Construction of nitrogen-heterocyclic compounds through zirconium mediated intramolecular alkene-carbonyl coupling reaction of N-(o-alkenylaryl)carbamate derivatives

Article abstract of DOI:10.1016/j.tet.2003.08.079

Intramolecular alkene-carbonyl coupling reaction of N-benzyl-N-(o- alkenylaryl)carbamate derivative derived from o-aminostyrene, o-(aminomethyl)styrene and o-aminoallylbenzene smoothly proceeded by treating with zirconocene-butene complex to give the corresponding lactam derivative.

Full text of DOI:10.1016/j.tet.2003.08.079

Tetrahedron 60 (2004) 1385–1392
Construction of nitrogen-heterocyclic compounds through
zirconium mediated intramolecular alkene-carbonyl coupling
reaction of N-(o-alkenylaryl)carbamate derivatives
Yasushi Takigawa,a Hisanaka Ito,b Katsunori Omodera,a Maiko Itoa and Takeo Taguchia
,
*
aSchool of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
bSchool of Life Science, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received 20 June 2003; accepted 11 August 2003
Abstract—Intramolecular alkene-carbonyl coupling reaction of N-benzyl-N-(o-alkenylaryl)carbamate derivative derived from o-amino-
styrene, o-(aminomethyl)styrene and o-aminoallylbenzene smoothly proceeded by treating with zirconocene–butene complex to give the
corresponding lactam derivative.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
depending on the ability as a leaving group (–NBn vs –NTs
vs Ot-Bu), lactam derivative 3a is formed from the substrate
1a having an electron donating group such as benzyl group
(path a), while g-aminobutyric acid derivative 4a is
obtained from the substrate 2a having an electron with-
drawing group such as sulfonyl group (path b).
Low valent zirconium-mediated intramolecular coupling
reaction of unsaturated functional groups has been exten-
sively developed as a powerful mean for the construction of
cyclic compounds.1 While such zirconium-mediated intra-
molecular coupling reactions were limited to the cases of
alkene, alkyne and imine derivatives,2,3 we have recently
demonstrated successful examples of intramolecular
alkene-carbonyl coupling reaction by using N-alkenyl-N-
substituted tert-butyl carbamate derivatives as the sub-
strates.4 One of the characteristic features of the present
reaction is the effect of the substituent on the nitrogen atom
on the reaction course. That is, as shown in Scheme 1,
Furthermore, not only electronic nature of the substituent on
the nitrogen atom, steric effect of carbamate moiety maybe
influences the reactivity and the reaction pathway. For
example, the coupling reaction of sterically bulky tert-butyl
carbamate of N-4-pentenyl-N-tosylamide 2b proceeded
after migration of zirconium into the inner site resulting in
the formation of g-aminobutyric acid derivative 4b, while
the benzyl carbamate 2c gave d-aminopentanoic acid
derivative 4c (Scheme 2).4,5
Based on our findings mentioned above, we extended the
present zirconium-mediated intramolecular coupling
reaction to N-(o-alkenylaryl)carbamate derivatives 1c–m
(N-benzyl derivatives), 2d–g (N-tosyl derivatives) to
examine the substituent effect of the carbamate moiety on
the reactivity as well as to develop an efficient method for
the preparation of nitrogen-containing heterocyclic
compounds (Chart 1).6
Scheme 1.
2. Results and discussion
Keywords: Zirconocene–butene complex; N-Aryl carbamate; Ester
transfer; Indoline derivative; Quinolone derivative; Isoquinolone
derivative.
Since N-tosyl tert-butyl carbamates are good substrates in
the zirconium mediated intramolecular alkene-carbonyl
coupling reaction as reported in our preliminary results,4
N-Boc-N-tosyl substituted o-aminostyrene 2d and
*
Corresponding author. Tel./fax: þ81-426-76-3257;
e-mail address: taguchi@ps.toyaku.ac.jp
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.08.079

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Y. Takigawa et al. / Tetrahedron 60 (2004) 1385–1392
o-aminoallylbenzene 2e were chosen as a starting material.
Reaction of o-aminostyrene derivative 2d with zircono-
cene–butene complex7 did not give the desired ester
transfer product but exclusively afforded the desufonylated
carbamate 6d in 71% isolated yield. As shown in Scheme 3,
the reaction pathway to the carbamate 6d possibly involves
the zirconium-promoted 1,4-elimination of sulfonyl group
to form o-quinodimethane intermediate 5d and the sub-
sequent re-aromatization.8 With one carbon elongated
allylbenzene derivative 2e, both alkene-carbonyl coupling
reaction and desulfonylation reaction competitively
proceeded. In this case, unlike the aliphatic substrate 2b
(Scheme 2), the alkene-carbonyl coupling reaction
proceeded without migration of zirconium to give the
a-methylated ester derivative 4e as a minor product (28%
yield) and the major product was the E isomer of
desulfonylated compound 6e (59% yield) derived after
migration of zirconium (Scheme 4).
Scheme 2.
We found that in the case of allylbenzene derivatives, the
desired alkene-carbonyl coupling reaction can be controlled
to be a major reaction by using sterically less hindered
carbamate by changing tert-butyl ester to primary or
secondary alkyl ester such as benzyl carbamate 2f and
cyclohexyl carbamate 2g. That is, with these substrates prior
to migration of zirconium into the inner site (see Scheme 4),
alkene-carbonyl coupling reaction smoothly occurred to
give the ester transfer product 4f and 4g in good yields as
shown in Scheme 5. It is also noted that reaction of trans-2-
phenylcyclohexyl carbamate 2g proceeded in a highly
diastereoselective manner (isomer ratio 12:1) obtaining the
a-methylated ester derivative 4g, although the relative
stereochemistry was not determined. In contrast to the
allylbenzene derivatives mentioned above, desulfonylation
was a major pathway in the reaction of benzyl carbamate of
o-(tosylamino)styrene with zirconocene–butene complex.
Chart 1.
Scheme 3.
Scheme 4.

Y. Takigawa et al. / Tetrahedron 60 (2004) 1385–1392
1387
Thus, reaction of N-benzyl carbamates 1c–h derived from
o-aminostyrene, 1i, 1j from o-aminoallylbenzene and 1k,
1m from o-(aminomethyl)styrene with in situ generated
zirconocene–butene complex were conducted and results
are summarized in Table 1.
Contrary to the N-tosyl derivative 2d (Scheme 3), N-benzyl
derivative 1c smoothly reacted with zirconocene–butene
complex to give the intramolecular alkene-carbonyl
coupling product 3c in moderate yield (51%, entry 1, see
also Scheme 7). Yield of the lactam derivative 3c slightly
varied by changing the steric demand of the ester part. Thus,
the benzyl ester 1d gave a higher yield of 3c than either
sterically hindered tert-butyl ester 1c or less hindered ethyl
ester 1f (see entries 1, 2, 4). With the substrates 1g, 1h
having an additional methoxyl group on the aromatic ring
gave the corresponding 3-methylindoline derivatives 1g and
1h, respectively (entries 5, 6).
Scheme 5.
Six-membered ring forming reaction from o-aminoallyl-
benene derivatives 1i, 1j and o-(aminomethyl)styrene
derivatives 1k, 1m proceeded much more effectively giving
rise to the coupling product in good yields (entries 7–10). In
the case of conversion into dihydroquinolone 3i, benzyl
ester 1j gave a higher yield than tert-butyl ester 1i, and in
both cases 3-ethylindolinone derivative, possibly formed
via migration of zirconium, was not detected (entries 7, 8).
Efficient formation of these six-membered ring compounds
3i, 3k via alkene-carbonyl coupling reaction should be
mainly due to ortho-substituted benzene structure of the
substrate, because such an efficient cyclization reaction
could not be achieved with the substrate of linear chain
structure. For example, upon treating N-4-pentenyl benzyl
carbamate 1b with zirconocene–butene complex, two
coupling products, piperidone 3b-1 (4%) and pyrrolidone
3b-2 (15%), were obtained in low yields along with the
isolation of the pentenyl chain lacked N-benzyl carbamate 8
as a main product (48%). It is likely that formation of the
dealkenylated product 8 involves the stepwise migration of
zirconium leading to the intermediacy allylic zirconium
species 7 (Scheme 6).9
As mentioned above, since the present alkene-carbonyl
coupling reaction cannot be applied to the N-sulfonyl
carbamate of o-aminostyrene such as 2d or the correspond-
ing benzyl carbamate due to the facile desulfonylation
reaction, N-benzyl derivatives were examined as substrates.
Table 1. ‘Cp2Zr’ mediated coupling reaction of N-benzyl carbamate
derivatives
Entry
Substrate
Product
Yield
(%)
1
2
3
4
1c R¼t-Bu
3c
51
59
48
40
1d R¼Bn
1e R¼i-Pr
1f R¼Et
To clarify the reaction pathway, deuterium oxide (D2O)
quenching of the reaction mixture was examined. After
treatment of 1c with zirconocene–butene complex under
similar conditions as before (Table 1, entry 1), the reaction
mixture was quenched with D2O. High level (.90%) of
deuterium incorporation was observed at both 3-position
and at the methyl group of indoline derivative 3c-D
(Scheme 7). The reaction pathway possibly involves the
intramolecular alkene-carbonyl coupling reaction
followed by the formation of the lactam structure 9
having zirconated methyl substituent at the 3-position. In
the next stage, it would be likely that zirconium tert-
butoxide in the intermediate 9 acts as a base to deprotonate
at the 3-position to form the five-membered zirconium
enolate form 10, which converted to the bisdeuterated
indoline 3c-D.
5
6
1g R1¼OMe R2¼H
1h R1¼H R2¼OMe
3g
3h
45
49
7
8
1i R¼t-Bu
1j R¼Bn
3i
69
88
In the cases of six-membered ring forming reaction with the
substrates 1j and 1k, deuterium incorporation was observed
at the methyl group, giving rise to 3i-D and 3k-D in high
yields (Scheme 8). When the reaction mixture was
9
10
1k R¼t-Bu
1m R¼Bn
3k
69
62

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Y. Takigawa et al. / Tetrahedron 60 (2004) 1385–1392
Scheme 6.
Scheme 7.
quenched by the addition of iodine instead of D2O,
iodomethyl derivative 11 was isolated in 50% yield in the
case of 1j and methylene derivative 12 was obtained in 22%
yield in the case of 1k (Scheme 9).
3. Conclusion
Zirconocene–butene complex mediated intramolecular
alkene-carbonyl coupling reaction can be applied to
N-benzyl carbamate derivatives derived from o-amino-
styrene, o-aminoallylbenzene and o-(aminomethyl)styrene to
give the corresponding nitrogen-heterocyclic compounds.
4. Experimental
4.1. General
Toluene (dehydrated), THF (dehydrated, no stabilizer) and
zirconocene dichloride are available commercially. All
1
reactions were conducted under an argon atmosphere. H
and 13C NMR spectra were measured in CDCl3 and the
chemical shifts are given in ppm using CHCl3 (7.26 ppm) in
Scheme 8.
1
CDCl3 for H NMR and CDCl3 (77.01 ppm) for 13C NMR
as internal standard, respectively. Mass spectra and HRMS
were recorded by electrospray ionization. Column chroma-
tography was performed on silica gel (70–230 mesh).
Medium-pressure liquid chromatography (MPLC) was
performed on a 30 cm£2.2 cm i.d. prepacked column (silica
gel, 50 mm) with a UV or RI detector.
4.2. Procedure for the preparation of the carbamate
derivative 1 and 2
To a mixture of 2-vinylbenzoic acid (741 mg, 5 mmol),
triethylamine (1.05 ml, 7.5 mmol) in benzene (50 ml) was
Scheme 9.

Y. Takigawa et al. / Tetrahedron 60 (2004) 1385–1392
1389
added diphenylphosphoryl azide (DPPA, 1.62 ml,
7.5 mmol) at room temperature. After being stirred for 1 h
at the same temperature, 2-methyl-2-propanol (4.8 ml,
50 mmol) was added and the reaction mixture was heated
at reflux. After being stirred for 3 h until gas evolution had
ceased, the reaction mixture was poured into sat. NaHCO3
and then extracted with ether. The organic layer was washed
with brine, dried over MgSO4, and then concentrated under
reduced pressure. The residue was chromatographed on
silica gel (hexane/AcOEt¼20:1) to give tert-butyl 2-vinyl-
CDCl3, 50 8C) d; 7.54 (1H, dd, J¼7.8, 1.3 Hz), 7.28–7.18
(6H, m), 7.13 (1H, dd, J¼7.6, 1.4 Hz), 6.84 (1H, d,
J¼7.4 Hz), 6.33 (1H, dd, J¼17.5, 11.1 Hz), 5.65 (1H, dd,
J¼17.6, 0.9 Hz), 5.29 (1H, dd, J¼11.0, 0.9 Hz), 5.05 (1H,
brs), 4.40 (1H, brs), 4.14 (2H, brs), 1.14 (3H, brs). 13C NMR
(100.6 MHz, CDCl3, 50 8C) d; 156.1, 139.4, 137.6, 135.7,
132.6, 129.2, 129.0, 128.3, 128.2, 127.6, 127.5, 126.1,
115.8, 61.7, 54.3, 14.6. MS m/z: 304 (MþNa)þ. Anal. calcd
for C18H19NO2: C, 76.84; H, 6.81; N, 4.98. Found: C, 76.84;
H, 6.81; N, 4.83.
1
phenylcarbamate 6d (800 mg, 73% yield) whose H NMR
data were in good agreement with those described in the
literature.10 The above carbamate (439 mg, 2 mmol)
dissolved in DMF was added dropwise to sodium hydride
(96.0 mg, 2.4 mmol) in DMF (20 ml) at room temperature.
After being stirred for 30 min at the same temperature,
benzyl bromide (0.36 ml, 3 mmol) was added and the whole
was stirred overnight. The reaction mixture was quenched by
the addition of 1N HCl and extracted with ether. The organic
layer was washed with sat. NaHCO3 and brine, dried over
MgSO4, and then concentrated under reduced pressure. The
residue was chromatographed on silica gel (hexane/
AcOEt¼20:1) to give 1c (616 mg, quantitative yield).
4.2.5. Benzyl benzyl(3-methoxy-2-vinylphenyl)carba-
mate 1g. White solid: mp 64.0–65.0 8C. IR (KBr) n;
1
1697 cm21. H NMR (400 MHz, CDCl3, 50 8C) d; 7.39–
7.14 (10H, m), 7.06 (1H, t, J¼8.1 Hz), 6.83 (1H, d,
J¼8.2 Hz), 6.54 (1H, dd, J¼17.9, 12.0 Hz), 6.48 (1H, brs),
5.79 (1H, dd, J¼18.0, 2.2 Hz), 5.41 (1H, dd, J¼6.0, 2.1 Hz),
5.17 (3H, brs), 4.23 (1H, d, J¼14.0 Hz), 3.85 (3H, s). 13C
NMR (100.6 MHz, CDCl3, 50 8C) d; 158.6, 155.9, 140.5,
137.6, 136.9, 129.0, 128.8, 128.3, 127.7, 127.4, 124.7,
122.2, 119.9, 110.4, 67.3, 55.8, 54.2. MS m/z: 396
(MþNa)þ. Anal. calcd for C24H23NO3: C, 77.19; H, 6.21;
N, 3.75. Found: C, 77.19; H, 6.15; N, 3.73.
4.2.1. tert-Butyl benzyl(2-vinylphenyl)carbamate 1c.
Colorless oil. IR (neat) n; 1698 cm21
4.2.6. Benzyl benzyl(5-methoxy-2-vinylphenyl)carba-
mate 1h. Colorless oil. IR (neat) n; 1703 cm21. H NMR
1
.
1H NMR
(400 MHz, CDCl3, 50 8C) d; 7.58 (1H, d, J¼7.6 Hz),
7.33–7.23 (6H, m), 7.18 (1H, t, J¼7.2 Hz), 6.91 (1H,
brs), 6.71(1H, dd, J¼17.5, 11.1 Hz), 5.71 (1H, d,
J¼17.6 Hz), 5.29 (1H, d, J¼11.0 Hz), 5.07 (1H, brs), 4.45
(1H, brs), 1.43 (9H, brs). 13C NMR (100.6 MHz, CDCl3,
50 8C) d; 115.1, 140.1, 138.1, 135.7, 133.0, 129.1, 128.8,
128.3, 128.1, 127.3, 127.2, 125.9, 115.4, 80.2, 53.8, 28.3.
MS m/z: 310 (MþH)þ. Anal. calcd for C20H23NO2: C,
77.64; H, 7.49; N, 4.53. Found: C, 77.51; H, 7.63; N, 4.45.
(400 MHz, CDCl3, 50 8C) d; 7.48 (1H, d, J¼8.7 Hz), 7.26–
7.22 (10H, m), 6.82 (1H, dd, J¼8.7, 2.5 Hz), 6.55 (1H, dd,
J¼17.8, 11.1 Hz), 6.33 (1H, brs), 5.55 (1H, d, J¼17.5 Hz),
5.16 (3H, brs), 5.11 (1H, d, J¼11.1 Hz), 4.35 (1H, brs), 3.61
(3H, s). 13C NMR (100.6 MHz, CDCl3, 50 8C) d; 159.5,
155.8, 140.1, 137.5, 136.8, 131.9, 129.1, 128.3, 128.3,
127.8, 127.6, 127.0, 114.4, 114.3, 113.9, 67.4, 55.3, 54.3.
MS m/z: 396 (MþNa)þ. Anal. calcd for C24H23NO3: C,
77.19; H, 6.21; N, 3.75. Found: C, 77.30; H, 6.09; N, 3.79.
4.2.2. Benzyl benzyl(2-vinylphenyl)carbamate 1d. Color-
less oil. IR (neat) n; 1704 cm21
4.2.7. tert-Butyl 2-allylphenyl(benzyl)carbamate 1i.
Colorless oil. IR (neat) n; 1697 cm21 1H NMR
.
.
1H NMR (400 MHz,
CDCl3, 50 8C) d; 7.56 (1H, d, J¼7.8 Hz), 7.26–7.21 (11H,
m), 7.15 (1H, t, J¼7.6 Hz), 6.86 (1H, brs), 6.63 (1H, dd,
J¼17.5, 11.1 Hz), 5.66 (1H, d, J¼17.5 Hz), 5.22 (1H, d,
J¼11.1 Hz), 5.16 (1H, brs), 4.41 (1H, brs). 13C NMR
(100.6 MHz, CDCl3, 50 8C) d; 155.9, 139.2, 137.4, 136.8,
135.7, 132.4, 129.3, 129.0, 128.3, 128.3, 128.2, 127.8,
127.5, 126.2, 116.0, 67.3, 54.4. MS m/z: 366 (MþNa)þ.
Anal. calcd for C23H21NO2: C, 80.44; H, 6.16; N, 4.08.
Found: C, 80.36; H, 6.33; N, 4.13.
(400 MHz, CDCl3, 50 8C) d; 7.37–7.24 (7H, m), 7.18
(1H, t, J¼6.8 Hz), 7.04–6.87 (1H, brs), 5.94–5.78 (1H, m),
5.13 (1H, d, J¼10.0 Hz), 5.12 (1H, d, J¼18.2 Hz), 5.02 (1H,
d, J¼14.6 Hz), 4.53 (1H, d, J¼14.6 Hz), 3.40–3.12 (2H,
m), 1.49 (9H, brs). 13C NMR (100.6 MHz, CDCl3, 50 8C) d;
155.0, 140.8, 138.2, 138.0, 136.7, 129.8, 128.9, 128.3,
127.4, 127.3, 126.7, 116.1, 80.1, 54.1, 35.2, 28.4. MS m/z:
324 (MþH)þ. Anal. calcd for C21H25NO2: C, 77.98; H,
7.79; N, 4.33. Found: C, 77.88; H, 7.79; N, 4.07.
4.2.3. Isopropyl benzyl(2-vinylphenyl)carbamate 1e.
1H NMR
4.2.8. Benzyl 2-allylphenyl(benzyl)carbamate 1j. Color-
less oil. IR (neat) n; 1703 cm21 1H NMR (400 MHz,
.
Colorless oil. IR (neat) n; 1696 cm21
.
(400 MHz, CDCl3, 50 8C) d; 7.61 (1H, d, J¼7.6 Hz),
7.34–7.26 (6H, m), 7.20 (1H, t, J¼7.6 Hz), 6.92 (1H,
brs), 6.70 (1H, dd, J¼17.4, 11.1 Hz), 5.73 (1H, d,
J¼17.6 Hz), 5.30 (1H, d, J¼11.0 Hz), 5.11–5.02 (2H, m),
4.47 (1H, brs), 1.22 (6H, brs). 13C NMR (100.6 MHz,
CDCl3, 50 8C) d; 155.7, 139.6, 137.4, 137.8, 135.7, 132.7,
129.2, 129.0, 128.3, 128.1, 127.5, 127.4, 126.1, 115.6, 69.2,
54.2, 22.0. MS m/z: 318 (MþNa)þ. Anal. calcd for
C19H21NO2: C, 77.26; H, 7.17; N, 4.74. Found: C, 77.12;
H, 7.30; N, 4.68.
CDCl3, 50 8C) d; 7.33–7.15 (13H, m), 6.95 (1H, brs), 5.77
(1H, brs), 5.22 (2H, brs), 5.09 (1H, d, J¼14.8 Hz), 5.06 (1H,
d, J¼8.3 Hz), 5.04 (1H, d, J¼15.3 Hz), 4.55 (1H, d,
J¼14.5 Hz), 3.31–3.07 (2H, m). 13C NMR (100.6 MHz,
CDCl3, 50 8C) d; 155.9, 139.9, 138.1, 137.5, 136.8, 136.4,
130.0, 129.1, 129.0, 128.4, 127.7, 127.6, 126.9, 116.2, 67.3,
54.5, 35.2. MS m/z: 380 (MþNa)þ. Anal. calcd for
C24H23NO2: C, 80.64; H, 6.49; N, 3.92. Found: C, 80.53;
H, 6.60; N, 3.84.
4.2.9. tert-Butyl benzyl(2-vinylbenzyl)carbamate 1k.
Colorless oil. IR (neat) n; 1703 cm21 1H NMR
.
(400 MHz, CDCl3, 50 8C) d; 7.48 (1H, d, J¼7.5 Hz),
4.2.4. Ethyl benzyl(2-vinylphenyl)carbamate 1f. Color-
1H NMR (400 MHz,
less oil. IR (neat) n; 1702 cm21
.

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Y. Takigawa et al. / Tetrahedron 60 (2004) 1385–1392
7.32–7.13 (8H, m), 6.91 (1H, dd, J¼17.1, 11.1 Hz), 5.59
(1H, d, J¼17.3 Hz), 5.26 (1H, d, J¼11.0 Hz), 4.52 (2H, s),
4.33 (2H, s), 1.50 (9H, s). 13C NMR (100.6 MHz, CDCl3,
50 8C) d; 155.9, 138.2, 137.4, 134.9, 134.4, 128.5, 127.8,
127.6, 127.1, 126.3, 116.0, 80.1, 49.1, 47.1, 28.5. MS m/z:
346 (MþNa)þ. Anal. calcd for C21H25NO2: C, 77.98; H,
7.79; N, 4.33. Found: C, 77.93; H, 7.99; N, 4.38.
(0.5H, d, J¼7.8 Hz), 6.13 (1H, d, J¼7.8 Hz), 5.88 (1H, ddt,
J¼16.9, 10.0, 6.9 Hz), 5.68–5.58 (0.5H, m), 5.16–4.99
(3H, m), 4.92–4.81 (1.5H, m), 3.44 (1H, dd, J¼15.8,
7.1 Hz), 3.32 (1H, dd, J¼15.7, 6.4 Hz), 3.07 (0.5H, dd,
J¼16.0, 6.2 Hz), 2.73 (0.5H, dd, J¼16.0, 7.3 Hz), 2.50 (3H,
s), 2.47 (1.5H, s), 2.44–2.31 (1.5H, m), 2.16–2.11 (1.5H,
m), 1.82–1.78 (3H, m), 1.71–1.68 (1.5H, m), 1.49–1.16
(3H, m). 13C NMR (100.6 MHz, CDCl3) d; 151.4, 151.3,
144.5, 142.4, 142.3, 140.2, 136.2, 135.8, 135.8, 129.9,
129.3, 129.2, 129.2, 129.1, 129.0, 128.9, 128.3, 128.0,
127.5, 127.3, 126.9, 126.7, 126.5, 126.2, 116.8, 116.7, 79.8,
79.3, 49.6, 49.2, 35.7, 34.7, 34.1, 33.9, 32.0, 31.9, 25.5,
24.6, 24.5, 21.7, 15.3. HRMS calcd for C29H31NO4S:
512.1883 (MþNa)þ. Found: 512.1872.
4.2.10. Benzyl benzyl(2-vinylbenzyl)carbamate 1m.
Colorless oil. IR (neat) n; 1699 cm21
.
1H NMR
(400 MHz, CDCl3, 50 8C) d; 7.48 (1H, d, J¼7.3 Hz),
7.34–7.12 (14H, m), 6.86 (1H, brs), 5.57 (1H, d,
J¼17.1 Hz), 5.26 (1H, s) 5.22 (1H, d, J¼10.9 Hz), 4.59
(2H, brs), 4.41 (2H, brs). 13C NMR (100.6 MHz, CDCl3,
50 8C) d; 156.6, 137.5, 136.8, 134.2, 128.5, 128.5, 128.0,
127.8, 127.7, 127.3, 126.4, 116.4, 67.6, 49.1, 47.2. MS m/z:
380 (MþNa)þ. Anal. calcd for C24H23NO2: C, 80.64; H,
6.49; N, 3.92. Found: C, 80.70; H, 6.76; N, 3.90.
4.3. General procedure for zirconocene–butene complex
mediated reaction of carbamate derivatives
A solution of N-benzyl-N-benzyloxycarbonyl 2-amino-
styrene 1d (172 mg, 0.5 mmol) in THF (2 ml) was added
to a solution of ‘Cp2Zr’, prepared from Cp2ZrCl2 (175 mg,
0.6 mmol) and n-BuLi (1.30 M in hexane 0.92 ml,
1.2 mmol) in THF (2 ml) at 278 8C. After being stirred
for 2 h at room temperature, the reaction mixture was
quenched by the addition of 1 N HCl and then extracted
with ether. The organic extracts were washed with brine
and dried over MgSO4. Purification of the residue obtained
by evaporation of the solvent, by silica gel column
chromatography (hexane–AcOEt, 10:1) gave the indoline
derivative 3c (71 mg, 59% yield).
4.2.11. tert-Butyl (4-methylphenyl)sulfonyl(2-vinyl-
phenyl)carbamate 2d. White solid: mp 85.0–86.0 8C. IR
1
(KBr) n; 1739 cm21. H NMR (400 MHz, CDCl3) d; 7.93
(2H, d, J¼8.2 Hz), 7.67 (1H, d, J¼7.8 Hz), 7.41–7.30 (4H,
m), 7.18 (1H, d, J¼7.8 Hz), 6.74 (1H, dd, J¼17.4, 11.0 Hz),
5.79 (1H, d, J¼17.4 Hz), 5.32 (1H, d, J¼11.1 Hz), 2.47 (3H,
s), 1.32 (9H, s). 13C NMR (100.6 MHz, CDCl3) d; 150.6,
144.6, 137.4, 136.6, 134.3, 131.9, 130.0, 129.3, 129.3,
129.1, 128.4, 125.9, 116.9, 84.2, 27.8, 21.7. MS m/z: 396
(MþNa)þ. Anal. calcd for C20H23NO4S: C, 64.32; H, 6.21;
N, 3.75. Found: C, 64.36; H, 6.09; N, 3.78.
4.2.12. tert-Butyl 2-allylphenyl[(4-methylphenyl)sul-
fonyl]carbamate 2e. White solid: mp 92.0–93.0 8C. IR
4.3.1. 1-Benzyl-3-methyl-1,3-dihydro-2H-indol-2-one
3c.11 White solid: mp 117.0–118.0 8C. IR (KBr) n;
.
1715 cm21 1H NMR (400 MHz, CDCl3) d; 7.34–7.24
1
(KBr) n; 1730 cm21. H NMR (400 MHz, CDCl3) d; 8.03
(2H, d, J¼8.3 Hz), 7.46–7.44 (4H, m), 7.37–7.33 (1H, m),
7.16 (1H, d, J¼7.7 Hz), 6.04 (1H, ddt, J¼16.9, 10.2,
6.8 Hz), 5.27 (1H, ddd, J¼17.4, 3.3, 1.6 Hz), 5.21(1H, ddd,
J¼10.0, 2.7, 1.2 Hz), 3.63 (1H, dd, J¼15.8, 7.0 Hz), 3.53
(1H, dd, J¼15.7, 6.5 Hz), 2.57 (3H, s), 1.44 (9H, s). 13C
NMR (100.6 MHz, CDCl3) d; 150.7, 144.6, 140.3, 136.8,
135.9, 135.4, 130.2, 129.3, 129.2, 128.9, 127.0, 116.8, 84.1,
35.7, 27.8, 21.7. MS m/z: 410 (MþNa)þ. Anal. calcd for
C21H25NO4S: C, 65.09; H, 6.50; N, 3.61. Found: C, 65.18;
H, 6.46; N, 3.62.
(6H, m), 7.16 (1H, t, J¼7.3 Hz), 7.02 (1H, t, J¼7.5 Hz),
6.72 (1H, d, J¼7.8 Hz), 4.91 (2H, s), 3.54 (1H, q,
J¼7.6 Hz), 1.54 (3H, d, J¼7.6 Hz). 13C NMR
(100.6 MHz, CDCl3) d; 178.7, 143.1, 136.0, 130.6, 128.7,
127.8, 127.5, 127.3, 123.5, 122.4, 108.9, 43.6, 40.5, 15.6.
MS m/z: 238 (MþH)þ. HRMS calcd for C16H15NO:
238.1232 (MþH)þ. Found: 128.1222.
4.3.2. 1-Benzyl-4-methoxy-3-methyl-1,3-dihydro-2H-
indol-2-one 3g. White solid: mp 88.0–89.0 8C. IR (KBr)
1
n; 1717 cm21. H NMR (400 MHz, CDCl3) d; 7.21–7.10
4.2.13. Benzyl 2-allylphenyl[(4-methylphenyl)sulfonyl]-
carbamate 2f. White solid: mp 92.0–93.0 8C. IR (KBr) n;
(5H, m), 7.00 (1H, t, J¼8.2 Hz), 6.46 (1H, t, J¼8.4 Hz),
6.27 (1H, d, J¼7.8 Hz), 4.80 (1H, d, J¼15.7 Hz), 4.74 (1H,
d, J¼15.7 Hz), 3.73 (3H, s), 3.46 (1H, q, J¼7.5 Hz), 1.45
(3H, d, J¼7.6 Hz). 13C NMR (100.6 MHz, CDCl3) d; 179.5,
156.4, 144.7, 136.6, 129.4, 129.1, 127.9, 127.6, 117.0,
105.9, 102.8, 55.7, 44.2, 40.0, 14.9. MS m/z: 268 (MþH)þ.
Anal. calcd for C17H17NO2: C,76.38; H, 6.41; N, 5.24.
Found: C, 76.22; H, 6.47; N, 5.14.
1
1736 cm21. H NMR (400 MHz, CDCl3) d; 8.04 (2H, d,
J¼8.3 Hz), 7.55–7.38 (8H, m), 7.25–7.20 (3H, m), 5.97
(1H, ddt, J¼16.9, 10.2, 6.8 Hz), 5.26–5.15 (4H, m), 3.60
(1H, dd, J¼16.1, 7.4 Hz), 3.54 (1H, dd, J¼16.1, 6.9 Hz),
2.59 (3H, s). 13C NMR (100.6 MHz, CDCl3) d; 152.4,
145.3, 140.8, 136.5, 136.0, 135.3, 135.1, 130.8, 130.1,
129.8, 129.6, 129.6, 128.8, 128.7, 128.2, 127.5, 117.3, 69.0,
36.1, 22.1. MS m/z: 444 (MþNa)þ. Anal. calcd for
C24H23NO4S: C, 68.39; H, 5.50; N, 3.32. Found: C, 68.45;
H, 5.47; N, 3.35.
4.3.3. 1-Benzyl-6-methoxy-3-methyl-1,3-dihydro-2H-
indol-2-one 3h. White solid: mp 76.0–77.0 8C. IR (KBr)
1
n; 1694 cm21. H NMR (400 MHz, CDCl3) d; 7.29–7.19
(5H, m), 7.08 (1H, dd, J¼8.2, 0.8 Hz), 6.47 (1H, dd, J¼8.1,
2.3 Hz), 6.27 (1H, d, J¼2.2 Hz), 4.83 (2H, s), 3.68 (3H, s),
3.43 (1H, q, J¼7.6 Hz), 1.46 (3H, d, J¼7.6 Hz). 13C NMR
(100.6 MHz, CDCl3) d; 179.4, 159.8, 144.2, 135.9, 128.7,
127.6, 127.3, 124.0, 122.7, 106.0, 97.2, 55.4, 43.7, 40.0,
15.9. MS m/z: 268 (MþH)þ. Anal. calcd for C17H17NO2:
4.2.14. trans-2-Phenylcyclohexyl 2-allylphenyl[(4-
methylphenyl)sulfonyl]carbamate 2g. White solid: mp
128.5–129.5 8C. IR (KBr) n;1732 cm21
.
1H NMR
(400 MHz, CDCl3) d; 7.87 (1H, d, J¼8.2 Hz), 7.79 (1H,
d, J¼8.2 Hz), 7.34–7.02 (12H, m), 6.86–6.83 (3H, m), 6.78

Y. Takigawa et al. / Tetrahedron 60 (2004) 1385–1392
1391
C,76.38; H, 6.41; N, 5.24. Found: C, 76.20; H, 6.49; N,
5.16.
C24H25NO4S: C, 68.06; H, 5.95; N, 3.31. Found: C, 67.93;
H, 6.06; N, 3.31.
4.3.4. 1-Benzyl-3-methyl-3,4-dihydro-2(1H)-quinolinone
4.3.9. trans-2-Phenylcyclohexyl 2-methyl-3-(2-{[(4-
methylphenyl)sulfonyl]amino} phenyl)propanoate 4g.
White solid: mp 110.0–112.0 8C. IR (KBr) n; 3263,
3i.12 White solid: mp 79.5–80.5 8C. IR (KBr) n; 1671 cm21
.
1H NMR (400 MHz, CDCl3) d; 7.33–7.21 (5H, m), 7.17
(1H, d, J¼7.3 Hz), 7.11 (1H, td, J¼7.8, 1.2 Hz), 6.98 (1H,
td, J¼7.4, 0.6 Hz), 6.87 (1H, d, J¼8.1 Hz), 5.28 (1H, d,
J¼16.2 Hz), 5.09 (1H, d, J¼16.2 Hz), 3.06–2.98 (1H, m),
2.85–2.75 (2H, m), 1.35 (3H, d, J¼6.5 Hz). 13C NMR
(100.6 Hz, CDCl3) d; 173.2, 139.7, 137.2, 128.7, 128.0,
127.3, 127.0, 126.3, 125.7, 122.8, 115.3, 46.4, 35.6, 33.4,
15.7. MS m/z: 252 (MþH)þ. Anal. calcd for C17H17NO: C,
81.24; H, 6.82; N, 5.57. Found: C, 81.02; H, 6.79; N, 5.41.
1704 cm21 1H NMR (400 MHz, CDCl3) d; 7.86 (1H,
.
brs), 7.59 (1H, d, J¼8.3 Hz), 7.36 (2H, dd, J¼8.0, 0.9 Hz),
7.23 (2H, d, J¼7.0 Hz), 7.20–7.11 (6H, m), 7.04 (1H, dd,
J¼7.5, 1.2 Hz), 6.91(1H, dd, J¼7.6, 1.4 Hz), 4.93 (1H, td,
J¼10.9, 4.2 Hz), 2.60 (1H, td, J¼11.6, 3.4 Hz), 2.37 (3H, s),
2.31–2.24 (2H, m), 1.98 (1H, dd, J¼13.1, 3.2 Hz), 1.94–
1.88 (1H, m), 1.84–1.73 (3H, m), 1.53–1.16 (4H, m), 0.56
(3H, d, J¼6.8 Hz). 13C NMR (J¼100.6 Hz, CDCl3) d;
176.6, 143.2, 142.9, 137.3, 134.5, 133.4, 130.5, 129.4,
128.3, 127.5, 127.3, 127.1, 126.5, 125.9, 125.4, 76.7, 49.4,
41.7, 34.0, 33.5, 32.1, 25.7, 24.7, 21.5, 17.8. MS m/z: 514
(MþNa)þ. Anal. calcd for C29H33NO4S: C, 70.85; H, 6.77;
N, 2.85. Found: C, 70.79; H, 6.84; N, 2.84.
4.3.5. 2-Benzyl-4-methyl-1,4-dihydro-3(2H)-isoquinoli-
none 3k. Pale yellow oil (unstable). IR (neat) n;
.
1651 cm21 1H NMR (400 MHz, CDCl3) d; 7.35–7.18
(8H, m), 7.07 (1H, d, J¼7.5 Hz), 4.79 (1H, d, J¼14.8 Hz),
4.54 (1H, d, J¼14.9 Hz), 4.44 (1H, d, J¼15.7 Hz), 4.29 (1H,
d, J¼15.7 Hz), 3.66 (1H, q, J¼7.3 Hz), 1.55 (3H, d,
J¼7.4 Hz). 13C NMR (100.6 MHz, CDCl3) d; 172.3,
137.9, 136.8, 131.0, 128.7, 127.8, 127.7, 127.5, 126.4, 126.2,
125.2, 50.1, 49.6, 41.6, 18.1. MS m/z: 274 (MþNa)þ. HRMS
calcd for C17H17NO: 274.1208 (MþH)þ. Found: 174.1205.
4.4. Iodination reaction of the intermediate
After treating 1j (179 mg, 0.5 mmol) with zirconocene–
butene complex in THF as described in general
procedure, to the reaction mixture was added iodine
(508 mg, 2.0 mmol) dissolved in THF (2 ml), and then
the whole was stirred for 1 h at 220 8C. Usual extractive
work-up and purification of the crude material by silica
gel column (hexane–AcOEt, 20:1) gave the iodide 11 in
50% yield.
4.3.6. tert-Butyl 2-methyl-3-(2-{[(4-methylphenyl)sul-
fonyl]amino}phenyl)-propanoate 4e. White solid: mp
1
113.0–114.0 8C. IR (KBr) n; 3263, 1704 cm21. H NMR
(400 MHz, CDCl3) d; 7.92 (1H, brs), 7.62 (2H, d,
J¼8.3 Hz), 7.20 (2H, d, J¼8.1 Hz), 7.16 (1H, td, J¼7.6,
1.6 Hz), 7.10 (1H, td, J¼7.4, 1.2 Hz), 7.04 (1H, dd, J¼7.5,
1.6 Hz), 2.52–2.43 (2H, m), 2.38 (3H, s), 2.18–2.10 (2H,
m), 1.32 (9H, s), 1.13 (3H, d, J¼6.6 Hz). 13C NMR
(100.6 Hz, CDCl3) d; 176.7, 143.3, 137.3, 134.6, 133.6,
130.6, 129.4, 127.4, 127.1, 126.0, 125.6, 81.4, 42.6, 33.8,
27.9, 21.5, 18.5. MS m/z: 412 (MþNa)þ. Anal. calcd for
C21H27NO4S: C, 64.75; H, 6.99; N, 3.60. Found: C, 64.52;
H, 6.88; N, 3.61.
4.4.1. 1-Benzyl-3-(iodomethyl)-3,4-dihydro-2(1H)-
quinolinone 11. Light yellow solid: mp 92.0–93.0 8C. IR
(KBr) n; 1674 cm21. 1H NMR (400 MHz, CDCl3) d; 7.33–
7.19 (6H, m), 7.14 (1H, t, J¼7.8 Hz), 7.01 (1H, t,
J¼7.2 Hz), 6.89 (1H, d, J¼8.1 Hz), 5.26 (1H, d,
J¼16.2 Hz), 5.09 (1H, d, J¼16.2 Hz), 3.74 (1H, dd,
J¼10.1, 3.8 Hz), 3.38 (1H, dd, J¼10.0, 8.8 Hz), 3.19 (1H,
dd, J¼15.3, 5.4 Hz), 3.01 (1H, dd, J¼15.3, 11.3 Hz),
2.88 (1H, dddd, J¼11.1, 8.9, 5.4, 3.6 Hz). 13C NMR
(100.6 Hz, CDCl3) d; 169.4, 139.2, 136.7, 128.8, 128.4,
127.8, 127.2, 126.3, 124.6, 123.3, 115.5, 46.6, 42.7, 32.1,
4.9. MS m/z: 400 (MþNa)þ. Anal. calcd for C17H16INO:
C, 54.13; H, 4.28; N, 3.71. Found: C, 53.91; H, 4.53; N,
3.61.
4.3.7. tert-Butyl 2-[(E)-1-propenyl]phenylcarbamate 6e.
Colorless oil. IR (KBr) n; 3346, 1732 cm21 1H NMR
.
(400 MHz, CDCl3) d; 7.79 (1H, d, J¼6.9 Hz), 7.30 (1H, d,
J¼7.7 Hz), 7.21 (1H, t, J¼7.5 Hz), 7.03 (1H, t, J¼7.5 Hz),
6.45 (1H, d, J¼15.6 Hz), 6.40 (1H, brs), 6.11 (1H, dq,
J¼15.6, 6.6 Hz), 1.93 (3H, dd, J¼6.6, 1.6 Hz), 1.53 (9H, s).
13C NMR (100.6 Hz, CDCl3) d; 153.1, 134.7, 130.0, 129.2,
127.6, 127.1, 126.0, 123.8, 121.3, 80.5, 28.4, 18.9. MS m/z:
178 (MþNa)þ. Anal. calcd for C14H19NO2: C, 72.07; H,
8.21; N, 6.00. Found: C, 71.90; H, 8.45; N, 5.82.
4.4.2. Benzyl-4-methylene-1,4-dihydro-3(2H)-isoquinoli-
none 12. Pale yellow oil (unstable). IR (neat) n; 1649 cm21
.
1H NMR (400 MHz, CDCl3) d; 7.66 (1H, d, J¼7.5 Hz),
7.34–7.24 (7H, m), 7.08 (1H, d, J¼7.3 Hz), 6.53 (1H, s),
6.09 (1H, s), 4.85 (2H, s), 4.47 (2H, s). 13C NMR (100.6 Hz,
CDCl3) d; 163.9, 136.6, 134.6, 131.1, 129.5, 128.7, 128.2,
128.1, 127.7, 127.6, 125.6, 123.8, 119.6, 50.5, 49.7. MS m/z:
250 (MþH)þ. HRMS calcd for C17H15NO: 250.1232
(MþH)þ. Found: 250.1234.
4.3.8. Benzyl 2-methyl-3-(2-{[(4-methylphenyl)sulfonyl]-
amino}phenyl)propanoate 4f. White solid: mp 52.0–
53.0 8C. IR (KBr) n; 3330, 1734 cm21
.
1H NMR
(400 MHz, CDCl3) d; 7.70 (1H, brs), 7.61 (2H, d,
J¼8.3 Hz), 7.36–7.29 (4H, m), 7.20–7.14 (5H, m), 7. 09
(1H, td, J¼7.4, 1.3 Hz), 7.04 (1H, td, J¼7.6, 1.7 Hz),
5.07 (1H, d, J¼12.3 Hz), 5.01 (1H, d, J¼12.3 Hz),
2.70–2.59 (2H, m), 2.37 (3H, s), 2.32–2.24 (1H, m), 1.19
(3H, d, J¼6.7 Hz). 13C NMR (100.6 Hz, CDCl3) d; 176.9,
143.4, 137.2, 135.5, 134.6, 133.5, 130.6, 129.5, 128.5,
128.2, 128.0, 127.5, 127.1, 126.2, 125.7, 66.7, 41.5, 33.8,
21.5, 18.3. MS m/z: 424 (MþH)þ. Anal. calcd for
References and notes
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2. Zirconium-mediated intermolecular coupling reaction of

1392
Y. Takigawa et al. / Tetrahedron 60 (2004) 1385–1392
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was reported Takahashi, T.; Xi, C.; Ura, Y.; Nakajima, K.
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butene complex Hanzawa, Y.; Ikeuchi, Y.; Nakamura, T.;
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