Preparation of vinylogous 2-sulfonylindolines by the palladium-catalyzed heteroannulation of o-iodoanilines with dienyl sulfones and their further transformation to indoles and carbazoles

Article abstract of DOI:10.1021/jo016080m

The palladium-catalyzed heteroannulation of o-iodoanilines with dienyl sulfones provides a convenient route to vinylogous 2-sulfonylindolines 3. The reaction proceeds in DMF/water in the presence of potassium carbonate and catalytic palladium(II) acetate and is compatible with both electron-donating and -withdrawing substituents in the para position of the aniline, and with an alkyl substituent at C-2 of the dienyl sulfone. The indolines underwent oxidation with DDQ to afford the corresponding indoles 4. The latter were then employed as dienes in Diels-Alder reactions with dimethyl acetylenedicarboxylate (DMAD), methyl propiolate, or methyl acrylate. In the case of the latter two dienophiles, the cycloadditions were highly regioselective, affording the corresponding 1,3-products (with respect to the relative positions of the sulfone and ester groups), exclusively. The cycloadducts from acetylenic dienophiles were converted to the corresponding carbazoles by elimination of the sulfone moiety with DBU, and that from methyl acrylate was subjected to reductive desulfonylation and oxidation to the corresponding carbazole with DDQ. The method thus provides access to carbazoles with various substituents at the 3-, 4-, and 6-positions.

Full text of DOI:10.1021/jo016080m

J . Org. Chem. 2001, 66, 8599-8605
8599
P r ep a r a tion of Vin ylogou s 2-Su lfon ylin d olin es by th e
P a lla d iu m -Ca ta lyzed Heter oa n n u la tion of o-Iod oa n ilin es w ith
Dien yl Su lfon es a n d Th eir F u r th er Tr a n sfor m a tion to In d oles a n d
Ca r ba zoles
Thomas G. Back,* Richard J . Bethell, Masood Parvez, and J erry A. Taylor
Department of Chemistry, University of Calgary, Calgary, Alberta, Canada T2N 1N4
tgback@ucalgary.ca
Received September 1, 2001
The palladium-catalyzed heteroannulation of o-iodoanilines with dienyl sulfones provides a
convenient route to vinylogous 2-sulfonylindolines 3. The reaction proceeds in DMF/water in the
presence of potassium carbonate and catalytic palladium(II) acetate and is compatible with both
electron-donating and -withdrawing substituents in the para position of the aniline, and with an
alkyl substituent at C-2 of the dienyl sulfone. The indolines underwent oxidation with DDQ to
afford the corresponding indoles 4. The latter were then employed as dienes in Diels-Alder reactions
with dimethyl acetylenedicarboxylate (DMAD), methyl propiolate, or methyl acrylate. In the case
of the latter two dienophiles, the cycloadditions were highly regioselective, affording the corre-
sponding 1,3-products (with respect to the relative positions of the sulfone and ester groups),
exclusively. The cycloadducts from acetylenic dienophiles were converted to the corresponding
carbazoles by elimination of the sulfone moiety with DBU, and that from methyl acrylate was
subjected to reductive desulfonylation and oxidation to the corresponding carbazole with DDQ.
The method thus provides access to carbazoles with various substituents at the 3-, 4-, and
6-positions.
The Heck reaction1 provides a versatile method for the
coupling of vinyl or aryl halides with alkenes to afford
conjugated products in the presence of catalytic amounts
of palladium(0) species.2 When dienes are employed in
place of alkenes, a π-allylpalladium intermediate is
formed that can undergo either elimination of the metal
or substitution by an appropriate nucleophile such as a
secondary amine (Scheme 1).1a,b Furthermore, in cases
where the amine (or other nucleophile) is tethered to the
aryl halide precursor, the possibility arises for heteroan-
nulations with acetylenes,3 dienes,4 allenes,5 and vinyl-
cyclopropanes and cyclobutanes6 to afford the correspond-
ing nitrogen heterocycles. Many types of unsaturated
substrates have been investigated in Heck reactions and
related palladium-catalyzed coupling reactions. However,
there are relatively few examples where unsaturated
sulfones7,8 have been employed in this context. In par-
ticular, it appears that the use of dienyl sulfones in
palladium-catalyzed heteroannulation reactions has not
yet been reported. Since the sulfone group is a useful
functionality that can be either exploited in further
transformations of the products7a or removed at the end
of a synthetic sequence by appropriate desulfonylation
methods,9 such processes are of potential value in the
synthesis of various types of heterocycles.
(3) Roesch, K. R.; Larock, R. C. Org. Lett. 1999, 1, 553. (b) Larock,
R. C.; Yum, E. K.; Refvik, M. D. J . Org. Chem. 1998, 63, 7652. (c)
Larock, R. C.; Yum, E. K. J . Am. Chem. Soc. 1991, 113, 6689. (d)
Roesch, K. R.; Larock, R. C. J . Org. Chem. 1998, 63, 5306. (e) Beydoun,
N.; Pfeffer, M. Synthesis 1990, 729. (f) Mukhopadhyay, R.; Kundu, N.
G. Synlett 2001, 1143. (g) Mahanty, J . S.; De, M.; Das, P.; Kundu, N.
G. Tetrahedron 1997, 53, 13397. (h) Kundu, N. G.; Khan, M. W.
Tetrahedron 2000, 56, 4777. (i) Bouyssi, D.; Cavicchioli, M.; Balme,
G. Synlett 1997, 944. (j) Chen, C.; Lieberman, D. R.; Larsen, R. D.;
Reamer, R. A.; Verhoeven, T. R.; Reider, P. J .; Cottrell, I. F.; Houghton,
P. G. Tetrahedron Lett. 1994, 35, 6981. (k) J eschke, T.; Wensbo, D.;
Annby, U.; Gronowitz, S.; Cohen, L. A. Tetrahedron Lett. 1993, 34,
6471. (l) Wensbo, D.; Eriksson, A.; J eschke, T.; Annby, U.; Gronowitz,
S.; Cohen, L. A. Tetrahedron Lett. 1993, 34, 2823.
(4) Larock, R. C.; Berrios-Pen˜a, N.; Narayanan, K. J . Org. Chem.
1990, 55, 3447. (b) Larock, R. C.; Guo, L. Synlett 1995, 465. (c) Larock,
R. C.; Berrios-Pen˜a, N. G.; Fried, C. A.; Yum, E. K.; Tu, C.; Leong, W.
J . Org. Chem. 1993, 58, 4509. (d) O’Connor, J . M.; Stallman, B. J .;
Clark, W. G.; Shu, A. Y. L.; Spada, R. E.; Stevenson, T. M.; Dieck, H.
A. J . Org. Chem. 1983, 48, 807.
* Tel: (403) 220-6256. Fax: (403) 289-9488.
(1) Heck, R. F. Acc. Chem. Res. 1979, 12, 146. (b) Heck, R. F. Org.
React. 1982, 27, 345. (c) Daves, G. D., J r.; Hallberg, A. Chem. Rev.
1989, 89, 1433. (d) de Meijere, A.; Meyer, F. E. Angew. Chem., Int.
Ed. Engl. 1994, 33, 2379. (e) Cabri, W.; Candiani, I. Acc. Chem. Res.
1995, 28, 2. (f) Shibasaki, M.; Boden, C. D. J .; Kojima, A. Tetrahedron
1997, 53, 7371. (g) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000,
100, 3009.
(2) For reviews of palladium-catalyzed coupling reactions, including
cyclizations, see: (a) Heck, R. F. Palladium Reagents in Organic
Synthesis; Academic Press: New York, 1985. (b) Trost, B. M.; Verho-
even, T. R. In Comprehensive Organometallic Chemistry; Wilkinson,
G., Ed.; Pergamon Press: Oxford, 1982; Volume 8, pp 799-938. (c)
Hegedus, L. S. Angew. Chem., Int. Ed. Engl. 1988, 27, 1113. (d)
Hegedus, L. S. In Organometallics in Synthesis; Schlosser, M., Ed.;
Wiley: Chichester, 1994; Chapter 5. (e) Tsuji, J . Palladium Reagents
and Catalysts; Wiley: Chichester, 1995. (f) Li, J . J .; Gribble, G. W.
Palladium in Heterocyclic Chemistry; Pergamon: New York, 2000. (g)
Negishi, E.; Cope´ret, C.; Ma, S.; Liou, S.-Y.; Liu, F. Chem. Rev. 1996,
96, 365.
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1991, 56, 2615.
(6) Larock, R. C.; Yum, E. K. Synlett 1990, 529.
(7) For
a general review of sulfones, see: (a) Simpkins, N. S.
Sulphones in Organic Synthesis; Pergamon Press: Oxford, 1993. (b)
For acetylenic and allenic sulfones, see: Back, T. G. Tetrahedron 2001,
57, 5263. (c) For vinyl sulfones, see: Simpkins, N. S. Tetrahedron 1990,
46, 6951. (d) For dienyl sulfones, see: Ba¨ckvall, J .-E.; Chinchilla, R.;
Na´jera, C.; Yus, M. Chem. Rev. 1998, 98, 2291.
10.1021/jo016080m CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/15/2001

8600 J . Org. Chem., Vol. 66, No. 25, 2001
Back et al.
Ta ble 1. Heter oa n n u la tion of o-Iod oa n ilin es 1 w ith
Dien yl Su lfon es 2
Sch em e 1
reaction
isolated
entry
R
R1
R2 R3 no. time (days) yield (%)a,b
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
Me
Me
Me
OMe
OMe
H
Cbz
Ts
H
H
H
H
H
Me
H
H
Me
H
H
H
H
H
3a
3b
3c
3d
5
5
5
5
6
16
8
12
19
12
11
31c
83
66
41
66
t-Boc
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Sch em e 2
Me 3e
H
H
Me 3h
H
H
3f
3g
81
53
3i
3j
10
11
12
78
25
73
H
H
Me 3k
3l
CO2Me Cbz
H
0.5
a
An excess of 2 was generally employed to compensate for its
b
competing partial polymerization. The yield is based on 1.
c Product 3a underwent rapid oxidation to 4a upon exposure to
air.
to Pd(0) did not improve the yields of the corresponding
indolines 3. Presumably, oxidation of a small amount of
the dienyl sulfone (or other component of the reaction
mixture) with Pd(II) in situ generates the required Pd(0)
catalyst. Since some polymerization of the dienyl sulfone
2 accompanied the cyclization, slightly better yields were
obtained when an excess of 2 was employed. The reac-
tions were conducted at room temperature because
heating resulted in more complex product mixtures and
lower yields of 3.
When o-iodoaniline, a primary amine, was used in the
heteroannulation, a relatively poor yield of the indoline
3a was obtained (Table 1, entry 1). Moreover, the product
was readily oxidized to the corresponding indole 4a upon
exposure to air (Scheme 3). Several N-protected o-
iodoanilines were then investigated, and the use of the
N-carbobenzyloxy (N-Cbz) derivative (entry 2) proved
more efficacious than the corresponding N-p-toluene-
sulfonyl (N-Ts) or N-tert-butoxycarbonyl (N-t-Boc) ana-
logues (entries 3 and 4, respectively). Thus, all further
experiments were conducted with N-Cbz-anilines. The
N-protected indolines 3b-d were stable toward aerial
oxidation.
We now report that the palladium-catalyzed reactions
of variously p-substituted o-iodoanilines 1 with dienyl
sulfones 2 afford vinylogous 2-sulfonylindolines 3.10 We
also report that the products 3 undergo facile oxidation
with DDQ to the corresponding indoles 4, which in turn
can be employed as dienes in highly regioselective Diels-
Alder cycloaddditions that lead, after desulfonylation, to
carbazoles containing substituents at the 3-, 4-, and/or
6-positions (Scheme 2). Indole and carbazole ring systems
comprise the core structures of numerous naturally
occurring alkaloids11 and synthetic analogues of medici-
nal importance. Thus, the development of new methods
for their synthesis is of current interest.
Resu lts a n d Discu ssion
The results of the heteroannulation of o-iodoanilines
1 with dienyl sulfones 2 to afford vinylogous sulfonylin-
dolines 3 is summarized in Table 1. In general, the
reactions were performed in aqueous DMF solution
containing potassium carbonate and 5-10 mol % of
palladium diacetate. The addition of triphenylphosphine
to the reaction mixture to reduce the palladium diacetate
In general, an additional methyl substituent in the
2-position of the dienyl sulfone 2 (R3 ) Me) resulted in
(11) For selected reviews of indole and carbazole alkaloids, see: (a)
Cordell, G. A. Introduction to Alkaloids; Wiley: New York, 1981;
Chapter 9. (b) Indole and Biogenetically Related Alkaloids; Phillipson,
J . D., Zenk, M. H., Eds.; Academic Press: London, 1980. (c) Marion,
L. In The Alkaloids; Manske, R. H. F., Holmes, H. L., Eds.; Academic
Press: New York, 1952; Vol. 2, Chapter 13. (d) Saxton, J . E. In The
Alkaloids; Manske, R. H. F., Ed.; Academic Press: New York, 1960;
Vol. 7, Chapter 10. (e) Saxton, J . E. In The Alkaloids; Manske, R. H.
F., Ed.; Academic Press: New York, 1968; Vol. 10, Chapter 10. (f) Kapil,
R. S. In The Alkaloids; Manske, R. H. F., Ed.; Academic Press: New
York, 1971; Vol. 13, Chapter 6. (g) Husson, H.-P. In The Alkaloids;
Brossi, A., Ed.; Academic Press: Orlando, 1985; Vol. 26, Chapter 1.
(h) Moody, C. J . Synlett 1994, 681. (i) Bhattacharyya, P.; Chakraborty,
D. P. In Progress in the Chemistry of Natural Products; Herz, W.,
Grisebach, H., Kirby, G. W., Tamm, C., Eds.; Springer-Verlag: Wien,
1987; Vol. 52, pp 159-209. (j) Chakraborty, D. P.; Roy, S. In Progress
in the Chemistry of Natural Products; Herz, W., Kirby, G. W., Steglich,
G. W., Tamm, C., Eds.; Springer-Verlag: Wien, 1991; Vol. 57, pp 71-
152.
(8) For examples of other types of Pd-catalyzed coupling reactions
of vinyl sulfones, see: (a) J in, Z.; Fuchs, P. L. Tetrahedron Lett. 1996,
37, 5253. (b) J in, Z.; Fuchs, P. L. Tetrahedron Lett. 1993, 34, 5205. (c)
Lee, S. W.; Fuchs, P. L. Tetrahedron Lett. 1993, 34, 5209. (d) Trost, B.
M.; Seoane, P.; Mignani, S.; Acemoglu, M. J . Am. Chem. Soc. 1989,
111, 7487. (e) Trost, B. M.; Grese, T. A.; Chan, D. M. T. J . Am. Chem.
Soc. 1991, 113, 7350. (f) Trost, B. M.; Grese, T. A. J . Am. Chem. Soc.
1991, 113, 7363. (g) Takayama, H.; Suzuki, T. J . Chem. Soc., Chem.
Commun. 1988, 1044. (h) Harrington, P. J .; DiFiore, K. A. Tetrahedron
Lett. 1987, 28, 495. (i) Berteina, S.; Wendeborn, S.; De Mesmaeker, A.
Synlett 1998, 1231. (j) Garrido, J . L.; Alonso, I.; Carretero, J . C. J .
Org. Chem. 1998, 63, 9406. (k) Monteiro, N.; Balme, G. J . Org. Chem.
2000, 65, 3223. (l) Marino, J . P.; Long, J . K. J . Am. Chem. Soc. 1988,
110, 7916.
(9) Na´jera, C.; Yus, M. Tetrahedron 1999, 55, 10547.
(10) Preliminary communication: Back, T. G.; Bethell, R. J . Tetra-
hedron Lett. 1998, 39, 5463.

Preparation of Vinylogous 2-Sulfonylindolines
J . Org. Chem., Vol. 66, No. 25, 2001 8601
Sch em e 3
Sch em e 4
lower yields of 3 compared to the corresponding unsub-
stituted dienyl sulfone (compare entries 2 vs 5, and 7 vs
8 and 10 vs 11). The presence of a 4-methyl substituent
(R2 ) Me) suppressed the reaction completely, and no
indoline product was obtained even after prolonged
reaction times (entries 6 and 9). When the unsubstituted
dienyl sulfone (2, R2, R3 ) H) was employed, the vinyl
sulfone moieties in the indoline products 3 were formed
as the trans-isomers, as evidenced by relatively large
coupling constants J trans of ca. 15 Hz. The absence of an
NOE between the vinyl methyl group and the olefinic
hydrogen atom in each of 3e, 3h , and 3k suggests the
E-configuration, where these two substituents are trans.
The heteroannulation reaction proved compatible with
both electron-donating and -withdrawing substituents in
the para position of the o-iodoaniline 1. Thus, comparable
yields of 3 were produced when the unsubstituted dienyl
sulfone was allowed to react with o-iodoanilines contain-
ing a methyl (entry 7), methoxy (entry 10), ester (entry
12), or no p-substituent (entry 2). However, we noted that
the electron-withdrawing ester group (entry 12) resulted
in the fastest reaction time.
The oxidation of indolines 3b, 3g, and 3l to indoles 4b,
4g, and 4l, respectively, was smoothly achieved with
DDQ12 in refluxing toluene (Scheme 3), regardless of the
nature of the substituent at the 6-position. Furthermore,
deprotection of 4b with anisole in the presence of a Lewis
acid13 provided a more efficient preparation of the free
indole 4a (Scheme 3) than the cyclization of unprotected
o-iodoaniline in entry 1 of Table 1, followed by aerial
oxidation of 3a . Attempted deprotection of 4b via hydro-
genolysis resulted in simultaneous hydrogenation of the
vinyl sulfone moiety.
p-toluenesulfinic acid occurred, resulting in aromatiza-
tion to afford carbazoles 5, 6, and 7, respectively, in good
to excellent yield.
The similar cycloaddition of indoles 4b, 4g, and 4l with
the unsymmetrical dienophile methyl propiolate, followed
by elimination with DBU, produced carbazoles 9, 10, and
11, respectively, as single regioisomers (Scheme 4).
Carbazole 9 was unequivocally identified as the indicated
regioisomer by hydrogenolysis of the Cbz protecting group
to afford 12. Since both 12, where the ester moiety
occupies the 4-position, and the corresponding 3-isomer
14 are known compounds,14 the structural assignment
of 12 and therefore also that of 9 were easily confirmed.
The structure of the 6-methyl derivative 10 could not be
obtained unequivocally by NMR spectroscopy because of
overlapping signals. However, an X-ray crystallographic
structure of 10 clearly indicated the same regiochemistry
as was observed in 9. Carbazole 11 was easily distin-
guished from its regioisomer 15 by NMR spectroscopy,
since the symmetrical structure of the latter would be
We then investigated the Diels-Alder cycloadditions
of the variously substituted indole derivatives with
representative dienophiles (Scheme 4). The symmetrical
dienophile dimethyl acetylenedicarboxylate (DMAD) re-
acted readily with 4b, 4g, and 4l in refluxing toluene.
The inclusion of a small amount of the radical inhibitor
2,6-di-tert-butyl-4-methylphenol (butylated hydroxytolu-
ene, BHT) improved the yields of the cycloaddition
products, presumably by suppressing competing polymer
formation. The initial cycloadducts 8 could not be isolated
in a pure state because of partial double bond isomer-
ization. However, when the crude product mixtures were
treated with DBU in dichloromethane, elimination of
1
expected to produce H and 13C NMR spectra consider-
ably simpler than those of the actual product 11. The
cycloaddition of the unprotected indole 4a with methyl
propiolate, followed by treatment with DBU, provided
carbazole 12, which was identical to the sample obtained
previously from the hydrogenolysis of 9, in 76% yield.
(12) Braude, E. A.; Brook, A. G.; Linstead, R. P. J . Chem. Soc. 1954,
3569.
(13) Tsuji, T.; Kataoka, T.; Yoshioka, M.; Sendo, Y.; Nishitani, Y.;
Hirai, S.; Maeda, T.; Nagata, W. Tetrahedron Lett. 1979, 2793.
(14) For 12, see: (a) Carter, P. H.; Plant, S. G. P.; Tomlinson, M. J .
Chem. Soc. 1957, 2210. For 14, see: (b) Li, W.-S.; McChesney, J . D.;
El-Feraly, F. S. Phytochemistry 1991, 30, 343.

8602 J . Org. Chem., Vol. 66, No. 25, 2001
Back et al.
Sch em e 5
We also investigated the Diels-Alder reaction of the
N-Cbz-protected indole 4b with methyl acrylate (Scheme
4). The cycloadduct 13 was obtained with high regiose-
lectivity but with undetermined stereochemistry. At-
tempts to eliminate p-toluenesulfinic acid cleanly from
13 with DBU and other bases failed. The mixture was
therefore subjected to reductive desulfonylation and
removal of the Cbz protecting group with magnesium in
refluxing methanol,15 followed by oxidation with DDQ,
to afford carbazole 12, again identical to the products
derived from 9 and 4a .
The regiochemistry of the above Diels-Alder reactions
deserves further comment. Frontier MO analyses have
been reported of interactions between variously substi-
tuted dienes and dienophiles containing an electron-
withdrawing group.16a In general, an electron-donating
group in the 1-position of the diene produces chiefly the
1,2-disubstituted cycloadduct (with respect to the diene
and dienophile substituents), whereas a similar substitu-
ent in the 2-position favors the 1,4-regioisomer. An
electron-withdrawing group at the 1- or 4-position of the
diene affords mainly the 1,2-isomer. In the present case,
the diene unit of the sulfonylindoles 4 can be considered
to possess donating groups at both the 1- and 2-positions
(D1 ) o-nitrogen-substituted aryl group; D2 ) nitrogen
substituent, respectively) and a withdrawing group at the
4-position (W1 ) sulfone moiety) (Scheme 5). Thus, the
nitrogen atom and sulfone group of 4 are expected to
direct the cycloaddition with an unsymmetrical dieno-
phile such as methyl propiolate to produce 16 preferen-
tially, whereas the aryl substituent, as well as any steric
interactions between the sulfone group and the dieno-
phile ester moiety, are expected to favor the formation
of 17 (Scheme 5). The exclusive formation of products
derived from 17 suggests that the latter effects are
dominant.16b
Other cycloaddition mechanisms were also considered.
A stepwise process involving diradical intermediates was
ruled out on the basis of the salutary effects of BHT, a
radical inhibitor, upon the yields of the cycloadducts.
Although a stepwise dipolar mechanism cannot be com-
pletely ruled out, the lack of observable effects upon the
reaction rate or regiochemistry of the cycloaddition
caused by the presence of electron-donating, -withdraw-
ing, or no substituents at C-6 of the indole moiety (i.e.,
compare 4b, 4g, and 4l in Scheme 4) suggests that
charged intermediates are not produced in the reaction.
It has also been established that dienyl sulfones are
capable of both normal and inverse electron demand in
Diels-Alder cycloadditions.7d,17 Although the reactions
of dienes 4 with electron-deficient dienophiles such as
methyl propiolate or methyl acrylate are expected to
proceed with normal electron demand, we nevertheless
tested the possibility of inverse demand by attempting
the reaction of 4b with an electron-rich dienophile. Thus,
when 4b was refluxed in neat n-butyl vinyl ether18 for
extended periods, no cycloadduct was obtained. The
preference of 4b for reactions with electron-deficient
dienophiles therefore indicates that 4b undergoes cy-
cloadditions via normal electron demand.
In conclusion, the palladium-catalyzed heteroannula-
tion of o-iodoanilines with dienyl sulfones provides a
convenient route to vinylogous 2-sulfonylindolines. The
method is compatible with both electron-donating and
-withdrawing substituents in the para position of the
aniline and with an alkyl substituent at C-2 of the dienyl
sulfone. The indolines are readily oxidized to indoles with
DDQ, which can then be employed in highly regioselec-
tive Diels-Alder reactions. The resulting cycloadducts
afford the corresponding carbazoles after elimination of
the sulfone moiety. Other synthetically useful transfor-
mations of sulfonylindoles 4 are under continued inves-
tigation.
Exp er im en ta l Section
1H and 13C NMR spectra were recorded in deuteriochloro-
form and are reported relative to residual chloroform or TMS
as the internal standard, unless otherwise indicated. Mass
spectra were obtained by EI at 70 eV. Chromatography refers
to flash chromatography on silica gel (230-400 mesh), unless
otherwise noted. The following materials were prepared by
literature procedures: (E)-1-(p-toluenesulfonyl)-1,3-butadi-
ene,19 2-methyl-1-(p-toluenesulfonyl)-1,3-butadiene,19 1-(p-tolu-
enesulfonyl)-1,3-pentadiene,19 N-(p-toluenesulfonyl)-2-iodo-
aniline,20 N-t-Boc-2-iodoaniline,21 2-iodo-4-toluidine,22 4-amino-
3-iodophenol,23 and methyl 4-amino-3-iodobenzoate.24
(17) The dual electron demand nature of 2-(phenylsulfonyl)-1,3-
dienes in Diels-Alder reactions has been studied extensively: (a)
Ba¨ckvall, J .-E.; J untunen, S. K. J . Am. Chem. Soc. 1987, 109, 6396.
1-(Arylsulfonyl)-1,3-dienes have also been reported to undergo cycload-
ditions with both electron-deficient and electron-rich dienophiles. (b)
For cycloaddition with methyl acrylate, see: Cuvigny, T.; Herve´ du
Penhoat, C.; J ulia, M. Tetrahedron 1986, 42, 5321. (c) For cycloaddition
with N-(1-cyclohexenyl)piperidine, see: Flitsch, W.; Lubisch, W.;
Rosche, J . Liebigs. Ann. Chem. 1987, 655.
(18) Cycloadditions of 2-(arylsulfonyl)-1,3-dienes with enol ethers
have been reported; see ref 17a and Ba¨ckvall, J .-E.; Rise, F. Tetrahe-
dron Lett. 1989, 30, 5347.
(19) Barluenga, J .; Martinez-Gallo, J . M.; Na´jera, C.; Fan˜ana´s, F.
J .; Yus, M. J . Chem. Soc., Perkin Trans. 1 1987 2605.
(15) Brown, A. C.; Carpino, L. A. J . Org. Chem. 1985, 50, 1749.
(16) Fleming, I. Frontier Orbitals and Organic Chemical Reactions;
Wiley: Chichester, 1976; Chapter 4. (b) Semiempirical MO calculations
(AM1) indicated that the diene HOMO of 4 (R ) H, R1 ) Ac) has a
larger coefficient at C-3 of the indole moiety than at the R-position of
the sulfone group. This leads to the expectation that 16 would be the
dominant regioisomer, in contrast to experimental results.
(20) Luo, F.-T.; Wang, R.-T. Heterocycles 1991, 32, 2365.
(21) Kelly, T. A.; McNeil, D. W. Tetrahedron Lett. 1994, 35, 9003.
(22) Kajigaeshi, S.; Kakinami, T.; Yamasaki, H.; Fujisaki, S.;
Okamoto, T. Bull. Chem. Soc. J pn. 1988, 61, 600.

Preparation of Vinylogous 2-Sulfonylindolines
J . Org. Chem., Vol. 66, No. 25, 2001 8603
N-Ca r b ob en zyloxy-2-iod oa n ilin e. 2-Iodoaniline was
treated with benzyl chloroformate under standard conditions25
to afford the corresponding Cbz derivative in 80% yield: mp
H), 6.87 (s, 1 H), 6.70 (d, J ) 15.4 Hz, 1 H), 2.44 (s, 3 H); 13C
NMR (100 MHz) δ 144.4, 138.1, 137.9, 132.1, 131.1, 130.1,
128.2, 127.6, 125.3, 124.4, 121.8, 120.9, 111.4, 110.6, 21.6; MS
m/z (%) 297 (M+, 1), 232 (100), 218 (65), 140 (89); HRMS calcd
for C17H15NO2S 297.0824, found 297.0849.
1
60.5-62 °C; IR (film) 1740, 1206 cm-1; H NMR (200 MHz) δ
8.07 (d, J ) 8.2 Hz, 1 H), 7.76 (d, J ) 8.0 Hz, 1 H), 7.42-7.25
(m, 6 H), 7.04 (broad s, 1 H), 6.80 (t, J ) 7.4 Hz, 1 H), 5.22 (s,
2 H); MS m/z (%) 353 (M+, 16), 245 (94), 91 (88), 90 (100). Anal.
Calcd for C14H12INO2: C, 47.61; H, 3.43; N, 3.97. Found: C,
47.73; H, 3.32; N, 3.95.
N-Car boben zyloxy-2-[(E)-2-(p-tolu en esu lfon yl)eth en yl]-
in d olin e (3b). Typ ica l P r oced u r e (Ta ble 1, en tr y 2).
N-Cbz-2-iodoaniline (182 mg, 0.516 mmol), (E)-1-(p-toluene-
sulfonyl)-1,3-butadiene (214 mg, 1.03 mmol), K2CO3 (71 mg,
0.51 mmol), and 10 mol % of Pd(OAc)2 were added to DMF-
H2O (6 mL, 10:1). The reaction mixture was stirred at room
temperature under argon for 5 days. Chloroform (10 mL) was
added, and the reaction mixture was filtered and concentrated
in vacuo. The crude material was purified by chromatography
(hexanes-ethyl acetate, 2:1), to afford 3b (183 mg, 83%, based
on N-Cbz-2-iodoaniline) as a white crystalline solid: mp
145.5-146.5 °C (from dichloromethane-hexanes); IR (film)
1711, 1317, 1145 cm-1; 1H NMR (200 MHz) δ 7.69 (d, J ) 8.4
Hz, superimposed on m, 3 H), 7.32-7.16 (m, 9 H), 7.12-6.85
(m, 2 H), 6.37 (d, J ) 15.2 Hz, 1 H), 5.23-4.90 (m, 3 H), 3.50
(dd, J ) 16.1, 10.5 Hz, 1 H), 2,88 (dd, J ) 16.4, 2.9 Hz, 1 H),
2.42 (s, 3 H); MS m/z (%) 433 (M+, 11), 389 (16), 208 (33), 91
(100). Anal. Calcd for C25H23NO4S: C, 69.26; H, 5.30; N, 3.20.
Found: C, 68.81; H, 4.93; N, 3.24.
N-Ca r boben zyloxy-2-iod o-4-tolu id in e. 2-Iodo-4-toluidine
was treated with benzyl chloroformate under standard condi-
tions25 to afford the corresponding Cbz derivative in 96%
yield: mp 65.5-66 °C; IR (film) 1736, 1690, 1217, 1200 cm-1
;
1H NMR (200 MHz) δ 7.89 (d, J ) 8.2 Hz, 1 H), 7.60 (d, J )
1.9 Hz, 1 H), 7.44-7.33 (m, 5 H), 7.13 (d, J ) 8.5 Hz, 1 H),
6.93 (broad s, 1 H), 5.23 (s, 2 H), 2.26 (s, 3 H); MS m/z (%) 367
(M+, 25), 259 (87), 91 (91), 77 (100). Anal. Calcd for C15H14
-
INO2: C, 49.07; H, 3.84; N, 3.82. Found: C, 48.73; H, 3.48; N,
3.73.
N-Ca r boben zyloxy-4-m eth oxy-2-iod oa n ilin e. 4-Amino-
3-iodophenol was treated with benzyl chloroformate under
standard conditions25 to afford the corresponding Cbz deriva-
tive in 93% yield: mp 143-144 °C; IR (film) 3350, 1698, 1233,
1207 cm-1; 1H NMR (DMSO-d6, 200 MHz) δ 9.76 (s, 1 H), 8.86
(broad s, 1 H), 7.38-7.30 (m, 5 H), 7.24 (d, J ) 2.6 Hz, 1 H),
7.1 (d, J ) 8.8 Hz, 1 H), 6.77 (dd, J ) 8.5, 2.7 Hz, 1 H), 5.01
(s, 2 H); MS m/z (%) 369 (M+, 5), 260 (44), 91 (100). Anal. Calcd
for C14H12INO3: C, 45.55; H, 3.28; N, 3.80. Found: C, 45.51;
H, 3.05; N, 3.69.
The above product (1.5 g, 4.0 mmol) and KOH (283 mg, 5.05
mmol) were dissolved in anhydrous DMSO (50 mL). Dimethyl
sulfate (0.42 mL 4.0 mmol) was added, and the solution was
stirred for 24 h. Ether (100 mL) was then added, followed by
a small amount of chloroform to form a homogeneous mixture.
The mixture was washed with saturated NaCl solution, dried
(MgSO4), and evaporated. Chromatography of the crude
product (hexanes-ethyl acetate, 2:1) afforded N-Cbz-4-meth-
oxy-2-iodoaniline (675 mg, 43%): mp 95-98 °C; IR (film) 1706,
1694, 1283, 1257, 1237, 1220 cm-1; 1H NMR (200 MHz) δ 7.82
(d, J ) 10.1 Hz, 1 H), 7.43-7.29 (m, 6 H), 6.90 (dd, J ) 9.1,
2.7 Hz, 1 H), 6.74 (broad s, 1 H), 5.21 (s, 2 H), 3.77 (s, 3 H);
MS m/z (%) 383 (M+, 71), 275 (100), 260 (86). Anal. Calcd for
The other products in Table 1 were prepared similarly. The
properties of the products 3c-l are given below.
N-(p-Tolu en esu lfon yl)-2-[(E)-(2-p-tolu en esu lfon yl)eth en -
yl]in d olin e (3c) (Ta ble 1, en tr y 3). Mp 158-159 °C (from
dichloromethane-hexanes); IR (film) 1596, 1349, 1314, 1163,
1
1136 cm-1; H NMR (200 MHz) δ 7.76 (d, J ) 8.4 Hz, 2 H),
7.64 (d, J ) 8.0 Hz, 1 H), 7.50 (d, J ) 8.4 Hz, 2 H), 7.37-7.15
(m, 6 H), 7.05 (m, 1 H), 6.95 (dd, J ) 14.8, 5.1 Hz, 1 H), 6.68
(dd, J ) 14.9, 1.3, 1 H), 4.93-4.87 (m, 1 H), 3.00 (dd, J ) 15.7,
10.1 Hz, 1 H), 2.70 (dd, J ) 16.5, 3.0 Hz, 1 H), 2.45 (s, 3 H),
2.36 (s, 3 H); MS m/z (%) 453 (M+, 70), 299 (87), 154 (99), 76.4
(100). Anal. Calcd for C24H23NO4S2: C, 63.55; H, 5.11; N, 3.09.
Found: C, 63.55; H, 5.11; N, 3.05.
N-(ter t-Bu tyloxyca r bon yl)-2-[(E)-(2-p-tolu en esu lfon yl)-
eth en yl]in d olin e (3d ) (Ta ble 1, en tr y 4). White solid foam;
IR (film) 1702, 1601, 1384, 1316, 1141 cm-1 1H NMR (200
;
MHz) δ 7.74 (d, J ) 8.4 Hz, superimposed on m,3 H), 7.32 (d,
J ) 8.4 Hz, 2 H), 7.20 (d, J ) 7.4 Hz, 1 H), 7.12 (d, J ) 8.4 Hz,
1 H), 7.00-6.82 (m, 2 H), 6.37 (d, J ) 14.9 Hz, 1 H), 5.1-4.9
(m, 1 H), 3.47 (dd, J ) 16.2, 10.6 Hz, 1 H), 2.86 (dd, J ) 16.4,
3.1 Hz, 1 H), 2.42 (s, 3 H), 1.35 (s, 9 H); 13C NMR (100 MHz)
δ 151.7, 144.5, 143.7, 137.3, 131.0, 130.0, 129.9, 127.9, 127.8,
124.9, 123.0, 115.1, 58.7, 33.8, 29.7, 28.0, 21.6; MS m/z (%)
399 (M+, 2), 343 (22), 142 (100); HRMS calcd for C22H25NO4S
399.1504, found 399.1515.
C
15H14INO3: C, 47.02; H, 3.68; N, 3.66. Found: C, 46.60; H,
3.22; N, 3.63.
Met h yl N-Ca r b ob en zyloxy-4-a m in o-3-iod ob en zoa t e.
Methyl 4-amino-3-iodobenzoate was treated with benzyl chlo-
roformate under standard conditions25 to afford the corre-
sponding Cbz derivative in 70% yield: mp 99-102 °C; IR (film)
1742, 1720, 1203 cm-1 1H NMR (200 MHz) δ 8.43 (dd, J )
;
N-Ca r b ob en zyloxy-2-[(E)-1-m et h yl-2-(p -t olu en esu lfo-
n yl)eth en yl]in d olin e (3e) (Ta ble 1, en tr y 5). Mp 126-127
°C; IR (film): 1711, 1316, 1147; 1H NMR (200 MHz) δ 7.69 (d,
J ) 8.4 Hz, superimposed on m, 3 H), 7.36-6.94 (m, 10 H),
6.26 (s, 1 H), 5.20 (d, J ) 11.8 Hz, 1 H), 5.17-4.87 (m, 1 H),
4.84 (dd, J ) 10.3, 3.9 Hz,1 H), 3.51 (dd, J ) 16.5, 10.9 Hz, 1
H), 2.84 (dd, J ) 16.6, 4.0 Hz, 1 H), 2.41 (s, 3 H), 2.07 (d, J )
1.2 Hz, 3 H); MS m/z (%) 447 (M+, 21), 403 (29), 208 (71), 91
(100). Anal. Calcd for C26H25NO4S: C, 69.78; H, 5.63; N, 3.13.
Found: C, 69.72; H, 5.77; N, 3.17.
2.0, 0.4 Hz, 1 H), 8.23 (d, J ) 8.6 Hz, 1 H), 8.00 (dd, J ) 8.8,
2.0 Hz, 1 H), 7.42-7.38 (m, 5 H), 7.26 (s, 1 H), 5.24 (s, 2 H),
3.90 (s, 3 H); MS m/z (%) 411 (M+, 15), 303 (100), 272 (99), 91
(89). Anal. Calcd for C16H14INO4: C, 46.74; H, 3.43; N, 3.41.
Found: C, 46.62; H, 3.38; N, 3.33.
2-[(E)-2-(p-Tolu en esu lfon yl)eth en yl]in dolin e (3a) (Table
1, en tr y 1) a n d 2-[(E)-2-(p-Tolu en esu lfon yl)eth en yl]in -
d ole (4a ). o-Iodoaniline (250 mg, 1.14 mmol), (E)-1-(p-tolu-
enesulfonyl)-1,3-butadiene (237 mg, 1.14 mmol), K2CO3 (157
mg, 1.14 mmol), and 10 mol % of Pd(OAc)2 were dissolved in
DMF-H2O (5 mL, 10:1). The reaction mixture was stirred at
room temperature under argon for 5 days. Chloroform (5 mL)
was added, the mixture was filtered through Celite, the filtrate
was concentrated in vacuo, and the residue was purified by
chromatography (elution with ethyl acetate-hexanes, 2:1) to
afford indoline 3a (105 mg, 31%) as a dark oil. Indoline 3a
was readily oxidized upon exposure to air while stirring for 1
h in chloroform to give indole 4a (100 mg, 95%) as a dark
N-Ca r b ob en zyloxy-6-m et h yl-2-[(E)-(2-p -t olu en esu lfo-
n yl)eth en yl]in d olin e (3g) (Ta ble 1, en tr y 7). Mp 139.5-
140.5 °C (from dichloromethane-hexanes); IR (film) 1710,
1
1318, 1146 cm-1; H NMR (200 MHz) δ 7.69 (d, J ) 8.2 Hz,
superimposed on m, 3 H), 7.36-7.25 (m, 7 H), 7.05-6.85 (m,
3 H), 6.35 (d, J ) 15.6 Hz, 1 H) 5.25-4.9 (m, 3 H), 3.45 (dd, J
) 16.7, 10.4 Hz, 1 H), 2.83 (dd, J ) 16.4, 3.1 Hz, 1 H), 2.42 (s,
3 H), 2.29 (s, 3 H);13C NMR (50 MHz) δ 152.3, 144.4, 143.4,
138.7, 137.0, 135.6, 133.1, 131.0, 129.8, 128.5, 128.4. 128.2,
128.0, 127.6, 127.3, 125.6, 115.0, 67.5, 58.7, 34.0, 21.6, 20.8;
MS m/z (%) 447 (M+, 23), 403 (61), 91 (100); HRMS calcd for
solid: IR (film) 3351, 1606, 1301, 1137 cm-1 1H NMR (200
;
MHz) δ 8.5 (s, 1 H), 7.83 (d, J ) 8.4 Hz, 2 H), 7.69 (d, J ) 15.4
Hz, 1 H), 7.62 (m, 1 H), 7.36-7.30 (m, 3 H), 7.23-7.08 (m, 1
C
26H25NO4S 447.1504, found 447.1489.
N-Ca r boben zyloxy-6-m eth yl-2-[(E)-1-m eth yl-2-(p-tolu -
(23) Kvalnes, D. E. J . Am. Chem. Soc. 1934, 56, 667.
(24) Hill, M. L.; Raphael, R. A. Tetrahedron Lett. 1986, 27, 1293.
(25) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3rd ed.; Wiley: New York, 1999; pp 531-535.
en esu lfon yl)eth en yl]in d olin e (3h ) (Ta ble 1, en tr y 8). Oil;
IR (film) 1710, 1635, 1313, 1302, 1147 cm-1 1H NMR (200
MHz) δ 7.81 (d, J ) 8.4 Hz, superimposed on m, 3 H),
;

8604 J . Org. Chem., Vol. 66, No. 25, 2001
Back et al.
7.42-7.13 (m, 7 H), 6.97 (d, J ) 9.1 Hz, 1 H), 6.92 (s, 1 H),
6.25 (s, 1 H), 5.21-5.13 (m, 1 H), 5.05-4.86 (m, 1 H), 4.81
(dd, J ) 10.8, 3.6 Hz, 1 H), 3.47 (dd, J ) 16.6, 11.1 Hz, 1 H),
2.80 (dd, J ) 16.6, 3.8 Hz, 1 H), 2.40 (s, 3 H), 2.28 (s, 3 H),
2.05 (d, J ) 1.2 Hz, 3 H); 13C (100 MHz) δ 154.8, 144.0, 139.1,
135.7, 133.1, 130.4, 129.8, 129.7, 128.6, 128.5, 128.2, 127.8,
127.2, 127.0, 125.7, 125.4, 114.7, 67.4, 64.6, 34.2, 21.5, 20.8,
13.7; MS m/z (%) 461 (M+, 45), 434 (59), 418 (79), 91 (100);
HRMS calcd for C27H27NO4S 461.1661, found 461.1671
N-Ca r boben zyloxy-6-m eth oxy-2-[(E)-(2-p-tolu en esu lfo-
n yl)eth en yl]in d olin e (3j) (Ta ble 1, en tr y 10). Mp 141-
142.5 °C; IR (film) 1706, 1320, 1145 cm-1; 1H NMR (200 MHz)
δ 7.69 (d, J ) 8.0 Hz, superimposed on m, 3 H), 7.31-7.17 (m,
7 H), 6.90 (dd, J ) 14.9, 6.5 Hz, 1 H), 6.71 (s, superimposed
on m, 2 H), 6.35 (d, J ) 15.4 Hz, 1 H), 5.19-4.92 (m, 3 H),
3.77 (s, 3 H), 3.48 (dd, J ) 16.2, 10.3 Hz, 1 H), 2.84 (dd, J )
16.5, 2.7 Hz, 1 H), 2.42 (s, H); 13C NMR (50 MHz) δ 156.3,
152.4, 144.4, 143.3, 137.0, 135.7, 131.1, 129.9, 128.8, 128.5,
128.3, 128.2, 127.9, 127.7, 115.9, 112.8, 111.2, 67.5, 58.9, 55.7,
34.2, 21.6; MS m/z (%) 463 (M+, 5), 419 (6), 328 (8), 91 (100);
HRMS calcd for C26H25NO5S 463.1453, found 463.1489.
N-Ca r boben zyloxy-6-m eth oxy-2-[(E)-(1-m eth yl-2-p-tol-
u en esu lfon yl)eth en yl]in d olin e (3k ) (Ta ble 1, en tr y 11).
a
white crystalline solid: mp 180-182 °C (from dichlo-
romethane-hexanes); IR (film) 1705, 1609, 1314, 1287, 1149
cm-1; 1H NMR (200 MHz) δ 8.34-8.14 (m, 3 H), 8.01 (dd, J )
9.0, 1.6 Hz, 1 H), 7.75 (d, J ) 8.4 Hz, 2 H), 7.55-7.42 (m, 5
H), 7.32 (d, J ) 8.5 Hz, 2 H), 6.97 (s, 1 H), 6.82 (d, J ) 15.2
Hz, 1 H), 5.53 (s, 2 H), 3.93 (s, 3 H), 2.44 (s, 3 H); MS m/z (%)
489 (M+, 1), 445 (6), 199 (61), 91 (100). Anal. Calcd for C27H23
-
NO6S: C, 66.24; H, 4.74; N, 2.86. Found: C, 66.23; H, 4.39;
N, 2.93.
Alter n a tive P r ep a r a tion of 4a . Indole 4b (45 mg, 0.10
mmol) was dissolved in dichloromethane (5 mL) and cooled to
0 °C. AlCl3 (41 mg, 0.31 mmol) and anisole (0.07 mL, 0.6 mmol)
were added. The reaction mixture was stirred for 2 h and was
then washed with aqueous NH4OH, dried with MgSO4, filtered,
and concentrated in vacuo. The crude material was purified
by chromatography (hexanes-ethyl acetate, 10:1) to afford a
dark solid (21 mg, 68%) with a 1H NMR spectrum and TLC
that were identical to those of 4a obtained by the oxidation of
indoline 3a (vide supra).
Dim eth yl N-Car boben zyloxy-car bazole-3,4-dicar boxyl-
a te (5). Indole 4b (125 mg, 0.290 mmol), DMAD (0.36 mL,
2.9 mmol), and BHT (10 mg) were refluxed in toluene (5 mL)
under an argon atmosphere for 18 h. The reaction mixture was
concentrated in vacuo, and the residue was dissolved in 5 mL
of dichloromethane. DBU (0.04 mL, 0.3 mmol) was added to
the reaction mixture dropwise over 5 min. The reaction
mixture was stirred for 2 h, concentrated in vacuo, and
separated by chromatography (elution with hexanes-ethyl
acetate, 5:1) to afford carbazole 5 (97 mg, 81%, based on 4b)
as a white crystalline solid: mp 215-216 °C (from dichlo-
Oil; IR (film) 1708, 1315, 1146 cm-1 1H NMR (200 MHz) δ
;
7.70 (d, J ) 8.4 Hz, superimposed on m, 3 H), 7.36-7.20 (m,
7 H), 6.68 (s superimposed on m, 2 H), 6.27 (s, 1 H), 5.24-
4.79 (m, 3 H), 3.77 (s, 3 H), 3.49 (dd, J ) 16.8, 10.9 Hz, 1 H),
2.81 (dd, J ) 16.8, 3.8 Hz, 1 H), 2.42 (s, 3 H), 2.07 (d, J ) 1.2
Hz, 3 H); 13C NMR (50 MHz) δ 156.2, 154.6, 144.0, 139.0, 135.7,
129.7, 129.6, 128.6, 128.4, 128.3, 128.2, 127.8, 127.0, 125.8,
115.6, 112.7, 111.1, 67.3, 64.7, 55.7, 34.2, 21.6, 13.7; MS m/z
(%) 477 (M+, 39), 433 (22), 342 (63), 91 (100); HRMS calcd for
romethane-hexanes); IR (film) 1733, 1266, 1150 cm-1 1H
;
NMR (200 MHz) δ 8.46 (d, J ) 8.9 Hz, 1 H), 8.33 (d, J ) 8.0
Hz, 1 H), 8.15 (d, J ) 8.9 Hz, 1 H), 7.83 (d, J ) 8.7 Hz, 1 H),
7.56-7.38 (m, 7 H), 5.60 (s, 2 H), 4.15 (s, 3 H), 3.96 (s, 3 H);
MS m/z (%) 417 (M+, 1), 373 (60), 164 (43), 91 (100). Anal.
Calcd for C24H19NO6: C, 69.06; H, 4.59; N, 3.36. Found: C,
68.81; H, 4.53; N, 3.39.
C
27H27NO5S 477.1610, found 477.1594.
Meth yl N-Car boben zyloxy-2-[(E)-(2-p-tolu en esu lfon yl)-
eth en yl]in d olin e-6-ca r boxyla te (3l) (Ta ble 1, en tr y 12).
Mp 189-190 °C (from dichloromethane-hexanes); IR (film)
1711, 1609, 1323, 1145 cm-1; 1H NMR (200 MHz) δ 7.92 (d, J
) 9.1 Hz, 1 H), 7.82 (s, 1 H), 7.68 (d, J ) 8.2 Hz, 2 H), 7.36-
7.24 (m, 8 H), 6.90 (dd, J ) 14.9, 6.6 Hz, 1 H), 6.36 (d, J )
14.9 Hz, 1 H), 5.25-5.01 (m, 3 H), 3.89 (s, 3 H), 3.51 (dd, J )
16.2, 10.8 Hz, 1 H), 2.92 (dd, J ) 16.7, 3.0 Hz, 1 H), 2.43 (s, 3
H); MS m/z (%) 491 (M+, 2), 447 (19), 91 (100). Anal. Calcd for
Dim et h yl N-Ca r b oben zyloxy-6-m et h ylca r b a zole-3,4-
d ica r boxyla te (6). Indole 4g (137 mg, 0.308 mmol), DMAD
(0.38 mL, 3.1 mmol), and BHT (7 mg) were refluxed in toluene
(5 mL) under an argon atmosphere for 18 h. The product was
treated with DBU and worked up as in the preparation of 5
to afford carbazole 6 (92 mg, 69%, based on 4g) as a white
crystalline solid: mp 112-112.5 °C (from dichloromethane-
hexanes); IR (film) 1732, 1712 1306, 1248, 1151 cm-1; 1H NMR
(200 MHz) δ 8.43 (d, J ) 8.9 Hz 1 H), 8.18 (d, J ) 8.7 Hz, 1
H), 8.13 (d, J ) 8.9 Hz, 1 H), 7.65-7.28 (m, 7 H), 5.58 (s, 2 H),
4.15 (s, 3 H), 3.96 (s, 3 H), 2.49 (s, 3 H); MS m/z (%) 431 (M+,
1), 387 (64), 178 (74), 91 (100). Anal. Calcd for C25H21NO6: C,
69.60; H, 4.91; N, 3.25. Found: C, 69.34; H, 5.04; N, 3.21.
Tr im eth yl N-Ca r boben zyloxy-ca r ba zole-3,4,6-tr ica r -
boxyla te (7). Indole 4l (114 mg, 0.233 mmol), DMAD (0.29
mL, 2.3 mmol), and BHT (5 mg) were refluxed in toluene (5
mL) under an argon atmosphere for 18 h. The product was
treated with DBU and worked up as in the preparation of 5
to afford carbazole 7 (67 mg, 61%, based on 4l) as a white
crystalline solid: mp 165-167 °C (from dichloromethane-
hexanes); IR (film) 2946, 1717, 1263, 1147 cm-1; 1H NMR (400
MHz) 8.51 (d, J ) 1.3 Hz, 1 H), 8.44 (d, J ) 8.9 Hz, 1 H), 8.36
(d, J ) 8.9 Hz, 1 H), 8.20 (dd, J ) 8.9, 1.7 Hz, 1 H), 8.17 (d, J
) 8.9 Hz, 1 H), 7.55 (dd, 8.0, 1.8 Hz, 1 H), 7.50-7.41 (m, 4 H),
5.61 (s, 2 H), 4.20 (s, 3 H), 3.97 (s, 3 H), 3.96 (s, 3 H); 13C NMR
(100 MHz) δ 168.9, 166.6, 165.8, 151.6, 141.7, 141.6, 134.3,
129.7, 129.6, 129.4, 129.2, 129.0, 128.9, 126.0, 123.5, 123.1,
122.6, 122.2, 116.9, 116.1, 69.8, 53.1, 52.6, 52.3; MS m/z (%)
475 (M+, <1), (431 (28), 310 (33), 91 (100); HRMS calcd for
C
27H25NO6S: C, 65.97; H, 5.13; N, 2.85. Found: C, 66.15; H,
5.14; N, 2.86.
N-Car boben zyloxy-2-[(E)-(2-p-tolu en esu lfon yl)eth en yl]-
in d ole (4b). Indoline 3b (590 mg, 1.36 mmol) and DDQ (618
mg, 2.72 mmol) were refluxed 18 h in toluene (25 mL) under
an argon atmosphere. The reaction mixture was concentrated
in vacuo, and the residue was separated by chromatography
(elution with hexanes-ethyl acetate-chloroform, 4:2:1) to yield
indole 4b (486 mg, 83%) as a white crystalline solid: mp 186-
187 °C (from dichloromethane-hexanes); IR (film) 1726, 1314,
1
1141 cm-1; H NMR (200 MHz) δ 8.31 (d, J ) 15.9 Hz, 1 H),
8.12 (d, J ) 8.4 Hz, 1 H), 7.75 (d, J ) 8.4 Hz, 2 H), 7.59-7.20
(m, 10 H), 6.95 (s, 1 H), 6.79 (d, J ) 15.4 Hz, 1 H), 5.51 (s, 2
H), 2.42 (s, 3 H); MS m/z (%) 431 (M+, 7), 387 (16), 232 (76),
141 (86), 91 (100). Anal. Calcd for C25H21NO4S: C, 69.59; H,
4.91; N, 3.25. Found: C, 69.67; H, 5.22; N, 3.35.
N-Ca r boben zyloxy-6-m eth yl-2-[(E)-(2-p-tolu en esu lfon -
yl)eth en yl]in d ole (4g). Indoline 3g (110 mg, 0.246 mmol) was
treated with DDQ (111 mg, 0.489 mmol) as in the preparation
of 4b to afford indole 4g (88 mg, 81%) as a white crystalline
solid: mp 163-164.5 °C (from dichloromethane-hexanes); IR
(film) 1726, 1602, 1314, 1135 cm-1; 1H NMR (200 MHz) δ 8.32
(d, J ) 15.2 Hz, 1 H), 7.99 (d, J ) 8.5 Hz, 1 H), 7.75 (d, J )
8.4 Hz, 2 H), 7.54-7.43 (m, 5 H), 7.32 (d, J ) 8.5 Hz, 2 H),
7.30 (s, 1 H), 7.15 (d, J ) 8.9 Hz, 1 H), 6.87 (s, 1 H), 6.77 (d,
J ) 15.2 Hz, 1 H), 5.50 (s, 2 H), 2.44 (s, 3 H), 2.40 (s, 3 H); MS
m/z (%) 445 (M+,1), 290 (69), 246 (68), 154 (100), 91 (89). Anal.
Calcd for C26H23NO4S: C, 70.09; H, 5.20; N, 3.14. Found: C,
69.97; H, 5.13; N, 3.20.
C
26H21NO8 475.1267, found 475.1245.
Meth yl N-Car boben zyloxy-car bazole-4-car boxylate (9).
Indole 4b (90 mg, 0.21 mmol), methyl propiolate (0.19 mL, 2.1
mmol), and BHT (5 mg) were refluxed in toluene (5 mL) under
an argon atmosphere for 18 h. The reaction mixture was
concentrated in vacuo, and the residue was dissolved in 5 mL
of dichloromethane. DBU (0.04 mL, 0.29 mmol) was added to
the reaction mixture dropwise over 5 min. The reaction
mixture was stirred for 2 h, concentrated in vacuo, and
Meth yl N-Car boben zyloxy-2-[(E)-(2-p-tolu en esu lfon yl)-
eth en yl]in d ole-6-ca r boxyla te (4l). Indoline 3l (120 mg,
0.244 mmol) was treated with DDQ (110 mg, 0.485 mmol) as
in the preparation of 4b to afford indole 4l (101 mg, 85%) as

Preparation of Vinylogous 2-Sulfonylindolines
J . Org. Chem., Vol. 66, No. 25, 2001 8605
separated by chromatography (elution with hexanes-ethyl
acetate, 5:1) to afford carbazole 9 (57 mg, 76%, based on 4b)
as a white crystalline solid: mp 123.5-125 °C (from dichlo-
125.7, 125.3, 124.8, 122.7, 121.9, 119.8, 114.9, 110.3, 52.1; MS
m/z (%) 225 (M+, 10), 194 (91), 166 (82), 89 (100); HRMS calcd
for C14H11NO2 225.0790, found 225.0790.
romethane-hexanes); IR (film) 1717, 1321, 1142 cm-1
;
1H
Alternatively, indole 4a (90 mg, 0.30 mmol), methyl propi-
olate (0.27 mL, 3.0 mmol), and BHT (4 mg) were refluxed in
toluene (5 mL) under an argon atmosphere for 18 h. The
reaction mixture was concentrated in vacuo, and the residue
was dissolved in 5 mL of dichloromethane. DBU (0.04 mL, 0.30
mmol) was added to the reaction mixture dropwise over 5 min.
The reaction mixture was stirred for 2 h, concentrated in
vacuo, and separated by chromatography (elution with hex-
anes-ethyl acetate, 5:1) to afford carbazole 12 (51 mg, 76%),
identical (1H NMR, TLC) to the sample prepared above.
Meth yl N-Car boben zyloxy-2-(p-tolu en esu lfon yl)-1,2,3,4-
tetr a h yd r oca r ba zole-4-ca r boxyla te (13). Indole 4b (212
mg, 0.492 mmol), methyl acrylate (0.48 mL, 5.3 mmol), and
BHT (11 mg) were refluxed in toluene (10 mL) under an argon
atmosphere for 18 h. The reaction mixture was concentrated
in vacuo and separated by chromatography (elution with
hexanes-ethyl acetate, 5:1) to afford 13 (192 mg, 76%, based
on 4b) as a white crystalline solid: mp 216-216.5 °C (from
dichloromethane-hexanes); IR (film) 1726, 1712, 1307, 1136
cm-1; 1H NMR (400 MHz) 8.12 (d, J ) 8.5 Hz, 1 H), 7.70 (d, J
) 8.2 Hz, 2 H), 7.51-7.32 (m, 5 H), 7.30 (d, J ) 8.1 Hz, 2 H),
7.28-7.20 (m, 3 H), 5.44 (s, 2 H), 3.80-3.90 (m, 1 H), 3.76 (s,
3 H), 3.51 (dd, J ) 17.2, 4.6 Hz, 1 H), 3.30-3.40 (m, 1 H), 3.15
(m, 1 H), 2.77 (dd, J ) 12.4, 5.7 Hz, 1 H), 2.47 (s, 3 H), 2.03 (q,
J ) 12.3 Hz, 1 H); MS m/z (%) 517 (M+, 1), 488 (1), 168 (28),
91 (100). Anal. Calcd for C29H27NO6S C, 67.30; H, 5.26; N, 2.71.
Found C, 66.90; H, 5.04; N, 2.71.
NMR (400 MHz) δ 8.68 (d, J ) 8.9 Hz, 1 H), 8.63 (d, J ) 8.4
Hz, 1 H), 8.35 (d, J ) 8.4 Hz, 1 H), 7.88 (d, J ) 7.7 Hz, 1 H),
7.55-7.33 (m, 8 H), 5.60 (s, 2 H), 4.06 (s, 3 H); 13C NMR (100
MHz) δ 168.1, 152.1, 139.2, 138.9, 135.0, 128.9, 128.7, 128.6,
128.1, 126.2, 125.9, 125.5, 124.8, 124.7, 124.4, 123.4, 120.1,
115.9, 69.0, 52.0; MS m/z (%) 359 (M+, 0.2), 315 (29), 164 (63),
91 (100); HRMS calcd for C22H17NO4 359.1158, found 359.1122.
When a 5-fold excess of DBU was employed, simultaneous
deprotection of the Cbz group occurred to afford 12 (vide infra)
in 65% yield.
Met h yl N-Ca r b ob en zyloxy-6-m et h ylca r ba zole-4-ca r -
boxyla te (10). Indole 4g (105 mg, 0.236 mmol), methyl
propiolate (0.21 mL, 2.4 mmol), and BHT (5 mg) were refluxed
in toluene (5 mL) under an argon atmosphere for 18 h. The
product was treated with DBU and worked up as in the
preparation of 9 to afford carbazole 10 (63 mg, 73%, based on
4g) as a white crystalline solid: mp 99-100 °C (from dichlo-
romethane-hexanes); IR (film) 1727, 1301, 1146 cm-1 1H
;
NMR (200 MHz) δ 8.62 (d, J ) 8.6 Hz 1 H), 8.46 (s, 1 H), 8.22
(d, J ) 8.7 Hz, 1 H), 7.86 (d, J ) 8.7 Hz, 1 H), 7.60-7.28 (m,
7 H), 5.58 (s, 2 H), 4.07 (s, 3 H), 2.52 (s, 3 H); MS m/z (%) 373
(M+, 4), 329 (65), 178 (85), 91 (100). Anal. Calcd for C23H19
-
NO4: C, 73.98; H, 5.13; N, 3.75. Found: C, 73.84; H, 4.94; N,
3.80. See Supporting Information for X-ray crystallographic
data for 10.
Dim eth yl N-Ca r boben zyloxy-ca r ba zole-4,6-d ica r boxy-
la te (11). Indole 4l (79 mg, 0.16 mmol), methyl propiolate (0.14
mL, 1.6 mmol), and BHT (4 mg) were refluxed in toluene (4
mL) under an argon atmosphere for 18 h. The product was
treated with DBU and worked up as in the preparation of 9
to afford carbazole 11 (44 mg, 65%, based on 4l) as a white
crystalline solid: mp 246-250 °C; IR (film) 1717, 1311, 1238
cm-1; 1H NMR (200 MHz) δ 9.41 (s, 1 H), 8.63 (d, J ) 8.4 Hz,
1 H), 8.41 (d, J ) 8.9 Hz, 1 H), 8.20 (d, J ) 8.9 Hz, 1 H), 7.95
(d, J ) 7.7 Hz, 1 H) 7.62-7.31 (m, 6 H), 5.61 (s, 2 H), 4.11 (s,
3 H), 3.99 (s, 3 H); 13C NMR (100 MHz) δ 167.8, 167.2, 151.8,
141.7, 139.7, 134.6, 129.3, 129.0, 128.9, 128.7, 128.2, 128.0,
126.9, 126.4, 125.8, 125.3, 124.3, 120.1, 115.6, 69.4, 52.5, 52.2;
MS m/z (%) 417 (M+, 1), 373 (88), 164 (50), 91 (100); HRMS
calcd for C24H19NO6 417.1212, found 417.1232.
Con ver sion of Tetr a h yd r oca r ba zole 13 to Ca r ba zole
12. Magnesium powder (36 mg, 1.5 mg atom) was added to
refluxing methanol (4 mL), followed by tetrahydrocarbazole
13 (80 mg, 0.15 mmol). The mixture was refluxed for an
additional 20 h and was then filtered through Celite and
concentrated in vacuo. Toluene (5 mL) was added to the
residue along with DDQ (34 mg, 0.15 mmol), and the mixture
was refluxed for 16 h. It was then concentrated in vacuo and
separated by chromatography (hexanes-ethyl acetate, 5:1) to
1
afford carbazole 12 (17 mg, 51%). The H NMR spectrum and
TLC of the product were identical to those of 12 obtained from
the deprotection of 9 (vide supra).
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada (NSERC)
for financial support. We thank Dr. R. Yamdagni, Ms.
D. Fox, and Ms. Q. Wu for elemental analyses and mass
spectra.
Meth yl Ca r ba zole-4-ca r boxyla te (12). Carbazole 9 (35
mg, 0.097 mmol) was dissolved in methanol (5 mL), 5% Pd-C
(10 mg) was added, and the reaction mixture was stirred for
16 h under 1 atm of hydrogen, maintained with a balloon. The
reaction mixture was filtered through Celite, concentrated in
vacuo, and purified by chromatography (hexanes-ethyl ac-
etate, 2:1) to afford carbazole 12 (21 mg, 95%): mp 94-96 °C
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR spectra of new compounds without satisfactory elemental
analyses and X-ray crystallographic data for 10. This material
is available free of charge via the Internet at http://pubs.acs.org.
1
(lit.14a 96-97 °C); IR (film) 3386, 1717, 1258 cm-1; H NMR
(200 MHz, acetone-d6) δ 10.7 (s, 1 H), 8.86 (d, J ) 7.7 Hz, 1
H), 7.84-7.76 (m, 2 H), 7.57-7.40 (m, 3 H), 7.19 (m, 1 H), 4.02
(s, 3 H); 13C NMR (100 MHz) δ 168.4, 140.2, 130.0, 129.4, 126.8,
J O016080M