Photo-induced aziridination of alkenes with N-sulfonyliminoiodinanes

Article abstract of DOI:10.1248/cpb.c18-00198

Activation of N-sulfonyliminiodinanes was achieved by photo-irradiation at 375nm, which enabled the reaction with several alkenes to afford the corresponding aziridines. Mechanistic studies suggested that the reaction would proceed through a stepwise mech

Full text of DOI:10.1248/cpb.c18-00198

688
Chem. Pharm. Bull. 66, 688–690 (2018)
Vol. 66, No. 6
Note
Photo-Induced Aziridination of Alkenes with N-Sulfonyliminoiodinanes
Sota Masakado, Yusuke Kobayashi, and Yoshiji Takemoto*
Graduate School of Pharmaceutical Sciences, Kyoto University; 46–29 Yoshida-Shimo-Adachi, Sakyo-ku, Kyoto
606–8501, Japan.
Received March 8, 2018; accepted March 22, 2018
Activation of N-sulfonyliminiodinanes was achieved by photo-irradiation at 375nm, which enabled the
reaction with several alkenes to afford the corresponding aziridines. Mechanistic studies suggested that the
reaction would proceed through a stepwise mechanism via radical intermediates rather than through a con-
certed process.
Key words aziridination; hypervalent iodine; iminoiodinane; photoreaction
Aziridines are important synthetic intermediates for vari- (–CH2OMe, –NO2) iminoiodinanes under photo-irradiation at
ous nitrogen-containing compounds via ring opening1,2) and 375 nm.
ring expansion reactions.3–6) Also, they are often found in
We first synthesized several N-sulfonyliminoiodinanes bear-
natural products and biologically active compounds,7) and ing ortho-nitro substituents (Chart 1). According to the syn-
therefore a variety of methods have been developed for the thesis of N-tosyliminoiodinane 1a,24) new iminoiodinanes 1b,
synthesis of aziridines.8) Among them, transition-metal- c bearing 2-nitrobenzenesulfonyl- and 5-methylpyridine-2-sul-
catalyzed aziridination of alkenes is one of the most reliable fonyl groups were successfully obtained in high yields from
approaches, where N-haloamine salts,9) organic azides,10,11) 2-nitroiodobenzene diacetate with the corresponding sulfon-
and iminoiodinanes12–15) were employed as nitrene precur- amides in basic methanol solution (Chart 1). These N-sulfonyl
sors. Recently, metal-free aziridination16–19) and catalyst-free groups would increase the reactivity of the corresponding
aziridination20–22) of alkenes have emerged as greener alter- aziridines and allow it easier to be deprotected from the ni-
natives, but only limited approaches are available and there trogen atom.25,26) In addition, new iminoiodinane 1d was pre-
still remains to be solved for the development of this research pared from 2-nitroiodobenzene diacetate and methanesulfon-
area. Very recently, we have developed newly designed N- amide in pyridine–ether solution. Although 1b (o-Ns) showed
acyliminoiodinanes, which were found to be activated under low solubility in CHCl3 and CH2Cl2, the other iminoiodinanes
photo-irradiation conditions and utilized as N-acylnitrene 1c, 1d exhibited enough solubility to take NMR in CDCl3. It
equivalent.23) The coordination of the oxygen atom of ortho- is worth noting that these resulting off-white or yellow solid
substituent (–OMe, –CH2OMe) to the iodine atom seemed to could be stored for several months at room temperature.
be essential for the photo-activation of N-acyliminoiodinanes
We next investigated the aziridination of alkenes with the
as well as N-sulfonyliminoiodinanes, and silyl enol ethers synthesized iminoiodinanes under photo-irradiation condi-
were successfully α-aminated using those iminoiodinanes tions (Table 1). The reaction of styrene 3a under the previ-
under photo-irradiation. We envisioned that such ortho-sub- ously reported conditions23) (with iminoiodinane 2a27) in
stituted iminoiodinanes could be similarly applied to a photo- dichloromethane under photo-irradiation at 375nm) gave the
induced aziridination of alkenes without using any catalysts. corresponding aziridine 4a in 73% yield, while the use of
We also anticipated that iminoiodinanes bearing ortho-nitro PhI=NTs12–15) gave no desired product. To our delight, re-
substituents would be applicable to photoreactions due to the placement of iminoiodinane 2a with 1a improved the chemical
coordination of the ortho-nitro group to the iodine atom,24) yield of 4a to 98%.
and that electron-withdrawing property of the ortho-nitro sub-
With these optimized conditions in hand, we next investi-
stituents would increase the electrophilicity of iminoiodinanes, gated the substrate scope of the photo-induced aziridination
leading to high reactivity toward alkenes. Herein, we report a of alkenes 3a–g (Table 1). Styrenes having several substitu-
catalyst-free aziridination of alkenes using ortho-substituted ents on the aromatic rings 3b–d were tolerant to the photo-
Chart 1. Synthesis of Iminoiodinanes 1a–d
*To whom correspondence should be addressed. e-mail: takemoto@pharm.kyoto-u.ac.jp
© 2018 The Pharmaceutical Society of Japan

Vol. 66, No. 6 (2018)
Chem. Pharm. Bull.
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Table 1. Substrate Scope of Photo-Induced Aziridination of Alkenes with Iminoiodinanesa,b
a Reaction conditions: styrene (0.1mmol), iminodinane (0.15mmol), dichloromethane (2mL), 0°C, 12h. b Yields of isolated prod-
1
ucts unless otherwise noted. c Yields in parenthesis were determined by H-NMR using dimethylsulfone as internal standard.
Experimental
Styrene 3a (0.10mmol, 10.4mg) and iminoiodinane 1a
(0.15mmol, 62.7mg) were suspended in dichloromethane
(2.0mL), and the reaction mixture was stirred at 0°C for 12h
under photo-irradiation by light-emitting diode (LED) light
(peak wavelength 375 3nm). After the resulting yellow so-
lution was concentrated under reduced pressure, the crude
products were directly purified by silica gel column chroma-
tography to give aziridine 4a (19.9mg, 73%).
Chart 2. Reaction of cis- or trans-8
Acknowledgment This work is supported in part by
Takeda Science Foundation and “Targeted Proteins Research
irradiation conditions to afford the corresponding aziridines Program” and “Platform for Drug Design, Discovery and
4b–d in 44–72% yields. However, substrates 3e and 3f hav- Development” from Ministry of Education, Culture, Sports,
ing electron-rich aromatic rings gave the desired products Science and Technology (MEXT) of Japan.
4e and 4f in low yields, presumably due to their instability
during purification on silica gel column chromatography.17,28)
Conflict of Interest The authors declare no conflict of
Importantly, the aliphatic alkene 3g was also applicable to the interest.
catalyst-free reaction to give aziridine 4g in 41% yield. Fur-
thermore, the aziridines bearing different N-sulfonyl groups
Supplementary Materials The online version of this ar-
5a–7a were successfully obtained in 50–68% yields using ticle contains supplementary materials.
2b,23) 2c,23) and 1d as nitrogen source, respectively, although
newly synthesized iminoiodinanes 1b and 1c did not furnish
the corresponding products because of their poor solubility in
dichloromethane.
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