Study on Radical Amidation onto Aromatic Rings with (Diacyloxyiodo)arenes

Article abstract of DOI:10.1021/jo980450y

Sulfonamides of primary amines bearing an aromatic ring at the γ-position were treated with (diacyloxyiodo)arenes and iodine under irradiation conditions with a tungsten lamp to give the corresponding 1,2,3,4-tetrahydroquinoline derivatives in moderate to good yields. Here, the reactivity depends on the Z-group (protecting group) of the starting amides. Under the same reaction conditions, some sulfonamides were treated with (diacetoxyiodo)benzene and iodine in the presence of aromatics to give the corresponding N-arylated amides. These reactions proceed through the intramolecular and intermolecular amidations onto aromatic rings via the sulfonamidyl radicals formed.

Full text of DOI:10.1021/jo980450y

J . Org. Chem. 1998, 63, 5193-5200
5193
Stu d y on Ra d ica l Am id a tion on to Ar om a tic Rin gs w ith
(Dia cyloxyiod o)a r en es
Hideo Togo,*,†,‡ Yoichiro Hoshina,† Takahito Muraki,† Hiromasa Nakayama,† and
Masataka Yokoyama*,†,‡
Graduate School of Science and Technology and Department of Chemistry, Faculty of Science,
Chiba University, Inage-ku, Chiba 263-8522 J apan
Received March 10, 1998
Sulfonamides of primary amines bearing an aromatic ring at the γ-position were treated with
(diacyloxyiodo)arenes and iodine under irradiation conditions with a tungsten lamp to give the
corresponding 1,2,3,4-tetrahydroquinoline derivatives in moderate to good yields. Here, the
reactivity depends on the Z-group (protecting group) of the starting amides. Under the same reaction
conditions, some sulfonamides were treated with (diacetoxyiodo)benzene and iodine in the presence
of aromatics to give the corresponding N-arylated amides. These reactions proceed through the
intramolecular and intermolecular amidations onto aromatic rings via the sulfonamidyl radicals
formed.
In tr od u ction
alkylation of π-deficient heteroaromatic compounds, the
addition to the activated olefins having electron-with-
drawing groups, and functionalization. Oxygen-centered
radicals, such as carbonyloxy radicals and alkoxy radi-
cals, were used for intramolecular cyclization5 and frag-
mentation. In the case of nitrogen-centered radicals, the
Hofmann-Lo¨ffler-Freytag-type reaction of nitroamines
and cyanoamides derived from steroidal compounds, with
(diacetoxyiodo)benzene or iodosobenzene, has been stud-
ied by Sua´rez et al.4 However, the cyclic amination onto
aromatics has been not studied.6
Many natural products contain six- or five-membered
heterocyclic rings bearing nitrogen atoms. 1,2,3,4-Tet-
rahydroquinoline skeletons are of particular interest
because of their importance in the total synthesis of
natural products as well as in medicinal chemistry;7
virantmycin8 and 2,3-dihydro-4-quinolone derivatives9
may serve as examples. Extensive studies on the prepa-
Trivalent iodine compounds have been used for various
organic syntheses. For example, oxidation, halogenation,
alkylation, and arylation have been studied, and most
of these reactions proceed through ionic reaction path-
ways.1 On the other hand, the reactions through radical
pathways have also been studied extensively as follows.
For instance, (diacyloxyiodo)arenes can generate alkyl,2
alkoxy3 and aminyl radicals4 by the reactions of carboxy-
lic acids, alcohols, and amines. Here, the alkyl radicals
formed were used for C-C bond formation such as the
† Graduate School of Science and Technology.
‡ Department of Chemistry.
(1) (a) Varvoglis, A. Synthesis 1984, 709. (b) Umemoto, T. Yuki Gosei
Kagaku Kyokaishi 1983, 41, 251. (c) Ochiai, M.; Nagao, Y. Yuki Gosei
Kagaku Kyokaishi 1986, 44, 660. (d) Moriarty, R. M.; Vaid, R. K.
Synthesis 1990, 431. (e) Moriarty, R. M.; Vaid, R. K.; Koser, G. F.
Synlett 1990, 365. (f) Kitamura, T. Yuki Gosei Kagaku Kyokaishi 1995,
53, 893. (g) Prakash, O.; Saini, N.; Sharma, P. K. Synlett 1994, 221.
(h) Kita, Y.; Takada, T.; Tohma, H. Pure Appl. Chem. 1996, 68, 627 (i)
Muraki, T.; Togo, H.; Yokoyama, M. Rev. Heteroatom Chem. 1997, 17,
213. (j) Zhdankin, V. V. Rev. Heteroatom Chem. 1997, 17, 133.
(2) (a) Togo, H.; Aoki, M.; Yokoyama, M. Tetrahedron Lett. 1991,
32, 6559. (b) Togo, H.; Aoki, M.; Yokoyama, M. Chem. Lett. 1991, 1691.
(c) Togo, H.; Aoki, M.; Yokoyama, M. Tetrahedron 1993, 49, 8241. (d)
Togo, H.; Aoki, M.; Kuramochi, T.; Yokoyama, M. J . Chem. Soc., Perkin
Trans. 1 1993, 2417. (e) Togo, H.; Aoki, M.; Yokoyama, M. Chem. Lett.
1992, 2169. (f) Togo, H.; Taguchi, R.; Yamaguchi, K.; Yokoyama, M.
J . Chem. Soc., Perkin Trans. 1 1995, 2135. (g) Togo, H.; Muraki, T.;
Yokoyama, M. Synthesis 1995, 155. (h) Minisci, F.; Vismara, E.;
Fontana, F.; Barbosa, M. C. N. Tetrahedron Lett. 1989, 30, 4569. (i)
Singh, R.; J ust, G. Synth. Commun. 1988, 18, 1327. (j) Concepcio´n, J .
I.; Francisco, C. G.; Freire, R.; Herna´ndez, R.; Salazar, J . A.; Sua´rez,
E. J . Org. Chem. 1986, 51, 402.
(3) (a) Concepcio´n, J . I.; Francisco, C. G.; Herna´ndez, R.; Salazar,
J . A.; Sua´rez, E. Tetrahedron Lett. 1984, 25, 1953. (b) Francisco, C.
G.; Freire, R.; Rodriguez, M. S.; Sua´rez, E. Tetrahedron Lett. 1987,
28, 3397. (c) Freire, R.; Herna´ndez, R.; Rodriguez, M. S.; Sua´rez, E.
Tetrahedron Lett. 1987, 28, 981. (d) Furuta, K.; Nagata, T.; Yamamoto,
H. Tetrahedron Lett. 1988, 29, 2215. (e) Brimble, M. A.; Williams, G.
M.; Baker, R.; J ames, M. Tetrahedron Lett. 1990, 31, 3043. (f) de
Armas, P.; Francisco, C. G.; Sua´rez, E. Angew. Chem., Int. Ed. Engl.
1992, 31, 1, 772. (g) de Armas, P.; Francisco, C. G.; Sua´rez, E. J . Am.
Chem. Soc. 1993, 115, 8865. (h) Boto, A.; Betancor C.; Sua´rez, E.
Tetrahedron Lett. 1994, 35, 5509. (i) Boto, A.; Betancor C.; Sua´rez, E.
Tetrahedron Lett. 1994, 35, 6993. (j) Arencibia, T.; Salazar, J . A.;
Sua´rez, E. Tetrahedron Lett. 1994, 35, 7463. (k) de Armas, P.;
Francisco, C. G.; Sua´rez, E. Tetrahedron Lett. 1993, 34, 7731. (l)
Francisco, C. G.; Gonza´lez, C. C.; Sua´rez, E. Tetrahedron Lett. 1996,
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1 1989, 405. (o) Herna´ndez, R.; Marrero, J . J .; Sua´rez, E. Tetrahedron
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L.; Francisco, C. G.; Sua´rez, E. J . Chem. Soc., Chem. Commun. 1989,
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Herna´ndez, R.; Medina, M. C.; Salazar, J . A.; Sua´rez, E. Tetrahedron
Lett. 1987, 28, 2533. (e) Carrau, R.; Herna´ndez, R.; Sua´rez, E. J . Chem.
Soc., Perkin Trans. 1 1987, 943.
(5) (a) Togo, H.; Muraki, T.; Yokoyama, M. Tetrahedron Lett. 1995,
36, 7089. (b) Muraki, T.; Togo, H.; Yokoyama, M. Tetrahedron Lett.
1996, 37, 2441. (c) Togo, H.; Muraki, T.; Hoshina, Y.; Yamaguchi, K.;
Yokoyama, M. J . Chem. Soc., Perkin Trans. 1 1997, 787.
(6) Preliminary report: Togo, H.; Hoshina, Y.; Yokoyama, M.
Tetrahedron Lett. 1996, 37, 6129.
(7) (a) Magnus, P.; Parry, D.; Iliadis, T.; Eisenbeis, S. A.; Fairhurst,
R. A. J . Chem. Soc., Chem. Commun. 1994, 1543. (b) Morimoto, Y.;
Matsuda, F. Shirahama, H. Synlett 1991, 202. (c) Staub, G. M.; Gloer,
J . B.; Wicklow, D. T.; Dowd, P. F. J . Am. Chem. Soc. 1992, 114, 1015.
(d) Neville, C. F.; Grundon, M. F.; Ramachandran, V. N.; Reisch, J . J .
Chem. Soc., Perkin Trans. 1 1991, 259. (e) Gellerman, G.; Babad, M.;
Kashman, Y. Tetrahedron Lett. 1993, 34, 1827. (f) Toyota, M.; Asoh,
T.; Fukumoto, K. Tetrahedron Lett. 1996, 37, 4401.
(8) (a) Omura, S.; Nakagawa, A.; Hashimoto, H.; Oiwa, R.; Iwai,
Y.; Hirano, A.; Shibukawa, N.; Kojima, Y. J . Antibiot. 1980, 33, 1395.
(b) Nakagawa, A.; Iwai, Y.; Hashimoto, H.; Miyazaki, N.; Oiwa, R.;
Takahashi, Y.; Hirano, A.; Shibukawa, N.; Kojima, Y.; Omura, S. J .
Antibiot. 1981, 34, 1408.
S0022-3263(98)00450-2 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/03/1998

5194 J . Org. Chem., Vol. 63, No. 15, 1998
Togo et al.
Ta ble 1. Rela tion sh ip betw een Ch em ica l Sh ift of
ration of these skeletons have been carried out, mainly
with condensation and cycloaddition methods.10 Among
these preparations, the method with radical reaction is
very useful.11 However, study on the radical cyclization
onto the aromatic ring via an aminyl radical is extremely
limited, i.e., the formation of an aminium radical gener-
ated by the photolytic or ferrous ion-catalyzed decomposi-
tion of N-chloroamines in strong acidic media,12 and the
yields in these reactions are less than satisfactory.
Here, we would like to report a good preparative
method of six-membered cyclic aromatic amines from
primary amines bearing an aromatic ring at the γ-posi-
tion, which is easily operable under neutral conditions,
through the radical amination onto the aromatic ring.
The intermolecular reactions between sulfonamides and
aromatics under the same conditions were also carried
out in further extension of the methodology.
Sta r tin g Su lfon a m id es 1 a n d Yield s of Com p ou n d 2
Resu lts a n d Discu ssion
Con ver sion to 1,2,3,4-Tetr a h yd r oqu in olin e De-
r iva tives. To carry out the cyclization to 1,2,3,4-tet-
rahydroquinoline derivatives via an aminyl radical,
3-phenyl-1-propylamine was protected by several kinds
of protecting groups to prevent the oxidation of the amino
group by (diacyloxyiodo)arenes. At first, the amide 1e
protected by a tosyl group was treated with (diacetoxy-
iodo)benzene and iodine in 1,2-dichloroethane under
irradiation with a tungsten lamp, and the desired cy-
clization product, N-tosyl-1,2,3,4-tetrahydroquinoline 2e,
could be obtained in moderate yield under the best
conditions. The addition of trifluoroacetic acid or potas-
sium carbonate to the solution retarded the formation of
compound 2e. Then, other sulfonamides protected with
various kinds of sulfonyl groups were treated with
(diacetoxyiodo)benzene and iodine under the same condi-
tions, and the corresponding cyclization products were
obtained in moderate to good yields as shown in Table
1. However, when the amine was protected by p-
methylbenzoyl 1h , trifluoroacetyl 1i, ethoxycarbonyl, and
ethyl oxalyl groups, the cyclization onto the aromatic ring
did not occur at all, and the starting amides were
recovered. The amide protected by diethyl phosphate did
not give the cyclized product (Table 1, entry 7) and the
starting amide was recovered again. Here, the electron-
withdrawing substituents on the aromatic ring in para-
substituted benzenesulfonamides accelerated the reac-
tivity and gave the cyclized products in good yields.
Thus, the trifluoromethanesulfonyl group, the most
a
CDCl3-TMS. b Yield in 6-iodo compound of 2. c Starting amide
was recovered in >80% yield.
powerful electron-withdrawing group, showed the best
reactivity. A good relationship between the 13C NMR
chemical shift of the NHCH2 group in the starting
compound 1 and the yield of the cyclized product 2 was
observed, though the difference is small. Thus, the
reaction requires a chemical shift value lower field than
42 ppm in compound 1. Namely, this reactivity probably
depends on the acidity of sulfonamides and the stability
of sulfonamidyl radicals. Practically, there is ∼10 order
difference in pKa values of the NH proton between
sulfonamides and amides.13 Sulfonamide protected by
2-nitrobenzenesulfonyl group 1j was also treated, and the
desired compound 2j was obtained in 34% yield together
with an iodinated compound at the 6-position (2j-I) of
compound 2j in 17% yield. It might be caused by the
reduction of electron-withdrawing ability by steric hin-
drance at the ortho position. These cyclization reactions
do not proceed with iodine alone or with (diacyloxyiodo)-
arene and bromine instead of iodine. Moreover, galvi-
noxyl radical (1.0 equiv based on compound 1a ) com-
pletely retarded these reactions. The present reactions
proceed under fluorescent lighting, instead of under
irradiation with a tungsten lamp. However, the irradia-
tion with ultrasonic wave was ineffective.
(9) (a) Atwal, M. S.; Bauer, L.; Dixit, S. N.; Gearien, J . E.; Megahy,
M.; Morris, R.; Pokorny, C. J . Med. Chem. 1969, 12, 994. (b) Daruwala,
A. B.; Gearien, J . E.; Dunn, W. J ., III; Benoit, P. S.; Bauer, L. J . Med.
Chem. 1974, 17, 819.
(10) Comprehensive Heterocyclic Chemistry; Katrizky, A. R., Rees,
C. W., Eds.; Pergamon Press: New York, 1984.
(11) (a) Neumann, W. P. Synthesis 1987, 665. (b) Curran, D. P.
Synthesis 1988, 417 and 489. (c) Smadja, W. Synlett 1994, 1. (d) Giese,
B. Radicals in Organic Synthesis: Formation of Carbon-Carbon
Bonds; Baldwin, J . E., Ed.; Pergamon Press: Oxford, 1986.
(12) Amination onto aromatic ring via aminyl radical: (a) Minisci,
F.; Galli, R. Tetrahedron Lett. 1966, 2531. (b) Glover, S. A.; Goosen,
A.; Laue, H. A. H. J . Chem. Soc., Perkin Trans. 1 1973, 1647.
Amination onto aromatic ring via iminyl radical: (c) Forrester, A. R.;
Gill, M.; Thomson, R. H. J . Chem. Soc., Chem. Commun. 1976, 677.
(d) Forrester, A. R.; Gill, M.; Sadd, J . S.; Thomson, R. H. J . Chem.
Soc., Chem. Commun. 1975, 291. Hofmann-Lo¨ffler-Freytag reac-
tion: (e) Corey, E. J .; Hertler, W. R. J . Am. Chem. Soc. 1960, 82, 1657.
(f) Hertler, W. R.; Corey, E. J . J . Org. Chem. 1959, 24, 572. (g)
Buchschacher, P.; Kalvoda, J .; Arigoni, D.; J eger, O. J . Am. Chem. Soc.
1958, 80, 2905.
A plausible reaction mechanism for the present reac-
tion is shown in Scheme 1. Here, the formation of
monosubstituted trivalent iodine compound A from sul-
fonamide 1a and (diacetoxyiodo)benzene was not ob-
served by NMR. Addition of iodine gave the N-iodinated
(13) (a) Bordwell, F. G.; J i, Guo-T.; Zhang, X. J . Org. Chem. 1991,
56, 5254. (b) Bordwell, F. G.; Zhang, X.; Filler, R. J . Org. Chem. 1993,
58, 6067. (c) Ratcliffe, A. J .; Warner, I. Tetrahedron Lett. 1995, 36,
3881.

Radical Amidation onto Aromatic Rings
J . Org. Chem., Vol. 63, No. 15, 1998 5195
Ta ble 3. Solven t Effect in th e Rea ction w ith
Com p ou n d s 1a a n d 1b
Sch em e 1
recovery of
entry
1
solvent
2 yield/%
1a or 1b/%
1
2
3
4
5
1a
1a
1b
1b
1b
AcOEt
EtOH
AcOEt
CHCl3
73
0
60
53
5
0
88
22
37
86
CH3OCH2CH2OCH3
Ta ble 4. Con ver sion of Va r iou s Am id es to 6-Mem ber ed
Cyclic Am id es (I)
Ta ble 2. Su bstitu en t Effect of (Dia cyloxyiod o)a r en es 3
in th e Cycliza tion of Com p ou n d 1b
yields/%
W - hν
60-70 °C
fluorescent
lamp rt
entry
1
X
R
1
2
3
4
5
1k
1l
1m
1n
1o
CHCH3
O
CH2
CH2
CH2
H
H
CH3
Ph
n-C4H9
80
72a
43
28
26
6
43
13b
a
6-Iodo compound (2l-I) was also formed in ∼9% yield. b PhI(O-
Ac)2 (2.4 equiv) and I2 (1.5 equiv).
alkyl-branched amines were converted to the correspond-
ing cyclic aromatic sulfonamides in good yields. Since
the yields in alkyl-branched sulfonamides were low due
to the occurrence of side reactions (â-fragmentation of
the formed sulfonamidyl radical), they were treated
under milder conditions, at room temperature under
irradiation with fluorescent lighting, instead of a tung-
sten lamp. However, each yield went down (Table 3,
entries 3-5). The sulfonamides having a naphthyl (1p )
group and a biphenyl (1q) group were also converted to
the corresponding cyclized products 2p and 2q, respec-
tively, in moderate to good yields as shown in Scheme 2.
Here, it is noteworthy that the ratio of 2r and 2r -I was
largely inverted by changing the solvents. Therefore,
deliberate control of the products is possible.
The following sulfonamide 1s was used to study the
electrophilicity of sulfonamidyl radical intermediate D
(Scheme 3). As a consequence, the sulfonamidyl radical
D seems to be less selective than the corresponding
alkoxy radical intermediate E, which is formed from the
corresponding alcohol 4, because of the formation of 2s-
II. Probably, this is due to the more reactive character
of sulfonamidyl radical D than the corresponding alkoxy
radical E.
compound B in the NMR sample tube. Thus, compound
B is one of the reactive intermediates, and the homolytic
cleavage of N-I bond occurs to give the sulfonamidyl
radical C under the irradiation conditions. Finally, the
radical added to the aromatic ring to give the compound
2a via oxidative aromatization. The present reaction
does not proceed at all in the dark or without (diacetoxy-
iodo)benzene.
The substituent effect of (diacyloxyiodo)arenes was
studied under the same conditions as shown in Table 2;
however, no big difference was observed. [Bis(trifluoro-
acetoxy)iodo]benzene 3vii and [bis(trifluoroacetoxy)iodo]-
pentafluorobenzene 3xi did not give the compound 2b.
The solvent effect was studied continuously as shown
in Table 3. Ethyl acetate gave the compound 2 as well
as 1,2-dichloroethane (Table 3, entry 1). Though chlo-
roform also gave the compound 2, the yield was decreased
slightly (Table 3, entry 4). In ethanol and 1,2-dimethox-
yethane, the reactions were inhibited and the starting
amides were recovered in nearly 90% yield (Table 3,
entries 2 and 5).
The cyclic products obtained here could be easily
deprotected by using lithium aluminum hydride or
thiophenol14 in good yields (>90%) (Scheme 4). Thus, the
present reaction is a good method for preparation of
1,2,3,4-tetrahydroquinoline derivatives, which can be
converted to a quinoline skeleton in good yields by
Other amides protected by a trifluoromethanesulfonyl
group were treated with (diacetoxyiodo)benzene and
iodine under the best conditions. The results are shown
in Table 4. The sulfonamides derived from primary
(14) Fukuyama, T.; J ow, C.-K.; Cheung, M. Tetrahedron Lett. 1995,
36, 6373.

5196 J . Org. Chem., Vol. 63, No. 15, 1998
Togo et al.
Sch em e 2
Sch em e 3
treatment with DDQ under refluxing conditions in
toluene. Therefore, the present reaction is finally a good
method for the preparation of quinoline derivatives from
primary amines containing an aromatic ring at the
γ-position.
In addition, as one of the synthetic uses of the present
reaction, a model study for virantmycin was carried out
to give the compound 7 in good yield as shown in Scheme
5.
Con ver sion to Oth er Cyclic Am in es. Next, we
worked on changing the number of methylene units. The
sulfonamide bearing an aromatic ring at the â-position
was treated under the same conditions. However, the
dihydroindole skeleton was not formed, but benzyl iodide
was obtained mainly. It was caused by the â-fragmenta-
tion of the corresponding sulfonamidyl radical formed.
This â-fragmentation reaction occurred even at 0 °C. On
the other hand, the sulfonamides bearing an aromatic
ring at the δ-position 8t-v gave the pyrrolidine deriva-
tives 9t-v via the Hofmann-Lo¨ffler-Freytag-type reac-
tion15 in good yields without formation of seven-mem-
bered cyclic amides (Table 5). Here, the p-nitrobenzene-
sulfonyl group gave the products in better yield than the
trifluoromethanesulfonyl group.
Sch em e 4
In t er m olecu la r R ea ct ion s. At first, saccharin 10
that has lower pKa value than the general sulfonamides
was warmed to 60-70 °C in the presence of (diacetoxy-
iodo)benzene and iodine in benzene under irradiation
with a tungsten lamp to give N-phenylsaccharin 11c′
(Table 6). The reaction requires 3 equiv of (diacetoxy-
iodo)benzene to increase the yield of N-phenylsaccharin,
and here, the compound was obtained in 83% yield.
Anisole, toluene, chlorobenzene, and nitrobenzene were
treated as a solvent under the same conditions, and the
corresponding N-arylsaccharins 11 could be obtained in
good yields in toluene and chlorobenzene, respectively.
However, anisole, a π-electron-rich aromatic, gave little
product due to the formation of iodoanisole. In the case
of nitrobenzene, the reactivity seems to be poor because
of the strong electron-withdrawing group. Then, naph-
thalene (5 equiv) and benzothiophene (5 equiv) were
treated in 1,2-dichloroethane as a solvent under the same
conditions. Though the yields were not so good (56% and
42% yields, respectively), the substitution products could
be obtained with high regioselectivity.
Next, N-alkylsulfonamides were treated under the
same conditions. Methylamine protected by the p-
nitrobenzenesulfonyl group was phenylated in good yield.
(15) (a) Neale, R. S. Synthesis 1971, 1. (b) Wolff, M. E. Chem. Rev.
1963, 63, 55.

Radical Amidation onto Aromatic Rings
J . Org. Chem., Vol. 63, No. 15, 1998 5197
Ta ble 8. N-Ar yla tion of N-Meth ylsu lfon a m id es
Sch em e 5
entry
X
X
13
yield/%
o:m:p/%
1
CH3
Cl
CH3
H
H
CH3
13n ′
13o′
13p ′
90
71
60
66:17:17
66:17:17
2
3a
a
PhI(OAc)2 (4.0 equiv) and I2 (3 equiv).
p-nitrobenzenesulfonyl group were also arylated with
toluene, chlorobenzene, and p-xylene in good yields,
respectively.
Ta ble 5. Cycliza tion w ith
N-(4-P h en ylbu tyl)-4-n itr oben zen esu lfon a m id es:
Con ver sion to P yr r olid in e Der iva tive
Finally, phthalimide was treated in benzene under the
same conditions, and N-phenylphthalimide was obtained
in 56% yield and phthalimide was recovered in 32% yield
under the same conditions as above. This is due to the
poor solubility of phthalimide in benzene. Finally, 3.0
equiv of (diacetoxyiodo)benzene and 2.0 equiv of iodine
were added twice at 2-h intervals, to increase the yield
of N-phenylphthalimide to 79%.
In conclusion, the present reactions are very useful for
the preparation of 1,2,3,4-tetrahydroquinoline derivatives
and pyrrolidine derivatives from primary amines bearing
an aromatic ring at the γ- and δ-positions, respectively,
because the reaction proceeds by a simple operation and
under mild and neutral conditions.
entry
8
Z
R
yield/%
1
2
3
8t
SO2CF3
H
54
8u
8v
SO2C6H4NO2-p
SO2C6H4NO2-p
H
CH3
84
71a
a
cis:trans ) 35:65.
Ta ble 6. Con ver sion to N-Ar ylsa cch a r in s (I)
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined on an
electrothermal apparatus in open capillary tubes and are
uncorrected. 1H NMR spectra were recorded on 400 and 500
MHz spectrometers and 13C NMR spectra were recorded on
100 and 125 MHz spectrometers. Chemical shifts are reported
as ppm downfield from tetramethylsilane (TMS) in δ units.
Mass spectra were measured with J EOL-J MS-AMII15 (EI),
and high-resolution mass spectra (HRMS) were measured with
a J EOL-HX 110A mass spectrometer. Wakogel C-200 and
C-300 were used for column chromatography, Kieselgel 60
F254 (Merck) was used for TLC, and Wakogel B-5F was used
for pTLC.
entry
X
11
yield/%
orientation
1
2
3
4
5
OCH3
CH3
H
11a ′
11b′
11c′
11d ′
11e′
5
75
83
80
18
o:p ) 42:58
o:p ) 50:50
Cl
o:p ) 60:40
m alone
NO2
Ta ble 7. N-P h en yla tion of N-Alk ylsu lfon a m id es
Ma ter ia ls. (Diacetoxyiodo)benzene and [bis(trifluoroac-
etoxy)iodo]benzene are commercially available. The other
(diacetoxyiodo)arenes were prepared by the oxidation of the
corresponding iodoarenes.2f,16 Most sulfonamides are prepared
by reaction with sulfonyl chlorides, triethylamine, and amines,
which are commercially available or prepared by the Mit-
sunobu reaction from the corresponding alcohols.17
entry
R
13
yield/%
recovery of 12/%
Typ ica l P r oced u r es. Con ver sion of Am id es to th e
Cor r esp on d in g Cyclic Am id es. (Diacyloxyiodo)arene and
iodine were added to a solution of sulfonamide (0.5 mmol) in
1,2-dichloroethane (7 mL). The mixture was irradiated with
a tungsten lamp (500 W) at 60-70 °C (or irradiated with
fluorescent lighting at room temperature) for 2 h under an
argon atmosphere. After the reaction, the mixture was poured
into saturated aqueous sodium sulfite solution and extracted
with ethyl acetate three times. The organic layer was dried
over sodium sulfate. After removal of the solvent under
reduced pressure, the residue was chromatographed by pre-
1a
2b
3b
4
5
6
CH3
C2H5
n-C4H9
CH(CH3)2
C(CH3)3
OCH3
13h ′
13i′
13j′
13k ′
13l′
13m ′
90
52
7
trace
0
0
9
9
80
96
7
0
a
b
I2 (1.0 equiv). PhI(OAc)2 (4.0 equiv).
Again, N-phenyl compound 13 was not obtained in the
dark. The p-nitrobenzenesulfonyl group gave the reac-
tion product 13 in better yield than the tosyl group.
Other N-alkylsulfonamides were treated in benzene to
give the corresponding N-alkyl-N-phenylsulfonamide;
however, the yields were decreased as the alkyl group
tended to be bulky. N-Methylamides protected by the
(16) (a)Mckillop, A.; Kemp, D. Tetrahedron 1989, 45, 3299. (b)
Schmeisser, M.; Dahmen, K.; Sartori, P. Chem. Ber. 1967, 100, 1633.
(17) (a) Mitsunobu, O.; Wada, M.; Sano, T. J . Am. Chem. Soc. 1972,
94, 679. (b) Mitsunobu, O. Synthesis 1981, 1.

5198 J . Org. Chem., Vol. 63, No. 15, 1998
Togo et al.
parative TLC (pTLC) on silica gel using hexane and ethyl
acetate (2:1-8:1) as an eluent.
) 6.0 Hz, 2H), 7.00 (d, J ) 7.3 Hz, 1H), 7.07 (t, J ) 7.3 Hz,
1H), 7.17-7.19 (m, 3H), 7.47 (d, J ) 8.4 Hz, 2H), 7.79 (d, J )
8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 21.51 (p), 26.54 (s),
46.47 (s), 124.92 (t), 126.45 (t), 127.03 (t), 129.03 (t), 129.51
(t), 130.62 (q), 136.72 (q), 136.83 (q), 143.45 (q); HRMS (EI)
found M+ 287.0965, calcd for C16H17NO2S M 287.0980. Anal.
Calcd for C16H17NO2S: C, 66.87; H, 5.96; N, 4.87. Found: C,
66.74; H, 6.07; N, 4.72.
Con ver sion of Su lfon a m id es to N-Ar ylsu lfon a m id es
w ith Ar om a tics a s a Solven t. (Diacetoxyiodo)benzene and
iodine were added to a solution of sulfonamide (0.5 mmol) in
an aromatic (10 mL). The mixture was irradiated with a
tungsten lamp (500 W) at 60-70 °C for 2 h under an argon
atmosphere. After the reaction, the mixture was poured into
saturated aqueous sodium sulfite solution and extracted with
ethyl acetate three times. The organic layer was dried over
sodium sulfate. After removal of the solvent under reduced
pressure, the residue was chromatographed by pTLC on silica
gel using hexane and ethyl acetate as an eluent.
N-(4′-Meth oxyben zen esu lfon yl)-1,2,3,4-tetr ah ydr oqu in -
olin e (2f), N-(4′-m eth oxyben zen esu lfon yl)-6-iod o-1,2,3,4-
tetr a h yd r oqu in olin e (2f-I) 1:1 m ixtu r e: IR (KBr) 2930,
2830, 1600, 1500, 1340, 1260, 1180 cm-1; 1H NMR (400 MHz,
CDCl3) δ 1.58-1.65 (m), 2.40-2.47 (m), 3.74-3.80 (m), 3.82
(s), 3.84 (s), 6.84-6.89 (m), 7.00 (d, J ) 7.3 Hz), 7.06 (t, J )
7.5 Hz), 7.18 (t, J ) 8.1 Hz), 7.34 (s), 7.46-7.57 (m), 7.79 (d,
J ) 8.4 Hz); HRMS (EI) found M+ 303.0919 and 428.9907,
calcd for C16H17NO3S M 287.0980 and C16H16NO3SI M 428.9896.
N-(2′-Nitr oben zen esu lfon yl)-1,2,3,4-tetr a h yd r oqu in o-
lin e (2j): mp 130.5-132.0 °C; IR (KBr) 2940, 1530, 1490,
Con ver sion of Su lfon a m id es to N-Ar ylsu lfon a m id es
w ith Ar om a tics in 1,2-Dich lor oeth a n e. (Diacetoxyiodo)-
benzene and iodine were added to a solution of the appropriate
sulfonamide (0.5 mmol) and aromatic (2.5 mmol) in 1,2-
dichloroethane (10 mL). The mixture was irradiated with a
tungsten lamp (500 W) at 60-70 °C for 2 h under an argon
atmosphere. After the reaction, the mixture was poured into
saturated aqueous sodium sulfite solution and extracted with
ethyl acetate three times. The organic layer was dried over
sodium sulfate. After removal of the solvent under reduced
pressure, the residue was chromatographed on silica gel by
pTLC using hexane and ethyl acetate as eluent.
1340, 1160, 1100 cm-1 1H NMR (400 MHz, CDCl3) δ 1.89
;
(quint, J ) 6.4 Hz, 2H), 2.63 (t, J ) 6.8 Hz, 2H), 3.87 (t, J )
6.0 Hz, 2H), 7.07-7.19 (m, 3H), 7.51-7.62 (m, 3H), 7.65-7.72
(m, 2H). Anal. Calcd for C15H14N2O4S: C, 56.59; H, 4.43; N,
8.80. Found: C, 56.44; H, 4.24; N, 8.66.
N-(2′-Nitr oben zen esu lfon yl)-6-iod o-1,2,3,4-tetr a h yd r o-
qu in olin e (2j-I): mp 122.0-123.5 °C; IR (KBr) 2950, 1540,
N-(Tr iflu or om eth a n esu lfon yl)-1,2,3,4-tetr a h yd r oqu in -
olin e (2a ): oil; IR (neat) 2900, 1580, 1480, 1220, 1200 cm-1
;
1480, 1360, 1250, 1160 cm-1 1H NMR (400 MHz, CDCl3) δ
;
1H NMR (400 MHz, CDCl3) δ 2.11 (quint, J ) 6.4 Hz, 2H),
2.88 (t, J ) 6.8 Hz, 2H), 3.87 (t, J ) 6.0 Hz, 2H), 7.15-7.22
(m, 3H), 7.52 (d, J ) 7.7 Hz, 1H); 13C NMR (125 MHz, CDCl3)
δ 23.39 (s), 26.13 (s), 47.94 (s), 120.11 (q, J C-F ) 328 Hz, q,
CF3), 123.34 (t), 126.15 (t), 126.79 (t), 129.46 (t), 130.91 (q),
135.31 (q); HRMS (EI) found M+ 265.0390, calcd for C10H10F3-
NO2S M 265.0384.
1.85 (quint, J ) 6.4 Hz, 2H), 2.61 (t, J ) 6.8 Hz, 2H), 3.84 (t,
J ) 6.0 Hz, 2H), 7.29 (d, J ) 8.5 Hz, 1H), 7.43-7.48 (m, 2H),
7.58-7.64 (m, 2H), 7.71 (t, J ) 8.3 Hz, 1H), 7.75 (d, J ) 7.7
Hz, 1H); HRMS (EI) found M+ 443.9638, calcd for C15H13N2O4-
SI M 443.9639.
N-(Tr iflu or om eth an esu lfon yl)-4-m eth yl-1,2,3,4-tetr ah y-
d r oqu in olin e (2k ): oil; IR (neat) 2900, 1480, 1400, 1230, 1200
N-(4′-Nitr oben zen esu lfon yl)-1,2,3,4-tetr a h yd r oqu in o-
lin e (2b): mp 116.5-117.5 °C; IR (KBr) 3080, 2930, 1600,
1
cm-1; H NMR (400 MHz, CDCl3) δ 1.36 (d, J ) 7.0 Hz, 3H),
1.70-1.79 (m, 1H), 2.11-2.29 (m, 1H), 2.97-3.02 (m, 1H),
3.83-3.90 (m, 2H), 7.18-7.22 (m, 2H), 7.25-7.28 (m, 1H), 7.51
(d, J ) 9.5 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 21.49 (p),
30.12 (t), 31.70 (s), 46.37 (s), 118.35 (q), 121.56 (q), 123.19 (t),
126.23 (t), 126.74 (t), 127.97 (t), 134.61 (q), 135.80 (q); HRMS
(EI) found M+ 279.0540, calcd for C11H12F3NO2S M 279.0540.
N-(Tr iflu or om eth a n esu lfon yl)-5,6-d id eh yd r o-5,6-ben -
zom or p h olin e (2l): oil; IR (neat) 1580, 1500, 1400, 1320,-
1520, 1340, 1160 cm-1 1H NMR (400 MHz, CDCl3) δ 1.66
;
(quint, J ) 6.4 Hz, 2H), 2.43 (t, J ) 6.6 Hz, 2H), 3.86 (t, J )
6.0 Hz, 2H), 7.03 (d, J ) 7.7 Hz, 1H), 7.13 (t, J ) 7.4 Hz, 1H),
7.23 (t, J ) 8.6 Hz, 1H), 7.75 (d, J ) 8.8 Hz, 2H), 7.79 (d, J )
9.2 Hz, 1H), 8.24 (d, J ) 8.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 21.73 (s), 26.40 (s), 46.88 (s), 124.13 (t), 124.89 (t),
125.79 (t), 126.83 (q), 128.22 (t), 129.34 (t), 130.89 (q), 135.91
(t), 145.22 (q), 149.99 (q); HRMS (EI) found M+ 318.0684, calcd
for C15H14N2O4S M 318.0674. Anal. Calcd for C15H14N2O4S:
C, 56.59; H, 4.43; N, 8.80; S, 10.07. Found: C, 56.37; H, 4.41;
N, 8.77; S, 9.99.
1
1260, 1230, 1200 cm-1; H NMR (400 MHz, CDCl3) δ 3.97 (t,
J ) 4.6 Hz, 2H), 4.37 (t, J ) 4.6 Hz, 2H), 6.91-6.96 (m, 2H),
7.13 (t, J ) 7.7 Hz, 1H), 7.56 (d, J ) 8.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 45.53 (s), 65.11 (s), 118.04 (t), 118.09 (q),
121.14 (t), 121.31 (q), 122.13 (q), 122.51 (t), 127.18 (t), 146.43
(q); HRMS (EI) found M+ 267.0169, calcd for C9H8F3NO3S M
267.0177.
N-(4′-Br om oben zen esu lfon yl)-1,2,3,4-tetr a h yd r oqu in o-
lin e (2c): mp 128.0-129.0 °C; IR (KBr) 3050, 2900, 1560,
1480, 1340, 1160 cm-1 1H NMR (400 MHz, CDCl3) δ 1.65
;
(quint, J ) 6.3 Hz, 2H), 2.45 (t, J ) 6.6 Hz, 2H), 3.81 (t, J )
6.0 Hz, 2H), 7.02 (d, J ) 7.7 Hz, 1H), 7.09 (t, J ) 7.4 Hz, 1H),
7.20 (t, J ) 7.8 Hz, 1H), 7.44 (d, J ) 8.8 Hz, 2H), 7.53 (d, J )
8.8 Hz, 2H), 7.77 (d, J ) 7.3 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 21.60 (s), 26.49 (s), 46.64 (s), 124.93 (t), 125.31 (t),
126.61 (t), 127.68 (q), 128.51 (t), 129.18 (t), 130.77 (q), 132.17
(t), 136.40 (q), 138.65 (q); HRMS (EI) found M+ 350.9941, calcd
N-(Tr iflu or om eth an esu lfon yl)-2-m eth yl-1,2,3,4-tetr ah y-
d r oqu in olin e (2m ): oil; IR (neat) 2900, 1480, 1450, 1380,
1
1220, 1200 cm-1; H NMR (400 MHz, CDCl3) δ 1.27 (d, J )
6.6 Hz, 3H), 1.57-1.70 (m, 1H), 2.37-2.46 (m, 1H), 2.76 (t, J
) 6.7 Hz, 2H), 4.55-4.65 (m, 1H), 7.15-7.25 (m, 3H), 7.50 (d,
J ) 7.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 20.9 (p), 24.44
(s), 31.08 (s), 54.57 (s), 118.55 (q), 121.78 (q), 125.54 (t), 126.70
(t), 126.99 (t), 128.41 (t), 133.22 (q); HRMS (EI) found M+
279.0550, calcd for C11H12F3NO2S M 279.0540.
for C15H1479BrNO2S M 350.9929; Anal. Calcd for C15H14
-
BrNO2S: C, 51.15; H, 4.01; N, 3.98; S, 9.12. Found: C, 51.03;
H, 3.85; N, 4.05; S, 8.97.
N-(Tr iflu or om eth an esu lfon yl)-2-ph en yl-1,2,3,4-tetr ah y-
d r oqu in olin e (2n ): mp 62.0-64.0 °C; IR (KBr) 2960, 1500,
N -(B e n ze n e s u lfo n y l)-1,2,3,4-t e t r a h y d r o q u in o lin e
(2d ): oil; IR (neat) 3030, 2900, 1600, 1580, 1480, 1440, 1340,
1
1390, 1200 cm-1; H NMR (400 MHz, CDCl3) δ 2.04 (bs, 1H),
1
1160 cm-1; H NMR (400 MHz, CDCl3) δ 1.62 (quint, J ) 6.3
2.64-2.72 (m, 2H), 2.75-2.82 (m, 1H), 5.52 (dd, J ) 6.8, 6.8
Hz, 1H), 7.15-7.30 (m, 8H), 7.67 (d, J ) 8.1 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 25.45 (s), 33.16 (s), 61.88 (t), 125.24 (t),
125.84 (t), 126.83 (t), 127.44 (t), 127.57 (t), 128.26 (t), 128.71
(t), 134.52 (q); HRMS (EI) found M+ 341.0673, calcd for
Hz, 2H), 2.41 (t, 6.8 Hz, 2H), 3.80 (t, J ) 6.0 Hz, 2H), 7.00 (d,
J ) 7.3 Hz, 1H), 7.07 (t, J ) 7.4 Hz, 1H), 7.18 (t, J ) 7.5 Hz,
1H), 7.39 (t, J ) 7.7 Hz, 2H), 7.52 (t, J ) 7.5 Hz, 1H), 7.59 (d,
J ) 7.7 Hz, 2H), 7.78 (d, J ) 8.1 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 21.54 (s), 26.43 (s), 46.48 (s), 124.90 (t), 125.00 (t),
126.45 (t), 126.96 (t), 128.89 (t), 129.02 (t), 130.70 (q), 132.64
(t), 136.69 (q), 139.58 (q); HRMS (EI) found M+ 273.0820, calcd
for C15H15NO2S M 273.0824.
C
16H14F3NO2S M 341.0697. Anal. Calcd for C16H14F3NO2S:
C, 56.30; H, 4.13, N, 4.10. Found: C, 56.15; H, 4.16; N, 3.92.
N-(Tr iflu or om eth a n esu lfon yl)-2-bu tyl-1,2,3,4-tetr a h y-
d r oqu in olin e (2o): oil; IR (neat) 2900, 2850, 1480, 1450,
N-(4′-Meth ylben zen esu lfon yl)-1,2,3,4-tetr a h yd r oqu in -
olin e (2e): mp 83.0-85.0 °C; IR (KBr) 3000, 2900, 2850, 1580,
1
1390, 1220, 1180 cm-1; H NMR (400 MHz, CDCl3) δ 0.86 (t,
1
1480, 1330 cm-1; H NMR (400 MHz, CDCl3) δ 1.63 (quint, J
J ) 7.1 Hz, 3H), 1.25-1.74 (m, 7H), 2.37-2.42 (m, 1H), 2.77
(t, J ) 7.0 Hz, 2H), 4.41 (m, 1H), 7.15-7.26 (m, 3H), 7.52 (d,
) 6.3 Hz, 2H), 2.38 (s, 3H), 2.44 (t, J ) 6.6 Hz, 2H), 3.80 (t, J

Radical Amidation onto Aromatic Rings
J . Org. Chem., Vol. 63, No. 15, 1998 5199
J ) 6.6 Hz, 1H); HRMS (EI) found M+ 321.1018, calcd for
N-(Tr iflu or om et h a n esu lfon yl)-2-p h en ylp yr r olid in e
(9t): mp 56.0-57.5 °C; IR (KBr) 3000, 1600, 1500, 1450, 1380,
1230, 1180 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.01-2.12 (m,
3H), 2.40-2.49 (m, 1H), 3.76-3.80 (m, 2H), 5.12 (dd, J ) 7.0,
2.9 Hz, 1H), 7.25-7.30 (m, 3H), 7.36 (t, J ) 7.2 Hz, 2H); HRMS
(EI) found M+ 279.0553, calcd for C11H12F3NO2S M 279.0540.
N -(4′-N it r o b e n ze n e s u lfo n y l)-2-p h e n y lp y r r o lid in e
(9u ): mp 131.5-132.0 °C; IR (KBr) 3080, 2950, 2850, 1600,
C
14H18F3NO2S M 321.1010.
N-(Tr iflu or om eth yl)ben zo[f]-1,2,3,4-tetr a h yd r oqu in o-
lin e (2p ): mp 82.0-84.0 °C; IR (KBr) 2950, 2360, 1600, 1520,
1
1400, 1200 cm-1; H NMR (500 MHz, CDCl3) δ 2.29 (quint, J
) 6.4 Hz, 2H), 3.24 (t, J ) 7.1 Hz, 2H), 3.90 (t, J ) 5.5 Hz,
2H), 7.49 (t, J ) 7.5 Hz, 1H), 7.54 (t, J ) 7.6 Hz, 1H), 7.62 (d,
J ) 9.2 Hz, 1H), 7.68 (d, J ) 9.2 Hz, 1H), 7.81 (d, J ) 8.5 Hz,
1H), 7.92 (d, J ) 8.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ
22.73 (s), 23.29 (s), 44.88 (s), 119.86 (q, J ) 324 Hz, q, CF3),
122.22 (t), 124.83 (q), 125.93 (t), 126.91 (t,), 127.12 (t), 128.53
(t), 133.40 (q), 132.02 (q), 132.86 (q); MS (EI) M+ 315. Anal.
Calcd for C14H12F3NO2S: C, 53.33; H, 3.84; N, 4.44. Found:
C, 53.40; H, 3.72; N, 4.42.
1
1520, 1340, 1160 cm-1; H NMR (500 MHz, CDCl3) δ 1.80-
1.92 (m, 2H, 3,4-H), 1.94-2.01 (m, 1H, 4-H), 2.14-2.21 (m,
1H, 3-H), 3.59-3.66 (m, 2H, 5-H), 4.87 (dd, J ) 7.8, 4.4 Hz,
1H, 2-H), 7.17 (d, J ) 6.8 Hz, 2H, Ph(o)-H), 7.22-7.25 (m, 3H,
Ph(m,p)-H), 7.80 (d, J ) 8.9 Hz, 2H, 2′,6′-H), 8.22 (d, J )
8.9 Hz, 2H, 3′,5′-H); 13C NMR (125 MHz, CDCl3) δ 24.20 (s,
4-C), 35.93 (s, 3-C), 49.40 (s, 5-C), 63.67 (t, 2-C), 123.95 (t, 3′,5′-
C), 126.37 (t, Ph-2′′,6′′-C), 127.44 (t, Ph-4′′-C), 128.27 (t, 2′,6′-
C), 128.38 (t, Ph-3′′,5′′-C), 141.79 (q, Ph-1′′-C), 144.66 (q, 1′-
C), 149.74 (q, 4′-C); MS (EI) M+ 322. Anal. Calcd for
C16H16N2O4S: C, 57.82; H, 4.85; N, 8.43; S, 9.65. Found: C,
57.59; H, 4.82; N, 8.41; S, 9.65.
N -(T r iflu o r o m e t h y l)-5,6-d ih y d r o p h e n a n t h r id in e
(2q): mp 61.0-62.0 °C; IR (KBr) 3020, 1480, 1440, 1390, 1220,
1
1200, 1140 cm-1; H NMR (500 MHz, CDCl3) δ 4.87 (s, 2H),
7.27 (d, J ) 7.5 Hz, 1H), 7.36 (t, J ) 7.5 Hz, 1H), 7.37 (t, J )
7.6 Hz, 1H), 7.41 (t, J ) 7.5 Hz, 1H), 7.45 (t, J ) 7.6 Hz, 1H),
7.67 (d, J ) 7.9 Hz, 1H), 7.81 (d, J ) 7.6 Hz, 1H), 7.83 (d, J )
7.6 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 50.59 (s), 119.82
(q, J ) 325 Hz, q, CF3), 123.74 (t), 124.52 (t), 125.28 (t), 125.71
(t,), 127.97 (t), 128.58 (t), 128.98 (t), 130.10 (q), 130.89 (q),
131.91 (q), 134.05 (q); MS (EI) M+ 313. Anal. Calcd for
N-(4′-Nitr oben zen esu lfon yl)-2-m eth yl-5-p h en ylp yr r o-
lid in e (9v) (cis): mp 174.0-175.5 °C; IR (KBr) 2970, 1600,
1
1520, 1350, 1160 cm-1; H NMR (400 MHz, CDCl3) δ 1.49 (d,
J ) 6.3 Hz, 3H), 1.59-1.66 (m, 1H), 1.82-1.99 (m, 2H), 2.01-
2.10 (m, 1H), 4.08-4.16 (m, 1H), 4.78 (dd, J ) 6.8, 6.8 Hz,
1H), 7.20-7.30 (m, 5H), 7.83 (d, J ) 8.9 Hz, 2H), 8.24 (d, J )
9.2 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 22.46 (p), 32.19 (s),
34.71 (s), 58.08 (t), 65.39 (t), 123.94 (t), 126.55 (t), 127.45 (t),
128.43 (t), 128.57 (t), 141.41 (q), 144.87 (q), 149.81 (q). Anal.
Calcd for C17H18N2O4S: C, 58.95; H, 5.24; N, 8.09. Found: C,
58.96; H, 4.95; N, 7.85. (tr a n s): mp 113.0-114.0 °C; IR (KBr)
C
14H10F3NO2S: C, 53.67; H, 3.22; N, 4.47. Found: C, 53.56;
H, 2.97; N, 4.19.
N-(Tr iflu or om et h a n esu lfon yl)-2,3-d ih yd r on a p h t h o-
[2,1-e]m or p h olin e (2r ): mp 104.0-106.0 °C; IR (KBr) 1580,
1480, 1380, 1220, 1180, 1120 cm-1; 1H NMR (400 MHz, CDCl3)
δ 4.04 (t, J ) 4.5 Hz, 2H), 4.58 (t, J ) 4.6 Hz, 2H), 7.40 (d, J
) 9.3 Hz, 1H), 7.47-7.53 (m, 2H), 7.64 (d, J ) 9.0 Hz, 1H),
7.74-7.78 (m, 1H), 8.14-8.17 (m, 1H); MS (EI) M+ 317. Anal.
Calcd for C13H10F3NO3S: C, 49.21; H, 3.18; N, 4.41. Found:
C, 49.17; H, 3.19; N, 4.36.
1600, 1520, 1350, 1160 cm-1 1H NMR (400 MHz, CDCl3) δ
;
1.49 (d, J ) 6.3 Hz, 3H), 1.69-1.74 (m, 1H), 1.79-1.85 (m,
1H), 2.29-2.40 (m, 1H), 2.50-2.62 (m, 1H), 4.30-4.37 (m, 1H),
5.01 (dd, J ) 8.9, 1.2 Hz, 1H), 6.94 (d, J ) 7.7 Hz, 2H), 7.06 (t,
J ) 7.4 Hz, 2H), 7.14 (t, J ) 6.6 Hz, 1H), 7.52 (d, J ) 9.2 Hz,
2H), 8.02 (d, J ) 8.9 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ
22.31 (p), 31.89 (s), 32.92 (s), 58.20 (t), 63.70 (t), 123.41 (t),
126.95 (t), 127.37 (t), 128.86 (t), 128.17 (t), 141.19 (q), 147.20
(q), 149.10 (q).
N-(Tr iflu or om eth an esu lfon yl)-2,3-dih ydr o-4′-iodon aph -
th o[2,1-e]m or p h olin e (2r -I): mp 72.5-73.5 °C; IR (KBr)
1600, 1400, 1230, 1200, 1180, 1140, 1120, 1090, 1020 cm-1
;
1H NMR (400 MHz, CDCl3) δ 4.02 (t, J ) 4.5 Hz, 2H), 4.59 (t,
J ) 4.6 Hz, 2H), 7.53 (t, J ) 7.6 Hz, 1H), 7.59 (t, J ) 7.6 Hz,
2H), 7.99 (d, J ) 8.4 Hz, 1H), 8.14 (d, J ) 7.7 Hz, 1H), 8.22 (s,
1H); HRMS (EI) found M+ 442.9296, calcd for C13H9F3NO3SI
M 442.9300.
N-(4-Meth oxyph en yl)sacch ar in (11a ′) (or th o, par a m ix-
tu r e): IR (KBr) 3080, 2840, 1740, 1520, 1340, 1180 cm-1; 1H
NMR (400 MHz, CDCl3) δ 3.84 (s), 3.87 (s), 7.06 (d, J ) 9.0
Hz), 7.08-7.12 (m), 7.43 (d, J ) 9.0 Hz), 7.48-7.55 (m), 7.85-
7.96 (m), 8.00 (d, J ) 8.1 Hz), 8.15 (d, J ) 7.8 Hz); HRMS (EI)
found M+ 289.0419, calcd for C14H11NO4S M 289.0419.
N-(4-Meth ylp h en yl)sa cch a r in (11b ′) (or th o, p a r a m ix-
tu r e): IR (KBr) 3100, 1740, 1460, 1340, 1320, 1180 cm-1; 1H
NMR (400 MHz, CDCl3) δ 2.32 (s), 2.43 (s), 7.34-7.46 (m),
7.87-7.94 (m), 7.98-8.02 (m); HRMS (EI) found M+ 273.0461,
calcd for C14H11NO3S M 273.0460.
N-(Tr iflu or om eth a n esu lfon yl)-4-[4′-(tr iflu or om eth yl)-
p h en yl]-7-m eth yl-1,2,3,4-tetr a h yd r oqu in olin e (2s-I): oil;
IR (neat) 2940, 1620, 1500, 1400, 1330, 1200, 1130, 1070 cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.09-2.19 (m, 1H), 2.34 (s, 3H),
2.40-2.49 (m, 1H), 3.79-3.86 (m, 1H), 3.98-4.04 (m, 1H), 4.27
(dd, J ) 7.7, 7.7 Hz, 1H), 6.75 (d, J ) 8.0 Hz, 1H), 6.93 (d, J
) 7.7 Hz, 1H), 7.23 (d, J ) 8.0 Hz, 2H), 7.43 (s, 1H), 7.58 (d,
J ) 8.0 Hz, 2H); HRMS (EI) found M+ 423.0716, calcd for
C
18H15F6NO2S M 423.0728.
4-[4′-(Tr iflu or om et h yl)p h en yl]-6-iod o-7-m et h ylch r o-
N-P h en ylsa cch a r in (11c′): mp 189.0-191.0 °C; IR (KBr)
1740, 1720, 1590, 1340, 1300, 1180 cm-1; 1H NMR (400 MHz,
CDCl3) δ 7.51-7.58 (m, 5H), 7.88 (t, J ) 7.1 Hz, 1H), 7.93 (t,
J ) 7.5 Hz, 1H), 8.00 (d, J ) 7.8 Hz, 1H), 8.16 (d, J ) 7.6 Hz,
1H); 13C NMR (125 MHz, CDCl3) δ 121.20 (t), 125.61 (t), 127.17
(q), 128.74 (t), 129.90 (t), 130.08 (t), 134.43 (t), 135.06 (t),
137.60 (q), 158.37 (q); MS (EI) M+ 259. Anal. Calcd for C13H9-
NO3S: C, 60.22; H, 3.50; N, 5.40; S, 12.37. Found: C, 59.89;
H, 3.48; N, 5.37; S, 12.29.
N-(4-Ch lor op h en yl)sa cch a r in (11d ′) (or th o, p a r a m ix-
tu r e): IR (KBr) 3100, 1740, 1490, 1340, 1320, 1190 cm-1; 1H
NMR (400 MHz, CDCl3) δ 7.42-7.56 (m), 7.57-7.65 (m), 7.85-
8.04 (m), 8.13-0.20 (m); HRMS (EI) found M+ 294.9898, calcd
for C13H8NO3S37Cl M 294.9886.
N-(4-Nitr op h en yl)sa cch a r in (11e′) (m eta , m a jor ): mp
153.0-156.0 °C; IR (KBr) 3100, 2920, 1740, 1520, 1350, 1300,
1190 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.73-7.78 (m), 7.82-
7.87 (m), 7.90-8.05 (m), 8.17-8.28 (m), 8.37-8.44 (m), 8.48
(s); HRMS (EI) found M+ 304.0129, calcd for C12H8N2O5S M
304.0154.
m a n e (5): mp 94.5-95.5 °C; IR (KBr) 2950, 1620, 1550, 1320,
1
1070 cm-1; H NMR (500 MHz, CDCl3) δ 1.98-2.07 (1H, m,
3-H), 2.25-2.32 (1H, m, 3-H), 2.35 (3H, s, CH3), 4.08-4.22 (3H,
m, 2, 4-H), 6.81 (1H, s, 8-H) 7.19 (1H, s, 5-H), 7.24 (2H, d, J )
8.1 Hz, 2′, 6′-H), 7.57 (2H, d, J ) 8.1 Hz, 3′, 5′-H); 13C NMR
(125 MHz, CDCl3) δ 27.70 (p, CH3), 31.35 (s, 3-C), 40.21 (t,
4-C), 63.53 (s, 2-C), 89.63 (q, 6-C), 118.36 (t, 8-C), 123.39 (q,
10-C), 125.59 (t, 3′, 5′-C), 128.87 (t, 2′, 6′-C), 139.90 (t, 5-C),
141.33 (q, 1′-C), 149.10 (q, 7-C), 155.37 (q, 9-C); HRMS (FAB)
found M+ 418.0025, calcd for C17H14OF3I M 418.0042. Anal.
Calcd for C17H14OF3I: C, 48.82; H, 3.37. Found: C, 48.86; H,
3.28.
N-(Tr iflu or om eth a n esu lfon yl)-1,2,3,4-tetr a h yd r oqu in -
olin e-6-ca r boxylic a cid (7): mp 153.0-155.0 °C; IR (KBr)
3000, 1700, 1610, 1380, 1200 cm-1; 1H NMR (500 MHz, CDCl3)
δ 2.15 (quint, J ) 6.3 Hz, 2H, 3-H), 2.96 (t, J ) 6.8 Hz, 2H,
4-H), 3.93 (t, J ) 5.9 Hz, 2H, 2-H), 7.67 (d, J ) 9.3 Hz, 1H,
5-H), 7.93-7.95 (m, 2H, 7,8-H); 13C NMR (125 MHz, CDCl3) δ
22.95 (s, 3-C), 26.42 (s, 4-C), 48.27 (s, 2-C), 120.10 (q, J C-F
328 Hz, q, CF3), 122.89 (t), 126.50 (q), 128.77 (t), 130.42 (q),
131.74 (t), 140.12 (q), 171.39 (q, CO2H). Anal. Calcd for
)
N-(1-Na p h th yl)sa cch a r in (11f ′): mp 219.0-221.0 °C; IR
(KBr) 3080, 1740, 1600, 1500, 1480, 1400, 1340, 1300, 1180
1
C
11H10NO4S: C, 40.41; H, 3.39; N, 4.71; S, 10.79. Found: C,
41.85; H, 3.23; N, 4.74; S, 10.36.
cm-1; H NMR (400 MHz, CDCl3) δ 7.53-7.58 (m, 2H), 7.62
(t, J ) 7.8 Hz, 1H), 7.70 (d, J ) 7.3 Hz, 1H), 7.83-7.86 (m,

5200 J . Org. Chem., Vol. 63, No. 15, 1998
Togo et al.
1H), 7.90-7.99 (m, 3H), 8.05-8.08 (m, 2H), 8.21 (d, J ) 7.6
Hz, 1H); MS (EI) M+ 309. Anal. Calcd for C17H11NO3S: C,
66.01; H, 3.58; N, 4.53. Found: C, 66.02; H, 3.43; N, 4.46.
N-(3-Ben zoth ien yl)sa cch a r in (11g′): mp 209-210 °C; IR
(KBr) 3100, 1740, 1440, 1340, 1290, 1260, 1180 cm-1; 1H NMR
(400 MHz, CDCl3) δ 7.41-7.45 (m, 2H), 7.61 (s, 1H), 7.83-
7.87 (m, 2H), 7.93 (t, J ) 7.1 Hz, 1H), 7.97 (t, J ) 7.9 Hz, 1H),
8.04 (d, J ) 6.8 Hz, 1H), 8.21 (d, J ) 7.7 Hz, 1H); HRMS (EI)
found M+ 315.0039, calcd for C15H9NO3S2 M 315.0024.
N -M e t h y l-N -p h e n y l-4-n i t r o b e n z e n e s u lfo n a m i d e
(12h ′): mp 117.0-118.5 °C; IR (KBr) 1610, 1520, 1350, 1300,
3.27 (s), 6.80 (d, J ) 8.3 Hz), 6.93-6.96 (m), 7.12 (d, J ) 7.8
Hz), 7.20 (t, J ) 7.7 Hz), 7.72-7.76 (m), 8.29-8.32 (m); HRMS
(EI) found M+ 303.0663, calcd for C14H14N2O4S M 306.0673.
N-(Ch lor op h en yl)-N-m et h yl-4-n it r ob en zen esu lfon a -
m id e (13o′) (or th o, m eta , p a r a m ixtu r e): IR (KBr) 3100,
1600, 1520, 1480, 1350, 1160 cm-1; 1H NMR (400 MHz, CDCl3)
(or th o) δ 3.30 (s, 3H), 7.29-7.35 (m, 3H), 7.38-7.42 (m, 1H),
7.94 (d, J ) 9.0 Hz, 2H), 8.35 (d, J ) 8.8 Hz, 2H): (or th o,
m eta , p a r a m ixtu r e) δ 3.21 (s), 3.22 (s), 3.30 (s), 6.98-7.05
(m), 7.12-7.14 (m), 7.26-7.35 (m), 7.37-7.42 (m), 7.72-7.77
(m), 7.72-7.76 (m), 7.90-7.96 (m), 8.29-8.37 (m); HRMS (EI)
found M+ 328.0091, calcd for C13H11N2O4S37Cl M 328.0101.
N-(2′,5′-Dim et h ylp h en yl)-N-m et h yl-4-n it r ob en zen e-
su lfon a m id e (13p ′): mp 116.0-168.0 °C; IR (KBr) 3100,
2920, 1600, 1530, 1350, 1320, 1170 cm-1; 1H NMR (400 MHz,
CDCl3) δ 2.18 (s, 3H), 2.30 (s, 3H), 3.18 (s, 3H), 6.38 (s, 1H),
7.06 (d, J ) 6.8 Hz, 1H), 7.18 (d, J ) 7.8 Hz, 1H), 7.91 (d, J )
9.0 Hz, 2H), 8.37 (d, J ) 9.0 Hz, 2H); MS (EI) M+ 320. Anal.
Calcd for C15H16N2O4S: C, 56.24; H, 5.03; N, 8.74. Found: C,
55.86; H, 4.79; N, 8.64.
1
1150 cm-1; H NMR (400 MHz, CDCl3) δ 3.24 (s, 3H), 7.07-
7.10 (m, 2H), 7.31-7.36 (m, 3H), 7.73 (d, J ) 8.8 Hz, 2H), 8.30
(d, J ) 9.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 38.32 (p),
123.94 (t), 126.53 (t), 127.92 (t), 128.91 (t), 129.19 (t), 140.54
(q), 142.27 (q), 150.90 (q); MS (EI) M+ 292. Anal. Calcd for
C
13H12N2O4S: C, 53.41; H, 4.14; N, 9.58. Found: C, 53.25; H,
3.96; N, 9.54.
N-Eth yl-N-p h en yl-4-n itr oben zen esu lfon a m id e (12i′):
mp 120.0-122.0 °C; IR (KBr) 3100, 3000, 1600, 1520, 1350,
1310, 1180 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.12 (t, J ) 7.2
Hz, 3H), 3.66 (q, J ) 7.2 Hz, 2H), 7.02-7.06 (m, 2H), 7.33-
7.36 (m, 3H), 7.78 (d, J ) 8.8 Hz, 2H), 8.31 (d, J ) 9.0 Hz,
2H); MS (EI) M+ 306. Calcd for C14H14N2O4S: C, 54.89; H,
4.61; N, 9.11. Found: C, 54.79; H, 4.46; N, 9.08.
Ack n ow led gm en t. H.T. is grateful for Financial
support from a Grant-in-Aid for Scientific Research
(08640670) and a Grant-in-Aid for Developmental Sci-
entific Research (08554031) from the Ministry of Educa-
tion, Science, and Culture of J apan. The authors thank
Ms. Ritsuko Hara for measurement of HRMS and Dr.
Hiroko Seki for measurement of elemental analysis in
Chemical Analysis Center of Chiba Unibersity.
N-Bu tyl-N-p h en yl-4-n itr oben zen esu lfon a m id e (12j′):
mp 93.0-95.0 °C; IR (KBr) 3100, 2960, 1590, 1530, 1350, 1160,
1
1080 cm-1; H NMR (400 MHz, CDCl3) δ 0.88 (t, J ) 7.2 Hz,
3H), 1.24-1.47 (m, 4H), 3.58 (t, J ) 7.0 Hz, 2H), 7.00-7.05
(m, 2H), 7.33-7.36 (m, 3H), 7.76 (d, J ) 8.8 Hz, 2H), 8.30 (d,
J ) 8.8 Hz, 2H); HRMS (EI) found M+ 334.0970, calcd for
C
16H18N2O4S M 334.0987.
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
N-Meth yl-N-(4-m eth ylp h en yl)-4-n itr oben zen esu lfon a -
spectra for all compounds described (48 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
m id e (13n ′) (or th o, m eta , p a r a m ixtu r e): IR (KBr) 3010,
1600, 1520, 1350, 1160 cm-1 1H NMR (400 MHz, CDCl3)
;
(or th o) δ 2.39 (s, 3H), 3.20 (s, 3H), 6.54 (d, J ) 7.8 Hz, 1H),
7.08 (t, J ) 7.6 Hz, 1H), 7.25 (t, J ) 6.8 Hz, 1H), 7.31 (d, J )
6.6 Hz, 1H), 7.90 (d, J ) 8.8 Hz, 2H), 8.37 (d, J ) 8.8 Hz, 2H):
(m eta a n d p a r a 1:1 m ixtu r e) δ 2.33 (s), 2.35 (s), 3.21 (s),
J O980450Y