Domino carbocationic rearrangement of α-[bis(methylthio)methylene]alkyl-2-arylcyclopropyl carbinols: Facile access to 1-arylindanes

Full text of DOI:10.1021/jo001488p

J . Org. Chem. 2001, 66, 1503-1508
1503
stereoselective fashion. Also in a recent paper9 we
reported the unexpected formation of the bicyclo[3.2.1]-
octane framework by domino carbocationic transforma-
tion of 1-styryl-2-bis(methylthio)methylene cyclopropyl
carbinols through a series of rearrangement and termi-
nation events. In continuation of these studies, we now
report further on our findings on one-pot domino car-
bocationic cyclization of the cyclopropyl carbinols with
general structures 3-5 to substituted 1-arylindanes. The
overall transformation entails the concomitant formation
of two strategic carbon-carbon bonds leading to a
substituted benzene and cyclopentane ring from acyclic
precursors in one synthetic operation.
Dom in o Ca r boca tion ic Rea r r a n gem en t of
r-[Bis(m eth ylth io)m eth ylen e]a lk yl-2-a r yl-
cyclop r op yl Ca r bin ols: F a cile Access to
1-Ar ylin d a n es
P. K. Mohanta, S. Peruncheralathan, H. Ila,*,† and
H. J unjappa*
Department of Chemistry, Indian Institute of Technology,
Kanpur-208 016, India
hila@iitk.ac.in
The carbinol substrates 3a -h , 4a ,b, and 5a were easily
prepared by addition of the various allyl Grignard
reagents 2a -c to the cyclopropyl ketones6b,c 1a -h under
our earlier described standard reaction conditions.10 We
anticipated that the initially generated benzylic carboca-
tion 18 in the presence of Lewis acid would be intercepted
by a pendant bis(methylthio)methylene and allylic double
bond in a domino fashion leading to concomitant forma-
tion of indane framework after subsequent aromatization
(Scheme 3). Thus, with these carbinols in hand, common
Lewis acids were surveyed and BF3‚Et2O was found to
cleanly effect the desired transformation. When the
carbinol 3a obtained from addition of methallyl Grignard
reagent to 1a was treated with BF3‚Et2O in nitromethane
at 0 °C for 12 h, a single new product was formed. After
Received October 17, 2000
Domino or tandem processes occupy a central role in
the syntheses of complex organic compounds and confer
great strategic value in molecular construction.1 These
reactions typically entail the formation of multiple new
bonds and rings in a single operation in high yields with
good regio- and stereocontrol.2 The carbocationic cycliza-
tion of polyolefinic precursors into fused polycyclic prod-
ucts exemplifies these reactions and has proven especially
useful in the construction of six-membered rings.3 Ap-
plication of these carbocationic cyclizations to cyclopen-
tanoid syntheses has also been reported.4,5 We have
previously described a new synthesis of substituted
cyclopentanes via acid-induced rearrangement of 1-aryl-
2-bis(methylthio)methylene cyclopropyl ketones and
carbinols.6 The overall transformation involves Lewis
acid assisted cyclopropyl ring opening and intramolecular
5-exo-trig capture of the resulting carbocationic interme-
diate by the bis(methylthio)methylene double bond.
These rearrangements can be regarded as modified
Nazarov reactions in which one double bond of the
pentadiene system is replaced by a cyclopropyl group.4,7
We subsequently realized that this transformation is a
potential candidate for domino process, since the initial
cyclization results in the formation of a new carbon-
carbon bond and cyclopentanoid ring while also producing
a reactive bis(methylthio)methyl carbocationic intermedi-
ate. Thus, in the subsequent papers,8 we demonstrated
that a pendant electron rich arene or olefinic nucleophile
can intercept this carbocation to furnish functionalized
cyclopentanoindane and diquinane derivatives in highly
(6) (a) Deb, B.; Asokan, C. V.; Ila, H.; J unjappa, H. Tetrahedron
Lett. 1988, 29, 2111.
† Fax: 91-0512-597436, 91-0512-590260.
(1) (a) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993,
32, 131. (b) Bunce, R. A. Tetrahedron 1995, 51, 13103. (c) Thebtra-
nonth, C.; Thebtranonth, Y. Tetrahedron 1990, 46, 1385. (d) Ho, T.-L.
Tandem Reactions in Organic Synthesis; Wiley-Interscience: New
York, 1992.
(2) (a) Tietze, L. F. Chem. Rev. 1996, 96, 115. (b) Hudlicky, T. Chem.
Rev. 1996, 96, 3. (c) Thematic issue, Frontiers in Organic Synthesis;
Wender, P. A., guest editor. Chem. Rev. 1996, 96, 31.
(3) (a) J ohnson, W. S. Angew. Chem., Int. Ed. Engl. 1976, 15, 9. (b)
Corey, E. J .; Virgil, S. C.; Sarshar, S. J . Am. Chem. Soc. 1991, 113,
8171. (d) Corey, E. J .; Virgil, S. C. J . Am. Chem. Soc. 1991, 113, 4025.
(4) (a) West, F. G.; Fisher, P. V.; Arif, A. M. J . Am. Chem. Soc. 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,
F. G. Synlett 1999, 1363. (e) West, F. G.; Willoughby, D. M. J . Org.
Chem. 1993, 58, 3796.
(5) (a)Mehta, G.; Rao, K. S.; Reddy, M. S. J . Chem. Soc., Perkin
Trans. 1 1991, 693. (b) Wender, P. A.; Correia, C. R. D. J . Am. Chem.
Soc. 1987, 109, 2523. (c) Amupitan, J . A.; Scovell, E. G.; Sutherland,
J . K. J . Chem. Soc., Perkin Trans. 1 1983, 755.
(b) Deb, B.; Ila, H.; J unjappa, H. J . Chem. Res., Synop. 1990, 356; J .
Chem. Res., Miniprint 1990, 2728. (c) Patro, B.; Deb, B.; Ila, H.;
J unjappa, H. J . Org. Chem. 1992, 57, 2257. (d) Patro, B.; Deb, B.; Ila,
H.; J unjappa, H. Tetrahedron 1994, 50, 255.
(7) Reviews: (a) Habermas, K. L.; Denmark, S. E.; J ones, T. K.
Org. React. (N.Y.) 1994, 45, 1. (b) Denmark, S. E. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,
1991; Vol. 5, pp 751-784. (c) Ramaiah, M. Synthesis 1984, 529. (d)
Santelli-Rouvier, C.; Santelli, M. Synthesis 1983, 429. (e) See also:
Tius, M. A. In Studies in Natural Product Chemistry; Atta-ur-Rahman,
Ed.; Elsevier: Amsterdam, 1994; Vol. 14, pp 583-630.
(8) (a) Patra, P. K.; Patro, B.; Ila, H.; J unjappa, H. Tetrahedron Lett.
1993, 34, 3951. (b) 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. J . Chem.
Soc., Perkin Trans. 1 2000, 1547.
(10) (a) Patra, P. K.; Suresh, J . R.; Ila, H.; J unjappa, H. Tetrahedron
1998, 54, 10167. (b) Basaveswara Rao, M. V.; Syam Kumar, U. K.;
Ila, H.; J unjappa, H. Tetrahedron 1999, 55, 11563.
10.1021/jo001488p CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/24/2001

1504 J . Org. Chem., Vol. 66, No. 4, 2001
Notes
Sch em e 1
Ta ble 1. Syn th esis of Su bstitu ted 1-Ar ylin d a n es
workup and isolation, the spectral analysis of the new
product was found to be consistent with 1-(4-methox-
yphenyl)-5-methyl-7-(methylthio)indane (6a ) (Table 1).
All the carbinols 3b-g obtained by addition of methallyl
Grignard reagents to 1b-g were transformed into the
corresponding 1-arylindanes 6b-g (Scheme 1, Table 1)
in facile manner, when subjected to the above reaction
conditions (A). However, the corresponding phenyl-
substituted carbinol 3h did not yield the desired 1-phe-
nylindane and the product isolated (62%) was charac-
terized as the substituted benzene derivative 7.
whereas at room temperature (A) formation of only 2-(1-
methallyl)cyclopentene carbothioate 11a (65%) was ob-
served.
We next investigated the rearrangement of the carbinols
13a and 14a obtained by addition of allyl Grignard
reagents to R-[bis(methylthio)methylene]ethyl arylcyclo-
propyl ketone 12a with a view to examine the effect of
an alkyl substituent in the carbinol side chain on product
formation (Scheme 2). Thus, 13a yielded only the 1-meth-
yl-2-allylcyclopentene carbothioate 15a under the influ-
ence of BF3‚Et2O (A) whereas cyclization of 14a under
these conditions (A) resulted only in multiple products
that cannot be characterized. Interestingly, in refluxing
benzene (B), both the carbinols 13a and 14a were
efficiently transformed to single products, which were
found to be the isomeric 1-arylindanes 16a and 17a ,
respectively on the, basis of spectral and analytical data
(Scheme 2).
The carbinol 4a formed by addition of allyl Grignard
reagent to 1a gave only the 2-allylcyclopentene carboth-
ioate 8a , when subjected to cyclization under the above
reaction conditions (A). However, when 4a was treated
with BF3‚Et2O in refluxing benzene (3 h) (B), the desired
1-(4-methoxylphenyl)-7-methlythioindane (9a ) was ob-
tained in 65% yield (Table 1, entry 9). Similarly, the
dimethoxyphenylcyclopropyl carbinol 4b was readily
transformed into 1-arylindane 9b in 69% yield under
similar conditions (B). The carbinol 5a from crotyl
Grignard reagent also required refluxing conditions for
domino transformation to 4-methyl-1-arylindane 10a ,
The probable mechanism for the formation of various
products is shown in Scheme 3. The initial Lewis acid
assisted cleavage of the hydroxy group in all the carbinols
followed by ring cleavage of the resulting cyclopropyl-
carbinyl carbocationic intermediate affords the new ben-
zylic carbocation 18. The cation 18 is then trapped

Notes
J . Org. Chem., Vol. 66, No. 4, 2001 1505
Sch em e 2
Sch em e 3
intramolecularly by the bis(methylthio)methylene double
bond in a 5-exo-cycilzation, establishing a new C-C bond
and a highly stable tertiary bis(methylthio)methyl car-
bocation 19, which is probably captured concomitantly
by the pendant methallyl side chain (R ) H, R1 ) Me) at
room temperature in a 6-endo cyclization, leading to a
new C-C bond and a six-membered carbocyclic ring in
the tertiary carbocationic intermediate 20, which under-
goes subsequent aromatization under reaction conditions
to afford 1-arylindanes in good yields. In the case of the
carbinols with allyl or crotyl side chains (R ) R1 ) H or
R1 ) H, R ) Me), the overall cyclization and aromatiza-
tion process takes place only under refluxing conditions,
whereas at room temperature, initially formed bis-
(methylthio)methyl cyclopentenyl carbocation 19 fails to
undergo 6-endo cyclization due to the formation of less
stable secondary carbocation 20 (R1 ) H) and yields only
hydrolyzed carbothioates 8a or 11a . When Ar ) C6H5,
benzylic carbocation 18 is not stable enough to be
intercepted by the bis(methylthio)methylene double bond
via the 5-exo-trig process in line with our earlier
observations,6a,b and furnishes only aromatized product
7 after quenching of carbocation 21 by methylmercaptan
generated during the cycloaromatization process. In the
case of carbinols 13a and 14a with a bis(methylthio)-
propenyl side chain (R2 ) Me) (Scheme 2), we believe that
carbocation 18 (R1 ) H or Me; R2 ) Me) undergoes
concurrent 5-exo and 6-endo cyclizations under refluxing
conditions (B) to yield the bicyclic carbocationic inter-
mediate 22. Subsequently, 22 rearranges itself to ther-
modynamically more stable aromatized intermediate 23
with a pendant carbocationic side chain, which is inter-
cepted by electron rich benzene ring to afford the
observed rearranged arylindanes 16a or 17a in good
yields (Scheme 3).
In summary, a successful domino carbocationic pro-
cess11 has been demonstrated, leading to formation of a
fused cyclopentane and a substituted benzene ring from
cyclopropyl carbinol precursors. The overall process
combines our aromatic annelation protocol12 and cyclo-

1506 J . Org. Chem., Vol. 66, No. 4, 2001
Notes
Sch em e 4
40% conversion to carbinol 28a was observed. Our effort
to increase the yield of carbinol 28a was not successful.
When 27a was refluxed with BF3‚Et2O in benzene (B),
the corresponding 1-aryl-2-carboethoxyindane 29a was
obtained in 50% yield. Treatment of the crude carbinol
28a (along with 25a ) with BF3‚Et2O at room temperature
(A) furnished indane 30a along with cyclopentanone
derivative 31 which is evidently formed from the rear-
rangement of unreacted cyclopropyl ketone 25a . These
observations suggest that the present domino process
could be applicable for the synthesis of more complex
highly substituted arylindane targets. Additional studies
of the scope of this reaction and further examples of
synthetically useful transformations involving the ketene-
dithioacetal moiety as terminator and initiator in the
domino carbocationic process will be reported elsewhere.
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 conducted by column chromatography
using 60-120 mesh silica gel obtained from Acme Synthetic
Chemicals. THF, diethyl ether, and benzene were distilled over
sodium/benzophenone and stored over sodium wire before use.
All reagents were purchased commercially and used as such
unless until stated otherwise.
pentane ring construction via oxoketene dithioacetals in
a single one-pot synthetic operation. The reaction pro-
vides facile access to substituted 1-arylindane frame-
works. Alkyl-substituted arylindanes are shown to be
highly valuable monomers for NLO polymeric materi-
als,13 whereas the 1,3-diarylidan-2-carboxylic acid motif
has been identified as a useful scaffold to build new
potent and selective non-peptide endothelin receptor
antagonists.14 Thus, in an effort toward constructing part
of this structural motif involving our domino carboca-
tionic process, we investigated possible rearrangement
of the carbinols 27a and 28a to 1-aryl-2-carboethoxyin-
danes 29a and 30a , respectively (Scheme 4). The 2-car-
boethoxycyclopropyl ketone 25a was prepared by addition
of ethoxycarbonyl dimethylsulfonium methylide15 to cin-
namoyl ketenedithioacetal6 24a . However, the desired
carbinols 27a and 28a could not be obtained by direct
addition of allyl and methallyl Grignard reagents to
cyclopropyl ketone 25a since the reaction was compli-
cated by simultaneous addition to the ester carbonyl
group, leading to complex product mixture. We therefore
examined addition of allyl and 2-methallylindium16 to
25a for obtention of the carbinols 27a and 28a . Thus,
the addition of allylindium to 25a proceeded smoothly
at room temperature to afford the corresponding carbinol
27a exclusively, whereas with 2-methallylindium16 only
All the bis(methylthio)methylene arylcyclopropyl ketones
1a -h and 12 were prepared according to the earlier reported6c
procedure.
Gen er a l P r oced u r e for th e Ad d ition of Allylic Gr ign a r d
Rea gen ts to Cyclop r op yl Keton es. To a well-stirred suspen-
sion of metallic magnesium (0.21 g) in dry ether (30 mL) was
added a solution of the appropriate allyl halide 2 (5 mmol) in
dry ether (10 mL) at room temperature under a nitrogen
atmosphere. After 1 h, a solution of cyclopropyl ketone (3.4
mmol) in dry THF (15 mL) was added dropwise and the resulting
mixture was stirred at room temperature for 3 h (monitored by
TLC). It was then diluted with saturated ammonium chloride
solution and extracted with ether (3 × 30 mL). The organic
extracts were combined, washed with brine, dried over anhy-
drous Na2SO4, and concentrated under reduced pressure to
afford the respective carbinol, which was used as such for the
next reaction.
All the carbinols 3a -h , 4a ,b, 5a , 13a , a n d 14a were char-
1
acterized by their IR and H and 13C NMR spectra. The spectral
data for one of the representative carbinols, 3a , is given below.
3-[2-(4-Meth oxyph en yl)cyclopr opan -1-yl]-5-m eth yl-1-bis-
(m eth ylth io)h exa -1,5-d ien -3-ol (3a ). Colorless oil: Rf ) 0.5 (3:
17; ethyl acetate:hexane); IR (neat) 3366, 2924, 1258, 739 cm-1
;
1H NMR δ 6.91 (dd, J ) 8.8, 3.0 Hz, 2H), 6.72 (dd, J ) 8.8, 3.0
Hz, 2H), 6.0 (s, 1H), 4.93-4.44 (m, 2H), 3.68 (s, 3H), 3.50-3.36
(m, 1H), 3.18 (br s, 1H), 2.42-2.38 (m, 1H), 2.25 (s, 3H), 2.17 (s,
3H), 2.08-192 (m, 1H), 1.90-1.85 (m, 1H), 1.71-1.63 (m, 1H),
1.18 (s, 3H), 1.07-0.77 (m, 1H); 13C NMR δ 157.6, 142.1, 139.5,
139.2, 135.0, 131.3, 127.2, 115.1, 113.7, 55.3, 50.3, 32.8, 29.7,
24.6, 18.3, 17.9, 16.9, 10.9.
(11) For other domino process leading to the indane framework, see
the following. By radical cyclization: (a) Parsous, P. J . Synlett 1998,
1215. (b) Via Fischer-carbene complex: Herndron, J . W Tetrahedron
2000, 56, 1257. (c) Enyne-cumulene cyclization: Schmittel, M.; Keller,
M.; Kiau, S.; Strittmatter, M. Chem. Eur. J . 1997, 3, 807. (d) Cobalt
carbonyl [Co2(CO)8] catalyzed tandem cycloaddition of diynes: Hong,
S. H.; Kim, J . W.; Choi, D. S.; Chung, Y. K.; Lee, S.-G. J . Chem. Soc.,
Chem. Commun. 1999, 2099.
Gen er a l P r oced u r e for th e BF 3‚Et2O-In d u ced Cycliza -
tion of Ca r bin ols 3-5, 13a , a n d 14a : Syn th esis of 1-Ar ylin -
d a n es a n d Cyclop en ten e Ca r both ioa tes: Rea ction Con -
d ition s A. To a solution of crude carbinol (3-5, 13a , 14a )
obtained from an earlier reaction in nitromethane (10 mL) was
added BF3‚Et2O (5 mmol, 0.65 mL) at 0 °C, and the reaction
mixture was stirred at ambient temperature for 12-15 h
(monitored by TLC). It was diluted with ice-cooled bicarbonate
solution (15 mL) and extracted with ethyl acetate (3 × 30 mL).
The organic extracts were combined, washed with water, and
(12) (a) J unjappa, H.; Ila, H.; Asokan, C. V. Tetrahedron 1990, 46,
5423. (b) J unjappa, H.; Ila, H. Phosphorus Sulfur Silcon 1994, 95-96,
35-54.
(13) Zhang, M.; Kazlauskas, R. J . Org. Chem. 1999, 64, 7498.
(14) (a) Pridgen, L. N.; Huang, K.; Shilcrat, S.; Tickner-Eldrige, A.;
DeBrosse, P.; Halti-Wangner, R. C. Synlett 1999, 1612. (b) Guillon,
J .; Dallemagne, P.; Stiebing, S.; Lantos, I.; Bauy, P. R.; Rault, S. Synlett
1999, 1263. (c) Clark, W. M.; Tickner-Eldridge.; Huang, G. K.; Pridgen,
L. N.; Olsen, M. A.; Mills, R. J .; Lantos, I.; Baine, N. H. J . Am. Chem.
Soc. 1998, 120, 4550. (d) Pridgen, L. N.; Kris Huang, G. Tetrahedron
Lett. 1998, 39, 8421.
(16) For reviews on indium related reactions, see: (a) Li, C. J .; Chan,
T. H. Tetrahedron 1999, 55, 11149. (b) Cintas, P. Synlett 1995, 1087.
(c) Li, C. J . Chem. Rev. 1993, 93, 2023. (d) Paquette, L. A. In Green
Chemistry, Frontiers in benign Chemical Synthesis Processes; Anastas,
P., Williamson, T. C., Eds.; Oxford University Press: 1998.
(15) Pyane, G. B. J . Org. Chem. 1967, 32, 3351.

Notes
J . Org. Chem., Vol. 66, No. 4, 2001 1507
dried over anhydrous Na2SO4. The solvent was removed under
reduced pressure to afford arylindanes 6a -6g or 7 or cyclopen-
tene carbothioate 8a , 11a , or 15a , which was purified by column
chromatography on silica gel using hexanes-ethyl acetate (97:
3) as eluent to obtain analytically pure product.
3H), 2.04 (ddt, J ) 18.1, 8.6, 3.0 Hz, 1H); 13C NMR δ 148.8, 147.2,
144.7, 143.2, 137.4, 135.6, 127.9, 122.5, 120.8, 119.1, 111.1, 110.9,
55.7, 55.1, 50.1, 35.7, 31.5, 15.2; MS m/e 300.0 (M+, 100), 253
(43.9), 162 (41.3). Anal. Calcd for C18H20O2S (300.43): C, 71.96;
H, 6.71. Found: C, 72.13; H, 6.96.
1-(4-Meth oxyph en yl)-4-m eth yl-7-(m eth ylth io)in dan e (10a).
Yield 61% (0.59 g). Colorless oil: Rf ) 0.4 (1:9; ethyl acetate:
hexane); IR (neat) 2949, 1509, 1458, 1437 cm-1; 1H NMR δ 7.05
(d, J ) 8.3 Hz, 1H), 6.94 (br d, J ) 8.8 Hz, 3H), 6.78 (d, J ) 8.8
Hz, 2H), 4.44 (dd, J ) 9.0, 2.7 Hz, 1H,), 3.74 (s, 3H), 2.97 (ddd,
J ) 16.1, 8.3, 8.5 Hz, 1H), 2.89 (ddd, J ) 15.9, 9.4, 3.2 Hz, 1H),
2.58 (ddt, J ) 15.9, 9.4, 3.2 Hz, 1H), 2.28 (s, 3H), 2.26 (s, 3H),
2.0 (ddt, J ) 17.1, 8.6, 8.0 Hz, 1H);); 13C NMR δ 157.8, 143.8,
143.6, 137.4, 132.1, 130.5, 128.7, 128.4, 123.8, 113.7, 55.1, 50.0,
35.3, 30.3, 18.9, 15.7; MS m/e 285 (M+, 100), 270 (94), 237(46).
Anal. Calcd for C18H20OS (284.43): C, 76.01; H, 7.08. Found:
C, 76.18; H, 7.14.
S-Meth yl 2-(Bu t-1-en e-3-yl)-5-(4-m eth oxyp h en yl)cyclo-
p en t-2-en -1-ca r both ioa te (11a ). Yield 65% (0.67 g). Colorless
oil: Rf ) 0.55 (1:9; ethyl acetate:hexane); IR (neat) 2927, 1680,
1581, 1512, 1447 cm-1; 1H NMR δ 7.13-7.09 (m, 2H), 6.82 (dd,
J ) 8.8, 2.7 Hz, 2H), 5.93-5.59 (m, 2H), 5.06-4.95 (m, 2H), 3.77
(s, 3H), 3.75 (br s, 1H), 3.63-3.55 (m, 1H), 3.03-2.89 (m, 2H),
2.42 (br d, J ) 14.2 Hz, 1H), 2.29 (s, 3H), 1.23 (dd, J ) 6.8, 3.3
Hz, 3H); 13C NMR δ 201.9, 158.2, 144.6, 141.3, 137.8, 127.7,
126.9, 114.4, 113.9, 69.4, 55.2, 48.4, 41.0, 38.3, 18.8, 11.7; MS
m/e 302 (M+, 35.7), 226 (100). Anal. Calcd for C18H22O2S
(302.44): C, 71.49; H, 7.33. Found: C, 71.62; H, 7.16.
1-(4-Meth oxyph en yl)-4-m eth yl-5-(m eth ylth io)in dan e (16a).
Yield 65% (0.63 g). Colorless crystals (pentane): mp 64-65 °C;
Rf ) 0.5 (1:9 ethyl acetate:hexane); IR (KBr) 2998, 1609, 1511,
1454 cm-1; 1H NMR δ 7.0 (dd, J ) 8.8, 1.9 Hz, 2H), 6.92 (d, J )
7.8 Hz, 1H), 6.75 (dd, J ) 8.4, 1.9 Hz, 2H), 6.67 (d, J ) 7.8 Hz,
1H), 4.17 (d, J ) 8.3 Hz, 1H), 3.68 (s, 3H), 2.90 ((ddd, J ) 15.8,
9.1, 3.2 Hz, 1H), 2.74 (ddd, J ) 16.1, 8.3, 8.5 Hz, 1H), 2.45 (ddt,
J ) 12.7, 10.0, 6.3 Hz, 1H)), 2.32 (s, 3H), 2.24 (s, 3H), 1.9 (ddt,
J ) 13.0, 9.6, 6.3 Hz, 1H); 13C NMR δ 158.1, 144.3, 143.8, 137.6,
135.2, 132.1, 129.0, 124.7, 122.7, 113.8, 55.2, 50.9, 36.3, 30.8,
16.5, 16.4; MS m/e 284 (M+, 100), 237 (63). Anal. Calcd for
Rea ction Con d ition s B. To a solution of crude carbinol
(4a ,b, 5a , 13a , 14a ) obtained from an earlier reaction mixture
in dry benzene (25 mL) was added BF3‚Et2O (5 mmol, 0.65 mL)
at room temperature, and the reaction mixture was refluxed for
3 h (for carbinols 4a ,b, 5a ) or 5 h (13a ) or 15 h (for 14a )
(monitored by TLC). The reaction mixture was cooled to room
temperature, poured into an ice-cooled bicarbonate solution (15
mL), and extracted with ethyl acetate (3 × 30 mL). The organic
extracts were combined, washed with water, and dried over
anhydrous Na2SO4. The solvent was removed under reduced
pressure to afford substituted arylindane, which was purified
by column chromatography on silica gel using hexanes-ethyl
acetate (97:3) as eluent to obtain analytically pure product.
1-(4-Meth oxyph en yl)-5-m eth yl-7-(m eth ylth io)in dan e (6a).
Yield17 79% (0.76 g). Colorless needles (ether): mp 78-79 °C; Rf
) 0.7 (3:17; ethyl acetate:hexane); IR (KBr) 2910, 1580, 1550,
1425 cm-1 1H NMR δ 6.93 (dd, J ) 6.8, 2.2 Hz, 2H), 6.90 (s,
;
1H), 6.79 (s, 1H), 6.77 (dd, J ) 6.8, 2.2 Hz, 2H), 4.37 (dd, J )
8.8, 2.7 Hz, 1H), 3.74 (s, 3H), 3.04 (ddd, J ) 15.9, 8.3, 8.8 Hz,
1H), 2.83 (ddd, J ) 15.9, 9.4, 3.2 Hz, 1H), 2.53 (ddt, J ) 18.0,
10.9, 7.1 Hz, 1H), 2.37 (s, 3H), 2.31 (s, 3H), 1.97 (ddt, J ) 18.1,
8.8, 8.0 Hz, 1H); 13C NMR δ 157.8, 144.9, 140.7, 137.6, 137.3,
135.0, 128.4, 123.3, 121.7, 113.7, 55.1, 49.2, 36.1, 31.4, 21.4, 15.1;
MS m/e 285 (M+, 100), 270 (94), 237 (46). Anal. Calcd for C18H20
-
OS (284.43): C, 76.0; H, 7.08. Found: C, 76.22; H 7.19.
1-(2-Meth oxyph en yl)-5-m eth yl-7-(m eth ylth io)in dan e (6b).
Yield 75% (0.73 g). Colorless oil: Rf ) 0.7 (3:17; ethyl acetate:
hexane); IR (neat) 2954, 1596, 1564, 1489, 1457 cm-1; 1H NMR
δ 7.18-7.14 (m, 1H), 6.91 (s, 1H), 6.89 (d, J ) 8.3 Hz, 1H), 6.82
(s, 1H), 6.76-6.72 (m, 1H), 6.52 (d, J ) 8.8 Hz, 1H), 4.76 (d, J
) 8.8 Hz, 1H), 3.89 (s, 3H), 2.95 (ddd, J ) 16.1, 8.2, 8.8 Hz, 1H),
2.79 (ddd, J ) 15.7, 8.8, 2.4 Hz, 1H), 2.50 (ddt, J ) 18.1, 10.3,
8.8 Hz, 1H), 2.37 (s, 3H), 2.28 (s, 3H), 1.94 (ddt, J ) 12.7, 8.3,
2.4 Hz, 1H); 13C NMR δ 156.9, 145.8, 140.2, 137.4, 134.9, 132.7,
127.2, 127.1, 123.2, 121.6, 120.2, 110.4, 55.5, 43.0, 34.3, 31.3,
21.5, 15.2; MS m/e 284 (M+, 68.7), 269 (37.7), 237 (100). Anal.
Calcd for C18H20OS (284.43): C, 76.0; H, 7.08. Found: C, 76.29;
H, 7.21.
3-[3-(Met h ylt h io)-3-p h en ylp r op yl]-5-(m et h ylt h io)t olu -
en e (7). Yield 62% (0.64 g). Yellow oil: Rf ) 0.7 (1:10; ethyl
acetate:hexane); IR (neat) 2916, 1579, 1490, 1449 cm-1; 1H NMR
δ 7.26-7.13 (m, 5H), 6.80 (s, 1H), 6.74 (s, 1H), 6.63 (s, 1H), 3.54
(t, J ) 6.8 Hz, 1H), 2.47 (t, J ) 6.8 Hz, 2H), 2.35 (s, 3H), 2.19 (s,
3H), 2.14-2.0 (m, 2H); 1.75 (s, 3H); 13C NMR δ 142.0, 141.9,
138.4, 138.0, 128.4, 127.8, 127.0, 126.1, 124.7, 123.6, 50.6, 37.2,
33.5, 21.2, 15.7, 14.1; MS m/e 302 (M+, 43.8), 253 (35.8), 151
(100). Anal. Calcd for C18H22S2 (302.50): C, 71.47; H, 7.33.
Found: C, 71.59; H, 7.18.
1-(4-Meth oxyp h en yl)-7-(m eth ylth io)In d a n e (9a ). Yield
65% (0.60 g). Colorless crystals (ether): mp 68-69 °C; Rf ) 0.65
(3:17; ethyl acetate:hexane); IR (KBr) 2949, 1512, 1454, 1438
cm-1; 1H NMR δ 7.26-7.21 (m, 1H), 7.11 (d, J ) 7.4 Hz, 1H), 7.
01 (d, J ) 7.8 Hz, 1H), 6.97 (dd, J ) 8.8, 3.6 Hz, 2H), 6.81(dd,
J ) 8.8, 3.2 Hz, 2H), 4.42 (d, J ) 9.0 Hz, 1H), 3.78 (s, 3H), 3.11
(ddd, J ) 16.01, 8.4, 8.8 Hz, 1H), 2.90 (ddd, J ) 15.8, 8.8, 2.2
Hz, 1H), 2.59 (ddt, J ) 15.3, 10.4, 9.0 Hz), 2.33 (s, 3H), 2.0 (ddt,
J ) 16.3, 9.4, 2.9 Hz, 1H); 13C NMR δ 157.8, 144.7, 143.5, 137.0,
135.5, 128.4, 127.8, 122.4, 120.8, 113.7, 55.1, 49.6, 35.8, 31.5,
15.1; MS m/e 270 (M+, 100), 255 (85). Anal. Calcd for C17H18OS
(270.40): C, 75.51; H, 6.71. Found: C, 75.68; H, 6.97.
C
18H20OS (284.43): C, 76.01; H, 7.09. Found: C, 76.21; H, 7.18.
4,7-Dim e t h yl-1-(4-m e t h oxyp h e n yl)-5-(m e t h ylt h io)in -
d a n e (17a ). Yield 61% (0.62 g). Colorless oil: Rf ) 0.45 (1:9; ethyl
acetate:hexane); IR (neat) 2919, 1510, 1458, 1437 cm-1; 1H NMR
δ 6.93 (dd, J ) 6.6, 2.0 Hz, 2H), 6.85 (s, 1H), 6.78 (dd, J ) 6.6,
2.0 Hz, 2H), 4.34 (dd, J ) 8.8, 1.6 Hz, 1H), 3.77 (s, 3H), 3.93 (m,
1H), 2.86-2.79 (m, 1H), 2.53 (m, 1H), 2.45 (s, 3H), 2.31 (s, 3H),
2.94 (ddt, J ) 12.7, 10.3, 6.6 Hz, 1H)), 1.92 (s, 3H); 13C NMR δ
157.8, 143.9, 141.9, 138.0, 132.5, 129.5, 128.3, 127.5, 126.2, 113.8,
55.2, 49.6, 35.7, 30.7, 18.9, 16.4, 16.2; MS m/e 298 (M+, 100),
250 (56.3). Anal. Calcd for C19H22OS (298.45): C, 76.47; H, 7.43.
Found: C, 76.34; H, 7.29.
Eth yl 2-{[Bis(m eth ylth io)m eth ylen e]a cetyl}-3-(4-m eth -
oxyp h en yl)cyclop r op a n eca r boxyla te (25a ). To a well-stirred
solution of ethyl (dimethylsulfuranylidine)acetate (EDSA)15 (15
mmol) in chloroform (50 mL) at 0 °C was injected cinnamoyl
ketenedithioacetal 24a (2.8 g, 10 mmol) in chloroform (20 mL),
and the reaction mixture was stirred at room temperature for
(2 h) and then refluxed for 30 h (monitored by TLC). It was then
cooled and concentrated under reduced pressure to afford crude
25a , which was purified by being passes through a silica gel
column using hexanes-ethyl acetate (24:1) as eluent. Yellow oil:
yield 71% (2.6 g); Rf ) 0.5 (1:4; ethyl acetate:hexane); IR (neat)
1
2980, 1729, 1695, 1512, 1302, 1249 cm-1; H NMR δ 7.10 (d, J
) 8.3 Hz, 2H), 6.73 (d, J ) 8.3 Hz, 2H), 6.25 (s, 1H), 3.94-3.86
(q, J ) 7.0 Hz, 2H), 3.70 (s, 3H), 3.04-3.01 (m, 1H), 2.93-2.90
(m, 1H), 2.58-2.56 (m, 1H), 2.45 (s, 3H), 2.43 (s, 3H), 1.01 (t, J
) 7.0 Hz, 3H); 13C NMR δ 190.2, 169.3, 165.5, 158.5, 130.0, 127.1,
113.5, 112.4, 60.6, 55.1, 34.0, 33.7, 31.6, 17.2, 14.9, 14.1; MS m/e
366 (M+, 25.5), 293 (49), 147 (100). Anal. Calcd for C18H22O4S2
(366.50): C, 58.99; H, 6.05. Found: C, 59.11; H, 6.27.
1-(3,4-Dim eth oxyph en yl)-7-(m eth ylth io)in dan e (9b). Yield
69% (0.7 g). Viscous liquid: Rf ) 0.6 (3:17; ethyl acetate:hexane);
IR (neat) 2984, 1589, 1573, 1441 cm-1 1H NMR δ 7.27-7.22
;
(m, 1H), 7.12 (d, J ) 7.6 Hz, 1H), 7.02 (d, J ) 7.6 Hz, 1H), 6.75
(d, J ) 8.3 Hz, 1H), 6.65 (d, J ) 2.0 Hz, 1H), 6.52 (dd, J ) 8.0,
1.9 Hz, 1H), 4.42 (dd, J ) 9.0, 2.9 Hz, 1H), 3.88 (s, 3H), 3.82 (s,
3H), 3.12 (ddd, J ) 15.9, 8.3, 8.7 Hz, 1H), 2.9 (ddd, J ) 15.9,
9.4, 3.2 Hz, 1H), 2.60 ((ddt, J ) 17.8, 10.8, 7.0 Hz, 1H), 2.34 (s,
Gen er a l P r oced u r e for th e Ad d ition of Allylic In d iu m
Rea gen ts to 2-Ca r boeth oxycyclop r op yl Keton e (25a ). To
a suspension of indium powder (0.68 g) in dry DMF (5 mL) was
injected allyl bromide (or methallyl bromide) (9.0 mmol) through
a septum, and the reaction mixture was stirred for 1 h at room
temperature. A solution of 25a (3 mmol) in dry DMF (3 mL)
was added, and the stirring was continued for 24-30 h (moni-
(17) The reported yields of all substituted arylindanes are the overall
yields from their respective cyclopropyl ketones.

1508 J . Org. Chem., Vol. 66, No. 4, 2001
Notes
tored by TLC). The reaction mixture was poured into a saturated
sodium chloride solution and extracted with ethyl acetate (3 ×
30 mL). The organic layers were combined, washed with water,
dried over anhydrous Na2SO4, and evaporated under reduced
pressure to afford carbinol 27a or 28a (along with cyclopropyl
(neat) 2926, 1731, 1610, 1579, 1302, 1250 cm-1; [exists as a
mixture of two isomers (3:1), NMR value of minor isomer is given
inside bracket]; 1H NMR δ 7.01[6.89] (d, J ) 8.6 Hz, 2H),
[6.93]6.88 (br s, 1H), 6.81-6.79[6.74-6.68] (m, 3H), 4.69 (d, J
) 4.24 Hz, 1H) [4.66] (d, J ) 9.3 Hz, 1H), 4.15[3.84] (q, J ) 6.8
Hz, 2H), 3.76[3.71] (s, 3H), 3.30[3.77] (dd, J ) 16.1, 9.0 Hz, 1H),
3.21[3.60] (dd, J ) 16.0, 5.2 Hz, 1H), 3.15-3.09 (ddd, J ) 9.0,
4.9, 4.8 Hz, 1H)[2.97] (dd, J ) 15.9, 8.0 Hz), [2.35]2.34 (s, 3H),
2.27[2.26] (s, 3H), 1.25[1.06] (t, J ) 6.2 Hz, 3H);13C NMR δ 174.8-
[172.3], 158.4[158.2], 142.6[142.3], [139.6]138.6, 138.1, 136.1-
[134.7], 135.3, 131.5 [130.0], 129.7, 128.7 [128.6], 124.2[124.1],
121.7[121.0], 113.8[113.3], 60.7[60.3], 55.1[55.0], 53.7[51.8], 53.4-
[50.2], [35.6]34.9, [21.5]21.4, 15.3[15.1], 14.3[14.0]; MS m/e 356
(M+, 100), 341 (75.18), 282 (92.58), 235 (89.01), 135 (77.94). Anal.
Calcd for C21H24O3S (356.49): C, 70.33; H, 6.79. Found: C, 70.16;
H, 6.56.
1
ketone 25a ) which was characterized by IR and H and 13C NMR
data and used as such for the next reaction.
2-Ca r b oet h oxy-1-(4-m et h oxyp h en yl)-7-(m et h ylt h io)in -
d a n e (29a ). The title compound was obtained as a yellow oil by
treatment of carbinol 27a (2.4 mmol) with BF3‚Et2O (0.65 mL,
5 mmol) in refluxing benzene (3 h) under reaction conditions B.
Yield 50% (0.51 g). Chromatography (1:19; ethyl acetate:hexane),
Rf ) 0.5 (13:87; ethyl acetate:hexane): IR (neat) 2927, 1732, 1691,
1
1513, 1249 cm-1; H NMR δ 7.24 (t, J ) 7.8 Hz, 1H), 7.07 (d, J
) 7.6 Hz, 1H), 7.03-7.0 (m, 3H), 6.81 (dd, J ) 8.6, 2.0 Hz, 2H),
4.75 (d, J ) 4.6 Hz, 1H), 4.16 (q, J ) 7.1 Hz, 2H), 3.77 (s, 3H),
3.32 (dd, J ) 16.4, 9.0 Hz, 1H), 3.26 (dd, J ) 16.4, 5.1 Hz, 1H),
3.14 (ddd, J ) 9.0, 4.6, 6.6 Hz, 1H), 2.29 (s, 3H), 1.26 (t, J ) 7.1
Hz, 3H); 13C δ NMR 174.7, 158.2, 142.3, 141.3, 135.8, 128.7,
128.3, 128.2, 123.2, 120.6, 113.8, 60.8, 55.2, 53.1, 53.4, 35.0, 15.3,
14.2; MS m/e 342 (M+, 100), 268 (90), 221 (81.5). Anal. Calcd for
Ack n ow led gm en t. Financial assistance from CSIR,
New Delhi, is acknowledged. H.J . and P.K.M. thank
CSIR, New Delhi, for an Emeritus Scientistship and a
Senior Research Fellowship, respectively.
C
20H22O3S (342.46): C, 70.15; H, 6.47. Found: C, 70.09; H, 6.28.
1-(4-Met h oxyp h en yl)-2-ca r b oet h oxy-5-m et h yl-7-m et h -
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectral data for compounds 6c-g, 8a , 15a , and 31. This
material is available free of charge via the Internet at
http://pubs.acs.org.
ylth ioin d a n e (30a ). The title compound 30a was obtained along
with 31 by treatment of the reaction mixture, resulting from
addition of methallylindium reagent 26b to 25a , with BF3‚Et2O
(0.65 mL, 5 mmol) in nitromethane (12 h) under reaction
conditions A. Yield 29% (0.31 g). Chromatography (1:19; ethyl
acetate:hexane), Rf ) 0.55 (13:87; ethyl acetate:hexane): IR
J O001488P