Synthesis of new pyrrolobenzazepines via Pictet-Spengler cyclization

Article abstract of DOI:10.1055/s-2008-1078567

A new six-step divergent strategy was developed allowing access to pyrrolobenzazepine structures from pyrrole. This strategy was based on a regioselective Friedel-Crafts acylation followed by a Pictet-Spengler cyclization. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1078567

1852
LETTER
Synthesis of New Pyrrolobenzazepines via Pictet–Spengler Cyclization
Synthesis of
N
t
ewPyr
é
rolobenza
z
p
epines hanie Gracia, Jürgen Schulz,* Stéphane Pellet-Rostaing,* Marc Lemaire
Laboratoire de Catalyse et de Synthèse Organique, ICBMS, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Université
Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne, France
Fax +33(4)72431408; E-mail: jurgen.schulz@univ-lyon1.fr
Received 15 March 2008
R
Abstract: A new six-step divergent strategy was developed allow-
ing access to pyrrolobenzazepine structures from pyrrole. This strat-
egy was based on a regioselective Friedel–Crafts acylation followed
by a Pictet–Spengler cyclization.
Pictet–Spengler cyclization
H
O2N
O
N
Key words: azepine, pyrrole, fused-ring systems, Pictet–Spengler
reaction
N
X
N
Ts
H
Friedel–Crafts
acylation
The pyrrolo[2,3-c]azepine scaffold is an original structure
found in various natural products such as stevensine, hy-
menin, or hymenialdisine (Figure 1). These alkaloids
were extracted from marine sponges belonging to the gen-
era Axinella, Acanthella, Hymeniacidon, and Pseudoax-
inyssa. Their structures were elucidated preliminarily
from spectral studies in comparison with biogenetically
and structurally related sponge metabolites1 and the X-ray
crystal structure of hymenialdisine has already been re-
ported.2
X = CH2, CO
R = CN, NO2, CF3, Cl, OMe
N
H
Friedel–Crafts
acylation
O
X
NH
O2N
N
H
N
Ts
Pictet–Spengler cyclization
These compounds have shown significant biological ac-
tivities. For example, hymenin possesses potent a-adreno-
ceptor blocking properties,3 and hymenialdisine was
found to be an inhibitor of mitogen-activated protein ki-
nase-1 (MEK-1), cyclin-dependent kinases (CDK-1), or
glycogen synthase kinase-3b (GSK-3b).4
R
Scheme 1 Retrosynthetic pathway and strategic bond disconnec-
tions of pyrrolo[2,3-c]benzazepine and pyrrolo[3,2-c]benzazepine
core
ester with pyrrole-2-carboxylic acid. Recently, Horne et
al. described the synthesis of the pyrroloazepine moiety
based on a four-step strategy starting from pyrrole.6 While
this product class was characterized by the presence of a
caprolactam moiety, we were interested in the synthesis of
amino and amino ketone analogues.
The first total synthesis of hymenialdisine was described
by Annoura et al.5 It was synthesized via the preparation
of a dihydropyrrolo[2,3,c]azepinedione intermediate (ald-
isine) obtained by the condensation of b-alanine methyl
H
H
Our synthetic strategy involved, starting from free pyr-
role, two key steps: a regioselective Friedel–Crafts acyla-
tion of the N-protected pyrrole and a Pictet–Spengler
cyclization with various aromatic aldehydes (Scheme 1).
Such a strategy, in combination with the possibility of us-
ing a wide range of commercially available reagents (aryl
aldehydes and aryl acids), should allow the functionaliza-
tion of the aromatic rings and could be suitable for the
preparation of a wide library of compounds.
N
H2N
N
H2N
N
N
Br
Br
NH
NH
N
H2N
Br
Br
O
N
N
H
H
O
O
HN
hymenin
stevensine
NH
R
N
The first key step of our synthetic approach is the regiose-
lective acylation of the 1-(p-toluenesulfonyl)pyrrole (1)
developed by Varvounis et al.7 In fact, 1-(p-toluenesulfo-
nyl)pyrrole (1), synthesized in phase-transfer conditions,8
could be acylated at C-2 or C-3 position depending on the
Lewis acid used during the reaction. Thus, the acylation of
1-(p-toluenesulfonyl)pyrrole (1) by o-nitrobenzoyl chlo-
ride in the presence of SnCl4 as Lewis acid allowed to ob-
tain the 2-acyl pyrrole derivative as the main product
H
O
hymenialdisine (R = Br)
debromohymenialdisine (R = H)
Figure 1 Stevensine, hymenin, and hymenialdisine structures
SYNLETT 2008, No. 12, pp 1852–1856
x
x
.x
x
.2
0
0
8
Advanced online publication: 02.07.2008
DOI: 10.1055/s-2008-1078567; Art ID: G07708ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of New Pyrrolobenzazepines
1853
N
H
a
N
Ts
b
c
1
O
O2N
O2N
N
N
d
d
Ts
O
2
Ts
3
O2N
e
e
O2N
N
Ts
N
4
5
Ts
e
e
O
H2N
H2N
H2N
H2N
N
N
Ts
Ts
N
N
O
8
Ts
Ts
6
7
9
Scheme 2 Reagents and conditions: (a) TsCl (1.4 equiv), n-Bu4NHSO4 (0.1 equiv), NaOH, CH2Cl2, 0 °C to r.t., 15 h (96%); (b) SnCl4 (1.5
equiv), o-nitrobenzoyl chloride (1.4 equiv), DCE, –10 °C, 2 h (78%); (c) AlCl3 (1.5 equiv), o-nitrobenzoyl chloride (1.4 equiv), DCE, –10 °C,
2 h (62%); (d) t-BuNH2·BH3 (6 equiv), AlCl3 (3 equiv), CH2Cl2, 0 °C to r.t., 15 h (65–70%); (e) Pd/C 10% (0.1 equiv), CH2Cl2, r.t., 4 h (72–
89%).
whereas the use of AlCl3 led mainly to the formation of 3- were investigated as substrates for the Pictet–Spengler cy-
acyl pyrroles via reaction of organoaluminum intermedi- clization.14 These condensations led either to azepine or
ate as recently reported by Huffman (Scheme 2).9
pyridine rings fused with the heteroaromatic moiety. To
the best of our knowledge, only a few examples described
the use of the Pictet–Spengler for the condensation of an
amine onto a pyrrole ring to synthesize a pyridine fused
ring.15 Moreover, no example of synthesis of azepine
fused with pyrrole ring using Pictet–Spengler reaction has
been described.
The two regioisomers 2 and 3 were next selectively re-
duced to 4 and 5 by reductive deoxygenation of the aryl
ketone using tert-butylamine borane complex and AlCl3
as described by Lau et al.10 The anilines 6, 7 and 8, 9 were
then obtained starting, respectively, from the nitro or from
the keto compounds by catalytic hydrogenation under at-
mospheric pressure at room temperature. This straightfor- With amines 6–9, we investigated whether these com-
ward pathway allowed us to synthesize amines 6–9 on pounds could undergo a Pictet–Spengler-type cyclization
gram scale, starting from free pyrrole, in overall yields be- in the presence of an aryl aldehyde (Scheme 3).
tween 37% and 66% (Scheme 2).
First, we studied the cyclization of compound 7 in the
The Pictet–Spengler reaction generally refers to conden- presence of p-cyanobenzaldehyde. In this case, cycliza-
sation of tryptamines or tryptophans with aldehydes or ke- tion may occur either at the C-2 position or at the C-4 po-
tones to give the corresponding b-carboline derivatives.11 sition of the pyrrole ring. A similar case was studied by
This reaction is also a powerful method for the prepara- Dodd et al.16 for the condensation of methyl-2-amino-3-
tion of tetrahydroisoquinoline having been applied to the [3-N-(benzenesulfonyl)pyrrolyl]propanoate with formal-
racemic or diastereoselective synthesis of aryl and het- dehyde to form tetrahydro-6-azaindole. The authors only
eroaryl tetraisoquinolines.12 This methodology has also observed the formation of the product resulting from the
been used in our laboratory to fuse benzazepine ring with condensation at the C-2 position of the pyrrole ring.
benzo[b]thiophene.13 Recently, Pictet–Spengler reaction
The amine 7 was condensed with p-cyanobenzaldehyde in
was applied to electron-rich heteroaromatic rings. Thus,
refluxing toluene to give intermediate imine with total
heteroaromatics such as imidazole, thiazole or pyrazole
conversion (followed by 1H NMR). The formation of the
Synlett 2008, No. 12, 1852–1856 © Thieme Stuttgart · New York

1854
S. Gracia et al.
LETTER
11a X = CH2, R = CN
11b X = CH2, R = NO2
11c X = CH2, R = CF3
11d X = CH2, R = Cl
11e X = CH2, R = OMe
X
X
13a X = CO, R = CN
13b X = CO, R = NO2
13c X = CO, R = CF3
13d X = CO, R = Cl
13e X = CO, R = OMe
H2N
NH
N
N
Ts
7
Ts
X = CH2
X = CO
9
1. p-RPhCHO, toluene, reflux
2. acid
or
R
or
10a X = CH2, R = CN
10b X = CH2, R = NO2
10c X = CH2, R = CF3
10d X = CH2, R = Cl
10e X = CH2, R = OMe
R
H2N
X
N
H
N
Ts
6 X = CH2
8 X = CO
12a X = CO, R = CN
12b X = CO, R = NO2
12c X = CO, R = CF3
12d X = CO, R = Cl
12e X = CO, R = OMe
X
N
Ts
Scheme 3 Pictet–Spengler cyclization of pyrrole derivatives 6–9
imine was relatively fast (60 min) due to the electron-
withdrawing effect of the cyano group. Treatment of the
resulting imine under the conditions described by Kundu
et al.14b [i.e., PTSA (0.1 equiv), toluene, reflux] did not
give any cyclized adduct. However, using Ohwada’s pro-
cedure,17 with five equivalents of TFA in toluene at room
temperature, only one product was observed after one
hour of reaction. The structure of the azepine 11a was elu-
cidated by H NMR. In fact, the observation in the H
NMR spectrum, of two doublets at d = 6.28 and 7.30 ppm
with a coupling constant of 3.4 Hz indicated the presence
of two vinylic protons onto the pyrrole ring. So, as expect-
ed, the cyclization occurred only at the C-2 position of the
pyrrole ring. Moreover, the regioselectivity of the Pictet–
Spengler condensation was unambiguously confirmed by
X-ray crystallography of a single crystal of the azepine
11a.18
Table 1 Pictet–Spengler Cyclization with Amines 6 and 719
Entry
Product
R
Temp Yield (%)a
(°C)
1
2
3
4
5
11a CN
11b NO2
11c CF3
11d Cl
20
20
20
20
98
83
87
82
38b
NH
N
1
1
11e OMe 70
Ts
R
6
7
8
9
10
10a CN
10b NO2
10c CF3
10d Cl
20
20
20
20
83
76
75
35
23b
R
H
10e OMe 70
N
This methodology was extended to the preparation of pyr-
rolobenzazepines 10a–e and 11b–e.19 As already reported
by our group for the synthesis of benzothienobenz-
azepines,13 reaction times for the formation of imines
were relatively short with electron-poor benzaldehyde de-
rivatives (R = CN, NO2, CF3) at room temperature in tol-
uene whereas the use of electron-rich benzaldehydes
(R = OMe) required longer reaction times in refluxing tol-
uene. Treatment of the imine with TFA in the conditions
described by Ohwada17 allowed us to isolate pyrrolo[3,2-
c]benzazepines 10a–e and pyrrolo[2,3-c]benzazepines
11a,b (Table 1).
N
Ts
a 1 M in toluene, addition of TFA (5 equiv).
b 1 M in toluene, addition of TFA (10 equiv).
tet–Spengler cyclization which occurred via a SE-type
mechanism.
With keto analogues 8 and 9 (Scheme 3), the imine forma-
tion was not complete. Likewise, the cyclization was more
difficult to complete and required heating (70 °C). Addi-
tion of a desiccant to favor the imine formation (MgSO4)
allowed to increase the yields in cyclized product of about
30% (Table 2).
As can be seen in Table 1, the yields were generally good
to excellent. We only obtained poor yields when p-meth-
oxybenzaldehyde or p-chlorobenzaldehyde were used
(entries 5, 9, and 10). We assumed that the electronic en-
richment of the iminium intermediate, due to the electron-
donating group onto the benzaldehyde, penalized the Pic-
Although the deprotection of sulfonyl groups could be
achieved by basic hydrolysis with KOH or NaOH20 or by
reduction21 in the presence of Na(Hg) or Na2HPO4, rela-
tively drastic conditions are generally required. Yasuhara
Synlett 2008, No. 12, 1852–1856 © Thieme Stuttgart · New York

LETTER
Synthesis of New Pyrrolobenzazepines
1855
15a X = CH2, R = CN
15b X = CH2, R = NO2
15c X = CH2, R = CF3
15d X = CH2, R = Cl
15e X = CH2, R = OMe
X
X
NH
17a X = CO, R = CN
17b X = CO, R = NO2
17c X = CO, R = CF3
17d X = CO, R = Cl
17e X = CO, R = OMe
N
N
N
H
Ts
TBAF (1 M in THF)
10 equiv, 70 °C
or
R
or
R
R
R
14a X = CH2, R = CN
14b X = CH2, R = NO2
14c X = CH2, R = CF3
14d X = CH2, R = Cl
14e X = CH2, R = OMe
H
N
N
X
16a X = CO, R = CN
16b X = CO, R = NO2
16c X = CO, R = CF3
16d X = CO, R = Cl
16e X = CO, R = OMe
N
X
N
Ts
H
10–13
Scheme 4 Deprotection of compounds 10–13
Table 2 Pictet–Spengler Cyclization with Amines 8 and 913
Table 3 Deprotection of Azepine 10–1324
Entry Product
R
Temp (°C) Yield (%)a Entry Azepine
Product
X
R
Yield (%)a
R
1
13a CN
13b NO2 70
13c CF3 70
13d Cl
13e OMe 70
70
47 (15)c
63 (23)c
43 (41)c
53 (5)c
1
2
3
4
5
6
7
8
9
14a
14b
14c
14d
14e
16a
16b
16c
16d
16e
CH2 CN 77
CH2 NO2 52
CH2 CF3 74
O
2
3
4
70
CH2 Cl
73
NH
H
15 (–)b,c
CH2 OMe 24
CO CN 86
CO NO2 56
CO CF3 85
N
N
5
Ts
X
N
Ts
CO Cl
97
10–12
R
10
CO OMe 60
6
7
8
9
10
12a CN
12b NO2 70
12c CF3 70
12d Cl
12e OMe 70
70
43 (20)c
41 (29)c
51 (6)c
R
11
12
13
14
15
16
17
18
19
20
15a
15b
15c
15d
15e
17a
17b
17c
17d
17e
CH2 CN 88
CH2 NO2 70
CH2 CF3 46
X
70
31 (16)c
62 (–)b,c
CH2 Cl
21
NH
NH
CH2 OMe 56
CO CN 91
CO NO2 84
CO CF3 50
N
Ts
N
Ts
O
CO Cl
84
a 1 M in toluene, addition of TFA (5 equiv).
R
CO OMe 69
b 1 M in toluene, addition of TFA (10 equiv).
c Values in parentheses are yields without using MgSO4.
11–13
a 1 M TBAF in THF (10 equiv), reflux.
and Sakamoto22 described the use of 1 M TBAF in reflux-
ing THF (10 equiv) to deprotect N-tosyl nitrogen heteroar-
omatic compounds. We chose this mild and neutral
method to deprotect all of our compounds. In fact, in our
case, basic hydrolysis is not compatible with base-sensi-
tive functions such as cyano group. Deprotected azepines
14–17 were obtained in good yields (Scheme 4, Table 3).
presence of TBAF was already reported by Bianchi and
Kaufman for the synthesis of a tricyclic lactone.23
A new six-step, highly divergent strategy was developed
allowing access to hymenialdisine analogues starting
from pyrrole. Based on a regioselective Friedel–Crafts
acylation followed by a Pictet–Spengler cyclization, pyr-
rolobenzazepines 14, 15 and the corresponding pyr-
rolobenzazepinones 16, 17 were obtained.
1
However, the absence in the H NMR spectrum of the
benzylic proton on the deprotected azepine revealed that
we did not obtain the expected azepine but the corre-
sponding imine (Scheme 4). Furthermore, no intermedi-
ary product was detected by TLC during the course of the
deprotection. As far as we know, only one example of this
‘oxidative desulfonation’ of nitrogen heterocycles in the
References and Notes
(1) Eder, C.; Proksh, P.; Wray, V.; Steube, K.; Bringmann, G.;
van Soest, R. W. M.; Sudarsono, ; Fernandus, E.; Pattisina,
Synlett 2008, No. 12, 1852–1856 © Thieme Stuttgart · New York

1856
S. Gracia et al.
LETTER
(18) The X-ray crystal structure has been filed with the
L. A.; Wiryowidagdo, S.; Moka, W. J. Nat. Prod. 1999, 62,
184.
Cambridge Crystallographic Centre with deposition number
CCDC 640594.
(2) (a) Cimino, G.; De Rosa, S.; De Stefano, D.; Mazzarella, L.;
Puliti, R.; Sodano, G. Tetrahedron Lett. 1982, 23, 767.
(b) Kitagawa, I.; Kobayashi, M.; Kitanaka, K.; Kido, M.;
Kyogoku, Y. Chem. Pharm. Bull. 1983, 31, 2321.
(3) (a) Kobayashi, J.; Ohizumi, Y.; Nakamura, H.; Hirata, Y.;
Wakamatsu, K.; Miyazawa, T. Experientia 1986, 42, 1064.
(b) Kobayashi, J.; Nakamura, H.; Ohizumi, Y. Experientia
1988, 47, 86.
(4) (a) Tasdemir, D.; Mallon, R.; Greenstein, M.; Feldberg, L.
R.; Kim, S. C.; Collins, K.; Wojciechowicz, D.;
Mangalindan, G. C.; Concepcion, G. P.; Harper, M. K.;
Ireland, C. M. J. Med. Chem. 2002, 45, 529. (b) Meijer, L.;
Flajolet, M.; Greengard, P. Trends Pharmacol. Sci. 2004, 25,
471. (c) Knockaert, M.; Greengard, P.; Meijer, L. Trends
Pharmacol. Sci. 2002, 23, 417. (d) Meijer, L.; Thunnissen,
A. M. W. H.; White, A. W.; Garnier, M.; Nikolic, M.; Tsai,
L. H.; Walter, J.; Cleverley, K. E.; Salinas, P. C.; Wu, Y. Z.;
Biernat, J.; Mandelkow, E. M.; Kim, S. H.; Pettit, G. R.
Chem. Biol. 2000, 7, 51. (e) Wan, Y.; Hur, W.; Cho, C. Y.;
Liu, Y.; Adrian, F. J.; Lozach, O.; Bach, S.; Mayer, T.;
Fabbro, D.; Meijer, L.; Gray, N. S. Chem. Biol. 2004, 11,
247.
(5) Annoura, H.; Tatsuoka, T. Tetrahedron Lett. 1995, 36, 413.
(6) (a) Xu, Y. Z.; Yakushijin, K.; Horne, D. A. J. Org. Chem.
1997, 62, 456. (b) Barrios Sosa, A. C.; Yakushijin, K.;
Horne, D. A. J. Org. Chem. 2000, 65, 610. (c) Papeo, G.;
Posteri, H.; Borghi, D.; Vasari, M. Org. Lett. 2005, 7, 5641.
(7) Kimbaris, A.; Varvounis, G. Tetrahedron 2000, 56, 9675.
(8) Anderson, H. J.; Loader, C. E.; Xu, R. X.; Le, N.; Gognan,
N. J.; McDonald, R.; Edwards, L. G. Can. J. Chem. 1985, 63,
896.
(19) General Procedure for Preparation of Compounds 10–13
To a stirred 1 M solution of amine 6, 7, 8, or 9 in anhyd
toluene was added the para-substituted benzaldehyde
derivative (1.1 equiv), under argon atmosphere (in the case
of amines 8 and 9, 4 equiv of MgSO4 were added). The
mixture was heated at reflux until total conversion of the
amine into the intermediary imine (followed by 1H NMR).
Then, the mixture was cooled to r.t. to add TFA (5 or 10
equiv). The resulting mixture was left at specified
temperature (r.t. or 70 °C) until completion of the reaction.
Residual TFA was neutralized at 0 °C with an aq sat.
NaHCO3 solution. The reaction mixture was extracted with
CH2Cl2. The combined organic layers were successively
washed with H2O and brine, dried over MgSO4, filtered, and
solvents removed under reduced pressure. The crude product
was purified by flash chromatography.
Analytical Data of Compound 11a
Pale yellow solid obtained in 98% yield after flash
chromatography (cyclohexane–EtOAc, 9:1). 1H NMR (300
MHz, CDCl3): d = 2.33 (s, 3 H), 3.63 (d, J = 16.2 Hz, 1 H),
3.73 (br s, 1 H), 4.14 (d, 16.2 Hz, 1 H), 6.06 (m, 1 H), 6.08
(dd, J = 1.3, 7.3 Hz, 1 H), 6.28 (d, J = 3.4 Hz, 1 H), 6.73 (d,
J = 8.3 Hz, 2 H), 6.85 (m, 2 H), 6.97 (d, J = 8.3 Hz, 2 H), 7.04
(d, J = 8.3 Hz, 2 H), 7.11 (dd, J = 1.3, 7.1 Hz, 1 H), 7.15 (d,
J = 8.3 Hz, 2 H), 7.30 (d, J = 3.4 Hz, 1 H). HRMS: m/z =
439.5326.
(20) Sundberg, R. J.; Laurino, J. P. J. Org. Chem. 1984, 49, 249.
(21) Boyles, D. A.; Nichols, D. E. J. Org. Chem. 1988, 53, 5128.
(22) Yasuhara, A.; Sakamoto, T. Tetrahedron Lett. 1998, 39, 595.
(23) (a) Ko, E. Y.; Lim, C. H.; Chung, K.-H. Bull. Korean Chem.
Soc. 2006, 27, 432. (b) Bianchi, A. A.; Kaufman, T. S.
ARKIVOC 2003, (x), 178.
(9) Huffman, J. W.; Smith, V. J.; Padgett, L. W. Tetrahedron
2008, 64, 2104.
(10) Lau, C. K.; Tardif, S.; Dufresne, C.; Scheigetz, J. J. Org.
Chem. 1989, 54, 491.
(11) Pictet, A.; Spengler, T. Ber. Dtsch. Chem. Ges. 1911, 44,
2030.
(12) Aubry, S.; Pellet-Rostaing, S.; Faure, R.; Lemaire, M.
J. Heterocycl. Chem. 2006, 43, 139.
(13) David, E.; Rangheard, C.; Pellet-Rostaing, S.; Lemaire, M.
(24) General Procedure for Preparation of Compounds 14–17
A mixture of the azepine 10a–e, 11a–e, 12a–e, or 13a–e (1
equiv) and TBAF 1 M solution in THF (10 equiv) was heated
at 70 °C for 10 h. The mixture was washed with H2O. The
aqueous phase was extracted with CH2Cl2. The combined
organic layers were dried over MgSO4, filtered, and solvents
removed under reduced pressure. The crude product was
purified by flash chromatography.
Synlett 2006, 2016.
(14) (a) Kundu, B.; Sawant, D.; Chhabra, R. J. Comb. Chem.
2005, 7, 317. (b) Kundu, B.; Sawant, D.; Partani, P.;
Kesarwani, A. P. J. Org. Chem. 2005, 70, 4889.
(c) Duggineri, S.; Sawant, D.; Saha, B.; Kundu, B.
Tetrahedron 2006, 62, 3228.
Analytical Data of Compound 15a
Yellow solid obtained in 88% yield after flash
chromatography (heptane–EtOAc, 8:2). 1H NMR (300
MHz, CDCl3): d = 3.75 (s, 2 H), 6.21 (t, J = 2.6 Hz, 1 H),
6.93 (t, J = 2.6 Hz, 1 H), 7.2 (dd, J = 1.7, 6.6 Hz, 1 H), 7.22
(td, J = 1.7, 6.6 Hz, 1 H), 7.29 (td, J = 1.7, 6.6 Hz, 1 H), 7.48
(dd, J = 1.7, 7.2 Hz, 1 H), 7.76 (d, J = 8.3 Hz, 2 H), 8.0 (d,
J = 8.3 Hz, 2 H), 8.24 (br s, 1 H). 13C NMR (300 MHz,
CDCl3): d = 32.6, 108.7, 114.1, 118.9, 123.3, 123.5, 126.9,
127.8, 128.2, 128.7, 130.5, 132.0, 132.8, 133.4, 144.2,
147.0, 155.0. HRMS: m/z = 437.5148.
(15) Testa, M. L.; Lamartina, L.; Mingoia, F. Tetrahedron 2004,
60, 5873.
(16) Rousseau, J. F.; Dodd, R. H. J. Org. Chem. 1998, 63, 2731.
(17) Yokoyama, A.; Ohwada, T.; Shudo, K. J. Org. Chem. 1999,
64, 611.
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