a cis/trans
mixture. Isomers of 40 were separated by HPLC. Trans isomer: ee 98%
(Chiralcel OD; hexane/2-propanol/diethylamine 50:50:0.2; 254 nm;
hexane/ethanol 95:5; 370 nm; 1 mLminÀ1
;
tmajor =13.7 min, tminor =
18.3 min); [a]2D5 =+39 (c=0.69 in CH2Cl2); 1H NMR (300 MHz, CDCl3):
d=À0.09 (s, 9H), 0.93–1.06 (m, 2H), 2.87–2.99 (m, 2H), 4.41 (d, J=
5.0 Hz, 1H), 5.20 (d, J=5.0 Hz, 1H), 7.46–7.51 (m, 3H), 7.52–7.55 (m,
4H), 7.73–7.75 (m, 2H), 8.02 (dd, J1 =8.0, J2 =0.4 Hz, 2H), 8.48–8.50 ppm
(m, 3H); 13C NMR (75 MHz, CDCl3): d=À2.7, 8.9, 47.6, 50.2, 50.4, 124.3,
124.6, 124.6, 125.8, 128.2, 128.5, 128.6, 128.7, 128.8, 130.4, 130.8,
132.6 ppm; IR (KBr): n˜ =3065, 2952, 1679, 1331, 1285, 1251, 1143, 859,
1 mLminÀ1
;
t
major =45.4 min,
t
minor =72.4 min); 1H NMR (600 MHz,
CDCl3): d=4.59 (d, J=5.0 Hz, 1H), 4.98 (d, J1 =5.0 Hz, 1H), 7.40–7.50
(m, 4H), 7.53–7.69 (m, 8H), 7.79 (brs, 1H), 7.81–7.84 (m, 2H), 8.21 (d,
J=7.6 Hz, 1H), 8.67 (d, J=8.1 Hz, 1H), 8.72 ppm (d, J=8.1 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=50.6, 51.0, 122.1, 122.7, 123.7, 123.9,
126.2, 126.4, 126.4, 126.5, 126.8, 127.0, 127.2, 127.9, 128.3, 128.6, 128.6,
129.9, 130.2, 130.4, 130.4, 130.5, 131.3, 132.3, 132.6, 133.6 ppm; IR (KBr):
n˜ =3064, 2925, 1543, 1364, 1341, 1164, 1127 cmÀ1. Cis isomer: ee 98%
(Chiralcel OD; hexane/2-propanol/diethylamine 50:50:0.2; 254 nm;
1 mLminÀ1; tmajor =24.2 min, tminor =31.2 min); [a]2D5 =+16.7 (c=0.54 in
CH2Cl2); 1H NMR (300 MHz, CDCl3): d=4.72 (d, J=7.3 Hz, 1H), 4.92
843 cmÀ1
; elemental analysis calcd (%) for cis/trans mixture of
C27H29NO2SSi (459): C 70.55, H 6.36, N 3.05; found: C 70.85, H 6.56, N
2.74.
2-Phenyl-3-(tert-butyl)-1-(2-trimethylsilylethanesulfonyl)aziridine
(36):
Compound 36 was prepared as described above starting from 16 (120 mg,
0.48 mmol), and isolated as a colorless viscous oil after workup and silica
11750
www.chemeurj.org
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 11744 – 11752

N-Protected Aziridines
FULL PAPER
(dd, J1 =1.0, J2 =7.3 Hz, 1H), 6.95–6.96 (m, 3H), 7.16–7.18 (m, 2H),
7.53–7.55 (m, 1H), 7.57–7.61 (m, 3H), 7.78–7.83 (m, 5H), 8.05–8.08 (m,
1H), 8.38–8.40 (m, 1H), 8.55 (d, J=8 Hz, 1H), 8.59–8.60 ppm (m, 1H);
13C NMR (75 MHz, CDCl3): d=48.6, 49.8, 122.4, 123.2, 123.5, 124.7,
125.7, 126.6, 126.7, 126.8, 126.9, 127.3, 127.7, 127.9, 128.0, 129.0, 129.9,
130.1, 130.2, 131.0, 131.5, 131.5, 131.6, 132.3, 134.9ppm; IR (KBr): n˜ =
3067, 2924, 1541, 1364, 1340, 1168, 1125, 911 cmÀ1; elemental analysis
calcd (%) for cis/trans mixture of C28H20N2O4S (480): C 69.98, H 4.20, N
5.83; found: C 69.65, H 4.31, N 5.50.
[3] a) V. K. Aggarwal, A. Thompson, R. V. H. Jones, M. C. H. Standen,
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ACHTUNGTRENNUNG(2R,3S)-2-Phenyl-3-tert-butyl-1-tosylaziridine (37): Tetrabutylammonium
fluoride (0.42 mL, 1m in THF, 0.42 mmol, 2 equiv) was added to a solu-
tion of 36 (70 mg, 0.21 mmol, 1 equiv) in anhydrous THF (5 mL) and the
reaction mixture was stirred for 48 h at 608C. After cooling, H2O
(20 mL) was added and the mixture was extracted with dichloromethane
(3ꢄ10 mL). The combined organic extracts were dried with Na2SO4, fil-
tered, and concentrated under vacuum. Crude 2-phenyl-3-tert-butylaziri-
dine (40 mg) was obtained and used in the next step without further pu-
rification. 2-Phenyl-3-tert-butylaziridine (40 mg) was dissolved in CH2Cl2
(2 mL) and tosyl chloride (48 mg, 0.25 mmol) and diisopropylethylamine
(0.39 mL, 2.3 mmol) were added. The reaction mixture was stirred for
20 h at RT. Water acidified with phosphoric acid (pH 3, 10 mL) was
added, and the mixture was extracted with CH2Cl2 (3ꢄ5 mL). The com-
bined organic extracts were dried with Na2SO4, filtered, and concentrated
under vacuum. The crude product was purified by silica gel column chro-
matography (CH2Cl2/hexane 8:2) and the title compound 37 was isolated
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ˇ
´
3494–3498; c) A. Solladiꢁ-Cavallo, A. Diep-Vohuule, V. Sunjic, V.
´
Vinkovic, Tetrahedron: Asymmetry 1996, 7, 1783–1788; d) A. Solla-
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ˇ
´
´
diꢁ-Cavallo, M. Roje, T. Isarno, V. Sunjic, V. Vinkovic, Eur. J. Org.
Chem. 2000, 1077–1080.
as a white powder (37 mg, 54%). Rf =0.36 (CH2Cl2/hexane 8:2); [a]D25
=
ˇ
´
[6] A. Solladiꢁ-Cavallo, M. Roje, R. Welter, V. Sunjic, J. Org. Chem.
2004, 69, 1409–1412.
À129 (c=1.6 in CHCl3) {in an accordance with the original data[20] for
the (2R,3S)-2-phenyl-3-tert-butyl-1-tosylaziridine}; 1H NMR (300 MHz,
CDCl3): d=0.67 (s, 9H), 2.45 (s, 3H), 2.77 (d, J=7.5 Hz, 1H), 3.92 (d,
J=7.5 Hz, 1H), 7.16–7.25 (m, 5H), 7.33–7.36 (m, 2H), 7.90–7.93 ppm (m,
2H). 13C NMR (75 MHz, CDCl3): d=21.7, 27.5, 31.9, 46.0, 54.3, 127.4,
127.7, 128.1, 128.3, 129.7, 133.8, 135.0, 144.5 ppm.
´
ˇ
[7] I. Stipetic, M. Roje, Z. Hamersak, Synlett 2008, 3149–3152.
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3113.
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[10] N-SES imines and N-Ts imines were prepared according to:
a) W. R. McKay, G. R. Proctor, J. Chem. Soc. Perkin Trans. 1 1981,
2435–2442; b) W. B. Jennings, C. J. Lovely, Tetrahedron 1991, 47,
5561–5568. N-Boc imines were prepared according to: c) A. M. Ka-
nazawa, J. Denis, A. E. Greene, J. Org. Chem. 1994, 59, 1238–1240;
d) B. M. Trost, J. Jaratjaroonphong, V. Reutrakul, J. Am. Chem. Soc.
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Acknowledgements
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b) Y. Xu, G. Lu, S. Matsunaga, M. Shibasaki, Angew. Chem. 2009,
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We thank the Ministry of Science, Education and Sports of the Republic
of Croatia for financing (grant nos. 098-0982933-2908 and 098-0352851-
2921).
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À À À
S C C N dihedral angle of approximately +608 or À608. The geo-
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Chem. Eur. J. 2010, 16, 11744 – 11752
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11751

ˇ
Z. Hamersak et al.
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[20] An original sample of (2R,3S)-2-phenyl-3-tert-butyl-1-tosylaziridine
was obtained from the author, and we measured the optical rotation
to be [a]2D5 =À132 (c=1.0 in CHCl3).
Received: May 24, 2010
Published online: September 8, 2010
11752
www.chemeurj.org
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 11744 – 11752