Synthesis of cyclic dienamide using ruthenium-catalyzed ring-closing metathesis of ene-ynamide

Article abstract of DOI:10.1016/j.tet.2005.11.083

Ring-closing metathesis of ene-ynamide, which has alkene and ynamide moieties in a molecule, using a second-generation ruthenium carbene complex produced nitrogen-containing heterocycles, which have a dienamide moiety, in high yields. Diels-Alder reaction

Full text of DOI:10.1016/j.tet.2005.11.083

Tetrahedron 62 (2006) 3872–3881
Synthesis of cyclic dienamide using ruthenium-catalyzed
ring-closing metathesis of ene–ynamide
b
c
c
b
Miwako Mori,a, Hideaki Wakamatsu, Nozomi Saito, Yukako Sato, Rie Narita,
*
Yoshihiro Satoc, and Reiko Fujita
b
*
aHealth Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
bTohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
cGraduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Received 14 November 2005; accepted 26 November 2005
Available online 28 February 2006
Abstract—Ring-closing metathesis of ene–ynamide, which has alkene and ynamide moieties in a molecule, using a second-generation
ruthenium carbene complex produced nitrogen-containing heterocycles, which have a dienamide moiety, in high yields. Diels–Alder reaction
of the cyclized product with dienophile proceeded smoothly to give an indole or quinoline derivative in high yield.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Ynamide is an interesting moiety because nitrogen is
conjugated with an alkyne part.4 Thus, the metathesis of
ene–ynamide, which has an electron-rich ynamide moiety
and an alkene moiety in a molecule, is interesting. If the
reaction of ene–ynamide I with ruthenium carbene complex
1 proceeds, ruthenacyclobutene III would be formed and
ring opening of III would give ruthenium carbene complex
IV, whose ruthenium carbene would react with an alkene
intramolecularly to give ruthenacyclobutane V. Ring open-
ing of this would give cyclic dienamide II, which should be
reactive toward an electron-deficient agent or a dienophile
in the Diels–Alder reaction (Scheme 2).5
A transition metal carbene complex-catalyzed olefin, enyne,
and diyne metatheses are recognized as powerful and useful
methodologies in synthetic organic chemistry.1 Ring-
closing metathesis (RCM), ring-opening metathesis
(ROM), and cross-metathesis (CM) are now widely used
for the synthesis of complex molecules, including natural
products and biologically active substances. An intra-
molecular enyne metathesis is a particularly interesting
reaction because carbon–carbon bond formation occurs
between the double and triple bonds and the double bond of
the enyne is cleaved, and the cleaved alkylidene part of the
double bond migrates to the alkyne carbon to afford a
cyclized compound having a diene moiety (Scheme 1).2 We
have recently developed enyne metathesis using a Grubbs’
ruthenium carbene complex 1 and have reported some
applications, including natural product synthesis.3
The starting ene–ynamides were synthesized according to
the procedure shown in Scheme 3.6 Coupling reaction of
N-tosylformamide 2a and alcohol 3 in the presence of
DEAD and PPh3 followed by treatment with CCl4 and PPh3
gave 4a or 6a, which was treated with BuLi to give desired
ene–ynamides 5a and 7a in high yields, respectively. In a
similar manner, ene–ynamide 7b was synthesized from 2a
and alcohol 3c. Ene–ynamides 5b, 7c, and 7d having an aryl
group on an alkyne were synthesized using Negishi-
coupling reaction of the alkynylzinc of the terminal alkyne
and ArX in the presence of palladium catalyst.7 An
ethoxycarbonyl group on the alkyne of ene–ynamide 5c
was introduced by treatment of 4a with BuLi and then
ClCO2Et. Ene–ynamides E-5d and Z-5d having a sub-
stituent on the alkene were prepared from 2b and alcohol
E-3d or Z-3d by a procedure similar to that used for the
synthesis of 5a, 7a and 7b.8
Scheme 1. Ring-closing enyne metathesis.
Keywords: Ene–ynamide; Dienamide; Enyne metathesis; Indole; Quino-
line; Ethylene.
Corresponding authors. Tel.: C81 11 706 4982; fax: C81 11 706 4982
(M.M.); (Y.S.); e-mail: mori@pharm.hokudai.ac.jp
*
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.11.083

M. Mori et al. / Tetrahedron 62 (2006) 3872–3881
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Scheme 2. Plan for synthesis of cyclic dienamide using RCM.
2. Results and discussion
2.1. Synthesis of dihydropyrrolidine derivatives using
RCM of ene–ynamide
When a CH2Cl2 solution of ene–ynamide 5a was stirred in
the presence of 5 mol% of the first-generation ruthenium
carbene complex 1a9a under ethylene gas3e at rt for 24 h,
desired cyclic compound 12a having a dienamide moiety
was obtained in 10% yield along with the starting material
in 35% yield. Although the yield was low, it is clear that
cyclic dienamide 12a was obtained from 5a using RCM
(Scheme 4).
To improve the yield of the desired compound, the reaction
was carried out under various conditions. The yield of 12a
was further decreased when the CH2Cl2 solution was
refluxed overnight (entry 2). However, interestingly, the
use of the second-generation ruthenium carbene complex
1b9b instead of 1a improved the yield of 12a to 66% and the
reaction time was shortened (entry 3). Toluene can be used
as a solvent, and the reaction was carried out at 80 8C for
only 15 min to give 12a in 83% yield (entry 4).10 The yield
was slightly decreased when the reaction was carried out
under argon gas (entry 5) (Table 1).11
Scheme 3. Synthesis of various ene–ynamides.
The substituent effect on the enyne, especially that on the
alkyne, was interesting. The substituent effect on the alkyne
was first examined. Ene–ynamide 5b having a phenyl group
on the alkyne gave cyclic dienamide 12b in 85% yield when
the reaction was carried out using 10 mol% of 1b at 80 8C in
toluene under ethylene gas. (Table 2, entry 1). Even 5 mol%
of the catalyst gave a good result (entry 2). In this case,
ethylene gas was effective because the yield was decreased
to 31% when the reaction was carried out under argon (entry
3). The electron-withdrawing group on the alkyne tolerates
in this reaction and desired cyclic compound 12c was
obtained from 5c having an ethoxycarbonyl group on the
alkyne in 87% yield after only 30 min.
Scheme 4. Synthesis of cyclic dienamide.
Next, the substituent effect on the alkene was examined.
When a toluene solution of ene–ynamide Z-5d was warmed
at 80 8C for 15 min under ethylene gas, surprisingly, cyclic
dienamide 12a, which was previously obtained from 5a,
was obtained in 66% yield. Presumably, the methylidene
carbene complex generated from 1b and ethylene reacts
with an alkyne part of Z-5d to give ruthenacyclobutene VI,

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M. Mori et al. / Tetrahedron 62 (2006) 3872–3881
Table 1. Ring-closing metathesis of 5a using 1a or 1ba
Entry
Catalyst
Solvent
Temperature (8C)
Time (h)
Yield of 12a (%)
1
2
3
1a
1a
1b
1b
1b
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
Toluene
rt
24
24
4
0.25
0.5
10b
7b
66
83
76
Reflux
Reflux
80
4
5c
80
a All reactions were carried out using 5 mol% of the catalyst under ethylene atmosphere except entry 5.
b Starting material 5a was recovered in 35% (run 1) and 36% (run 2) yields, respectively.
c The reaction was carried out under Ar.
Table 2. Synthesis of various cyclic using 1b
Entry
R
1b (mol%)
Atmosphere
Time (h)
Yield of 12 (%)
1
2
3
4
Ph
Ph
Ph
CO2Et
5b
5b
5b
5c
10
5
5
CH2]CH2
CH2]CH2
Ar
0.25
0.5
22
0.5
85
78
31a
87
5
CH2]CH2
a Starting material was recovered in 47% yield.
which converts into ruthenium carbene complex VII. Then
intramolecular reaction occurs to give ruthenacyclobutane
VIII, whose ring opening gives 12a and propylidene
carbene complex IX. However, this complex IX would
react with ethylene to form methylidene ruthenium carbene
complex and propene. Thus, the real species in this reaction
would be methylidene ruthenium carbene complex, not
propylidene carbene complex IX, and 12a would therefore
be formed from Z-5d (Scheme 5).
the catalyst increased the yield of 12d, and the ratio to
E- to Z- was 1–4.1 (entry 2). However, a longer reaction
time did not improve the yield of 12d (entry 3). From E-5d,
the same compound 12d was obtained in 48% yield, and the
isomeric ratio was 1.5–1. In this case, the use of 5 mol% of
the catalyst also increased the yield of 12d to 57% with a
ratio to 1–2.6. These results indicated that a smaller amount
of the catalyst improved the yield and that the ratio of
the Z-isomer of the product was raised, but the reason for
this is not clear.
2.2. Synthesis of piperidine derivatives using metathesis
of ene–ynamide
Since the synthesis of dihydropyrrole derivative 12 from
ene–ynamide 5 was achieved, the reaction of ene–ynamide
7, which has a one-carbon elongated substituent on nitrogen,
using 1b was carried out. In this case, tetrahydropiperidine
derivative 13 would be produced. When a toluene solution
of 7a was warmed in the presence of 5 mol% of 1b under
ethylene gas at 80 8C for 20 h, desired piperidine derivative
13a was obtained, though the yield was low (entry 1). A
lower reaction temperature decreased the yield of 13a
(entry 2). When the solvent was changed from toluene to
CH2Cl2, the yield of desired compound 13a was slightly
improved (entry 3), and an increase of the amount of the
catalyst 1b to 10 mol% increased the yield of 13a to 85%
(entry 4). The same reaction was carried out under argon gas
to afford 13a in almost the same yield (entry 5). Cyclic
dienamide 13b was obtained from ene–ynamide 7b using
these reaction conditions under ethylene gas in 61% yield
(entry 6). Ene–ynamide 7c having a phenyl group on the
alkyne was treated in a similar manner to give cyclic
dienamide 13c in 76% yield (entry 7). In this case, the use of
toluene as a solvent improved the yield of 13c (entry 8).
Scheme 5. Synthesis of cyclic dienamide from ene–ynamide having a
substituent on alkene.
Thus, the reaction of Z-5d and 1b was carried out under
argon gas, and a mixture of desired cyclic dienamides E-12d
and Z-12d was obtained in 39% yield in a ratio to 1 to 1
(Table 3, entry 1). The use of a smaller amount of

M. Mori et al. / Tetrahedron 62 (2006) 3872–3881
3875
Table 3. Reaction of E-5d or Z-5d with 1b
then DMAD was added after cooling. The toluene solution
was warmed at 60 8C for 12 h under argon to give desired
indole derivative 14a in 80% yield. Furthermore, when
1-phenyl-1H-pyrrole-2,5-dione was used as a dienophile,
tricyclic compound 15 was obtained in 68% yield. In a
similar manner, Z-5d was stirred in the presence of 1b in
toluene, and then to the toluene solution was added DMAD
and the whole solution was warmed at 100 8C for 3 h. The
resultant product was treated with DDQ in toluene at 80 8C
for 20 h to give indoline 16 and indole 17 derivatives in 20
and 12% yields, respectively, via three steps (Scheme 6).
Entry
Substrate
cat.
(mol%)
Yield (%)
Ratio of 12d
(E/Z)
1
Z-5d
Z-5d
Z-5d
E-5d
E-5d
10
5
5
10
5
39
48
41
48
57
1:1
Furthermore, synthesis of quinoline derivatives was
examined. A toluene solution of cyclic dienamide 13a and
DMAD was heated at 100 8C for 12 h to give quinoline
derivative 18b in 71% yield. On the other hand, to a toluene
solution of the reaction product 13a, obtained from 7a using
10 mol% of 1b, was added DMAD and the solution was
heated at 100 8C for 12 h to give quinoline derivative 18a in
57% yield (Scheme 7).
2
1:4.1
1:5.9
1.5:1
1:2.6
3a
4
5
a Reaction time, 30 min.
However, ene–ynamide 7d having an ortho-bromophenyl
group on the alkyne did not give a good result even when
20 mol% of the catalyst was used due to the steric hindrance
(entry 9) (Table 4).
These results indicated that indole and quinoline deriva-
tives, which are important skeletons in natural products or
biologically active substances, could be synthesized from
ene–ynamide using RCM followed by Diels–Alder reaction
as a one-pot reaction. The reason why the reaction of the
isolated product 12a or 13a gave isomerization product 14b
or 18b of the double bond is not clear.
Thus, a cyclic dienamide could be synthesized from ene–
ynamide using ring-closing enyne metathesis.
2.3. Synthesis of indole and quinoline derivatives from
cyclic dienamide by Diels–Alder reaction
Since the products obtained by the present RCM reaction
have a dienamide moiety, they should be good Diels–Alder
precursors. A toluene solution of 12a was warmed at 60 8C
in the presence of dimethyl but-2-ynedioate (DMAD) to
give tetrahydroindole derivatives 14a and 14b in 52% yield
in a ratio of 1.3–1. Compound 14b is an isomerization
product of the double bond of 14a. Since the cyclic
dienamide is unstable, a one-pot reaction from ene–ynamide
5a was examined. A toluene solution of 5a and 10 mol% of
1b was stirred under ethylene gas at 80 8C for 15 min, and
3. Conclusions
Since an alkyne part of ynamide is conjugated with nitrogen,
the reactivity of ynamide is very interesting. It was expected
that metathesis of enyne containing ynamide would give a
cyclic dienamide, whose reactivity is also interesting. Thus,
metathesis of enyne containing ynamide was examined. As
a result, cyclic dienamides were obtained from ene–
ynamide using the second-generation ruthenium carbene
Table 4. Ring-closing metathesis of 7 using catalyst 1b
Entry
Substrate
1b (mol%)
Solvent
Temperature (8C)
Product
Time (h)
Yield (%)
1
2
3
4
5b
6
7
8
9
7a
7a
7a
7a
7a
7b
7c
7c
7d
5
5
5
10
10
10
10
5
Toluene
Toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
Toluene
80
60
13a
13a
13a
13a
13a
13b
13c
13c
13d
20
20
27
6
5
6
70
0.5
41
22
19a
36a
85
Reflux
Reflux
Reflux
Reflux
Reflux
80
82
61
76
88
20
80
34a
a Starting material was recovered in 20% (run 2), 38% (run 3) and 23% (run 9) yields, respectively.
b The reaction was carried out under Ar.

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M. Mori et al. / Tetrahedron 62 (2006) 3872–3881
was purified by passage through the aqueous CuCl solution
(2 g of CuCl in 180 mL of saturated NH4Cl solution) and
concentrated H2SO4 and then KOH tubes. Ruthenium
complexes were purchased from Strem Chemicals or
Aldrich Chemical Company. All other solvents and reagents
were purified when necessary using standard procedure.
4.2. Typical procedure for the metathesis reaction
A solution of 5a (91.5 mg, 0.37 mmol) and 1b (15.6 mg,
0.018 mmol) in toluene was stirred at 80 8C for 15 min
under ethylene atmosphere (1 atm). After the solution was
cooled to rt, a few drops of ethyl vinyl ether was added. The
solvent was removed under reduced pressure and the residue
was purified by flash column chromatography on silica gel
(hexane/Et2O/Et3N 100:5:1) to give 12a (76.2 mg, 83%) as
colorless oil.
4.3. Spectral data of metathesis products
4.3.1. 1-p-Toluenesulfonyl-5-vinyl-2,3-dihydro-1H-
pyrrole (12a). IR (neat) n 1647, 1589, 1343, 1147 cmK1
;
1H NMR (270 MHz, CDCl3) d 2.10 (ddd, JZ8.4, 8.4,
3.0 Hz, 2H), 2.40 (s, 3H), 3.77 (dd, JZ8.4, 8.4 Hz, 2H),
5.20 (d, JZ10.8 Hz, 1H), 5.35 (dd, JZ3.0, 3.0 Hz, 1H),
5.53 (d, JZ17.6 Hz, 1H), 6.60 (dd, JZ17.6, 10.8 Hz, 1H),
7.26 (d, JZ8.4 Hz, 2H), 7.64 (d, JZ8.4 Hz, 2H); 13C NMR
(67.8 MHz, CDCl3) d 21.5, 27.5, 50.5, 103.9, 113.5, 117.0,
127.9, 128.8, 129.5, 133.9, 143.6; EI-LRMS m/z 249 (MC),
184, 155, 91; EI-HRMS m/z calcd for C13H15O2NS (MC)
249.0823, found 149.0831.
Scheme 6. Synthesis of indole derivatives.
4.3.2. 5-(1-Phenyl-vinyl)-1-p-toluenesulfonyl-2,3-dihydro-
1H-pyrrole (12b). IR (KBr) n 1597 (w), 1350 (m), 1167
1
(s) cmK1; H NMR (270 MHz, CDCl3) d 2.12 (dt, JZ2.9,
8.3 Hz, 2H), 2.42 (s, 3H), 3.95 (t, JZ8.3 Hz, 2H), 5.48 (t, JZ
2.9 Hz, 1H), 5.50 (s, 2H), 7.25–7.43 (m, 7H), 7.68 (d, JZ
8.4 Hz, 2H); 13C NMR (67.8 MHz, CDCl3) d 21.5, 28.0, 51.2,
116.5, 119.8, 127.1, 127.7, 127.8, 128.1, 129.4, 134.6, 138.9,
142.2, 143.6, 144.5; EI-LRMS m/z 325 (MC), 260, 246, 186,
168, 103, 91; EI-HRMS m/z calcd for C19H19O2NS (MC)
325.1137, found 325.1147.
Scheme 7. Synthesis of quinoline derivatives.
4.3.3. Ethyl 2-(1-p-toluenesulfonyl-4,5-dihydro-1H-
pyrrol-2-yl)-acrylate (12c). IR (KBr) n 1721 (s), 1598
(m), 1352 (s), 1164 (s) cmK1; 1H NMR (270 MHz, CDCl3) d
1.36 (t, JZ7.1 Hz, 3H), 2.18 (dt, JZ2.8, 8.7 Hz, 2H), 2.43
(s, 3H), 3.85 (t, JZ8.7 Hz, 2H), 4.31 (q, JZ7.1 Hz, 2H),
5.44 (t, JZ2.8 Hz, 1H), 5.88 (d, JZ1.3 Hz, 1H), 6.29 (d,
JZ1.3 Hz, 1H), 7.30 (d, JZ8.2 Hz, 2H), 7.66 (d, JZ
8.2 Hz, 2H); 13C NMR (67.8 MHz, CDCl3) d 14.1, 21.5,
28.0, 50.2, 61.2, 118.4, 127.2, 127.8, 129.5, 133.9, 134.8,
140.6, 143.7, 165.2; EI-LRMS m/z 321 (MC), 276, 182,
166, 155, 120, 92; EI-HRMS m/z calcd for C16H19O4NS
(MC) 321.1035, found 321.1010.
complex. The cyclic dienamide is good precursor toward the
Diels–Alder reaction and afforded an indole or quinoline
derivative under mild conditions in high yield. These
compounds are important skeletons of natural products or
biologically active substances. Further investigations of
RCM of ene–ynamide should give various interesting
compounds.
4. Experimental
4.1. General
4.3.4. 5-But-1-enyl-1-p-toluenesulfonyl-2,3-dihydro-1H-
pyrrole (12d). IR (neat) n 2964, 1598, 1351, 1164 cmK1; 1H
NMR (270 MHz, CDCl3) d 1.03 (t, JZ7.4 Hz, 1.5H), 1.09
(t, JZ7.4 Hz, 1.5H), 2.08–2.31 (m, 4H), 2.42 (s, 3H), 3.76
(t, JZ8.2 Hz, 1H), 3.78 (t, JZ7.8 Hz, 1H), 5.10 (t, JZ
2.8 Hz, 0.5H), 5.22 (t, JZ2.8 Hz, 0.5H), 5.73 (dt, JZ11.5,
7.1 Hz, 0.5H), 6.07 (dt, JZ15.8, 6.3 Hz, 0.5H), 6.24
The metathesis reactions were carried out under an
atmosphere of ethylene (1 atm) unless otherwise mentioned.
All other manipulations were carried out under an
atmosphere of argon unless otherwise mentioned. Solvents
were distilled under an atmosphere of argon from sodium–
benzophenone (toluene) or CaH2 (CH2Cl2). Ethylene gas

M. Mori et al. / Tetrahedron 62 (2006) 3872–3881
3877
(m, 1H), 7.27 (m, 2H), 7.69 (m, 2H); EI-LRMS m/z 277
(MC), 198, 184, 155, 122, 91; EI-HRMS m/z calcd for
C15H19O2NS (MC) 277.1136, found 277.1144.
(1.5 mL, 17 mmol) and DEAD (2.7 mL, 17 mmol) at 0 8C,
and the mixture was stirred at rt for 14 h. After the solvent
was evaporated, the residue was purified by short column
chromatography on silica gel (hexane/AcOEt 10:1) to give
an inseparable mixture of N-alkylated product and
O-alkylated product (2.9 g, in the ratio of 1.3:1). To a
solution of the above mixture (2.9 g) in THF (38 mL) were
added PPh3 (9.0 g, 35 mmol) and CCl4 (11 mL, 115 mmol)
at rt, and the mixture was stirred at 60 8C for 6 h. To the
mixture was added saturated NaHCO3 solution, and the
aqueous layer was extracted with Et2O. The organic layer
was washed with saturated NaCl solution, dried over
Na2SO4, and concentrated. The residue was purified by
flash column chromatography on silica gel (hexane/AcOEt
20:1) to give 4a (1.9 g, 42%, two steps) as a colorless
crystal. Mp 53–55 8C; IR (Nujol) n 1642, 1597, 1357,
1165 cmK1; 1H NMR (400 MHz, CDCl3) d 2.28 (dt, JZ6.8,
7.3 Hz, 2H), 2.44 (s, 3H), 3.41 (t, JZ7.3 Hz, 2H), 5.05 (d,
JZ10.2 Hz, 1H), 5.08 (d, JZ17.0 Hz, 1H), 5.70 (ddt, JZ
17.0, 10.2, 6.8 Hz, 1H), 6.31 (s, 1H), 7.32 (d, JZ8.1 Hz,
2H), 7.68 (d, JZ8.1 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 21.6, 32.9, 48.5, 117.4, 124.1, 124.7, 127.1, 129.7, 133.9,
135.3, 144.0; EI-LRMS m/z 319 (MC), 278, 223, 164, 155,
91; EI-HRMS m/z calcd for C13H15O2NS35Cl2 (MC)
319.0200, found 319.0190.
4.3.5. 1-p-Toluenesulfonyl-6-vinyl-1,2,3,4-tetrahydro-
1
pyridine (13a). IR (neat) n 1654, 1343, 1161 cmK1; H
NMR (400 MHz, CDCl3) d 1.20–1.30 (m, 2H), 1.90–1.97
(m, 2H), 2.42 (s, 3H), 3.58–3.63 (m, 2H), 5.04 (d, JZ
10.7 Hz, 1H), 5.39 (d, JZ17.2 Hz, 1H), 5.50 (dd, JZ4.0,
4.0 Hz, 1H), 6.51 (dd, JZ17.2, 10.7, 1 Hz), 7.27 (d, JZ
8.5 Hz, 2H), 7.63 (d, JZ8.5 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 19.9, 21.6, 22.8, 46.4, 112.8, 116.0, 127.2, 129.4,
136.4, 136.5, 137.6, 143.3; EI-LRMS m/z 263 (MC), 198,
155, 108, 91; EI-HRMS m/z calcd for C14H17O2NS (MC)
263.0980, found 263.0965.
4.3.6. 3,3-Dimethyl-1-p-toluenesulfonyl-6-vinyl-1,2,3,4-
tetrahydro-pyridine (13b). IR (neat) n 1635, 1598, 1349,
1
1163 cmK1; H NMR (400 MHz, CDCl3) d 0.93 (s, 6H),
1.83 (d, JZ3.8 Hz, 2H), 2.41 (s, 3H), 3.34 (s, 2H), 4.98 (d,
JZ10.6 Hz, 1H), 5.13 (t, JZ3.8 Hz, 1H), 5.32 (d, JZ
16.9 Hz, 1H), 6.47 (dd, JZ16.9, 10.6 Hz, 1H), 7.26 (d, JZ
8.0 Hz, 2H), 7.68 (d, JZ8.0 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 21.5, 26.4, 29.5, 37.5, 56.9, 110.0, 114.3, 127.0,
129.4, 134.3, 136.4, 138.2, 143.0; EI-LRMS m/z 291 (MC),
276, 262, 248, 155, 136, 91; EI-HRMS m/z calcd for
C16H21O2NS (MC) 291.1293, found 291.1289.
4.4.2. N-But-3-enyl-N-ethynyl-p-toluenesulfonamide
(5a). To a solution of 4a (200 mg, 0.64 mmol) in THF
(12 mL) was added BuLi (1.58 M solution in hexane,
0.87 mL, 1.37 mmol) at K78 8C, and the solution was
stirred for 1 h. To the solution was added saturated NH4Cl
solution, and the aqueous solution was extracted with Et2O.
The organic layer was washed with saturated NaCl solution,
dried over MgSO4, and concentrated. The residue was
purified by flash column chromatography on silica gel
(hexane/AcOEt 5:1) to give 5a (137.1 mg, 88%) as colorless
4.3.7. 6-(1-Phenyl-vinyl)-1-p-toluenesulfonyl-1,2,3,4-
tetrahydro-pyridine (13c). IR (KBr) n 1599 (w), 1357
1
(m), 1166 (s) cmK1; H NMR (270 MHz, CDCl3) d 1.52–
1.62 (m, 2H), 2.12 (dt, JZ3.8, 6.8 Hz, 2H), 2.37 (s, 3H),
3.48–3.53 (m, 2H), 5.30 (d, JZ1.6 Hz, 1H), 5.35 (d, JZ
1.6 Hz, 1H), 5.61 (t, JZ3.8 Hz, 1H), 7.14 (d, JZ8.2 Hz,
2H), 7.27–7.33 (m, 5H), 7.40 (d, JZ8.2 Hz, 2H); 13C NMR
(67.8 MHz, CDCl3) d 20.5, 21.3, 22.8, 46.2, 113.8, 120.6,
127.2, 127.3, 127.3, 127.8, 129.2, 136.5, 138.5, 139.6,
143.1, 149.1; EI-LRMS m/z 339 (MC), 274, 184, 170, 156,
142, 130, 103, 91; EI-HRMS m/z calcd for C20H21O2NS
(MC) 339.1293, found 339.1292.
1
oil. IR (Nujol) n 3260, 2150, 1374, 1167 cmK1; H NMR
(270 MHz, CDCl3) d 2.40 (dt, JZ7.3, 7.6 Hz, 2H), 2.46 (s,
3H), 2.75 (s, 1H), 3.38 (t, JZ7.6 Hz, 2H), 5.05 (d, JZ
10.2 Hz, 1H), 5.10 (d, JZ17.3 Hz, 1H), 5.71 (ddt, JZ17.3,
10.2, 7.3 Hz, 1H), 7.35 (d, JZ8.4 Hz, 2H), 7.81 (d, JZ
8.4 Hz, 2H); 13C NMR (67.8 MHz, CDCl3) d 21.6, 32.0,
50.5, 59.4, 75.9, 117.8, 127.6, 129.8, 133.4, 134.6, 144.7;
EI-LRMS m/z 248 (MCKH), 184, 155, 96, 55; EI-HRMS
m/z calcd for C13H14O2NS (MCKH) 248.0745, found
248.0736.
4.3.8. 6-[1-(2-Bromo-phenyl)-vinyl]-1-p-toluenesulfonyl-
1,2,3,4-tetrahydro-pyridine (13d). IR (neat) n 1598 (m),
1
1348 (s), 1165 (s) cmK1; H NMR (270 MHz, CDCl3) d
1.48–1.58 (m, 2H), 2.06 (dt, JZ4.0, 6.9 Hz, 2H), 2.39 (s,
3H), 3.42–3.46 (m, 2H), 5.17 (d, JZ1.3 Hz, 1H), 5.60 (d,
JZ1.3 Hz, 1H), 5.71 (t, JZ4.0 Hz, 1H), 7.15 (ddd, JZ1.8,
7.4, 7.9 Hz, 1H), 7.18 (d, JZ8.2 Hz, 2H), 7.29 (ddd, JZ1.3,
7.4, 7.5 Hz, 1H), 7.42 (d, JZ8.2 Hz, 2H), 7.51 (dd, JZ1.8,
7.5 Hz, 1H), 7.54 (dd, JZ1.3, 7.9 Hz, 1H); 13C NMR
(67.8 MHz, CDCl3) d 20.3, 21.5, 22.8, 46.2, 117.1, 122.9,
123.4, 127.1, 127.6, 128.6, 129.4, 132.7, 133.6, 136.8,
138.6, 140.9, 143.4, 148.3; EI-LRMS m/z 419 (MC, 81Br),
417 (MC, 79Br), 338, 274, 262, 182, 91; EI-HRMS m/z calcd
for C20H20O2NS81Br (MC) 419.0378, found 419.0361, m/z
calcd for C20H20O2NS79Br (MC) 417.0398, found
419.0362.
4.4.3. N-(2,2-Dichloro-vinyl)-N-pent-4-enyl-p-toluene-
sulfonamide (6a). A crude product, which was obtained
from 2a (3.44 g, 17 mmol), PPh3 (6.34 g, 24 mmol), 3b
(2.4 mL, 23 mmol) and DEAD (10.2 mL, 22 mmol), was
purified by short column chromatography on silica gel
(hexane/AcOEt 5:1) to give an inseparable mixture of
N-alkylated product and O-alkylated product (4.46 g, in the
ratio of 1.8:1). To a solution of the above mixture (4.46 g)
and PPh3 (11.32 g, 43 mmol) in THF (38 mL) was added
CCl4 (14 mL, 142 mmol) at 60 8C for 3 h, and the mixture
was stirred continuously at 60 8C for 12 h. To the mixture
was added saturated NaHCO3 solution, and the aqueous
layer was extracted with Et2O. The organic layer was
washed with saturated NaCl solution, dried over MgSO4,
and concentrated. The residue was purified by flash column
chromatography on silica gel (hexane/AcOEt 10:1) to give
4.4. Procedure for the synthesis of 5 and 7
4.4.1. N-But-3-enyl-N-(2,2-dichlorovinyl)-p-toluene-
sulfonamide (4a). To a solution of 2a (2.9 g, 14 mmol) in
THF (29 mL) were added PPh3 (4.9 g, 19 mmol), 3a

3878
M. Mori et al. / Tetrahedron 62 (2006) 3872–3881
6a (2.79 g, 48%, two steps) as a colorless crystal. Mp 73–
75 8C; IR (Nujol) n 1638, 1597, 1351, 1161 cmK1; 1H NMR
(400 MHz, CDCl3) d 1.62 (tt, JZ7.4, 7.4 Hz, 2H), 2.08 (dt,
JZ6.8, 7.4 Hz, 2H), 2.44 (s, 3H), 3.32 (t, JZ7.4 Hz, 2H),
4.99 (d, JZ10.2 Hz, 1H), 5.02 (d, JZ16.9 Hz, 1H), 5.75
(ddt, JZ16.9, 10.2, 6.8 Hz, 1H), 6.26 (s, 3H), 7.32 (d, JZ
8.1 Hz, 2H), 7.68 (d, JZ8.1 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 21.5, 27.5, 30.5, 48.6, 115.3, 124.6, 124.7, 127.0,
129.7, 135.0, 136.9, 144.0; EI-LRMS m/z 333 (MC), 318,
298, 278, 237, 178, 91; EI-HRMS m/z calcd for C14H17O2-
NS35Cl2 (MC) 333.0357, found 333.0354.
JZ8.2 Hz, 2H), 7.79 (d, JZ8.2 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 21.7, 25.1, 35.9, 44.4, 58.3, 61.6,
78.6, 117.9, 127.6, 129.5, 135.1, 134.2, 144.6; EI-LRMS
m/z 291 (MC), 290, 276, 262, 250, 155, 136, 91; EI-HRMS
m/z calcd for C16H21O2NS (MC) 291.1293, found
291.1287.
4.4.7. N-But-3-enyl-N-phenylethynyl-p-toluenesulfon-
amide (5b). To a solution of 4a (300 mg, 0.94 mmol) in
THF (6 mL) was added BuLi (1.58 M solution in hexane,
1.3 mL, 2.1 mmol) at K78 8C, and the mixture was stirred
for 1 h. Then, a solution of ZnBr2 (253 mg, 1.12 mmol) in
THF (4 mL) was added via syringe and the solution was
stirred at rt for 30 min. The whole mixture was transferred
via cannula to a solution of Pd2dba3$CHCl3 (48.5 mg,
0.05 mmol), PPh3 (49.1 mg, 0.19 mmol) and iodobenzene
(0.13 mL, 1.12 mmol) in THF (5 mL), and the solution
stirred at rt for 18 h. The volatiles were removed and the
residue was dissolved in AcOEt (30 mL). The organic layer
was washed with saturated NaCl solution, dried over
MgSO4, and concentrated. The residue was purified by
flash column chromatography on silica gel (hexane/AcOEt/
Et3N 250:50:3) to give 5b (130.4 mg, 43%). IR (neat) n
4.4.4. N-Ethynyl-N-pent-4-enyl-p-toluenesulfonamide
(7a). In a similar manner to that for the synthesis of 5a
from 4a, 7a (262 mg, 99%) was synthesized from 6a
(347 mg, 1.0 mmol) and BuLi (1.66 M solution in hexane,
1.4 mL, 2.3 mmol). IR (neat) n 3297, 2132, 1641, 1597,
1
1364, 1169 cmK1; H NMR (400 MHz, CDCl3) d 1.75 (tt,
JZ7.2, 7.2 Hz, 2H), 2.09 (dt, JZ6.6, 7.2 Hz, 2H), 2.45 (s,
3H), 2.73 (s, 1H), 3.31 (t, JZ7.2 Hz, 2H), 4.99 (d, JZ
10.1 Hz, 1H), 5.02 (d, JZ16.9 Hz, 1H), 5.75 (ddt, JZ16.9,
10.1, 6.6 Hz, 1H), 7.35 (d, JZ8.3 Hz, 2H), 7.80 (d, JZ
8.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 21.6, 26.8,
30.2, 50.6, 59.1, 75.9, 115.5, 127.4, 129.6, 134.3, 136.8,
144.6; FAB-LRMS m/z 264 (MCCH), 237, 198, 155, 108,
91; FAB-HRMS m/z calcd for C14H18O2NS 264.1058
(MCCH), found 264.1034.
1
2235 (s), 1598 (m), 1367 (s), 1171 (s) cmK1; H NMR
(270 MHz, CDCl3) d 2.41–2.50 (m, 2H), 2.45 (s, 3H), 3.47
(t, JZ7.3 Hz, 2H), 5.06 (dd, JZ1.4, 10.2 Hz, 1H), 5.11 (dd,
JZ1.4, 17.1 Hz, 1H), 5.75 (ddt, JZ10.2, 17.1, 6.9 Hz, 1H),
7.27–7.39 (m, 7H), 7.84 (d, JZ8.4 Hz, 2H); 13C NMR
(67.8 MHz, CDCl3) d 21.6, 32.2, 50.9, 70.9, 82.1, 117.7,
122.8, 127.7, 127.8, 128.2, 129.7, 131.3, 133.6, 134.5,
144.6; EI-LRMS m/z 325 (MC), 260, 233, 186, 170, 155,
128, 105, 91; EI-HRMS m/z calcd for C19H19O2NS (MC)
325.1137, found 325.1138.
4.4.5. N-(2,2-Dichloro-vinyl)-N-(2,2-dimethyl-pent-4-
enyl)-p-toluenesulfonamide (8). To a solution of 2a
(1.6 g, 8.0 mmol) in THF (26 mL) were added PPh3
(2.5 g, 20 mmol), 3c (1.1 g, 9.6 mmol) and DIAD
(1.9 mL, 9.7 mmol) at 0 8C, and the mixture was stirred at
50 8C for 16 h. After the solvent was evaporated, the residue
was purified by short column chromatography on silica gel
(hexane/AcOEt 10:1) to give an inseparable mixture of
N-alkylated product and O-alkylated product (1.5 g, in the
ratio of 1:1.4). To a solution of the above mixture (1.5 g) in
THF (17 mL) were added PPh3 (1.0 g, 15 mmol) and CCl4
(4.9 mL, 51 mmol) at rt, and the mixture was stirred at 60 8C
for 24 h. To the mixture was added saturated NaHCO3
solution, and the aqueous layer was extracted with Et2O.
The organic layer was washed with saturated NaCl solution,
dried over Na2SO4, and concentrated. The residue was
purified by flash column chromatography on silica gel
(hexane/AcOEt 20:1) to give 8 (675 mg, 23%, two steps) as
colorless oil. IR (Nujol) n 1638, 1598, 1358, 1168 cmK1; 1H
NMR (400 MHz, CDCl3) d 0.94 (s, 6H), 2.03 (d, JZ7.3 Hz,
2H), 2.44 (s, 3H), 3.02 (s, 2H), 5.02 (d, JZ16.9 Hz, 1H),
5.05 (d, JZ9.2 Hz, 1H), 5.77 (ddt, JZ16.9, 9.2, 7.3 Hz,
1H), 7.32 (d, JZ8.1 Hz, 2H), 7.65 (d, JZ8.1 Hz, 2H); 13C
NMR (100 MHz, CDCl3) d 21.5, 25.3, 35.4, 44.6, 59.8,
117.7, 127.2, 127.3, 127.7, 129.7, 134.1, 135.1, 143.9.
4.4.8. N-Pent-4-enyl-N-phenylethynyl-p-toluenesulfon-
amide (7c). In a similar manner to that for the synthesis
of 5b from 4a, 7c (260 mg, 84%) was synthesized from 6a
(303 mg, 0.91 mmol), BuLi (1.58 M solution in hexane,
1.3 mL, 2.0 mmol), ZnBr2 (245 mg, 1.08 mmol), Pd2-
dba3$CHCl3 (46.9 mg, 0.05 mmol), PPh3 (47.9 mg,
0.18 mmol) and iodobenzene (0.12 mL, 1.09 mmol). IR
1
(neat) n 2236 (s), 1598 (m), 1367 (s), 1171 (s) cmK1; H
NMR (270 MHz, CDCl3) d 1.75–1.87 (m, 2H), 2.08–2.18
(m, 2H), 2.45 (s, 3H), 3.41 (t, JZ7.2 Hz, 2H), 4.97–5.09 (m,
2H), 5.78 (ddt, JZ10.2, 16.8, 6.6 Hz, 1H), 7.26–7.39 (m,
7H), 7.84 (d, JZ8.4 Hz, 2H); 13C NMR (67.8 MHz, CDCl3)
d 21.6, 27.1, 30.2, 51.0, 70.6, 82.3, 115.6, 122.8, 127.6,
127.7, 128.2, 129.7, 131.3, 134.4, 137.0, 144.6; EI-LRMS
m/z 339 (MC), 274, 184, 170, 142, 130, 116, 105, 91; EI-
HRMS m/z calcd for C20H21O2NS (MC) 339.1293, found
339.1317.
4.4.9. N-(2-Bromo-phenylethynyl)-N-pent-4-enyl-p-
toluenesulfonamide (7d). In a similar manner to that for
the synthesis of 5b from 4a, 7d (142.5 mg, 35%) was
synthesized from 6a (329.6 mg, 0.99 mmol), BuLi (1.60 M
solution in hexane, 1.4 mL, 2.17 mmol), ZnBr2 (266.5 mg,
1.18 mmol), Pd2dba3$CHCl3 (51.0 mg, 0.05 mmol), PPh3
(51.7 mg, 0.20 mmol) and 2-bromo-iodobenzene (0.15 mL,
1.18 mmol). IR (neat) n 2236 (s), 1597 (m), 1369 (s), 1172
4.4.6. N-(2,2-Dimethyl-pent-4-enyl)-N-ethynyl-p-toluene-
sulfonamide (7b). In a similar manner to that for the
synthesis of 5a from 4a, 7b (247 mg, 84%) was synthesized
from 8 (366 mg, 1.0 mmol) and BuLi (1.66 M solution in
hexane, 1.4 mL, 2.3 mmol). IR (neat) n 3302, 2134, 1638,
1
1597, 1367, 1170 cmK1; H NMR (400 MHz, CDCl3) d
1
1.01 (s, 6H), 2.10 (d, JZ7.5 Hz, 2H), 2.23 (s, 3H), 2.68 (s,
1H), 3.13 (s, 2H), 5.03 (d, JZ10.3 Hz, 1H), 5.04 (d, JZ
16.9 Hz, 1H), 5.81 (ddt, JZ16.9, 10.3, 7.5 Hz, 1H), 7.35 (d,
(s) cmK1; H NMR (270 MHz, CDCl3) d 1.86 (tt, JZ7.1,
7.3 Hz, 2H), 2.14 (dt, JZ6.6, 7.3 Hz, 2H), 2.45 (s, 3H),
3.45 (t, JZ7.1 Hz, 2H), 4.99 (d, JZ10.2 Hz, 1H), 5.05

M. Mori et al. / Tetrahedron 62 (2006) 3872–3881
3879
(d, JZ16.8 Hz, 1H), 5.78 (ddt, JZ10.2, 16.8, 6.6 Hz, 1H),
7.11 (dd, JZ7.6, 7.9 Hz, 1H), 7.24 (dd, JZ7.6, 7.6 Hz, 1H),
7.35 (d, JZ8.2 Hz, 2H), 7.39 (d, JZ7.6 Hz, 1H), 7.54 (d,
JZ7.9 Hz, 1H), 7.88 (d, JZ8.2 Hz, 2H); 13C NMR
(67.8 MHz, CDCl3) d 21.7, 27.0, 30.3, 51.1, 70.0, 86.8,
115.6, 124.6, 125.2, 126.9, 127.7, 128.6, 129.8, 132.3,
132.5, 134.6, 137.1, 144.7; EI-LRMS m/z 419 (MC, 81Br),
417 (MC, 79Br), 354, 338, 274, 262, 182, 91; EI-HRMS m/z
calcd for C20H20O2NS81Br (MC) 419.0378, found
419.0367, m/z calcd for C20H20O2NS79Br (MC) 417.0398,
found 419.0389.
4.4.12. (E)-N-Formyl-N-hex-3-enyl-p-toluenesulfon-
amide ((E)-10). In a similar manner to that for the synthesis
of (Z)-10 from (Z)-9, (E)-10 (0.21 g, 14%, two steps) was
synthesized from (E)-9 (2.51 g, 7.10 mmol), TFA (2.5 mL,
34.1 mmol), DMAP (0.12 g, 1.01 mmol), Formic acid
(0.57 mL, 15.2 mmol) and DCC (3.09 g, 15.2 mmol), and
(E)-N-hex-3-enyl-p-toluenesulfonamide (0.94 g, 73%) was
recovered. Colorless oil; IR (neat) n 2934, 1705, 1597, 1360,
1
1166 cmK1; H NMR (270 MHz, CDCl3) d 0.93 (t, JZ
7.5 Hz, 3H), 1.95 (dq, JZ6.9, 7.5 Hz, 2H), 2.20 (dt, JZ6.2,
7.7 Hz, 2H), 2.46 (s, 3H), 3.45 (t, JZ7.7 Hz, 2H), 5.22 (dt,
JZ15.3, 6.9 Hz, 1H), 5.45 (dtt, JZ15.3, 6.2 Hz, 1H), 7.37
(d, JZ8.5 Hz, 2H), 7.74 (d, JZ8.5 Hz, 2H), 9.08 (s, 1H);
EI-LRMS m/z 281 (MC), 184, 155, 126, 91, 82; EI-HRMS
m/z calcd for C14H19O3NS (MC) 281.1086, found
281.1106.
4.4.10. Ethyl (but-3-enyl-p-toluenesulfonyl-amino)-
propiolate (5c). To a solution of 4a (220.4 mg, 0.69 mmol)
in THF (14 mL) was added BuLi (1.58 M solution in hexane,
0.96 mL, 1.51 mmol) at K78 8C. After the stirring for 1 h,
ClCO2Et (0.13 mL, 1.38 mmol) was added, and the mixture
was stirred at K50 8C for 0.5 h. To the mixture was added
saturated NH4Cl solution, and the aqueous layer was extracted
with AcOEt. The organic layer was washed with saturated
NaCl solution, dried over MgSO4, and concentrated. The
residue was purified by flash column chromatography on
silica gel (hexane/AcOEt/Et3N 80:20:1) to give 5c (199.5 mg,
90%). IR (neat) n 2218 (s), 1705 (s), 1597 (m), 1376 (s),
4.4.13.
(Z)-N-(2,2-Dichloro-vinyl)-N-hex-3-enyl-p-
toluenesulfonamide ((Z)-11). To a solution of (Z)-10
(0.59 g, 2.10 mmol) and PPh3 (1.72 g, 6.57 mmol) in THF
(18 mL) was added CCl4 (2.11 mL, 21.9 mmol) at 60 8C for
6 h, and the mixture was stirred continuously at 60 8C for
18 h. To the mixture was added saturated NaHCO3 solution,
and the aqueous layer was extracted with Et2O. The organic
layer was washed with saturated NaCl solution, dried over
MgSO4, and concentrated. The residue was purified by flash
column chromatography on silica gel (hexane/AcOEt 7:1)
to give (Z)-11 (0.67 g, 93%) as a colorless needle. Mp 68–
70 8C; IR (KBr) n 2967, 1597, 1355, 1165 cmK1; 1H NMR
(270 MHz, CDCl3) d 0.95 (t, JZ7.4 Hz, 3H), 2.01 (dq, JZ
6.7, 7.4 Hz, 2H), 2.29 (dt, JZ6.8, 7.4 Hz, 2H), 2.44 (s, 3H),
3.38 (t, JZ7.4 Hz, 2H), 5.22 (dt, JZ12.1, 6.7 Hz, 1H), 5.46
(dt, JZ12.1, 6.8 Hz, 1H), 6.37 (s, 1H), 7.32 (d, JZ8.2 Hz,
2H), 7.69 (d, JZ8.2 Hz, 2H); 13C NMR (67.8 MHz, CDCl3)
d 14.2, 20.6, 21.6, 26.6, 48.7, 123.5, 123.8, 124.8, 127.2,
129.8, 134.7, 135.7, 144.1; EI-LRMS m/z 347 (MC), 319,
278, 155, 91; EI-HRMS m/z calcd for C15H19O2NS35Cl2
(MC) 347.0514, found 347.0483.
1
1175 (s) cmK1; H NMR (270 MHz, CDCl3) d 1.31 (t, JZ
7.1 Hz, 3H), 2.41(dt, JZ6.8, 7.4 Hz, 2H), 2.47(s, 3H), 3.49(t,
JZ7.4 Hz, 2H), 4.23 (q, JZ7.1 Hz, 2H), 5.05 (dd, JZ1.4,
10.2 Hz, 1H), 5.09 (dd, JZ1.4, 17.0 Hz, 1H), 5.67 (ddt,
JZ10.2, 17.0, 6.8 Hz, 1H), 7.38 (d, JZ8.4 Hz, 2H), 7.82 (d,
JZ8.4 Hz, 2H); 13C NMR (67.8 MHz, CDCl3) d 14.1, 21.6,
32.1, 50.5, 61.4, 67.9, 82.1, 118.3, 127.7, 130.0, 132.8, 134.1,
145.5, 154.0; EI-LRMS m/z 321 (MC), 276, 256, 242, 228,
184, 155, 91; EI-HRMS m/z calcd for C16H19O4NS (MC)
321.1035, found 321.1059.
4.4.11. (Z)-N-Formyl-N-hex-3-enyl-p-toluenesulfon-
amide ((Z)-10). To
a solution of (Z)-9 (1.98 g,
5.60 mmol) in CH2Cl2 (11 mL) was added TFA (2.1 mL,
27.7 mmol) at 0 8C, and the mixture was stirred at rt for 3 h.
The mixture was extracted with AcOEt, and the organic
layer was washed with saturated NaHCO3 solution and
saturated NaCl solution, dried over MgSO4, and concen-
trated. The residue was purified by flash column chroma-
tography on silica gel (hexane/AcOEt 3:1) to give (Z)-N-
hex-3-enyl-p-toluenesulfonamide (1.36 g, 96%) as colorless
oil. To a solution of (Z)-N-hex-3-enyl-p-toluenesulfonamide
(1.26 g, 4.97 mmol), DMAP (0.218 mg, 1.78 mmol) and
formic acid (0.39 mL, 10.4 mmol) in CH2Cl2 (26 mL) was
added DCC (2.66 g, 13.2 mL) at 0 8C, and the mixture was
refluxed for 18 h. Undissolved materials were removed by
filtration through the Celite pad, and filtrate was concen-
trated. The residue was purified by flash column chroma-
tography on silica gel (hexane/AcOEt 5:1) to give (Z)-10
(0.59 g, 40%, two steps) as colorless oil along with
recovered (Z)-N-hex-3-enyl-p-toluenesulfonamide (0.70 g,
4.4.14.
(E)-N-(2,2-Dichloro-vinyl)-N-hex-3-enyl-p-
toluenesulfonamide ((E)-11). In a similar manner to that
for the synthesis of (Z)-11 from (Z)-10, (E)-11 (0.37 g,
64%) was synthesized from (E)-10 (0.47 g, 1.67 mmol),
PPh3 (1.31 g, 5.01 mmol) and CCl4 (1.61 mL, 16.7 mmol).
A colorless needle; mp 60–65 8C; IR (KBr) n 2969, 1598,
1357, 1161 cmK1; H NMR (270 MHz, CDCl3) d 0.94 (t,
1
JZ7.5 Hz, 3H), 1.98 (dq, JZ6.6, 7.5 Hz, 2H), 2.21 (dt,
JZ6.5, 7.5 Hz, 2H), 2.44 (s, 3H), 3.38 (t, JZ7.5 Hz, 2H),
5.26 (dt, JZ15.3, 6.6 Hz, 1H), 5.52 (dt, JZ15.3, 6.5 Hz,
1H), 6.32 (s, 1H), 7.32 (d, JZ8.5 Hz, 2H), 7.69 (d, JZ
8.5 Hz, 2H); 13C NMR (67.8 MHz, CDCl3) d 13.6, 21.6,
25.6, 31.9, 49.1, 123.8, 124.3, 124.9, 127.2, 129.8, 135.4,
135.7, 144.1; EI-LRMS m/z 347 (MC), 319, 278, 155, 91;
EI-HRMS m/z calcd for C15H19O2NS35Cl2 (MC)
347.0514, found 347.0517.
1
56%). IR (neat) n 2934, 1701, 1597, 1359, 1166 cmK1; H
NMR (270 MHz, CDCl3) d 0.93 (t, JZ7.5 Hz, 3H), 2.00
(dq, JZ6.7, 7.5 Hz, 2H), 2.27 (dt, JZ7.5, 7.9 Hz, 2H), 2.46
(s, 3H), 3.40 (t, JZ7.9 Hz, 2H), 5.19 (dt, JZ10.7, 6.7 Hz,
1H), 5.45 (dt, JZ10.7, 7.5 Hz, 1H), 7.37 (d, JZ8.2 Hz, 2H),
7.75 (d, JZ8.2 Hz, 2H), 9.10 (s, 1H); EI-LRMS m/z 281
(MC), 184, 155, 126, 91, 82; EI-HRMS m/z calcd for
C14H19O3NS (MC) 281.1086, found 281.1104.
4.4.15. (Z)-N-Ethynyl-N-hex-3-enyl-p-toluenesulfon-
amide ((Z)-5d). In a similar manner to that for the synthesis
of 5a from 4a, (Z)-5d (0.46 g, 92%) was synthesized from
(Z)-11 (0.63 g, 1.81 mmol) and BuLi (1.58 M solution in
hexane, 3.6 mL, 5.70 mmol). A pale yellow oil; IR (neat) n
3301, 2964, 2137, 1597, 1370, 1171 cmK1 1H NMR
;
(270 MHz, CDCl3) d 0.94 (t, JZ7.5 Hz, 3H), 2.01

3880
M. Mori et al. / Tetrahedron 62 (2006) 3872–3881
(dq, JZ7.2, 7.5 Hz, 2H), 2.38 (dt, JZ7.7, 7.5 Hz, 2H), 2.45
(s, 3H), 2.75 (s, 1H), 3.31 (t, JZ7.5 Hz, 2H), 5.22 (dt, JZ
12.1, 7.2 Hz, 1H), 5.46 (dt, JZ12.1, 7.7 Hz, 1H), 7.35 (d,
JZ8.2 Hz, 2H), 7.80 (d, JZ8.2 Hz, 2H); 13C NMR
(67.8 MHz, CDCl3) d 14.1, 20.6, 21.6, 25.7, 50.9, 59.2,
75.9, 123.3, 127.6, 129.8, 134.6, 135.1, 144.7; EI-LRMS m/
z 276 (MC), 198, 184, 155, 122, 91; EI-HRMS m/z calcd for
C15H19O2NS (MC) 277.1136, found 277.1122.
2.0, 2.0 Hz, 1H), 6.95 (d, JZ8.3 Hz, 2H), 7.21 (br d, JZ
8.3 Hz, 2H), 7.34–7.42 (m, 3H), 7.68 (br d, JZ8.3 Hz, 2H);
13C NMR (67.8 Hz, CDCl3) d 21.3, 21.5, 21.6, 29.4, 39.5,
42.1, 49.0, 115.1, 126.2, 127.3, 128.6, 129.1, 129.9, 131.6,
134.2, 138.8, 143.9, 174.5, 177.1; EI-LRMS m/z 422 (MC),
267, 155, 120, 91; EI-HRMS m/z calcd for C23H22O4N2S
(MC) 422.1300, found 422.1301. The stereochemistry of 15
was determined by NOE experiment.
4.4.16. (E)-N-Ethynyl-N-hex-3-enyl-p-toluenesulfonamide
((E)-5d). In a similar manner to that for the synthesis of 5a
from 4a, (E)-5d (0.21 g, 99%) was synthesized from (E)-11
(0.27 g, 0.78 mmol) and BuLi (1.58 M solution in hexane,
1.3 mL, 2.10 mmol). Colorless oil; IR (neat) n 3299, 2963,
2136, 1597, 1369, 1170 cmK1; 1H NMR (270 MHz, CDCl3)
d 0.94 (t, JZ7.4 Hz, 3H), 1.96 (dq, JZ6.8, 7.4 Hz, 2H),
2.33 (dt, JZ7.0, 7.2 Hz, 2H), 2.45 (s, 3H), 2.75 (s, 1H), 3.33
(t, JZ7.2 Hz, 2H), 5.26 (dt, JZ15.2, 6.8 Hz, 1H), 5.53 (dt,
JZ15.2, 7.0 Hz, 1H), 7.35 (d, JZ8.2 Hz, 2H), 7.80 (d, JZ
8.2 Hz, 2H); 13C NMR (67.8 MHz, CDCl3) d 13.5, 21.6,
25.5, 30.9, 51.1, 59.3, 75.9, 123.6, 127.6, 129.8, 134.7,
135.6, 144.6; EI-LRMS m/z 276 (MC), 198, 184, 155, 91;
EI-HRMS m/z calcd for C15H19NO2S (MC) 277.1136,
found 277.1147.
4.6.3. Dimethyl 6-ethyl-1-p-toluenesulfonyl-2,3-dihydro-
1H-indole-4,5-dicarboxylate (16) and dimethyl 6-ethyl-
1-p-toluenesulfonyl-1H-indole-4,5-dicarboxlate (17). To
a solution of diastereoisomeric mixture (22.7 mg,
54.1 mmol) in toluene (2 mL), which was prepared from
(Z)-5d, 1b and DMAD according to typical procedure, was
added DDQ (113 mg, 0.497 mmol), and the mixture was
stirred at 80 8C for 20 h. After the volatiles were removed
under reduce pressure, the residue was purified by flash
column chromatography on silica gel (hexane/AcOEt 3:1)
to give 16 (13.7 mg, 20%, three steps) as a colorless crystal
and 17 (7.9 mg, 12%, three steps) as pale yellow oil. 16: IR
4.5. Typical procedure for the Diels–Alder reaction
A solution of 5a (55 mg, 0.22 mmol) and 1b (10 mg,
0.012 mmol) in toluene (7 mL) was refluxed for 30 min
under ethylene gas (1 atm). After the reaction solution was
cooled to rt, the atmosphere of ethylene gas was replaced by
argon gas. To this solution was added DMAD (0.14 mL,
1.2 mmol), and the resulting mixture was stirred at 60 8C
for 12 h. After the volatiles were removed under
reduce pressure, the residue was purified by flash
column chromatography on silica gel (hexane/AcOEt 3:1)
to give 14a (69 mg, 80%, two steps) as colorless oil.
(Scheme 6, Eq. 2).
1
(KBr) n 2967, 1729, 1598, 1364, 1167 cmK1; H NMR
(270 MHz, CDCl3) d 1.24 (t, JZ7.5 Hz, 3H), 2.39 (s, 3H),
2.68 (q, JZ7.5 Hz, 2H), 3.15 (t, JZ8.8 Hz, 2H), 3.81 (s,
3H), 3.87 (s, 3H), 3.93 (t, JZ8.8 Hz, 2H), 7.26 (d, JZ
8.1 Hz, 2H), 7.67 (d, JZ8.1 Hz, 2H), 7.68 (s, 1H); EI-
LRMS m/z 417 (MC), 385, 327, 262, 230, 198, 91; EI-
HRMS m/z calcd for C21H23O6NS (MC) 417.1246, found
417.1259. Compound 17: IR (neat) n 2953, 1732, 1597,
1
1378, 1168 cmK1; H NMR (270 MHz, CDCl3) d 1.27 (t,
JZ7.5 Hz, 3H), 2.35 (s, 3H), 2.76 (q, JZ7.5 Hz, 2H), 3.92
(s, 6H), 7.13 (d, JZ3.7 Hz, 1H), 7.23 (d, JZ8.6 Hz, 2H),
7.65 (d, JZ3.7 Hz, 1H), 7.70 (d, JZ8.6 Hz, 2H), 8.07 (s,
1H); EI-LRMS m/z 415 (MC), 383, 325, 228, 91; EI-HRMS
m/z calcd for C21H21O6NS (MC) 415.1090, found
415.1084.
4.6. Spectral data of Diels–Alder products
4.6.1. Dimethyl 1-p-toluenesulfonyl-2,3,3a,6-tetrahydro-
1H-indole-4,5-dicarboxylate (14a). IR (neat) n 1733, 1646,
1
1597, 1359, 1163 cmK1; H NMR (400 MHz, CDCl3) d
1.65 (dddd, JZ11.8, 11.8, 11.3, 8.2 Hz, 1H), 2.15 (ddd, JZ
11.8, 6.0, 6.0 Hz, 1H), 2.43 (s, 3H), 2.94 (m, 1H), 3.08 (ddd,
JZ22.5, 11.3, 2.2 Hz, 1H), 3.24 (ddd, JZ22.5, 7.0, 5.6 Hz,
1H), 3.35 (ddd, JZ10.0, 6.0, 6.0 Hz, 1H), 3.75 (s, 3H), 3.76
(s, 3H), 3.79 (dd, JZ10.0, 8.2 Hz, 1H), 5.79 (dd, JZ5.6,
2.2 Hz, 1H), 7.29 (d, JZ8.2 Hz, 2H), 7.69 (d, JZ8.2 Hz,
2H); 13C NMR (67.8 Hz, CDCl3) d 21.6, 27.3, 28.8, 39.5,
48.9, 52.3, 52.4, 101.4, 127.2, 133.4, 134.3, 134.7, 136.4,
144.1, 167.3, 167.4; EI-LRMS m/z 391 (MC), 236, 159, 91;
EI-HRMS m/z calcd for C19H21O6NS (MC) 391.1080,
found 391.1089.
4.6.4. Dimethyl 1-p-toluenesulfonyl-1,2,3,4,4a,7-hexa-
hydro-quinoline-5,6-dicarboxylate (18a). Mp 129 8C
1
(decomp.); IR (Nujol) n 1724, 1594, 1346, 1156 cmK1; H
NMR (400 MHz, CDCl3) d 1.30–1.55 (m, 2H), 1.75 (br d,
JZ13.3 Hz, 1H), 1.87 (m, 1H), 2.43 (s, 3H), 2.77 (m, 1H),
3.03 (m, 1H), 3.05 (ddd, JZ23.7, 8.3, 3.7 Hz, 1H), 3.20
(ddd, JZ23.7, 8.1, 3.8 Hz, 1H), 3.75 (s, 6H), 4.17 (br d, JZ
13.4 Hz, 1H), 5.83 (ddd, JZ3.6, 3.6, 1.4 Hz, 1H), 7.29 (d,
JZ8.4 Hz, 2H), 7.71 (d, JZ8.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 21.5, 24.0, 27.7, 30.5, 36.6, 47.8,
52.1, 52.3, 119.5, 126.9, 127.8, 129.6, 133.2, 137.8, 138.4,
143.4, 166.6, 168.0; EI-LRMS m/z 405 (MC), 374, 282,
218, 131, 91; EI-HRMS m/z calcd for C20H23O6NS (MC)
405.1246, found 405.1226.
4.6.2. (3aS*,8aS*,8bR*)-2-Phenyl-6-p-toluenesulfonyl-
4,6,7,8,8a,8b-hexahydro-3aHL2,6-diaza-as-indacene-
1
1,3-dione (15). IR (Nujol) n 1707, 1348, 1162 cmK1; H
NMR (400 MHz, CDCl3) d 2.18 (m, 1H), 2.26 (m, 1H), 2.35
(s, 3H), 2.60 (m, 1H), 2.82 (m, 1H), 2.89 (ddd, JZ15.6, 7.8,
1.5 Hz, 1H), 3.20 (ddd, JZ10.7, 7.3, 1.5 Hz, 1H), 3.29 (dd,
JZ9.3, 7.3 Hz, 1H), 3.61–3.71 (m, 2H), 5.65 (ddd, JZ7.8,
4.6.5. Dimethyl 1-p-toluenesulfonyl-1,2,3,4,7,8-hexa-
hydro-quinoline-5,6-dicarboxylate (18b). IR (neat) n
1734, 1708, 1635, 1596, 1343, 1162 cmK1 1H NMR
;

M. Mori et al. / Tetrahedron 62 (2006) 3872–3881
3881
Lett. 2001, 3, 1161. (i) Mori, M.; Kitamura, T.; Sato, Y.
Synthesis 2001, 654. (j) Kitamura, T.; Sato, Y.; Mori, M. Chem.
Commun. 2001, 1258. (k) Mori, M.; Kuzuba, Y.; Kitamura, T.;
Sato, Y. Org. Lett. 2002, 4, 3855. (l) Kitamura, T.; Sato, Y.;
Mori, M. Adv. Synth. Catal. 2002, 344, 678. (m) Mori, M.;
Tonogaki, K.; Nishiguchi, N. J. Org. Chem. 2002, 67, 224. (n)
Saito, N.; Sato, Y.; Mori, M. Org. Lett. 2002, 4, 803.
(o) Tonogaki, K.; Mori, M. Tetrahedron Lett. 2002, 43, 2235.
(p) Mori, M.; Tomita, T.; Kita, Y.; Kitamura, T. Tetrahedron
Lett. 2004, 45, 4397. (q) Kitamura, T.; Kuzuba, Y.; Sato, Y.;
Wakamatsu, H.; Fujita, R.; Mori, M. Tetrahedron 2004, 60,
7375. (r) Kitamura, T.; Sato, Y.; Mori, M. Tetrahedron 2004, 60,
9649. (s) Mori, M.; Wakamatsu, H.; Tonogaki, K.; Fujita, R.;
Kitamura, T.; Sato, Y. J. Org. Chem. 2005, 70, 1066.
(400 MHz, CDCl3) d 1.45–1.54 (m, 2H), 1.96–2.02 (m, 2H),
2.44 (s, 3H), 2.48–2.55 (m, 2H), 2.75–2.85 (m, 2H), 3.63–
3.68 (m, 2H), 3.78 (s, 3H), 3.81 (s, 3H), 7.31 (d, JZ8.3 Hz,
2H), 7.65 (d, JZ8.3 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 20.8, 21.6, 22.8 (2C), 26.6, 46.5, 52.0, 52.3, 115.3, 120.8,
128.9, 129.8, 136.7, 139.2, 142.0, 144.0, 166.0, 168.8;
EI-LRMS m/z 405 (MC), 374, 250, 218, 190, 158;
EI-HRMS m/z calcd for C20H23O6NS (MC) 405.1246,
found 405.1234.
References and notes
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