An Efficient Aziridination of Styrenes Promoted by Visible Light

Article abstract of DOI:10.1055/s-0035-1561635

Styrenes reacted with sulfonamide in the presence of potassium carbonate and iodine in CHCl₃ under visible light irradiation to produce the corresponding aziridines in moderate to good yields. A reaction mechanism to explain the formation of aziridines is also proposed.

Full text of DOI:10.1055/s-0035-1561635

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–F
paper
A
K. Matsuzawa et al.
Paper
Synthesis
An Efficient Aziridination of Styrenes Promoted by Visible Light
Kazuki Matsuzawa
Yoshitomo Nagasawa
Eiji Yamaguchi
Norihiro Tada
Akichika Itoh*
Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi,
Gifu 501-1196, Japan
itoha@gifu-pu.ac.jp
Received: 17.03.2016
Accepted after revision: 06.04.2016
Published online: 19.05.2016
N1C1 + C1
addition
NR'
(a)
(b)
"C1" = carbene precursor
(diazo compound)
R
R
DOI: 10.1055/s-0035-1561635; Art ID: ss-2016-t0191-op
NR'
ylide, carbanion having LG
Abstract Styrenes reacted with sulfonamide in the presence of potas-
sium carbonate and iodine in CHCl3 under visible light irradiation to
produce the corresponding aziridines in moderate to good yields. A re-
action mechanism to explain the formation of aziridines is also pro-
posed.
R
C2 + N1
addition
"N1" = nitrene precursor
(iminoiodinane, haloamine,
azide compound)
primary amine, oxidant
Key words aziridine, environment-friendly, visible light, molecular io-
dine, radical reaction
Scheme 1 General aziridination reaction routes: (a) N1C1 + C1 (b) C2
+ N1
Aziridines are an important class of structural motif fre-
quently found in various natural products and pharmaceu-
ticals.1 Aziridines are also important intermediates in syn-
thetic organic chemistry.2 Therefore, several synthetic
methods for aziridines have been developed.3 The prepara-
tion of aziridines is typically performed by means of intra-
molecular cyclization reaction such as Wenker type reac-
tion of amino alcohols or their derivatives.4 Although this
process is reliable to construct aziridines, the starting mate-
rials require multistep synthesis.5
Meanwhile, there are two ways to synthesize aziridine
by intermolecular [2+1] cyclization reaction; one is the ad-
dition of imines with carbenes (N1C1 + C1 addition) and
the other alkenes with amines or nitrenes (C2 + N1 addi-
tion) (Scheme 1).
Aziridination reaction of imines are well-known meth-
odologies such as imino Corey–Chaykovsky reaction, aza-
Darzens reaction, and carbene insertion into C=N double
bond.6–8 And many methodologies leading to aziridines
from alkenes as the substrate have been developed during
the last decade because the imines are often expensive and
difficult to store due to their instability. The nitrene cy-
cloaddition to alkenes is one of the powerful and straight-
forward method to form aziridines. Regarding aziridination
of alkenes using nitrenes, several methods generating ni-
trenes have been developed including photolysis, thermoly-
sis, and transition-metal catalysis of precursors such as
chloramine-T, PhI=NTs, and azides.9–11 An interesting ap-
proach for aziridination using nitrenes was also reported
using sulfonamide or phthalimide as nitrene precursor via
transition-metal catalysis using hypervalent iodine re-
agent.12,13 These reactions are reliable methods for aziridi-
nation, however, they are generally labile, explosive, and re-
quire careful handling.
Our laboratory had developed photo-aerobic oxidation
methodology using molecular iodine and visible light,
which allowed us to synthesize β-hydroxysulfone from so-
dium sulfinate derivatives (Scheme 2). We assumed that
sulfur radical, which was generated by homolytical cleav-
age of sulfur–iodine bond by visible light irradiation is the
active intermediate.14 Thus, we hypothesized that this radi-
cal generation methodology is also applicable to construct
aziridine. Nitrogen radical could be generated by using ni-
trogen–iodine bond homolytical cleavage,15 and N-centered
radicals generated react with styrenes to give iodo-aminat-
ed intermediates followed by aziridine ring formation
through cyclization (Scheme 2). Herein, we report a practi-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

B
K. Matsuzawa et al.
Paper
Synthesis
cal transition-metal-free aziridination method of styrene
derivatives with p-toluenesulfonamide (TsNH2) as nitrogen
source using molecular iodine and visible light.
Table 1 Optimization of the Reaction Conditionsa
Ar, fluorescent lamp
I2 (1 equiv)
Ts
N
additive
+
TsNH2
Previous work
tBu
O
solvent, 20 h
OH
I2
tBu
S
Ar1
SO2Ar2
+
Ar2
O–Na+
Ar1
1a (0.3 mmol)
2 (2 equiv)
3a
MeCN, AcOH
AcOH, I2
Entry
Additive (equiv)
Solvent (mL)
Yield (%)b
visible light
irradiation
O
S
O
S
O
S
Ar2
I
Ar2
1
2
–
CH2Cl2 (3)
CH2Cl2 (3)
PhCl (3)
0
Ar2
OI
S–I bond
cleavage
O
O
K2CO3 (1)
K2CO3 (1)
K2CO3 (1)
K2CO3 (2)
K2CO3 (3)
K2CO3 (5)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
34
This work
Ts
N
I2, base
solvent
3
4
Ar2NH2
I2, base
Ar1
+
4
CHCl3 (3)
CH2Cl2 (3)
CH2Cl2 (3)
CH2Cl2 (3)
CH2Cl2 (5)
CHCl3 (5)
CHCl3 (5)
33
Ar1
visible light
irradiation
5
38
I
Ar2NH
Ar2
N
6
25
N–I bond
cleavage
H
plausible
active species
7
18
8
83
Scheme 2 Working hypothesis for the construction of aziridine
9
81
10
87 (86)c
To test this hypothesis, optimization of reaction condi-
tions were carried out (Table 1 and the Supporting Informa-
tion). The reaction did not proceed without additives (Table
1, entry 1). When K2CO3 was used as an additive, the de-
sired product 3a was obtained in 34% yield (entry 2). After
screening of various solvents, dichloromethane was found
to be the crucial solvent for the reaction (entries 2–4), and 2
equivalents of K2CO3 were the best proportion as the addi-
tive (entries 2, 5–7). When the reaction was performed in
low concentration to improve light permeability,16 the yield
of aziridine 3a rose dramatically (entry 8). When the reac-
tion was conducted at 60 °C, the desired product was ob-
tained in 86% isolated yield (entry 10). The consumption of
styrene was observed in all solvents attempted. In polar
solvents, polymerization of styrene was detected.
With the optimized conditions in hand, this reaction
conditions were applied to various styrenes (Table 2). p-
Substituted styrenes containing electron-donating 1a,b,
electron-withdrawing 1c,d, or electron-neutral (1e) were
reacted with sulfonamide to form the corresponding aziri-
dines 3a–e in excellent yields (Table 2, entries 1–5). In addi-
tion, 3 mmol of styrene 1a was also converted to the aziri-
dine in moderate yield (entry 1). o-Substituted and m-sub-
stituted styrenes were also transformed in good yield
(entries 6, 7). When trans-β-methylstyrene was used as the
substrate, a mixture of cis- and trans-isomers was obtained
(entry 8). On the other hand, the reaction of α-methylsty-
rene under these conditions produced the product in low
yield (entry 9). Moreover, allylbenzene and cyclohexene
gave no product and the substrate alkenes were recovered
(entries 10, 11).
a General procedure : A solution of 4-tert-butylstyrene (1a; 0.3 mmol),
TsNH2 (2; 2 equiv), I2 (1 equiv), and additive in anhyd solvent was stirred for
20 h at r.t. under an argon atmosphere and irradiated with 22 W fluores-
cent lamps.
b The yields were determined by 1H NMR analysis with 1,1,2,2-tetrachlo-
roethane as an internal standard; isolated yield is shown in parentheses.
c The reaction was performed at 60 °C.
ger to the optimal conditions, the reaction was completely
suppressed (Table 3, entry 1). Hence some radical species
might be involved in the reaction mechanism. The yield of
the desired product was also decreased under the dark re-
action condition at 60 °C (entry 2). Therefore, the photoir-
radiation may have a key role in this reaction. Furthermore,
the reaction was also suppressed under an air atmosphere
(entry 3). It is supposed that the radical species, which was
produced in situ, captured the molecular oxygen.17 18-
crown-6 completely inhibited the reaction, while potassi-
um ion is crucial for the reaction (entry 4). However, the
role of potassium cation is still unclear at this point.
Based on these results, a plausible reaction mechanism
for the aziridination is proposed (Scheme 3). First, TsNH2
reacts with molecular iodine to produce intermediate I.
Next, nitrogen-centered radical II, generated by photolysis
of N–I bond, react with styrene to form the carbon centered
radical. The concentration of the reaction mixture may be a
concern in this process. Generated radical III can react with
molecular iodine or iodine radical to produce IV. Finally,
target aziridine is formed by ring-closure reaction of IV. An-
other possibility to form aziridine is the radical chain type
reaction initiated by III abstracting iodine from I to gener-
ate IV and II. However, this process might be minor due to
stronger dissociation energy of N–I bond compared to I–I
bond.
To find out the reaction mechanism, controlled experi-
ments were conducted (Table 3). When 2,2,6,6-tetrameth-
ylpiperidine 1-oxyl (TEMPO) was added as a radical scaven-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

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K. Matsuzawa et al.
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Table 2 Substrate Scope and Limitationsa
Ar, fluorescent lamp
I2 (1 equiv)
K2CO3 (2 equiv)
Ts
N
+
TsNH2
R
R
CHCl3 (5 mL), 60 °C, 20 h
1 (0.3 mmol)
2 (2 equiv)
3
Entry
Substrate
Product
Yield (%)b
1
2
3
4
5
6
7
1a
R = 4-t-Bu
R = 4-Me
R = 4-Cl
R = 4-Br
R = 4-H
3a
3b
3c
3d
3e
3f
86
1b
1c
1d
1e
1f
83
Ts
85
N
R
77
R
81 (73)c
76
R = 3-Me
R = 2-Me
1g
3g
82
Ts
Me
N
N
8
9
1h
1i
3h
3i
72d
17
Me
Ts
Me
Me
10
11
1j
3j
0
0
N
Ts
1k
3k
N
Ts
a General procedure: A solution of substrate 1 (0.3 mmol), TsNH2 (2; 2 equiv), I2 (1 equiv), and K2CO3 (2 equiv) in CHCl3 was stirred for 20 h at 60 °C under an
argon atmosphere and irradiated with 22 W fluorescent lamps.
b Isolated yields.
c The reaction was performed with 3.0 mmol of 1e.
d cis/trans = 49:51 determined by 1H NMR spectroscopy.
In conclusion, we have demonstrated an aziridination of
styrenes using molecular iodide under an argon atmo-
Table 3 Controlled Experiments to Elucidate the Reaction Mechanism
sphere with irradiation using fluorescent lamp. This novel
Ar, fluorescent lamp
Ts
I2 (1 equiv)
metal-free aziridination is beneficial as an environmentally
benign method using inexpensive molecular iodide as oxi-
dant, commercially available p-toluenesulfonamide as a ni-
trogen source, and harmless visible light.
N
K2CO3 (2 equiv)
+
TsNH2
tBu
1a (0.3 mmol)
CHCl3 (5 mL), 60 °C, 20 h
tBu
2 (2 equiv)
3a
Entry
Changes from standard conditions
Yield (%)a
visible light
I
I2
irradiation
Ts
N
TsNH2
Ts
N
1
2
3
4
TEMPO (1 equiv) added
in the dark
3
N–I bond
cleavage
H
H
II
2
I
27
30
0
radical chain
reaction
Ar
under air
I
NHTs
NHTs
18-crown-6 (4 equiv) added
Ar
Ar
I2 or I
NTs
a The yields were determined by 1H NMR spectroscopy with 1,1,2,2-tetra-
chloroethane as an internal standard.
III
IV
Ar
K2CO3
3
Scheme 3 Plausible reaction mechanism for aziridination
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

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K. Matsuzawa et al.
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13C NMR (125 MHz, CDCl3): δ = 144.8, 134.7, 134.1, 133.5, 129.7,
128.7, 127.9, 127.8, 40.2, 36.0, 21.6.
Unless otherwise noted, all reagents including anhydrous solvents
were obtained from commercial suppliers and used as received. The
fluorescent lamps were EFR25ED 22 W from Panasonic. Analytical
TLC was carried out using 0.25 mm commercial silica gel plates (Mer-
ck silica gel 60 F254). Flash column chromatography was performed
with Kanto silica gel 60N (Spherical, Neutral, 40–50 mm). The devel-
N-(p-Tolylsulfonyl)-2-(4-bromophenyl)aziridine (3d)18
Prepared according to the general procedure from 4-bromostyrene.
The product was isolated as a white solid; yield: 81 mg (77%); Rf =
0.29 (hexane/EtOAc, 17:3).
1
oped chromatogram was analyzed by UV lamp (254 nm). H and 13C
NMR spectra were obtained on a JEOL ECA 500 spectrometer (500
MHz for 1H NMR and 125 MHz for 13C NMR) or a JEOL AL 400 spec-
trometer (400 MHz for 1H NMR and 100 MHz for 13C NMR). Chemical
shifts (δ) are expressed in parts per million and are internally refer-
enced [0.00 ppm (TMS) for 1H NMR and 77.0 ppm, (CDCl3) for 13C
NMR].
1H NMR (500 MHz, CDCl3): δ = 7.85 (d, J = 8.6 Hz, 2 H), 7.41 (d, J = 8.6
Hz, 2 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.09 (d, J = 8.6 Hz, 2 H), 3.71 (dd, J =
7.1, 4.6 Hz, 1 H), 2.97 (d, J = 7.1 Hz, 1 H), 2.42 (s, 3 H), 2.34 (d, J = 4.6
Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 144.7, 134.6, 134.1, 131.6, 129.7,
128.1, 127.8, 122.2, 40.2, 35.9, 21.6.
N-(p-Tolylsulfonyl)-2-phenylaziridine (3e);18 Typical Procedure
N-(p-Tolylsulfonyl)-2-(3-methylphenyl)aziridine (3f)18
A solution of styrene (1e; 31 mg, 0.3 mmol), p-toluenesulfonamide
(2; 103 mg, 0.6 mmol), molecular I2 (76 mg, 0.3 mmol), K2CO3 (83 mg,
0.6 mmol) in CHCl3 (5.0 mL) was stirred at 60 °C with irradiation us-
ing fluorescent lamps under an argon atmosphere for 20 h. The reac-
tion mixture was treated with sat. aq Na2S2O3 (20 mL) and the aque-
ous layer was extracted with Et2O (3 × 5 mL). The combined organic
layers were dried (Na2SO4) and filtered. The solvent was removed by
rotary evaporation and the crude product is purified by flush column
chromatography to give 3e; yield: 66.5 mg (81%); Rf = 0.29 (hex-
ane/EtOAc, 9:1).
1H NMR (500 MHz, CDCl3): δ = 7.87 (d, J = 8.0 Hz, 2 H), 7.33 (d, J = 8.0
Hz, 2 H), 7.31–7.26 (m, 3 H), 7.23–7.19 (m, 2 H), 3.77 (dd, J = 7.4, 4.6
Hz, 1 H), 2.98 (d, J = 7.4 Hz, 1 H), 2.43 (s, 3 H), 2.38 (d, J = 4.6 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 144.6, 134.9, 134.8, 129.7, 128.5,
128.26, 127.9, 126.5, 40.9, 35.9, 21.6.
Prepared according to the general procedure from 3-methylstyrene.
The product was isolated as a yellow oil; yield: 71.8 mg (82%); Rf =
0.29 (hexane/EtOAc, 17:3).
1H NMR (500 MHz, CDCl3): δ = 7.87 (d, J = 8.6 Hz, 2 H), 7.32 (d, J = 8.0
Hz, 2 H), 7.19–7.16 (m, 1 H), 7.08 (d, J = 8.0 Hz, 1 H), 7.02–7.01 (m, 2
H), 3.74 (dd, J = 7.4, 4.6 Hz, 1 H), 2.95 (d, J = 7.4 Hz, 1 H), 2.41 (s, 3 H),
2.37 (d, J = 4.6 Hz, 1 H) 2.30 (s, 3 H).
13C NMR (125 MHz, CDCl3):4 δ = 144.6, 138.2, 134.8, 129.7, 129.0,
128.4, 127.9, 127.1, 123.6, 41.0, 35.8, 21.6, 21.2.
N-(p-Tolylsulfonyl)-2-(2-methylphenyl)aziridine (3g)19
Prepared according to the general procedure from 2-methylstyrene.
The product was isolated as a white solid; yield: 71.6 mg (83%); Rf =
0.30 (hexane/EtOAc, 17:3).
1H NMR (500 MHz, CDCl3): δ = 7.89 (d, J = 8.6 Hz, 2 H), 7.34 (d, J = 8.0
Hz, 2 H), 7.19–7.15 (m, 1 H), 7.12 (d, J = 8.0 Hz, 1 H), 7.11–7.09 (m, 2
H), 3.86 (dd, J = 7.4, 4.6 Hz, 1 H), 2.98 (d, J = 7.4 Hz, 1 H), 2.44 (s, 3 H),
2.38 (s, 3 H), 2.31 (d, J = 4.6 Hz, 1 H).
13C NMR (125 MHz, CDCl3):4 δ = 144.6, 136.6, 134.8, 133.1, 129.8,
129.7, 127.9, 126.0, 125.8, 39.4, 35.0, 21.6, 19.0.
N-(p-Tolylsulfonyl)-2-(4-tert-butylphenyl)aziridine (3a)18
Prepared according to the general procedure from 4-tert-butylsty-
rene. The product was isolated as a yellow oil; yield: 85.8 mg (86%);
Rf = 0.30 (hexane/EtOAc, 9:1).
1H NMR (500 MHz, CDCl3): δ = 7.86 (d, J = 8.0 Hz, 2 H), 7.33–7.30 (m, 4
H), 7.14 (d, J = 8.0 Hz, 2 H), 3.76 (dd, J = 7.4, 4.6 Hz, 1 H), 2.95 (d, J = 6.9
Hz, 1 H), 2.42 (s, 3 H), 2.37 (d, J = 4.6 Hz, 1 H), 1.27 (s, 9 H).
cis- and trans-N-(p-Tolylsulfonyl)-2-methyl-3-aziridine (3h)
13C NMR (125 MHz, CDCl3): δ = 151.3, 144.5, 134.9, 131.9, 129.7,
127.9, 126.2, 125.4, 40.9, 35.7, 34.5, 31.2, 21.6.
Prepared according to the general procedure from trans-β-methylsty-
rene. The product was isolated as a white solid; yield: 62.1 mg (72%);
Rf = 0.30 (hexane/EtOAc, 17:3).
1H NMR (500 MHz, CDCl3): δ (trans-isomer) = 7.81 (d, J = 8.0 Hz, 2 H),
7.29–7.13 (m, 5 H), 7.15–7.13 (m, 2 H), 3.79 (d, J = 4.0 Hz, 1 H), 2.90
(dq, J = 5.7, 4.0 Hz, 1 H), 2.37 (s, 3 H), 1.84 (d, J = 5.7 Hz, 3 H); δ (cis-
isomer) = 7.88 (d, J = 8.0 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H), 7.29–7.19
(m, 5 H), 3.92 (d, J = 7.4 Hz, 1 H), 3.18 (dq, J = 7.4, 5.7 Hz, 1 H), 2.42 (s,
3 H), 1.01 (d, J = 5.7 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 144.3, 143.8, 137.8, 135.4, 135.2,
132.6, 129.6, 129.4, 128.4, 128.2, 128.0, 127.7, 127.4, 127.1, 126.2,
49.1, 49.0, 46.0, 41.75, 21.5, 21.5, 14.0, 11.8 (one carbon peak was
overlapped).
N-(p-Tolylsulfonyl)-2-(4-methylphenyl)aziridine (3b)18
Prepared according to the general procedure from 4-methylstyrene.
The product was isolated as a white solid; yield: 71 mg (82%); Rf =
0.29 (hexane/EtOAc, 9:1).
1H NMR (500 MHz, CDCl3): δ = 7.86 (d, J = 8.6 Hz, 2 H), 7.31 (d, J = 8.0
Hz, 2 H), 7.09 (s, 4 H), 3.73 (dd, J = 7.1, 4.6 Hz, 1 H), 2.96 (d, J = 7.1 Hz,
1 H), 2.42 (s, 3 H), 2.37 (d, J = 4.6 Hz, 1 H), 2.30 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 144.5, 138.1, 135.0, 131.9, 129.6,
129.2, 127.8, 126.4, 41.0, 35.7, 21.6, 21.1.
N-(p-Tolylsulfonyl)-2-(4-chlorophenyl)aziridine (3c)18
N-(p-Tolylsulfonyl)-2-methyl-2-phenylaziridine (3i)18
Prepared according to the general procedure from 4-chlorostyrene.
The product was isolated as a white solid; yield: 78.8 mg (85%); Rf =
0.30 (hexane/EtOAc, 17:3).
1H NMR (500 MHz, CDCl3): δ = 7.85 (d, J = 8.0 Hz, 2 H), 7.33 (d, J = 8.6
Hz, 2 H), 7.25 (d, J = 8.6 Hz, 2 H), 7.14 (d, J = 8.0 Hz, 2 H), 3.73 (dd, J =
6.9, 4.5 Hz, 1 H), 2.98 (d, J = 6.9 Hz, 1 H), 2.43 (s, 3 H), 2.34 (d, J = 4.5
Hz, 1 H).
Prepared according to the general procedure from trans-α-methylsty-
rene. The product was isolated as a white solid; yield: 14.4 mg (17%);
Rf = 0.10 (hexane/EtOAc, 20:1).
1H NMR (500 MHz, CDCl3): δ = 7.87 (d, J = 8.0 Hz, 2 H), 7.38 (d, J = 7.4
Hz, 2 H), 7.33–7.30 (m, 4 H), 7.28–7.26 (m, 1 H), 2.96 (s, 1 H), 2.52 (s, 1
H), 2.43 (s, 3 H), 2.04 (s, 3 H).
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13C NMR (125 MHz, CDCl3): δ = 143.9, 140.9, 137.6, 129.5, 128.3,
127.7, 127.4, 126.5, 51.7, 41.8, 21.6, 20.9.
Ostovar, M.; Chen, C. C.; Haddow, M. F.; Thibault, S. N.; Lusi, M.;
McGarrigle, E. M.; Aggarwal, V. K. J. Am. Chem. Soc. 2013, 135,
11951.
(7) (a) Sweeney, J. Eur. J. Org. Chem. 2009, 4911. For some examples
of aza-Darzens reaction, see: (b) Devis, F. A.; Liu, H.; Zhou, P.;
Fang, T.; Reddy, G. V.; Zhang, Y. J. Org. Chem. 1999, 64, 7559.
(c) Troisi, L.; Granito, C.; Carlucci, C.; Bona, F.; Florio, S. Eur. J.
Org. Chem. 2006, 775. (d) Larson, S. E.; Li, G.; Rowland, G. B.;
Junge, D.; Huang, R.; Woodcock, H. L.; Antilla, J. C. Org. Lett.
2011, 13, 2188. (e) Boultwood, T.; Affron, D. P.; Trowbridge, A.
D.; Bull, J. A. J. Org. Chem. 2013, 78, 6632.
(8) (a) Müller, P.; Fruit, C. Chem. Rev. 2003, 103, 2905. For some
examples of carbene insertion, see: (b) Hashimoto, T.; Gálvez, A.
O.; Maruoka, K. J. Am. Chem. Soc. 2013, 135, 17667. (c) Künzi, S.
A.; Morandi, B.; Carreira, E. M. Org. Lett. 2012, 14, 1900.
(d) Guan, Y.; López-Alberca, M. P.; Lu, Z.; Zhang, Y.; Desai, A. A.;
Patwardhan, A. P.; Dai, Y.; Vetticatt, M. J.; Wulff, W. D. Chem.
Eur. J. 2014, 20, 13894.
(9) (a) Minakata, S.; Komatsu, M. J. Synth. Org. Chem. Jpn. 2003, 61,
706. For some examples using chloramine-T as nitrogen source,
see: (b) Rubin, A. E.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl.
1997, 36, 2637. (c) Ando, T.; Kano, D.; Minakata, S.; Ryu, I.;
Komatsu, M. Tetrahedron 1998, 54, 13485. (d) Jain, S. L.; Sharma,
V. B.; Sain, B. Tetrahedron Lett. 2004, 45, 8731. (e) Karabal, P. U.;
Chouthaiwale, P. V.; Shaikh, T. M.; Suryavanshi, G.; Sudalai, A.
Tetrahedron Lett. 2010, 51, 6460.
(10) (a) Chang, J. W. W.; Ton, T. M. U.; Chan, P. W. H. Chem. Rec. 2011,
11, 331. For some examples using PhI=NTs as nitrogen source,
see: (b) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Am. Soc. Chem.
1994, 116, 2742. (c) Gillespie, K. M.; Sanders, C. J.;
O’Shaughnessy, P.; Westmoreland, I.; Thickitt, C. P.; Scott, P.
J. Org. Chem. 2002, 67, 3450. (d) Zdilla, M. J.; Abu-Omar, M.
J. Am. Chem. Soc. 2006, 126, 16971. (e) Kiyokawa, K.; Kosaka, T.;
Minakata, S. Org. Lett. 2013, 15, 4858.
(11) (a) Uchida, T.; Katsuki, T. Chem. Rec. 2014, 14, 117. For some
examples using azide as nitrogen source, see: (b) Omura, K.;
Uchida, T.; Irie, R.; Komatsu, T. Chem. Commun. 2004, 2060.
(c) Abu-Omar, M. M.; Shields, C. E.; Edwards, N. Y.; Eikey, R. A.
Angew. Chem. Int. Ed. 2005, 44, 6203. (d) Cramer, S. A.; Jenkins,
D. M. J. Am. Chem. Soc. 2011, 133, 19342. (e) Zardi, P.; Pozzoli,
A.; Ferretti, F.; Manca, G.; Meaklli, C.; Gallo, E. Dalton Trans.
2015, 44, 10479. (f) Scholz, S. O.; Farney, E. P.; Kim, S.; Bates, D.
M.; Yoon, T. P. Angew. Chem. Int. Ed. 2016, 55, 2239.
(12) For some examples using sulfonamide as nitrogen source, see:
(a) Dauban, P.; Sanière, L.; Tarrade, A.; Dodd, R. H. J. Am. Chem.
Soc. 2001, 123, 7707. (b) Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.;
Che, C.-M. J. Org. Chem. 2004, 69, 3610. (c) Li, Z.; Ding, X.; He, C.
J. Org. Chem. 2006, 71, 5876. For metal-free aziridination, see:
(d) Yoshimura, A.; Nemykin, V. N.; Zhdankin, V. V. Chem. Eur. J.
2011, 17, 10538.
(13) For some examples using phthalimide as nitrogen source, see:
(a) Anderson, D. J.; Glichrist, T. L.; Horwell, D. C.; Rees, C. W.
J. Chem. Soc. C 1970, 576. (b) Atkinson, R. S.; Malpass, J. R.
J. Chem. Soc., Perkin Trans. 1 1977, 2242. (c) Li, J.; Liang, J.-L.;
Chan, P. W. H.; Che, C.-M. Tetrahedron Lett. 2004, 45, 2685.
(d) Richardson, R. D.; Desaize, M.; Wirth, T. Chem. Eur. J. 2007,
13, 6745. For metal-free aziridinaion, see: (e) Yoshimura, A.;
Middleton, K. R.; Zhu, C.; Nemykin, V. N.; Zhdankin, V. V. Angew.
Chem. Int. Ed. 2012, 51, 8059. (f) Chen, J.; Yan, W.-Q.; Lam, C. M.;
Zeng, C.-C.; Hu, L.-M.; Little, R. D. Org. Lett. 2015, 17, 986.
Acknowledgment
This research was supported by Takeda Science Foundation.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561635.
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References
(1) (a) Ismail, F. M. D.; Levitsky, D. O.; Dembitsky, V. M. Eur. J. Med.
Chem. 2009, 44, 3373. (b) Majundar, K. C.; Chattopadhyay, S. K.
Heterocycles in Natural Product Synthesis; Wiley-VCH: Wein-
heim, 2011, Chap. 1. (c) Thibodeaux, C. J.; Chang, W-C.; Liu, H-
W. Chem. Rev. 2012, 112, 1681. (d) Bass, P. D.; Guble, D. A.; Judd,
T. C.; Williams, R. M. Chem. Rev. 2013, 113, 6816.
(e) Vandekerckhove, S.; D’hooghe, M. Bioorg. Med. Chem. 2013,
21, 3643.
(2) (a) Yudin, A. K. Aziridines and Epoxides in Organic Synthesis;
Wiley-VCH: Weinheim, 2006. (b) Comprehensive Heterocyclic
Chemistry III; Vol. I; Katrizky, A. R.; Ramsden, C. A.; Scriven, E. F.
V.; Taylor, R. J. K., Eds.; Elsevier: Amsterdam, 2008. (c) Sweeney,
J. B. Chem. Soc. Rev. 2002, 31, 247. (d) Lu, P. Tetrahedron 2010,
66, 2549. (e) Stanković, S.; D’hooghe, M.; Catak, S.; Eum, H.;
Waroquier, M.; Speybroeck, V. V.; De Kimpe, N.; Ha, H-J. Chem.
Soc. Rev. 2012, 41, 643. (f) Cardoso, A. L.; Pinho e Melo, T. M. V.
D. Eur. J. Org. Chem. 2012, 6479. (g) Hao, Y. M.; Paek, S-M. Mole-
cules 2013, 18, 9650. (h) Ha, H-J.; Jung, J-H.; Lee, W. K. Asian J.
Org. Chem. 2014, 3, 1020. (i) Lim, D. S. W.; Anderson, E. A. Syn-
thesis 2012, 44, 983.
(3) (a) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599.
(b) McCoull, W.; Davis, F. A. Synthesis 2000, 1347. (c) Singh, G.
S.; D’hooghe, M.; De Kimpe, N. Chem. Rev. 2007, 107, 2080.
(d) Degennaro, L.; Trinchera, P.; Luisi, R. Chem. Rev. 2014, 114,
7881. (e) Pellissier, H. Adv. Synth. Catal. 2014, 356, 1899.
(f) Ohno, H. Chem. Rev. 2014, 114, 7784. (g) Zhu, Y.; Wang, Q.;
Cornwall, R. G.; Shi, Y. Chem. Rev. 2014, 114, 8199. (h) Callebaut,
G.; Meiresonne, T.; De Kimpe, N.; Mangelinckx, S. Chem. Rev.
2014, 114, 7954.
(4) (a) Wenker, H. J. Am. Chem. Soc. 1935, 57, 2328. (b) Olofsson, B.;
Wijtmans, R.; Somfai, P. Tetrahedron 2002, 58, 5979. (c) Buckley,
B. R.; Patel, A. P.; Wijayantha, K. G. U. J. Org. Chem. 2013, 78,
1289.
(5) (a) Zu, J. Tetrahedron: Asymmetry 2002, 13, 1129. (b) Li, X.;
Chen, N.; Xu, J. Synthesis 2010, 3423.
(6) (a) Li, A.-H.; Dai, L-X.; Aggarwal, V. K. Chem. Rev. 1997, 97, 2341.
For some examples of imino Corey–Chaykovski reaction, see:
(b) Aggarwal, V. K.; Thompson, A.; Jones, R. V.; Standen, M. C. H.
J. Org. Chem. 1996, 61, 8368. (c) Saito, T.; Sakairi, M.; Akiba, D.
Tetrahedron Lett. 2001, 42, 5451. (d) Kokotos, C. G.; Aggarwal, V.
K. Org. Lett. 2007, 9, 2099. (e) Rejeev, R.; Sunoj, R. B. Org. Biomol.
Chem. 2011, 9, 2123. (f) Huang, M-T.; Wu, H-Y.; Chein, R-J. Chem.
Commun. 2014, 50, 1101. (g) Illa, O.; Namutebi, M.; Saha, C.;
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

F
K. Matsuzawa et al.
Paper
Synthesis
(14) Kariya, A.; Yamaguchi, T.; Nobuta, T.; Tada, N.; Miura, Y.; Itoh, A.
RSC Adv. 2014, 4, 13191.
(17) Nobuta, T.; Hirashima, S.; Tada, N.; Miura, T.; Itoh, A. Synlett
2010, 2335.
(15) For cleavage of N–I bond by visible light, see: O’Broin, C. Q.;
Fernández, P.; Martínez, C.; Muñiz, K. Org. Lett. 2016, 18, 436.
(16) Nagasawa, Y.; Tanba, K.; Tada, N.; Yamaguchi, E.; Itoh, A. Synlett
2015, 26, 412.
(18) Guang-Yao, G.; Harden, J. D.; Zhang, X. P. Org. Lett. 2005, 7, 3191.
(19) Chung-Yang, H.; Doyle, A. G. J. Am. Chem. Soc. 2012, 134, 9541.
(20) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Am. Chem. Soc. 1994,
116, 2742.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F