Sodium-iodoxybenzoate mediated highly chemoselective aziridination of olefins

Article abstract of DOI:10.1016/j.tet.2014.06.029

Herein we utilized, for the first time, sodium 2-iodoxybenzoate as a highly specific oxidant for PhthNH₂ to create a highly chemoselective aziridination reagent. This method efficiently effects aziridination of electron-rich, electron-deficient, allylic alcohol and alkenyl bromide C=C bonds in good to excellent yields. Inter and intramolecular chemoselectivity was demonstrated between electron-rich and electron-deficient alkenes by using this efficient and metal free protocol.

Full text of DOI:10.1016/j.tet.2014.06.029

Tetrahedron 70 (2014) 5884e5894
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Sodium-iodoxybenzoate mediated highly chemoselective
aziridination of olefins
*
Ananthan Bakthavachalam, Hui-Chun Chuang, Tu-Hsin Yan
Department of Chemistry, National Chung Hsing University, Taichung, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Herein we utilized, for the first time, sodium 2-iodoxybenzoate as a highly specific oxidant for PhthNH2
to create a highly chemoselective aziridination reagent. This method efficiently effects aziridination of
electron-rich, electron-deficient, allylic alcohol and alkenyl bromide C]C bonds in good to excellent
yields. Inter and intramolecular chemoselectivity was demonstrated between electron-rich and electron-
deficient alkenes by using this efficient and metal free protocol.
Received 10 March 2014
Received in revised form 7 June 2014
Accepted 8 June 2014
Available online 13 June 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
N-Aminophthalimide
Aziridination
Hypervalent compounds
Sodium iodoxybenzoate
Oxidation
1. Introduction
m-CPBA/Ar-I18 and m-CPBA/Bu4NI derived hypoiodite19 have been
reported to effect metal-free aziridination of aromatic olefins and
Great attention is being gained by the strained and smallest
three membered aziridines,1e5 which are important building blocks
for various nitrogen-containing intermediates synthesis. Keen ef-
forts have been devoted in the improvement of various aziridina-
tion methods.2e5 Number of synthetically useful aziridination
processes are based, predominantly, on the use of metal salts or
complexes as catalyst and N-tosyliminodanes or haloamine-T as
nitrogen precursors.6e9 In economical and eco-friendly regards,
developing a non-metallic and chemoselective reaction condition
with non-toxic oxidant and inexpensive amine precursor is the
longstanding goal for aziridine chemistry.10
Various research groups have been studying aziridination of
olefins with N-aminophthalimide (PhthNH2) as the amine pre-
cursor.10e29 Recently, Xue et al. investigated the effect of NeH bond
dissociation energies of various amine source on the reactivity of
the amidation reaction with (diacetoxyiodo)benzene (DIB) as an
oxidant on styrene. Interestingly, PhthNH2 was found as one of the
most preferable choice for amidation reactions.30 Notably, aziridi-
nation promoted by the electrochemical oxidation of PhthNH2 has
found to be good method.10e13 More interestingly, DIB mediated
aziridination of olefins with PhthNH2 has proven to be synthetically
useful transformations.14e17 Recently, recyclable systems, such as
simple alkenes in moderate to good yields. These previously re-
ported aziridination systems were remain limited due to the usage
of excessive oxidizing reagent, poor chemoselectivity, narrow range
substrate scope (e.g., not suitable for the coupling with allylic al-
cohol C]C bonds or electron-deficient alkenes) and in-
compatibility with wide range of functional groups. The significant
limitation on the metal-free alkeneeaziridination often arises from
using less selective oxidants to mediate the coupling of alkenes
with hydrazine derivatives.10e29 Therefore, the search for new en-
try of metal-free aziridination reagents, which are highly chemo-
selective and suitable for broad range of substrates, such as
electron-deficient, electron-rich and allylic alcohol C]C bonds,
continues to stimulate much thought from a synthetic point of
view. Among the various metal-free iodo-based oxidizing reagents,
o-iodoxybenzoic acid (IBX)31,32 is one of the mildest oxidizing re-
agents and inexpensive to prepare,33,34 and more tolerant to
moisture and generally promotes clean transformation in many
new oxidation-based applications reported by Nicolaou group and
others.34e45 Most importantly, some useful transformations have
been reported by utilizing IBX coupled with N-methyl morpho-
line37 and 2-hydroxypyridine (HyP).45 Nevertheless, the reactivity
of IBX with base requires further investigation. Compared with IBX,
its conjugate base should be a more selective oxidant. We envi-
sioned the feasibility of a highly chemoselective coupling of
PhthNH2 with alkenes promoted by a conjugate base of IBX.32
* Corresponding author. E-mail address: thyan@mail.nchu.edu.tw (T.-H. Yan).
URL: http://www.nchu.edu.tw/~chem/thyan.htm
http://dx.doi.org/10.1016/j.tet.2014.06.029
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

A. Bakthavachalam et al. / Tetrahedron 70 (2014) 5884e5894
5885
Herein we utilized, for the first time, sodium 2-iodoxybenzoate
as a highly specific oxidant for PhthNH2 to generate a highly che-
moselective aziridination reagent. This novel protocol efficiently
effects aziridination of electron-deficient, electron-rich, alkenyl
bromide and allylic alcohol C]C bonds in good to excellent yields.
to find that, when 1a reacts with IBX, PhthNH2 and Na2CO3 in EA
(Table 1, entry 9) the desired adduct 2a was produced in 84% iso-
lated yield with an additional trace (<5%) of the oxidation product
3. Addition of additives (e.g., iodine, acetic anhydride) does not
meliorate the yield in this CeN bond formation.49 Altering the
concentration of this reaction lead to diminutive yield. We also got
discontented results while increasing or decreasing the equivalents
of IBX, PhthNH2 and Na2CO3.49
2. Results and discussion
Having established this ripest novel aziridination procedure, its
generality and selectivity with respect to the structure of alkenes
were investigated. We were delighted to find that the chemistry
was successful for a diverse range of olefins. Thus the inclusion of
a ketone, an ester, an acetonide, an amide, an imide, a secondary or
even a primary hydroxyl group did not hinder the desired reaction.
In other words, functional group tolerance is excellent by this
protocol. In general, electron-deficient alkenes were found to pro-
ceed well than electron rich alkenes.
For exploring iodine (V) reagents mediated aziridination re-
action conditions, we carefully examined the reactions of 1a and
PhthNH2 with broad range of oxidants (like, SIBX, DMP and IBX).
Additionally, in the search to find an efficient and selective conju-
gate base, we examined various bases (including, TEA, Pyridine,
DBU, DMAP, K2CO3 and Na2CO3). Furthermore, we also investigated
the utilisation of many additives and various solvents at different
temperatures to improve reaction yield (Table 1 and please see
Supplementary data Table S1).
Table 1
Optimization of reaction conditions for aziridination of olefin 1aa
Entry
Oxidant
Base
Time (h)
T (ꢀC)
2a (%)b
3 (%)
1
2
3
4
5
6
7
8
SIBX
DMP
IBX-HyP
IBX
IBX
IBX
IBX
IBX
IBX
IBX
K2CO3
K2CO3
K2CO3
d
30
12
24
30
27
27
30
27
27
27
12
25
Reflux
25
[13]
[27]
[30]
0
[7]
22
21
77
84
[41]
[46]
[12]
[13]
d
Reflux
Reflux
Reflux
25
Reflux
Reflux
Reflux
Reflux
[39]
[26]
[7]
[2]
[10]
[5]
TEA
Li2CO3
K2CO3
K2CO3
Na2CO3
NaHCO3
KOAc
9
10
11
[20]
[13]
IBX
a
Reactions were performed in 0.25 mmol scale with PhthNH2 (1.5 equiv), Oxidant (1.4 equiv), Base (2.8 equiv).
Isolated yield; NMR ratio is in parenthesis.
b
Initial studies centred on the aziridination of alkene containing
Fortunately, exposing 1b and 1c to the IBX/Na2CO3/PhthNH2
system gave 79% and 81% yield of 2b and 2c, respectively (Table 2,
entries 1 and 2). Notably, the ability to effect monoaziridination of
the double bond of allylic alcohol in geraniol 1b highlights the
chemoselectivity of this aziridination regent. Even though oxida-
tion of geraniol 1b and cinnamyl alcohol 1a were reported by using
IBX in EA,46 we predominantly got the desired aziridine. In-
terestingly, this aziridination reagent is also suitable for the azir-
idination of phenyl vinyl carbinol 1d (entry 3), which is sensitive to
benzylic oxidation. On the other hand, aziridination onto cyclic
allylic alcohol 1e was also effective (entry 4). Changing alkene to 1f
in which the hydroxyl group was further removed from the double
bond also gave satisfactory results with IBX/Na2CO3/PhthNH2 with
exclusive formation of the cis-aziridine 2f (entry 5), which could
serve as an important building block for Amarylidaceae alkaloids
synthesis, which is an ongoing research in our lab. The cis re-
lationship between aziridine and hydroxyl group indicates the syn
directing effect of the hydroxyl group. The cis-aziridine structure of
2f, studied with the single crystal X-ray analysis (Fig. 1) confirms
the stereochemistry. Similarly varying alkene to 1g, the structural
analogue of 1e, in which the hydroxyl group was protected with
benzyl group, also gave good yield (entry 6). To further demonstrate
the scope of this aziridine-forming methodology, the utility of this
oxidation-sensitive groups, such as hydroxyl group and C]C bond.
Due to the known sensitivity of the allylic primary alcohol to oxi-
dants, such as IBX,46 Dess-Martin periodinane (DMP),47 and m-
CPBA48 at 0 ꢀC, we intentionally chose 1a to devise a suitable
condition for the aziridination of olefin substrates bearing sensitive
functional groups. On exposing PhthNH2 to either SIBX (Table 1,
entry 1), or DMP (entry 2), or IBX-HyP (entry 3) for the aziridination
of alkene 1a gave unsatisfactory results. Inspection of optimization
entries (Table 1 and Supplementary data Table S1) unveils that
under basic conditions the intermolecular aziridination of 1a with
IBX as oxidant is a better choice than the other iodine (v)
reagents.49
We believe that the choice of a base plays a vital role in this
transformation. Unlike DIB and Pb(OAc)4 we did not observe the
expected product in the absence of base (entry 4). The only product
observed was cinnamaldehyde 3. In general, inorganic bases were
the best choice than organic bases. Specifically, carbonate bases
were better than bicarbonate and acetate bases (entries 5e11).49
Out of bases tested,49 Na2CO3 is the best choice (entry 9). Pre-
viously reported aziridination methods, predominantly, used toxic
halogenated solvents. We found that, among various solvents ex-
amined, ethyl acetate (EA) is the most effective.49 We were pleased

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A. Bakthavachalam et al. / Tetrahedron 70 (2014) 5884e5894
Table 2
a
Sodium 2-iodoxybenzoate mediated aziridination of electron rich alkenes with PhthNH2
Entry
1
Substrate
Product
Yieldb
79
2
3
81
75
4
5
61
70
6
67
7
8
82
84
9
55
53
51
10
11
12
13
71
31c
14
88

A. Bakthavachalam et al. / Tetrahedron 70 (2014) 5884e5894
5887
Table 2 (continued )
Entry
Substrate
Product
Yieldb
15
74
16
17
62
85
a
Reaction was performed in refluxing EA for 27 h by using alkene (1 equiv), PhthNH2 (1.5 equiv), IBX (1.4 equiv) and Na2CO3 (2.8 equiv).
Isolated yield.
Reaction was performed over 39 h.
b
c
In the light of our versatile aziridination protocol, we extend the
substrate scope to alkenyl bromides. However, the previous report
used non basic condition.29 Our optimized condition has applied
directly in this reaction and the required product was obtained.
Thus 1-bromo-propene (1q) was subjected to this aziridination
reaction condition to give a
-bromoaziridine 2q29 in 62% isolated
yield (Table 2, entry 16). The column purification was performed by
using cold water circulation to achieve better yield.
The a-bromoaziridines are known to be thermally labile. Hence
this will yield corresponding hydrazones through an electrocyclic
rearrangement, which allows a highly regioselective product. In
addition to this, stability of carbocation is an important phenom-
enon for this rearrangement.29
b-bromostyrene, which is a pro-
Fig. 1. X-ray crystal structure of 2f (hydrogen atoms omitted).
genitor of stable carbocation prepared by our in-house TieMg
method,57 was tested with the optimized condition and smoothly
yielded 2r29 in 85% as the only product (Table 2, entry 17).
With an eye to extend these observations to other electron-
deficient alkenes, we explored the aziridination of alkenes bear-
ing electron-withdrawing groups. Thus, either unsaturated ester 1s
or amide 1t reacted efficiently with IBX/Na2CO3/PhthNH2 derived
aziridination reagent to give 86% and 65% yield of the desired
aziridination adducts 2s and 2t, respectively (Table 3, entries 1 and
2). Interestingly, imide 1u also proved to be a satisfactory trap
(entry 3). On the other hand, this aziridination reagent reacted ef-
ficiently with unsaturated ketone 1v to give the desired aziridinyl
ketone 2v in a remarkable 90% yield (entry 4). Moreover, the re-
action directly scales up; thus, aziridinyl ketone 2v was obtained in
68% yield on a 10-mmol scale. Changing the ketone to benzylidene
ketone 1w, 1x and 1y have also been yielded satisfactory results
(entries 5e7). Most delightfully, aziridination with dibenzylide-
neacetone 1z led to smooth aziridination with formation of mon-
oaziridination adduct 2z in 92% yield (entry 8). Many of the
products (Table 2, entries 1e17 and Table 3, entries 1e8) were
found to form in higher yield than the previously reported
procedures.
protocol was examined in the aziridination of alkenes without
directing functional group. Gratifyingly, aziridination of various
alkenes 1h, 1i, 1j, 1k and 1l under the standard conditions was
equally effective in the formation of aziridines 2h, 2i, 2j, 2k and 2l
(entries 7e11). We achieved complete conservation of stereo-
chemistry in the case of trans-stilbene 1i (see mechanism part for
detailed discussion). Conformationally restricted olefin 1H-indene
1m (Table 2, entry 12) was also found to undergo aziridination by
this protocol to give aziridine in 71% yield. Biologically important
molecule cholesteryl acetate 1n (Table 1, entry 13) was tested with
this present aziridination method, corresponding aziridine product
2n was obtained.14 Aziridination of norbornene 1o was found to be
effective (entry 14). The aziridination product 2o was obtained in
88% yield. To further ascertain the viability of this system, terminal
alkene 1p was studied under optimum conditions gave desired
product 2p (entry 15), in good yield.
a
-Halogenated hydrazones and imines have acquired significant
attraction due to their usage in the preparation of pyrrolidines,50
pyrroles,51,52 cyclopropylamines,53 diimines51,54 and epox-
yimines.55 The synthesis of
a-haloimine and
a-halohydrazone
To evaluate further the chemoselectivity of this IBX/Na2CO3/
PhthNH2 system mediated transformation, it becomes necessary to
ascertain whether this aziridination proceeds with preference over
electronically different types of double bond. Therefore, a series of
inter- and intramolecular competition reactions were, therefore,
undertaken. Gratifyingly, exposure of a mixture of 1-acetyl-1-
cyclohexene 1v and 2-cyclohexene-1-ol 1e at optimized condition
commonly involves
a-halogenation of imines or hydrazones and
condensation of primary amine hydrazine with
a-halogenated
carbonyl compounds.29 Unfortunately, either halogenation of im-
ines and hydrazones or aforementioned condensation reaction
suffers with poor chemoselectivity.56 To avoid these issues Yudin
et al. proposed DIB based protocol to prepare
a-bromoaziridines
and
a
-bromohydrazones.29

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A. Bakthavachalam et al. / Tetrahedron 70 (2014) 5884e5894
Table 3
Table 4
Sodium 2-iodoxybenzoate mediated aziridination of electron-deficient alkenes with
PhthNH2
Chemoselectivity in sodium 2-iodoxybenzoate/PhthNH2 mediated aziridination of
olefins
a
Entry
1
Substrate
Product
Yieldb
86
Entry
1
Alkene mixturea
Products
Yield (%)b
2v (80%)
2e (0%)c
2
65
67
2
3
2v (86%)
2j (0%)c
3
4
2l (0%)c
2y (83%)d
90
68c
4
5
2l (0%)c
2v (84%)
5
6
80
2aa (79%)
91
7d
8
90
92
a
0.25 mmol of each substrate was used.
Isolated yield.
b
c
Determined by 1H NMR on the crude mixture.
d
Ar¼4-Methoxyphenyl.
a
radical mechanism. In addition to this, we performed a competitive
reaction to get further evidence against radical intermediate 9
(Scheme 1). 1,1-Diphenylethene 11 is a known and preferential trap
for radical intermediate.20 Preferential reaction over trans-stilbene
was observed while PhthNH2 was oxidized with IBX/Na2CO3 in the
presence of 1:1 mixture of trans-stilbene and 1,1 diphenylethene
(Scheme 2). Based on the experimental results, we conclude the
proposed radical intermediate 9 is not involved in this aziridination
reaction.
Focus was next turned to the phthalimidonitrene 8, which was
thought to be involved in Pb(OAc)4 mediated aziridination of al-
kenes.21 Nevertheless, there are some questions to be answered,
before claiming phthalimidonitrene 8 as the intermediate for IBX/
Na2CO3 mediated aziridine reaction, such as how this nitrene
controls its rapid inter-conversion between singlet and triplet
states to yield the product stereo-selectively.
Atkinson et al. investigated the possibility of nitrene in-
termediate by selectivity trials.22b He generated phthalimidoni-
trene 8 from 13 (Scheme 3) by thermolysis in refluxing benzene,
which undergoes irreversible reaction with 1:1 mixture of styrene
1h and methyl acrylate 14 yielded preferential reaction over methyl
acrylate in 3:1 product ratio (Scheme 3, Eq. 1).22b In contrast,
preferential reaction over styrene 1h was observed (1:1.5) while
the reaction was performed by using PhthNH2 and Pb(OAc)4 in
refluxing benzene (Eq. 2).22b Interestingly, when the reaction was
performed by using PhthNH2 and DIB, preferential reaction was
detected with methyl acrylate in 1.2:1 product ratio (Eq. 3).20 We
did an identical reaction employing PhthNH2 and IBX in the pres-
ence of Na2CO3 and found preferential reaction with methyl
Reaction was performed in refluxing EA for 27 h by using alkene (1 equiv),
PhthNH2 (1.5 equiv), IBX (1.4 equiv) and Na2CO3 (2.8 equiv).
b
Isolated yield.
Reaction was performed on 10 mmol scale.
Ar¼4-Methoxyphenyl.
c
d
has produced exclusively 2v (Table 4, entry 1). Highly selective
aziridination onto a mixture of 1-acetyl-1-cyclohexene 1v and
cyclohexene 1j was equally effective (entry 2). As expected, ex-
posing a mixture of benzylidene ketone 1y and 1-methyl-1-
cyclohexene 1l to the IBX/Na2CO3/PhthNH2 system also led to
highly selective aziridination (entry 3). Intramolecular competition
reaction was demonstrated already in 1b, (Table 2, entry 1). How-
ever, another example 1aa manifests the chemoselectivity of this
method (Table 4, entry 5).
In order to understand the mechanism of this chemoselective
aziridination reaction, we also proposed the possible mecha-
nisms20 and examined each in turn (Scheme 1). However, Yudin15
and Che14 proposed that the alkene aziridination mechanism pro-
ceeds via PhthNHOCOR using hypervalent iodine species and
PhthNH2. This reaction is proceeding well in the absence of acetic
anhydride or trifluoroacetic anhydride. Therefore, we rejected the
possibility of involvement of acyloxyamine 10 (Scheme 1) in this
reaction.
We examined the possibility of radical mechanism by account-
ing the reactivity of trans-stilbene and cis-2-hexene-1-ol. We ob-
served complete conservation of stereochemistry in the case of 2c
and 2i (Table 2, entries 2 and 7). It revealed the concerted formation
of aziridine ring. Therefore the reaction may not proceed through

A. Bakthavachalam et al. / Tetrahedron 70 (2014) 5884e5894
5889
Scheme 1. Possible intermediates for this aziridination reaction.
3, Eq. 8). On the other hand, non preferential result was observed
while TEA was used as base in the same reaction. At this juncture
we would like to highlight that employment of base for the azir-
idination reaction is indispensible. Based on these experimental
insights, we observed different selectivity trend while changing the
base. So we presume that the involvement of aminoiodane along
with base in transition state of this aziridine reaction.
The above results58 strongly implicates a tentative reaction
mechanism as shown in Scheme 4, wherein the less electrophilic
sodium iodoxybenzoate acts as a highly specific oxidant for the
amino group of PhthNH2 to provide aminoiodane 7. The amino-
iodane, presumably, exist in equilibrium between electrophilic (7a)
and nucleophilic (7b) equivalents and the role of base is crucial here
to move the equilibrium towards the nucleophilic side. Reduction at
the iodine centre most likely proceeds through ionic pathway40 to
render sodium o-iodosobenzoate59,60 along with required aziridine.
Left unanswered by this proposal are the specific oxidizing proper-
ties of sodium iodoxybenzoate, the novel nucleophilic character of
aminoiodane under basic conditions and the unique electrophilic
behaviour of HyP/IBX/PhthNH2. Further mechanistic insights are
required before any definite conclusions can be reached.
Scheme 2. Investigating possible radical intermediate.
acrylate but in 2.4:1 product ratio (Eq. 4), whereas when the same
reaction performed in refluxing EA we noticed insignificant dif-
ference in product ratio. This was an interesting result because we
got a similar trend in preferential reactivity like the case of Eqs. 1
and 3 (Scheme 3), however, product ratio was found to be different.
Based on these experimental results, we tentatively propose the
non-involvement of phthalimidonitrene 8 in the transition state of
this sodium-iodoxybenzoate mediated aziridination reaction.
In an attempt to understand the mechanism, we investigated
the role aminoiodane 7 in transition state of this reaction. Since
3. Conclusions
PhthNH2 does not possess a-amino hydrogen atom and it would
form a complex with IBX.40 Recently, Wirth et al. proposed the
possible involvement of aminoiodane (from DIB and PhthNH2,
Fig. 2) by the experimental insights.20 Nicolaou et al. illustrated the
change in reactivity of IBX by modifying the ligand.37 In the same
way, we envisioned that the change in base would show the dif-
ference in selectivity if IBX conjugate base participates in the
transition state.
The successful application of the sodium 2-iodoxybenzoate
promoted aziridination of PhthNH2 with a variety of alkenes illus-
trates the extraordinary reactivity of this new aminoiodane species.
Not only is this IBX/Na2CO3/PhthNH2 system highly reactive, it also
seems highly chemoselective and might become a practical azir-
idination reagent applicable to large scale synthesis. Our work ex-
emplifies the chemoselective rational aziridination without
hazardous metal catalyst and super-stoichiometric oxidant. The
operational simplicity of this novel procedure provides access to
aziridines, those are difficult to prepare but utile. The highly specific
oxidizing properties of sodium iodoxybenzoate suggested several
intriguing directions, which are currentlyunderactiveinvestigation.
As anticipated, we observed a difference in selectivity while
changing the base (Scheme 3, Eqs. 5e9). This is also serves as fur-
ther evidence for the non-involvement of phthalimidonitrene 8 in
the transition state. The preferential ratio in Scheme 3 also reveals
the importance of base for this CeN bond formation reaction. When
the reaction was performed in the presence of Na2CO3, Imidazole,
Li2CO3 preferential reaction over methyl acrylate was observed
(Eqs. 5e7). On the contrary, an identical reaction employed with
HyP as base and detected that preferential reaction over styrene but
in 1.4:1 (2g/15) product ratio (Eq. 8). The preferential reaction over
electron rich substrate in the case of HyP/IBX/PhthNH2 reveals the
involvement of different type of intermediate than others (Scheme
4. Experimental section
4.1. General information
All reactions were conducted in flame-dried glassware under
nitrogen atmosphere. Ethyl acetate (EA) was distilled from CaH2

5890
A. Bakthavachalam et al. / Tetrahedron 70 (2014) 5884e5894
Phth
N
13
3 equiv
Ph
Ac
O
Eq - 1
MeOOC
Ph
2h
1h
N
N
+
Benzene, reflux
Phth
Phth
15
MeOOC
3 equiv
14
1
:
3
3 equiv
Pb(OAc)
PhthNH2,
4
Ph
MeOOC
Ph
2h
1h
N
N
+
Benzene, reflux
Eq - 2
Phth
Phth
15
MeOOC
3 equiv
14
1.5
:
1
3 equiv
PhI(OAc)2
PhthNH2,
Ph
MeOOC
Ph
2h
1h
N
N
+
Benzene, reflux
Eq - 3
Phth
Phth
15
MeOOC
3 equiv
14
1.
:
1.2
3 equiv
PhthNH2,
reflux
IBX
Ph
MeOOC
Ph
2h
1h
N
N
+
Phth
Phth
15
MeOOC
3 equiv
14
Benzene
Na2CO3
1.0
:
2.2
Eq - 4
Eq - 5
Eq - 6
EA
EA
Na2CO3
1.0
1.0
:
:
2.4
1.9
Imidazole
EA
EA
EA
Li2CO3
Hyp
1.0
1.4
1.0
:
:
:
3.3
1.0
1.0
Eq - 7
Eq - 8
Eq - 9
TEA
Scheme 3. Investigation of possible intermediates in IBX mediated aziridination of alkenes. (a) 3 equiv of each starting materials and 2.8 equiv of base with respect to IBX were
used. (b) All the reactions were performed in 210 min at reflux temperature. (c) Ratios were determined by 1H NMR on the crude mixture.
resolution ESI mass spectrometer. Mass spectra were obtained us-
ing double focussing apparatus from high resolution EI and FAB
mass spectrometer. IR spectra were recorded as a thin film and
expressed in cmꢁ1
.
4.2. (E)-1-(2-(Allyloxy)phenyl)-3-phenylprop-2-en-1-one (1aa)
To a stirred solution of 2-hydroxychalcone (1.12 g, 5 mmol) in
DMF (2.5 mL), allyl bromide (0.91 g, 7.5 mmol) and K2CO3 (1.04 g,
7.5 mmol) were added successively. The reaction mixture was stirred
1 h at 25 ꢀC then diluted with water (10 mL) and hexane (10 mL). The
aqueous phase was extracted with hexane. The combined organic
extracts was washed with brine and dried over MgSO4, filtered and
concentrated under reduced pressure. The residue was purified by
flash chromatography on silica gel (hexane/EA¼3.5:1) to afford
Fig. 2. Aminoiodane intermediate proposed by Wirth et al.
and CH2Cl2 was distilled from P2O5. IBX and PhthNH2 were dried to
constant weight under vacuum. Na2CO3 was dried to constant
weight at 150 ꢀC under vacuum prior to use. Flash chromatography
was performed over silica gel 60 (230e400 mesh). All commercially
available reagents were purchased and used as received. 1H NMR
(400 MHz) and 13C NMR (100 MHz) spectra were recorded using
indicated solvent at ambient temperature. Chemical shifts have
been reported in parts per million and coupling constants (J) (H,H)
are given in Hertz, spectral splitting patterns have been assigned as
singlet (s), doublet (d), triplet (t), quadruplet (q), broad (br), broad
band (br b), multiplet or more overlapping signals (m), etc. Mass
spectra were obtained using orbitrap apparatus from high
1.28 g (97%) of 1aa. 1H NMR (400 MHz, CDCl3)
d
8.12 (d, J¼16 Hz, 1H),
8.0 (d, J¼7.2 Hz, 2H), 7.67e7.62 (m, 2H), 7.56 (t, J¼7.2 Hz, 1H), 7.48 (t,
J¼7.6 Hz, 2H), 7.34 (t, J¼7.8 Hz, 1H), 6.99 (t, J¼7.4 Hz, 1H), 6.92 (d,
J¼8 Hz, 1H), 6.09 (dtd, J¼16, 10.6, 5.2 Hz, 1H), 5.44 (dd, J¼17.4, 1.4 Hz,
1H), 5.31 (dd, J¼10.4, 1.2 Hz, 1H), 4.63 (d, J¼5.2 Hz, 2H).; 13C NMR
(100 MHz, CDCl3):
d 190.87, 157.67, 140.28, 138.36, 132.69, 132.39,
131.50,129.29,128.38,124.04, 122.86,120.82,117.77, 112.44, 60.03; IR
(neat) cmꢁ1 3065, 1660, 1598, 1486, 1016, 752; HRMS (ESI [MþH]):
265.1224 (calcd for C18H17O2: 265.1223).

A. Bakthavachalam et al. / Tetrahedron 70 (2014) 5884e5894
5891
Scheme 4. Proposed mechanism for IBX/Na2CO3/PhthNH2 mediated aziridination.
4.3. General procedure of aziridination of alkene
by column chromatography using hexane/EA (4.5:1) over silica gel
gave aziridine 2v (54.8 mg, 80%).
Anhydrous Na2CO3 (0.7 mmol) was added to the suspension of
IBX (0.35 mmol) and PhthNH2 (0.375 mmol) in EA (2 mL) under
nitrogen. After stirring 10 min at room temperature, alkene 1
(0.25 mmol) was added to the reaction mixture and then refluxed
for 27 h. The reaction mixture was quenched with water. The
separated organic layer was dried over MgSO4, filtered and con-
centrated under reduced pressure. The residue was purified by
flash chromatography on silica gel using hexane/ EA (3.5:1 for
2aef; 4.5:1 for 2geaa) to afford aziridine 2.
4.6. Procedure for aziridination of
kenes and their rearrangement
a-Bromo substituted al-
Anhydrous Na2CO3 (0.7 mmol) was added to the suspension of
IBX (0.35 mmol) and PhthNH2 (0.375 mmol) in EA (2 mL) under
nitrogen. After stirring 10 min at room temperature, alkene 1q or 1r
(0.25 mmol) was added to the reaction mixture and then refluxed
for 20 h. The reaction mixture was quenched with water. The
separated organic layer was dried over MgSO4, filtered and con-
centrated under reduced pressure. The residue was purified by
flash chromatography on silica gel using hexane/EA (8:1) to afford
product 2q or 2r.
4.4. Aziridination of alkene 1v in 10 mmol scale
Anhydrous Na2CO3 (2.97 g, 28 mmol) was added to the sus-
pension of IBX (3.92 g, 14 mmol) and PhthNH2 (2.43 g, 15 mmol) in
EA (12 mL) under nitrogen atmosphere. After stirring 10 min at
room temperature, alkene 1v (1.24 g, 10 mmol) was added to the
reaction mixture and then refluxed for 33 h. The reaction mixture
was quenched with water. The separated organic layer was dried
over MgSO4, filtered and concentrated under reduced pressure. The
residue was purified by column chromatography using hexane/EA
(4:1) over silica gel gave aziridine 2v (1.86 g, 68%).
4.6.1. 1-Phthalimido-2-hydroxymethyl-3-phenylaziridine (2a).11 1H
NMR (400 MHz, CDCl3):
d
7.82e7.71 (m, 3H), 7.61 (d, J¼4 Hz, 1H),
7.43e7.21 (m, 5H), 4.26e4.16 (m, 1H), 4.02 (d, J¼4 Hz, 0.3H),
3.83e3.79 (m, 0.6H), 3.35e3.48 (m, 2H), 3.21e3.18 (m, 0.7H), 2.44
(t, J¼6 Hz, 0.29H); 13C NMR (100 MHz, CDCl3):
d 166.62, 135.76,
134.53, 133.98, 130.45, 129.45, 128.8, 128.6, 128.22, 128.19, 127.22,
123.43, 122.96, 59.13, 52.24, 46.10; IR (neat) cmꢁ1 2360, 1712, 1376,
1145; HRMS (ESI [MþNa]): 317.0889 (calcd for C17H14N2O3Na:
317.0897).
4.5. Representative procedure for chemoselectivity trials
Anhydrous Na2CO3 (68.89 mg, 0.65 mmol) was added to the
suspension of IBX (91.0 mg, 0.325 mmol) and PhthNH2 (54.80 mg,
0.338 mmol) in EA (2 mL) under nitrogen. After stirring 10 min at
room temperature, alkene mixture [0.25 mmol of substrate 1e
(24.54 mg) and 1v (31 mg)] was added to the reaction mixture and
then refluxed for 27 h. The reaction mixture was quenched with
water. The separated organic layer was dried over MgSO4, filtered
and concentrated under reduced pressure. The residue was purified
4.6.2. 2-(3-(Hydroxymethyl)-2-methyl-2-(4-methylpent-3-en-1-yl)
aziridine-1-yl)-isoindoline-1,3-dione (2b).23 1H NMR (400 MHz,
CDCl3):
d 7.75e7.73 (m, 2H), 7.67e7.64 (m, 2H), 4.98 (m, 1H), 3.94
(d, J¼10.8 Hz, 1H), 3.65 (dd, J¼11.6, 8.8 Hz, 1H), 3.32 (br s, 1H), 2.70
(dd, J¼8.8, 3.6 Hz, 1H), 2.17 (br s, 1H), 2.0e1.97 (m, 3H), 1.61 (s, 3H),
1.54 (s, 3H), 1.38 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 166.21,
134.12, 132.53, 130.63, 123.08, 122.86, 61.45, 54.41, 51.25, 34.94,
25.60, 25.32, 17.62, 17.58; IR (neat) cmꢁ1 2925, 1715, 1375, 1051, 711,

5892
A. Bakthavachalam et al. / Tetrahedron 70 (2014) 5884e5894
647; HRMS (ESI [MþNa]): 337.1526 (calcd for C18H22N2O3Na:
2H), 7.66 (dd, J¼5.6, 3.2 Hz, 2H), 7.48e7.44 (m, 2H), 7.35 (t, J¼7.4 Hz,
2H), 7.30e7.25 (m, 1H), 4.86 (q, J¼12.0 Hz, 2H), 4.00 (dd, J¼9.0,
5.4 Hz, 1H), 2.90 (d, J¼7.6 Hz, 1H), 2.87e2.81 (m, 1H), 2.33 (dt, J¼9.6,
4.9 Hz, 1H), 1.89e1.74 (m, 2H), 1.51 (d, J¼6.8 Hz, 1H), 1.35e1.21 (m,
337.1523).
4.6.3. 2-(2-(Hydroxymethyl)-3-propylaziridin-1-yl)-isoindoline-1,3-
dione (2c). 1H NMR (400 MHz, CDCl3):
d
7.72 (s, 2H), 7.66 (dd, J¼4.8,
2H); 13C NMR (100 MHz, CDCl3):
d 165.08, 138.57, 133.97, 130.56,
3.2 Hz, 2H), 3.93 (br s,1H), 3.63e3.58 (m,1H), 3.44 (br s,1H), 2.88 (t,
J¼7.2 Hz, 1H), 2.57e2.55 (m, 1H), 1.75e1.47 (m, 4H), 0.98 (t,
128.36, 127.91, 127.54, 122.94, 72.89, 70.89, 46.57, 44.63, 27.74,
23.02,15.88; IR (neat) cmꢁ1 3032, 2942, 2870,1767,1715,1376,1154,
889, 706; HRMS (EI) : 348.1480 (calcd for C21H20N2O3: 348.1474).
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 165.37, 134.17, 130.27,
123.11, 60.50, 50.92, 47.78, 29.93, 20.35, 13.92; IR (neat) cmꢁ1 1708,
1373, 1176, 1041, 898, 782; HRMS (EI): 260.1151 (calcd for
4.6.8. trans-N-(2,3-Diphenylaziridin-1-yl)-phthalimide
(2i).20 1H
C
14H16N2O3: 260.1161).
NMR (400 MHz, CDCl3): d 7.64e7.54 (m, 6H), 7.42e7.31 (m, 5H),
7.24e7.23 (m, 3H), 4.93 (d, J¼4 Hz, 1H), 3.96 (d, J¼4 Hz, 1H); 13C
4.6.4. 2-(2-(Hydroxyl(phenyl)methyl)aziridine-1-yl)-isoindoline-1,3-
dione (2d). 1H NMR (400 MHz, CDCl3):
NMR (100 MHz, CDCl3): d 165.51, 136.58, 133.86, 131.29, 130.16,
d
7.78 (dd, J¼5.6, 3.2 Hz, 2H),
129.37, 128.71, 128.60, 128.22, 128.13, 127.23, 122.86, 53.59, 46.52;
IR (neat) cmꢁ1 2923, 1716, 1372, 896, 749, 698; HRMS (ESI [MþH]):
341.1275 (calcd for C22H17N2O2: 341.1285).
7.70 (dd, J¼5.6, 3.2 Hz, 2H), 7.45e7.43 (m, 2H), 7.38e7.34 (m, 2H),
7.32e7.28 (m, 1H), 4.45 (br s, 1H), 4.33 (d, J¼8 Hz, 1H), 2.82e2.77
(m, 1H), 2.64e2.57 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 165.44,
139.90, 134.35, 130.18, 128.56, 128.11, 126.18, 123.33, 75.77, 50.55,
35.83; IR (neat) cmꢁ1 2992, 1711, 1378, 1049, 708; HRMS (ESI
[MþNa]): 317.0899 (calcd for C17H14N2O3Na: 317.0897).
4.6.9. 2-(7-Azabicyclo[4.1.0]heptan-7-yl)isoindoline-1,3-dione
(2j).14,19 1H NMR (400 MHz, CDCl3):
d 7.71e7.68 (m, 2H), 7.63e7.60
(m, 2H), 2.70 (d, J¼4 Hz, 2H), 2.21e2.18 (m, 2H), 1.93 (br s, 2H),
1.39e1.34 (m, 2H), 1.28e1.22 (m, 2H); 13C NMR (100 MHz, CDCl3):
4.6.5. 2-(2-Hydroxy-7-azabicyclo[4.1.0]heptan-7-yl)-isoindoline-1,2-
d
165.15, 133.76, 130.62, 122.74, 43.81, 23.09, 20.04; IR (neat) cmꢁ1
dione (2e). 1H NMR (400 MHz, CDCl3):
d
7.74 (dd, J¼5.6, 3.2 Hz, 2H),
2937, 1715, 1458, 178, 712; HRMS (EI): 242.1053 (calcd for
C14H14N2O2: 242.1055).
7.67e7.65 (m, 2H), 4.09e4.06 (m, 1H), 3.56 (d, J¼7.2, 1H), 3.19 (ddd,
J¼7.4, 4.8, 2.4 Hz, 1H), 2.78 (dd, 7.6, 4 Hz, 1H), 2.02e1.98 (m, 2H),
1.70e1.67 (m, 1H), 1.57e1.54 (m, 1H), 1.41e1.32 (m, 1H), 1.22e1.17
4.6.10. 2-(7-Azabicyclo[4.1.0]hept-3-en-7-yl)isoindoline-1,3-dione
(2k).24 1H NMR (400 MHz, CDCl3):
7.71e7.70 (m, 2H), 7.63e7.62
(m, 1H); 13C NMR (100 MHz, CDCl3):
d
165.42, 134.17, 130.23, 123.11,
d
66.69, 49.17, 45.89, 29.05, 21.72, 19.18; IR (neat) cmꢁ1 2938, 1704,
(m, 2H), 6.20e6.18 (m,1H), 5.91e5.88 (m,1H), 3.13 (d, J¼6.8 Hz,1H),
1373, 1153, 790; HRMS (ESI [MþH]): 259.1074 (calcd for
2.84 (br s, 1H), 2.53e2.48 (m, 1H), 2.17e2.11 (m, 1H), 2.07e1.99 (m,
C
14H15N2O3: 259.1077).
1H),1.68e1.60 (m,1H); 13C NMR (100 MHz, CDCl3):
d 164.97,133.86,
132.13, 130.34, 122.82, 121.34, 46.23, 40.23, 20.89, 18.17; IR (neat)
cmꢁ1 3034, 2922, 1711, 1463, 1380, 1151, 787; HRMS (EI): 240.0905
(calcd for C14H12N2O2: 240.0899).
4.6.6. 2-((3aR,4S,5aR,6aR,6bS)-4-Hydroxy-2,2-dimethyldihydro-
3aH-[1,3]dioxolo[40,50:3,4]benzo[1,2-b]azirin-6(4H,6aH,6bH)-yl)iso-
indoline-1,3-dione (2f). 1H NMR (400 MHz, CDCl3):
d
7.75 (dd, J¼5.6,
3.2 Hz, 2H), 7.67 (dd, J¼5.6, 3.2 Hz, 2H), 4.9 (d, J¼6 Hz, 1H), 4.29 (dd,
J¼5.8, 3.4 Hz, 1H), 3.94 (d, J¼3.2 Hz, 1H), 3.75 (d, J¼11.2 Hz, 1H), 3.10
(d, J¼7.2 Hz, 1H), 2.96 (d, J¼7.6 Hz, 1H), 2.51e2.47 (m, 1H), 2.29 (dd,
J¼4, 2.4 Hz,1H),1.41 (s, 3H),1.35 (s, 3H); 13C NMR (100 MHz, CDCl3):
4.6.11. 2-(1-Methyl-7-azabicyclo[4.1.0]heptan-7-yl)isoindoline-1,3-
dione (2l).19 1H NMR (400 MHz, CDCl3):
d 7.66e7.58 (m, 4H), 2.82
(d, J¼5.2 Hz, 1H), 2.15e2.06 (m, 2H), 1.95e1.94 (m, 1H), 1.65e1.58
(m, 1H), 1.37e1.34 (m, 2H), 1.25e1.17 (m, 5H); 13C NMR (100 MHz,
d
164.48, 134.22, 130.21, 123.22, 109.51, 74.78, 70.07, 64.7, 44.66,
CDCl3): d 166.1, 133.64, 130.72, 122.54, 48.19, 47.10, 30.29, 23.53,
43.34, 27.42, 25.23, 23.75; IR (neat) cmꢁ1 2913, 1778, 1723, 1467,
20.23, 20.07, 19.91; IR (neat) cmꢁ1 2934, 1726, 1370, 1147, 711;
HRMS (EI): 256.1206 (calcd for C15H16N2O2: 256.1212).
1376, 1265, 708; HRMS (ESI [MþH]): 331.12882 (calcd for
C
17H19N2O5: 331.12885). Single crystals of product 2f suitable for X-
ray crystallographic analysis were obtained by slow crystallization
from dichloromethane/hexane solution. CCDC number for 2f is
994392. Crystal data for 2f; empirical formula¼C17H18N2O5, for-
4.6.12. 1-Aminophthalimide-2-6,6a-dihydroindeno[1,2-b]aziridine
(2m).19 1H NMR (400 MHz, CDCl3)
d
7.78 (dd, J¼5.2, 3.2 Hz, 2H),
7.68 (dd, J¼5.4, 3.0 Hz, 3H), 7.24 (br s, 3H), 4.15 (d, J¼5.2 Hz, 1H),
mula
weight¼330.33,
temperature¼296
(2)
K,
3.77 (dd, J¼5.0 Hz, 1H), 3.49 (d, J¼18 Hz, 1H), 3.27 (dd, J¼17.8,
wavelength¼1.54178 A, Crystal system¼orthorhombic, space
4.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 165.11, 143.13, 138.88,
ꢀ
ꢀ
group¼P 21 21 21, unit cell dimensions a¼6.8269 (2) A, b¼10.9827
134.05, 130.52, 128.62, 126.79, 125.54, 125.33, 123.05, 53.32, 48.79,
35.1; IR (neat) cmꢁ1 2920,1714,1374,1140, 707; HRMS (ESI [MþH]):
277.0976 (calcd for C17H13N2O2: 277.0972).
(4) A, c¼21.5999 (7) A,
a
¼90ꢀ,
b
¼90ꢀ,
g
¼90ꢀ, volume¼1619.51
ꢀ
ꢀ
(9) A , Z¼4, density (calculated)¼1.351 Mg/m3, absorption
3
ꢀ
coefficient¼0.841
mmꢁ1
mm3,
,
F(000)¼692,
theta range
crystal
data
size¼0.48ꢂ0.12ꢂ0.04
for
4.6.13. 3-Phthalimido-3-azatricyclo[3.2.1.02,4]-octane
(2o).25 1H
collection¼4.09e67.35ꢀ, index ranges¼ꢁ8ꢃhꢃ4, ꢁ13ꢃkꢃ12,
NMR (400 MHz, CDCl3): 7.73e7.71 (m, 2H), 7.64e7.62 (m, 2H),
d
ꢁ25ꢃlꢃ25,
reflections
collected¼24,722,
Independent
2.77 (br s, 2H), 2.73 (br s, 2H), 1.59e1.55 (m, 1H), 1.47 (d, J¼8.8 Hz,
reflections¼2890 [R(int)¼0.0351], completeness to theta (67.35ꢀ)¼
99.6%, absorption correction¼semi-empirical from equivalents,
max. and min. transmission¼0.9671 and 0.6883, refinement
method¼full-matrix least-squares on F2, data¼2890, restraints¼0,
parameters¼222, goodness-of-fit on F2¼0.997, Final R indices
2H), 1.26e1.24 (m, 2H), 0.78 (d, J¼10 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d 165.33, 133.83, 130.47, 122.78, 45.15, 36.21, 27.69, 26.11; IR
(neat) cmꢁ1 2959, 1711, 1376, 1135, 704; HRMS (EI): 254.1051 (calcd
for C15H14N2O2: 254.1055).
[I>2sigma(I)] R1¼0.0384, wR2¼0.1131,
R
indices (all data)
4.6.14. Methyl
4-((1-(1,3-dioxoisoindolin-2-yl)aziridin-2-yl)me-
R1¼0.0398, wR2¼0.1150, absolute structure parameter¼0.0(3),
thoxy)benzoate (2p). 1H NMR (400 MHz, CDCl3):
d
7.98 (d, J¼8.8 Hz,
extinction coefficient¼0.0028(5), largest diff. peak and hole¼0.395
2H), 7.77 (dd, J¼5.8, 3.0 Hz, 2H), 7.68 (dd, J¼5.2, 3.2 Hz, 2H), 6.98 (d,
J¼9.2 Hz, 2H), 4.47 (dd, J¼10.6, 4.6 Hz, 1H), 4.21 (dd, J¼11, 5 Hz, 1H),
3.86 (s, 3H), 3.07e3.03 (m, 1H), 2.68e2.61 (m, 2H); 13C NMR
ꢀꢁ3
and ꢁ0.177 e A
.
4.6.7. 2-(2-(Benzyloxy)-7-azabicyclo[4.1.0]heptan-7-yl)isoindoline-
1,3-dione (2g). 1H NMR (400 MHz, CDCl3):
7.75 (dd, J¼5.4, 3.0 Hz,
(100 MHz, CDCl3):
131.6, 130.25, 123.53, 123.13, 114.29, 67.41, 51.81, 40.56, 35.69; IR
d 167.84, 166.74, 164.96, 162.14, 134.22, 134.14,
d

A. Bakthavachalam et al. / Tetrahedron 70 (2014) 5884e5894
5893
(neat) cmꢁ1 2951, 1716, 1605, 1377, 1170; HRMS (ESI [MþH]):
1717, 1425, 1147, 707; HRMS (ESI [MþH]): 429.1449 (calcd for
C25H21N2O5: 429.1445).
353.1145 (calcd for C19H17N2O5: 353.1132).
4.6.15. Methyl 1-(1,3-dioxoisoindolin-2-yl)-3-methylaziridine-2-
carboxylate (2s).26 According to the general procedure reaction of
(E/Z) methyl crotonate (1s) yielded 86% of product 2s in 5:1 ratio. 1H
4.6.22. (E)-2-(2-Cinnamoyl-3-phenylaziridin-1-yl)-isoindoline-1,3-
dione (2z).28 1H NMR (400 MHz, CDCl3):
7.74e7.71 (m, 2H),
d
7.65e7.63 (m, 2H), 7.58e7.56 (m, 2H), 7.50e7.48 (m, 2H), 7.41e7.33
(m, 7H), 7.09 (d, J¼16.0 Hz, 1H), 4.58 (d, J¼4.8 Hz, 1H), 3.97 (d,
NMR (400 MHz, CDCl3):
d
7.72e7.69 (m, 2H), 7.62 (dd, J¼5.6, 3.2 Hz,
2H), 3.65 (s, 3H), 3.35e3.32 (m, 1H), 3.01 (d, J¼5.2 Hz, 1H), 1.48 (d,
J¼4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 189.23, 164.58, 144.60,
J¼6.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
167.47, 164.74, 133.87,
135.33, 134.23, 133.94, 131.02, 130.38, 129.0, 128.75, 128.67, 128.54,
127.20, 125.98, 123.14, 50.80, 50.22; IR (neat) cmꢁ1 2923, 1716, 1674,
1450, 1146, 703; HRMS (ESI [MþH]): 395.1383 (calcd for
130.32, 122.99, 52.63, 44.93, 44.73, 16.31; IR (neat) cmꢁ1: 2954,
1717, 1441, 1137, 709; HRMS (ESI [MþH]) 261.0879 (calcd for
C
13H13N2O4: 261.0870).
C25H19N2O3: 395.1390).
4.6.16. 2-(2-(Morpholine-4-carbonyl)-3-phenyaziridin-1-yl)-iso-
indoline-1,3-dione (2t). 1H NMR (400 MHz, CDCl3):
4.6.23. 2-(2-(2-(Allyloxy)benzoyl)-3-phenylaziridin-1-yl)-isoindo-
line-1,3-dione (2aa). 1H NMR (400 MHz, CDCl3):
d
7.74 (dd, J¼5.2,
d
8.03 (d, J¼7.6 Hz,
3.2 Hz, 2H), 7.65 (dd, J¼5.2, 2.8 Hz, 2H), 7.46 (d, J¼6.4 Hz, 2H),
7.39e7.31 (m, 3H), 4.69 (d, J¼4.8 Hz, 1H), 4.04e4.00 (m, 2H),
3.81e3.79 (m, 2H), 3.72e3.62 (m, 3H), 3.52 (d, J¼4.8 Hz, 1H),
2H), 7.71 (dd, J¼5.2, 3.2 Hz, 2H), 7.63 (dd, J¼5.2, 2.8 Hz, 2H), 7.57 (d,
J¼7.6 Hz, 2H), 7.48 (t, J¼8 Hz, 2H), 7.29 (d, J¼8 Hz, 1H), 7.0 (t,
J¼7.6 Hz, 1H), 6.86 (d, J¼8.4 Hz, 1H), 5.87 (ddd, J¼15.6, 10.0, 4.8 Hz,
1H), 5.26 (d, J¼17.2 Hz,1H), 5.10 (d, J¼10.4 Hz,1H), 4.81 (d, J¼4.8 Hz,
1H), 4.56e4.48 (m, 2H), 4.19 (d, J¼4.8 Hz, 1H); 13C NMR (100 MHz,
3.43e3.40 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 164.66, 162.59,
135.39, 134.24, 133.94, 130.41, 128.59, 128.34, 127.11, 123.46, 123.03,
66.41, 66.20, 48.31, 46.77, 45.66, 42.99; IR (neat) cmꢁ1 2964, 1774,
1718, 1464, 1377, 1144, 707; HRMS (EI): 377.1367 (calcd for
CDCl3):
d 191.04, 164.66, 156.88, 137.66, 134.30, 133.85, 133.29,
132.82, 130.44, 129.24, 128.64, 127.91, 123.59, 123.08, 121.00, 117.04,
111.69, 66.84, 48.46, 47.48; IR (neat) cmꢁ1 1771, 1718, 1666, 1451,
1379, 1178, 705; HRMS (ESI [MþH]): 425.1500 (calcd for
C
21H19N3O4: 377.1376).
4.6.17. 2-(2-(2-Oxooxazolidine-3-carbonyl-3-phenylaziridin-1-yl)-
isoindoline-1,3-dione (2u).27 1H NMR (400 MHz, CDCl3):
7.75 (br s,
C26H21N2O4: 425.1496).
d
2H), 7.68 (br s, 2H), 7.49 (d, J¼7.2 Hz, 2H), 7.37 (dd, J¼12.8, 7.2 Hz,
Acknowledgements
3H), 5.16 (d, J¼5.2 Hz, 1H), 4.49e4.44 (m, 3H), 4.07e3.88 (m, 2H);
13C NMR (100 MHz, CDCl3):
d 164.89, 164.65, 153.34, 134.32, 134.06,
133.99, 128.66, 128.62, 127.47, 123.09, 62.19, 50.59, 43.99, 43.02; IR
(neat) cmꢁ1 2920, 1774, 1709, 1361, 1106, 696; HRMS (EI): 377.1017
(calcd for C20H15N3O5: 377.1012).
We thank the National Science Council of the Republic of China
for generous financial support. B.A. thanks MOFA for Taiwan
scholarship programme.
Supplementary data
4.6.18. 2-(1-Acetyl-7-azabicyclo[4.1.0]heptan-7yl)-isoindoline-1,3-
dione (2v). 1H NMR (400 MHz, CDCl3):
d
7.67 (dd, J¼5.4, 3.0 Hz, 2H),
Copies of 1H and 13C NMR spectra are available. Supplementary
data related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2014.06.029.
7.60 (dd, J¼5.2, 3.2 Hz, 2H), 3.61 (d, J¼5.6 Hz, 1H), 2.64e2.56 (m,
1H), 2.40 (s, 3H), 2.29e2.18 (m, 2H), 2.07e1.99 (m, 1H), 1.56e1.41
(m, 3H), 1.24e1.21 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 201.28,
165.07, 133.74, 130.54, 122.8, 52.5, 48.6, 28.22, 25.98, 23.04, 20.18,
19.59; IR (neat) cmꢁ1 2938, 1712, 1377, 1153, 710; HRMS (EI):
284.1160 (calcd for C16H16N2O3: 284.1161).
References and notes
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