Novel aziridination of olefins: Direct synthesis from sulfonamides using t-BuOI

Article abstract of DOI:10.1039/b606499j

tert-Butyl hypoiodite (t-BuOI) was found to be a powerful reagent for synthesis of aziridines from olefins and sulfonamides. The aziridination of olefins was achieved by using sulfonamides with t-BuOI. Our preliminary findings represent the example of met

Full text of DOI:10.1039/b606499j

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Novel aziridination of olefins: direct synthesis from sulfonamides using
t-BuOI{
Satoshi Minakata,* Yoshinobu Morino, Yoji Oderaotoshi and Mitsuo Komatsu*
Received (in Cambridge, UK) 9th May 2006, Accepted 12th June 2006
First published as an Advance Article on the web 30th June 2006
DOI: 10.1039/b606499j
chloramine-T and a halogen catalyst system.9 The direct prepara-
tert-Butyl hypoiodite (t-BuOI) was found to be a powerful
tion of aziridines from sulfonamides and olefins without the use of
heavy metal catalysts would enhance the scope and synthetic value
of the reaction.10 In this context we report herein on the unusual
metal-free aziridination of olefins with readily accessible sulfona-
mides as a nitrogen source, in which tert-butyl hypoiodite (t-BuOI)
plays an important role as a powerful oxidant. Although t-BuOI is
known as an iodination reagent which can readily be prepared
from t-BuOCl and NaI,11 examples of using the reagent in organic
transformations are rarely reported to date.12
reagent for synthesis of aziridines from olefins and sulfon-
amides. The aziridination of olefins was achieved by using
sulfonamides with t-BuOI. Our preliminary findings represent
the example of metal-free aziridination of olefins with readily
accessible sulfonamides as a nitrogen source.
The aziridination of olefins is an extremely important transforma-
tion since aziridines are useful synthetic intermediates and are often
present as substructures in natural products and frequently show
diverse biological activities.1 Among the various methods for the
synthesis of aziridines, the transfer of a nitrogen atom onto an
olefin is the shortest route and offers a method for the practical
formation of aziridines. To generate an active nitrogen species for
olefin aziridination, great progress has been made with combina-
tions of nitrogen sources and catalysts and/or activators as shown
in Scheme 1. The reagent [N-(p-toluenesulfonyl)imino]-phenylio-
dinane (PhILNTs) has been extensively used as a primary nitrene
source for transition metal-catalyzed aziridination2 including
asymmetric versions.3 However, the reagent suffers from several
drawbacks such as its commercial unavailability, the high cost of
its source, and the fact that an equimolar amount of iodobenzene
is generated. Although alternative nitrogen sources, azides,4
chloramine-T,5 bromamine-T,6 nitrido complexes,7 and combina-
tions of sulfonamides and terminal oxidants8 have been widely
applied to olefin aziridination, catalytic or stoichiometric amounts
of metals are required for the processes except for methods using
We began our investigation with styrene and p-toluenesulfona-
mide as a model aziridination. As illustrated in Table 1, treatment
of p-toluenesulfonamide and styrene (2 equiv) with t-BuOI
(1 equiv) at room temperature in acetonitrile provided N-
(p-toluenesulfonyl)-2-phenylaziridine (1) in moderate yield
(entry 1). Screening of the amount of t-BuOI required (entries
2–4) showed 1.5 mmol of t-BuOI to be optimal, to give aziridine 1
in excellent yield (entry 4). These results suggest that more than
one equivalent of t-BuOI relative to p-toluenesulfonamide is
required for the aziridination to be complete.
In order to confirm the superiority of the system, other
representative iodinating reagents, bis(pyridine)iodine tetrafluoro-
borate (IPy2BF4), NIS and I2, were evaluated to the aziridination.
Since IPy2BF4 and I2 did not give the desired aziridine and the
efficiency was rather low to afford 1 in 18% yield by NIS, t-BuOI
was found to be a powerful reagent for the reaction.
The scope of substrates in the aziridination by t-BuOI with
p-toluenesulfonamide was then explored using a range of olefins
under the optimized conditions (Table 2). The reaction of 1,2-
dihydronaphthalene with p-toluenesulfonamide proceeded
smoothly to afford the desired aziridine in good yield (entry 1).
In the case of a-methylstyrene, the corresponding aziridine was
Table 1 Aziridination of styrene with p-toluenesulfonamide using
t-BuOIa
Entry
t-BuOCI/mmol
NaI/mmol
Yield (%)b
Scheme 1 Representative methods for generating active nitrogen species
1
2
3
4
a
0.5
1.0
1.2
1.5
0.5
1.0
1.2
1.5
46
84
93
95
for olefin aziridination.
Department of Applied Chemistry, Graduate School of Engineering,
Osaka University, Yamadaoka 2-1, Suita, Osaka, 565-0871, Japan.
E-mail: minakata@chem.eng.osaka-u.ac.jp; Fax: +81-6-6879-7402
{ Electronic supplementary information (ESI) available: Procedure of
synthesis and experimental data of aziridines. See DOI: 10.1039/b606499j
Reaction conditions: styrene (1.0 mmol), p-toluenesulfonamide
b
(0.5 mmol), MeCN (3 mL), rt, 5 h. Isolated yields based on
p-toluenesulfonamide.
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Chem. Commun., 2006, 3337–3339 | 3337

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Table 2 Olefin aziridination using the present systema
Table 3 Aziridination of styrene with sulfonamides using t-BuOIa
Entry
1
Olefin
Aziridine
Yield (%)b
76c
Entry Amide
1
Time/h Product
12
Yield (%)b
66c
2
3
a
5
3
92
97
2
3
81d,e
66f,g
Reaction conditions: sulfonamide (0.5 mmol), styrene (1.0 mmol),
b
t-BuOCl (1.5 mmol), NaI (1.5 mmol), MeCN (3 mL), rt. Isolated
4
5
58h
77
c
yields based on a sulfonamide. t-BuOCl and NaI: 1 mmol.
N-unsubstituted aziridines more readily, we attempted to synthe-
size N-[2-(trimethylsilyl)ethanesulfonyl]aziridines (N-SES-aziri-
dine), whose SES group can easily be deprotected under mild
conditions.14 Treatment of styrene with 2-(trimethylsilyl)ethane-
sulfonamide (SESNH2) in the presence of t-BuOI led to the
production of N-SES-aziridine in 97% yield (entry 3).
6
7
a
63
82
In summary, an efficient and convenient method for the
synthesis of aziridines from olefins and sulfonamides using t-BuOI
has been developed.15 Our preliminary findings represent the first
example of the metal-free aziridination of olefins using readily
available sulfonamides as a nitrogen source. Mechanistic con-
siderations and expanding the generality of the reaction are
currently underway.
Reaction conditions: p-toluenesulfonamide (0.5 mmol), olefin
(1.0 mmol), t-BuOCl (1.5 mmol), NaI (1.5 mmol), MeCN (3 mL), rt,
96 h. Isolated yields based on p-toluenesulfonamide. Reaction
b
c
time: 0.5 h. Reaction time: 2 h. e 1H-NMR yield. Reaction time:
d
f
g
h
5 h. Cis/trans 5 41/59. t-BuOCl and NaI: 1 mmol.
This work was partially supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan. One of the authors (Y.M.)
expresses his special thanks to the 21st century center of excellence
(21COE) program, ‘‘Creation of Integrated EcoChemistry of
Osaka University’’. We also wish to acknowledge the Instrumental
Analysis Center, Faculty of Engineering, Osaka University.
produced in high yield (entry 2). When cis-b-methylstyrene was
employed, a mixture of diastereomers was formed (entry 3). The
present reaction system was also found to be applicable to the
aziridination of aliphatic olefins. Cyclic and acyclic terminal olefins
such as cyclohexene and 1-octene underwent aziridination in good
to moderate yields (entries 4 and 5). It is noteworthy that the
reaction of trans-2-octene proceeded with complete stereo-
selectivity, giving a trans-substituted aziridine as the sole product
(entry 6). In contrast to cis-b-methylstyrene (entry 3), the
aziridination of cis-2-octene was stereoselective and gave the
corresponding cis-aziridine exclusively in good yield (entry 7).
These complete stereoselective and stereospecific aziridinations are
fully consistent with a reaction pathway involving a cyclic
iodonium intermediate.
Notes and references
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Some other sulfonamides function as competent nitrogen
sources in the present aziridination, as summarized in Table 3.
When aziridination was performed with o-nitrobenzenesulfona-
mide (o-NsNH2), the desired product was formed in moderate
yield (entry 1). An alkylsulfonamide, n-butanesulfonamide, was
found to be applicable to the reaction, giving an
N-butanesulfonylaziridine in high yield (entry 2). Although
arenesulfonyl groups attached to the nitrogen of aziridines can
be removed under reducing conditions, undesirable reactions such
as the ring-opening of the aziridine sometimes occurs.13 To obtain
3338 | Chem. Commun., 2006, 3337–3339
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15 General procedure for the synthesis of aziridines. To a mixture of the
sulfonamide (0.5 mmol), the olefin (1.0 mmol) and NaI (1.0–1.5 mmol)
in MeCN (3 mL) was added t-BuOCl (1.0–1.5 mmol). The mixture was
allowed to stir in the dark at room temperature for indicated time under
an atmosphere of nitrogen, quenched with 0.3 M aqueous Na2S2O3
(3 mL), extracted with CH2Cl2, dried over MgSO4, and concentrated
under vacuum. The residue was purified by flash column chromato-
graphy on silica gel (eluent: hexane/ethyl acetate).
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10 An electrochemical process and a method using hypervalent iodine for
aziridination are known as alternative metal-free procedures. See T. Siu
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Chem. Commun., 2006, 3337–3339 | 3339