1,3-Dipolar cycloaddition of alkynyliodonium salts with a nitrile oxide. Synthesis and reactivity of isoxazolyliodonium salts

Article abstract of DOI:10.1016/S0022-328X(01)01322-5

1,3-Dipolar cycloaddition reaction of alkynyliodonium salts with 2,4,6-trimethylbenzonitrile N-oxide has been examined with respect to inactivated alkynyliodonium salts. The cycloaddition with the nitrile oxide has been found to proceed successful to give

Full text of DOI:10.1016/S0022-328X(01)01322-5

Journal of Organometallic Chemistry 646 (2002) 196–199
www.elsevier.com/locate/jorganchem
1,3-Dipolar cycloaddition of alkynyliodonium salts with a nitrile
oxide. Synthesis and reactivity of isoxazolyliodonium salts
Tsugio Kitamura *, Yoichiro Mansei, Yuzo Fujiwara
Department of Applied Chemistry, Faculty of Engineering, Kyushu Uni6ersity, Hakozaki, Fukuoka 812-8581, Japan
Received 18 July 2001; accepted 26 September 2001
Abstract
1,3-Dipolar cycloaddition reaction of alkynyliodonium salts with 2,4,6-trimethylbenzonitrile N-oxide has been examined with
respect to inactivated alkynyliodonium salts. The cycloaddition with the nitrile oxide has been found to proceed successful to give
the corresponding isoxazolyliodonium salts in good to high yields. The reactivity of the selected isoxazolyliodonium salts has been
examined. © 2002 Elsevier Science B.V. All rights reserved.
Keywords: 1,3-Dipolar cycloaddition; Alkynyliodonium salt; Nitrile oxide; Isoxazolyliodonium salt
However, the reported reactions are limited to the
alkynyliodonium salts with aryl and b-activated groups.
Thus, we report here the 1,3-dipolar cycloaddition of
different types of alkynyliodonium salts, that is, alkyl
and silyl groups, in the case of 2,4,6-trimethylbenzoni-
trile N-oxide as the 1,3-dipole. The cycloadducts
derived from arylethynyliodonium salts resist against
the nucleophilic substitution [4], while those derived
from b-activated ethynyliodonium salts readily undergo
the loss of the iodonium moiety [6]. The reactivity of
the cycloadduct still remains unclear.
1. Introduction
Alkynyliodonium salts are useful compounds in or-
ganic chemistry because they have carbonꢀcarbon triple
bonds available for mechanistic and synthetic purposes
[1]. Recently, the electron-deficient nature of the
alkynyl moiety has been applied to cycloaddition reac-
tions. Stang has extensively explored the Diels–Alder
reactions of alkynyliodonium salts that have additional
electron-withdrawing groups at the b position [2].
1,3-Dipolar cycloaddition is one of the useful meth-
ods for synthesizing heterocycles [3]. However, only few
examples are reported in the literatures on the 1,3-dipo-
lar cycloaddition of alkynyliodonium salts. Varvoglis
and coworkers have reported the first 1,3-dipolar cy-
cloaddition of arylethynyl(phenyl)iodonium salts with
nitrile oxides and a nitrone [4]. Maas and Stang have
developed the 1,3-dipolar cycloaddition to the b-acti-
vated ethynyl(phenyl)iodonium salts [5], involving the
reactions with diazoketones and azides. Very recently,
Stang and Murch have reported the 1,3-dipolar cy-
cloaddition with a diazoester, a nitrone and a nitrile
oxide [6].
2. Results and discussion
2.1. 1,3-Dipolar cycloaddition of
(phenyl)[(trimethylsilyl)ethynyl]iodonium triflate (1a)
with 2,4,6-trimethylbenzonitrile N-oxide (2)
We examined the cycloaddition reaction of
(phenyl)[(trimethylsilyl)ethynyl]iodonium triflate (1a)
and 2,4,6-trimethylbenzonitrile N-oxide (2). Compound
2 was selected as a stable nitrile oxide to be able to
conduct the cycloaddition reaction conveniently. When
a mixture of (trimethylsilyl)iodonium triflate (1a) and
nitrile oxide (2) was reacted in CH2Cl2 at room temper-
ature, (phenyl)[3-(2,4,6-trimethylphenyl)-5-(trimethylsi-
* Corresponding author. Tel.: +81-92-6423549; fax: +81-92-
6515606.
E-mail address: tkitatcf@mbox.nc.kyushu-u.ac.jp (T. Kitamura).
0022-328X/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(01)01322-5

T. Kitamura et al. / Journal of Organometallic Chemistry 646 (2002) 196–199
197
lyl)isoxazol-4-yl]iodonium triflate (3a) was formed as
crystals in 91% yield (Eq. (1)). The cycloaddition reac-
tion proceeded smoothly at room temperature to give
the high yield of single cycloadduct 3a. The structure of
the cycloadduct 3a was confirmed by the spectral data
and elemental analysis and is consistent with the related
isoxazolyliodonium salts [4]. The NOE experiment sup-
ported the regiochemistry of the cycloadduct 3a. The
irradiation of the ortho methyl of mesityl group showed
the enhancement (1.2%) of the ortho proton of phenyl
group, but no enhancement was observed at the signal
of trimethylsilyl group.
(2)
2.3. Reaction of isoxazolyliodonium salts 3
Although Varvoglis and coworkers reported the reac-
tion of aryl-substituted isoxazolyliodonium tosylates 3
with some nucleophiles [4], the displacement of
phenyliodonio group by the nucleophile was not ob-
served. We also examined the substitution reaction of
isoxazolyliodonium tosylates 3 with potassium thio-
cyanate, KSCN, but could not obtain any substitution
products.
(1)
Recently, we have found that reaction of (phenyl)[2-
(trimethylsilyl)phenyl]iodonium triflate with Bu4NF
generates benzyne efficiently under very mild conditions
to give the benzyne adduct with furan quantitatively [7].
[3-(2,4,6-Trimethylphenyl)-5-(trimethylsilyl)isoxazol-4-
yl]iodonium triflate (3a) has the similar structure bear-
ing trimethylsilyl and phenyliodonio groups at two
adjacent positions on the isoxazole ring. If the reaction
of isoxazolyliodonium triflate (3a) proceeds in a similar
manner to the benzyne formation, the generation of
4,5-didehydro-5-(2,4,6-trimethylphenyl)isoxazole (4) is
expected (Eq. (3)). Thus, we examined the reaction of
isoxazolyliodonium triflate (3a) with Bu4NF.
2.2. 1,3-Dipolar cycloaddition of
alkynyl(phenyl)iodonium tosylates (1) with
2,4,6-trimethylbenzonitrile N-oxide (2)
As the trimethylsilylethynyliodonium salt (1a) under-
went smoothly the cycloaddition with 2,4,6-trimethyl-
benzonitrile N-oxide (2), we examined the
cycloaddition of alkyl-substituted ethynyliodonium to-
sylates 1. When the iodonium tosylates 1 were reacted
with 2 under the same reaction conditions as above,
(phenyl)[5-alkyl-3-(2,4,6-trimethylphenyl)isoxazol-4-yl]-
iodonium tosylates (3) were obtained in good to high
yields, respectively (Eq. (2)). There seems to be no
difference between the counteranions, triflate and tosy-
late. Therefore, the 1,3-dipolar cycloaddition of
alkynyliodonium salts with a nitrile oxide provides a
good methodology for preparing the isoxazolyliodinium
salts (Table 1).
(3)
Treatment of isoxazolyliodonium triflate (3a) with
Bu4NF in the presence of cyclopentadiene in CH2Cl2
gave 2,4,6-trimethylbenzonitrile (5) in 86% yield to-
gether with almost quantitative amount of iodobenzene
(Eq. (4)). No cycloadducts derived from 4,5-didehy-
droisoxazole (4) and cyclopentadiene were detected.
Attempted trapping reactions of didehydroisoxazole 4
with some agents such as furan, 1,3-diphenylisobenzo-
furan and tetraphenylcyclopentadienone were failed.
Only benzonitrile 5 was formed as the product derived
from the isoxazole component. This result suggests that
an isoxazolyl anion generated by desilylation with
fluoride ion undergoes the ring-cleavage [8] to benzoni-
Table 1
Cycloaddition of alkynyl(phenyl)iodonium tosylates (1) with 2,4,6-
trimethylbenzonitrile N-oxide (2)
Entry
Iodonium salt 1
Product 3
Yield (%) a
1
2
3
4
5
1b, R=Bu
1c, R=Hex
1d, R=Dec
1e, R=t-Bu
1f, R=Ph
3b, R=Bu
3c, R=Hex
3d, R=Dec
3e, R=t-Bu
3f, R=Ph
80
73
43
83
72
trile
5 without generating a high strained 4,5-
a Isolated yields based on alkynyl(phenyl)iodonium tosylates (1).
dedihydroisozazole.

198
T. Kitamura et al. / Journal of Organometallic Chemistry 646 (2002) 196–199
mmol) in CH2Cl2 (10 ml) was stirred at r.t. under
nitrogen with protection from daylight for 12 h. The
solvent was removed in vacuo and Et2O was added to
give the precipitation of isoxazolyliodonium tosylate
(3).
(4)
3.3.1. [5-Butyl-3-(2,4,6-trimethylphenyl)isoxazol-4-
yl](phenyl)iodonium tosylate (3b)
3. Experimental
Compound 3b: 0.495 g (80%); m.p. 194–195 °C
(CH2Cl2ꢀhexane); H-NMR (CDCl3) l 0.95 (t, J=7.4
3.1. Measurements and materials
1
Hz, 3H, Me), 1.35–1.47 (m, 2H, CH2), 1.66 (s, 6H,
Me), 1.76–1.84 (m, 2H, CH2), 2.30 (s, 3H, Me), 2.35 (s,
3H, Me), 3.14 (t, J=7.7 Hz, 2H, CH2), 6.84 (s, 2H,
ArH), 6.97–7.15 (m, 4H, ArH), 7.29–7.46 (m, 5H,
ArH); 13C-NMR (CDCl3) l 13.70, 19.47, 21.20 (two
signals overlapped), 22.37, 27.07, 29.15, 85.51, 116.38,
122.97, 125.66, 128.27, 128.45, 130.60, 131.14, 135.24,
137.79, 139.39, 139.96, 141.85, 162.89, 179.06. Anal.
Calc. for C29H32INO4S: C, 56.40; H, 5.22; N, 2.27.
Found: C, 56.37; H, 5.19; N, 2.26%.
Melting points were measured with a YANACO
micro melting point apparatus and are uncorrected.
1H-NMR spectra were recorded on a JEOL JNM-A
SERIES FT-NMR (300 MHz) spectrometer, and chem-
ical shifts (l) were expressed in part per million
downfield from tetramethylsilane. 13C-NMR spectra
were recorded on a JEOL JNM-A SERIES FT-NMR
(75 MHz) spectrometer, and chemical shifts (l) were
expressed in part per million downfield from te-
tramethylsilane. Elemental analyses were performed by
the Service Center of the Elementary Analysis of Or-
ganic Compounds, Faculty of Science, Kyushu
University.
(Phenyl)[(trimethylsilyl)ethynyl]iodonium triflate (1a)
[9] and alkynyl(phenyl)iodonium tosylates 1b–f [10]
were prepared according to the literature method. 2,4,6-
Trimethylbenzonitrile N-oxide (2) was prepared by the
method described in the literature [11]. Other materials
were commercially available and used without further
purification.
3.3.2. [5-Hexyl-3-(2,4,6-trimethylphenyl)isoxazol-4-
yl](phenyl)iodonium tosylate (3c)
Compound 3c: 0.469 g (73%); m.p. 202–204 °C
1
(CH2Cl2ꢀhexane); H-NMR (CDCl3) l 0.86–0.90 (m,
3H, Me), 1.18–1.39 (m, 6H, CH2), 1.64 (s, 6H, Me),
1.75–1.85 (m, 2H, CH2), 2.29 (s, 3H, Me), 2.33 (s, 3H,
Me), 3.10–3.15 (m, 2H, CH2), 6.82 (s, 2H, ArH),
6.94–7.08 (m, 4H, ArH), 7.18–7.41 (m, 5H, ArH);
13C-NMR (CDCl3) l 13.89, 19.40, 21.12 (two signals
overlapped), 22.38, 27.02, 27.30, 28.90, 31.28, 85.52,
116.28, 122.95, 125.62, 128.21, 128.38, 130.50, 131.06,
135.20, 137.74, 139.30, 139.87, 141.81, 162.80, 179.00.
Anal. Calc. for C31H36INO4S: C, 57.67; H, 5.62; N,
2.17. Found: C, 57.61; H, 5.54; N, 2.16%.
3.2. Reaction of phenyl(trimethylsilylethynyl)iodonium
triflate (1a) with 2,4,6-trimethylbenzonitrile N-oxide (2)
A solution of phenyl(trimethylsilylethynyl)iodonium
triflate (1a) (2.0 mmol) and 2,4,6-trimethylbenzonitrile
N-oxide (2) (2.4 mmol) in CH2Cl2 (15 ml) was stirred at
room temperature (r.t.) under nitrogen with protection
from daylight for 12 h. The solvent was removed in
vacuo and Et2O was added to give the precipitation of
(phenyl)[3 - (2,4,6 - trimethylphenyl) - 5 - (trimethylsilyl)-
isoxazol-4-yl]iodonium triflate (3a) (1.11 g, 91%): m.p.
3.3.3. [5-Decyl-3-(2,4,6-trimethylphenyl)isoxazol-4-
yl](phenyl)iodonium tosylate (3d)
Compound 3d: 0.302 g (43%); m.p. 145–146 °C
1
(CH2Cl2ꢀhexane); H-NMR (CDCl3) l 0.87–0.92 (m,
3H, Me), 1.10–1.27 (m, 14H, CH2), 1.67 (s, 6H, Me),
1.76–1.83 (m, 2H, CH2), 2.30 (s, 3H, Me), 2.35 (s, 3H,
Me), 3.10–3.15 (m, 2H, CH2), 6.85 (s, 2H, ArH),
6.97–7.15 (m, 4H, ArH), 7.25–7.47 (m, 5H, ArH);
13C-NMR (CDCl3) l 14.08, 19.49, 21.20 (two signals
overlapped), 22.63, 27.18, 27.39, 29.26, 29.28, 29.32,
29.47, 29.50, 31.84, 85.56, 116.43, 123.01, 125.69,
128.28, 128.47, 130.59, 131.13, 135.29, 137.81, 139.36,
139.97, 141.90, 162.89, 179.11. Anal. Calc. for
C35H44INO4S: C, 59.91; H, 6.32; N, 2.60. Found: C,
59.86; H, 6.31; N, 1.96%.
1
176–178 °C; H-NMR (CDCl3) l 0.64 (s, 9H, SiCH3),
1.70 (s, 6H, Me), 2.38 (s, 3H, Me), 6.91 (s, 2H, ArH),
7.25–7.58 (m, 5H, ArH); 13C-NMR (CDCl3) l −1.38,
19.56, 21.27, 92.17, 114.24, 119.76, 119.77, 128.73,
131.44, 132.32, 135.15, 137.95, 140.55, 161.90, 185.79.
Anal. Calc. for C22H25F3INO4SSi: C, 43.21; H, 4.12; N,
2.29. Found: C, 43.19; H, 4.12; N, 2.33%.
3.3. General procedure for the reaction of
alkynyl(phenyl)iodonium tosylates (1) with
2,4,6-trimethylbenzonitrile N-oxide (2)
3.3.4. [5-tert-Butyl-3-(2,4,6-trimethylphenyl)isoxazol-4-
yl](phenyl)iodonium tosylate (3e)
A solution of alkynyliodonium tosylate (1) (1.0
mmol) and 2,4,6-trimethylbenzonitrile N-oxide (2) (1.2
Compound 3e: 0.517 g (83%); m.p. 211–213 °C
(dec.) (CH2Cl2ꢀhexane); H-NMR (CDCl3) l 1.64 (s,
1

T. Kitamura et al. / Journal of Organometallic Chemistry 646 (2002) 196–199
199
9H, Me), 1.67 (s, 6H, Me), 2.32 (s, 3H, Me), 2.36 (s,
Acknowledgements
3H, Me), 6.85 (s, 2H, ArH), 7.00–7.18 (m, 4H, ArH),
7.26–7.48 (m, 5H, ArH); 13C-NMR (CDCl3) l 19.61,
21.25 (two signals overlapped), 29.67, 35.57, 81.29,
116.93, 123.02, 125.83, 128.35, 128.58, 130.80, 131.40,
135.03, 138.10, 139.37, 140.22, 142.10, 164.30, 182.98.
Anal. Calc. for C29H32INO4S: C, 56.40; H, 5.22; N,
2.27. Found: C, 56.14; H, 5.23; N, 2.25%.
This work was supported by a Grant-in-Aid for
Scientific Research (B) from the Ministry of Education,
Science, Sports and Culture, Japan.
References
[1] For recent reviews on hypervalent iodine compounds including
alkynyliodonium salts, see: (a) V.V. Zhdankin, P.J. Stang, Tetra-
hedron 54 (1998) 10927;
3.3.5. (Phenyl)[5-phenyl-3-(2,4,6-trimethylphenyl)-
isoxazol-4-yl]iodonium tosylate (3f)
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Compound 3f: 0.458 g (72%); m.p. 170–173 °C
(CH2Cl2ꢀhexane) (lit. [4] 173–176 °C); 1H-NMR
(CDCl3) l 1.73 (s, 6H, Me), 2.30 (s, 3H, Me), 2.39 (s,
3H, Me), 6.89 (s, 2H, ArH), 6.95–7.61 (m, 12H, ArH),
8.13–8.16 (m, 2H, ArH); 13C-NMR (CDCl3) l 19.61,
21.18, 21.25, 84.76, 117.24, 122.77, 125.26, 125.77,
128.33, 128.54, 128.62, 129.28, 130.69, 131.22, 131.86,
134.83, 138.05, 139.36, 140.16, 141.72, 164.44, 173.29.
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3.4. Reaction of isoxazolyliodonium triflate (3a) with
Bu4NF in the presence of trapping agents
To a solution of [3-(2,4,6-trimethylphenyl)-5-(trime-
thylsilyl)isoxazol-4-yl](phenyl)iodonium triflate (3a) (1.0
mmol) and cyclopentadiene (5.0 mmol) in CH2Cl2 (15
ml) was added dropwise a THF solution of Bu4NF (1.0
M, 1.2 ml) at 0 °C, and the reaction mixture was
stirred at r.t. for 30 min. Water was added and then the
resulting mixture was extracted with CH2Cl2. The or-
ganic extracts were dried over anhydrous Na2SO4 and
concentrated. The residue was purified by column chro-
matography on silica gel using hexaneꢀCH2Cl2 as the
eluent. Evaporation of the solvent gave colorless crys-
tals of 2,4,6-trimethylbenzonitrile (5) (0.125 g, 86%):
m.p. 47–50 °C (lit. [12] 50–52 °C). IR (KBr) 2219.7
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1
cm−1; H-NMR (CDCl3) l 2.32 (s, 3H, Me), 2.48 (s,
6H, Me), 6.93 (s, 2H, ArH); 13C-NMR (CDCl3) l 20.5,
21.5, 110.5, 117.4, 128.2, 141.9, 142.8.