Formation of new 5,11b-bridged isoindolo[2,1-b]isoquinolinones alkaloids through a tandem Pummerer/ π-cationic cyclization

Article abstract of DOI:10.1021/ol005545c

(formula presented) The tandem Pummerer/π-aromatic cyclization of α-acyliminium ion, leading efficiently in "one pot" to thioepoxyareno-bridged isoindoloisoquinolinone incorporating the arylthio group, has been demonstrated for the first time. During this

Full text of DOI:10.1021/ol005545c

ORGANIC
LETTERS
2000
Vol. 2, No. 9
1201-1204
Formation of New 5,11b-Bridged
Isoindolo[2,1-b]isoquinolinones
Alkaloids through a Tandem Pummerer/
π-Cationic Cyclization
Nicolas Hucher, Adam Daich,* and Bernard Decroix
URCOM, UniVersite´ du HaVre, Faculte´ des Sciences et Techniques,
25 rue Philippe Lebon, B.P: 540, 76058 Le HaVre Cedex, France
adam.daich@uniV-lehaVre.fr
Received January 13, 2000
ABSTRACT
The tandem Pummerer/π-aromatic cyclization of r-acyliminium ion, leading efficiently in “one pot” to thioepoxyareno-bridged isoindoloiso-
quinolinone incorporating the arylthio group, has been demonstrated for the first time. During this sequence the angular hydroxylated
isoindoloisoquinolinone, resulting from the Pummerer-type cyclization, was also obtained.
The Pummerer reaction initiated by several types of thionium
ions has been proven to be a powerful synthetic tool for the
preparation of R-substituted sulfides.1
When thionium ions are intramolecularly intercepted, this
process becomes a versatile methodology to obtain polycyclic
(or heterocyclic) systems such as A.1,2 Structures such as
C,3 which include the heteronucleophile in the formed
thiacycles, have been little explored.4
addition, N-acyliminium ion cyclization, or Mannich cy-
clization have been recently developed, by the Padwa
group5-13 and others,14,15 for the construction of various
complex polyheterocyclic ring systems. Prominent targets
(4) (a) Yale, H. L. J. Heterocycl. Chem. 1978, 15, 331. (b) Abe, H.;
Shibaike, K.; Fujii, H.; Tsuchida, D.; Akiyama, T.; Harayama, T. Hetero-
cycles 1999, 50, 291. (c) Stridsberg, B.; Allemark, S. Acta Chem. Scand. B
1974, 28, 591.
Tandem processes involving the Pummerer reaction and
lactonization, Diels-Alder cycloaddition, 1,3-dipolar cyclo-
(5) (a) Kuethe, J. T.; Cochran, J. E.; Padwa, A. J. Org. Chem. 1995, 60,
7082. (b) Kappe, C. O.; Cochran, J. E.; Padwa, A. Tetrahedron Lett. 1995,
36, 9285. (c) Padwa, A. J. Chem. Soc., Chem. Commun. 1998, 1417.
(6) Cochran, J. E.; Padwa, A. Tetrahedron Lett. 1995, 36, 3495.
(7) Padwa, A.; Cochran, J. E.; Kappe. C. O. J. Org. Chem. 1996, 61,
3706.
(8) Cochran, J. E.; Padwa, A. J. Org. Chem. 1995, 60, 3938.
(9) Kappe, C. O.; Padwa, A. J. Org. Chem. 1996, 61, 6166.
(10) Kuethe, J. T.; Padwa, A. J. Org. Chem. 1997, 62, 774.
(11) Padwa, A.; Kappe, C. O.; Reger, T. S. J. Org. Chem. 1996, 61,
4888.
(12) Padwa, A.; Hennig, R.; Kappe, C. O.; Reger, T. S. J. Org. Chem.
1998, 63, 1144.
(13) Padwa, A.; Waterson, A. G. Tetrahedron Lett. 1998, 39, 8585.
(14) De Groot, A.; Jansen, B. J. M. J. Org. Chem. 1984, 49, 2034.
(15) Jansen, B. J. M.; Bouwmann, C. T.; De Groot, A. Tetrahedron Lett.
1994, 35, 2977.
(1) (a) Russell, G. A.; Mikol, G. J. In Mechanisms of Molecular
Migrations; Thyagarajan, B. S., Eds., Wiley-Interscience: New York, 1968;
Vol. 1, p 157. (b) Padwa, A.; Gunn, D. E., Jr.; Osterhout, M. H. Synthesis
1997, 1353.
(2) Jousse, C.; Desmae¨le, D. Eur. J. Org. Chem. 1999, 909, 9.
(3) (a) Rills, R. W.; Murray, R. D. H.; Raphael, R. A. J. Chem. Soc.,
Chem. Commun. 1971, 555. (b) Blair, I. A.; Mander, L. N.; Mundill, P. H.
C. Aust. J. Chem. 1981, 34, 1235. (c) Ishibashi, H.; Sato, K.; Akiyama, A.;
Nomura, K.; Ikeda, M. J. Heterocycl. Chem. 1986, 23, 1163. (d) Wang, H.
M.; Lin, M. C.; Chen, L. C. J. Chin. Chem. Soc. 1994, 41, 217. (e) Wang,
H. M.; Lin, M. C.; Chen, L. C. Heterocycles 1994, 38, 1519. (f) Garofalo,
A.; Campiani, G.; Nacci, V.; Fiorini, I. Heterocycles 1992, 34, 51 and
references therein.
10.1021/ol005545c CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/05/2000

of these structures were exemplified by isodrimerin,14 (()-
confertifolin,15 sulfanyl-substituted naphthalenes,6-8 taiwanin
C,7 justicidin E,7 indeno[4,5-b]thiophenes,8 furo[3,4-b]in-
doles,9 thienopyridones,10 and 3,4-benzoerythrinane alka-
loid.11 In all cases the thioalkyl (or aryl) group, which
induced the sulfonium ion, was present in the final structure
in an exocyclic position7,10,11,14,15 or eliminated in an ultimate
step.6,8-10
Scheme 3
In view of our interest in the formation-cleavage of the
thioether linkage in N,S-fused polyheterocyclic systems,16
we describe herein an interesting short pathway, using a
tandem Pummerer/N-acyliminium ion cyclization, to bridged
isoindoloisoquinolinone alkaloids such as B (Scheme 1). In
Scheme 1
lead, through an intramolecular R-amidoalkylation cycliza-
tion, to the highly condensed alkaloids derivatives 6. Finally,
subsequent hydration or hydration-deprotonation of, re-
spectively, 8 or 9 should ultimately lead to the hydroxylated
product 5.
To establish the generality and versatility of the synthetic
approach depicted in Scheme 2, the elaboration of different
aromatic models, substituted by phenyl, bromophenyl, or
naphthyl groups on the aromatic moiety, was explored.
The requisite sulfoxide 3, 4 diastereomers were obtained
in three steps successively by S-alkylation, Grignard carbo-
philic addition, and S-oxidation (Scheme 3). The alkylation
reaction was carried out by condensation of N-chlorometh-
ylphthalimide with a slight excess of aryl mercaptan in an
alkaline medium.17 Treatment of the resulting N-alkylated
phthalimides 1a,b,c with benzylmagnesium chloride (1.5-2
equiv) at room temperature afforded the expected ω-benzyl-
ω-carbinol lactams 2a,b,c in 51%, 61%, and 73% yields,
respectively.
this methodology, the phenylthio group as a sulfonium ion
precursor, was incorporated in the thiazacyclic bridge.
As depicted in Scheme 2, our strategy envisioned the
synthesis of intermediate thionium ion 7 in order to obtain
Scheme 2
To avoid the formation of sulfones during m-chloroper-
benzoic acid (mCPBA) oxidation of sulfides 2,18 a short
reaction time (1-3 min at 0 °C) was necessary. The 1H, 13
C
NMR, and GC-MS data for the crude sulfoxides showed a
mixture of two diastereomers 3 and 4 in a variable ratio
depending on the aryl group.19,20
Indeed, the methylene protons in N-CH2-S and N-
C(OH)-CH2-Ar functionalities of the sulfoxides 3 and 4
appear as an AB system due to the diastereotopic effect with
a coupling constant of J ) 12.4-14.3 Hz for N-CH2-S
and J ) 12.9-14.5 Hz for N-C(OH)-CH2-Ar character-
1
istic of gem protons (in the H NMR spectra of sulfides 2,
the same facts were observed).20 Furthermore, these protons
were in general shifted to downfield compared to the parents
sulfides 2. This deshielding effect, notably in the functional-
ity, was due to the proximity of the sulfoxide SfO group.
the N-acyliminium ion precursor 5. These latter compounds
should be accessible from sulfide imide 1 (Scheme 3).
Indeed, taking into account that thionium-enamide ion 7,
derived from a Pummerer and dehydration reactions of
sulfoxides 3 and 4, could provide the 5-(phenylthio) lactam
8 via π-aromatic cyclization, its N-acyliminium ion 9 could
(17) (a) Hucher, N.; Daich, A.; Decroix, B. J. Heterocycl. Chem. 1998,
35, 1477. (b) Hucher, N.; Daich, A.; Decroix, B. Tetrahedron Lett. 1999,
40, 3363. (c) Imides 1a (90%) and 1c (94%) were obtained in another
pathway, in yields of 90 and 80%, respectively, as reported in the following
reference: Uchino, M.; Suzuki, K.; Sekiya, M. Chem. Pharm. Bull. 1979,
27, 1199.
(18) Terauchi, H.; Tanitame, A.; Tada, K.; Nishikawa, Y. Heterocycles
1996, 43, 1719.
(19) 1H NMR spectra of sulfoxides 3 and 4 have shown that sulfoxides
3a/4a and 3b/4b consist of 6.3:3.7 ratio while for 3c/4c, it was of 5.9:4.1.
(16) Daich, A.; Decroix, B. J. Heterocycl. Chem. 1991, 28, 1881.
1202
Org. Lett., Vol. 2, No. 9, 2000

1
Another oxidation of 2a derivative was performed at -20
°C; interestingly, the reaction occurred during 6 to 9 min,
leading to 3a/4a in a 7.5:2.5 ratio in favor of the major
component obtained above. The diastereoselectivity observed
during this process and the relative stereochemistry of these
compounds 3a/4a, which could not be separated chromato-
graphically, are not yet elucidated.
5.1:4.9 ratio. The H NMR spectrum of this mixture was
identical to the one discussed above. This result indicated
that the π-cyclization of N-acyliminium ion was interrupted
due to the presence of pyridine as a TFA scavenger.
On the other hand, when the reaction was conducted under
conditions i with addition of TFA, the reaction after 12 h at
room temperature produced only the bridged tricycle 6a (42%
after recrystallization from ethanol).26 In this case, the
intermediate ω-carbinol lactam 5a in acidic medium fur-
nished, by intramolecular R-amidoalkylation cyclization, the
expected product 6a. This latter product was also obtained
from isolated 5a (i.e., TFA, rt, 12 h) in 58% yield.27
In the first set of our Pummerer rearrangement experiments
(Scheme 4), a mixture of sulfoxides 3a and 4a was subjected
Scheme 4
(20) General procedure for preparation of 3a,b,c and 4a,b,c: To a stirred
solution of sulfides 2a,b,c (1 mmol) in dry CH2Cl2 (10 mL) was added in
one portion at 0 °C a solution of mCPBA (0.21 g, 1.2 mmol) in dry CH2Cl2
(5 mL). After 1-3 min of reaction, the mixture was alkalinized with a
saturated solution of NaHCO3 (15 mL). After a classical workup, the solid
residue was recrystallized from ethanol to give quantitatively (1 mmol) the
expected inseparable diastereosomers 3 and 4. Selected data for major isomer
of 3a+4a (6.3:3.7): solid; EIMS m/z 377 (M+); 1H NMR (CDCl3, 200.13
MHz) δ 3.22 (d, 1H, J ) 13.7, CH2Ar), 3.35 (d, 1H, J ) 13.7, CH2Ar),
4.14 (d, 1H, J ) 12.4, NCH2S), 5.00 (d, 1H, J ) 12.4, NCH2S), 5.75 (s,
1H, OH exchangeable with D2O), 6.78-7.72 (m, 14H, arom H). Anal. Calcd
For C22H19NO3S (377.46) (mixture): C, 70.00; H, 5.07; N, 3.71. Found:
C, 69.89; H, 4.99; N, 3.69. Selected data for minor isomer of 3a+4a (6.3:
1
3.7): solid; EIMS m/z 377 (M+); H NMR (CDCl3, 200.13 MHz) δ 3.22
(d, 1H, J ) 14.3, CH2Ar), 3.59 (d, 1H, J ) 14.3, CH2Ar), 4.76 (d, 1H, J
) 13.7, NCH2S), 5.23 (d, 1H, J ) 13.7, NCH2S), 6.40 (s, 1H, OH
exchangeable with D2O), 6.78-7.72 (m, 14H, H.-Aromatic). Selected data
for major isomer of 3b+4b (6.3: 3.7): solid; EIMS m/z 456 (M+); 1H
NMR (CDCl3, 200.13 MHz) δ 3.93 (d, 1H, J ) 12.9, CH2Ar), 4.02 (d, 1H,
J ) 12.4, NCH2S), 4.11 (d, 1H, J ) 12.4, NCH2S), 4.79 (d, 1H, J ) 12.9,
CH2Ar), 5.44 (s, 1H, OH exchangeable with D2O), 6.93-7.74 (m, 13H,
arom H). Anal. Calcd For C22H19BrNO3S (456.35) (mixture): C, 57.90;
H, 3.98; N, 3.07. Found: C, 57.79; H, 3.77; N, 3.01. Selected data for
minor isomer of 3b+4b (6.3:3.7): solid; EIMS m/z 456 (M+); 1H NMR
(CDCl3, 200.13 MHz) δ 3.24 (d, 1H, J ) 14.3, CH2Ar), 3.62 (d, 1H, J )
14.3, CH2Ar), 4.65 (d, 1H, J ) 14.3, NCH2S), 5.32 (d, 1H, J ) 14.3,
NCH2S), 6.52 (s, 1H, OH exchangeable with D2O), 6.93-7.74 (m, 13H,
arom H). Selected data for major isomer of 3c+4c (5.9:4.1): solid; EIMS
to trifluoroacetic anhydride (TFAA)21 in CH2Cl2 at room
temperature for 12 h. The 1H NMR and GC-MS analysis of
crude reaction products indicated the presence of three
compounds 5a + 6b with 6b as a major component (5a is a
mixture of two diastereomers in 6.2:3.8 ratio).
The major product was isolated by FC, and its structure
was established as 6a by an array of mono- and bidimen-
sional NMR experiments (homocorrelation 1H-1H and 13C-
13C, heterocorrelation 1H-13C, DEPT). The structures of the
inseparable diastereomers 5a were deducted by their mo-
lecular ions at mass 359 and from the presence in their NMR
spectrum of the altered alcohol proton after equilibration with
deuterium oxide.
Interestingly, the thionium ion 7 as the Pummerer inter-
mediate (Scheme 2)22 is intercepted by a π-aromatic to give
5a after an hydrolysis of 8 in equilibrium with 9 in an acidic
medium. Diastereomers 5a, in the presence of TFA,23 are in
facile equilibrium with ion 9 which was, in turn, capable of
an intramolecular capture of a π-aromatic as an internal
nucleophile.17,24 Under this sequential set, the reaction
produced polyheterocyclic system as 6a.
1
m/z 427 (M+); H NMR (CDCl3, 200.13 MHz) δ 4.24 (d, 1H, J ) 14.0,
CH2Ar), 4.78 (d, 1H, J ) 12.4, NCH2S), 5.08 (d, 1H, J ) 14.0, CH2Ar),
5.35 (d, 1H, J ) 12.4, NCH2S), 6.27 (s, 1H, OH exchangeable with D2O),
6.76-8.24 (m, 16H, arom H). Anal. Calcd For C26H21NO3S (427.52)
(mixture): C, 73.04; H, 4.95; N, 3.27. Found: C, 73.00; H, 4.88; N, 3.12.
Selected data for minor isomer of 3c+4c (5.9:4.1): solid; EIMS m/z 427
1
(M+); H NMR (CDCl3, 200.13 MHz) δ 3.23 (d, 1H, J ) 14.0, CH2Ar),
3.66 (d, 1H, J ) 14.0, CH2Ar), 4.71 (d, 1H, J ) 14.5, NCH2S), 5.45 (d,
1H, J ) 14.5, NCH2S), 5.80 (s, 1H, OH exchangeable with D2O), 6.76-
8.24 (m, 16H, arom H).
(21) Padwa, A.; Kuethe, J. T. J. Org. Chem. 1998, 63, 4256.
(22) For further details on the Pummerer mechanism, see ref 1.
(23) TFA was liberated in the medium from TFAA during Pummerer
rearrangement.
(24) (a) Speckamp, W. N.; Hiemstra, H. Tetrahedron 1985, 41, 4367.
(b) Hiemstra, H.; Speckamp, W. N. In The Alkaloids; Rossi, A., Eds.,
Academic Press: New York, 1988; Vol. 32, Chapter 4, p 271. (c) Hiemstra,
H.; Speckamp, W. N. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds., Pergamon Press: Oxford, 1991; Vol. 2, p 1047.
(25) Procedure for preparation of 11b-hydroxy-11b,12-dihydro-5-(phen-
ylthio)-5H-isoindolo[2,1-b]isoquinolin-7-one (5a): TFAA (8 mL, 57 mmol)
and pyridine (3 mL, 37 mmol) were added neat to a mixture of 3a and 4a
(377 mg, 1 mmol), and the mixture was stirred at room temperature for 5
h. Excess of TFAA and pyridine were removed under reduced pressure,
and the brown residue was diluted with H2O (15 mL) and neutralized with
5% aqueous Na2CO3. After classical workup, the oily residue was purified
by flash chromatography on a silica gel column eluting with CH2Cl2 to
provide 201 mg (56%) of 5a as 5.9:4.9 mixture of two diastereomers.
1
Selected data for major isomer of 5a: oil; EIMS m/z 359 (M+); H NMR
Afterward we decided to study the effect of different
reaction conditions on selectivity of the process. So, when
we used more than 1 equiv of pyridine relative to the
sulfoxides congeners 3 and 4 (i.e., TFAA, pyridine, rt, 5 h,
Scheme 4),25 the hydroxylated isoindoloisoquinolinone 5a
(56%) was isolated, as a mixture of two diastereomers in
(CDCl3, 200.13 MHz) δ 5.62 (s, 2H, CH2Ar), 6.04 (s, 1H, NCH), 6.92 (s,
1H, OH exchangeable with D2O), 7.14-8.23 (m, 13H, arom H). Anal. Calcd
for C22H17NO2S (359.45) (mixture): C, 73.51; H, 4.76; N, 3.89. Found:
C, 73.39; H, 4.66; N, 3.69. Selected data for minor isomer of 5a: oil; EIMS
m/z 359 (M+); 1H NMR (CDCl3, 200.13 MHz) δ 4.31 (s, 1H, OH
exchangeable with D2O), 5.57 (s, 2H, CH2Ar), 6.12 (s, 1H, NCH), 7.14-
8.23 (m, 13H, arom H). Anal. Calcd for C22H17NO2S (359.45) (mixture):
C, 73.51; H, 4.76; N, 3.89. Found: C, 73.39; H, 4.66; N, 3.69.
Org. Lett., Vol. 2, No. 9, 2000
1203

Finally as an extension of these studies, a mixture of
sulfoxides 3b and 4b (or 3c and 4c) were prepared similarly
as outlined in Scheme 3 to evaluate the effect of o-bromo
phenylthio substitution and another electron-rich arylthio
group in the cyclization step.
In a similar manner as above (i.e., TFAA, CH2Cl2, rt, 8
to 12 h then TFA, rt, 12 h, conditions iii in Scheme 4),25
these sulfoxides afforded the bridged products 6b or 6c in
62% and 41% yields, respectively. Although the presence
of the bromide atom seemed to facilitate the cyclization step,
there was no discernible preference for the naphthyl group
since more resignification was observed during the cycliza-
tion step into 6c (41%).
In conclusion, we have shown that our tandem cyclization
reaction involves an initial intramolecular arylation of
thionium ion, followed by a π-aromatic cyclization of
N-acyliminium ion. This process produces efficaciously
5,11b-bridged isoindoloisoquinolinone alkaloids 6. However,
in an interrupted π-aromatic intramolecular R-amidoalkyl-
ation cyclization, the N-acyliminium ion intermediate un-
dergoes a hydrolysis leading to the expected difunctionalized
isoindoloisoquinolinone alkaloid 5.
Supporting Information Available: Physical data of all
other products not described herein (1 and 2) and detailed
descriptions of experimental procedures. This material is
availabe available free of charge via the Internet at http://
pubs.acs.org. The data may also be obtained at the following
e-mail address: Adam@Daich@univ-lehavre.fr.
(26) General procedure for preparation of 6a,b,c: A solution containing
a mixture of sulfoxides 3a,b,c and 4a,b,c (1 mmol) and TFAA (8 mL, 57
mmol) in dry CH2Cl2 (5 mL) was stirred at room temperature. After 8-12
h of reaction (the reaction was monitored by TLC using an silica gel column
and CH2Cl2 as eluent), TFA (4 mL, 52 mmol) was added neat in one portion,
and the mixture was allowed to react again at the same temperature for 12
h. Solvents were removed under reduced pressure, and the residue was
diluted with CH2Cl2 (20 mL). After a classical workup, the residue was
passed through a short silica gel column with CH2Cl2 as eluent, and the
resulting solid was recrystallized from ethanol to give the expected product
6. Selected data for 11b,12-dihydro-5,11b-thioepoxy[1′,2′]benzeno-5H-
isoindolo[2,1-b]isoquinolin-7-one (6a): This product was obtained in 42%
yield (m ) 143 mg); mp 249 °C.; EIMS m/z 341 (M+); IR (KBr): ν 3013
Acknowledgment. The authors thank the region of Haute
Normandie and the University of Le Havre (France) for
financial support of this work (Regional Scholarship
1996-1999).
1
(CH), 2989 (CH), 1713 ( CdO) cm-1; H NMR (CDCl3, 200.13 MHz) δ
OL005545C
5.48 (s, 2H, CH2Ar), 6.12 (d, 1H, J ) 8.1 Hz, CH), 7.20-7.58 (m, 11H,
benzene 8H + isoindole 3H), 8.78 (d, 1H, J ) 7.5 Hz, isoindole H); 13C
NMR (CDCl3, 50.13 MHz) δ 44.5 (CH2), 119.6 (C), 122.5 (CH), 122.8
(CHAr), 128.0 (CHAr), 128.4 (C), 128.8 (CHAr), 129.1 (2CHAr), 129.4
(2CHAr), 129.6 (CHAr), 130.9 (CHAr), 131.1 (3CHAr), 133.1 (C), 134.8 (C),
136.2 (C), 137.7 (C), 139.8 (C), 166.2 (CdO). Anal. Calcd For C22H15-
NOS (341.43): C: 77.39; H, 4.43; N, 4.10. Found: C, 77.44; H, 4.49; N,
4.03. Selected data for 11b,12-dihydro-5,11b-(6′-bromothioepoxy[1′,2′]-
benzeno)-5H-isoindolo[2,1-b]isoquinolin-7-one (6b): This product was
obtained in 62% yield (m ) 260 mg); mp 258 °C.; EIMS m/z 420 (M+);
IR (KBr): ν 3010 (CH), 2991 (CH), 1721 ( CdO) cm-1; 1H NMR (CDCl3,
200.13 MHz) δ 5.51 (s, 2H, CH2Ar), 6.21 (d, 1H, J ) 8.1 Hz, CH), 7.06-
7.66 (m, 10H, benzene 7H + isoindole 3H), 8.78 (d, 1H, J ) 7.5 Hz,
isoindole H); 13C NMR (CDCl3, 50.13 MHz) δ 45.1 (CH2), 118.7 (C), 122.6
(CH), 122.9 (CHAr), 125.6 (C), 128.3 (2CHAr), 128.4 (C), 129.1 (CHAr),
129.8 (CHAr), 130.2 (CHAr), 131.3 (CHAr), 131.4 (3CHAr), 133.2 (C), 133.3
(CHAr), 134.7 (C), 137.1 (C), 137.4 (C), 14.1 (C), 166.1 (CdO). Anal. Calcd
for C22H14BrNOS (420.32): C: 62.86; H, 3.36; N, 3.33. Found: C, 62.79;
H, 3.33; N, 3.39. Selected data for 11b,12-dihydro-5,11b-thioepoxy[2′,1′]-
naphthaleno-5H-isoindolo[2,1-b]isoquinolin-7-one (6c): This product was
obtained in 41% yield (m ) 160 mg); mp 238 °C; EIMS m/z 390 (M+); IR
1
(KBr): ν 3019 (CH), 2982 (CH), 1709 ( CdO) cm-1; H NMR (CDCl3,
200.13 MHz) δ 5.31 (s, 2H, CH2Ar), 6.14 (d, 1H, J ) 8.1 Hz, CH), 7.02-
7.85 (m, 13H, naphthalene 6H + benzene 4H + isoindole 3H), 8.70 (d,
1H, J ) 8.6 Hz, isoindole H); 13C NMR (CDCl3, 50.13 MHz) δ 39.6 (CH2),
119.8 (C), 122.6 (CH), 122.8 (CHAr), 124.6 (CHAr), 126.7 (CHAr), 127.8
(2CHAr), 128.1 (CHAr), 128.4 (CHAr), 128.5 (C), 128.7 (CHAr), 129.2
(2CHAr), 129.6 (CHAr), 131.1 (3CHAr), 131.5 (C), 133.3 (C), 133.7 (C),
134.7 (C), 135.0 (C), 136.7 (C), 137.8 (C), 166.5 (CdO). Anal. Calcd for
C26H16NOS (390.48): C, 79.77; H, 4.38; N, 3.58. Found: C, 79.83; H,
4.33; N, 3.51.
(27) We have used the same procedure, as reported in ref 22, with TFA
instead TFAA and pyridine. The resulting solid was recrystallized from
ethanol to give 6a as yellow needles in 58% yield.
1204
Org. Lett., Vol. 2, No. 9, 2000