Access to ring-fused azepino[3,4-b]indole-1,5-dione derivatives by ring-closing olefin metathesis

Article abstract of DOI:10.1016/j.tet.2004.07.069

The new ring-fused azepino[5,6-b]indole derivatives 3, 4 and 5 were prepared from diene precursors 8, 9, 13 and 15 in fair yields via a final ring-closing olefin metathesis. Graphical Abstract

Full text of DOI:10.1016/j.tet.2004.07.069

Tetrahedron 60 (2004) 10099–10109
Access to ring-fused azepino[3,4-b]indole-1,5-dione derivatives by
ring-closing olefin metathesis
a
Julien Perron, Benoıt Joseph and Jean-Yves Merour
b
a,
*
ˆ
´
a
´ ´ ´
Institut de Chimie Organique et Analytique, UMR-CNRS 6005, Universite d’Orleans, B.P. 6759, 45067 Orleans Cedex 2, France
b
´ ˆ
Laboratoire de Chimie Organique 1, UMR-CNRS 5181, Universite Claude Bernard—Lyon 1, CPE—Batiment 308,
43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
Received 4 May 2004; revised 1 July 2004; accepted 12 July 2004
Available online 15 September 2004
Abstract—The new ring-fused azepino[5,6-b]indole derivatives 3, 4 and 5 were prepared from diene precursors 8, 9, 13 and 15 in fair yields
via a final ring-closing olefin metathesis.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
The azepino framework is encountered in several potent
kinase inhibitors such as natural marine hymenialdisine1
and some close derivatives of 1.2 Recently, Meijer et al.
have reported that 5-arylhydrazinoazepino[5,6-b]indole
exhibited good inhibitory activities against cyclin-depen-
dant kinases.3 In our ongoing research on new azepino[5,6-
b]indole derivatives,4 we have recently described the
preparation of the pyrrolo[1,2:10,20]azepino[5,6-b]indole 2,
related to the anthramycin structure, from indole-2-
carboxylic acid and a b-aminoester through an intra-
molecular electrophilic cyclisation (Fig. 1).5
Since the discovery of new well-defined catalysts
(efficiency, functional-group-tolerance) by Schrock and
Grubbs, the ring-closing metathesis (RCM) is considered
as one of the most powerful synthetic tools in organic
chemistry.6 RCM provides an efficient and mild route for
the synthesis of natural products, medium-ring and macro-
ring carbocyclic or heterocyclic motifs.7 Based on a RCM
approach, we investigated several synthetic pathways to
Figure 1. The structures of fused azepino[3,4-b]indole-1,5-diones.
access to the new ring-fused azepino[5,6-b]indole deriva-
tives 3,4 and 5 from the azepino[5,6-b]indoles 1a4b or 1b.4b
In this paper, we report in detail the introduction of olefin
2. Results and discussion
chains on an azepinic nucleus to generate the dienic
Focusing our initial attention on the preparation of the
precursors and the final RCM.
tetracyclic derivatives 3, a double alkylation of 1a on
positions-2 and 3 was investigated to generate the dienic
precursors 8 (Scheme 1). The first olefin chain was
introduced on the position-2 by a classical N-alkylation.
The reaction was carried out in the presence of sodium
hydride and bromoalkenes (3-bromopropene, 4-bromobutene,
Keywords: Indole; Azepino; Metathesis; Ring closure.
* Corresponding author. Tel.: C33-238-417-281; fax: C33-238-494-592;
e-mail: jean-yves.merour@univ-orleans.fr
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.069

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J. Perron et al. / Tetrahedron 60 (2004) 10099–10109
Scheme 1. Reaction conditions (a) NaH (1.1 equiv.), DMF, 0 8C, 1 h;
(b) R-Br (1.5 equiv.), DMF, rt, 1 or 12 h, (6a nZ1 88%, 6b nZ2 54%, 6c
nZ3 64%, 6d nZ4 76%); (c) LiHMDS (1.8 equiv.), THF, K78 8C, 2 h;
(d) Br2 (1 equiv.), THF, K78 8C, 15 min; (e) DBU (1.5 equiv.), DMF, rt,
2 h, (7a–d 80–83%); (f) TiCl4 (4 equiv.), allylTMS (6 equiv.), CH2Cl2,
K40 8C to rt, 15 h, (8a nZ1 69%, 8b nZ2 54%, 8c nZ3 50%, 8d nZ4
48%); (g) Grubb’s reagent (10% mol), 0.03 M solution, CH2Cl2, rt.
5-bromopentene or 6-bromohexene) in DMF. N-Substituted
derivatives 6 were obtained in 54–88% yields. The
C-allylation on the position-3 was more problematic. After
many experiments, the Sakurai reaction8 (1,4-addition) was
found to be the best method for the attachment of the allyl
chain on the azepinic ring. This route required the
preparation of a,b-ethylenic ketones 7. The a-bromination
of ketones 6 was effective using LiHMDS (1.8 equiv.) and
bromine (1 equiv.) to lead to unstable bromo intermediates
which were directly treated by DBU (1.5 equiv.) to afford
ketones 7 in 80–83% overall yields. The formation of a,a-
dibromo derivatives was also observed when either the
addition of bromine is too slow or with higher reagent
concentrations.
Scheme 2. Reaction conditions: (a) NaH (2 equiv.), THF, 0 8C, 3 h;
(b) 3-bromopropene (5 equiv.), THF, rt, 16 h, (77%); (c) LiHMDS
(1.8 equiv.), THF, K78 8C, 1 h; (d) NCCO2Et (1.1 equiv.), THF,
K78 8C, 15 min, (92%); (e) K2CO3 (5 equiv.), Br–(CH2)n–CH]CH2
(5 equiv.), acetone, rflx, 48–72 h, (11a nZ1 92%, 11b nZ2 47%, 11c nZ3
59%, 11d nZ4 68%); (f) LiOH.H2O (2 equiv.), EtOH/H2O, rflx, 30 min,
(12a–d 97–99%); (g) NaH (1.5 equiv.), THF, 0 8C, 1 h; (h) 3-bromo-
propene (1.2 equiv.), rt, 16 h, (13b nZ2 93%, 13c nZ3 89%); (i) Grubb’s
reagent (10% mol), 0.03 M solution, CH2Cl2, rt.
Compounds 7 were, then, subjected to the Sakurai allylation
reaction to afford the corresponding 3-allyl derivatives 8. It
should be noted that allyltrimethylsilane and TiCl4 were
used in excess to get fair 1,4-addition yield.
the desired dienes. The simplest way was a diallylation
reaction on position-4 of 2b to give 9 in 77% yield.
We achieved the RCM of 8a using the Grubb’s first
generation catalyst (bis-(tricyclo-hexylphosphine)benzyl-
idene ruthenium (IV) dichloride, 10% mol) in CH2Cl2 at
room temperature (Scheme 1). The tetracyclic compound 3a
was isolated in 84% yield. Similarly, the same reaction
conditions applied to 8b–d afforded the higher ring-sized
derivatives 3b–d in excellent yields (Table 1).
We needed an alternative way to introduce two different
olefin side chains since a monoallylation of 2b or an enolate
alkylation with bromoalkenes (4-bromobutene, 5-bromo-
pentene or 6-bromohexene) were unproductive. We then
thought to the ketoester derivative 10, as an interesting
intermediate, suitable for a monoalkylation on the position-
4 with a low reactive halide, then for decarboxylation prior
to perform the second C-alkylation with allyl bromide. We
easily obtained 10 (92% yield) by treating 2b with LiHMDS
(1.8 equiv.) in THF at K78 8C followed by addition of
NCCO2Et (1.1 equiv.). The enol form of 10 was observed
by NMR spectroscopy in CDCl3 solution (see Section 3).
The alkylation of 10 in the presence of K2CO3 and
bromoalkenes (3-bromopropene, 4-bromobutene, 5-bromo-
pentene or 6-bromohexene) in acetone gave C-alkylated
derivatives 11a–d in fair yields. The decarboxylation of 11
was carried out with lithium hydroxide hydrate at reflux of
EtOH to deliver derivatives 12 in almost quantitative yields.
The synthesis of the spiro derivatives 4 required two
successive C-alkylations on the same position (Scheme 2).
Two independent routes were developed to give access to
Table 1. RCM of dienes 8a–d
Olefin
Product
n
Time
(h)
Yield
(%)
8a
8b
8c
8d
3a
3b
3c
3d
1
2
3
4
1
2
1
48
84
96
98
86

J. Perron et al. / Tetrahedron 60 (2004) 10099–10109
10101
The final C-allylation on 12b and 12c was performed to
reach the suitable dienes 13b–c. As reported for the first
series, the dienes prepared above were submitted to ring
closure (Scheme 2). As can be seen from the results listed in
Table 2, the spiro derivatives 4 were again obtained in
excellent yields.
of 15a gave the corresponding diastereomer of 5a in the
same yield (96% yield).
An alternative way with the a,b-ethylenic ketone 169 as
starting product was also explored (Scheme 4). The Sakurai
reaction on 16 gave the 3-allyl derivative 17 in 66% yield.
The carboxylation of 17 on position-4 was carried out to
afford the ester 18 (91% yield). Unfortunately, the C-4
alkylation using the conditions developed for 10 failed in
our hands. In fact, the major product isolated was the
O-alkylated derivative 19 (56% yield), and not the
compound 20.
Table 2. Preparation of spiro derivatives 4 from dienes 9, 13
Olefin
Product
n
Time
(h)
Yield
(%)
9
13b
13c
4a
4b
4c
1
2
3
8
2
48
84
92
90
On the basis of the synthetic results collected from first two
families, we reasoned that combining the use of mono-
alkylated derivatives 12 as starting material and the Sakurai
reaction to introduce the alkenyl chain on position-3 could
provide the key diene 15. As shown in Scheme 3, a,b-
ethylenic ketones 14 were obtained following the bromina-
tion–elimination sequence and then, the allyl chain was
effectively introduced on the position-3 in fair yields by the
Sakurai reaction. Except for 15a, compounds 15 were
isolated as a mixture of diastereomers (ratio 4:5). According
to the RCM reactions described above, dienes 15 underwent
ring closure in very high yields to afford the derivatives 5
(Table 3). The RCM reaction applied on each diastereomer
Scheme 4. Reaction conditions (a) TiCl4 (4 equiv.), allylTMS (6 equiv.),
CH2Cl2, K40 8C to rt, 15 h, (66%); (b) LiHMDS (1.8 equiv.), THF,
K78 8C, 1 h; (c) NCCO2Et (1.5 equiv.), THF, K78 8C, 15 min, (91%);
(d) K2CO3 (5 equiv.), Br-(CH2)2–CH]CH2 (5 equiv.), acetone, rflx, 48 h,
(56%).
In conclusion, we have developed three new series of ring-
fused azepino[5,6-b]indole derivatives through a wide
preparation of diene precursors which were finally sub-
mitted to RCM.
Scheme 3. Reaction conditions (a) LiHMDS (1.5 equiv.), THF, K78 8C,
2 h; (b) Br2 (1.2 equiv.), rt, 2 h; (c) DBU (1.5 equiv.), 45 min (14a nZ1
88%, 14b nZ2 84%, 14c nZ3 87%); (d) TiCl4 (4 equiv.), allylTMS
(6 equiv.), CH2Cl2, K40 8C to rt, 15 h (15a nZ1 51%, 15b nZ2 56%, 15c
nZ3 68%); (e) Grubb’s reagent (10% mol), 0.03 M solution, CH2Cl2, rt.
3. Experimental
3.1. General experimental procedures
Table 3. RCM of dienes 15a–b
Melting points were determined using a Bu¨chi capillary
instrument and are uncorrected. The infrared spectra of
compounds were recorded on a Perkin–Elmer FTIR paragon
1000 spectrometer. NMR spectra were recorded at 300 K in
CDCl3 on a Bruker Avance DPX 250. Chemical shifts are
Olefin
Product
n
Time
(h)
Yield
(%)
15a
15b
5a
5b
1
2
8
12
96
93

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J. Perron et al. / Tetrahedron 60 (2004) 10099–10109
expressed in parts per million relative to tetramethylsilane
(TMS). Mass spectra were recorded on Perkin–Elmer
SCIEX API 300 using ionspray methodology. Thin-layer
chromatographies (TLC) were run on precoated silica gel
plates (Merck 60F254) and the spots were visualised using an
UV light at 254 nm. Flash chromatographies were carried
out on column using flash silica gel 60 Merck (40–63 mm)
using the indicated solvents (petroleum ether (PE): boiling
range 40–60 8C). All reactions were performed under a
nitrogen atmosphere and those requiring anhydrous con-
ditions were conducted in flame-dried apparatus.
(m, 2H, CH2), 2.90–3.01 (m, 1H, NCH2), 3.34–3.40 (m, 1H,
NCH2), 4.04 (s, 3H, NCH3), 4.30–4.37 (m, 1H, NCH), 5.54–
5.64 (m, 1H, ]CH), 5.85–5.96 (m, 1H, ]CH), 7.30–7.41
(m, 3H, HAr), 8.36 (d, 1H, JZ7.1 Hz, HAr); 13C NMR
(62.90 MHz, CDCl3) d 26.3 (CH2), 29.7 (CH2), 31.0 (CH2),
32.7 (NCH3), 45.4 (CH2), 49.0 (NCH2), 57.5 (NCH), 110.2
(CH), 115.6 (C), 123.4 (CH), 123.7 (CH), 125.0 (C), 125.5
(CH), 127.2 (CH), 133.1 (CH), 135.3 (C), 138.5 (C), 162.8
(CO), 195.5 (CO); MS (IS) m/z 309 (MC1)C. Anal. Calcd
for C19H20N2O2: C, 74.00; H, 6.54; N, 9.08. Found: C,
74.25; H, 6.72; N, 8.90.
3.2. General procedure for RCM
3.2.4. 5-Methyl-9,10,11,14,14a,15-hexahydroazonino-
[20,10:7,1]azepino[3,4-b]indole-6,16(5H,8H)-dione (3d).
Diene precursor: 8d, tZ48 h; chromatography eluent: PE/
EtOAc 7:3; yield: 86%. Mp 150–152 8C (EtOAc); IR (KBr)
Grubb’s reagent (0.03 mmol) was added to a solution of
diene precursor 8, 9, 13 or 15 (0.3 mmol) in anhydrous
CH2Cl2 (10 mL). The final solution was stirred for t h at
room temperature. The solvent was evaporated, and the
residue obtained was purified by column chromatography to
give 3, 4 or 5.
1
n1631 (CO) cmK1; H NMR (250 MHz, CDCl3) d 1.89–
2.17 (m, 6H, CH2), 2.53–2.71 (m, 2H, CH2), 2.83–2.96 (m,
2H, CH2), 3.22–3.29 (m, 1H, NCH2), 3.54–3.63 (m, 1H,
NCH2), 4.07 (s, 3H, NCH3), 4.82–4.89 (m, 1H, NCH), 5.48–
5.55 (m, 1H, ]CH), 5.72–5.78 (m, 1H, ]CH), 7.32–7.46
(m, 3H, HAr), 8.49 (d, 1H, JZ7.1 Hz, HAr); 13C NMR
(62.90 MHz, CDCl3): d 22.4 (CH2), 25.5 (CH2), 27.1 (CH2),
30.4 (CH2), 33.3 (NCH3), 46.7 (CH2), 49.7 (NCH2), 56.0
(NCH), 110.3 (CH), 115.4 (C), 123.9 (2CH), 125.0 (C),
125.5 (CH), 127.7 (CH), 132.3 (CH), 137.1 (C), 138.5 (C),
161.7 (CO), 193.0 (CO); MS (IS) m/z 323 (MC1)C. Anal.
Calcd for C20H22N2O2: C, 74.51; H, 6.88; N, 8.69. Found:
C, 74.22; H, 6.97; N, 8.86.
3.2.1. 5-Methyl-8,11,11a,12-tetrahydro-5H-pyrido[20,10:
7,1]azepino[3,4-b]indole-6,13-dione (3a). Diene precursor:
8a, tZ1 h; chromatography eluent: PE/EtOAc 6:4; yield:
84%. Mp 161–162 8C (EtOAc); IR (KBr) n 1641 (CO), 1614
1
(CO) cmK1; H NMR (250 MHz, CDCl3) d 2.23 (dd, 1H,
JZ2.7, 15.2 Hz, CH2CHN), 2.60 (dd, 1H, JZ.7, 15.2 Hz,
CH2CHN), 2.63 (dd, 1H, JZ0.6, 18.5 Hz, CH2CO), 3.14
(dd, 1H, JZ11.1, 18.5 Hz, CH2CO), 4.06 (s, 3H, NCH3),
4.13 (dd, 1H, JZ1.5, 16.1 Hz, NCH2), 4.23 (dd, 1H, JZ1.5,
16.1 Hz, NCH2), 4.65–4.73 (m, 1H, NCH), 6.05–6.07 (m,
2H, 2]CH), 7.31–7.40 (m, 3H, HAr), 8.34 (d, 1H, JZ
7.9 Hz, HAr); 13C NMR (62.90 MHz, CDCl3) d 29.8 (CH2),
32.8 (NCH3), 40.9 (CH2CO), 49.3 (NCH), 50.6 (NCH2),
110.3 (CH), 116.2 (C), 123.6 (CH), 123.9 (CH), 124.6 (CH),
125.1 (C), 125.2 (CH), 125.7 (CH), 135.1 (C), 138.7 (C),
162.0 (CO), 196.0 (CO); MS (IS) m/z 281 (MC1)C. Anal.
Calcd for C17H16N2O2: C, 72.84; H, 5.75; N, 9.99. Found:
C, 73.03; H, 5.94; N, 9.82.
3.2.5. 4-[Spiro(3-cyclopentenyl)]-2-(4-methoxybenzyl)-
10-methyl-3,4-dihydroazepino[3,4-b]indole-1,5(2H,
10H)-dione (4a). Diene precursor: 9, tZ8 h; chromato-
1
graphy eluent: PE/EtOAc 8:2; yield: 84%. Gum; H NMR
(250 MHz, DMSO-d6, 80 8C) d 2.28 (d 2H, JZ15.0 Hz,
CH2), 2.69 (d, 2H, JZ15.0 Hz, CH2), 3.60 (s, 2H, NCH2),
3.74 (s, 3H, OCH3), 4.04 (s, 3H, NCH3), 4.75 (s, 2H,
NCH2Ph), 5.65 (s, 2H, 2]CH), 6.91 (d, 2H, JZ8.7 Hz,
HAr), 7.27–7.32 (m, 3H, HAr), 7.41 (dd, 1H, JZ7.9, 8.1 Hz,
HAr), 7.64 (d, 1H, JZ8.1 Hz, HAr), 8.23 (d, 1H, JZ8.1 Hz,
HAr); 13C NMR (62.9 MHz, CDCl3) d 33.1 (NCH3), 41.9
(2CH2), 52.0 (2CH2), 55.6 (OCH3), 59.8 (C), 110.2 (CH),
114.3 (2CH), 116.1 (C), 123.7 (CH), 123.8 (CH), 125.5 (C),
125.7 (CH), 128. (C), 129.7 (2CH), 133.7 (C), 138.6 (C),
159.4 (C), 161.8 (CO), 200.9 (CO); MS (IS) m/z 415 (MC
H)C. Anal. Calcd for C25H24N2O3: C, 74.98; H, 6.04; N,
6.99. Found: C, 74.76; H, 6.17; N, 7.14.
3.2.2. 5-Methyl-9,12,12a,13-tetrahydroazepino[20,10:
7,1]azepino[3,4-b]indole-6,14(5H,8H)-dione (3b). Diene
precursor: 8b, tZ2 h; chromatography eluent: PE/EtOAc
1:1; yield: 96%. Mp 187–189 8C (EtOAc); IR (KBr) n1638
1
(CO), 1615 (CO) cmK1; H NMR (250 MHz, CDCl3) d
2.20–3.08 (m, 6H, CH2), 3.91–3.99 (m, 1H, NCH2), 4.06 (s,
3H, NCH3), 4.10–4.24 (m, 1H, NCH2), 4.54–4.65 (m, 1H,
NCH), 5.63–5.65 (m, 2H, 2]CH), 7.31–7.42 (m, 3H, HAr),
8.37 (d, 1H, JZ7.9 Hz, HAr); 13C NMR (62.90 MHz,
CDCl3) d 30.8 (CH2), 32.0 (CH2), 32.9 (NCH3), 39.0
(CH2CO), 50.9 (NCH2), 56.4 (NCH), 110.2 (CH), 116.0
(C), 123.5 (CH), 123.6 (CH), 123.7 (CH), 125.0 (C), 125.5
(CH), 130.7 (CH), 134.7 (C), 138.6 (C), 161.5 (CO), 195.4
(CO); MS (IS) m/z 295 (MC1)C. Anal. Calcd for
C18H18N2O2: C, 73.45; H, 6.16; N, 9.52. Found: C, 73.74;
H, 6.29; N, 9.34.
3.2.6. 4-[Spiro(3-cyclohexenyl)]-2-(4-methoxybenzyl)-
10-methyl-3,4-dihydroazepino[3,4-b]indole-1,5(2H,
10H)-dione (4b). Diene precursor: 13b. tZ2 h; chroma-
tography eluent: PE/EtOAc 4:6; yield: 92%. Gum; IR (film)
n 1644 (CO), 1627 (CO) cmK1 1H NMR (250 MHz,
;
CDCl3) d 1.56–1.66 (m, 2H, CH2), 2.02–2.30 (m, 3H, 2
CH2), 2.54 (d, 1H, JZ18.5 Hz, CH2), 3.49 (d, 1H, JZ
15.5 Hz, NCH2), 3.61 (d, 1H, JZ15.5 Hz, NCH2), 3.81 (s,
3H, OCH3), 4.11 (s, 3H, NCH3), 5.15–5.35 (m, 2H,
NCH2Ph), 5.83 (s, 2H, 2]CH), 6.88 (d, 2H, JZ8.8 Hz,
HAr), 7.27–7.43 (m, 5H, HAr), 8.34 (d, 1H, JZ7.9 Hz, HAr);
13C NMR (62.9 MHz, CDCl3) d 22.1 (CH2), 27.2 (CH2),
29.4 (CH2), 32.9 (NCH3), 48.7 (CH2), 50.8 (C), 50.9 (CH2),
55.4 (OCH3), 110.2 (CH), 114.3 (2CH), 116.1 (C), 123.5
(CH), 123.6 (CH), 124.9 (CH), 125.6 (CH), 125.8 (CH),
3.2.3. 5-Methyl-8,9,10,13,13a,14-hexahydro-5H-azocino-
[20,10:7,1]azepino[3,4-b]indole-6,15-dione (3c). Diene pre-
cursor: 8c, tZ1 h; chromatography eluent: PE/EtOAc 1:1;
yield: 98%. Mp 147–149 8C (EtOAc); IR (KBr) n1638
1
(CO), 1616 (CO) cmK1; H NMR (250 MHz, CDCl3) d
1.72–1.83 (m, 2H, CH2), 2.03–2.20 (m, 4H, CH2), 2.65–2.80

J. Perron et al. / Tetrahedron 60 (2004) 10099–10109
10103
129.1 (C), 129.7 (2CH), 130.0 (C), 133.5 (C), 138.7 (C),
159.3 (C), 162.2 (CO), 201.3 (CO); MS (IS) m/z 415 (MC
H)C. Anal. Calcd for C26H26N2O3: C, 75.34; H, 6.32; N,
6.78. Found: C, 74.93; H, 6.49; N, 6.95.
eluent: PE/EtOAc 8:2; yield: 93%. Gum; IR (film) n 1647
(CO); 1625 (CO) cmK1; 1H NMR and 13C NMR data were
not available due to a very bad resolution of the spectra; MS
(IS) m/z 415 (MCH)C. Anal. Calcd for C26H26N2O3: C,
75.34; H, 6.32; N, 6.76. Found: C, 75.11; H, 6.49; N, 6.95.
3.2.7. 4-[Spiro(3-cycloheptenyl)]-2-(4-methoxybenzyl)-
10-methyl-3,4-dihydroazepino[3,4-b]indole-1,5-(2H,
10H)-dione (4c). Diene precursor: 13c, tZ48 h; chroma-
tography eluent: PE/EtOAc 6:4; yield: 90%. Gum; IR (film)
3.3. Typical procedure for the synthesis of 6
Sodium hydride (96 mg, 2.41 mmol, 60% dispersed in oil)
was added portionwise to a solution of 2a (500 mg,
2.19 mmol) in DMF (10 mL) at 0 8C. The mixture was
stirred for 1 h at room temperature. Alkenyl bromide
(3.29 mmol) was slowly added and the final mixture was
stirred for 1 h at room temperature. Water (50 mL) was
added and the mixture was extracted with EtOAc (2!
20 mL). The organic layer was washed twice with saturated
aqueous NH4Cl solution then dried over MgSO4. After
evaporation, the crude residue was purified by column
chromatography to afford 6.
n 1647 (CO), 1622 (CO) cmK1 1H NMR (250 MHz,
.
CDCl3) d 1.65–2.30 (m, 7H, 3 CH2 CCH2), 2.90–2.96 (m,
1H, CH2), 3.58 (d, 1H, JZ15.2 Hz, NCH2), 3.62 (d, 1H, JZ
15.2 Hz, NCH2), 3.81 (s, 3H, OCH3), 4.10 (s, 3H, NCH3),
4.60–5.10 (m, 2H, NCH2Ph), 5.62–5.68 (m, 1H, ]CH),
6.07–6.12 (m, 1H, ]CH), 6.88 (d, 2H, JZ8.8 Hz, HAr),
7.27–7.42 (m, 5H, HAr), 8.27 (d, 1H, JZ7.9 Hz, HAr); 13C
NMR (62.9 MHz, CDCl3) d 18.0 (CH2), 21.2 (CH2), 29.1
(CH2), 32.8 (NCH3), 44.3 (CH2), 50.2 (CH2), 50.7 (CH2),
54.5 (C), 55.4 (OCH3), 110.2 (CH), 114.3 (2CH), 115.6 (C),
123.3 (CH), 123.4 (CH), 125.6 (CH), 125.8 (C), 127.1 (CH),
129.6 (C), 129.7 (2CH), 133.2 (C), 134.6 (CH), 138.7 (C),
159.3 (C), 162.6 (CO), 201.2 (CO); MS (IS) m/z 429 (MC
H)C. Anal. Calcd for C27H28N2O3: C, 75.68; H, 6.59; N,
6.54. Found: C, 76.02; H, 6.72; N, 6.40.
3.3.1. 2-Allyl-10-methyl-3,4-dihydroazepino[3,4-b]-
indole-1,5(2H,10H)-dione (6a). Alkenyl bromide: 3-
bromopropene; chromatography eluent: PE/EtOAc 7:3;
yield: 88%. Mp 139–141 8C (EtOAc); IR (KBr) n 1645
1
(CO), 1620 (CO) cmK1; H NMR (250 MHz, CDCl3) d
2.86–2.90 (m, 2H, CH2), 3.70–3.74 (m, 2H, CH2), 4.05 (s,
3H, NCH3), 4.29 (d, 2H, JZ6.0 Hz, NCH2), 5.27–5.34 (m,
2H, ]CH2), 5.84–5.99 (m, 1H, ]CH), 7.30–7.42 (m, 3H,
HAr), 8.41 (d, 1H, JZ8.1 Hz, HAr); 13C NMR (62.9 MHz,
CDCl3) d 32.8 (NCH3), 43.9 (CH2), 44.1 (CH2), 50.1
(NCH2), 110.2 (CH), 115.6 (C), 118.7 (CH2), 123.6 (CH),
123.8 (CH), 125.1 (C), 125.6 (CH), 132.8 (CH), 134.5 (C),
138.6 (C), 161.3 (CO), 195.6 (CO); MS (IS) m/z 269 (MC
H)C. Anal. Calcd for C16H16N2O2: C, 71.62; H, 6.01; N,
10.44. Found: C, 71.92; H, 5.88; N, 10.62.
3.2.8. 7-(4-Methoxybenzyl)-5-methyl-7a,8,11,11a-tetra-
hydroindolo[2,3-c][1]benzazepine-6,12(5H,7H)-dione
(5a). Diene precursor: 15a (Diastereomer 1), tZ8 h;
chromatography eluent: PE/EtOAc 8:2; yield: 96%. Gum;
IR (film) n 1641 (CO), 1622 (CO) cmK1 1H NMR
;
(250 MHz, CDCl3) d 2.09–2.25 (m, 2H, CH2), 2.41–2.53
(m, 1H, CH2), 2.87–2.90 (m, 1H, CH2), 3.04–3.14 (m, 1H,
CHCO), 3.82 (s, 3H, OCH3), 3.90 (broad s, 1H, NCH), 4.13
(s, 3H, NCH3), 4.55 (d, 1H, JZ14.2 Hz, NCH2), 5.17 (d,
1H, JZ14.2 Hz, NCH2), 5.40 (broad s, 1H, ]CH), 5.61
(broad s, 1H, ]CH), 6.89 (d, 2H, JZ8.5 Hz, HAr), 7.32–
7.43 (m, 5H, HAr), 8.50 (d, 1H, JZ7.8 Hz, HAr); 13C NMR
(62.9 MHz, CDCl3) d 28.1 (CH2), 29.4 (CH2), 33.4 (NCH3),
53.7 (NCH2), 55.0 (CH), 55.4 (CH3), 57.3 (NCH), 110.2
(CH), 114.4 (2CH), 115.5 (C), 123.8 (CH), 124.2 (CH),
125.4 (C), 125.6 (CH), 129.5 (C), 130.7 (2CH), 134.4 (CH),
135.5 (C), 136.5 (CH), 138.6 (C), 159.2 (C), 161.2 (CO),
193.7 (CO); MS (IS) m/z 401 (MCH)C. Diene precursor:
15a (Diastereomer 2), tZ8 h; chromatography eluent: PE/
EtOAc 8:2; yield: 96%. Gum; IR (film) n 1643 (CO), 1622
3.3.2. 2-(3-Butenyl)-10-methyl-3,4-dihydroazepino[3,4-
b]indole-1,5(2H,10H)-dione (6b). Alkenyl bromide: 4-
bromobutene; chromatography eluent: PE/EtOAc 8:2;
yield: 54%. Mp 113–115 8C (EtOAc/PE); IR (KBr) n 1635
1
(CO), 1618 (CO) cmK1; H NMR (250 MHz, CDCl3) d
2.43–2.46 (m, 2H, CH2), 2.86–2.90 (m, 2H, CH2), 3.70–3.75
(m, 4H, 2 NCH2), 4.01 (s, 3H, NCH3), 5.07–5.17 (m, 2H,
]CH2), 5.80–5.90 (m, 1H, ]CH), 7.23–7.40 (m, 3H, HAr),
8.39 (d, 1H, JZ8.0 Hz, HAr); 13C NMR (62.9 MHz, CDCl3)
d 32.8 (NCH3), 33.0 (CH2), 43.9 (CH2), 45.1 (CH2), 47.7
(CH2), 110.2 (CH), 115.4 (C), 117.5 (CH2), 123.5 (CH),
123.7 (CH), 125.0 (C), 125.5 (CH), 133.3 (C), 134.9 (CH),
138.4 (C), 161.4 (CO), 195.5 (CO); MS (IS) m/z 283 (MC
H)C. Anal. Calcd for C17H18N2O2: C, 72.32; H, 6.43; N,
9.92. Found: C, 72.04; H, 6.53; N, 9.77.
1
(CO) cmK1; H NMR (250 MHz, CDCl3) d 1.96–2.07 (m,
1H, CH2), 2.32–2.75 (m, 3H, CH2), 3.80 (s, 3H, OCH3),
4.10 (s, 3H, NCH3), 4.40–4.52 (m, 2H, NCH2CNCH), 5.28
(d, 1H, JZ15.6 Hz, NCH2), 5.60 (s, 2H, 2]CH), 6.86 (d,
2H, JZ8.5 Hz, HAr), 7.19 (d, 2H, JZ8.5 Hz, HAr), 7.28–
7.44 (m, 3H, HAr), 8.03 (d, 1H, JZ8.0 Hz, HAr); 13C NMR
(62.9 MHz, CDCl3) d 28.1 (CH2), 30.2 (CH2), 32.3 (NCH3),
44.6 (NCH2), 54.3 (CH), 54.8 (CH), 55.4 (OCH3), 110.2
(CH), 114.4 (2CH), 116.5 (C), 122.3 (CH), 123.2 (CH),
124.2 (CH), 125.2 (C), 125.4 (CH), 125.7 (CH), 128.5
(2CH), 130.7 (C), 134.4 (C), 138.9 (C), 159.0 (C), 163.7
(CO), 199.3 (CO); MS (IS) m/z 401 (MCH)C. Anal. Calcd
for C25H24N2O3: C, 74.98; H, 6.04; N, 6.99. Found: C,
74.93; H, 5.92; N, 6.90.
3.3.3. 10-Methyl-2-(4-pentenyl)-3,4-dihydroazepino[3,4-
b]indole-1,5(2H,10H)-dione (6c). Alkenyl bromide: 5-
bromopentene; chromatography eluent: PE/EtOAc 8:2;
yield: 64%. Mp 104–106 8C (EtOAc/PE); IR (KBr) n 1647
1
(CO), 1621 (CO) cmK1; H NMR (250 MHz, CDCl3) d
1.74–1.80 (m, 2H, CH2), 2.11–2.19 (m, 2H, CH2), 2.84–2.88
(m, 2H, CH2), 3.60–3.69 (m, 4H, 2 NCH2), 4.01 (s, 3H,
NCH3), 5.00–5.11 (m, 2H, ]CH2), 5.77–5.93 (m, 1H,
]CH), 7.31–7.39 (m, 3H, HAr), 8.38 (d, 1H, JZ8.1 Hz,
HAr); 13C NMR (62.9 MHz, CDCl3) d 27.9 (CH2), 31.5
(CH2), 33.1 (NCH3), 44.3 (CH2), 45.3 (CH2), 48.0 (CH2),
3.2.9. 7-(4-Methoxybenzyl)-5-methyl-7a,8,11,11a-tetra-
hydroindolo[2,3-c][1]benzazepine-6,12(5H,7H)-dione
(5b). Diene precursor: 15b. tZ12 h; chromatography

10104
J. Perron et al. / Tetrahedron 60 (2004) 10099–10109
110.0 (CH), 115.2 (C), 115.4 (CH2), 123.3 (CH), 123.5
(CH), 124.9 (C), 125.4 (CH), 134.8 (C), 137.4 (CH), 138.3
(C), 161.2 (CO), 195.4 (CO); MS (IS) m/z 297 (MCH)C.
Anal. Calcd for C18H20N2O2: C, 72.95; H, 6.16; N, 9.52.
Found: C, 72.83; H, 5.99; N, 9.64.
NCH2), 4.26 (s, 3H, NCH3), 5.09–5.18 (m, 2H, ]CH2),
5.79–5.90 (m, 1H, ]CH), 6.00 (d, 1H, JZ10.9 Hz,
]CHCO), 6.79 (d, 1H, JZ10.9 Hz, ]CHN), 7.38–7.55
(m, 3H, HAr), 8.88 (d, 1H, JZ8.1 Hz, HAr); 13C NMR
(62.9 MHz) d 33.4 (CH2), 34.4 (NCH3), 53.2 (NCH2), 110.2
(CH), 114.2 (CHCO), 118.3 (CH2), 121.4 (C), 123.7 (CH),
124.9 (C), 125.4 (CH), 127.4 (CH), 132.2 (C), 133.9 (CH),
135.2 (CH), 139.9 (C), 160.8 (CO), 182.6 (CO); MS (IS) m/z
281 (MCH)C. Anal. Calcd for C17H16N2O2: C, 72.84; H,
5.75; N, 9.99. Found: C, 73.12; H, 5.67; N, 10.08.
3.3.4. 2-(5-Hexenyl)-10-methyl-3,4-dihydroazepino[3,4-
b]indole-1,5(2H,10H)-dione (6d). Alkenyl bromide: 6-
bromohexene; chromatography eluent: PE/EtOAc 8:2;
yield: 76%. Gum; IR (film) n 1639 (CO), 1622 (CO)
1
cmK1;. H NMR (250 MHz, CDCl3) d 1.42–1.54 (m, 2H,
CH2), 1.64–1.76 (m, 2H, CH2), 2.03–2.18 (m, 2H, CH2),
2.86–2.90 (m, 2H, CH2), 3.62–3.71 (m, 4H, 2 NCH2), 4.06
(s, 3H, NCH3), 4.95–5.07 (m, 2H, ]CH2), 5.72–5.89 (m,
1H, ]CH), 7.27–7.40 (m, 3H, HAr), 8.42 (d, 1H, JZ8.1 Hz,
HAr); 13C NMR (62.9 MHz, CDCl3) d 26.2 (CH2), 27.8
(CH2), 32.8 (NCH3), 33.4 (CH2), 44.0 (CH2), 44.9 (CH2),
47.8 (CH2), 110.1 (CH), 115.0 (C), 115.3 (CH2), 123.5
(CH), 123.6 (CH), 125.0 (C), 125.5 (CH), 134.9 (C), 138.2
(CH), 138.4 (C), 161.3 (CO), 195.4 (CO); MS (IS) m/z 311
(MCH)C. Anal. Calcd for C19H22N2O2: C, 73.52; H, 7.14;
N, 9.02. Found: C, 73.85; H, 6.99; N, 9.21.
3.4.3. 10-Methyl-2-(4-pentenyl)azepino[3,4-b]indole-
1,5(2H,10H)-dione (7c). Chromatography eluent: PE/
EtOAc 7:3; yield: 81%. Mp 81–83 8C (EtOAc/PE); IR
(KBr) n 1640 (CO), 1625 (CO) cmK1; 1H NMR (250 MHz,
CDCl3) d 1.81–1.93 (m, 2H, CH2), 2.12–2.21 (m, 2H, CH2),
3.90–3.97 (m, 2H, NCH2), 4.18 (s, 3H, NCH3), 5.01–5.12
(m, 2H, ]CH2), 5.75–5.89 (m, 1H, ]CH), 5.93 (d, 1H, JZ
11.0 Hz, ]CHCO), 6.76 (d, 1H, JZ11.0 Hz, ]CHN),
7.31–7.49 (m, 3H, HAr), 8.83 (d, 1H, JZ8.1 Hz, HAr); 13C
NMR (62.9 MHz, CDCl3) d 27.9 (CH2), 30.7 (CH2), 34.3
(NCH3), 52.2 (NCH2), 110.1 (CH), 114.0 (CH), 115.7
(CH2), 121.1 (C), 123.5 (CH), 124.7 (C), 125.1 (CH), 127.2
(CH), 132.1 (C), 135.1 (CH), 137.1 (CH), 139.7 (C), 160.6
(CO), 182.4 (CO); MS (IS) m/z 295 (MCH)C. Anal. Calcd
for C18H18N2O2: C, 73.45; H, 6.16; N, 9.52. Found: C,
73.24; H, 6.32; N, 9.43.
3.4. Typical procedure for the synthesis of 7
A solution of LiHMDS 1 M in THF (1.34 mL, 1.34 mmol)
was added dropwise to a solution of 6 (0.75 mmol) in
anhydrous THF (30 mL) at K78 8C. After 1 h of stirring, a
solution of bromine (0.04 mL, 0.75 mmol) in anhydrous
THF (1 mL) was quickly added to the mixture at K78 8C.
After 10 min of stirring, a saturated aqueous NH4Cl solution
(5 mL) and EtOAc (20 mL) were added. The biphasic
solution was decanted and separated. The organic layer was
dried over MgSO4. After evaporation in vacuo, the crude
monobromide was directly used in the next step. DBU
(0.17 mL, 1.12 mmol) was added to a solution of crude
monobromide in DMF (5 mL). The mixture was stirred for
2 h at room temperature. 10% HCl solution (5 mL) was
added and the mixture was extracted with EtOAc (2!
10 mL); the organic layer was washed with brine (3!5 mL)
and dried over MgSO4. After evaporation, the residue was
purified by column chromatography to afford 7.
3.4.4. 2-(5-Hexenyl)-10-methylazepino[3,4-b]indole-
1,5(2H,10H)-dione (7d). Chromatography eluent: PE/
EtOAc 7:3; yield: 83%. Mp 96–98 8C (EtOAc/PE); IR
(KBr) n 1637 (CO), 1623 (CO) cmK1; 1H NMR (250 MHz,
CDCl3) d 1.42–1.57 (m, 2H, CH2), 1.64–1.78 (m, 2H, CH2),
2.10–2.16 (m, 2H, CH2), 3.93 (t, 2H, JZ7.5 Hz, NCH2),
4.18 (s, 3H, NCH3), 4.96–5.06 (m, 2H, ]CH2), 5.71–5.87
(m, 1H, ]CH), 5.95 (d, 1H, JZ11.0 Hz, ]CHCO), 6.75 (d,
1H, JZ11.0 Hz, ]CHN), 7.32–7.52 (m, 3H, HAr), 8.84 (d,
1H, JZ8.1 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 26.0
(CH2), 28.6 (CH2), 33.4 (CH2), 34.3 (NCH3), 53.6 (NCH2),
110.2 (CH), 114.1 (CH), 115.2 (CH2), 121.2 (C), 123.6
(CH), 124.8 (C), 125.2 (CH), 127.3 (CH), 132.2 (C), 135.1
(CH), 138.1 (CH), 139.7 (C), 160.7 (CO), 182.5 (CO); MS
(IS) m/z 309 (MCH)C. Anal. Calcd for C19H20N2O2: C,
74.00; H, 6.54; N, 9.08. Found: C, 73.77; H, 6.40; N, 9.19.
3.4.1. 2-Allyl-10-methylazepino[3,4-b]indole-1,5(2H,
10H)dione (7a). Chromatography eluent: PE/EtOAc 8:2;
yield: 83%. Mp 130–132 8C (EtOAc/PE); IR (KBr) n 1640
(CO), 1628 (CO) cmK1; 1H NMR (250 MHz, CDCl3) d 4.24
(s, 3H, NCH3), 4.60 (d, 2H, JZ5.5 Hz, NCH2), 5.25–5.33
(m, 2H, ]CH2), 5.92–6.07 (m, 1H, ]CH), 6.01 (d, 1H, JZ
10.9 Hz, ]CHCO), 6.76 (d, 1H, JZ10.9 Hz, ]CH), 7.36–
7.54 (m, 3H, HAr), 8.88 (d, 1H, JZ8.1 Hz, HAr); 13C NMR
(62.9 MHz, CDCl3) d 34.0 (NCH3), 54.7 (NCH2), 110.0
(CH), 113.6 (CH), 118.2 (CH2), 120.7 (C), 123.3 (CH),
124.5 (C), 124.8 (CH), 127.0 (CH), 131.7 (C), 132.0 (CH),
134.7 (CH), 139.4 (C), 160.2 (CO), 182.2 (CO); MS (IS) m/z
267 (MCH)C. Anal. Calcd for C16H14N2O2: C, 72.17; H,
5.30; N, 10.52. Found: C, 71.83; H, 5.45; N, 10.41.
3.5. Typical procedure for Sakurai allylation of 7
Allyltrimethylsilane (0.36 mL, 2.25 mmol) and a solution of
TiCl4 1 M in dichloromethane (1.50 mL, 1.50 mmol) was
added to a cooled solution (K40 8C) of 7 (0.37 mmol) in
anhydrous dichloromethane (3 mL). The mixture was then
stirred for 15 h at room temperature. A saturated aqueous
NH4Cl solution (5 mL) was added and the mixture was
extracted with dichloromethane (2!10 mL). The organic
layer was dried over MgSO4 and evaporated in vacuo. The
crude residue was purified by column chromatography to
afford 8 as a gum.
3.4.2. 2-(3-Butenyl)-10-methylazepino[3,4-b]indole-
1,5(2H,10H)-dione (7b). Chromatography eluent: PE/
EtOAc 7:3; yield: 80%. Mp 114–116 8C (EtOAc/PE); IR
(KBr) n 1638 (CO), 1627 (CO) cmK1; 1H NMR (250 MHz,
CDCl3) d 3.03–3.14 (m, 2H, CH2), 4.06 (t, 2H, JZ7.1 Hz,
3.5.1. 2,3-Diallyl-10-methyl-3,4-dihydroazepino[3,4-
b]indole-1,5(2H,10H)-dione (8a). Chromatography eluent:
PE/EtOAc 7:3; yield: 69%. IR (film) n 1640 (CO) cmK1; 1H
NMR (250 MHz, CDCl3) d 2.38–2.56 (m, 2H, CH2), 2.96
(dd, 1H, JZ5.9, 18.2 Hz, CH2CO), 3.13 (dd, 1H, JZ2.8,

J. Perron et al. / Tetrahedron 60 (2004) 10099–10109
10105
18.2 Hz, CH2CO), 3.79–3.83 (m, 1H, NCH), 4.01 (dd, 1H,
JZ5.8, 14.9 Hz, NCH2), 4.07 (s, 3H, NCH3), 4.57 (dd, 1H,
JZ5.8, 14.9 Hz, NCH2), 4.90–5.08 (m, 2H, ]CH2), 5.27–
5.38 (m, 2H, ]CH2), 5.63–5.74 (m, 1H, ]CH), 5.90–6.00
(m, 1H, ]CH), 7.36–7.48 (m, 3H, HAr), 8.49 (d, 1H, JZ
8.1 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 33.2 (NCH3),
36.1 (CH2), 47.7 (CH2), 51.3 (CH2), 55.2 (NCH), 110.3
(CH), 115.5 (C), 118.8 (CH2), 118.9 (CH2), 123.9 (2CH),
125.0 (C), 125.6 (CH), 133.3 (CH), 133.8 (CH), 135.8 (C),
138.5 (C), 161.0 (CO), 193.3 (CO); MS (IS) m/z 309 (MC
H)C. Anal. Calcd for C19H20N2O2: C, 74.0; H, 6.54; N,
9.09. Found: C, 73.72; H, 6.38; N, 8.92.
C22H26N2O2: C, 75.40; H, 7.48; N, 7.99. Found: C, 75.15;
H, 7.30; N, 8.15.
3.5.5. 4,4-Diallyl-2-(4-methoxybenzyl)-10-methyl-3,4-
dihydroazepino[3,4-b]indole-1,5(2H,10H)-dione (9). At
0 8C, a solution of compound 2b (200 mg, 0.57 mmol) in
anhydrous THF (2 mL) was added dropwise to a suspension
of sodium hydride (50 mg, 1.21 mmol, 60% dispersed in oil)
in anhydrous THF (2 mL). The mixture was stirred for 3 h at
room temperature. 3-Bromopropene (0.25 mL, 2.87 mmol)
was added and the final solution was stirred overnight at
room temperature. A saturated aqueous NH4Cl solution
(5 mL) and EtOAc (10 mL) were added and the mixture
obtained was extracted. The organic layer was dried over
MgSO4 and evaporated in vacuo. The residue was purified
by column chromatography (eluent PE/EtOAc 8:2) to afford
9 (190 mg, 77%) as a solid. Mp 123–124 8C (EtOAc/PE); IR
(KBr) n 1642 (CO), 1628 (CO) cmK1; 1H NMR (250 MHz,
CDCl3) 2.37–2.46 (m, 2H, CH2), 2.52–2.61 (m, 2H, CH2),
3.59 (broad s, 2H, NCH2), 3.81 (s, 3H, OCH3), 4.10 (s, 3H,
NCH3), 4.76 (broad s, 2H, NCH2Ph), 5.03–5.12 (m, 4H,
2]CH2), 5.66–5.82 (m, 2H, 2]CH), 6.90 (d, 2H, JZ
8.5 Hz, HAr), 7.27–7.43 (m, 5H, HAr), 8.35 (d, 1H, JZ
7.9 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 32.9 (NCH3),
40.2 (2CH2), 51.5 (NCH2), 51.9 (NCH2), 55.4 (C), 55.6
(OCH3), 110.3 (CH), 114.3 (2CH), 116.7 (C), 119.0 (2CH2),
123.5 (CH), 123.6 (CH), 125.3 (C), 125.7 (CH), 128.5 (C),
129.6 (2CH), 133.0 (2CH), 133.3 (C), 138.6 (C), 159.3 (C),
162.0 (CO), 199.2 (CO); MS (IS) m/z 429 (MCH)C. Anal.
Calcd for C27H28N2O2: C, 75.68; H, 6.59; N, 6.54. Found:
C, 75.90; H, 6.43; N, 6.39.
3.5.2. 3-Allyl-2-(3-butenyl)-10-methyl-3,4-dihydro-
azepino[3,4-b]indole-1,5(2H,10H)-dione (8b). Chroma-
tography eluent: PE/EtOAc 8:2; yield: 54%. IR (film) n
1645 (CO), 1630 (CO) cmK1; 1H NMR (250 MHz, CDCl3)
d 2.40–2.56 (m, 4H, 2 CH2), 2.98 (dd, 1H, JZ5.8, 17.9 Hz,
CH2CO), 3.22 (dd, 1H, JZ2.8, 17.9 Hz, CH2CO), 3.37–
3.48 (m, 1H, NCH2), 3.74–3.80 (m, 1H, NCH), 4.07 (s, 4H,
NCH3CNCH2), 4.91–5.21 (m, 4H, 2]CH2), 5.62–5.96 (m,
2H, 2]CH), 7.28–7.38 (m, 3H, HAr), 8.55 (d, 1H, JZ
8.1 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 33.2 (NCH3),
33.3 (CH2), 36.2 (CH2), 47.8 (CH2), 49.2 (CH2), 56.3
(NCH), 110.3 (CH), 115.4 (C), 117.5 (CH2), 118.9 (CH2),
123.9 (2CH), 125.0 (C), 125.6 (CH), 133.8 (CH), 135.0
(CH), 136.1 (C), 138.5 (C), 161.0 (CO), 193.1 (CO); MS
(IS) m/z 323 (MCH)C. Anal. Calcd for C20H22N2O2: C,
74.51; H, 6.88; N, 8.69. Found: C, 74.78; H, 6.97; N, 8.54.
3.5.3. 3-Allyl-10-methyl-2-(4-pentenyl)-3,4-dihydro-
azepino[3,4-b]indole-1,5(2H,10H)-dione (8c). Chroma-
tography eluent: PE/EtOAc 7:3; yield: 50%. IR (film) n
1638 (CO) cmK1. 1H NMR (250 MHz, CDCl3) d 1.69–1.88
(m, 2H, CH2), 2.13–2.21 (m, 2H, CH2), 2.37–2.58 (m, 2H,
CH2), 2.95–3.21 (m, 2H, CH2), 3.34–3.45 (m, 1H, NCH2),
3.78–3.96 (m, 2H, NCHCNCH2), 4.06 (s, 3H, NCH3),
4.90–5.12 (m, 4H, 2]CH2), 5.64–5.87 (m, 2H, 2]CH),
7.34–7.46 (m, 3H, HAr), 8.49 (d, 1H, JZ8.1 Hz, HAr); 13C
NMR (62.9 MHz, CDCl3): d 27.9 (CH2), 31.3 (CH2), 33.2
(NCH3), 36.3 (CH2), 47.9 (CH2), 49.1 (CH2), 56.2 (NCH),
110.3 (CH), 115.4 (C), 115.6 (CH2), 118.9 (CH2), 123.9
(2CH), 125.0 (C), 125.6 (CH), 133.8 (CH), 136.2 (C), 137.5
(CH), 138.5 (C), 161.0 (CO), 193.1 (CO); MS (IS) m/z 337
(MCH)C. Anal. Calcd for C21H24N2O2: C, 74.97; H, 7.19;
N, 8.33. Found: C, 75.25; H, 7.31; N, 8.40.
3.5.6. Ethyl 5-hydroxy-2-(4-methoxybenzyl)-10-methyl-
1-oxo-1,2,3,10-tetrahydroazepino[3,4-b]indole-4-car-
boxylate (10). At K78 8C, LiHMDS 1 M in THF (0.78 mL,
0.78 mmol) was slowly added to a solution of 2b (150 mg,
0.43 mmol) in anhydrous THF (5 mL). After 1 h, ethyl
cyanoformate (0.05 mL, 0.47 mmol) was added dropwise
and the final solution was stirred at K78 8C for 15 min. 10%
Aqueous HCl solution (5 mL) was added and the mixture
was extracted with EtOAc (3!10 mL). The organic layer
was dried over MgSO4 and evaporated. The residue was
purified by column chromatography (eluent PE/EtOAc 7:3)
to afford 10 (167 mg, 92%) as a solid. Mp 128–130 8C
(EtOAc); IR (KBr) n 1736 (CO), 1628 (CO) cmK1; 1H NMR
(250 MHz, CDCl3) d 1.36 (t, 3H, JZ7.1 Hz, CH3), 3.81 (s,
3H, OCH3), 4.13 (s, 3H, NCH3), 4.23 (q, 2H, JZ7.1 Hz,
OCH2), 4.50 (broad s, 2H, CH2), 4.97 (broad s, 2H, CH2Ph),
6.89 (d, 2H, JZ8.5 Hz, HAr), 7.29–7.45 (m, 5H, HAr), 8.23
(d, 1H, JZ8.0 Hz, HAr), 12.71 (s, 1H, OH); 13C NMR
(62.9 MHz, CDCl3) d 14.4 (CH3), 32.6 (NCH3), 43.1 (CH2),
49.4 (CH2), 55.3 (OCH3), 60.8 (OCH2), 97.2 (C), 110.2
(CH), 112.9 (C), 114.0 (2CH), 122.2 (CH), 123.2 (CH),
124.1 (C), 125.4 (CH), 129.5 (C), 129.6 (2CH), 134.6 (C),
138.4 (C), 159.2 (C), 160.7 (CO), 169.4 (C), 170.9 (CO);
MS (IS) m/z 421 (MCH)C. Anal. Calcd for C24H24N2O5: C,
68.56; H, 5.75; N, 6.66. Found: C, 68.27; H, 5.93; N, 6.49.
3.5.4. 3-Allyl-2-(5-hexenyl)-10-methyl-3,4-dihydro-
azepino[3,4-b]indole-1,5(2H,10H)-dione (8d). Chroma-
tography eluent: PE/EtOAc 8:2; yield: 48%. IR (film) n
1639 (CO), 1629 (CO) cmK1; 1H NMR (250 MHz, CDCl3)
d 1.44–1.52 (m, 2H, CH2), 1.64–1.76 (m, 2H, CH2), 2.09–
2.18 (m, 2H, CH2), 2.33–2.57 (m, 2H, CH2), 2.93–3.20 (m,
2H, CH2), 3.32–3.44 (m, 1H, NCH2), 3.70–3.81 (m, 1H,
NCH), 3.85–3.96 (m, 1H, NCH2), 4.05 (s, 3H, NCH3), 4.90–
5.08 (m, 4H, 2]CH2), 5.60–5.89 (m, 2H, 2]CH), 7.31–
7.48 (m, 3H, HAr), 8.48 (d, 1H, JZ8.3 Hz, HAr); 13C NMR
(62.9 MHz, CDCl3) d 26.4 (CH2), 28.2 (CH2), 33.2 (NCH3),
33.5 (CH2), 36.3 (CH2), 47.9 (CH2), 49.2 (CH2), 56.1
(NCH), 110.3 (CH), 115.1 (CH2), 115.4 (C), 118.9 (CH2),
123.90 (CH), 123.92 (CH), 125.0 (C), 125.6 (CH), 133.9
(CH), 136.3 (C), 138.4 (CH), 138.5 (C), 160.9 (CO), 193.2
(CO); MS (IS) m/z 351 (MCH)C. Anal. Calcd for
3.6. Typical procedure for the C-alkylation of 10
A mixture of compound 10 (150 mg, 0.357 mmol),
potassium carbonate (246 mg, 1.79 mmol) and alkenyl
bromide (1.79 mmol) in acetone (5 mL) was heated at

10106
J. Perron et al. / Tetrahedron 60 (2004) 10099–10109
reflux for t h. After cooling, EtOAc (10 mL) and water
(5 mL) were added, the final biphasic solution was decanted
and separated. The organic phase was dried over MgSO4
and evaporated. The residue was purified by column
chromatography (eluent PE/EtOAc 8:2) to give 11 as a gum.
JZ7.8 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 14.2
(CH3), 23.5 (CH2), 33.0 (NCH3), 34.2 (CH2), 35.2 (CH2),
50.7 (CH2), 51.4 (CH2), 55.4 (OCH3), 62.1 (OCH2), 63.0
(C), 110.3 (CH), 114.3 (2CH), 115.1 (CH2), 116.1 (C),
123.7 (CH), 123.9 (CH), 125.4 (C), 125.8 (CH), 128.5 (C),
129.6 (2CH), 133.4 (C), 137.9 (CH), 138.5 (C), 159.4 (C),
161.6 (CO), 171.9 (CO), 193.4 (CO); MS (IS) m/z 489 (MC
H)C. Anal. Calcd for C29H32N2O5: C, 71.29; H, 6.60; N,
5.73. Found: C, 71.02; H, 6.77; N, 5.91.
3.6.1. Ethyl 4-allyl-2-(4-methoxybenzyl)-10-methyl-1,5-
dioxo-1,2,3,4,5,10-hexahydroazepino[3,4-b]indole-4-car-
boxylate (11a). Alkenyl bromide: 3-bromopropene; tZ
24 h; chromatography eluent: PE/EtOAc 8:2; yield: 92%. IR
(film) n 1731 (CO), 1643 (CO), 1621 (CO) cmK1; 1H NMR
(250 MHz, CDCl3) d 1.22 (t, 3H, JZ7.1 Hz, CH3), 2.67–
2.76 (m, 1H, CH2), 3.10–3.17 (m, 1H, CH2), 3.65 (d, 1H,
JZ15.2 Hz, NCH2), 3.80 (s, 3H, OCH3), 3.99 (d, 1H, JZ
15.2 Hz, NCH2), 4.09 (s, 3H, NCH3), 4.14–4.30 (m, 3H,
OCH2CNCH2Ph), 4.98 (d, 1H, JZ10.0 Hz, ]CH2), 5.10
(d, 1H, JZ17.0 Hz, ]CH2), 5.42 (d, 1H, JZ14.3 Hz,
NCH2Ph), 5.59–5.72 (m, 1H, ]CH), 6.89 (d, 2H, JZ
8.5 Hz, HAr), 7.27–7.43 (m, 5H, HAr), 8.43 (d, 1H, JZ
7.6 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 14.2 (CH3),
32.9 (NCH3), 39.8 (CH2), 50.7 (CH2), 51.4 (CH2), 55.3
(OCH3), 62.2 (OCH2), 62.6 (C), 110.3 (CH), 114.3 (2CH),
115.9 (C), 119.7 (CH2), 123.6 (CH), 123.8 (CH), 125.3 (C),
125.7 (CH), 128.5 (C), 129.5 (2CH), 132.1 (CH), 133.5 (C),
138.5 (C), 159.3 (C), 161.5 (CO), 171.4 (CO), 193.0 (CO);
MS (IS) m/z 461 (MCH)C. Anal. Calcd for C27H28N2O5: C,
70.42; H, 6.13; N, 6.08. Found: C, 70.71; H, 6.25; N, 5.96.
3.6.4. 4-(5-Hexenyl)-2-(4-methoxybenzyl)-10-methyl-1,5-
dioxo-1,2,3,4,5,10-hexahydroazepino[3,4-b]indole-4-car-
boxylate (11d). Alkenyl bromide: 6-bromohexene; tZ48 h;
chromatography eluent: PE/EtOAc 8:2; yield: 68%. IR
(film) n 1732 (CO), 1641 (CO), 1617 (CO) cmK1; 1H NMR
(250 MHz, CDCl3) d 1.21 (t, 3H, JZ7.0 Hz, CH3), 1.21–
1.23 (m, 2H, CH2), 1.25–1.39 (m, 2H, CH2), 1.90–2.03 (m,
3H, CH2CCH2), 2.25–2.35 (m, 1H, CH2), 3.65 (d, 1H, JZ
15.1 Hz, NCH2), 3.80 (s, 3H, OCH3), 4.04 (d, 1H, JZ
15.1 Hz, NCH2), 4.10 (s, 3H, NCH3), 4.15–4.26 (m, 3H,
OCH2CNCH2Ph), 4.86–4.96 (m, 2H, ]CH2), 5.44 (d, 1H,
JZ14.9 Hz, NCH2Ph), 5.63–5.79 (m, 1H, ]CH), 6.90 (d,
2H, JZ8.8 Hz, HAr), 7.27–7.45 (m, 5H, HAr), 8.43 (d, 1H,
JZ7.6 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 14.2
(CH3), 23.6 (CH2), 29.4 (CH2), 33.0 (NCH3), 33.3 (CH2),
35.5 (CH2), 50.6 (CH2), 51.4 (CH2), 55.4 (OCH3), 62.1
(OCH2), 63.0 (C), 110.3 (CH), 114.3 (2CH), 114.7 (CH2),
116.1 (C), 123.7 (CH), 123.8 (CH), 125.4 (C), 125.8 (CH),
128.6 (C), 129.6 (2CH), 133.4 (C), 137.9 (CH), 138.5 (C),
159.4 (C), 161.6 (CO), 171.9 (CO), 193.5 (CO); MS (IS) m/z
503 (MCH)C. Anal. Calcd for C30H34N2O5: C, 71.69; H,
6.82; N, 5.57. Found: C, 72.03; H, 6.71; N, 5.68.
3.6.2. Ethyl 4-(3-butenyl)-2-(4-methoxybenzyl)-10-
methyl-1,5-dioxo-1,2,3,4,5,10-hexahydroazepino[3,4-
b]indole-4-carboxylate (11b). Alkenyl bromide: 4-bromo-
butene; tZ72 h; chromatography eluent: PE/EtOAc 7:3;
yield: 47%. IR (film) n 1729 (CO), 1643 (CO), 1622 (CO)
cmK1 1H NMR (250 MHz, CDCl3) d 1.22 (t, 3H, JZ
;
3.7. Typical procedure for the decarboxylation of 11
6.9 Hz, CH3), 2.01–2.04 (m, 3H, CH2CCH2), 2.34–2.45
(m, 1H, CH2), 3.68 (d, 1H, JZ15.4 Hz, NCH2), 3.81 (s, 3H,
OCH3), 4.04 (d, 1H, JZ15.4 Hz, NCH2), 4.10 (s, 3H,
NCH3), 4.12–4.30 (m, 3H, OCH2CNCH2Ph), 4.89–4.99
(m, 2H, ]CH2), 5.43 (d, 1H, JZ14.9 Hz, NCH2Ph), 5.65–
5.84 (m, 1H, ]CH), 6.90 (d, 2H, JZ8.5 Hz, HAr), 7.26–
7.45 (m, 5H, HAr), 8.43 (d, 1H, JZ7.8 Hz, HAr); 13C NMR
(62.9 MHz, CDCl3) d 14.2 (CH3), 28.5 (CH2), 33.0 (NCH3),
34.7 (CH2), 50.7 (CH2), 51.4 (CH2), 55.4 (OCH3), 62.2
(OCH2), 63.0 (C), 110.3 (CH), 114.3 (2CH), 115.4 (CH2),
116.1 (C), 123.7 (CH), 123.9 (CH), 125.5 (C), 125.8 (CH),
128.5 (C), 129.6 (2CH), 133.3 (C), 137.5 (CH), 138.6 (C),
159.4 (C), 161.6 (CO), 171.7 (CO), 193.3 (CO); MS (IS) m/z
475 (MCH)C. Anal. Calcd for C28H30N2O5: C, 70.87; H,
6.37; N, 5.90. Found: C, 70.64; H, 6.44; N, 5.99.
A solution of 11 (0.22 mmol) and lithium hydroxide hydrate
(18 mg, 0.43 mmol) in ethanol/water (v/v 3:1, 15 mL) was
stirred at reflux for 30 min. After cooling, water (5 mL) and
EtOAc (10 mL) were added and the mixture was separated.
The organic layer was dried over MgSO4 and evaporated to
give 12 as a gum.
3.7.1. 4-Allyl-2-(4-methoxybenzyl)-10-methyl-3,4-di-
hydroazepino[3,4-b]indole-1,5(2H,10H)-dione (12a).
1
Yield: 98%. IR (film) n 1645 (CO), 1622 (CO) cmK1; H
NMR (250 MHz, CDCl3) d 2.13–2.23 (m, 1H, CH2), 2.52–
2.59 (m, 1H, CH2), 2.70–2.79 (m, 1H, CHCO), 3.47 (d, 1H,
JZ14.9 Hz, NCH2), 3.75 (d, 1H, JZ14.9 Hz, NCH2), 3.80
(s, 3H, OCH3), 4.09 (s, 3H, NCH3), 4.48 (d, 1H, JZ14.1 Hz,
NCH2Ph), 5.03–5.10 (m, 3H, ]CH2CNCH2Ph), 5.54–5.70
(m, 1H, ]CH), 6.88 (d, 2H, JZ8.5 Hz, HAr), 7.26–7.42 (m,
5H, HAr), 8.38 (d, 1H, JZ7.8 Hz, HAr); 13C NMR
(62.9 MHz, CDCl3) d 32.9 (NCH3), 33.8 (CH2), 47.7
(CH2), 50.4 (CH2), 51.8 (CH), 55.4 (OCH3), 110.2 (CH),
114.3 (2CH), 116.0 (C), 117.8 (CH2), 123.6 (C), 123.7
(CH), 125.3 (C), 125.6 (CH), 129.0 (C), 130.0 (2CH), 134.1
(C), 137.8 (CH), 138.6 (C), 159.5 (C), 161.6 (CO), 197.0
(CO); MS (IS) m/z 389 (MCH)C. Anal. Calcd for
C24H24N2O3: C, 74.21; H, 6.23; N, 7.21. Found: C, 73.90;
H, 6.36; N, 7.34.
3.6.3. Ethyl 2-(4-methoxybenzyl)-10-methyl-4-(4-pent-
enyl)-1,5-dioxo-1,2,3,4,5,10-hexahydroazepino[3,4-b]-
indole-4-carboxylate (11c). Alkenyl bromide: 5-
bromopentene; tZ48 h; chromatography eluent: PE/
EtOAc 8:2; yield: 59%. IR (film) n 1729 (CO), 1644
(CO), 1622 (CO) cmK1; 1H NMR (250 MHz, CDCl3) d 1.21
(t, 3H, JZ7.1 Hz, CH3), 1.28–1.38 (m, 2H, CH2), 1.95–2.06
(m, 3H, CH2CCH2), 2.25–2.38 (m, 1H, CH2), 3.66 (d, 1H,
JZ14.9 Hz, NCH2), 3.80 (s, 3H, OCH3), 4.04 (d, 1H, JZ
14.9 Hz, NCH2), 4.10 (s, 3H, NCH3), 4.13–4.29 (m, 3H,
OCH2CNCH2Ph), 4.90–4.99 (m, 2H, ]CH2), 5.43 (d, 1H,
JZ15.0 Hz, NCH2Ph), 5.62–5.79 (m, 1H, ]CH), 6.90 (d,
2H, JZ8.5 Hz, HAr), 7.26–7.45 (m, 5H, HAr), 8.43 (d, 1H,
3.7.2. 4-(3-Butenyl)-2-(4-methoxybenzyl)-10-methyl-3,4-
dihydroazepino[3,4-b]indole-1,5(2H,10H)-dione (12b).

J. Perron et al. / Tetrahedron 60 (2004) 10099–10109
10107
Yield 99%. IR (film) n 1640 (CO), 1612 (CO) cmK1; H
NMR (250 MHz, CDCl3) d 1.49–1.60 (m, 1H, CH2), 1.95–
2.13 (m, 3H, 2 CH2), 2.54–2.60 (m, 1H, CHCO), 3.49 (d,
1H, JZ14.1 Hz, NCH2), 3.75 (d, 1H, JZ14.1 Hz, NCH2),
3.81 (s, 3H, OCH3), 4.10 (s, 3H, NCH3), 4.57 (d, 1H, JZ
14.4 Hz, NCH2Ph), 4.96–5.06 (m, 3H, ]CH2CNCH2Ph),
5.67–5.83 (m, 1H, ]CH), 6.90 (d, 2H, JZ8.5 Hz, HAr),
7.28–7.43 (m, 5H, HAr), 8.39 (d, 1H, JZ7.7 Hz, HAr); 13C
NMR (62.9 MHz, CDCl3) d 28.5 (CH2), 31.2 (CH2), 32.9
(NCH3), 48.1 (CH2), 50.6 (CH2), 51.8 (CH), 55.4 (OCH3),
110.2 (CH), 114.4 (2CH), 115.6 (CH2), 116.0 (C), 123.7
(2CH), 125.4 (C), 125.6 (CH), 128.9 (C), 129.8 (2CH),
133.9 (C), 137.7 (CH), 138.6 (C), 159.5 (C), 161.7 (CO),
198.0 (CO); MS (IS) m/z 403 (MCH)C. Anal. Calcd for
C25H26N2O3: C, 74.60; H, 6.51; N, 6.96. Found: C, 74.91;
H, 6.45; N, 7.10.
0.40 mmol) was added. The solution was stirred for 16 h at
room temperature. Water (10 mL) was added and the
mixture was extracted with EtOAc (2!10 mL). The
organic layer was dried over MgSO4 and evaporated. The
residue was purified by column chromatography to give 13
as a gum.
1
3.8.1. 4-Allyl-4-(3-butenyl)-2-(4-methoxybenzyl)-10-
methyl-3,4-dihydroazepino[3,4-b]indole-1,5(2H,10H)-
dione (13b). Yield: 93%. IR (film) n 1640 (CO), 1612 (CO)
1
cmK1; H NMR (250 MHz, CDCl3) d 1.73–1.78 (m, 2H,
CH2), 2.03–2.10 (m, 2H, CH2), 2.41–2.60 (m, 2H, CH2),
3.61 (broad s, 2H, NCH2), 3.81 (s, 3H, CH3), 4.10 (s, 3H,
OCH3), 4.84 (broad s, 2H, NCH2Ph), 4.89–5.13 (m, 4H,
2]CH2), 5.67–5.79 (m, 2H, 2]CH), 6.90 (d, 2H, JZ
8.8 Hz, HAr), 7.28–7.43 (m, 5H, HAr), 8.36 (d, 1H, JZ
8.1 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 28.3 (CH2),
33.0 (NCH3), 39.9 (CH2), 51.4 (CH2), 51.5 (CH2), 52.0
(CH2), 55.1 (C), 55.4 (OCH3), 110.3 (CH), 114.4 (2CH),
115.1 (CH2), 116.6 (C), 119.0 (CH2), 123.6 (CH), 123.7
(CH), 125.4 (C), 125.7 (CH), 128.8 (C), 129.6 (2CH), 129.9
(C), 133.2 (CH), 138.8 (CH), 138.6 (C), 159.4 (C), 162.0
(CO), 199.4 (CO); MS (IS) m/z 443 (MCH)C. Anal. Calcd
for C28H30N2O3: C, 75.99; H, 6.83; N, 6.33. Found: C,
76.33; H, 6.95; N, 6.47.
3.7.3. 2-(4-Methoxybenzyl)-10-methyl-4-(4-pentenyl)-
´
3,4-dihydroazepino[3,4-b]indole-1,5(2H,10H)-dione
(12c). Yield: 97%. IR (film) n 1641 (CO), 1614 (CO) cmK1
;
1H NMR (250 MHz, CDCl3) d 1.22–1.55 (m, 3H, 2CH2),
1.82–2.05 (m, 3H, 2CH2), 2.45–2.50 (m, 1H, CHCO), 3.48
(d, 1H, JZ14.4 Hz, NCH2), 3.77 (d, 1H, JZ14.4 Hz,
NCH2), 3.80 (s, 3H, OCH3), 4.10 (s, 3H, NCH3), 4.48 (d,
1H, JZ14.4 Hz, NCH2Ph), 4.94–5.02 (m, 2H, ]CH2), 5.11
(d, 1H, JZ14.4 Hz, NCH2Ph), 5.68–5.84 (m, 1H, ]CH),
6.90 (d, 2H, JZ8.8 Hz, HAr), 7.28–7.43 (m, 5H, HAr), 8.39
(d, 1H, JZ7.7 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d
26.4 (CH2), 28.9 (CH2), 32.9 (NCH3), 33.8 (CH2), 48.2
(CH2), 50.6 (CH2), 52.5 (CH), 55.4 (OCH3), 110.2 (CH),
114.4 (2CH), 115.0 (CH2), 116.0 (C), 123.6 (CH), 123.7
(CH), 125.4 (C), 125.6 (CH), 128.9 (C), 129.9 (2CH), 133.9
(C), 138.2 (CH), 138.6 (C), 159.5 (C), 161.7 (CO), 198.0
(CO); MS (IS) m/z 417 (MCH)C. Anal. Calcd for
C26H28N2O3: C, 74.98; H, 6.78; N, 6.73. Found: C, 74.67;
H, 6.64; N, 6.90.
3.8.2. 4-Allyl-2-(4-methoxybenzyl)-10-methyl-4-(4-pen-
tenyl)-3,4-dihydroazepino[3,4-b]indole-1,5(2H,10H)-
dione (13c). Yield: 89%. IR (film) n 1641 (CO), 1622 (CO)
1
cmK1; H NMR (250 MHz, CDCl3) d 1.37–1.40 (m, 2H,
CH2), 1.60–1.75 (m, 2H, CH2), 1.97–2.04 (m, 2H, CH2),
2.45–2.59 (m, 2H, CH2), 3.59 (broad s, 2H, NCH2), 3.81 (s,
3H, NCH3), 4.10 (s, 3H, OCH3), 4.83 (broad s, 2H,
NCH2Ph), 4.90–5.12 (m, 4H, 2]CH2), 5.64–5.80 (m, 2H,
2]CH), 6.90 (d, 2H, JZ8.8 Hz, HAr), 7.27–7.43 (m, 5H,
HAr), 8.36 (d, 1H, JZ8.1 Hz, HAr); 13C NMR (62.9 MHz,
CDCl3) d 23.3 (CH2), 33.0 (NCH3), 34.4 (CH2), 40.1
(2CH2), 51.5 (CH2), 52.1 (CH2), 55.3 (C), 55.4 (OCH3),
110.2 (CH), 114.3 (2CH), 115.1 (CH2), 116.7 (C), 118.8
(CH2), 123.7 (2CH), 125.4 (C), 125.7 (CH), 128.8 (C),
129.6 (2CH), 133.2 (C), 133.4 (CH), 138.2 (CH), 138.6 (C),
159.4 (C), 162.0 (CO), 199.7 (CO); MS (IS): m/z 457 (MC
H)C. Anal. Calcd for C29H32N2O3: C, 76.29; H, 7.06; N,
6.14. Found: C, 75.93; H, 7.17; N, 6.02.
3.7.4. 4-(5-Hexenyl)-2-(4-methoxybenzyl)-10-methyl-3,4-
dihydroazepino[3,4-b]indole-1,5(2H,10H)-dione (12d).
1
Yield: 99%. IR (film) n 1644 (CO), 1617 (CO) cmK1; H
NMR (250 MHz, CDCl3) d 1.15–1.52 (m, 5H, 3CH2), 1.84–
1.98 (m, 1H, CH2), 2.01–2.06 (m, 2H, CH2), 2.44–2.52 (m,
1H, CHCO), 3.48 (d, 1H, JZ14.9 Hz, NCH2), 3.72–3.79 (d,
1H, JZ14.9 Hz, NCH2), 3.80 (s, 3H, OCH3), 4.10 (s, 3H,
NCH3), 4.49 (d, 1H, JZ14.4 Hz, NCH2Ph), 4.93–5.04 (m,
2H, ]CH2), 5.11 (d, 1H, JZ14.4 Hz, NCH2Ph), 5.70–5.85
(m, 1H, ]CH), 6.89 (d, 2H, JZ8.5 Hz, HAr), 7.28–7.44 (m,
5H, HAr), 8.39 (d, 1H, JZ7.8 Hz, HAr); 13C NMR
(62.9 MHz, CDCl3) d 26.6 (CH2), 28.9 (CH2), 29.2 (CH2),
32.9 (NCH3), 33.6 (CH2), 48.2 (CH2), 50.6 (CH2), 52.6
(CH), 55.4 (OCH3), 63.0 (C), 110.2 (CH), 114.4 (2CH),
114.7 (CH2), 116.0 (C), 123.6 (CH), 123.7 (CH), 125.4 (C),
125.6 (CH), 128.9 (C), 129.9 (2CH), 133.9 (C), 138.6 (CH),
159.1 (C), 161.7 (CO), 198.1 (CO); MS (IS) m/z 431 (MC
H)C. Anal. Calcd for C27H30N2O3: C, 75.32; H, 7.02; N,
6.51. Found: C, 75.68; H, 6.92; N, 6.37.
3.8.3. 4-Allyl-2-(4-methoxybenzyl)-10-methylazepino-
[3,4-b]indole-1,5(2H,10H)-dione (14a). Following the
procedure used for the preparation of 7, compound 14a
was obtained from 13a in 88% yield. Chromatography
eluent PE/EtOAc 7:3. Mp 89–91 8C (EtOAc/PE); IR (KBr) n
1
1630 (CO) cmK1; H NMR (250 MHz, CDCl3) d 3.33 (d,
2H, JZ6.3 Hz, CH2), 3.80 (s, 3H, OCH3), 4.26 (s, 3H,
NCH3), 5.06–5.13 (m, 2H, ]CH2), 5.14 (s, 2H, NCH2),
5.84–6.01 (m, 1H, ]CH), 6.89 (d, 2H, JZ8.8 Hz, HAr),
6.98 (s, 1H, NCH), 7.29 (d, 2H, JZ8.8 Hz, HAr), 7.35–7.42
(m, 1H, HAr), 7.51–7.53 (m, 2H, HAr), 8.87 (d, 1H, JZ
8.6 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 34.2 (CH3),
36.0 (CH2), 55.4 (CH3), 55.7 (CH2), 110.2 (CH), 114.4
(2CH), 116.7 (CH2), 121.7 (C), 123.6 (CH), 123.9 (C),
125.3 (C), 125.4 (CH), 127.4 (CH), 128.6 (C), 129.3 (2CH),
131.6 (C), 134.5 (CH), 136.5 (CH), 139.9 (C), 159.5 (C),
160.4 (CO), 182.0 (CO); MS (IS) m/z 387 (MCH)C. Anal.
3.8. Typical procedure for the allylation of 12b–c
At 0 8C, sodium hydride (16 mg, 0.40 mmol, 60% in
dispersed oil) was slowly added to a solution of 12
(0.20 mmol) in anhydrous THF (5 mL). The mixture was
stirred for 1 h at 0 8C and 3-bromopropene (0.04 mL,

10108
J. Perron et al. / Tetrahedron 60 (2004) 10099–10109
Calcd for C24H22N2O3: C, 74.59; H, 5.74; N, 7.25. Found:
C, 75.79; H, 5.61; N, 7.33.
135.5 (C), 136.5 (CH), 138.5 (C), 159.6 (C), 161.2 (CO),
193.7 (CO); MS (IS) m/z 429 (MCH)C. Diastereomer 2 (cis
or trans): IR (film) n 1644 (CO), 1614 (CO) cmK1; 1H NMR
(250 MHz, CDCl3) d 2.03–2.54 (m, 4H, 2 CH2), 2.86–2.92
(m, 1H, CHCO), 3.56–3.64 (m, 1H, NCH), 3.82 (s, 3H,
OCH3), 4.15 (s, 3H, NCH3), 4.46 (d, 1H, JZ13.9 Hz,
NCH2), 4.67–5.12 (m, 4H, 2]CH2), 5.23 (d, 1H, JZ
13.9 Hz, NCH2), 5.35–5.45 (m, 1H, ]CH), 5.68–5.85 (m,
1H, ]CH), 6.88 (d, 2H, JZ8.8 Hz, HAr), 7.32–7.48 (m, 5H,
HAr), 8.58 (d, 1H, JZ8.1 Hz, HAr); 13C NMR (62.9 MHz,
CDCl3) d 33.8 (NCH3), 35.1 (CH2), 37.3 (CH2), 55.1
(NCH2), 55.4 (OCH3), 55.5 (CH), 58.4 (CH), 110.4 (CH),
114.2 (2CH), 114.5 (C), 117.6 (CH2), 118.6 (CH2), 124.0
(CH), 124.3 (CH), 125.5 (C), 127.8 (CH), 129.0 (C), 130.9
(2CH), 133.8 (CH), 135.5 (C), 135.7 (CH), 138.6 (C), 159.6
(C), 161.2 (CO), 195.3 (CO); MS (IS) m/z 429 (MCH)C.
Anal. Calcd for C27H28N2O3: C, 75.68; H, 6.59; N, 6.54.
Found: C, 75.93; H, 6.44; N, 6.67.
3.8.4. 4-(3-Butenyl)-2-(4-methoxybenzyl)-10-methyl-
azepino[3,4-b]indole-1,5(2H,10H)-dione (14b). Following
the procedure used for the preparation of 7, compound 14b
was obtained from 13b in 84% yield. Chromatography
eluent EP/AcOEt 7:3. Gum; IR (film) n 1631 (CO), 1612
1
(CO) cmK1; H NMR (250 MHz, CDCl3) d 1.60–1.74 (m,
2H, CH2), 2.59–2.65 (m, 2H, CH2), 3.79 (s, 3H, OCH3),
4.24 (s, 3H, NCH3), 4.90–5.01 (m, 2H, ]CH2), 5.13 (s, 2H,
NCH2), 5.69–5.79 (m, 1H, ]CH), 6.88 (d, 2H, JZ8.8 Hz,
HAr), 6.96 (s, 1H, NCH), 7.26–7.50 (m, 5H, HAr), 8.87 (d,
1H, JZ8.0 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 28.2
(CH2), 29.6 (CH2), 34.1 (NCH3), 55.4 (OCH3), 55.5
(NCH2), 110.2 (CH), 114.4 (2CH), 115.4 (CH2), 121.7
(C), 123.5 (CH), 124.9 (C), 125.2 (C), 125.3 (CH), 127.3
(CH), 128.6 (C), 129.2 (2CH), 131.5 (C), 134.2 (CH), 138.0
(CH), 139.8 (C), 159.5 (C), 160.4 (CO), 182.3 (CO); MS
(IS) m/z 401 (MCH)C. Anal. Calcd for C25H24N2O3: C,
74.98; H, 6.04; N, 6.99. Found: C, 75.25; H, 6.19; N, 7.12.
3.8.7. 3-Allyl-4-(3-butenyl)-2-(4-methoxybenzyl)-10-
methyl-3,4-dihydroazepino[3,4-b]indole-1,5(2H,10H)-
dione (15b). Following the procedure used for the
preparation of 8, compound 15b was obtained from 14b in
56% yield as a mixture of non-separable diastereomers
(ratio 6:4 determined by 1H NMR). Chromatography eluent
EP/AcOEt 8:2. Gum; IR (film) n 1635 (CO), 1621 (CO)
3.8.5. 2-(4-Methoxybenzyl)-10-methyl-4-(4-pentenyl)-
azepino[3,4-b]indole-1,5(2H,10H)-dione (14c). Following
the procedure used for the preparation of 7, compound 14c
was obtained from 13c in 87% yield. Chromatography
eluent EP/AcOEt 7:3. Gum; IR (film) n 1631 (CO), 1612
1
cmK1; H NMR (250 MHz, CDCl3) d 1.11–2.76 (m, 7H, 3
1
(CO) cmK1; H NMR (250 MHz, CDCl3) d 1.59–1.68 (m,
CH2CCHCO), 3.52–3.57 (m, 1H, NCH), 3.81 (s, 3H,
OCH3), 4.00 (d, 1H, JZ14.1 Hz, NCH2Ph), 4.12 (s, 1.2H,
NCH3), 4.15 (s, 1.8H, NCH3), 4.68 (d, 1H, JZ14.1 Hz,
NCH2Ph), 4.81–5.02 (m, 4H, 2]CH2), 5.46–5.72 (m, 2H,
2]CH), 6.89 (d, 2H, JZ8.5 Hz, HAr), 7.32–7.45 (m, 5H,
HAr), 8.53 (d, 1H, JZ8.1 Hz, HAr); No 13C NMR data due a
bad resolution of the spectrum; MS (IS) m/z 443 (MCH)C.
Anal. Calcd for C28H30N2O3: C, 75.99; H, 6.83; N, 6.33.
Found: C, 75.76; H, 6.97; N, 6.19.
2H, CH2), 2.01–2.10 (m, 2H, CH2), 2.51–2.57 (m, 2H,
CH2), 3.78 (s, 3H, OCH3), 4.24 (s, 3H, NCH3), 4.91–4.99
(m, 2H, ]CH2), 5.13 (s, 2H, NCH2), 5.71–5.87 (m, 1H,
]CH), 6.88 (d, 2H, JZ8.8 Hz, HAr), 6.96 (s, 1H, NCH),
7.28 (d, 2H, JZ8.8 Hz, HAr), 7.34–7.51 (m, 3H, HAr), 8.87
(d, 1H, JZ8.3 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d
29.0 (CH2), 32.6 (CH2), 33.5 (CH2), 34.1 (NCH3), 55.4
(OCH3), 55.5 (NCH2), 110.2 (CH), 114.4 (2CH), 114.8
(CH2), 121.8 (C), 123.6 (CH), 125.3 (C), 125.4 (CH), 125.7
(C), 127.3 (CH), 128.6 (C), 129.2 (2CH), 131.5 (C), 133.8
(CH), 138.7 (CH), 139.8 (C), 159.5 (C), 160.5 (CO), 182.4
(CO); MS (IS) m/z 415 (MCH)C. Anal. Calcd for
C26H26N2O3: C, 75.34; H, 6.32; N, 6.76. Found: C, 75.25;
H, 6.19; N, 6.88.
3.8.8. 3-Allyl-2-(4-methoxybenzyl)-10-methyl-4-(4-pen-
tenyl)-3,4-dihydroazepino[3,4-b]indole-1,5(2H,10H)-
dione (15c). Following the procedure used for the
preparation of 8, compound 15c was obtained from 14c in
68% yield as a mixture of non-separable diastereomers
(ratio 6:4 determined by 1H NMR). Chromatography eluent
EP/AcOEt 8:2. Gum; IR (film) n 1634 (CO), 1622 (CO)
3.8.6. 3,4-Diallyl-2-(4-methoxybenzyl)-10-methyl-3,4-
dihydroazepino[3,4-b]indole-1,5(2H,10H)-dione (15a).
Following the procedure used for the preparation of 8,
compound 15a was obtained from 14a in 51% yield. The
two diastereomers were isolated by column chromatography
(eluent PE/EtOAc 9:1) as colorless gum (ratio 44:56).
Diastereomer 1 (cis or trans): IR (film) n 1647 (CO), 1622
1
cmK1; H NMR (250 MHz, CDCl3) d 0.88–2.71 (m, 9H,
4CH2CCHCO), 3.52–3.60 (m, 1H, NCH), 3.81 (s, 3H,
OCH3), 3.92 (d, 1H, JZ14.6 Hz, NCH2Ph), 4.12 (s, 1.2H,
NCH3), 4.15 (s, 1.8H, NCH3), 4.60 (d, 1H, JZ14.6 Hz,
NCH2Ph), 4.79–5.03 (m, 4H, 2]CH2), 5.49–5.75 (m, 2H,
2]CH), 6.88 (d, 2H, JZ8.1 Hz, HAr), 7.29–7.48 (m, 5H,
HAr), 8.53 (d, 1.2H, JZ8.1 Hz, HAr), 8.58 (d, 1.8H, JZ
8.3 Hz, HAr); No 13C NMR data due a bad resolution of the
spectrum; MS (IS) m/z 457 (MCH)C. Anal. Calcd for
C29H32N2O3: C, 76.29; H, 7.06; N, 6.14. Found: C, 75.95;
H, 6.97; N, 6.14.
1
(CO) cmK1; H NMR (250 MHz, CDCl3) d 1.80–1.94 (m,
1H, CH2), 2.11–2.17 (m, 1H, CH2), 2.27–2.40 (m, 1H,
CH2), 2.77–2.82 (m, 1H, CH2), 2.91–2.97 (m, 1H, CHCO),
3.66–3.70 (m, 1H, NCH), 3.82 (s, 3H, OCH3), 3.96 (d, 1H,
JZ15.9 Hz, NCH2Ph), 4.12 (s, 3H, NCH3), 4.82 (d, 1H, JZ
15.9 Hz, NCH2Ph), 4.94–5.00 (m, 3H, ]CH2), 5.11–5.24
(m, 1H, ]CH), 5.54–5.60 (m, 2H, ]CHC]CH2), 6.88 (d,
2H JZ8.5 Hz, HAr), 7.29–7.45 (m, 5H, HAr), 8.53 (d, 1H,
JZ8.1 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 32.6
(CH2), 32.7 (CH2), 33.4 (NCH3), 53.0 (NCH2), 55.0 (CH),
55.5 (OCH3), 57.3 (CH), 110.3 (CH), 114.2 (2CH), 115.5
(C), 117.7 (CH2), 118.2 (CH2), 123.9 (CH), 124.1 (CH),
125.4 (C), 125.5 (CH), 129.3 (C), 130.7 (2CH), 134.4 (CH),
3.8.9. 3-Allyl-2-(4-methoxybenzyl)-10-methyl-3,4-di-
hydroazepino[3,4-b]indole-1,5(2H,10H)-dione (17). Fol-
lowing the procedure used for the preparation of 8,
compound 17 was obtained from 169 in 66% yield.
Chromatography eluent EP/AcOEt 7:3. Gum; IR (film) n
1648 (CO), 1625 (CO) cmK1; 1H NMR (250 MHz, CDCl3)
d 2.36–2.44 (m, 2H, CH2), 2.72–2.92 (m, 2H, CH2), 3.80 (s,

J. Perron et al. / Tetrahedron 60 (2004) 10099–10109
10109
4H, CH3CNCH), 4.11 (s, 3H, NCH3), 4.40 (d, 1H, JZ
Acknowledgements
This research work was supported by a grant from the
` ´
Ministere de l’Enseignement Superieur et de la Recherche
14.4 Hz, NCH2Ph), 4.86 (dd, 1H, JZ1.2, 16.9 Hz, ]CH2),
5.01 (dd, 1H, JZ1.2, 9.0 Hz, ]CH2), 5.22 (d, 1H, JZ
14.4 Hz, NCH2Ph), 5.50–5.64 (m, 1H, ]CH), 6.88 (d, 2H,
JZ8.5 Hz, HAr), 7.30–7.44 (m, 5H, HAr), 8.48 (d, 1H, JZ
7.6 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 33.1 (NCH3),
35.9 (CH2), 47.4 (CH2), 51.1 (CH2), 55.0 (NCH), 55.1
(OCH3), 110.2 (CH), 114.1 (2CH), 115.3 (C), 118.5 (CH2),
123.6 (CH), 123.7 (CH), 124.8 (C), 125.4 (CH), 129.2 (C),
129.7 (2CH), 133.7 (CH), 135.9 (C), 138.5 (C), 159.3 (C),
161.1 (CO), 193.1 (CO); MS (IS) m/z 389 (MCH)C. Anal.
Calcd for C24H24N2O3: C, 74.21; H, 6.23; N, 7.21. Found:
C, 74.65; H, 6.36; N, 7.11.
to J.P.
References and notes
1. Cimino, G.; De Rosa, S.; De Stephano, S.; Mazzarella, L.;
Puliti, R.; Sodano, G. Tetrahedron Lett. 1982, 23, 767–768.
2. Lago, M.A. Patent 2001 WO 0,164,680; Chem. Abstr., 135,
211033.
3.8.10. Ethyl 3-allyl-5-hydroxy-2-(4-methoxybenzyl)-10-
methyl-1-oxo-1,2,3,10-tetrahydroazepino[3,4-b]indole-
4-carboxylate (18). According to the procedure described
for for 10, compound 18 was prepared in 91% yield from 17.
Chromatography eluent EP/AcOEt 7:3. Gum; IR (film) n
1738 (CO), 1628 (CO) cmK1; 1H NMR (250 MHz, CDCl3)
d 1.24 (t, 3H, JZ7.1 Hz, CH3), 2.18 (m, 2H, CH2), 3.78 (s,
3H, OCH3), 4.01–4.15 (m, 2H, OCH2), 4.13 (s, 3H, NCH3),
4.53 (d, 1H, JZ14.4 Hz, NCH2), 4.65–4.90 (m, 3H,
]CH2CNCH), 5.06 (d, 1H, JZ14.4 Hz, NCH2), 5.34–
5.48 (m, 1H, ]CH), 6.86 (d, 2H, JZ8.6 Hz, HAr), 7.22–
7.47 (m, 5H, HAr), 8.28 (d, 1H, JZ8.0 Hz, HAr), 13.24 (s,
1H, OH); 13C NMR (62.9 MHz, CDCl3) d 14.2 (CH3), 32.5
(NCH3), 35.4 (CH2), 52.3 (NCH2), 53.4 (NCH), 55.2
(OCH3), 60.8 (OCH2), 100.0 (C), 110.2 (CH), 112.1 (C),
113.8 (2CH), 117.6 (CH2), 122.2 (CH), 123.5 (CH), 124.2
(CH), 125.5 (C), 129.5 (C), 130.0 (2CH), 134.2 (C), 134.6
(CH), 138.3 (C), 159.1 (C), 160.5 (CO), 168.0 (C), 171.1
(CO); MS (IS) m/z 461 (MCH)C. Anal. Calcd for
C27H28N2O5: C, 70.42; H, 6.13; N, 6.08. Found: C, 70.63;
H, 5.94; N, 6.20.
3. Wan, Y.; Hur, W.; Cho, C. Y.; Liu, Y.; Adrain, F. J.; Lozach, O.;
Bach, S.; Mayer, T.; Fabbro, D.; Meijer, L.; Gray, N. S. Chem.
Biol. 2004, 11, 247–259.
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4. (a) Chacun-Lefevre, L.; Joseph, B.; Merour, J.-Y. Synlett 2001,
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848–850. (b) Chacun-Lefevre, L.; Joseph, B.; Merour, J.-Y.
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6553–6556.
6. (a) Fu¨rstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012–3043.
(b) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34,
18–29. (c) Blechert, S.; Connon, S. J. Angew. Chem., Int. Ed.
2003, 42, 1900–1923.
7. (a) Bertinato, P.; Sorensen, E. J.; Meng, D.; Danishefsky, S. J.
J. Org. Chem. 1996, 61, 8000–8001. (b) Nicolaou, K. C.; He,
Y.; Vourloumis, D.; Vallberg, H.; Roschangar, F.; Sarabia, F.;
Ninkovic, S.; Yang, Z.; Trujillo, J. I. J. Am. Chem. Soc. 1997,
119, 7960–7973. (c) Fu¨rstner, A.; Langemann, K. J. Am. Chem.
Soc. 1997, 119, 9130–9136. (d) Stefinovic, M.; Snieckus, V.
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O. R.; Kindler, N.; Bartkowska, B. J. Org. Chem. 2000, 65,
7990–7995. (f) Labrecque, D.; Charron, S.; Rej, R.; Blais, C.;
Lamothe, S. Tetrahedron Lett. 2001, 42, 2645–2648.
(g) Fu¨rstner, A.; Langemann, K. Synthesis 1997, 792–803.
(h) Goldring, W. P. D.; Hodder, A. S.; Weiler, L. Tetrahedron
Lett. 1998, 39, 4955–4958. (i) Dirat, O.; Vidal, T.; Langlois, Y.
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Laurent, P.; Moody, C. J. Chem. Commun. 2000, 1771–1772.
(k) Crimmins, M. T.; King, B. W.; Zuercher, W. J.; Choy, A. L.
J. Org. Chem. 2000, 65, 8499–8509. (l) Lane, C.; Snieckus, V.
Synlett 2000, 1294–1296. (m) Boyer, F.-D.; Hanna, I.; Nolan,
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Toste, F. D.; Goldberg, S. D.; Grubbs, R. Pure Appl. Chem.
3.8.11. Ethyl 3-allyl-5-(3-butenyloxy)-2-(4-methoxy-
benzyl)-10-methyl-1-oxo-1,2,3,10-tetrahydroazepino-
[3,4-b]indole-4-carboxylate (19). According to the pro-
cedure described for for 11a, compound 19 was prepared in
56% yield from 18. Chromatography eluent EP/AcOEt 8:2.
1
Gum; IR (film) n 1716 (CO), 1628 (CO) cmK1; H NMR
(250 MHz, CDCl3) d 1.26 (t, 3H, JZ7.1 Hz, CH3), 1.94–
2.16 (m, 4H, 2 CH2), 2.50 (q, 2H, JZ6.7 Hz, OCH2), 3.79
(s, 3H, OCH3), 4.12 (s, 3H, NCH3), 4.05–4.18 (m, 2H,
OCH2), 4.53–4.61 (m, 2H, ]CH2), 4.74–4.84 (m, 2H,
]CH2), 4.93–5.11 (m, 3H, NCH2CNCH), 5.31–5.45 (m,
1H, ]CH), 5.71–5.82 (m, 1H, ]CH), 6.85 (d, 2H, JZ
8.2 Hz, HAr), 7.23–7.49 (m, 5H, HAr), 7.98 (d, 1H, JZ
7.9 Hz, HAr); 13C NMR (62.9 MHz, CDCl3) d 14.4 (CH3),
32.2 (NCH3), 34.4 (CH2), 34.5 (CH2), 52.3 (NCH2), 53.5
(C), 55.3 (CH3), 56.2 (NCH), 60.7 (OCH2), 72.1 (OCH2),
110.4 (CH), 112.4 (C), 113.9 (2CH), 117.2 (CH2), 117.5
(CH2), 122.2 (CH), 122.6 (CH), 124.1 (C), 125.2 (CH),
129.8 (C), 130.2 (2CH), 134.3 (CH), 134.6 (CH), 134.7 (C),
137.9 (C), 159.2 (C), 159.9 (C), 160.6 (CO), 166.4 (CO);
MS (IS) m/z 515 (MCH)C. Anal. Calcd for C31H34N2O5: C,
72.35; H, 6.66; N, 5.44. Found: C, 72.72; H, 6.54; N, 5.30.
` ´ ´
2003, 75, 421–425. (o) Chacun-Lefevre, L.; Beneteau, V.;
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Joseph, B.; Merour, J.-Y. Tetrahedron 2002, 58, 10181–10188.
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´
9. Perron, J.; Joseph, B.; Merour, J.-Y. Tetrahedron 2003, 59,
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