Electrophilic cyclization of N-alkenylamides using?a chloramine-T/I2 system

Article abstract of DOI:10.1016/j.tet.2006.10.003

A new protocol for the cyclization of N-alkenylamides using chloramine-T and iodine is described. When N-alkenylsulfonamides are treated with chloramine-T and iodine, three- to six-membered N-heterocycles are obtained with complete stereoselectivity. The method is compatible with the cyclization of the allylbenzamide or allylbenzthioamide to afford an oxazoline or thiazoline derivative, respectively. Mechanistic studies indicate that the chloramine-T/I₂ system functions as an effective iodonium species.

Full text of DOI:10.1016/j.tet.2006.10.003

Tetrahedron 62 (2006) 12247–12251
Electrophilic cyclization of N-alkenylamides using a
chloramine-T/I2 system
*
Yoshinobu Morino, Ikumasa Hidaka, Yoji Oderaotoshi, Mitsuo Komatsu and Satoshi Minakata
*
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan
Received 28 August 2006; revised 4 October 2006; accepted 5 October 2006
Available online 27 October 2006
Abstract—A new protocol for the cyclization of N-alkenylamides using chloramine-Tand iodine is described. When N-alkenylsulfonamides
are treated with chloramine-Tand iodine, three- to six-membered N-heterocycles are obtained with complete stereoselectivity. The method is
compatible with the cyclization of the allylbenzamide or allylbenzthioamide to afford an oxazoline or thiazoline derivative, respectively.
Mechanistic studies indicate that the chloramine-T/I2 system functions as an effective iodonium species.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Ts
N
R2
R3
Cl
I2 (cat)
The functionalization of a double bond activated by an elec-
trophile is one of the most useful reactions in organic synthe-
sis. Ring formation through the reaction of a heteroatom and
a cyclic onium ion is a versatile method for the stereocon-
trolled synthesis of heterocycles.1 The electrophilic cycliza-
tion of nonconjugated olefinic carboxylic acids was initially
exploited by Bougault.2 Electrophiles, such as halogens, halo
reagents, selenium derivatives, and certain metallic salts, for
the activation of the olefinic moiety have been developed for
R2
R3
+
N
Ts
ð1Þ
Na
R1
R1
Ts
N
Cl
N
Ts
I2
Na
+
NaCl
ꢀ
use in this type of cyclization. Barluenga and Gonzalez
NaI
reported on a versatile reagent, bis(pyridine)iodine tetra-
fluoroborate (IPy2BF4), not only for the cyclization3 but
also for many other useful and unique transformations.4
Quite recently, we reported that tert-butyl hypoiodite
(t-BuOI)5 is a powerful reagent for the cyclization of
N-alkenylamides6 and the aziridination of olefins with
sulfonamides.7 Since the polarity of the O–I of the reagent
should be an important factor in such reactions, an N–I
bond having electron-withdrawing groups on the nitrogen
would be expected to act in a similar fashion. Our group
(Eq. 1)8 and the Sharpless group9 simultaneously reported
on the iodine- or bromine-catalyzed aziridination of olefins
using chloramine-T. In our study, we proposed that a reactive
species having N–I bond, generated from chloramine-T and
iodine, is involved in the reaction path and functions as a key
intermediate (Scheme 1). From these points of view, we re-
port here on the use of inexpensive chloramine-T and I2 as
reagents for the cyclization of N-alkenylamides (Scheme 2).
I
Cl
I
N
Ts
Cl
N
Ts
Ts
N
I
Cl
Scheme 1. Proposed path for the I2-catalyzed aziridination of olefins using
chloramine-T.
Cl
+
I2
N
Ts
Na
Cl
N
rt
Ts
EWG
N
I
H
N
EWG
n
I
n
Keywords: Alkenylamides; Chloramine-T; Iodine; Heterocycles.
* Corresponding authors. Tel.: +81 6 6879 7400; fax: +81 6 6879 7402
(S.M.); e-mail: minakata@chem.eng.osaka-u.ac.jp
Scheme 2. A reactive species having an N–I bond for the cyclization of
N-alkenylamides.
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.10.003

12248
Y. Morino et al. / Tetrahedron 62 (2006) 12247–12251
Table 3. Cyclization of a variety of alkenylsulfonamides using the chlor-
amine-T/I2 system
2. Results and discussion
Chloramine-T / I2
MeCN, rt, 24 h
To evaluate the ability of the chloramine-T/I2 system in the
electrophilic cyclization of N-(4-pentenyl)-p-toluenesulfon-
amide (1a), some related reagents were employed in the
reaction (Table 1). Although the desired cyclization in the
presence of the only iodine proceeded, the yield of iodo-
methylated N-tosylpyrrolidine 2a was moderate, under the
reaction conditions used. The addition of t-BuONa to the
above conditions was ineffective. As expected, the use of
a combination of iodine and chloramine-T successfully
caused efficient cyclization, giving 2a in 98% yield. The
use of sodium iodide as an ‘I’ source instead of iodine vastly
decreased the efficiency. The presence of species acting as an
iodonium ion should be important to induce this cyclization.
substrate
product
Substrate
Product
Yield (%)
Bb
Aa
Ts
N
H
81
8
54
(1b)
(1c)
N
(2b)
Ts
I
I
Ts
N
H
I
8
(2c)
(2d)
N
Ts
Ts
N
H
45
40
(1d)
N
Ts
Table 1. Evaluation of iodinating reagents in the cyclization of N-(4-pent-
enyl)-p-toluenesulfonamide
“ I ” source (0.5 mmol)
H
Ts
N
Ts
N
H
N
78c
37c
additive (0.5 mmol)
N
Ts
I
(1e)
(1f)
I
(2e)
(2f)
Ts
MeCN (3 mL), rt, 5 h
1a (0.5 mmol)
2a
Ts
N
H
80c
62c
‘I’ source
Additive
Yield (%)
Recovery (%)
N
I
Ts
I2
I2
I2
NaI
—
t-BuONa
61
63
25
37
0
a
Method A: substrate (0.50 mmol)/chloramine-T (0.50 mmol)/I2 (0.50 mmol).
Method B: substrate (0.50 mmol)/chloramine-T (0.25 mmol)/I2 (0.25 mmol).
Reaction time: 5 h.
Chloramine-T
Chloramine-T
98
52
b
c
46
obtained, under the conditions used. Although the efficiency
of cyclization of 1c was unsatisfactory, a four-membered
nitrogen heterocycle, an azetidine was obtained using these
methods. In the reaction, 3-iodo-N-tosylpyrrolidine via 5-
endo cyclization and ICl adduct to the C–C double bond
were obtained. When N-(5-hexenyl)-p-toluenesulfonamide
(1d) was employed in the reaction using both method A
and B, moderate yields of the corresponding piperidine
were obtained, in which ICl adduct was also observed.
Both trans- and cis-(4-hexenyl)-p-toluenesulfonamides, 1e
and 1f, were converted into the corresponding pyrrolidines
in good yields with complete stereoselectivities, indicating
that the present reaction proceeds through a three-membered
iodonium ion intermediate.
The effect of the amounts of the two reagents, iodine and
chloramine-T, on cyclization was examined as shown in
Table 2. Even if a half amount of either chloramine-T or
iodine against 1a was employed in the reaction, almost the
same efficiency was observed, compared with the use of stoi-
chiometric amounts of the two reagents. Interestingly, it was
found that a half amount of chloramine-T and iodine is
sufficient for the reaction to reach completion in almost
quantitative yield (entry 4). These results indicate that both
I atoms are able to serve as iodonium species.
Table 2. Optimization of the amount of the reagents
Ts
N
H
N
Chloramine-T / I2
MeCN (3 mL), rt, 5 h
I
Ts
Although the precise mechanism and the nature of the active
species are unclear at present, the following findings provide
support for the reaction pathway depicted in Scheme 3. As
proposed in our previous work,8 the reaction of chlor-
amine-T with iodine is very rapid, affording N-chloro-N-
iodo-p-toluenesulfonamide (3). If the active species having
an N–I bond reacts with N-alkenylsulfonamides 1 in a
manner similar to t-BuOI,6 the species 3 might iodinate
the nitrogen of the sulfonamides, not an olefinic moiety. In
fact, when a solution of N-methyl-p-toluenesulfonamide
(methyl, d 2.41 ppm) in CD3CN was treated with chlor-
amine-Tand I2, a new methyl singlet at d 3.14 ppm, identical
to the peak produced in the reaction of N-methyl-p-toluene-
sulfonamide and t-BuOI,6 appeared. The NMR study
supports the formation of N-iodo-N-alkenylsulfonamides 4
by the reaction of sulfonamides with species 3 generated
from chloramine-T and iodine. Cyclization of N-iodinated
alkenylsulfonamides would be expected to proceed via a
1a (0.5 mmol)
2a
Entry
Chloramine-T (mmol)
I2 (mmol)
Yield (%)
1
2
3
4
0.50
0.25
0.50
0.25
0.50
0.50
0.25
0.25
98
97
95
97
A variety of N-alkenylsulfonamides were examined using
the chloramine-T/I2 system under selected conditions
(method A and B) as shown in Table 3. In method A, stoi-
chiometric amounts of chloramine-T and I2 were used
against the N-alkenylsulfonamides and in method B a half
amount of the reagents were used. Method A gave good re-
sults for the formation of aziridine 2b by the cyclization of
N-allyl-p-toluenesulfonamide (1b). The aziridination of 1b
also proceeded by method B, a rather low yield was

Y. Morino et al. / Tetrahedron 62 (2006) 12247–12251
12249
three-membered iodonium ion, the generation of which
would be confirmed by the complete stereoselectivity shown
in Table 3. In order to investigate the fact that even a half
amount of chloramine-T and I2 against N-alkenylsulfon-
amides, especially 1a, is sufficient for the cyclization, the
following experiment was performed. Since it is likely that
N-chlorinated sulfonamide 5 and NaI would be formed after
the reaction of 1 and 3, sulfonamide 1a was treated with 5,
which was prepared separately,10 in the presence of NaI
under the reaction conditions, leading to efficient cyclization
(Scheme 4). These results suggest that compound 5 might
be converted into the active species 6 with NaI, after which
the species would function as a source of iodonium ions for
the cyclization.
stoichiometric amounts of chloramine-T and iodine in ace-
tonitrile at room temperature gave the iodomethylated ox-
azoline 8a in 70% yield. The thioamide derivative 7b was
allowed to react under the reaction conditions, affording
the corresponding thiazoline 8b in moderate yield.
3. Conclusions
A simple and efficient method for the cyclization of various
alkenylamides using chloramine-T and I2 was developed.
The precise mechanism of this reaction is presently unclear,
but auxiliary experiments suggest that N-iodo-N-alkenyl-
amides are generated as intermediates. Since the cyclization
pathway involves a cyclic iodonium ion, the stereochemistry
could be completely controlled. Chloramine-T and iodine
are both readily available, inexpensive and easily handled,
and the combination of these reagents enabled both I atoms
of iodine to function as iodonium species. Applications of the
system to other organic synthesis are currently in progress.
I2
Cl
N
Ts
Na
Cl
I
I
N
Ts
NaI
Ts
N
Ts
Ts
H
6
3
4. Experimental
H
N
Cl
H
4.1. General experimental method
H
N
N
n
1
Ts
All reactions were carried out under an atmosphere of nitro-
gen. Acetonitrile was freshly distilled over CaH2. 1H and 13
n
5
1
H2N Ts
I
C
Ts
N
NMR spectra were recorded at 270 and 68 MHz or 400
and 100 MHz, respectively. Flash column chromatography
(FCC) was performed using silica gel FL60D (Fuji Silysia
Chemical Co.). Analytical thin layer chromatography was
performed using EM reagent and 0.25 mm silica gel 60-F
plates. Visualization was accomplished with UV light and
spraying with an ethanolic phosphomolybdic acid solution
followed by heating.
I
N
N
Ts
Ts
I
n
n
n
4
2
Scheme 3. Plausible reaction pathway to N-heterocycles.
Ts
N
H
TsNHCl (1 eq), NaI (1 eq)
N
I
Ts
MeCN (3 mL), rt, 5 h
4.2. General procedure for the preparation of
N-alkenylamides
1a (0.5 mmol)
2a 93%
Scheme 4. Cyclization of N-alkenylamide in the presence of TsNHCl and
NaI.
Following the general procedure of Ing’s method,11 a mixture
of an alkenyl halide (50 mmol), potassium phthalimide
(100 mmol), and dimethylformamide (50 mL) was heated
at 85 ꢀC for 3 h. After cooling to room temperature, Et2O
(100 mL) and H2O (100 mL) were added to the reaction mix-
ture. The aqueous layer was extracted with Et2O (50 mLꢁ2).
The combined organic layer was washed successively
with water (100 mLꢁ2) and brine (100 mL) and dried over
K2CO3, and the solvent was removed under reduced pressure
to give the white solid. A slurry of the given phthalimide de-
rivative (50 mmol), EtOH (50 mL) and hydrazine hydrate
(100 mmol) was heated to reflux for 30 min. After cooling
to room temperature, the reaction mixture was filtered
through a paper filter, and the solid was washed with di-
chloromethane (250 mL) to give an alkenylamine. Triethyl-
amine (20 mL) and an acid chloride (50 mmol) was added to
the solution of the amine obtained at 0 ꢀC. The solution was
allowed towarm to room temperature over the course of 12 h.
After washing with 1 N hydrochloric acid (100 mL), 1 N
aqueous K2CO3 (100 mL), water (100 mLꢁ2), and brine
(100 mL) and dried over K2CO3, and the solvent was
removed under reduced pressure to give the yellow oil.
Although the cyclization of N-(4-pentenyl)amides having
benzoyl and Boc groups instead of tosyl group were carried
out to investigate the scope and limitation of the reagents,
the corresponding N-heterocycles were not obtained. From
these results, the acidity of the tosylamide moiety would
be important to perform the iodination with species 3.
However, N-allylbenzamide or N-allylbenzthioamide deriv-
atives were found to be employed in the cyclization (Scheme
5). The reaction of N-(2-propenyl)benzamide (7a) with
Ph
Chloramine-T (1 eq)
I2 (1 eq)
H
N
Ph
Q
N
MeCN (3 mL), rt, 5 h
Q
I
(0.5 mmol)
8a Q = O 70%
8b Q = S 46%
7a Q = O
7b Q = S
Scheme 5. Cyclization of N-allylbenz(thio)amides.

12250
Y. Morino et al. / Tetrahedron 62 (2006) 12247–12251
Purification by flash chromatography (hexane/ethyl acetate,
9:1) led to isolation of desired N-alkenylamide as a colorless
oil.
those of previously published material.12 Colorless crystal-
line solid; H NMR (CDCl3, 270 MHz): d 1.31–1.44 (m,
1
1H), 1.68–2.06 (m, 3H), 1.83 (d, 3H, J¼7.0 Hz), 2.45 (s,
3H), 3.27–3.36 (m, 1H), 3.44–3.53 (m, 1H), 3.96–4.02 (m,
1H), 4.75 (dq, 1H, J¼3.8, 7.0 Hz), 7.34 (d, 2H, J¼8.1 Hz),
7.72 (d, 2H, J¼8.1 Hz); 13C NMR (CDCl3, 68 MHz):
d 21.5, 24.4, 25.1, 30.4, 36.8, 49.3, 65.5, 127.5, 129.7,
135.1, 143.6.
4.3. General procedure for cyclization of
N-alkenylamides
Method A: chloramine-T (0.5 mmol) and iodine (0.5 mmol)
were added to a solution of N-alkenylamides (0.5 mmol) in
acetonitrile (3 mL). The mixture was allowed to stir in the
dark at room temperature for the indicated times under
an atmosphere of nitrogen, quenched with 0.3 M aqueous
Na2S2O3 (3 mL), extracted with CH2Cl2, dried over
MgSO4, and the extract was then concentrated under vac-
uum. The residue was purified by flash column chromato-
graphy on silica gel (eluent: hexane/ethyl acetate).
4.3.6. threo-2-(1-Iodoethyl)-1-(p-toluenesulfonyl)pyrrol-
idine (2f). Spectroscopic data were in agreement with those
of previously published material.12 Colorless crystalline
1
solid; H NMR (CDCl3, 270 MHz): d 1.33–1.43 (m, 1H),
1.78–1.93 (m, 3H), 1.87 (d, 3H, J¼7.0 Hz), 2.44 (s, 3H),
3.10–3.17 (m, 1H), 3.34–3.39 (m, 2H), 4.71–4.81 (m, 1H),
7.32 (d, 2H, J¼8.3 Hz), 7.74 (d, 2H, J¼8.3 Hz); 13C NMR
(CDCl3, 68 MHz): d 20.4, 21.6, 24.4, 28.5, 30.2, 51.4,
65.4, 127.6, 129.8, 133.7, 143.8.
Method B: chloramine-T (0.5 mmol) and iodine (0.5 mmol)
of method A was changed to chloramine-T (0.25 mmol) and
iodine (0.25 mmol).
4.3.7. 5-Iodomethyl-2-phenyl-2-oxazoline (8a). Spectro-
scopic data were in agreement with those of previously pub-
lished material.6 Colorless oil; 1H NMR (CDCl3, 270 MHz):
d 3.28–3.42 (m, 2H), 3.80 (dd, 1H, J¼6.6, 15.1 Hz), 4.17
(dd, 1H, J¼8.1, 15.1 Hz), 4.75–4.86 (m, 1H), 7.38–7.51
(m, 3H), 7.92–7.95 (m, 2H); 13C NMR (CDCl3, 68 MHz):
d 7.8, 60.7, 78.2, 127.3, 128.0, 128.2, 131.3, 163.2.
4.3.1. 2-Iodomethyl-1-(p-toluenesulfonyl)pyrrolidine
(2a). Spectroscopic data were in agreement with those of
previously published material.12 Colorless crystalline solid;
1H NMR (CDCl3, 400 MHz): d 1.50–1.55 (m, 1H), 1.76–
1.90 (m, 3H), 2.44 (s, 3H), 3.14–3.26 (m, 2H), 3.46–3.51
(m, 1H), 3.61 (dd, 1H, J¼2.8, 9.6 Hz), 3.70–3.76 (m, 1H),
7.34 (d, 2H, J¼8.0 Hz), 7.72 (d, 2H, J¼8.0 Hz); 13C NMR
(CDCl3, 68 MHz): d 11.5, 21.5, 23.8, 32.0, 50.1, 60.7,
127.5, 129.8, 134.2, 143.7.
4.3.8. 5-Iodomethyl-2-phenyl-2-thiazoline (8b). Spectro-
scopic data were in agreement with those of previously pub-
1
lished material.6 Yellow oil; H NMR (CDCl3, 270 MHz):
d 3.23 (dd, 1H, J¼10.0, 10.1 Hz), 3.38 (dd, 1H, J¼5.3,
10.0 Hz), 4.17–4.25 (m, 1H), 4.26 (dd, 1H, J¼8.1,
19.5 Hz), 4.62 (dd, 1H, J¼1.5, 19.5 Hz), 7.38–7.50 (m,
3H), 7.79–7.82 (m, 2H); 13C NMR (CDCl3, 68 MHz):
d 9.9, 51.5, 69.8, 128.4, 128.8, 131.4, 132.8, 166.3.
4.3.2. 2-Iodomethyl-1-(p-toluenesulfonyl)aziridine (2b).
Spectroscopic data were in agreement with those of previ-
ously published material.13 Colorless solid; 1H NMR
(CDCl3, 400 MHz): d 2.18 (d, 1H, J¼3.2 Hz), 2.45 (s, 3H),
2.83 (d, 1H, J¼6.8 Hz), 3.01–3.12 (m, 3H), 7.36 (d, 2H,
J¼8.2 Hz), 7.84 (d, 2H, J¼8.2 Hz); 13C NMR (CDCl3,
100 MHz): d 2.5, 21.8, 36.3, 41.1, 128.1, 129.5, 134.3, 144.7.
4.3.9. 3-Iodo-1-(p-toluenesulfonyl)pyrrolidine. Colorless
crystalline solid; mp 99–103 ꢀC; TLC Rf 0.17 (hexane/
EtOAc, 4:1); IR (KBr): 1345, 1159 cmꢂ1
;
1H NMR
4.3.3. 2-Iodomethyl-1-(p-toluenesulfonyl)azetidine (2c).
Spectroscopic data were in agreement with those of previ-
(CDCl3, 270 MHz): d 2.07–2.33 (m, 2H, –NCH2CHCH2–),
2.44 (s, 3H, ArCH3), 3.44 (t, 2H, J¼6.8 Hz,
–CHCH2CH2N–), 3.56 (dd, 1H, J¼4.7, 11.5 Hz,
–NCHHCH–), 3.90 (dd, 1H, J¼5.8, 11.5 Hz, –NCHHCH–),
4.13–4.21 (m, 1H, –NCH2CHCH2–), 7.34 (d, 2H, J¼8.0 Hz,
ArH), 7.73 (d, 2H, J¼8.0 Hz, ArH); 13C NMR (CDCl3,
68 MHz): d 17.3, 21.5, 38.1, 46.9, 58.6, 127.5, 129.8,
133.8, 143.8; MS (CI, methane): 352 ([M+1]+, 100), 224
([MꢂI]+, 14), 196 ([MꢂTs]+, 10), 184 (18), 155 (13);
Anal. Calcd for C11H14INO2S: C, 37.62; H, 4.02; N, 3.99.
Found: C, 37.84; H, 3.90; N, 3.92.
1
ously published material.6 Colorless crystalline solid; H
NMR (CDCl3, 270 MHz): d 1.85–1.99 (m, 1H), 2.03–2.15
(m, 1H), 2.47 (s, 3H), 3.28 (dd, 1H, J¼9.9, 10.0 Hz), 3.42
(dt, 1H, J¼8.3, 8.3 Hz), 3.54 (dd, 1H, J¼3.8, 9.9 Hz), 3.65
(dt, 1H, J¼3.7, 8.3 Hz), 3.89–4.00 (m, 1H), 7.38 (d, 2H,
J¼8.2 Hz), 7.72 (d, 2H, J¼8.2 Hz); 13C NMR (CDCl3,
68 MHz): d 9.8, 21.7, 24.1, 45.9, 62.9, 128.2, 129.8, 131.7,
144.2.
4.3.4. 2-Iodomethyl-1-(p-toluenesulfonyl)piperidine (2d).
Spectroscopic data were in agreement with those of
previously published material.12 Colorless oil; 1H NMR
(CDCl3, 270 MHz): d 1.25–1.58 (m, 5H), 2.03–2.12 (m,
1H), 2.43 (s, 3H), 2.94 (dt, 1H, J¼2.3, 14.2 Hz), 3.22 (dd,
1H, J¼5.0, 10.0 Hz), 3.36 (dd, 1H, J¼10.0, 10.0 Hz), 3.71
(dd, 1H, J¼3.5, 14.2 Hz), 4.24–4.28 (m, 1H), 7.30 (d, 2H,
J¼8.1 Hz), 7.72 (d, 2H, J¼8.1 Hz); 13C NMR (CDCl3,
68 MHz): d 4.0, 17.7, 21.5, 24.3, 26.2, 40.6, 53.8, 127.0,
129.8, 137.9, 143.3.
4.3.10. N-(3-Chloro-4-iodobutyl)-p-toluenesulfonamide
(A) and N-(4-chloro-3-iodobutyl)-p-toluenesulfonamide
(B). Compounds A and B obtained as an inseparable mix-
1
ture, 79:21 in 23% yield. Yellow oil; H NMR (270 MHz,
CDCl3) (A+B): d 1.76–1.93 (m, 2H, –CHHCH2NHTs,
A+B), 2.14–2.30 (m, 2H, –CHHCH2NHTs, A+B),
3.01–3.26 (m, 4H, –CH2CH2NHTs, A+B), 3.36 (dd, 1H,
J¼8.2, 10.3 Hz, B),y 3.55 (dd, 1H, J¼4.6, 10.3 Hz, B),y
3.76 (dd, 1H, J¼9.9, 11.1 Hz, A),y 3.95–4.06 (m, 1H,
y
4.3.5. erythro-2-(1-Iodoethyl)-1-(p-toluenesulfonyl)pyr-
rolidine (2e). Spectroscopic data were in agreement with
Identification of the chemical shifts was determined by the comparison of
those of the similar compounds.14

Y. Morino et al. / Tetrahedron 62 (2006) 12247–12251
12251
ClCH2CHICH2–, B),y 4.00 (dd, 1H, J¼4.3, 11.1 Hz, A),y
4.16–4.26 (m, 1H, ICH2CHClCH2–, A),y 7.37 (d, 4H,
ArH, J¼8.2 Hz, A+B), 7.76 (d, 4H, ArH, J¼8.2 Hz, A+B);
MS (CI, isobutane): m/z (relative intensity, %) (A and B):
388 ([M+1]+, 13), 352 ([MꢂCl]+, 19), 260 ([MꢂI]+, 44),
184 ([CH2NHTs]+, 100), 155 ([ArSO2], 27).
2. Bougault, M. J. C. R. Hebd. Seances Acad. Sci. 1904, 139,
864–868.
3. For a recent account: (a) Barluenga, J.; Trincado, M.; Rubio, E.;
ꢀ
Gonzalez, J. M. Angew. Chem., Int. Ed. 2006, 45, 3140–3143;
(b) Barluenga, J.; Trincado, M.; Marco-Arias, M.; Ballesteros,
ꢀ
A.; Rubio, E.; Gonzalez, J. M. Chem. Commun. 2005, 2008–
2010; (c) Barluenga, J.; Trincado, M.; Rubio, E.; Gonzalez,
ꢀ
J. M. J. Am. Chem. Soc. 2004, 126, 3416–3417; (d)
4.3.11. N-(5-Chloro-6-iodobutyl)-p-toluenesulfonamide
(C) and N-(6-chloro-5-iodobutyl)-p-toluenesulfonamide
(D). Compounds C and D obtained as an inseparable mix-
ꢀ
ꢀ
Barluenga, J.; Vazquez-Villa, H.; Ballesteros, A.; Gonzalez,
J. M. Org. Lett. 2003, 5, 4121–4123; (e) Appelbe, R.; Casey,
M.; Dunne, A.; Pascarella, E. Tetrahedron Lett. 2003, 44,
1
ture, 47:53 in 32% yield. Yellow oil; H NMR (270 MHz,
ꢀ
7641–7644; (f) Barluenga, J.; Vazquez-Villa, H.; Ballesteros,
A.; Gonzalez, J. M. J. Am. Chem. Soc. 2003, 125, 9028–
ꢀ
9029; (g) Barluenga, J.; Trincado, M.; Rubio, E.; Gonzalez,
CDCl3) (C+D): d 1.25–1.60 (m, 8H, –CH2CH2CH2NHTs,
C+D), 1.60–1.80 (m, 2H, –CHHCH2NHTs, C+D), 1.80–
2.05 (m, 2H, –CHHCH2NHTs, C+D), 2.86–3.02 (m, 4H,
–CH2CH2NHTs, C+D), 3.35 (dd, 1H, J¼8.4, 9.9 Hz, D),y
3.52 (dd, 1H, J¼4.9, 9.9 Hz, D),y 3.74 (dd, 1H, J¼10.1,
11.0 Hz, C),y 3.81–3.94 (m, 1H, ClCH2CHICH2–, D),y
3.99 (dd, 1H, J¼4.6, 11.0 Hz, C),y 4.04–4.17 (m, 1H,
ICH2CHClCH2–, C),y 7.32 (d, 4H, ArH, J¼8.2 Hz, C+D),
7.76 (d, 4H, ArH, J¼8.2 Hz, C+D); MS (CI, isobutane):
m/z (relative intensity, %) (C and D): 416 ([M+1]+, 13),
380 ([MꢂCl]+, 74), 288 ([MꢂI]+, 7), 254 (100).
ꢀ
J. M. Angew. Chem., Int. Ed. 2003, 42, 2406–2409.
ꢀ
ꢀ
ꢀ
4. For a recent account: (a) Fan˜anas, F. J.; Alvarez-Perez, M.;
´
Rodrıguez, F. Chem.—Eur. J. 2005, 11, 5938–5944; (b)
Barluenga, J.; Gonzalez-Bobes, F.; Murguıa, M. C.;
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´
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Ananthoju, S. R.; Gonzalez, J. M. Chem.—Eur. J. 2004, 10,
4206–4213; (c) Espun˜a, G.; Arsequell, G.; Valencia, G.;
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Barluenga, J.; Alvarez-Gutierrez, J. M.; Ballesteros, A.;
Gonzalez, J. M. Angew. Chem., Int. Ed. 2004, 43, 325–329;
ꢀ
ꢀ
´
(d) Barluenga, J.; Alvarez-Perez, M.; Rodrıguez, F.; Fananas,
F. J.; Cuesta, J. A.; Garcıa-Granda, S. J. Org. Chem. 2003,
ꢀ
˜
ꢀ
´
4.4. The NMR study of the iodination of N-methyl-p-
toluenesulfonamide
68, 6583–6586.
5. (a) Tanner, D. D.; Gidley, G. C.; Das, N.; Rowe, J. E.; Potter, A.
J. Am. Chem. Soc. 1984, 106, 5261–5267; (b) Kometani, T.;
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4731.
Chloramine-T (0.02 mmol) and iodine (0.02 mmol) were
added to a solution of N-methyl-p-toluenesulfonamide
(0.02 mmol) in CD3CN (0.5 mL). After 10 min, H NMR
of the mixture was measured. The conversion of 13%
of N-methyl-p-toluenesulfonamide to N-iodo-N-methyl-p-
toluenesulfonamide was observed.6
1
6. Minakata, S.; Morino, Y.; Oderaotoshi, Y.; Komatsu, M. Org.
Lett. 2006, 8, 3335–3337.
Acknowledgements
7. Minakata, S.; Morino, Y.; Oderaotoshi, Y.; Komatsu, M. Chem.
Commun. 2006, 3337–3339.
8. Ando, T.; Kano, D.; Minakata, S.; Ryu, I.; Komatsu, M.
Tetrahedron 1998, 54, 13485–13494.
9. Jeong, J. U.; Tao, B.; Sagasser, I.; Henniges, H.; Sharpless,
K. B. J. Am. Chem. Soc. 1998, 120, 6844–6845.
10. We have found that chlorinated sulfonamide 5 can be readily
prepared by reacting p-toluenesulfonamide with t-BuOCl in
MeOH.
This work was supported by a Grant-in-Aid for Scientific
Research from Ministry of Education, Culture, Sports,
Science and Technology, Japan. Y.M. expresses his special
thanks for 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.
11. Ing, H. R.; Manske, R. H. F. J. Chem. Soc. 1926, 2348–2351.
12. Minakata, S.; Kano, D.; Oderaotoshi, Y.; Komatsu, M. Org.
Lett. 2002, 4, 2097–2099.
References and notes
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Synthesis; Trost, B. M., Ed.; Pergamon: New York, NY,
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Tetrahedron 1990, 46, 3321–3408.
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4842–4845.
14. Bortolini, O.; Bottai, M.; Chiape, C.; Conte, V.; Pieraccini, D.
Green Chem. 2002, 4, 621–627.