Domino carbocationic cyclization of functionalized cyclopropyl ketones: Facile one-pot access to peri- and angularly fused polycyclic aromatic and heteroaromatic frameworks

Article abstract of DOI:10.1021/jo020230r

Conjugate adducts obtained by base-induced 1,4-addition-elimination of various aryl/heteroaryl acetonitriles with 1-(2-arylcyclopropyl)-3,3-(bismethylthio)-2-propen-l-ones have been shown to undergo facile acid-induced domino carbocationic rearrangement yielding a variety of substituted tricyclic aromatic and heteroaromatic frameworks in high yields in a one-pot operation. The methodology provides efficient, high-yield routes for synthesis of novel substituted dihydrophenalenes, dihydrobenzo [d,e] anthracene, cyclopenta[a] naphthalene, and fused heteroaromatics such as substituted 4,5-dihydrobenzo[c,d]indole, dihydronaphtho[1,8-b, c]thiophene, dihydroindeno[5,4-b]- and -[4,5-b]-thiophenes, cyclopenta[a]carbazole, and dihydrocyclopenta[e]indazol-3-one derivatives. The probable mechanism of this interesting domino process appears to involve stepwise or concomitant acid-induced ring opening and intramolecular cyclocondensation of cyclopropyl ketones to give benzo-fused arene (or heteroarene) intermediates bearing a reactive benzylic carbocation that is captured intramolecularly either by a preexisting aromatic (or heteroaromatic) ring or by a newly formed benzene ring to give either peri-fused or angularly fused products, respectively. Thus, the overall domino process entails formation of two C-C bonds, a substituted benzene ring along with a peri-fused cyclohexane or angularly fused cyclopentane ring in a single operation.

Full text of DOI:10.1021/jo020230r

Dom in o Ca r boca tion ic Cycliza tion of F u n ction a lized Cyclop r op yl
Keton es: F a cile On e-P ot Access to P er i- a n d An gu la r ly F u sed
P olycyclic Ar om a tic a n d Heter oa r om a tic F r a m ew or k s†
Sukumar Nandi, U. K. Syam Kumar, Hiriyakkanavar Ila,* and Hiriyakkanavar J unjappa*
Department of Chemistry, Indian Institute of Technology, Kanpur 208 106, U.P. India
hila@iitk.ac.in
Received April 3, 2002
Conjugate adducts obtained by base-induced 1,4-addition-elimination of various aryl/heteroaryl
acetonitriles with 1-(2-arylcyclopropyl)-3,3-(bismethylthio)-2-propen-1-ones have been shown to
undergo facile acid-induced domino carbocationic rearrangement yielding a variety of substituted
tricyclic aromatic and heteroaromatic frameworks in high yields in a one-pot operation. The
methodology provides efficient, high-yield routes for synthesis of novel substituted dihydrophe-
nalenes, dihydrobenzo[d,e]anthracene, cyclopenta[a]naphthalene, and fused heteroaromatics such
as substituted 4,5-dihydrobenzo[c,d]indole, dihydronaphtho[1,8-b,c]thiophene, dihydroindeno[5,4-
b]- and -[4,5-b]-thiophenes, cyclopenta[a]carbazole, and dihydrocyclopenta[e]indazol-3-one deriva-
tives. The probable mechanism of this interesting domino process appears to involve stepwise or
concomitant acid-induced ring opening and intramolecular cyclocondensation of cyclopropyl ketones
to give benzo-fused arene (or heteroarene) intermediates bearing a reactive benzylic carbocation
that is captured intramolecularly either by a preexisting aromatic (or heteroaromatic) ring or by a
newly formed benzene ring to give either peri-fused or angularly fused products, respectively. Thus,
the overall domino process entails formation of two C-C bonds, a substituted benzene ring along
with a peri-fused cyclohexane or angularly fused cyclopentane ring in a single operation.
In tr od u ction
double bond. Depending on the functionality present, the
carbocationic ring opening of cyclopropyl ketones and
endocyclic trapping of the formal or incipient carbocation
by a double bond or an aryl group represent an extremely
useful method for the construction of carbon skeleton
resulting in change of both the structure and the charge
polarity of the product.5 Our research interest in this
regard has been concerned with the elaboration of domino
reactions involving acid-induced rearrangements of 2-aryl
(or styryl)-cyclopropyl-[bis(methylthio)alkylidene] ketones
and carbinols leading to the formation of novel carbocyclic
frameworks.6 Thus, we have demonstrated in a series of
papers that the acid-induced cyclopropyl ring opening of
these compounds and subsequent intramolecular 5-exo-
trig capture of the resulting carbocation initially produces
The search for new and efficient methodologies that
allow the rapid construction of polycyclic structures in a
single operation is an important challenge today for
synthetic organic chemists.1 In this regard, formation of
polycyclic ring systems based on cationic stitching of
polyolefinic precursors has emerged as an extremely
powerful synthetic method.2,3 Cationic cyclizations also
play an important role in acid-induced rearrangements
of cyclopropyl ketones and carbinols.4 The utility of
cyclopropane in organic synthesis arises from the unique
characteristic of the strained three-membered ring and
the resemblance of its chemistry to that of carbon-carbon
† Dedicated to Prof. Lutz F. Tietze on his 60th birthday.
(1) (a)Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993,
32, 131. (b) Bunce, R. A. Tetrahedron 1995, 51, 13103. (c) Tietze, L. F.
Chem. Rev. 1996, 96, 115. (d) Hudlicky, T. Chem. Rev. 1996, 96, 3. (e)
Wender, P. A. Chem. Rev. 1996, 96, 1.
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Corey, E. J .; Virgil, S. C.; Sarshar, S. J . Am. Chem. Soc. 1991, 113,
8171. (c) Grieco, P. A.; Dai, Y. J . Am. Chem. Soc. 1998, 120, 5128. (d)
Grieco, P. A.; Kauffman, M. D.; Daeuble, J . F.; Saito, N. J . Am. Chem.
Soc. 1996, 118, 2095.
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1993, 115, 1595. (b) Bender, J . A.; Blize, A. E.; Browder, C. C.; Giese,
S.; West, F. G. J . Org. Chem. 1998, 63, 2430. (c) Wang, Y.; Arif, A. M.;
West, F. G. J . Am. Chem. Soc. 1999, 121, 876 (d) Browder, C. C.; West,
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W. S.; Wattanasin, S. J . Chem. Soc., Chem. Commun. 1980, 262. (f)
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1990, 356; J . Chem. Res., Miniprint 1990, 2728. (c) Patro, B.; Deb, B.;
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10.1021/jo020230r CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/14/2002
4916
J . Org. Chem. 2002, 67, 4916-4923

SCHEME 1
a cyclopentanoid ring bearing a reactive bis(methylthio)-
methyl carbocation that can be further intercepted in a
domino fashion by a pendant electron-rich arene or an
olefinic double bond to furnish cyclopentanoindane,7,8
diquinane,8 or bicyclo[3.2.1]octene derivatives9 in a highly
stereoselective manner. Also, in a recent paper,10 we have
successfully elaborated another domino carbocationic
process from strategically designed acyclic cyclopropyl
carbinol precursors leading to the formation of a fused
cyclopentane and a benzene ring in a cascade fashion to
afford 1-arylindanes in good yields. This overall process
combines our aromatic annelation protocol11 and cyclo-
pentane ring construction via oxoketene dithioacetals in
a single one-pot synthetic operation. In continuation of
these studies, we further considered it of interest to
examine acid-induced cascade cyclization of cyclopropyl
ketones of the general structure 3, which were readily
accessible in high yields via base-catalyzed conjugate
addition-elimination of various aryl and heteroarylac-
etonitriles with [bis(methylthio)methylene]-arylcyclopro-
pyl ketones 1. It was envisaged that the initial acid-
assisted ring opening of the cyclopropyl ketones 3 would
furnish the stable benzylic carbocation 4, which could be
intercepted by the electron-rich (methylthio)methylene
double bond via a 5-exo process followed by intramolecu-
lar cyclocondensation of the product cyclopentanones 5
to afford angularly fused benzo/heteroannelated indanes
6 (Scheme 1, pathway a). Alternatively, the cyclopropyl
ketones 3 may undergo either stepwise or concomitant
ring opening and intramolecular cyclocondensation to
give benzo/heteroannelated arenes 7 with a pendant
R-arylpropyl carbocationic side chain, which can be
captured intramolecularly via 5- or 6-exo cyclization to
yield either angularly fused indanes 6 or the novel peri-
cyclized carbo- and heterocyclic ring systems 8 (pathway
b). Indeed our studies revealed that both kind of products
6 and 8 are formed depending on the structure of the
aryl/heteroaryl ring in the cyclopropyl ketones 3. We
report the results of this investigation in the present
paper.
tion studies without further purification.12 The adduct
3a a was subjected to a detailed study for carbocationic
ring opening and cyclization under the influence of
various Lewis and protic acids (SnCl4/CH3NO2, SnCl4/
CH2Cl2, BF3‚Et2O/CH3NO2, BF3‚Et2O/CH2Cl2, PTSA/
C6H6, H3PO4), which showed the formation of only one
product (TLC) in almost all cases, characterized as the
1-arylphenalene derivative 9a on the basis of its spectral
and analytical data (Scheme 3). The corresponding
angularly fused cyclopenta[a]naphthalene structure 6
was ruled out on the basis of NOE studies between
thiomethyl and Ha proton signals and also by Raney Ni
(W2) dethiomethylation of 9a , which furnished the 6-me-
thylphenalene derivative 10a in 78% yield. Apparently,
the dethiomethylation is accompanied with concomitant
exhaustive reduction of the nitrile functionality to a
methyl group. The signals due to the aromatic protons
Resu lts a n d Discu ssion
1
(Ha and Hb) in the H NMR spectra of 10a appeared as
The adduct cyclopropyl ketones 3 were easily prepared
in nearly quantitative yields by conjugate addition-
elimination of the few selected aryl/heteroarylacetoni-
triles 2a -h with 2-arylcyclopropyl-[bis(methylthio)-
methylene] ketones 1a -c in the presence of sodium
hydride in DMF at room temperature. A few of the
adducts were purified and characterized with the help
of spectral and analytical data, whereas in the subse-
quent reactions, they were used as obtained for cycliza-
sharp doublets at δ 6.96 (J ) 6.8 Hz) and δ 7.11 (J ) 6.8
Hz), respectively, whereas in the corresponding reduced
cyclopenta[a]naphthalene derivative 11a , all three aro-
matic protons (Ha, Hb, and Hc) are expected to appear as
sharp singlets. The cationic cyclization of the adduct 3a a
to 9a was found to be the most facile and clean (in terms
of the yield and the workup) in H3PO4 (at 100 °C);
therefore, all subsequent cyclizations were carried out
in the presence of this acid. Thus, the cyclization of
cyclopropyl ketones 3ba and 3ca in the presence of H3-
(7) Patra, P. K.; Patro, B.; Ila, H.; J unjappa, H. Tetrahedron Lett.
1993, 34, 3951.
(8) Patra, P. K.; Sriram, V.; Ila, H.; J unjappa, H. Tetrahedron 1998,
54, 531.
(9) Syam Kumar, U. K.; Patra, P. K.; Ila, H.; J unjappa, H.;
Bharadwaj, P. K. J . Chem. Soc., Perkin. Trans. 1 2000, 1547.
(10) Mohanta, P. K.; Peruncheralathan, S.; Ila, H.; J unjappa, H. J .
Org. Chem. 2001, 66, 1503.
(12) 1H and 13C NMR spectra of adducts 3a a , 3ca , 3a b, and 3a h
showed them to exist only in the tautomeric form 3A as a complex
mixture of geometrical isomers (E)-3A and (Z)-3A along with cis and
trans geometrical isomers of a cyclopropyl ring.
(11) Reviews: (a) J unjappa, H.; Ila, H.; Asokan, C. V. Tetrahedron
1990, 46, 5423. (b) J unjappa, H.; Ila, H. Phosphorous, Sulfur Silicon
Relat. Elem. 1994, 95, 35. (c) Ila, H.; J unjappa, H.; Barun, O. J .
Organomet. Chem. 2001, 624, 34.
J . Org. Chem, Vol. 67, No. 14, 2002 4917

Nandi et al.
SCHEME 2
SCHEME 4
SCHEME 5
SCHEME 3
efficiently transformed into a single product (87%), which
was found to be the expected 3-arylcyclopenta[a]naph-
thalene derivative 12 on the basis of its spectral and
analytical data. On the other hand, the corresponding
adduct 3bd from 1-naphthylacetonitrile yielded only the
benzo[d,e]anthracene derivative 13 through peri cycliza-
tion under similar conditions with no trace of cyclopen-
tanophenanthrene 14 (Scheme 5).
We next examined the acid-induced cyclization of the
adduct cyclopropyl ketones (3a e-a h ) obtained from
conjugate addition of heteroarylacetonitriles to 1 as
illustrated in Schemes 6-8, which followed a trend
similar to that observed in the previous transformations.
Thus, the adduct 3a e from 1-methylpyrrole-2-acetonitrile
yielded a single product (93%) in the presence of H3PO4,
which was characterized as the tricyclic indole derivative
15 possessing the partial structural framework of several
naturally occurring alkaloids13 and biologically active
PO4 also afforded the dihydrophenalenes 9b-c in 65 and
83% yields, respectively. Both products 9b and 9c were
characterized with the help of 1H and 13C NMR data and
also by reductive desulfurization of 9b to 10b in 88%
yield. The adduct 3a b with an unsubstituted aryl group
also yielded only the peri-bridged naphthalene derivative
9d in 52% yield along with an intractable reaction
mixture on prolonged heating (6 h) in H3PO4 (Scheme
4).
The domino carbocationic cyclization studies were next
extended to cyclopropyl ketone adduct 3a c from 2,5-
dimethoxyphenylacetonitrile in which the peri cyclization
pathway is blocked by the presence of a methoxy group,
therefore deliberately steering the cyclization to another
site. Indeed the adduct 3a c, when heated in H3PO4, was
(13) (a) Rehacek, Z.; Sajdl, P. Ergot Alakloids: Chemistry, Biological
effects, Biotechnology; Elsevier Science Publishers: Amsterdam, 1990.
(b) Padwa, A.; Heidelbaugh, T. M.; Kuethe, J . T. J . Org. Chem. 2000,
65, 2368. (c) Ninomiya, I.; Kiguchi, T.; Naito, T. J . Chem. Soc., Perkin
Trans. 1 1980, 208. (d) Ponticello, G. S.; Baldwin, J . J .; Lumma, P. K.;
McClure, D. E. J . Org. Chem. 1980, 45, 4236. (e) Stadler, P. A.; Gigar,
K. A. Natural Products and Drug Development; Krogsgaard-Larsen,
P., Christensen, S. B., Koffod, H., Eds.; Munksgaard: Copenhagen,
1984; p 463.
4918 J . Org. Chem., Vol. 67, No. 14, 2002

SCHEME 6
SCHEME 9
SCHEME 7
of 15 (Scheme 6). Interestingly, the cationic cyclization
of the adduct 3a f from thiophene-2-acetonitrile under
identical conditions provided a 2:1 mixture of two prod-
ucts, which were identified as the peri-annelated 17 and
indeno[5,4-b]thiophene derivative 18 with the help of
their spectral and analytical data (Scheme 7). The
corresponding adduct 3a g from thiophene-3-acetonitrile,
in which the possibility of peri cyclization is blocked by
the presence of a sulfur heteroatom, underwent the
expected cycloaromatization-cyclopentane annelation
sequence under identical conditions to furnish only the
indeno[4,5-b]thiophene derivative 19 in 69% yield (Scheme
7). On the other hand, the carbocationic cyclization of the
indole-3-acetonitrile adduct 3a h in H3PO4 did not furnish
the expected cyclopenta[a]carbazole 21; the product
isolated in 78% yield was characterized as the 1-(1-
SCHEME 8
1
arylcycloprop-2-yl)carbazole 20 from its H and 13C NMR
data (Scheme 8). Our attempts to transform the product
20 to 21 in the presence of various Lewis and protic acids
were not successful. However, the adduct 3a h could be
transformed into the cyclopenta[a]carbazole 21 in 78%
yield upon treatment with SnCl4 in dichloromethane at
room temperature (Scheme 8).
Finally, these cascade cationic cyclization studies were
extended to the conjugate adduct 24 obtained from
3-lithiomethyl-2-methyl-1-phenylpyrazolin-5-one 23 and
[bis(methylthio)methylene]cyclopropyl ketone 1a (Scheme
9). We have shown in previous studies15 that the anion
23 derived from antipyrine 22 undergoes 1,4-addition-
elimination with various R-oxoketene dithioacetals fol-
lowed by BF3‚Et2O-assisted cycloaromatization to afford
substituted and fused indazolones in high yields. Thus,
the conjugate adduct 24 was obtained in good yield upon
treatment of the oxoketene dithioacetal 1a with the
lithiomethyl anion 23 under the reported conditions.15
The adduct 24 was smoothly transformed into the
expected cyclopenta[e]indazolone derivative 25 under
indole derivatives.14 The regiochemistry of the cyclization
was further supported by the structural assignment of
the product 16 obtained from Raney Ni desulfurization
(14) (a) Katayama, S.; Ae, N.; Nagata, R. J . Org. Chem. 2001, 66,
3474. (b) Moore, R. E.; Cheuk, C.; Yang, X.-Q. G.; Patterson, G. M. L.;
Bonjouklian, R.; Smitka, T. A.; Mynderse, J . S.; Foster, R. S.; J ones,
N. D.; Swartzendruber, J . K.; Deeter, J . B. J . Org. Chem. 1987, 57,
1036.
(15) Reddy, K. R.; Roy, A.; Ila, H.; J unjappa, H. Tetrahedron 1995,
51, 10941.
J . Org. Chem, Vol. 67, No. 14, 2002 4919

Nandi et al.
SCHEME 10
BF3‚Et2O-induced cyclization in refluxing benzene (Scheme
9). The spectral and analytical data of 25 were found to
be in conformity with the assigned structure, which was
further corroborated by its conversion to the dethiom-
ethylated product 26 in the presence of Raney Ni (W2)
(Scheme 9).
The probable mechanism for the formation of various
peri- and angularly fused products appears to be similar
to that proposed in the Scheme 1 involving either
stepwise or concomitant acid-induced ring opening and
intramolecular cyclocondensation of the cyclopropyl ke-
tones 3 to give the common carbocationic intermediate 7
(pathway b). The subsequent fate of the intermediate 7
of undergoing either 5- or 6-exo cyclization is governed
by the size of the newly formed ring (six vs five members)
and also by the nucleophilicity/availability of the site of
cyclization. Thus, the intermediate carbocations 7 (X )
CHdCH) derived from cyclopropyl ketones 3a a , 3ba , 3ca ,
3a b, and 3bd undergo more facile 6-exo cyclization16 on
the adjacent ring to afford the respective peri-fused
naphthalenes (9a -d ) and phenanthrene (13) (Schemes
3-5), whereas in the case of the ketone 3a c, the site of
6-exo cyclization is blocked by a methoxy group, thus
diverting the cyclization on the same ring to give cyclo-
penta[a]naphthalene derivative 12 (Scheme 4). Similarly,
the 4-indolyl carbocation 27 from the ketone 3a e also
undergoes the preferred 6-exo cyclization at the highly
electron-rich 3-position17 of the indole ring to give exclu-
sively the tricyclic indole derivative 15 in excellent yield.
On the other hand, the adduct cyclopropyl ketone 3a f
from thiophene 2-acetonitrile affords both peri- (17) and
cyclopenta- (18) fused benzothiophenes (2:1) by intramo-
lecular capture of the carbocation 28 at the C-3 and C-5
positions of the benzothiophene18 (Scheme 10), whereas
the adducts 3a g from thiophene 3-acetonitrile yielded
only the angularly fused benzothiophene 19 in the
absence of the possible 6-exo cyclization. In the case of
the conjugate adduct 3a h derived from indole 3-acetoni-
trile, the intramolecular ring closure of the ketone
appears to be faster than the cyclopropyl ring opening
(in the presence of a weaker acid such as H3PO4)
occurring first at the C-3 position of the indole to give
the corresponding spiro-3H-indolium cation 29 (Scheme
10).19 Subsequent rearrangement of 29 with concurrent
dehydration and deprotonation affords the 1-(1-aryl-2-
cyclopropyl)carbazole 20 as the sole product. However,
in the presence of a stronger Lewis acid (SnCl4), the
reaction follows a pathway similar to that suggested for
the other cyclopropyl ketones through concomitant ring
opening and cyclization followed by intramolecular 5-exo
trapping of the cation 30 to give only cyclopenta[a]-
carbazole 21 (Scheme 10).
Con clu sion
In summary, we have demonstrated that the easily
accessible acyclic conjugate adducts 3 with an appropri-
ately disposed cyclopropyl ketone functionality undergo
an efficient acid-induced domino carbocationic cyclization
to yield a range of novel functionalized tricyclic aromatic
and heteroaromatic frameworks in high yields. These
observations along with our earlier studies suggest that
a wide range of domino sequence may be possible using
carbocationic cyclization of strategically designed cyclo-
propyl ketone precursors. Our efforts in these directions
are underway.
(16) Friedel-Crafts-type cyclization of â-(1-naphthyl)propionoic acid
generally takes place at the peri position due to the formation of a
six-membered ring; see: Harvey, R. G. Polycyclic Aromatic Hydrocar-
bons; Wiley-VCH: New York, 1996; Chapter 3, p 44. (b) Sethna, S.
Friedel-Crafts and Related Reactions; Olah, G. A., Ed.; Interscience
Publishers: New York, 1964; Vol. 3, Chapter XXXV, p 920.
(17) J ones, R. A. Comprehensive Heterocyclic Chemistry; Bird, C. W.,
Cheeseman, G. W. H., Eds.; Pergamon Press: Elmsford, NY, 1984; Vol.
4, Part 3, Chapter 3.05, p 205.
(18) Friedel-Crafts cyclization of â-(4-benzo[b]thienyl)propionoic
acid 31 in the presence of hydrogen fluoride has been reported to give
a mixture of isomeric ketones 32 and 33; see: (a) Iddon, B.; Scrowston,
R. M. Advances in Heterocyclic Chemistry; Katritzky, A. R., Boulton,
A. J ., Eds.; Academic Press: New York, 1970; Vol. 11, p 346. (b)
Hawthorne, D. G.; Porter, Q. N. Aust. J . Chem. 1966, 19, 1909.
(19) For electrophilic alkylation of an indole at the C2 position by
first alkylation at C3 followed by rearrangement, see: (a) Katritzky,
A. R.; Rachwal, S.; Hitchings, G. J . Tetrahedron 1991, 47, 2683. (b)
Katritzky, A. R.; Lan, X. Chem Soc. Rev. 1994, 363. (c) Katritzky, A.
R.; Lan, X.; Fan, W.-Q. Synthesis 1994, 445. (d) J oule, J . A Heterocyclic
Chemistry; Chapman and Hall: London, U.K., 1995. (e) Biswas, K.
M.; J ackson, A. H. Tetrahedron 1969, 25, 227. (f) Hamel, P.; Preville,
P. J . Org. Chem. 1996, 61, 1573. (g) Katritzky, A. R.; Zhang, G.; Xie,
L.; Ghiviriga, I. J . Org. Chem. 1996, 61, 7558.
(20) (a) Henbest, H. B.; J ones, E. R. H.; Smith, G. F. J . Chem. Soc.
1953, 3796. (b) Snyder, H. R.; Eliel, A. R. J . Am. Chem. Soc. 1948, 70,
1857.
4920 J . Org. Chem., Vol. 67, No. 14, 2002

4,5-Dim eth oxy-1,2-d ih yd r o-3-(4-m eth oxyp h en yl)-8-m e-
th ylsu lfa n yl-3H-p h en a len e-7-ca r bon itr ile (9a ): yield 85%
(1.72 g); colorless crystals (chloroform-hexane); mp 144-145
°C; Rf 0.52 (97:3 hexanes-EtOAc); IR (KBr) 2924, 2208, 1508,
1261, 1242 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.16-2.20 (m,
2H), 2.64 (s, 3H), 2.80 (ddd, J ) 3.4, 7.4, 8.7 Hz, 1H), 2.92
(ddd, J ) 3.4, 7.4, 8.7 Hz, 1H), 3.49 (s, 3H), 3.74 (s, 3H), 4.02
(s, 3H), 4.85 (dd, J ) 3.1 Hz, 1H), 6.74 (d, J ) 8.8 Hz, 2H),
6.82 (d, J ) 8.8 Hz, 2H), 7.09 (s, 1H), 7.41 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 16.1, 25.8, 29.7, 37.7, 55.1, 55.7, 60.7,
102.8, 104.1, 113.5, 116.9, 120.2, 123.2, 128.8, 130.3, 131.9,
136.4, 141.9, 142.5, 145.9, 155.0, 157.9; MS (m/z, %) 405 (M+,
100), 266 (31.1). Anal. Calcd for C24H23NO3S (405.52): C, 71.08;
H, 5.72; N, 3.45. Found: C, 71.19; H, 5.70; N, 3.40.
Exp er im en ta l Section
Gen er a l. 1H NMR (400 MHz) and 13C NMR (100 MHz)
spectra were recorded in CDCl3, and TMS was used as an
internal reference. Melting points are uncorrected. Chromato-
graphic purification was done by column chromatography
using 60-120 mesh silica gel. All reactions were monitored
by TLC on a glass plate coated with silica gel containing 13%
calcium sulfate as a binder, and visualization was effected with
short-wavelength UV light (254 nm) or acidic KMnO4 solution.
All reagents were used directly as obtained commercially
unless otherwise noted. DMF was distilled over CaH2 and
stored over molecular sieves. THF was distilled over sodium
benzophenone ketyl prior to use. n-BuLi was purchased
commercially.
6,9-Dim eth oxy-3-(4-m eth oxyp h en yl)-4-m eth ylsu lfa n yl-
cyclop en ta [a ]n a p h th a len e-5-ca r bon itr ile (12): yield 87%
(1.77 g); colorless solid; mp 158-159 °C; Rf 0.52 (97:3 hexanes-
EtOAc); IR (KBr) 2930, 2215, 1508, 1455, 1243 cm-1; 1H NMR
(400 MHz, CDCl3) δ 2.10 (ddd, J ) 9.6, 6.5, 3.9 Hz, 1H), 2.21
(s, 3H), 2.54-2.72 (m, 2H), 3.74 (ddd, J ) 9.2, 6.4, 2.8 Hz, 1H),
3.75 (s, 3H), 3.90 (s, 3H), 4.00 (s, 3H), 4.80 (dd J ) 7.6, 2.9
Hz, 1H), 6.76 (dd, J ) 9.1, 2.8 Hz, 2H), 6.80 (d, J ) 8.96 Hz,
1H), 6.89 (d, J ) 8.9 Hz, 1H), 6.91 (dd, J ) 9.1, 2.8 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ 18.9, 34.2, 35.7, 50.5, 55.1, 55.6,
56.3, 106.0, 107.4, 110.8, 113.7, 118.1, 123.9, 127.2, 128.4,
137.9, 142.1, 145.4, 148.0, 148.5, 151.5, 157.8. MS (m/z, %) 407
(M+, 100), 359 (7.6), 239 (15.6), 166 (29.10). Anal. Calcd for
The cyclopropyl ketones 1a -d were prepared according to
our earlier reported procedure.6 All of the arylacetonitriles 2a -
d , N-methylpyrrole-2-acetontrile (2e), thiophene-2, 3-acetoni-
trile (2f,g), and antipyrine were purchased commercially,
whereas indole-3-acetonitrile was prepared by the reported
method.20
Gen er a l P r oced u r e for th e P r ep a r a tion of 1,4-Ad d i-
tion -Elim in a tion Ad d u cts 3a a -3a h . To a stirred suspen-
sion of NaH (0.60 gm, 40%, 10 mmol) in DMF (10 mL) at 0 °C
was added a solution of aryl/heteroarylacetonitrile (5 mmol)
in DMF (5 mL) dropwise over 15 min, and the reaction mixture
was further stirred at 0 °C for 45 min. Appropriate aryl
cyclopropyl ketone (5 mmol) in DMF (10 mL) was slowly added,
and the reaction mixture was allowed to warm to room
temperature with stirring over 8-10 h. The mixture was then
poured into saturated NH4Cl solution (200 mL) and extracted
with chloroform (3 × 50 mL). The combined organic layer was
washed with water (3 × 50 mL), dried (Na2SO4), and evapo-
rated to give the crude 1,4-addition-elimination adducts,
which were used as obtained for further cyclization. A few of
the adducts were purified by column chromatography, and
their spectral and analytical data are given below.
3-(3,4-Dim et h oxyp h en yl)-1-(2-P h en ylcyclop r op yl)-3-
m eth ylsu lfa n yl--2-p r op en -1-on e (3ca ): yield 80% (1.57 g);
E:Z ) 2.9:1; viscous liquid; Rf 0.46 (8:2 hexanes-EtOAc); IR
(CCl4) 2931, 2200, 1512, 1454 cm-1; 1H NMR (400 MHz, CDCl3)
δ 1.53 (E, ddd, J ) 9.4, 6.5, 3.8 Hz, 1H), 1.76 (Z, ddd, J ) 9.4,
6.5, 3.9 Hz, 1H), 1.84 (E, ddd, J ) 9.4, 6.5, 3.9 Hz, 1H), 2.16
(Z, ddd, J ) 9.4, 6.5, 3.9 Hz, 1H), 2.41 (Z, ddd, J ) 9.4, 6.5,
3.9 Hz, 1H), 2.27 (Z, s, 3H), 2.43 (E, ddd, J ) 9.4, 6.5, 3.9 Hz,
1H), 2.44 (E, s, 3H), 2.56 (Z, ddd, J ) 9.4, 6.5, 3.9 Hz, 1H),
2.62 (E, ddd, J ) 9.4, 6.5, 3.9 Hz, 1H), 3.77-3.78 (Z, m, 2H),
3.79 (Z, s, 3H), 3.83 (E, s, 3H), 3.84 (Z, s, 3H), 3.86 (E, s, 3H),
4.12-4.19 (E, m, 1H), 6.75 (E, d, J ) 5.9 Hz, 1H), 6.85 (Z, d,
J ) 8 Hz, 1H), 6.89 (E, s, 1H), 6.92 (E, d, J ) 1.5 Hz, 1H),
7.05 (Z, d, J ) 7.3 Hz, 1H), 7.13 (E, d, J ) 7.3 Hz, 1H), 7.20-
7.24 (Z, m, 5H), 7.26-7.31 (E, m, 5H); 13C NMR (100 MHz,
CDCl3) δ 15.1 (E), 15.4 (Z), 19.1 (E), 19.3 (Z), 30.3 (E), 30.0
(Z), 31.6 (E), 32.1 (Z), 49.6 (E), 47.3 (Z), 55.7 (E), 55.7 (Z), 55.8
(E), 55.8 (Z), 110.1 (E), 110.6 (Z), 111.0 (E), 111.2 (Z), 111.4
(E), 111.5 (Z), 111.6 (E), 111.2 (Z), 117.5 (E), 118.2 (Z), 121.9
(E), 121.2 (Z), 126.0 (E), 125.1 (Z), 126.7 (E), 126.8 (Z), 128.4
(E), 128.5 (Z), 139.2 (E), 139.4 (Z), 148.6 (E), 148.9 (Z), 149.3
(E), 149.2 (Z), 151.3 (E), 151.6 (Z), 202.2 (E), 203.1 (Z); MS
(m/z, %) 393 (M+, 63.3), 378 (32.8), 145 (100). Anal. Calcd for
C
24H23NO3S (405.52): C, 71.08; H, 5.72; N, 3.45. Found: C,
71.14; H, 5.62; N, 3.34.
6-(3,4-Dim eth oxyph en yl)-2-m eth ylsu lfan yl-4,5-dih ydr o-
6H-ben zo[d ,e]a n th r a cen e-1-ca r bon itr ile (13): yield 72%
(1.53 g); colorless crystals; mp 181-182 °C; Rf 0.62 (97:3
hexanes-EtOAc); IR (KBr) 2292, 2205, 1619, 1575, 1515 cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.27 (ddd, J ) 8.7, 7.4, 3.4 Hz,
1H), 2.34 (ddd, J ) 8.6, 6.4, 2.4 Hz, 1H), 2.69 (s, 3H), 3.18 (t,
J ) 6.3 Hz, 2H), 3.79 (s, 3H), 3.87 (s, 3H), 4.39 (dd, J ) 7.6,
2.9 Hz, 1H), 6.56 (dd, J ) 8.0, 2.1 Hz, 1H), 6.71 (s, 1H), 6.78
(d, J ) 8.0 Hz, 1H), 7.30 (s, 1H), 7.35 (s, 1H), 7.59-7.65 (m,
2H), 7.70 (d, J ) 7.6 Hz, 1H), 9.80 (d, J ) 8.0 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 15.9, 30.0, 30.5, 46.2, 55.8, 55.8,
111.0, 111.3, 119.4, 120.7, 122.6, 125.2, 126.3, 127.2, 127.4,
127.7, 128.2, 128.2, 128.4, 131.8, 133.2, 135.8, 137.0, 142.2,
146.0, 147.7, 149.0; MS (m/z, %) 425 (M+, 100), 394 (4.7), 287
(52), 240 (79.2). Anal. Calcd for C27H23NO2S (425.55): C, 76.20;
H, 5.44; N, 3.29. Found: C, 76.09; H, 5.38; N, 3.28.
1-N-Meth yl-3-(4-m eth oxyp h en yl)-7-m eth ylsu lfa n yl-4,5-
dih ydr o-3H-ben zo[c,d]in dole-8-car bon itr ile (15): yield 93%
(1.58 g); colorless crystals; mp 141-142 °C; Rf 0.42 (97:3
hexanes-EtOAc); IR (KBr) 2939, 2210, 1609, 1511, 1453 cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.03 (ddd, J ) 8.9, 5.3, 4.0 Hz,
1H), 2.22 (ddd, J ) 8.4, 6.3, 4.3 Hz, 1H), 2.60 (s, 3H), 2.97(m,
2H), 3.80 (s, 3H), 4.01 (s, 3H), 4.12 (dd, J ) 7.2, 3.4 Hz, 1H),
6.50 (s, 1H), 6.85 (d, J ) 8.5 Hz, 2H), 6.90 (s, 1H), 7.15 (d, J
) 8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 18.4, 27.0, 33.3,
34.1, 38.7, 55.2, 92.2, 113.8, 117.1, 117.4, 125.7, 125.8, 127.4,
128.6, 133.9, 136.6, 138.0, 138.2, 158.2; MS (m/z, %) 348 (M+,
100), 301 (48), 240 (34.2), 193 (40). Anal. Calcd for C21H20N2-
OS (348.46): C, 72.37; H, 5.79; N, 8.04. Found: C, 72.40; H,
5.70; N, 8.01.
C
23H23NO3S (393.51): C, 70.20; H, 5.89; N, 3.56. Found: C,
3-(4-Meth oxyph en yl)-7-m eth ylsu lfan yl-4,5-dih ydr o-3H-
n a p h th o[1,8-b,c]th iop h en e-8-ca r bon itr ile (17): yield 55%
(0.96 g); white crystals; mp 110-112 °C; Rf 0.57 (97:3 hex-
anes-EtOAc); IR (KBr) 2922, 2212, 1609, 1573, 1511, 1033
cm-1; 1H NMR (400 MHz, CDCl3) δ 2.11 (ddd, J ) 8.4, 6,3, 4.3
Hz, 1H), 2.22 (m, 1H), 2.57 (s, 3H), 2.96 (q, J ) 8.1, 2H), 3.74
(s, 3H), 4.06 (dd, J ) 7.3, 3.1 Hz, 1H), 6.71 (d, J ) 1.2 Hz,
1H), 6.81 (dd, J ) 6.6, 2.2 Hz, 2H), 7.05 (dd, J ) 6.6, 2.0 Hz,
2H), 7.09 (s, 1H); 13C (100 MHz, CDCl3) δ 17.3, 28.0, 32.3, 42.8,
55.2, 113.8, 114.0, 115.6, 121.6, 121.6, 128.8, 129.0, 135.2,
138.8, 140.6, 143.7, 146.7, 158.6. Anal. Calcd for C20H17NOS2
(351.49): C, 68.34; H, 4.88; N, 3.99. Found: C, 68.40; H, 4.89;
N, 3.97.
70.40; H, 5.80; N, 3.61.
Gen er a l P r oced u r e for th e Cycliza tion of Ad d u cts
3a a -a h w ith Or th op h osp h or ic Acid . The crude adduct 3
(∼5 mmol) obtained from an earlier reaction was dissolved in
H3PO4 (20 mL, 85%), and the reaction mixture was heated with
stirring at 100 °C for 3-6 h (monitored by TLC). The mixture
was then cooled, poured into ice-cold water (150 mL), and
extracted with chloroform (3 × 50 mL), and the combined
organic layer was washed with water (3 × 50 mL) and dried
over Na2SO4. The solvent was distilled out to give a crude
product that was purified by column chromatography over
silica gel using 97:3 hexanes-ethyl acetate as an eluent.
J . Org. Chem, Vol. 67, No. 14, 2002 4921

Nandi et al.
6-(4-Meth oxyph en yl)-4,5-dih ydr o-7-m eth ylsu lfan yl-6H-
in den o[5,4-b]th ioph en e-8-car bon itr ile (18): yield 26% (0.40
g); white crystals; mp 96-98 °C; Rf 0.58 (97:3 hexanes-
of diisopropylamine (2 mL, 14 mmol) in dry THF (10 mL) under
a nitrogen atmosphere was added n-BuLi (6.25 mL, 10 mmol,
1.6 M) at 0 °C, and the reaction mixture was further stirred
for 20 min. To the resulting solution of LDA at -78 °C was
added a solution of 22 (0.96 g, 5 mmol) in dry THF (30 mL)
followed by further stirring for 45 min. A solution of cyclopro-
pyl ketone 1a (1.45 g, 5 mmol) was added at -78 °C, and the
reaction mixture was brought to room temperature over 45
min and left overnight with continuous stirring. The mixture
was then poured into ice-cold saturated NH4Cl solution (150
mL) and extracted with chloroform (3 × 50 mL), and the
combined organic extracts were washed with water (3 × 50
mL), dried (Na2SO4), and concentrated to give crude adduct
24, which was dissolved in benzene (40 mL) followed by
addition of BF3‚Et2O (1.2 mL, 6 mmol). The reaction mixture
was refluxed for 1 h, cooled, poured into saturated NaHCO3
solution (100 mL), and extracted with chloroform (3 × 50 mL),
and the combined organic layer was washed with water (3 ×
50 mL), dried (Na2SO4), and concentrated to give crude 25,
which was purified by column chromatography over silica gel
using 19:1 hexanes-ethyl acetate as an eluent.
EtOAc); IR (KBr) 2922, 2212, 1609, 1573, 1511, 1033 cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.12 (s, 3H), 2.13 (m, 1H), 2.64
(ddd, J ) 9.6, 6.5, 3.9 Hz, 1H), 3.19 (ddd, J ) 9.6, 6.5, 3.9 Hz,
1H), 3.56 (ddd, J ) 9.6, 6.5, 3.9 Hz, 1H), 3.69 (s, 3H), 4.71 (dd,
J ) 9, 3.3 Hz, 1H), 6.71 (d, J ) 8.5 Hz, 2H), 6.85 (d, J ) 8.5
Hz, 2H), 7.3 (d, J ) 6.0 Hz, 1H), 7.56 (d, J ) 6.0 Hz, 1H); 13
C
(100 MHz, CDCl3) δ 19.4, 31.5, 34.8, 50.7, 55.1, 113.8, 114.1,
115.9, 121.6, 122.2, 128.5, 135.9, 137.8, 140.5, 140.9, 143.1,
146.9, 158.5; MS (m/z, %) 351 (M+, 100), 336 (4.7), 303 (52),
186 (79.2). Anal. Calcd for C20H17NOS2 (351.49): C, 68.34; H,
4.88; N, 3.99. Found: C, 68.41; H, 4.89; N, 3.98.
6-(4-Meth oxyph en yl)-7,8-dih ydr o-5-m eth ylsu lfan yl-6H-
in den o[4,5-b]th ioph en e-4-car bon itr ile (19): yield 69% (1.21
g); white crystals; mp 139-140 °C; Rf 0.53 (97:3 hexanes-
EtOAc); IR (KBr) 2920, 2211, 1608, 1509, 1429; 1H NMR (400
MHz, CDCl3) δ 2.17 (s, 3H), 2.21 (m, 1H), 2.71 (ddd, J ) 9.6,
6.5, 3.9 Hz, 1H), 3.26 (ddd, J ) 9.6, 6.5, 3.9 Hz, 1H), 3.44 (ddd,
2.5, 8.3, 16.5 Hz, 1H), 3.76 (s, 3H), 4.78 (dd, J ) 9.0, 3.4 Hz,
1H), 6.78 (dd, J ) 7.0, 2.0 Hz, 2H), 6.90 (dd, J ) 9.0, 2.3 Hz,
2H), 7.36 (d, J ) 5.3 Hz, 1H), 7.63 (d, J ) 5.64 Hz, 1H); 13C
(100 MHz, CDCl3) δ 19.4, 31.5, 34.8, 50.7, 55.1, 110.4, 113.7,
113.8, 114.0, 116.7, 122.2, 128.3, 128.9, 136.4, 137.4, 143.7,
146.7, 158.0; MS (M/z, %) 351 (87.9, M+), 336 (72.8), 303
(75.01), 196 (53.9). Anal. Calcd for C20H17NOS2 (351.49): C,
68.40; H, 4.88; N, 3.99. Found: C, 68.44; H, 4.87; N, 4.00.
9-N-Meth yl-1-[2-(4-m eth oxyp h en yl)cyclop r op yl]-3-m e-
th ylsu lfa n yl-ca r ba zole-4-ca r bon itr ile (20): yield 78% (1.55
g); colorless crystals; mp 168-169 °C; Rf 0.40 (97:3 hexanes-
EtOAc); IR (KBr) 2952, 2360, 2207, 1514, 1454 cm-1; 1H NMR
(400 MHz, CDCl3) δ 1.49 (ddd, J ) 8.0, 5.4, 3.7 Hz, 1H), 1.74
(ddd, J ) 8.6, 5.3, 2.9 Hz, 1H), 2.19 (ddd, J ) 7.9, 5.4, 3.3 Hz,
1H), 2.63 (s, 3H), 2.68 (ddd, J ) 8.4, 4.9, 3.7 Hz, 1H), 3.82 (s,
3H), 3.9 (s, 3H), 6.90 (d, J ) 8.5 Hz, 2H), 7.09 (dd, J ) 8.8, 2.6
Hz, 2H), 7.26 (dd, J ) 8.5, 2.6 Hz, 1H), 7.30-7.32 (m, 2H),
7.52 (t, J ) 7.3 Hz, 1H), 8.64 (d, J ) 8.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 16.6, 19.1, 25.7, 26.5, 32.4, 55.3, 104.6,
108.9, 114.2, 117.4, 119.9, 120.1, 121.1, 121.7, 124.6, 126.5,
127.5, 129.3, 132.0, 132.9, 138.9, 142.2, 158.1; MS (m/z, %) 398
(M+, 34), 351 (47.5), 242 (18), 145 (100). Anal. Calcd for
6-(4-Met h oxyp h en yl)-1-N-m et h yl-7-m et h ylsu lfa n yl-2-
N -p h e n yl-1,2-d ih yd r o-3H -cyclop e n t a [e]in d a zol-3-on e
(25): yield 73% (1.51 g); colorless crystals; mp 193-194 °C;
Rf 0.33 (97:1 hexanes-EtOAc); IR (KBr) 2923, 1674, 1608,
1506, 1442 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.11 (ddd, J )
9.0, 7.4, 3.8 Hz, 1H), 2.38 (s, 3H), 2.64 (ddd, J ) 9.0, 7.4, 3.7
Hz, 1H), 3.13 (s, 3H), 3.39 (ddd, J ) 9.0, 7.4, 3.76 Hz, 2H),
3.73 (s, 3H), 4.36 (dd, J ) 7.0, 2.9 Hz, 1H), 6.79 (d, J ) 7.8
Hz, 2H), 6.83 (s, 1H), 6.95 (d, J ) 7.8 Hz, 2H), 7.23 (t, J ) 7.8
Hz, 1H), 7.45 (t, J ) 7.3 Hz, 2H), 7.58 (d, J ) 8.2 Hz, 2H); 13
C
NMR (100 MHz, CDCl3) δ 14.8, 29.4, 36.3, 40.1, 48.7, 55.0,
104.7, 111.7, 113.7, 123.1, 128.3, 125.8, 128.9, 135.6, 136.6,
138.6, 142.3, 143.1, 152.9, 157.9, 162.5. MS (m/z, %) 416 (M+,
100), 401 (37.2), 324 (31.4), 85 (24.3), 121 (62.9). Anal. Calcd
for C25H24N2O2S (416. 54): C, 72.09; H, 5.80; N, 6.72. Found:
C, 72.01; H, 5.78; N, 6.61.
Gen er a l P r oced u r e for Deth iom eth yla tion -Red u ction
of 9a , 9b, 15, a n d 25 w ith Ra n ey Ni. To a solution of the
appropriate thiomethyl compound (2 mmol) in absolute ethanol
(25 mL) was added Raney Ni (W2, ∼0.8 g), and the suspension
was refluxed with stirring for 6-7 h (monitored by TLC). The
reaction mixture was then cooled and filtered through a
sintered funnel, and the residue was washed with ethanol. The
combined filtrate was evaporated under reduced pressure, and
the residue was dissolved in chloroform (50 mL), washed with
water (2 × 50 mL), dried (Na2SO4), and concentrated to give
a crude product that was purified by column chromatography
using 98:2 hexanes-ethyl acetate as an eluent.
4,5-Dim e t h oxy-1,2-d ih yd r o-3-(4-m e t h oxyp h e n yl)-7-
m eth yl-3H-p h en a len e (10a ): yield 78% (0.68 g); colorless
crystals; mp 150 °C; Rf 0.65 (98:2 hexanes-EtOAc); IR (KBr)
2930, 1512, 1463, 1245 cm1; 1H NMR (400 MHz, CDCl3) δ 2.06
(m, 2H), 2.57 (s, 3H), 2.67 (ddd, J ) 8.9, 7.4, 3.5 Hz, 1H), 2.81
(ddd, J ) 8.7, 7.4, 3.4 Hz, 1H), 3.41 (s, 3H), 3.63 (s, 3H), 3.90
(s, 3H), 4.79 (t, J ) 3.5 Hz, 1H), 6.63 (dd, J ) 7.8, 2.4 Hz, 1H),
6. 78 (dd, J ) 7.3, 2.4 Hz, 2H), 6.96 (d, J ) 6.8 Hz, 2H), 7.11
(d, J ) 6.8 Hz, 1H), 7.14 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 19.7, 25.1, 30.2, 38.1, 55.0, 55.3, 60.6, 102.5, 113.3, 122.3,
125.7, 125.8, 129.0, 129.8, 130.1, 130.4, 133.7, 137.7, 145.0,
151.2, 157.6. Anal. Calcd for C23H24N2O3: C, 79.28; H, 6.94.
Found: C, 79.19; H, 6.90.
C
25H22N2OS (398.52): C, 75.33; H, 5.57; N, 7.03. Found: C,
75.30; H, 5.55; N, 7.11.
P r oced u r e for Sn Cl4-In d u ced Cycliza tion of Cyclo-
p r op yl Keton e 3a h to 21. To a stirred solution of crude 3a h
(∼5 mmol) in CH2Cl2 (30 mL) at 0 °C was added SnCl4 (1.5
mL, 0.01 mol), and the reaction mixture was further stirred
at room temperature for 3 h. The mixture was then poured
into ice-cold aqueous NaHCO3 solution (100 mL) and extracted
with CH2Cl2 (3 × 50 mL). The combined organic extracts were
washed with water (3 × 50 mL), dried (Na2SO4), and evapo-
rated to give a viscous residue that was purified by column
chromatography using 9:1 hexanes-ethyl acetate as an eluent.
10-N-Meth yl-3-(4-m eth oxyp h en yl)-4-m eth ylsu lfa n ylcy-
clop en ta [a ]ca r ba zole-5-ca r bon itr ile (21): yield 78% (1.55
g); colorless crystals; mp 170-171 °C; Rf 0.33 (97:3 hexanes-
EtOAc); IR (KBr) 2921, 2215, 1610, 1581, 1510, 1061 cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.09 (s, 3H), 2.23 (ddd, J ) 9.0,
7.4, 3.7 Hz, 1H), 2.73 (ddd, J ) 9.0, 7.4, 3.7 Hz, 1H), 3.63 (ddd,
J ) 9.0, 7.4, 3.7 Hz, 1H), 3.71 (ddd, J ) 9.0, 7.4, 3.7 Hz, 1H),
3.77 (s, 3H), 4.09 (s, 3H), 4.88 (dd, J ) 8.0, 3.6 Hz, 1H), 6.77
(d, J ) 8.5 Hz, 2H), 6.92 (d, J ) 8.5 Hz, 2H), 7.34 (t, J ) 8.0
Hz, 1H), 7.43 (d, J ) 8.5 Hz, 1H), 7.57 (t, J ) 8.0, 1H), 8.70 (d,
J ) 8.04 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 19.8, 31.1,
31.2, 34.9, 50.2, 55.1, 108.7, 109.5, 113.7, 113.8, 117.9, 120.2,
120.5, 121.8, 127.4, 127.7, 128.3, 129.9, 136.5, 137.8, 141.9,
149.8, 157.9; MS (m/z, %) 398 (M+, 65), 352 (100), 243 (41),
145 (55). Anal. Calcd for C25H22N2OS (398.52): C, 75.33; H,
5.57; N, 7.03. Found: C, 75.38; H, 5.50; N, 7.01.
1-N-Meth yl-3-(4-m eth oxyp h en yl)-4,5-d ih yd r o-3H-8-m e-
th ylben zo[c,d ]in d ole (16): yield 94% (0.54 g); colorless
crystals; mp 141-142 °C; Rf 0.51 (97:3 hexanes-EtOAc); IR
(KBr) 2939, 1609, 1511, 1453 cm-1; 1H NMR (400 MHz, CDCl3)
δ 2.03 (ddd, J ) 8.5, 4.5, 2.6 Hz, 1H), 2.22 (ddd, J ) 8.5, 4.5,
2.6 Hz, 1H), 2.78 (s, 3H), 2.92 (m, 2H), 3.79 (s, 3H), 3.95 (s,
3H), 4.14 (dd, J ) 9.5, 4.4 Hz, 1H), 6.39 (s, 1H), 6.72 (d, J )
7.0 Hz, 1H), 6.84 (d, J ) 8.5 Hz, 2H), 7.17-7.19 (m, 3H); 13C
NMR (100 MHz, CDCl3) δ 18.9, 26.7, 34.2, 35.8, 39.4, 55.2,
113.6, 115.6, 116.3, 118.3, 124.2, 124.7, 128.1, 128.7, 129.8,
P r oced u r e for th e P r ep a r a tion of Ad d u ct 24 a n d Its
BF 3‚Et2O-In d u ced Cycliza tion to 25. To a stirring solution
4922 J . Org. Chem., Vol. 67, No. 14, 2002

133.6, 138.0, 157.9; MS (m/z, %) 291 (M+, 100), 276 (11), 232
(3.27), 184 (23). Anal. Calcd for C20H21NO (291.40): C, 82.43;
H, 7.26; N, 4.80. Found: C, 82.30; H, 7.20; N, 4.72.
123.3, 125.9, 128.8, 129.0, 129.3, 135.4, 137.5, 142.6, 151.7,
158.1, 162.5; MS (m/z, %) 370 (M+, 100), 355 (8.68). Anal. Calcd
for C24H22N2O (370.45): C, 77.81; H, 5.98; N, 7.56. Found: C,
77.68; H, 5.86; N, 7.50.
6-(4-Meth oxyph en yl)-1-N-m eth yl-2-N-ph en yl-1,2-dih dr o-
3H-cyclop en ta [e]in d a zol-3-on e (26): yield 70% (0.518 g);
colorless crystals; mp 146-147 °C; Rf 0.39 (9:1 hexanes-
EtOAc); IR (KBr) 3065, 2927, 1680, 1596, 1506 cm-1; 1H NMR
(400 MHz, CDCl3) δ 2.02 (ddd, J ) 9.0, 7.4, 3.7 Hz, 1H), 2.56
(ddd, J ) 9.0, 7.4, 3.7 Hz, 1H), 3.19 (s, 3H), 3.2 (ddd, J ) 9.0,
7.4, 3.7 Hz, 1H), 3.47 (ddd, J ) 9.0, 7.3, 3.4 Hz, 1H), 3.76 (s,
3H), 4.25 (dd, J ) 8.0, 3.1 Hz, 1H), 6.78 (dd, J ) 7.3, 2.4 Hz,
2H), 6.96 (dd, J ) 7.3, 2.4 Hz, 1H), 7.02 (d, J ) 8.5 Hz, 2H),
7.09 (d, J ) 8.3 Hz, 1H), 7.20 (t, J ) 7.9 Hz, 1H), 7.40 (t, J )
7.8 Hz, 2H), 7.53 (d, J ) 7.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 29.6, 37.0, 40.1, 49.8, 55.2, 110.6, 113.8, 113.9, 115.4,
Ack n ow led gm en t. S.N. and U.K.S. thank CSIR
New Delhi for senior research fellowships. Financial
assistant under CSIR scheme is also acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Full spectroscopic
and analytical data for compounds 9b-d and 10b. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O020230R
J . Org. Chem, Vol. 67, No. 14, 2002 4923